C H A P T E R

NINE

Further Reactions of
Alcohols and the
Chemistry of Ethers
O

o you remember the fizzing that occurred when you (or

your teacher) dropped a pellet of sodium into water? The
violent reaction that you observed was due to the conversion of the metal and water into NaOH and H2 gas. Alcohols, which
can be regarded as alkylated water (Section 8-2), undergo the
same reaction, albeit less vigorously, to give NaOR and H2. This
chapter will describe this and further transformations of the hydroxy
substituent.
Figure 9-1 depicts a variety of reaction modes available to alcohols. Usually at least one of the four bonds marked a, b, c, or d is
cleaved. In Chapter 8 we learned that oxidation to aldehydes and
ketones breaks bonds a and d. We found that the use of this reaction in combination with
additions of organometallic reagents provides us with the means of preparing alcohols of
considerable structural diversity.
To further explore the reactions of alcohols, we start by reviewing their acidic and
basic properties. Deprotonation at bond a furnishes alkoxides (Section 8-3), which are
valuable both as strong bases and as nucleophiles (Section 7-8). Strong acids transform
alcohols into alkyloxonium ions (Section 8-3), converting OH (a poor leaving group) into
H2O (a good leaving group). Subsequently, bond b may break, thereby leading to substitution; or elimination can take place by cleavage of bonds b and c. We shall see that the
carbocation intermediates arising from acid treatment of secondary and tertiary alcohols
have a varied chemistry.
An introduction to the preparation of esters and their applications in synthesis is
followed by the chemistry of ethers and sulfur compounds. Alcohols, ethers, and their
sulfur analogs occur widely in nature and have numerous applications in industry and
medicine.

Ethoxyethane (diethyl ether or

simply ether) was discovered
as an anesthetic in 1846,
prompting a newspaper
headline exclaiming We have
conquered pain. The photo
shows an ether inhaler from that
period. It consists of a glass
vessel that contains ethersoaked sponges, connected to
a facemask by tubing. Apart
from its flammability, ether
is fairly safe, but has the
undesirable postanesthetic
effects of headaches and
nausea. It has been superseded
by a host of more effective pain
killing drugs, but is still popular
in some developing nations.

334
334

CC hh aa pp tt ee rr 99

FF uu rr tthheerr

334

Chapter 9

Further

Four typical
Figure 9-1 Four
typical reaction
reaction
alcohols. In
In each
each mode,
mode,
modes of alcohols.
one
or more
the
four
of
Figure
9-1 of
Four
reaction
thetypical
four bonds
bonds
marked
a alcohols.
d are
(wavy
line
are cleaved
cleaved
(wavy
line
modes of
In each
mode,
denotes
bond
(a)
bond
one or more
ofcleavage):
the four bonds
cleavage):
(a) dedeprotonation
(b)
by
base;
(b) protonprotonmarked a dby
arebase;
cleaved
(wavy line
ation
by
unior
denotes
bondfollowed
cleavage):
followed
by (a)
uni-deor
ation by
by acid
acid
bimolecular
(b,
protonation
by
base; (b) protonsubstitution;
(b, c)
c)
bimolecular substitution;
elimination;
(a,
and
ation by acidand
followed
by uni- or
(a, d)
d) oxidation.
oxidation.
elimination;
bimolecular substitution; (b, c)
elimination; and (a, d) oxidation.

ions of Alcohols and the Chemistry of E

Reactions of Alcohols and the Chemistry of Ethers

AA
A OH
OC
Deprotonation
OC
Deprotonation
H
OC
OH
AAA O
Deprotonation
A
H
OC
O
A
Deprotonation
H
C
O
H
O
O
O
H
OC
H
O
AA O
O
HO
C
OO
H Deprotonation
OC
OOC
O
aa HH
Deprotonation
A
A
a
A
HO
CO
OO
H
OC
OO
OH
H
H
C
O
H
O
O
O
a a
AA
Aa

AA
A OH
OC
H
OC
AA O
H
OC
AA O
H
OC
O

A
H
O
OC
O
H

H
O
OC

AAHO
OC
O
H
O
OC
O
A

A
A
H
O
OC
O


H
O
OC
O
HOC
O
O
Alkoxide
A
Alkoxide
A
A
Alkoxide
Alkoxide
Alkoxide
Alkoxide

Alkoxide

AA
A O HA
OC
H
OC
HA O H
OC
OOC
AAA O
AO
H
OC
O
H
C
O
H
O
OC
HOH
CO
OO
H
O
HOH
HO
C
OA O
OC
O
O
AAA O
b H
b
bb O OH
A
H
C
O
O
HO C
O OH
AA O
bb

Substitution
Substitution
Substitution
Substitution
Substitution
Substitution

Ac
OC O H
Elimination
AA cc A
AO
HcOH
C O O OH
OC
OC
Elimination
cc H
HA b
OC
O
Elimination
AA O

c
AA O
H
OC
C
O
O
O
OH
H
OC
H
H
C
O
O
O
A
HO C
OO
H
OH
AA O
b
b
A
A
H
C
O
H
O
O
O
b
HO C
O
O
O
H
OC
O
AA b A H
b

HO C O O OH
a
AA d A

Elimination
Elimination
Elimination
Oxidation

AA
A A OH
OC
OC
AHO
OC
O
H
OC
OH
A
A A
A
H
OC
O
H
X
OC
O
H
HH
OC O X
AO
HOC
X
OC
OX
A A
A
AO
H
X
OC
H
OC
O
Haloalkane
and
Haloalkane
AA Xand
Haloalkane
and
other alkane
Haloalkane
and
other
alkane
derivatives
other
alkane
Haloalkane
and
other
alkane
Haloalkane
and
derivatives
derivatives
other
alkane
derivatives
other
alkane
H E
derivatives
C
derivatives
B

H E

H
CH
CE
E
EH
C
H HC
BE
HB E
BB H
EC
C
H
HE
E
A CH
H
H
C
E
H
C
H
O
O
Alkenes
E
H
H
Alkenes
A
H
Alkenes

B
C
Alkenes
C

Alkenes
EC N
Alkenes
AO

AA
A OH
Aldehydes
C
H
O
OC
Oxidation
H
C
OC
O
O
AA O
AA O
Oxidation
and
ketones
H
C
H
OC
O
O
OH
Oxidation
A
A
A
A
C
H
OC
OH
O
O
Oxidation
H
C
O
H
O
O
O
H
C
H
OC
O
O
Oxidation
H
C
H
C
E
AA N
HO
OO
H
O
OO
O
C
N
AAA O
E
dd C
a
O
N
E
aa H
AO
H
O
C O
d C
O
HO
C
OO
H
O
O
E
Aldehydes
AA O
NO of Alkoxides
EC N
actions
Alcohols
with Base: Preparation
dd of
aa
Aldehydes
O
Aldehydes
and ketones

9-1 Reactions
Alcoholswith
withBase:
Base:Preparation
Preparationof
ofAlkoxides
Alkoxides
Reactions of
of Alcohols
Alcohols
with
Base:
Preparation
of
Alkoxides
9-1
described in
in Section
Section8-3,
8-3,alcohols
alcoholscan
canbe
beboth
bothacids
acidsand
andbases.
bases.In
Inthis
thissection,
section,we
weshall
shall
As described
described
in
Section
8-3,
alcohols
can
be
both
acids
and
bases.
In
this
section,
we
shall
As
methodsby
bywhich
whichthe
thehydroxy
hydroxygroup
groupof
ofalcohols
alcoholsisisisdeprotonated
deprotonatedtoto
tofurnish
furnishtheir
their
review the
the methods
methods
by
which
the
hydroxy
group
of
alcohols
deprotonated
furnish
their
review
bases, the
the alkoxides.
alkoxides.
conjugate bases,
bases,
the
alkoxides.
conjugate

neededto
todeprotonate
deprotonatealcohols
alcoholscompletely
completely
Strong bases
bases are
are needed
needed
to
deprotonate
alcohols
completely
Strong
proton from
fromthe
theOH
OHgroup
groupof
ofan
analcohol
alcohol(Figure
(Figure9-1,
9-1,cleavage
cleavageofof
ofbond
bonda),
a),we
we
To remove
remove aaa proton
proton
from
the
OH
group
of
an
alcohol
(Figure
9-1,
cleavage
bond
a),
we
To
must use
use aabase
basestronger
strongerthan
thanthe
thealkoxide.
alkoxide.Examples
Examplesinclude
includelithium
lithiumdiisopropylamide
diisopropylamide(Sec(Secbase
stronger
than
the
alkoxide.
Examples
include
lithium
diisopropylamide
(Secmust
butyllithium (Section
(Section8-7),
8-7),and
andalkali
alkalimetal
metalhydrides
hydrides(Section
(Section8-6,
8-6,Exercise
Exercise8-4),
8-4),
tion 7-8),
7-8), butyllithium
butyllithium
(Section
8-7),
and
alkali
metal
hydrides
(Section
8-6,
Exercise
8-4),
tion
potassium hydride,
hydride,KH.
KH.Such
Suchhydrides
hydridesare
areparticularly
particularlyuseful
usefulbecause
becausethe
theonly
onlybybysuch as
as potassium
potassium
hydride,
KH.
Such
hydrides
are
particularly
useful
because
the
only
bysuch
the reaction
reaction isis
ishydrogen
hydrogengas.
gas.
product of
of the
the
reaction
hydrogen
gas.
product
ThreeWays
Waysof
ofMaking
MakingMethoxide
Methoxidefrom
fromMethanol
Methanol
Three
Ways
of
Making
Methoxide
from
Methanol
Three

with water
water vigorvigorSodium reacts with
hydrogen gas.
gas.
ously, releasing hydrogen

CH(CH33)3)2)22
CH(CH
CH(CH
AAA


OH 
Li
NCH(CH33)3)2)22
CH333OH
OH

Li
NCH(CH
 Li
CH
NCH(CH
pKaaa15.5
15.5
pK
15.5
pK

 CH
CH333CH
CH222CH
CH22CH
CH22Li
Li
CH333OH
OH 

CH
CH
CH
CH
2CH
2Li
pK
15.5
pKaaa15.5
15.5
pK

24.5
24.5
24.5
10
10
KKK10

Lithiumdiisopropylamide
diisopropylamide
Lithium
diisopropylamide
Lithium
34.5
34.5
34.5
10
10
KKK10

pK
pK
15.5
pKaa15.5
a15.5

Potassium
Potassium
Potassium
hydride
hydride
hydride

pK

40
pK
pK
4040
a a
a

CH33O
OLi
Li 
 CH
CH
CH
CH
CH
H
CH
Li

CH
CH
3O
33CH
22CH
22CH
22H
3CH
2CH
2CH
2H
pK
5050
pK

50
pK
a a
a

Butyllithium
Butyllithium
Butyllithium

CH
OH
K
H

CH333OH
OH 
 K
KH
H
CH

CH(CH
CH(CH
CH(CH
3)332))22
AAA


CH33O
OLi
Li
HNCH(CH
CH
Li

HNCH(CH
 HNCH(CH

CH
3O
3)332))22

22.5
22.5
22.5
10
KKK10
10

O
O
CH

K 
 HHH
O
CH
HHH
CH33O
OKK
3O
pK
38
pK
38
pK

38
a a
a

rCH
many
require
formmol
example,
catalytic
OH.reactions
Would itthat
be all
right catalytic
simply tobase,
add 10
of NaOH
to th
CH33OH.that
Would
itwould
be alllike
righttosimply
to add
10 mmolcontaining
of NaOH 10
to th
Assume
you
make
such
a
solution
m
9-1
mparing
pKa many
valuesreactions
is
enough.
Hint:
See
Section
2-2
9(Table
-2
2 R
R eee aaa2-2)
c tttiiiooonn
nsss not
later
that
require
catalytic
base,
for
example,
cata
ounter
o
f
A
l
c
o
h
o
l
s
w
i
t
h
S
t
r
o
n
g
A
c
id
dsss
2
R
c
o
f
A
l
c
o
h
o
l
s
w
i
t
h
S
t
r
o
n
g
A
c
i
d
9
c
o
f
A
l
c
o
h
o
l
s
w
i
t
h
S
t
r
o
n
g
A
c
i
mparing
pK
values
(Table
2-2)
is
not
enough.
Hint:
See
Section
2-2
a
- 2 right
R e a c simply
t i o n s oto
f A
l c o 10
h o lmmol
s w i t hofSNaOH
trong A
ds s
Hmethanol.
it be9that
all
add
toc ithe
3OH. Would
Assume
you
would
like
to
make
such
a
solution
containing
9-2 Reactions of Alcohols with Strong Acids
Chapter 9
335
ncounter
later
many
reactions
that
require
catalytic
base,
forSection
example,
cataly
ring
values
(Table
is not
enough.
Hint:
See
2-2.)
liter pK
of aCH
it2-2)
ofg NaOH
9-2 R
ebe
a c all
t i o right
n s o fsimply
A l c o htoo ladd
s w 10
i t hmmol
Stron
A c i d s to
3OH. Would
in methanol. Assume that you would like to make such a solution containing 1
comparing
pKa valuesalcohols
(Table 2-2) is
enough.
See Section
mply
lso
deprotonate
notbut
by Hint:
reduction
of2
Exercise
9-1

1 literdeprotonate
of CH OH. Would italcohols
be all right simply
to add
mmol of NaOH to
lso
but
by10reduction
oft
Exercise 9-1 3
imply
comparing
pKamany
values
(Table
not enough.
Hint:
Section
2-2
encounter later
later
requireiscatalytic
catalytic
base, for
for example,
example,See
catalytic
sodium
many
reactions
that 2-2)
require
catalytic
base,
for
example,
catalytic
sodium
We shall
encounter
reactions
that
require
base,
catalytic
sodium
way
of
obtaining
alkoxides
is
by
the
reaction
of
alcohols
o Exercise
deprotonate
alcohols

by
We
shall
later9
many
that
for
sodium
- 2alkoxides
Rreactions
e a cyou
t i owould
n s require
f by
Ato
lbut
cmake
othe
h such
osuch
lbase,
s reaction
i reduction
t hexample,
Scontaining
tcontaining
r oof
ncatalytic
g alcohols
A
c mmol
immol
d of
s of
methoxide
in methanol.
methanol.
Assume
that
you
would
like
tocatalytic
such
solution
10
mmol
ofH
9-1
Assume
that
to
make
aaawsolution
10
would
like
make
solution
containing
10
of
methoxide
in
way
of encounter
obtaining
isolike

r many reactions that require catalytic base, for example, catalytic sodium
Assume that you would like to make such a solution containing 10 mmol of
methoxide
in1allmethanol.
Assume
you
would
to make
a solution
containing
10
of
liter
of
CH
H3OH.
Would 33itin
be
rightof
simply
add Would
10that
mmol
NaOH
tolike
thesimply
solvent?
NaOCH
liter
CH
OH.
ititofbe
all
to
add
mmol
NaOH
solvent?
OH.
Would
be
all right
right
simply
to
add
10
mmol
of
NaOH
to
the
solvent?
right
simply
tosuch
add10
10
mmolof
of
NaOHto
tothe
themmol
solvent?
333to
NaOCH
1 liter
ofislater
CH
OH.
Would
it be
all right
to
add
10
mmol
of Section
NaOH
to
the solvent?
ringWe
pKa shall
values
(Table
2-2)
not 3enough.
See
Section
2-2.)
comparing
encounter
many
reactions
that
require
catalytic
base,
for See
example,
catalytic
sodium
3 in
(Caution:
Simply
comparing
pK
values
(Table
2-2)
isis
Hint:
2-2.)
pK
values
(Table
2-2)
not
enough.
Hint:
See
Section
2-2.)
Simply
2-2)simply
is not
notenough.
enough.
Hint:
See
Section
2-2.)
aHint:

alsSuch
alsometals
deprotonate
alcohols
but
byviolently
reduction
o
um.
reduce

some
cases,

to
Such
metalsalkoxides
reduce water
water
in
in
some
cases,ofviolently
wit
to
yum.
of
obtaining
is
by
the
reaction
alcohols
(Caution:
Simply
comparing
pK
values
2-2)
enough.
See
Section
2-2.)
nd
hydrogen
gas.
When
the
more
reactive
metals
(sodium,
etals
also
alcohols

by
reduction
methoxide
in methanol.
Assume
that
you(Table
would
like istonot
make
suchbut
aHint:
solution
containing
10 mmol of of
way
ofdeprotonate
obtaining
alkoxides
is
by
the
reaction
of
alcohol
mmon
nd
hydrogen
the
more
reactive
metals
1
NaOCH
in
liter ofgas.
CH OH.When
Would
it be
all
to add
10 mmolviolently
of NaOH to(sodium,
the
solvent?
Such
metals
reduce
right
inHsimply
some
cases,
to yie
Exercise
9-11water
o. deprotonate
alcohols
but
bywater
reduction
of
posed
to
in
air,
the
hydrogen
generated
can
ignite
1
1
1 spo
(Caution:
Simply
comparing
pK
values
(Table
2-2)
is
not
enough.
Hint:
See
Section
2-2.)
lithium.
Such
metals
reduce
water

in
some
cases,
violently

as
Alkali
deprotonate
by
metals
also
deprotonate
alcohols

but
by
reduction
of
H
mmon
way
of
obtaining
alkoxides
is
by
the
reaction
of
alcohols
alcohols

but
by
reduction
of
H
reduction
of
H
posed
to
water
in
air,
the
hydrogen
generated
can
ignite
spo
hydrogen
gas.
the
more
metals
(sodium,
pot
of obtaining
alkoxides
is byWhen
the reaction
of alcohols
withreactive
alkali
Alkali
deprotonate
alcohols
base,
but for
byexample,
reduction
H1
We shallmetals
encounter also
later many
reactions that require
catalytic
catalyticof
sodium
metals
reduce
water
inmetals
some
cases,reduce
violently
water
tothe
yield
alkali
and
hydrogen
gas.
When
more
reactive
metals
(sodium
xides
hSuch
as
lithium.
Such

in
some
cases,
violently

to
Another
way
of
obtaining
alkoxides
is
by
the
reaction
of
alcohols
with
alkali
common
way
of
obtaining
alkoxides
is
by
the
reaction
of
alcohols
with
alkali
is bysuch
thea solution
reaction
of alcohols
with
methoxide
inWhen
methanol.
Assume
that
youhydrogen
would
like topotassium,
make
containing
10 mmol
of alkali
ed
to gas.
water
in
air,
the
generated
can
ignite
hydrogen
the
more
metals
(sodium,
1sponta
Another
common
way
ofreactive
obtaining
alkoxides
is
by
the
reaction
of alcohols
with
alkali
metals,
lithium.
Such
metals
reduce
water

in
some
cases,
violently

toyield
yield
alkalis
such
lithium.
Such
metals
reduce
water
some
cases,

to
alkali
water

in
some
cases,
violently

to
yield
alkali
NaOCH
in air,
1 as
liter
of
CHwater
OH.
Would
it can
be
all
right
simply
toin
add
10 reactive
mmol
of violently
NaOH
to the
solvent?
Alkali
metals
also
deprotonate
alcohols

but
by
reduction
of
H
oxides
and
hydrogen
gas.
When
the
more
metals
(sodium,
exposed
to
in
air,
the
hydrogen
generated
can
ignite
are
ed
to
water
in
the
hydrogen
generated
ignite
spontaneously
metals,
such
as lithium.
Such
metals
reduce

in some
cases,
violently
to yield
alkali
 (sodium,
metal
and hydrogen
the
more
reactive
metals
(sodium,
potassium,
hydroxides
and
gas.
When
the
reactive
metals
potassium,
(Caution:
Simply
comparing
pK values
(Table
2-2)water
is
notmore
enough.
Hint:
See
Section
2-2.)
hydrogen
gas.
When
the
more
reactive
metals
(sodium,
potassium,
2
M

2
Na,
K,
Cs)

H

)H
arecesium)
exposed
to(Li,
water
ingas.
air,
hydrogen
can
ignite
2
Another
common
way
ofto
obtaining
ismore
by the
reaction
of OH
alcohols
with
alkali
metal
hydroxides
and
hydrogen
When
reactive
metals
(sodium,
potassium,
nate.
are
exposed
water
in
air,
the
hydrogen
generated
can
ignite
spontaneously
and
exposed
toNa,
water
in alkoxides
air,the
thethe
hydrogen
generated
can
ignite
spontaneously
H
2generated
M

2M
M
(Li,
K,
Cs)
OH

Hspo
aa
a

water in
in air,
air, the
the hydrogen
hydrogen
generated
can
ignite
spontaneously
hydrogen generated
generated can
canignite
ignitespontaneously
spontaneously
and cesium) are exposed
exposed to
to water
2
metals,
as
lithium.
Such
metals
in some
cases, violently
to yield alkali
and
are
exposed
to 2water
inreduce
air,
generated
can ignitespontaneously
MOH
 even
2cesium)
M such
(Li,
Na,
K,
Cs)
 the
Hwater
2 hydrogen
onate.
detonate.
or
1

metal
hydroxides
and
hydrogen
gas.
When
the
more
reactive
metals
(sodium,
potassium,
or
even
detonate.
Alkali
metals
also
deprotonate
alcohols
but
byMreduction
of 
Hthe

2
2
M
(Li,
Na,
K,
Cs)
OH
H
ct
similarly
on
the
alcohols
to
give
alkoxides,
but
transfo
imilarly
on
the
alcohols
to
give
alkoxides,
but
the
transformation
is
2
O
Hsimilarly
OH 2are
2OH
Mignite
on
2 
M
(Li,
Na,
K,
Cs)
OH
 H

ctAnother
toCs)
give alkoxides,
but
the
transfo

and
cesium)
to alcohols
water
in air,
hydrogen
generated
can
spontaneously
HOexposed
OH
222M
22 M
Na,
K,

HH
two
examples.
M
M (Li,
(Li,
Na, the
K,
Cs)
OH

222
M
OH
 with
H
OH the
Cs)

common
way
alkoxides
is by the reaction
of
alcohols
O
OH
2OH
M
2metals,
2obtaining
Mmetals
Na,
Cs)
 H2
HO
OH of
2 M
2examples.
2(Li,
M (Li,
Na,K,
K, Cs)
OH
H2 alkali
are
two
or H
even
detonate.
such
as
lithium.
Such
reduce water in some cases, violently to yield alkali
are
two
examples.
Alkoxides
from
Alcohols
and
Alkali
Metals
act
on
alcohols
give
alkoxides,
but
transformation
isisis
imilarly
on and
the
alcohols
to
givetotototoalkoxides,
butthe
The alkali
act similarly
similarly
on the
the
alcohols
give
alkoxides,
but
the
transformation
give
alkoxides,
but
thethe
transformation
alkali
metals
etals
act metals
similarly
on the
alcohols
give
alkoxides,
buttransform
the tran
metal
hydroxides
hydrogen
gas.
When
the more
reactive
metals
(sodium,
potassium,
The vigorous.
alkali
metals
on
the
alcohols
to give
alkoxides,
but
the
is


are
two
examples.
 act
2 Na
2similarly
CH
Na(Li,

HK,
O act
HHere
OH
MOH
2 similarly
3CH
Na,
 transformation
H2 the transf
less
Here
are
two
examples.
2OH
22OM
2 Cs) to give 2
vigorous.
the
alcohols
alkoxides,
but
and
cesium)
exposed
to on
water
generated
can
ignite spontaneously
 in
 air, the hydrogen
emetals
two
Alkoxides
from
Alcohols
and
Alkali
Metals
less
vigorous.
are
two
examples.
Here
are
two
.3COH
 examples.
2 KareHere
2examples.
(CH
)
CO
K

H
3 3
2
Alkoxides
from
Alcohols
and
Alkali
Metals
or
detonate.
Alkoxides
Alcohols
Metals
us.
Here
are two
examples.
Theeven
alkali
metals
act similarly
on from
the alcohols
toand
giveAlkali
alkoxides,
but the transformation is
Alcohols
Alkoxides
from
Alcohols
and
Alkali
Metals
and
Alkali
Metals
lcohols used in this process decreases
withfrom
increasing
substitution,
Alkoxides
Alcohols
and Alkali Metals


less vigorous.
Here
are2
two
examples.
 




CH
OH

Na
CH
CH
O
Na
H
eactive
and tertiary
alcohols
least
reactive.




from
Alcohols
Alkali
Metals
CH

Na
222and
CH
CH
O
Na

Alkoxides
from
Alcohols
Metals
O
OH
M
2 H2Alkoxides

2M
(Li,22Na,
K,and
Cs) 2Alkali
OH
H2 H
2
3
2
CH
OH

Na
CH
CH
O
Na

H
33CH
22OH
32
2
CH
CH
O
Na

H22
2
CH
3
2
22
3
2
3
2 
Na
CH2OH 2
2COH
Na from
2 CH
H22
2O

CH
OH
22Na
CH33CH
CH
Na
 HH2 
Alcohols




3CH
2O

Metals


22Alkoxides
(CH
))3332Alkoxides

K
2222and
(CH
)3Alkali
CO
K

(CH
COH

2
K
(CH
)
CO
K

H
333with
333
333
from
Alcohols
and
Alkali
Metals
(CH
)
CO
K

H2
22
lative
Reactivity
of
ROH
Alkali
Metals
3 CO
2
but
the
H
)
COH

2
K
(CH
)
K
H


The
alkali
metals
act similarly
onthe 2alcohols
to2give
alkoxides,
transformation
is2
3
3
3
3


2
(CH
)
COH
K
2
(CH
)
CO
K

H
3
3
3
3
2


)CH

2K
2 (CH
 HH
CH
OH

2tertiary
Na
2 CH
O
H
3OH
3COH
32)O
3CO
Na

3CH
3CH
2K
Na

HH252less
22Here
2 process
CH
primary
.2
secondary
.
areNa
two
3 .
2 2H 2
CH
2 Na
23CH
CH
Na2O
H substitution,
reactivity
of
the
alcohols
in
with
increasing
3CH
2OH
3CH
2 vigorous.
CH
OH
examples.
2used
Na
2decreases
CH
CH
Na

used
in this
this process
decreases
with
increasing
substitution,
The
the
alcohols
process
decreases
with
increasing
substitution,
reactivity
3CH
2of
32O
2

 2 substitution,

3with
 increasing
The
reactivity
ofmost
the3)reactive
alcohols
used
inKthisalcohols
process2 least
decreases
2
(CH
)
COH

2
K
2
(CH
)
CO
K

H
2
(CH
COH

2
(CH
)
CO
K

H
being
and
tertiary
reactive.


Decreasing
reactivity
3
3
3
2
3
3
3
and
tertiary
alcohols
least
reactive.
methanol
most
reactive
alcohols
least
reactive.
COH
 most
2 Alkoxides
Kin this
2alcohols
(CH
CO
K with
H2 H2 2 su
being
from
Alcohols
anddecreases
Alkali
Metals
used
3emethanol
3least
2 (CH
2 tertiary
Kprocess
2)3(CH
Kincreasing

3)3COH
3)3CO
being
and
reactive.
e alcohols
alcohols
usedreactive
in this
process
decreases
with
increasing
su


The
of
used
in this
process
decreases
substitution,
Relative
of
ROH
with
Metals
eacts
soreactivity
slowly that
it can
be2alcohols
used to
safely
destroy
potassium
resi2 CH
CH
OH
Reactivity
2 Na
2 least
CH
O
Nawith
increasing
H2
3the
3CHAlkali
2Alkali
Reactivity
of
ROH
with
Metals
st
reactive
and
tertiary
alcohols
reactive.
with
Alkali
Metals
Relative
ROH
of
the
alcohols
used
in
this
process
decreases
  Metals with increasing
y
Relative
Reactivity
of
ROH
with
Alkali
st
reactive
and
tertiary
alcohols
least
reactive.
methanol
being
most
reactive
and
tertiary
alcohols
least
reactive.
2
(CH
)
COH

2
K
2
(CH
)
CO
K

H
3 in
3
3 3decreases
2
ity
of theused
alcohols
used
inprimary
this
process
with
increasing
s
alcohols
this
process
decreases
with
increasing
subs
5
CH
secondary
.
33 .
.
primary
.
secondary
.
tertiary
Rseen
5 that
CHthey
good for? We have alreadyR
be useful.
reagents
in
secondary
. tertiary
tertiary
3 . can
ng
most
reactive
and
alcohols
least
reactive.
R5
CH
primary
. secondary
. tertiary
3tertiary
example,
the reaction
of
hindered
alkoxides
gives
eing
most
reactive
and
tertiary
alcohols
least
reactive.
The reactivity
of
the
alcohols
used
inwith
thishaloalkanes
process
decreases
with
increasing
substitution,
Relative
Reactivity
of
ROH
with
Alkali
Metals
eactive
and
tertiary
alcohols
least
reactive.
Relative
Reactivity
ofDecreasing
ROH
with
Alkali
Metals
reactivity

Decreasing
reactivity
Decreasing
reactivity
Decreasing
reactivity
Relative
ROH
with
Alkali Metals
methanol being Reactivity
most reactive and of
tertiary
alcohols
least reactive.
R 5 CH3 .Decreasing
primary .reactivity
secondary . tertiary
Relative
Reactivity
of
ROH
with
Alkali
Metals resiP
CH
CH
CH
CH

(CH
)
COH
 with
K Br Alkali
Relative
Reactivity
of
ROH
Metals
R
5
CH
.
primary
.
secondary
tertiary
2-Methyl-2-propanol
reacts
so
slowly
that
it
can
be
used
safely
destroy
Relative
Reactivity
of
ROH
with
Alkali
Metals
so slowly
that with
it reactivity
can
used
to.
safely
destroy
potassium
resi3 . reacts
2-Methyl-2-propanol
can be
elative
Reactivity
of
ROH
Metals
beAlkali
used to
safely
destroypotassium
potassiumresiresiDecreasing
R 5 CH
primary
.
tertiary
2-Methyl-2-propanol
reacts
so
slowly
thatsecondary
it can
be
used
toto.
safely
destroy
potassium
3

(CH3)3COK, (CH3)3COH
E2

3 3

RR55CH
secondary..tertiary
tertiary
CH .
. primary
primary . secondary

dues
the
sdues
attackin
primary
haloalkanes
by CH
the SN.
2 reaction
to give
ethers. This . tertiary
in
the
laboratory.
in
the laboratory.
laboratory.
R5
primary
. secondary
duesWhat
in
the
laboratory.
33 3for?
Section
9-6.
are
What
are alkoxides
alkoxides good
good
for? We
We have
have already
already seen
seen that
that they
they can
can be
be useful
useful reagents
reagents in
in

What
are .
alkoxides
good for?
Wesecondary
have
already
seen
that
theycan
can
beuseful
useful
reagents
R 2-Methyl-2-propanol
5What
CH
primary
.
.
Decreasing
reactivity
reacts
slowly
that
italready
can
beseen
used
totertiary
safely
destroy
potassium
resiare
goodsofor?
We
have
that
they
be
reagents
inin
3 alkoxides
Decreasing
reactivity
organic
synthesis.
For
example,
the
reaction
of hindered
alkoxides
with
haloalkanes
gives
Decreasing
reactivity

base
will convert
an alcohol
into an alkoxide
by an acid-base
reacsynthesis.
For
example,
the
of
alkoxides
with
haloalkanes
gives
organic
of hindered
hindered
alkoxides with
withhaloalkanes
haloalkanesgives
gives
synthesis.
For example,
example,
the reaction
reaction
dues
the
organic
synthesis.
For
the
of
hindered
alkoxides
Decreasing
reactivity
Decreasing
reactivity
elimination.
ase,
the in
more
thelaboratory.
equilibrium
is displaced
to thereaction
alkoxide side.
Alkali
elimination.
elimination.
What
are
alkoxides
good
for?
We
have
already
seentothat
they
can bepotassium
useful reagents
in
elimination.
hols
by reduction to generate
hydrogen
gas and
an
alkoxide.
This


2-Methyl-2-propanol
reacts
so
slowly
that
it
can
be
used
safely
destroy
resi



(CH
)
CO
K
,
(CH
)
COH


3
3
3
3
(CH
CO
K
,, (CH
(CH3333))3333COH
COH
(CH3333)))3333CO
COK
K,the
steric
organic
synthesis.
example,
of
alkoxides
haloalkanes
CH3hindrance.
CH
CHlaboratory.
CHhindered
 K
(CH3reaction
)3COH
dues
in 2the
2CH2BrFor (CH
3CH2CH P
3)3COH gives
3 3
PCH2 with(CH

Decreasing reactivity

lCHreacts
that
it can be
used
toCH
safely
destroy
33CH22CH
222 
333)3)33COH
Br
CH

2CH
CH333CH
CH222CH
CHP
CH
 (CH
(CH
COH pota
 K
K
E2
CH2so
CH22slowly
Br

E2
3CH 2CHso
2
2Br
3used
2CH P
2 
3
E2
lropanol
reacts
that
can
toCHcan
safely
destroy
pota
CH
CHseen
(CH
)33COH
K
3What
2 are2CH
2slowly
3CH
2that
2 be
3destroy
E2
elimination.
-propanol
reacts
so
slowly
that
it be
can
be
used
to
pota
alkoxides
good
for?
Weit
have
already
they
useful
reagents
in 
E2
reacts
so
slowly
that
can
be
used
tosafely
safely
destroy
po
3 3

3 3

good
for? We
We
have
already
seen
that they
they
can be
be useful
useful
reagents
Whatsynthesis.
are alkoxides
for?
have
already
that
can
reagents
inin gives
organic
synthesis.
Forgood
example,
the
reaction
ofseen
hindered
alkoxides
with
haloalkanes
giv
organic
For
example,
the
reaction
of
hindered
alkoxides
with
haloalkanes
synthesis.For
Forexample,
example,
the
reaction
of hindered
hindered
alkoxides
with
haloalkanes
gives
organic
reaction
of
hindered
alkoxides
with
haloalkanes
gives
synthesis.
For
example,
reaction
of
alkoxides
haloalkanes
organic
example,
thethe
reaction
of hindered
hindered
alkoxides
withwith
haloalkanes
givesgives
synthesis.
the
reaction
of
alkoxides
with
haloalkanes
gives
elimination.
elimination.
elimination.
elimination.

CH
CH
CH22CH
CH22Br
Br
CH333CH
CH222CH
CH
Br
CH
CH
CH
22CHBr
22Br
CH
CH
33

22

22

22

 
 K
(CH3)33)CO
, (CH )3COH
3CO
(CH


K
, (CH3)33COH




 

(CH
CO
(CH
COH
CO
K
(CH
3))
3COH
(CH
,,,(CH
33))3333CO
(CH
K,K
,K
(CH
COH
(CH
K
(CH
33CO
333)
333COH
33))33CO
33))33COH

E2
E2

E2
E2
E2E2
E2

CH CH CHP CH



3 2CH
2 P
3 3
CH
CH
CH

COH

K
 

3CH
2 2(CH
3)3COH
P22CH
CH
CH
CH
 3(CH
(CH

K
P
CH
CH


K
P
P

CHCH
CH
CH
CH

(CH
)(CH
COH
 KK
BrK
CH
CH


Br
2CH
3COH
3333CH
222P
2222 
333)3)33)3COH
3CH
3)(CH
3CH
22CH
33COH

(CH ) COH

Less
branchedalkoxides
alkoxides
attack
primary
haloalkanes
the
S222Nreaction
2reaction
reaction
to
give
ethers.
Th
branched
alkoxides
attack
primary
haloalkanes
by
S
reaction
to
give
ethers.
This
N2
Less
attack
primary
haloalkanes
by the
the
Sthe
togive
give
ethers.
This
attack
primary
haloalkanes
by
S
reaction
to
This
alkoxides
attack
primary
haloalkanes
byby
the
Sreaction
toethers.
give
ethers.
This
Less branched
primary
haloalkanes
by
the
S
reaction
to
give
ethers.
This
branched
alkoxides
attack
primary
haloalkanes
by
the
to
give
ethers.
This
N
NN22S
NN
N
describedinin
in
Section
9-6.
method
isdescribed
described
in
Section
9-6.
Section
9-6.
method
Section
9-6.
described
in
Section
9-6.
method isis
described
Section
9-6.

Summary AA
A
strong
base
will
convert
an
alcohol
into
an
alkoxide
by
an
acid-base
reacSummary
Astrong
strong
base
will
convert
analcohol
alcohol
into
alkoxide
by
an
acid-base
rea
In
base
will
convert
an
alcohol
into
an
alkoxide
by
acid-base
reacbase
will
convert
an an
alcohol
intointo
an
alkoxide
by an
an
acid-base
reac-reacstrong
base
will
convert
an
alcohol
into
anan
alkoxide
by
anacid-base
acid-base
reacIn Summary
convert
an
alcohol
into
an
alkoxide
by
an
acid-base
reacSummary
strong
base
will
convert
an
alkoxide
by
an

base,
the
more
the
equilibrium
isis displaced
to
side.
Thestronger
stronger
the
base,
the
more
the
equilibrium
is
displaced
to
the
alkoxide
side.
Alkali
tion.
the
more
thethe
equilibrium
displaced
tothe
the
alkoxide
side.Alkali
Alkali
strongerthe
the
base,
the
more
theequilibrium
equilibrium
displaced
to
alkoxide
side.
Alka
tion.
tion. The
the
equilibrium
is
displaced
to
the
alkoxide
side.
Alkali
stronger
the
base,
the
more
the
equilibrium
isis
displaced
toalkoxide
thethe
alkoxide
side.
Alkali
The
stronger
the
base,
the
more
is
displaced
to
the
alkoxide
side.
Alkali
by
reduction
to
generate
hydrogen
gas
and
an
alkoxide.
This
metals
byby
reduction
to to
generate
hydrogen
gas gas
and
an
alkoxide.
This This
react
with
alcohols
by
reduction
to
generate
hydrogen
gas
and
an
alkoxide.
This
metals
reactwith
withalcohols
alcohols
by
reduction
generate
hydrogen
gas
and
alkoxide.
Th
metals react
reduction
to
generate
hydrogen
gas
and
an
alkoxide.
This
react
with
alcohols
reduction
hydrogen
and
an
alkoxide.
with
alcohols
by
reduction
totogenerate
generate
hydrogen
gas
and
anan
alkoxide.
This
isisretarded
steric
hindrance.
process
steric
hindrance.
retarded
by
steric
hindrance.
process
retardedbyby
by
steric
hindrance.
retarded
steric
hindrance.
process is
by
steric
hindrance.

with
Strong
Acids:
Alkyloxonium
Ions
9-2 Reactions
Alcohols
with
Strong
Acids:
Alkyloxonium
IonsIons
Reactions
of
Alcohols
with
Strong
Acids:
Alkyloxonium
Ions
Reactionsofof
ofAlcohols
Alcohols
with
Strong
Acids:
Alkyloxonium
Ions
9-2
Reactions
Alcohols
with
Strong
Acids:
Alkyloxonium
Strong
Acids:
Alkyloxonium
Ions
of
Alcohols
with
Strong
Acids:
Alkyloxonium
Ions
in
Substitution
and
Elimination
Reactions
of
Elimination
Reactions
of Alcohols
Alcohols
in
Substitution
and
Elimination
Reactions
of
Alcohols
in Substitution
Substitution
and
Elimination
Reactions
of
Alcohols
in
and
Elimination
Reactions
of
Alcohols
Reactions
of
Alcohols
Substitution and Elimination Reactions of Alcohols
heterolytic cleavage
cleavage of
of the
the O
OH
H bond
bond in
in alcohols
alcohols isis readily
readily achieved
achieved
We have seen that heterolytic

have
seen
that
heterolytic
cleavage
of
the
O
H
bond
in
alcohols
is
readily
achieved
We have
that
heterolytic
cleavage
of
O
bond
in
alcohols
isis
cleavage
of
the
O
H
H
bond
in
alcohols
readily
achieved
seen
that
heterolytic
cleavage
the
H
bond
alcohols
is
readily
achieve
that
heterolytic
cleavage
ofofthe
the
OO
H
bond
inin
alcohols
isreadily
readily
achieved
We
strongseen
bases.
Can
we break
C
(bond
b,
Figure
9-1)
as
Yes,
but
with have
break the
the
CO
O linkage
linkage
(bond
b,
Figure
9-1)
as easily?
easily?
Yes,achieved
but
strong
bases.
Can
we
break
the
C
linkage
(bond
b,
Figure
9-1)
as
easily?
Yes,
but
with we
strong
Can
break
the
O
linkage
Figure
9-1)
as
Yes,
but
C
O
linkage
(bond
b,
Figure
9-1)
as
easily?
Yes,
but
bases.
Can
we
break
the
C
Owater
linkage
b,
9-1)
as
easily?
Yes,
butb
with
strong
bases.
Canwe
we
break2-2)
theC
C
O
O
linkage
b,
Figure
as
easily?
Yes,
now
needbases.
acid. Recall
(Section
that
has
a(bond
high
pK
ItIt9-1)
isis
aaeasily?
weak
acid.
(Section
2-2)
that
water
has(bond
a(bond
highb,
pK
(15.7):
weak
acid.
aFigure
a (15.7):
we
need
acid.
Recall
(Section
2-2)
that
water
has
pK
(15.7):
is
weak
acid.
now we
(Section
2-2)
that
water
has
aaaahigh
pK
ItItIt
isis
acid.
2-2)
that
water
has
high
pK
(15.7):
weak
acid.
hydroxide,
its
conjugate
base,
is
an
poor
leaving
group.
For
acid.
Recall
(Section
2-2)
that
water
has
high
pKpK
(15.7):
It
isaaais
aweak
weak
acid.
aaaaa(15.7):
now
need acid.
acid.Recall
Recall
(Section
2-2)
that
water
has
ahigh
high
It
aFor
weak
aci
we need
Consequently,
its
conjugate
base,
is
an exceedingly
exceedingly
poor
leaving
group.
a (15.7):
Consequently,
hydroxide,
its
conjugate
base,
is
an
exceedingly
poor
leaving
group.
For
hydroxide,
its
base,
is
exceedingly
poor
leaving
group.
For
to undergo
substitution
or
reactions,
the
fipoor
be
converted
Consequently,
conjugate
base,
is
an
exceedingly
poor
leaving
group.
For
hydroxide,
its
conjugate
base,
isisan
anan
exceedingly
poor
leaving
group.
ForF
alcohols
substitution
or elimination
elimination
reactions,
the OH
OH must
must
first
rst
be
converted
Consequently,
hydroxide,
itsconjugate
conjugate
base,
exceedingly
leaving
group.
to undergo
substitution
or
elimination
reactions,
the
OH
must
rst
be
converted
alcohols
a better
leaving
to
substitution
the
OH
must
fifififirst
be
alcohols
elimination
reactions,
the
OH
must
rst
be
converted
into
group.
undergo
substitution
or
elimination
reactions,
thethe
OH
must
rst
beconverted
converted
alcohols
to undergo
undergogroup.
substitutionor
orelimination
eliminationreactions,
reactions,
OH
must
first
be
converte
better leaving
leaving group.
group.
into aa
into
into
a better
better leaving
leaving group.
group.

Pr from
mary
kaneand
Synthes
s from
anaA coho
aloalkanes
alcohols
HX: Water
can be
group
in
2Bromoa
reactions
eaving
N
eaving
group
in S
Sprimary
N2 reactions
eaving
group
in
S
2
reactions

N
em
36
FFuurrtthheer r RReeaacct ti ioonns s oof f AAl cl co oh ho ol sl s a an nd d t ht h
e eCC
h eh m
i si tsrtyr yo fo fE tEht ehresr s
C hh aa pp tt ee rr 99

he
way
turning
the
hydroxy
substituent
in
into
aa good
leaving gro
he
simplest
way of
of 
turningHBr
the
hydroxy
substituent
in 3alcohols
alcohols
into2CH
good
gro

r Rsubstituent
Hsimplest
OH
CH
CHa2ninto
CH
OH

2CH
2

form
leaving
F u r t h ean
e a c t i o n s o f in
A lalcohols
c o h o l s Recall
d t ha
e good
C h e m2ileaving
y o2f group
E t h e r sth
336
C of
h a poxygen
ter 9
he
waythe
turning
the
hydroxy
6tosimplest
mi s t r y s tor f8-3)
6
F u r t to
h e r form
R e a c an
t i o nalkyloxonium
s o f A l c o h o l s ion.
a n d Recall
t h e C h e(Section
mm
E t h ethat
r s th
C h a p t e r the
9
to protonate
protonate
oxygen
to
alkyloxonium
ion.
(Section
8-3)
that
to protonate
the
oxygen
to formlone
an alkyloxonium
ion. aRecall
(Section
8-3)The
thatpositi
this
ocess
ties
up
one
of
the
oxygen
pairs
by
forming
bond
to
a
proton.
ocess ties up one of theHaloalkanes
oxygen lone
pairs
by alcohols
forming
a bond
to a can
proton.
positi
Haloalkanes
from
primary
alcoholsaand
and
HX:
Water
aThe
from
primary
HX:
Water
bebe
a2CH
CH
CH
ocess
ties up one of theon
oxygen
lone
pairs
byProtonation
forming
bond
to
a OH
proton.
The
positive
3can
2CH
arge
the
atom.
changes
from
abebad
leavi
arge therefore
therefore resides
resides on
the oxygen
oxygen
Protonation
changes
from
bad
Haloalkanes
primary alcohols
and HX:OH
Water
can a
a leavi
leaving
group
SSNpN2from
reactions
leaving
groupin
inatom.
2ma
reactions
Ha
oa
kane
om
a
coho
and
HX
Wa
e
can
be
a
arge into
therefore
resides
on
the
oxygen
atom.
Protonation
changes
OH
from
a
bad
leaving
Ha
oa
kane
om
p
ma
a
coho
and
HX
Wa
e
can
be
a
Haloalkanes
from
primary
alcohols
and
HX:
Water
can
be
a
oup
neutral
water,
a
good
leaving
group.
leaving
group
inthe
SNhydroxy
2hydroxy
reactions
oupPoorinto
water,The
a
good
leaving
group.
leaving
group
leavingneutral
group
simplest
way
of
turning
substituent
in
alcohols
into
a
good
leaving
group
The
simplest
way
of
turning
the
substituent
in
alcohols
into
a
good
leaving
group
ng
g
oup
eac
on
oup
into
neutral
water,
aea
group.
eagood
ng
gleaving
oup
noxygen
Sway
2 reactions
eac
on
leaving
group
inn
SS
22
Nnormal
This
reaction
is
and,
under
conditions,
the
equilibrium
on
the
si
Poor leaving
group
The simplest
oftoto
turning
the
substituent
inRecall
alcohols
into alies
good
leaving
group
isis to
the
form
ananhydroxy
alkyloxonium
ion.
(Section
8-3)
that
this
to protonate
protonate
the oxygen
form
alkyloxonium
ion.
Recall
(Section
8-3)
that
this
This
reaction
is reversible
reversible
and,
under
normal
conditions,
the
equilibrium
lies
on
the
si
on
of
pr
mary
a
coho
s
w
concen
ra
ed
HI
proceeds
m
w
This
reaction
is
reversible
and,
under
normal
conditions,
the
equilibrium
lies
on
the
side
is up
to
protonate
theh
oxygen
to form
an
alkyloxonium
ion.into
Recall
(Section
8-3)
thatn
process
ties
one
of
the
oxygen
lone
pairs
by
forming
a
bond
to
a
proton.
The
positive
m
w
process
ties
up
one
of
the
oxygen
lone
pairs
by
forming
a
bond
to
a
proton.
The
positive
The
simplest
way
of
turning
the
hydroxy
substituent
in
alcohols
a
good
leaving
group
unprotonated alcohol.
alcohol. However,
However,
this
is
immaterial
ifpairs
a bynucleophile
nucleophile
isa proton.
present
in thitt
unprotonated
this
is
immaterial
if
a
is
present
in
process
ties
up
one
of
the
oxygen
lone
forming
a
bond
to
The
positiv
m
m
R
charge
therefore
resides
on
the
oxygen
atom.
Protonation
changes
OH
from
a
bad
leaving
charge
therefore
resides
on
oxygen
atom.
Protonation
OHpresent
from8-3)
a bad
leaving
isHowever,
to protonate
the
oxygen
totheform
an alkyloxonium
ion. changes
Recall (Section
that
this


unprotonated
alcohol.
this
is
immaterial
if
a
nucleophile
is
in
the

O
O
O
H

H
R

H

charge
therefore
on
the
Protonation
OH from
a positive
baded
leaving
ixture odoa
thatROis
isO Ocapable
capable
of
trapping
the
oxonium
species.
For
example,
alkyloxonium
ioH
m
ary
kanes
(marg
n)
On
he
ooxygen
her
hand
concen
ra
group
into
neutral
water,
aoxygen
leaving
group.
m example,
group
into
neutral
water,
agood
good
leaving
group.
process
ties
up
one
of
the resides
lone
pairs
byatom.
forming
a bondchanges
to a alkyloxonium
proton.
The
ixture
that
trapping
the
oxonium
species.
For
io
H  H of
 capable
group
into
neutral
water,
aunder
goodnormal
leaving
group.
ixture
that
isprimary
ofcharge
trapping
the
oxonium
species.
For
example,
alkyloxonium
ions
m
OH
m
This
reaction
isisreversible
and,
conditions,
the
onon
the
side
This
reaction
reversible
and,
under
normal
conditions,
theequilibrium
equilibrium
lies
the
side
m Protonation
OHfromlies
mathe
therefore
resides
onto
the
oxygen
atom.
changes
OH
bad
leaving

rived
from
alcohols
are
subject
such
nucleophilic
attack.
Thus,
butylox
O
OH
Rrived
OO
H
H
H primary
This
reaction
is
reversible
and,
under
normal conditions,
theThus,
equilibrium
liesbutylox
on the
the sid
O
O


from
alcohols
are
subject
to
such
nucleophilic
the
R

w
of
alcohol.
However,
this
ifattack.
is ispresent
in
ary
a
coho
s
n
o
he
correspond
ng
ch
oroa
kanes
because
of unprotonated
unprotonated
alcohol.
However,
thisis
isimmaterial
immaterial
ifa anucleophile
nucleophile
present
in the
group
into
neutral
water,
good
leaving
group.
w toaalcohol.
rived
from
primary
alcohols
are
subject
such
nucleophilic
attack.
Thus,
the
butyloxoof
unprotonated
However,
this
is
immaterial
if
a
nucleophile
is
present
in
Good
um ion
ion resulting
resulting
fromGood
the
treatment
of ofof
1-butanol
with
concentrated
HBr
undergoes
Goodfrom
H
m
m
mixture
that
isiscapable
trapping
the
species.
For
alkyloxonium
H
mixture
that
capable
trapping
theoxonium
oxonium
species.
For
example,
alkyloxonium
ions
m oxonium
mundergoes
This
reaction
reversible
and,ofunder
normal
conditions,
theexample,
equilibrium
lies
on the ions
side
um
the
treatment
of
1-butanol
with
concentrated
ddth
H
mixtureisthat
is1-butanol
capable
trapping
the
species.
For HBr
example,
alkyloxonium
ion
leaving
D
um Rion
resulting
fromleaving
the
treatment
of
with
concentrated
HBr
undergoes
disleaving
D

from
primary
alcohols
are
subject
toimmaterial
nucleophilic
attack.
Thus,
thethe
butyloxoH
w
mm
 byeoph
D

derived
from
primary
alcohols
are
subject
tosuch
such
attack.
Thus,
butyloxoH
ws
mm
ofderived
unprotonated
alcohol.
However,
thisare
issubject
ifnucleophilic
a nucleophile
is(red)
present
inb
the
O
eak
nuc
e
Therefore
h
convers
on
wh
e
poss
e

group
acement
bromide
to
form
1-bromobutane.
The
originally
nucleophilic
oxygen

O
RO
OG
group
derived
from primary
alcohols
to nucleophilic
such
attack.
Thus,
the
butyloxo

O
R
O
acement
by
bromide
to
form
1-bromobutane.
The
originally
nucleophilic
(red)
oxygen
group
nium
resulting
from
treatment
of
with
HBr
m
m
m
acementDGHHby
bromide to mixture
form
1-bromobutane.
The
originally
nucleophilic
oxygen
isdis
nium ion
ion
resulting
from
the
treatment
of1-butanol
1-butanol
withconcentrated
concentrated
HBrundergoes
undergoes
disthat
is capable
ofthe
trapping
the
oxonium
For
example,
alkyloxonium
ions
m
mspecies.
m (red)
mdisnium
ion resulting
from
thegive
treatment
ofm
1-butanol
with
concentrated
HBr
undergoes
Hby theGH
otonated
electrophilic
proton
(blue)
to
the
alkyloxonium
ion,
containing
D H
placement
by
bromide
to
1-bromobutane.
The
originally
nucleophilic
(red)
oxygen
is re
m
m

placement
byprimary
bromide
toform
form
The
originally
nucleophilic
(red)
oxygen
otonated
by
the
electrophilic
proton
(blue)
to
give
the
alkyloxonium
ion,
containing
derived
from
alcohols
subject
such
nucleophilic
attack.
Thus,
the(red)
butyloxom
m
OO
RO
O by
placement
by
bromide
to1-bromobutane.
form
1-bromobutane.
The
originally
nucleophilic
reagen
s(blue)
(Sec
on
9-4)
Inelectrophilic
genera
ac
d-ca
asubsequent
yzed
S
22dis
R
otonated
proton
(blue)
toare
give
thetohe
alkyloxonium
ion,
containing
anis i
Alkyloxonium
ion
Noxygen
Alkyloxonium
ion the electrophilic
ion
G Alkyloxonium
protonated
by
the
proton
(blue)
to(blue)
the
alkyloxonium
ion,
containing
anrea
G
m
m
w
HB
protonated
by
the
electrophilic
proton
(blue)
togive
give
the
alkyloxonium
ion,
containing
anan
nium
ion H
resulting
from
theelectrophilic
treatment
of
1-butanol
with
concentrated
HBr
undergoes
protonated
bym
the
proton
to
give
the
alkyloxonium
ion,
containing
m
m
m
w
HB
ectrophilic
carbon
and
O
as
a
leaving
group
(green).
In
the
S
2
N
H
(blue) carbon
carbon
and
acarbon
leaving
group
(green).
In
subsequent
22isrea
2O
N
H (blue)
ectrophilic
HH2by
O
asas
acarbon
leaving
(green).
In(green).
thethe
subsequent
SNSoxygen
2S
electrophilic
(blue)
and
Hgroup
asm
group
InInthe
reacm
m
m
2O
N
electrophilic
(blue)
carbon
and
as a The
leaving
group
In
thepr
subsequent
S
reach
electrophilic
(blue)
and
H
asaHaleaving
leaving
group
(green).
the
subsequent
S2Nreac2Nreacplacement
bromide
to form
1-bromobutane.
originally
nucleophilic
(red)
mgood
mway
m
m
2O
2O
hectrophilic
HBr
HIas
snucleophile.
aand
of
prepar
ng
s (green).
mp
esubsequent
mary
m or
on,
bromide
acts
m
m
tion,
acts
asasaaacts
nucleophile.
tion,
bromide
as aproton
nucleophile.
on, bromide
bromide
acts as
as aaa nucleophile.
nucleophile.
tion, bromide
bromide
actselectrophilic
nucleophile.
protonated
by the
(blue) to give the alkyloxoniumm
mion, containing an
acts
m

(blue)
and HH
HOO
Oas a leaving group (green). In the subsequent S 2 reacdary and er aryelectrophilic
a coho
s?carbon
Bromoalkane
Synthesis
from
Alcohol
Primary
Bromoalkane
Synthesis
from
an Alcohol
m
tion, bromide
a nucleophile.
Primary
Bromoalkane
Synthesis
froman
an
Alcohol
m acts asPrimary
2

Primary
Bromoalkane
Synthesis
from
an
Alcohol



Primary
Bromoalkane
Synthesis
an
Alcohol

Primary
Bromoalkane
Synthesis
from
an
Alcohol

CH
from
OH
CH
CH

Br

CH
HBr
HBr

OH

CH
 2
Br
3CH
2CH
2
3CH
2CH
2OH



2CH
2
3CH
2CH
2CH
2OH

22OH

CH33CH
HBr
CH2CH
OH2CH
CH
Br
2CH2CH
2
3CH2CH
2CH

2 2  
m
B
m
A
Primary
Synthesis
m
m Bromoalkane
B 
m
man Alcohol
A
from


CH
CH
Br
2
O
CH

3
2CH
2
2
2
CH
HBr

CH
CH
CH
OH

CH
CH
CH
CH
OH

Br

Br

H
OH
CH

3CH
2CH
2
3CH
2CH
2CH
2OH
23CH
2CH







CH333CH
HBr

CH222CH
CH222CH
CH222
OH 
CH

Br
OH
HBr

CH
CH
CH
CH
OH


Br

CH
CH
Br

H
O
CH

2
2
2
2
3
2
2
2
2
3
2
2
2
2









CH
HB

CH
CH
CH
OH

CH
CH
CH
CH
B
CH
OH
CH
Br

CH3CH
HB

CH2CH
CH2CH
CH2
OH 
 HBr
CH3CH
CH2CH
CH2CH
CH
OH

B
2OH


 2 


OH




The of
reaction
of alcohols
primary alcohols
with concentrated
HI proceeds
in
similar
fashion
to
Iodoalkane
Synthesis The reaction
primary
with
concentrated
HI
proceeds
in
similar
fashion
to
Iodoalkane
Synthesis

CH
CH
CH
Br

H
O
CH

CH
CH
CH
B

H
O
CH

CH
CH
Br

Hsluggish
O
CH
The reaction
of primary
alcohols
withCH
concentrated
HI
proceeds
in2
similar
toin
Iodoalkane Synthesis

3
2
2
2

32
2CH
2

CH
CH
B
H
O22
CH


CH
Br
O





CH
Br

H
O
CH
furnish primary
iodoalkanes
(margin).
On
the
other
hand,
HCl
isfashion


3CH
2CH
2
2H
3CH
2CH
22 concentrated
2CH



furnish
in
HO(CH )6OH  2 HI
furnish primary
primaryiodoalkanes
iodoalkanes(margin).
(margin).On
Onthe
theother
otherhand,
hand,concentrated
concentratedHCl
HClis issluggish
sluggish
in
HO(CH ) OH  2 2HI

y and tertiary alcohols and HX: Water can be a

roup
to form
carbocations
in HISHI
1proceeds
and
E1
reacti
reaction
of
primary
alcohols
with
concentrated
similar
fashion
The reaction
of
alcohols
proceeds
in in
similar
fashion
to
N
reaction
of primary
primary
alcoholswith
withconcentrated
concentrated
HI
proceeds
in
similar
fashion
turning primary alcohols into the corresponding chloroalkanes, because chloride ion is

HO(CH22)66OH
 2 HI
1,6-Hexanediol
turning primary alcohols into the corresponding chloroalkanes, because chloride ion is a
turning
primary
into
the corresponding
because
chloride
ion carried
is
The reaction
ofalcohols
primary
alcohols
with
HI
in similar
to a
m
w
H
m
1,6-Hexanediol
relatively
weak
Therefore,
this chloroalkanes,
conversion,
while
possible,
usually
m nucleophile.
wthisconcentrated
H proceeds
m is fashion
1,6-Hexanediol
relatively out
weak
nucleophile.
Therefore,
conversion,
while
possible, Sis2usually
carried
byiodoalkanes
other
reagents
(Section On
9-4).
In conversion,
general,
the acid-catalyzed
ofcarried
primar
relatively
nucleophile.
Therefore,
while possible,
isreaction
furnish
primary
(margin).
the
other
hand,
concentrated
HCl
isusually
sluggish
in
m
m
O
HC
N
mweak
m
O this
HC
out by other
reagents
(Section
9-4).
general,
acid-catalyzed
SN2primary
reaction
of primaryWha
H
HO CH
CH OH
OH 
 H
H
HO
alcohols
with
HBr
orthe
HI
is In
aIngood
waythe
of
preparing
simple
haloalkanes.
out by
other
(Section
9-4).
general,
the
acid-catalyzed
SNHCl
2 reaction
ofion
primary
turning
primary
alcohols
into
corresponding
chloroalkanes,
because
chloride
is in
a
m
m reagents
rnish
primary
iodoalkanes
(margin).
On
the
other
hand,
concentrated
is
sluggish
I(CH
)
I

2
H
O
primary
iodoalkanes
(margin).
On
the
other
hand,
concentrated
HCl
is
sluggish
2
6
2
alcohols
with
HBr
or
HI
is
a
good
way
of
preparing
simple
primary
haloalkanes.
What
rnish
(margin).
On
the
hand,
concentrated
HCl
is sluggish
about HBr
secondary
tertiary
alcohols
with
or HIand
isTherefore,
a other
goodalcohols?
way
ofconversion,
preparing
simple
primary
What
relatively
weak
nucleophile.
this
while
ishaloalkanes.
usually
carried
w
w
I(CHprimary
H2iodoalkanes
O
2)6I  2 85%
w
w possible,
about
secondary
and tertiary alcohols?
I(CHprimary
O
2)6I  2 H2alcohols
rning
primary
alcohols
into
the
corresponding
chloroalkanes,
because
chloride
ion
into
the
corresponding
because
is
about
secondary
and(Section
tertiary alcohols?
by other
9-4).chloroalkanes,
In
general, the acid-catalyzed
SNchloride
2 reaction
ofion
primary
m ais
rning
primary
alcoholsout
into
thereagents
corresponding
chloroalkanes,
because
chloride
ion
is
85%
1,6-Diiodom
85%
hexane
alcohols
with
HBr
HI
isconversion,
atertiary
good way
of while
preparing
simple
primary
What
1,6-DiiodowSecondary
HB orthis
Hand
walcohols
mWater
m
W
latively
weak
nucleophile.
Therefore,
this
conversion,
while
possible,
is
carri
weak
nucleophile.
Therefore,
is
andpossible,
HX:
canusually
beusually
a carried
w
HB
H
w
m
m
W
CH

latively
Therefore,
this
conversion,
while
possible,
ishaloalkanes.
usually
carri
1,6-DiiodoO
CH

H
Onucleophile.
hexane weak
CH
 H
HO
about
secondary
and tertiary
tertiary
alcohols?
Secondary
and
alcohols
and HX: in
Water
can
be
a of primary
hexane
leaving
group
to
form
carbocations
S
1
and
E1
reactions
%
by
other
reagents
(Section
9-4).
In
general,
the
acid-catalyzed
S
2
reaction
ut
other
reagents
(Section
9-4).
In
general,
the
acid-catalyzed
S
2
reaction
of
prima
N
Secondary
and
tertiary
alcohols
and
HX:
Water
can
be
a
NSN2 reaction of prima
%
ut by %
other reagents (Section
the acid-catalyzed
Nreactions
leaving9-4).
groupIntogeneral,
form carbocations
in SN1 and E1

m ons der ved from secondary and er ary a coho s n c

n erpar s ose wa er w h ncreas ng ease o g ve he corres
Alkyloxonium
ions
derived
from
secondary
and
tertiary
alcohols,
in contrast n
withca
thei
leaving
group
tonform
carbocations
in She
1 primary
and
E1
reactions
isis
way
of
preparing
simple
primary
haloalkanes.
What
eason
forHBr
h orsor
dHI
fference
behav
orand
sHX:
dtocan
fference
cohols
with
HBr
good
way
of
preparing
simple
haloalkanes.
Wh
N
cohols with
with
HBr
or HI
HISecondary
isaaagood
good
way
of
preparing
simple
primary
haloalkanes.
Wh
and
tertiary
alcohols
Water
acorresponding
primary
counterparts,
water with
increasing
ease
givebe
the
carboca
Seconda
and
e
a
a
and
HX
Wa
e
can
be
a
Alkyloxonium
ions
derived
secondary
and
tertiary
alcohols,
in
contrast
their
Seconda
and
ederived
a from
alosecoho
coho
and
HX
Wa
ealcohols,
can
be
acontrastwith
secondary
tertiary
alcohols?
Alkyloxonium
ionsreason
from
secondary
and
tertiary
in in
with stability
their
secondary
and
tertiary
alcohols?
tions. The
for
thiswith
difference
inin
behavior
isgive
the
difference
carbocation
primary
counterparts,
lose
water
increasing
ease
to
thereactions
corresponding
carbocaoutPr
secondary
and
tertiary
alcohols?
leaving
group
to
form
carbocations
S
1
and
E1
ea
ng
g
oup
o
o
m
ca
boca
on
n
S
1
and
E1
eac
on
)out
mary and
carboca
ons
are
oo
h
gh
n
energy
o
be
access
b
N
ea
ng
greason
oup 7-5).
o olose
mdifference
cacarbocations
boca
onare too
n isShigh
1 and
E1the
eac
on under
primary
water
with
ease
toenergy
give
carboca(Section
Primary
to in
becorresponding
accessible
ordinary
tions.
Thecounterparts,
for this
in increasing
behavior
the indifference
carbocation
stability
Alkyloxonium
ions for
derived
from
andintertiary
alcohols,
in
with
theirwith
tions. The
reason
this difference
behavior
is
the
difference
in contrast
carbocation
laboratory
conditions,
whereas
secondary
and
tertiary
are generated
A
m
m
w
A(Section
m Primary
m secondary
w stability
7-5).
carbocations
areintoo
high
energy
to carboca
becarbocations
accessible
under
ordinary
ond ons whereas
secondary
and
er
ary
ons
ar
increasing
ease.
Thus,
alkyloxonium
only
S 2 reactions,
primary
lose
water
with
increasing
ease
toundergo
giveto the
corresponding
carboca(Section
7-5).
Primary
carbocations
tooand
hightertiary
inions
energy
be
accessible
underwhereas
ordinary
m
w
w
m counterparts,
w primary
w are
laboratory
conditions,
whereas
secondary
carbocations
are generated
withthei
econdary and
tertiary
alcohols
HX:
Water
can
be
a2 reactions,
secondary
and and
tertiary
relatives
enter
into
Stertiary
1 and
E1
processes.
good nucleophile
tions.
The
reaso
laboratory
conditions,
whereas
secondary
and undergo
carbocations
are generated
with
econdary
and
tertiary
alcohols
and
HX:
Water
can
a
increasing
ease.
Thus, primary
alkyloxonium
ions
only
Sbe
their
econdary
and
tertiary
alcohols
and
Water
can
be
ayWhen
are
present,
weprimary
observe
SHX:
1ons
products.
se Thus
prtomary
a ky
oxon
um
undergo
S whereas
2whereas
reac
m
increasing
ease.
Thus,
alkyloxonium
undergo
onlyon
SWhen
2 reactions,
their
m
secondary
and
tertiary
relatives
enter
into
S 1ions
andE1
E1 processes.
goodNnucleophiles
m
eaving
group
form
carbocations
in
S
1
and
reactions
N
eaving
group
to
form
carbocations
in
S
1
E1
reactions
ww
secondary
and
tertiaryww
relatives
enter
into
Sand
1 and E1
processes.
When good nucleophiles
N
are
present,
we observe
S 1 products.
eaving
group
to
form
carbocations
in
S
1
and
E1
reactions
w
w
N
Reactivity
of Oxonium
Ions
nd
er ary re derived
a ves
en secondary
erobserve
n mmmoS 1and
Sproducts.
and
E1
processes
When
mm
ww
are present,
we
N1
m alcohols,
w
lkyloxonium ions
from
tertiary
in contrast
with
their
lkyloxonium
ions
from
secondary
tertiary
alcohols,
with
Reactivity
of Oxonium
Ions in
Wcontrast
lkyloxonium
ionsSderived
derived
from
secondary and
and
tertiary
alcohols,
inWW
contrastcarbocawith the
the
ww sincreasing Reactivity
of
Oxonium
Ions
imary
counterparts,
lose
water
with
ease
to
give
the
corresponding
we
observe
1
produc
imary counterparts,Nlose water wwith increasing ease to give the corresponding carboc
N

N
N

Does not dissociate:

SN2 only

Dissociate:
SN1 and E1

Does not dissociate: 

Dissociate:


imary
counterparts,
losedifference
water with
ease
to give
theE1
corresponding
carboc
Ris
RsecSOOH

Rtert OOH2
prim OOH
2difference
2
DoesS not
dissociate:
Dissociate:
2 only
1 and in
ons.
The
reason
for
this
ininincreasing
behavior
thethe
carbocation
stability
R
O
m
ons.
The
reason
for
difference
behavior
is
difference
carbocation
stabili
S 2 only
Sm1 and E1in
O
ons.
The
reason
for this
this
difference
is
theease
difference
in
carbocation
stabili
R
 carbocation

R
O
maccessible
Increasing
of
formation
ection
7-5).
Primary
carbocations
areintoobehavior
high
in
energy
to
be
under
ordinary
OOH
Rprim
Rsec OOH
 accessible
Rtert OOH
 2in 
 2 be
2
ection
Primary
carbocations
are
high
energy
to
under ordina
ection 7-5).
7-5).
Primary whereas
carbocations
are too
too
high
in2 Oxon
energy
to
OOH
OOH
R
 R
Rtert
prim
sec OOH
2beaccessible
2 under ordina
boratory
conditions,
secondary
and
tertiary
carbocations
are
generated
with
React
v
ty
of
um
Ions
Increasing
ease of carbocation
formation are generated wi
boratory
conditions,
whereas
secondary
and
tertiary
carbocations
Synthetically,
thisIncreasing
fact
is exploited
in carbocation
thecarbocations
preparation
of tertiary
from tertiar
boratory
conditions,
whereas
secondary
and
tertiary
arehaloalkanes
generated
ease
of
creasing ease.
Thus, primary
alkyloxonium
undergo
only
2formation
reactions,
whereas
theirwi
OOH
OOH Saqueous
OOH
RR ions
 concentrated
R
Rhydrogen
N
OOH
OOH
alcohols in the presence
of excess
product form
OOH
OOH
OOHhalide. The
R ions
 R
R OOH
N2R
Rreactions,
creasing
ease.
Thus,
primary
alkyloxonium
undergo
only
S
whereas
the
creasing
ease.tertiary
Thus,
alkyloxonium
ions
only
SWhen
whereas
the
N2 reactions,
Doesprimary
noSynthetically,
d ssoc
a into
efact
Dofisssoc
ahaloalkanes
ereversenucleophiles
condary and
relatives
enter
SNexploited
1temperature.
and inundergo
E1
processes.
good
in minutes
at room
The
mechanism
precisely
the
offrom
that of
solvolysi
this
is
the
preparation
tertiary
tertiary
m
m
condary and
tertiary relatives
enter
into
S
1
and
E1
processes.
When
good
nucleophil
m
(Section
7-2).
N
m halide.
relatives
enter
into
S
1
and
E1
processes.
When
good
nucleophil
Synthetically,
this
fact
is
exploited
in
the
preparation
of
tertiary
haloalkanes
from
tertiary
in
the
presence
of
excess
concentrated
aqueous
hydrogen
The
product
forms
N
econdary
present,and
we tertiary
observe S
SNNalcohols
1
products.
2
on
y
S
1
and
E1
N
ee present,
we
observe
S
1
products.
presence
of excess
aqueous
hydrogen
halide.
Theof
product
forms
minutesinatthe
room
temperature.
Theconcentrated
mechanism is
precisely
the reverse
of that
solvolysis
N
present, we observe Sinalcohols
N1 products.
N

m solvolysis
at room temperature. The mechanism is precisely the reverse of that of
7-2).
(Section
in minutes

Does not dissociate:



Dissociate:


S 2 only
S 1 and E1
OOH
Rprim OOH
Rsec

Rtert OOH2
2 
2



N

Rprim OOH2  Rsec OOH2  Rtert OOH2

Increasing
of carbocation
Increasing ease
ease of carbocation
formation formation
Synthetically, this fact is exploited in the preparation of tertiary haloalkanes from tertiary

in the presence
of excess concentrated
aqueous hydrogenof
halide.
The product
forms
,alcohols
this fact
is exploited
in the preparation
tertiary
haloalk
in minutes at room temperature. The mechanism is precisely the reverse of that of solvolysis
he(Section
presence
7-2). of excess concentrated aqueous hydrogen halide.
room temperature. The mechanism is precisely the reverse o
).

9-2 Reactions of Alcohols with Strong

sm
with Hydrogen
9 - of
2 the
R e aScN1t iReaction
o 9n-s2 Ro ef a cof
At ilTertiary
s l Alcohols
ss
ocnos hoof l A
cw
o hi ot lhs wSi tt hr oSnt g
r o nA
g cAi cdi d

9-2 Reactions of Alcohols with Strong Acids

9 - 2 R e a c t i o n s o f A l c oh o l s w i t h S t r o n g A c i d s

ooo n
A
h
ooo n
n
A lll ccc ooo OH
h
w ii ttt h
h
S
n
A
d
9 999- 2--- 222 R RRRe aeee caaa tccci tttoiii n(CH
n sss ooo fff C
h ooo lll sss w
h S
S ttt rrr
n ggg A
A ccc iii d
d sss
 HOBr
s o f3)A
o h o
ls w
S t r o nBr
g Acids
3 lAc O
2 iwt hi 

version
of 2-Methyl-2-propanol
into
2-Bromo-2-methylpro
Conversion
of2-Methyl-2-propanol into
2-Bromo-2-methylpropane

Conversion of
of 2-Methyl-2-propanol
2-Methyl-2-propanol
into2-Bromo-2-methylpropane
2-Bromo-2-methylpropane

Conversion
into

 3)3CBr  H
(CH
COH
 HBr
HBr
(CH

(CH
into
2-Bromo-2-methylpropane
)Conversion
2-Methyl-2-propanol
(CH
O3)3(CH
3)3of
C 2-Bromo-2-methylpropane
Br
O2O H
(CH
 into
of(CH
2-Methyl-2-propanol
3H
3Conversion
3)3CBr
2O (
2COH
3)3HBr
2
of
2-Methyl-2-propanol
2-Bromo-2-methylpropane

COH
into
 H2OH
Conversion
of
2-Methyl-2-propanol
into
2-Bromo-2-methylpropane
3)3CBr
Conversion
of
2-Methyl-2-propanol
into
2-Bromo-2-methylpropane

(CH3of
) COH
 Excess
HBr
(CH3)3CBr  H2O
Conversion
2-Methyl-2-propanol
into 2-Bromo-2-methylpropane
(CH )3 COH
 HBr
(CH ) CBr  H O

(CH33)33COH Excess
 Excess
HBr

(CH33)33CBr

H22O

Excess
(CH
HBr
(CH
)))333CBr
H
R
333)
3
(CH
))3333COH
COH

HBr
(CH
CBr H

H
O
3
(CH
COH 
 HBr
HBr
(CH

H2222O
O
COH  (CH
HBr
(CH3)3CBr
3
Excess
3
3CBr
Excess
2O
(CH
H2O
3)33COH
3)3CBr
Excess
Excess
Excess
Excess
Mechanism
ofSthe
the
SNN11 Reaction
Reaction
ofTertiary
TertiaryAlcohols
Alcohols
withwith
Hydrogen
Halides Hali
chanism
of
the
1
Reaction
of
Alcohols
Hydrogen
Excess
N
Mechanism
of
S
of
Tertiary
with
Hydrogen
Halides
for the success of this process is that relatively low tempe

































 













 









Mechanism
the
S
of
TertiaryAlcohols
Alcohols
withHydrogen
Hydrogen
Halides
N1 Reaction
sm of
the SN1ofof
Reaction
ofof
Tertiary
Alcohols
withHalides
Hydrogen
Mechanism
the
S
1
Reaction
Tertiary
with
 
Mechanism
of
the
SNNNNBr
1
Reaction
Tertiary
Alcohols
with
Hydrogen
Halides
ofthe
the
1Reaction
Reaction
of
Tertiary
Alcohols
with
Hydrogen
Halides


Mechanism
SO
ofof
Tertiary
Hydrogen
Halides
O
O
OH
(CH
C Otertiary
OH of

H
(CH
)33CAlcohols
CO
preventing
Br

NS1N

 22 with




OH
(CH
))Mechanism
OH

H
Br
(CH

Br

ate
carbocation,
thus
largely
competin

33the
33C O
33))
O
O
O





OH
OH

H
Br
(CH
C

Br



3 with
2

2 22




M

e(CH
SN331)3333))C33Reaction
of
Tertiary
Alcohols
Hydrogen
Halides
O
O
OOH
OH
OH

H
Br
(CH3333)))3C
Br





33CO
O
(CH
C
OH

Br
(CH
Br


 
O
O
O
OH
(CH
COO
OH

H
Br
C

Br





 good
33C
2 

O
O
O
OH
(CH
OH
 HH
H
Br
(CH
)333)O
C
the
Br
3




(CH
O
OH
(CH
OH

Br
(CH
Br
33)C
3C
2 22in

3)3
3)33




Indeed,
temperatures
(or
absence
of




Ohigher
O


OH

Hat
Br
(CH
C

Br
OBr
H
O

)
C
Br
H
O

(CH
)3CO
Br
(CH


3
3
2
 
2 
H22
O
C
Br
H2
O
(CH
  (CH33)



 


33
3)33C







 HH

 Br
O
(CH
)3OH
C 
Br
OH
(CH
CO
Br
(CH
 why

3C
2



H2
OHHH
)33333C)))C
Br
O(CH


3)
O
22
3
O

Br
O
))33333C
Br

OBr

H
C

3O
2
3
O
H
O
C
Br
H
O

(CH
C)33
Br
(CH








omes
explains
secondary
3

3(CH
2 Br
O(CH
H
O This
3)(CH
C 
H2222
O2 
(CH
(CH
Br
(CH

3


 dominant.*
 H2


O2222(CH

O
3 333
3)O
3CBr
2
3)33
3)3C


 protonated
 alc

 Br



The
reason
for
the
success
of
this
process
is
that
relatively
low
temperatures
are
suf(
The reason
the
success
of )this
isfollowing
that
relativelySlow
are
suf

behavior
the
presence
ofprocess
HX,
SH
E1
H
Ofor

Br
Oand

(CH


N2,temperatures
N1,
2in
3C
2


The
reason
for
the
success
of3this
this
process
is
that
relatively
low
temperatures
are
suf
fi
cient
toreason
generate
the
tertiary
carbocation,
thus
largely
preventing
competing
E1
reactions
The
reason
for
the
of
this
process
is
that
relatively
low
temperatures
are
sufsuccess

the
tertiary
carbocation,
thus
largely
preventing
competing
E1
reactions
The
reason
for3the
the
of
this
process
is
that
relatively
low
temperatures
are
sufsuccess
O
The
for
success
of
process
is
that
relatively
low
temperatures
are
sufO

)
C
Br
H
O

(CH
)
C
Br
(CH

2
3
2
3
3




eason
for
theIndeed,
success
ofcarbocation,
this
process
is
that
relatively
temperature
ndered,
compared
their
primary
counterparts
(i.e.,
retarded
fi
cient
toto
generate
the
tertiary
carbocation,
thus
largely
preventing
competing
E1
reactions
cient
generate
the
thus
largely
preventing
competing
E1
reactions
(Section
7-6).
Indeed,
at with
higher
temperatures
(or
the
absence
of low
good
nucleophiles)
tertiary
fi
cient
to
generate
the
carbocation,
thus
largely
preventing
competing
E1
reactions
at
higher
temperatures
(or
ininpreventing
the
absence
of
good
fifi
the
carbocation,
thus
largely
competing
E1nucleophiles),
reactions
tertiary
ficient
cientto
togenerate
generate
thetertiary
carbocation,
thus
largely
preventing
competing
E1
reactions
(Section
7-6).
Indeed,
temperatures
(or
in
absence
of
nucleophiles),
(Section
7-6).
Indeed,
higher
temperatures
(or
inthe
the
absence
ofgood
good
nucleophiles)
generate
the
tertiary
carbocation,
thus
largely
preventing
competing
E1
elimination
becomes
dominant.*
This
explains
why
protonated
secondary
alcohols
show
the
(Section
7-6).
Indeed,
at
higher
temperatures
(or
in
the
absence
of
good
nucleophiles),
becomes
dominant.*
This
explains
why
protonated
secondary
alcohols
show
the
(Section
Indeed,
atat
temperatures
(or
in
the
absence
ofwith
good
nucleophiles),
(Section7-6).
7-6).
Indeed,
athigher
higher
temperatures
(or
in
the
absence
of
good
nucleophiles),
slow
in
forming
carbocations,
compared
their
tertia
elimination
becomes
dominant.*
This
explains
why
protonated
secondary
alcohols
show
the
elimination
becomes
dominant.*
This
explains
why
alcohols
show
the
most
complex
behavior
inof
thethis
presence
of HX,
HX,
following
SNsecondary
2,secondary
S
and
E1
pathways:
They
for
the
success
process
isprotonated
that
relatively
low
tempe
elimination
becomes
This
explains
why
protonated
alcohols
show
theThey
behavior
in
the
presence
of
following
Sthe
Sabsence
1,1,and
E1
pathways:
elimination
becomes
dominant.*
This
explains
why
protonated
secondary
alcohols
show
the
N2,
7-6).
Indeed,
atdominant.*
higher
temperatures
(or
inlow
of
good
nucl
NN
success
of
this
process
is
that
relatively
temperatures
are
sufmost
complex
behavior
presence
of
HX,
following
2,
S
1,
and
E1
They
reactivity);
review
Section
7-9.
Smost
complex
behavior
in
the
presence
of
HX,
following
S(i.e.,
and
E1pathways:
pathways:
They
N2,
N1,
N
N
most
complex
behavior
presence
of
HX,
following
S
2,
S
1,
and
E1
pathways:
They
are
hindered,
compared
with
their
primary
counterparts
retarded
SNN22reactivity),
reactivity)
N1
most
complex
behavior
in
of
HX,
following
SNS
2,S
S
E1
pathways:
They
N
N
inthe
thepresence
N
N
relatively
hindered,
with
their
primary
counterparts
retarded
S
most
complex
behaviorcompared
presence
of
HX,
following
S
S(i.e.,
1,
and
E1
pathways:
They
N
N
N1,
N2,
Nand
n
becomes
dominant.*
This
explains
why
protonated
secondary
alcohols
ate
the
tertiary
carbocation,
thus
largely
preventing
competin
are
relatively
hindered,
with
their
primary
counterparts
retarded
reactivity),
N
are
relatively
hindered,
compared
with
their
primary
counterparts
(i.e.,
retarded
S22NNreactions
2the
reactivity)
ertiary
carbocation,
thus
largely
preventing
competing
are
relatively
hindered,
with
their
primary
counterparts
(i.e.,
retarded
S
reactivity),
hindered,
compared
with
their
primary
counterparts
(i.e.,
retarded
SNE1
2S
reactivity),
and
slow
in
forming
carbocations,
compared
with
their
tertiary
counterparts
N
compared
relatively
slow
in
forming
carbocations,
compared
with
their
tertiary
arerelatively
relatively
hindered,
with
their
primary
counterparts
(i.e.,
retarded
Sin
reactivity),
N
N2counterparts
ction,
here
called
dehydration
because
it(i.e.,
loss
andrelatively
relatively
slow
informing
forming
carbocations,
compared
with
their
tertiary
counterparts
plex
behavior
the
presence
of
HX,
following
S
2,results
Stertiary
and
E1
pathw
and
relatively
forming
carbocations,
compared
with
their
tertiary
counterparts
Ntheir
N1,
slow
inin
carbocations,
compared
with
their
tertiary
counterparts
and
relatively
slow
in
carbocations,
compared
with
counterparts
reactivity);
review
Section
7-9.
(e.g.,
forming
1in
reactivity);
review
Section
7-9.
retarded
Sslow
Indeed,
at
temperatures
(or
in
the
absence
of
good
Nhigher
N
at
higher
temperatures
(or
in
the
absence
of
good
nucleophiles),
1
reactivity);
review
Section
7-9.
(e.g.,
retarded
e(e.g.,
9-1,
breaking
bonds
b
and
c;
see
also
Sections
9-3
and
9-7
N
1
reactivity);
review
Section
7-9.
(e.g.,
retarded
S
reactivity);
review
Section
7-9.
(e.g.,
retarded
SSNS
1
reactivity);
review
Section
7-9.
retarded
N
ely
hindered,
with
their
primary
counterparts
(i.e.,
retarded
S
reaction,
here
called
dehydration
because
it
results
in
the
loss
of
a
molecule
1
reactivity);
review
Section
7-9.
(e.g.,
retarded
SNN1compared
N
The
E1
reaction,
here
called
dehydration
because
it
results
in
the
loss
of
a
molecule
N
N2 r
minant.*
This
explains
why
protonated
secondary
the
omes
dominant.*
This
explains
why
secondary
alc
The
E1
reaction,
here
called
dehydration
because
it
in
the
loss
of
ashow
molecule
The
E1
here
called
dehydration
because
it protonated
results
in 9-3
the
loss
of
a molecule
The
E1
reaction,
here
dehydration
because
it
results
in
the
loss
of
molecule
The
E1
reaction,
here
called
dehydration
because
itresults
results
inalcohols
the
loss
of
aone
molecule
The
E1reaction,
reaction,
here
dehydration
because
itSections
results
in
the
loss
of
molecule
9-1,
breaking
bonds
and c;c;
see
also
9-3
and
9-7),
the
water
(Figure
9-1,
breaking
bonds
bb and
see
also
Sections
and
9-7),
isaaisone
ofofthe
vely
slow
in
forming
carbocations,
compared
with
their
tertiary
co
eof
synthesis
of
alkenes
(Section
11-7).
Rather
than
the
nuc
of
water
(Figure
9-1,
breaking
bonds
b
and
c;
see
also
Sections
9-3
and
9-7),
is
one
of
the
ofin
9-1,
bof
c; c;
see
also
Sections
9-3
and
9-7),
is1,
one
ofone
the
ofwater
water
(Figure
9-1,breaking
breaking
bonds
band
and
c;
see
also
Sections
9-3
and
9-7),
is is
one
of
the
the (Figure
presence
of
HX,
following
2,also
S
1,
and
E1
pathways:
They
of
water
(Figure
9-1,
breaking
bonds
b(Section
and
c;Ssee
see
also
Sections
9-3
and
9-7),
of
the
of
water
(Figure
9-1,
breaking
bonds
b
and
Sections
9-3
and
9-7),
is
one
of
the
methods
synthesis
of bonds
alkenes
11-7).
Rather
than
the
nucleophilic
acids
for
the
synthesis
of
alkenes
(Section
11-7).
Rather
than
the
nucleophilic
acids
N
N
behavior
in
the
presence
HX,
following
S
2,
S
and
E1
N
N
1
reactivity);
review
Section
7-9.
rded
S
methods
for
the
synthesis
of
alkenes
(Section
11-7).
Rather
than
the
nucleophilic
acids
methods
the
synthesis
ofof
(Section
11-7).
thethe
nucleophilic
acids
methods
for
the
synthesis
ofalkenes
alkenes
(Section
11-7).
than
nucleophilic
acids
called
because
the
conjugate
base
is
athan
good
nucleophile,
n
methods
for
the
synthesis
alkenes
(Section
11-7).
Rather
than
the
nucleophilic
acids
methods
for
thecalled
synthesis
alkenes
(Section
11-7).
Rather
than
the
nucleophilic
acids
HBr
called
because
the conjugate
conjugate
base
aRather
good
nucleophile,
nonnucleophilic
andNfor
HI,
so
because
the
base
isisRather
a(i.e.,
good
nucleophile,
nonnucleophilic
compared
with
their
primary
counterparts
retarded
S
2
reactivity),
N
HBr
and
HI,
so
called
because
the
conjugate
base
is
a
good
nucleophile,
nonnucleophilic
ndered,
compared
with
their
primary
counterparts
(i.e.,
retarded
HBr
and
HI,
so
called
because
the
conjugate
base
is
a
good
nucleophile,
nonnucleophilic
and
HI,
so
called
because
the
base
is
nucleophile,
nonnucleophilic
1HBr
reaction,
called
because
results in
the loss of a
HBr
and
HI,
so
called
the
conjugate
base
isisaaagood
good
nucleophile,
nonnucleophilic
HBr
and
HI,
called
because
conjugate
base
goodit
nucleophile,
nonnucleophilic
acids,
PO
or
H2are
SOdehydration
, are
areconjugate
employed.
such
asso
Hhere
H
employed.
2SO
33PO
44 or
44,the
H
SO
acids,
such
as
H
or4H,H
,, employed.
are
employed.
forming
carbocations,
compared
withalso
their
tertiary
counterparts
3PO
4 or
acids,
such
as
HH
are
employed.
32PO
2SO
acids,
such
as
H
PO
H
SO
are
3PO
4 44
2SO
4, 4
4oror
acids,
such
asforming
H
PO
employed.
acids,
such
as
H
SO
are
employed.
333PO
22bonds
444, are
3
44 or H2
Figure
9-1,
breaking
bemployed.
and c; see
Sections
9-3 their
and 9-7),
is o
slow
in
carbocations,
compared
with
tertia
tivity);
review Section
7-9.
Alcohol
Dehydration
by
the
E1
Mechanism
Alcohol
Dehydration
by
the
E1
Mechanism
or 1the
synthesis
of
alkenes
(Section
11-7).
Rather
than
the
nucleophi
reactivity);
review
Section
7-9.
S
R
Alcohol
Dehydration
Mechanism
Alcohol
byby
thethe
E1E1
Mechanism
N called dehydration
AlcoholDehydration
Dehydration
by
the
E1
Mechanism
Dehydration
by
the
E1
Mechanism
Alcohol
Dehydration
by
the
Mechanism
ere
because
results
in
the nucleophile,
loss of a molecule
HI,
so called
because
the
conjugateitbase
isE1aE1
good
nonnuc
OH
Alcohol
Dehydration
by
the
Mechanism
OH
ction,
here
called
dehydration
because
it results
in
the
loss
OH
OH
OH
OH
reaking
bonds
b
and
c;
see
also
Sections
9-3
and
9-7),
is
one
of
the
OH
h as H3PO4 or H2SO4, are employed.
esis9-1,
breaking
bonds11-7).
b Hand
seethan
alsotheSections
9-3 and
9-7
HHSO
, c;
130
140C
SO
130140C
140C
of alkenes
(Section
nucleophilic
acids
SO
, Rather
130
140C
H
,,, ,130
OH
H SO
SO
130
140C
H
SO
130
140C
H
,,
130
140C
H SO
SO
130
140C

HHO
OO

H
O

H
ebecause
synthesis
of
alkenes
(Section
11-7).
Rather
than
the
nuc
the conjugate base is a good

HO

O nucleophile, nonnucleophilic
HH
O
H
O the E1 Mechanism
Alcohol Dehydration
by
87%
r called
H2SO4,because
are employed.
87%
the conjugate
base
is87%
a87%
good nucleophile, n
87%
H
SO
,
130
140C
87%
Cyclohexanol
Cyclohexene
87%
Cyclohexanol
Cyclohexene
Cyclohexanol
Cyclohexene
Cyclohexanol
Cyclohexene
OH
Cyclohexanol
Cyclohexene
Cyclohexanol
Cyclohexene
H3PO4 or H2SO4, Cyclohexanol
are employed.
Cyclohexene
H O
22
2
24
2
2
2
2

44
4
4
4
4
4
4

22
2
2
2
2
2
2
2

Mechanism
thethe
Dehydration
of of
Cyclohexanol
Mechanism
of
the
Dehydration
ofCyclohexanol
Cyclohexanol
Alcohol Dehydration
by theofE1
Mechanism
Mechanism
of
the
Dehydration
Cyclohexanol
Mechanism
Dehydration
Mechanism
of
the
Dehydration
of
Mechanism of
of
the
Dehydration
ofofCyclohexanol
Cyclohexanol
H
HH OH
H Alcohol
O
OHH

H2SO
130Dehydration
140C
Mechanism
of4,the
of Cyclohexanol
HH
HH
H

H
87%
H

D H
G
D

HG

Hby
G
2O the E1 Mechanism
Dehydration
DH
G
D
H
H
GD

H2O

87%
87%
REACTION
Cyclohexene
Cyclohexene
87%
87%

Alcohol Dehydration by the E1 Mechanism

Cyclohexanol
Cyclohexanol

87%
Cyclohexene
Cyclohexene
Cyclohexene
Cyclohexene
Cyclohexene

Cyclohexanol
Cyclohexanol
OHCyclohexanol
Cyclohexanol
Cyclohexanol

Mechanism of
of the
the Dehydration
Dehydration of
of Cyclohexanol
Cyclohexanol
Mechanism
Mechanism
Mechanism
ofofthe
the
Dehydration
Dehydration
ofofCyclohexanol
Cyclohexano
Mechanism
of
the
Dehydration
ofofCyclohexanol
Cyclohexanol
Mechanism
of
the
Dehydrationof
Cyclohexanol
Mechanism
of
the
Dehydration
H2SO4, 130 140C

H2O

H  H
H
H
DH
H
HH
HGD
H

DD
G
OD
HCyclohexanol
H   HGGGH
O

G GD D OOO

H
H
OH
H

OO

OO
H

OO


 H


 H
H

87%
Cyclohexene

O
O






H
Mechanism of the Dehydration of Cyclohexanol
HHH

H  H
G D




 HH2
O

O



 HH2H2
O

O
2O

2


MECHANISM

HH


22,
 H
 the
H
O
HH
O

conjugate base
base of
of the
the acid
acid isis
the
poor nucleophile
nucleophile
HSO
and
proton

In the example,
the conjugate
poor
,H
proton
HSO

O
O
HH
42422
2,and
2

conjugate
base
of
the
acid
the
poor
nucleophile
HSO
and
proton
In the example,
proton
example, the
the conjugate
conjugatebase
baseof
ofthe
theacid
acidisisisthe
thepoor
poornucleophile
nucleophileHSO
HSO
and
proton
44 , ,and
2

4
carbocation is
is observed.
observed. Dehydration
Dehydration of
of tertiary
tertiary alcohols
alcohols
even
loss from the intermediate carbocation
isiseven
intermediate
carbocation
observed.
Dehydration
ofoftertiary
tertiary
alcohols
even
loss from
the
intermediate
carbocation
isisisobserved.
Dehydration
of
isisis
even
from
theoccurring
intermediate
carbocation
observed.
Dehydration
tertiaryalcohols
alcohols
even
slightly
above
room
temperature.
easier,
often
at
slightly
above
room
temperature.
2
In
the
example,
the
conjugate
base
of
the
acid
is
the
poor
nucleophile
HSO
,
and
proton
occurring
at
slightly
above
room
temperature.
easier,
easier, often
often occurring
occurring at
at slightly
slightlyabove
aboveroom
roomtemperature.
temperature.4

loss from the intermediate carbocation is observed. Dehydration of tertiary alcohols is even
easier, often occurring at slightly above room temperature.

Exercise 9-2
9-2
Exercise
he
the
conjugate
conjugate
base
baseofofthe
theacid
acidis isthe
thepoor
poornucleophile
nucleophileHSO
HSO
4
Exercise
9-2
Exercise 9-2
product is
thatis
you
expect from
fromDehydration
theDehydration
reaction of
of 4-methyl-1-pentanol
4-methyl-1-pentanol
with
Write
the
structure
of the product
that
you
expect
the
reaction
with
ntermediate
ermediate
carbocation
carbocation
observed.
observed.
of
of
tertiary
tertiary
alc
a
Write
the
structure
of
the
product
that
you
expect
from
the
reaction
of
4-methyl-1-pentanol
with
structure
of
the
product
that
you
expect
from
the
reaction
of
4-methyl-1-pentanol
with
Writethethe
structure
the Give
product
that
youtheexpect
the reaction ofwith
4-methyl-1-pentanol with
Give
the
mechanism
of its
itsfrom
formation.
Write
structure
of the of
product
that
you
expect
from
reaction
of
4-methyl-1-pentanol
concentrated
aqueous
HI.
the
mechanism
of
formation.
concentrated
aqueous
HI.
the
of
aqueous
HI.
Give
the
mechanism
of
its
formation.
concentrated
HI. Give
theGive
mechanism
ofroom
its room
formation.
concentrated
aqueous
HI.
Give
themechanism
mechanism
ofits
itsformation.
formation.
urring
curring
ataqueous
atslightly
slightly
above
above
temperature.
temperature.

*The
for elimination
at high temperatures
has its origin inhas
its relatively
largein
entropy large
elimination
at high
high temperatures
temperatures
has
its origin
origin
inpositive
its relatively
relatively
large positive
positiveentropy
entropy
*Thepreference
preference
for elimination
at
its
its
*The
preference
for elimination
at
high
has
its
inininits
relatively
large positive
entropy
at
high
has
its
origin
relatively
entropy
(Section
2-1), as two molecules
(alkene 1 H
resulttemperatures
from
one (alcohol),
and
theorigin
DS8
term
the
expression
2O)
*The preference
for elimination
elimination
at
high
temperatures
has
its
origin
inits
its
relatively
large
positive
entropy
molecules
(alkene
1temperatures
H
O)
result7-17).
from
one
(alcohol),
and
theDS8
DS8large
termpositive
in
theexpression
expression
(Section
2-1),
as two
two
molecules
(alkene
1
H
result
from
one
(alcohol),
and
the
term
the
2O)
2O)
DG8 5 DH8
2 TDS8
increases
with temperature
(see
also
Exercise
(Section
2-1),
as
molecules
(alkene
1
H
result
from
one
(alcohol),
and
the
DS8 term
ininthe
expression
1
one
(alcohol),
and
(Section
2-1),2
two molecules
molecules
(alkene
1 HH222O)
O)result
result
from
one
(alcohol),
andthe
theDS8
DS8term
termininthe
theexpression
expression
increases(alkene
with temperature
temperature
(seefrom
alsoExercise
Exercise
7-17).
DG8
5 DH8
DH8
2asTDS8
TDS8
increases
with
temperature
(see
also
Exercise
7-17).
DG8
5
increases
with
(see
also
7-17).
DG8 5 DH8 2 TDS8
TDS8 increases
increases with
with temperature
temperature (see
(seealso
alsoExercise
Exercise7-17).
7-17).

reureofofthetheproduct
productthat
thatyou
youexpect
expectfrom
fromthethereaction
reactionofof4-methyl-14-methyleous
ueousHI.
HI.Give
Givethethemechanism
mechanismofofitsitsformation.
formation.

orelimination
eliminationat athigh
hightemperatures
temperatureshashasitsitsorigin
originin initsitsrelatively
relativelylarge
largep
wo
molecules
molecules
(alkene
(alkene
11
H2H
O)
result
result
from
from
one
one
(alcohol),
(alcohol),
and
and
thethe
DS8
DS8
term
term
i
2O)
DS8
8 increases
increaseswith
withtemperature
temperature(see
(seealso
alsoExercise
Exercise7-17).
7-17).

MECHANISM
Chapter 9

337

Chapter 9

337

REACTION
REACTION

MECHANISM
MECHANISM
MATION
AN I

ANIMATED MECHANISM:
Alcohol dehydration

MECHANISM

H3 O

MECHANISM




REACTION

H3 O

9-3
Fu
u rr tt h
h ee rr
F

R ee aa ccc ttt iii ooo nn

n sss ooo fff AA
A lll cccooohh
hooolllsss aaann
ndd
d ttthh
heee CC
Chh
heeemm
mi iissst ttr rryyy ooof ff EE
Et tthh
heeer rrs ss
Further R

Further Reactions of Alcohols and the Chemistry of Ethers

338
Chapter 9
structure
products that
you expect from the reaction of 1-methylcyclohe
F
u rr tt h
h ee rrofR
Rthe
Fu
ee aa cc tt ii oo nn ss oo ff AA ll cc oo hhoollss aanndd tthhee CChheemmi isst tr ryy oof f EEt thheer rs s
trated HCl and (b) concentrated H2SO4. Compare and contrast the mechani
2
Exercise
9-3 Compare the relative
sses.
(Hint:
and HSO42. Caut
Exercise 9-3 nucleophilicity of Cl
echanisms,
use
arrow
pushing
to
depict
electron
fl
ow;
write
out
everywith
step
the structure of the products that you expect from the reaction of
1-methylcyclohexanol
with
structure of
of the
the products
productsWrite
that
you expect
expect
from
thereaction
reaction
1-methylcyclohexanol
with
Write
that
you
from
the
ofof
1-methylcyclohexanol
Write the
the structure
structure
of
the
products
that
you
expect
the
reaction
1-methylcyclohexanol
with
(a)
concentrated
HCl andfrom
(b) concentrated
H SO .of
Compare
and contrast the mechanisms
of the
Exercise
9-3
Exercise
9-3
complete
structures,
charges
and
relevant
electron
pairs;
and
dra
HCl and
and including
(b) concentrated
concentrated
H(Hint:
SO44Compare
Compare
andnucleophilicity
contrast
the
mechanisms
ofthe
the
(a)
HCl
(b)
HH
and
contrast
the
mechanisms
ofof
two processes.
the
relative
of Cl
and
HSO . Caution:
When
4... Compare
222SO
(a) concentrated
concentrated
HCl
and
(b)
concentrated
SO
Compare
and
contrast
the
mechanisms
the
2
2
2
2
writing
mechanisms,
use
arrow
pushing
to
depict
electron
fl
ow;
write
out
every
step
separately;
F(Hint:
u r tt hh eeCompare
E When
thhWhen
heeer rrsss
pp tt two
e r 9processes.
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tthe
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htheir
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yyCaution:
nucleophilicity
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(Hint:
Compare
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relative
nucleophilicity
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Cl
and
HSO
Caution:
F
u
rrr R
c
iiformulate
sss o
A
llintermediates
aaan
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ooooff ff and
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e
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p t Write
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9processes.
structures,
charges
relevant
pairs;
theconnect
structure
products
that
you
expect
from
the
ofCand
1-methylcyclohexanol
Write
structure
of use
the arrow
products
that
you
expect
from
the
reaction
ofand
1-methylcyclohexanol
with
writing
mechanisms,
to
depict
flfl
out
every
mechanisms,
use
arrow pushing
pushing
to
electron
flow;
ow;
write
outwith
every
stepseparately;
separately;
reaction arrows
todepict
connectelectron
starting materials
or write
intermediates
theirstep
respective
products. Dont
writing
mechanisms,
use
pushing
to
electron
ow;
write
out
every
step
separately;
HClsloppy!)
andarrow
(b) concentrated
concentrated
H2depict
SO44..beCompare
Compare
and
contrast
the
mechanisms
the
uts,(a)
and
dont
be
2SO
concentrated
HCl
and
(b)
H
and
contrast
the
mechanisms
ofofthe
use shortcuts,
and
sloppy!)
formulate
complete
structures,
including
charges
relevant
electron
pairs;
and
2 dont
4 and
complete
structures,
including
charges
and
relevant
electron
pairs;
anddraw
drawexplicit
explicit
2

2
2
formulate
complete
structures,
charges
and relevant
electron
pairs;
andCaution:
draw explicit
2
2 and
two
processes.
(Hint:
Compareincluding
the relative
relative
nucleophilicity
of Cl
Cl2
and HSO
HSO42
When
(Hint:
Compare
the
nucleophilicity
of
Caution:
4 . .products.
two
processes.
reaction
arrows
starting
materials
intermediates
their
Dont
4
to connect
connect
starting
materials or
or
intermediateswith
with
theirrespective
respective
products.When
Dont
reactionmechanisms,
arrows to
to
connect
starting
materials
or
intermediates
with
their
respective
products.
Dont
usebe
arrow
pushing
to depict
depict
electron
flwith
ow;strong
writeacid
outleads
every
stepseparately;
separately;
writing
mechanisms,
use
arrow
pushing
electron
write
out
every
step
Exercise
9-3
In SummarytoTreatment
of alcoholsflow;
to protonation
to give alkyl
use
and
dont
sloppy!)
Exercise
9-3
and
dont
be
sloppy!)
Exercise
9-3
use shortcuts,
shortcuts,
and
dont
be
sloppy!)
complete structures,
structures, including
including
charges
andprimary,
relevant
electron
pairs;inand
andpresence
drawof
explicit
oxonium ions,
which, when
undergo
SN2 reactions
the
good nucleo
formulate complete
charges
and
relevant
electron
pairs;
draw
explicit
philes.
Alkyloxonium
ionsexpect
from from
secondary
or
tertiary
convert
into carbocations
Write
the structure
structure
of
the
products
that
you
from
thereaction
reaction
ofalcohols
1-methylcyclohexanol
with
1-methylcyclohexanol
with
reaction
arrows to
to
connect
starting
materials
or
intermediates
with
their
respective
products.
Dont
Write
the
of
the
products
that
you
the
of
1-methylcyclohexanol
with
reaction
arrows
connect
starting
materials
or
intermediates
with
their
respective
products.
Dont
Write
the alcohols
structure
ofwhich
the
products
that
youofexpect
expect
from
the elimination
reaction
ofto
1-methylcyclohexanol
with
Treatment
of
with
strong
acid
protonation
to
products
substitution
andleads
(dehydration).
(a)dont
mechanismsofof
of the
the
concentrated
HCl
and furnish
(b) concentrated
concentrated
SO44..4. Compare
Compare
and contrast
contrast
themechanisms
mechanisms
(a)
concentrated
HCl
and
(b)
H
and
the
use shortcuts,
shortcuts, and
and
be sloppy!)
sloppy!)
(a)dont
concentrated
HCl
and
(b)
concentrated
HH2222SO
SO
the
mechanisms
of the
the
4 Compare and contrast
use
be
2
2
22
22
two
processes.
(Hint:
Compare
the
relative
nucleophilicity
of
Cl
and
HSO
.
Caution:
When
2 and
In Summary
Treatment
of
alcohols
with
acid
leads
toto
give
HSO
Caution:
When
two
Compare
the
relative
nucleophilicity
of
Cl
HSO
. .to
Caution:
When
Treatment
of(Hint:
alcohols
with
strong
acid
leads
protonation
givealkylalkyl44to
42
ons,
which, when
primary,
undergo
S
2
reactions
in
the
presence
of
go
In
Summary
Treatment
of
alcohols
with
strong
acid
leads
protonation
give
alkyltwo processes.
processes.
(Hint:
Compare
thestrong
relative
nucleophilicity
of protonation
Cl
and
HSO
Caution:
When
4 . to
N
X , S 2to
writing mechanisms, use arrow pushing to depict electron flow; write out every step separately;

ary

writing mechanisms,
mechanisms, use
use arrow
arrow pushing
pushing to
to depict
depict electron
electronflflow;
ow;write
write
outevery
every
stepseparately;
separately;
writing
RX out

H2
O step
N

oxonium ions,
primary,
undergo
SS
inin
presence
ofof
good
nucleowriting when
mechanisms,
use arrow
pushing
depict
electron
ow;
write
out every
step
separately;
which,
when
primary,
undergo
SNNN2tocharges
reactions
inflthe
theelectron
presence
ofand
good
nucleooxonium
ions, which,
which,
when
primary,
undergo
22reactions
reactions
the
presence
nucleoHand
formulate
complete
structures,
including
and relevant
relevant
pairs;
drawinto
explicitca
kyloxonium
ions
from
secondary
or
tertiary
alcohols
convert
andgood
draw
explicit
formulate
complete
structures,
including
charges
electron
pairs;
and
draw
explicit
formulate
complete
structures,
including
charges
and
relevant
electron
pairs;
and
draw
explicit
philes. Alkyloxonium
ions
from
secondary
or
alcohols
convert
into
carbocations,
Alkyloxonium
ions
from
secondary
or tertiary
tertiary
alcohols
convert
into
carbocations,
respective
products.
Dont
philes.
Alkyloxonium
ions
secondary
or
tertiary
alcohols
convert
into
carbocations,
reaction arrows
arrows
to
connect
starting
materials
or
intermediates
with
theirrespective
respective
products.
Dont

reaction
to
connect
starting
intermediates
their
products.
Dont
ROH
Ror
O
O
leads
In
Treatment
offrom
alcohols
with
strong
acid
leads towith
to
protonation
givealkylalkylSummary
Treatment
of
alcohols
with
strong
acid
protonation
toto
give
reaction
arrows
to
connect
starting
materials
or
intermediates
with
their
respective
products.
Dont
 materials
ish
products
of
substitution
and
elimination
(dehydration).
which
furnish
products
of
substitution
and
elimination
(dehydration).
use
shortcuts,
and
dont
be
sloppy!)
products
of substitution
substitution
and elimination
elimination
(dehydration).
use
and
dont
which furnish
of
and
RX nucleouse shortcuts,
shortcuts,
and
dont be
be sloppy!)
sloppy!)
H (dehydration).
oxonium
ions, products
which,
when
primary,
undergo
S 2 reactions
in the presence of good
R  prim

H


X , SN1

oxonium ions, which, when primary, undergo SNNN2 reactions in

H Othe presence of good nucleoR
, E1
R  sec, tert convertHinto
philes. Alkyloxonium
Alkyloxonium ions
ions from
from secondary
secondary or
or tertiary
tertiary alcohols
alcohols
carbocations,
convert into
carbocations,
Alkene
XX
,
S
2

,
S
2
 elimination
X
,elimination
SNN22with
which furnish products
products
of
substitution
and
(dehydration).
of
substitution
and
(dehydration).
givealkylalkyl
In
Summary
Treatment
of
alcohols
strong
acid
leads
to
Summary
Treatment
of
alcohols
with
strong
acid
leads
protonation to
give
alkylRX

H
O
X
,
S

N with strong
In Summary Treatment of alcohols
toto protonation
protonation
toto give
give
alkylRX acid
 leads
H22
O

2
RX

H
O

R

prim
R
 prim
prim
9-3
Carbocation
Rearrangements
goodnucleonucleooxonium
when
primary,
undergo
S
2
presence
oxonium ions,
ions, which,
which,
when
primary,
undergo
reactions
theH
presence
good
nucleoH
R
inininthe
O of
oxonium
ions,
which,
when
primary,
undergo
SSNNNNRX
22 reactions
reactions
the
presence
ofofgood
good
nucleoH
2

H
R

prim

philes.
carbocations,

philes.
Alkyloxonium
ions
from
secondary
or
tertiary
alcohols
convert
into
carbocations,
Alkyloxonium
ions
from
secondary
or
tertiary
alcohols
convert
into
carbocations,
When
alcohols
are,SStransformed
carbocations,
the carbocations
themselves
are subjec

philes.HH
ions
from
orinto
tertiary
alcohols
convert into
carbocations,
HAlkyloxonium
X

H
XX ,,secondary
S N222
O

ROH
O

to
The and
two
known

which furnish
which
of
elimination
furnishR
products
of substitution
substitution
andrearrangements,
elimination
(dehydration).
ROH
Rproducts
O
O
RX
HH222
O

rearrangements.
RX 
 (dehydration).
Oas hydride shifts and alkyl shifts, can

products
of
substitution
and
elimination
(dehydration).
ROH
O
O


 which furnishR



R
prim

primof carbocations. The Xrearranged
occur
with most
types
RR

prim
H
S1NN11 molecules can then undergo furthe
X, ,,SS
H
H
X

RX
SNH
1Hor E1 reactions.
is likely to be a complex mixture,

RX unless we can establish

H
OOThe result
ROH
R
RX
X
2
H
H
H
H O O
2

H
H
XX ,, ,S
SS
22
2O
driving
force
toward
specifi
c product.

 a thermodynamic
RR

RX

H
O
 one

RX
OS 1

R
2,

RO
O
O
H
,
E1

RX

HH222
O

ROH
R
O


RR
sec,

RR

prim
N
H
, E1X
prim
prim
H
sec,tert
tert R
H
 , E1
H
Alkene
R
sec,
tert
X
H
SS1
1N1
XX ,, ,S
Alkene
RX
Alkene
HHydride
H
shifts
give
HH
RX
RX
O new SN1 products
H

H
H RRO
H

H


H
O
ROH
O
2O

ROH
O
O
2O



ROH
RO
O


R

Treatment of 2-propanol with R
concentrated
hydrogen
bromide
gives
2-bromopropane,
a
R
 XX
REACTION 
,
S
1
,
S
1
X
,
S
1
H
,
E1
, S 1 , E1
XH
H, ,E1
E1
H
R
sec,
sec,
sec,tert
tert
RR

sec,
tert
RX

tert H
RX alcohol 3-methyl
expected.R
However,
the more highly substitutedAlkene
secondary
H
RX
O
Alkene
Hof
HH exposure
9-3
H
OO

Alkene

9-3 Carbocation
Carbocation Rearrangements
Rearrangements

2




N
N








N
NN
N




N
N





2
2








NN
N
N

R
2-butanol to the same reaction conditions
a surprising result. The expected
9-3 Carbocation Rearrangements
RR produces
H
H,, ,E1
, E1
E1
H
R
H
E1
sec,
sec,tert
tert
RR

sec,
tert
2 22
2





SN1 product, 2-bromo-3-methylbutane, is only a minor component

of the reaction mixture
Alkene
Alkene
Alkene

When
carbocations,
the
majorcarbocations,
product is 2-bromo-2-methylbutane.
When alcohols
alcohols are
are transformed
transformedtheinto
into
carbocations,
the carbocations
carbocationsthemselves
themselvesare
aresubject
subject
When
alcohols
are
transformed
into
the
carbocations
themselves
are
subject
Carbocation
Rearrangements
to
The
rearrangements,
known
as
hydride
shifts
and
shifts,
9-3
Rearrangements
to rearrangements.
rearrangements.
The two
two
rearrangements,
known
as
hydride
shifts
andalkyl
alkyl
shifts,can
can
to
rearrangements.
The
two
rearrangements,
known
shifts
and
alkyl
shifts,
can
Hydride
Shift inas
the hydride
SN1 Reaction
of an Alcohol
with HBr
Normal
SNtypes
1 Reaction
9-3
Carbocation
Rearrangements
Carbocation
Rearrangements
occur
with
most
of
carbocations.
The
rearranged
molecules
can
then
undergo
further
9-3
Carbocation
Rearrangements
occur with
with
most
types
of carbocations.
carbocations.
The
rearranged
molecules
can
then
undergo
further
of anare
Alcohol
occur
most
types
of
molecules
can
then
further
When
alcohols
transformed
into
carbocations,
the
themselves
are
subject
transformed
into
carbocations,
the carbocations
carbocations
themselves
are
subject
H The
OH rearranged
H Br
Br Hundergo
S
1
or
E1
reactions.
The
result
is
likely
to
be
a
complex
mixture,
unless
we
can
establish
When
alcohols
are
transformed
into
carbocations,
themselves
are
subject
Rearrangement)
WhenThe
are
subject
A Ato
Athe
Acarbocations
Athemselves
A
alcohols
are
transformed
into
carbocations,
the
carbocations
are
subject
When
alcohols
are
transformed
into
carbocations,
the
carbocations
themselves
are
subject
SNN11rearrangements.
or E1
E1(No
reactions.
The
result
is likely
likely
be
complex
mixture,
unless
we
can
establish
HBr,
0C as hydride
to
two
rearrangements,
known
shifts
and
alkyl
shifts,
can
S
or
reactions.
The
result
is
to
be
aa complex
mixture,
we
can
establish
The
two
rearrangements,
known
asCHhydride
shifts
and
alkyl
can
O
CH
CCH
 unless
CH
CCH
shifts,
HO OH
3Crearrangements,
3
3C O
3
3C O
3
The
two
known
as
hydride
shifts
and
alkyl
shifts,
can
shifts,
can
rearrangements.
The
two
rearrangements,
known
asCCH
hydride
shifts
and
alkyl
shifts,
can
aa Nthermodynamic
driving
force
toward
one
cc product.
to rearrangements.
rearrangements.
The
two
known
as
shifts
alkyl
shifts,
can
OHto
Arearrangements,
A specifi
A carbocations
A hydride
A and
A themselves
hols
are
into
carbocations,
the
thermodynamic
driving
force
toward
one
specifi
product.
with transformed
most
types
of
carbocations.
The
rearranged
molecules
can
then
undergo
further
aoccur
thermodynamic
driving
force
toward
one
specifi
crearranged
product.
A occur
types
ofmost
carbocations.
The
molecules
cancan
then
further
with
types
of
carbocations.
The
then
undergo
further
occur
undergo
further
H
H rearranged
H
Hmolecules
Hcan
Hundergo
with
most
types
of
carbocations.
The
rearranged
molecules
then
undergo
further
3C
3C
3C then
occur
with
most
types
of
carbocations.
The
rearranged
molecules
can
undergo
further
CH3CHCH3  HBr
Minor
product
Major
product
S
1
or
E1
reactions.
The
result
is
likely
to
be
a
complex
mixture,
unless
we
can
establish
S
1
or
E1
reactions.
The
result
is
likely
to
be
a
complex
mixture,
unless
we
can
establish
ements.
The
two
rearrangements,
known
as
hydride
shifts
and
alkyl
N
SN1 or E1 reactions.
The
result is
likely
be
a to
complex
mixture,
unless
wewe
can
or E1
establish
E1 reactions.
reactions.
The
resultto
likely
to be
be aa complex
complex
mixture,
unless
we
canestablish
establish
SNNN110Cor
The
result
isis likely
mixture,
unless
can
establish
3-Methyl-22-Bromo-32-Bromo-2aa thermodynamic
force
toward
one
ccc product.
shifts
give new
Stoward
products
a thermodynamic
driving
force
one
specifi
ccspecifi
product.
thermodynamic
driving
force
toward
one
specifi
product.
driving
force
toward
one
specifi
product.
N1
butanol
methylbutane
methylbutane
aHydride
thermodynamic
driving
forcedriving
one
specifi
product.
Hydride
shifts
give
new
Stoward
most
types
ofthermodynamic
carbocations.
The
rearranged
molecules
can then unde
N1 products
N
(Normal product)
(Rearranged product)
Br
A
Treatment ofCHCH
2-propanol
with
concentrated
hydrogen
bromidemixture,
gives 2-bromopropane,
asca
reactions.
is give
likely
toSSmechanism
be
aof complex
weundergo
HO OH
Hydride
shifts
1
products
3 The
3  result
TreatmentCHof
2-propanol
with
concentrated
bromideThe
gives
as
Hydride
What
is the
this transformation?
answer2-bromopropane,
is thatunless
carbocations can
shifts
give
new
SNNNhighly
1hydrogen
products
Hydride
shifts
give
new
1
products
shifts
give
new
S
11new
products
expected. However,
exposure
of
more
substituted
secondary
alcohol
3-methylHydride
new
SNthe
products
rearrangement
by hydride
shifts,
in which the secondary
hydrogen (yellow)
moves with
both electron
Nthe
expected.
However,
exposure
of
more
highly
substituted
alcohol
3-methylTreatment
of
2-propanol
with
concentrated
hydrogen
bromide
gives
2-bromopropane,
as
ynamic
driving
force
toward
one
specifi
c
product.
REACTION
2-bromopropane,
as
Treatment
of 2-propanol
2-propanol
with concentrated
concentrated
hydrogen
bromide
gives
2-bromopropane,
Treatment
bromide
2-bromopropane,
asas
REACTION
2-butanol to the
same
reaction
produces
a surprising
result.
The expected
fromconditions
its with
original
position
to the hydrogen
neighboring
carbon
atom.gives
Initially,
protonation
of the alcoho
ANIMATED
MECHANISM:of
Treatment to
of
2-propanol
with
concentrated
gives
2-bromopropane,
asas
expected.
However,
exposure
of
the
more
highly
secondary
alcohol
2-butanol
the
same
reaction
conditions
produces
asubstituted
surprising
result.
The
expected
Carbocation
rearrangement
by loss
of
water
gives
thebromide
expected
secondary
carbocation.
A shift3-methylof the tertiary
Treatment
of 2-bromo-3-methylbutane,
2-propanol
with followed
concentrated
hydrogen
bromide
gives
2-bromopropane,
3-methylexpected.
However,
exposure
ofonly
thehydrogen
more
highly
substituted
secondary
alcohol
3-methylexpected.
However,
exposure
of
the
more
highly
substituted
secondary
alcohol
3-methylSN1 product,
isthe
a minor
component
of
the
reaction
mixture;
hydrogen
to is
electron-defi
cient
neighbor
then
generates
a alcohol
tertiary
cation,
which
is mor
2-butanol
to
reaction
conditions
produces
aasecondary
surprising
result.
The
expected
SNN1 product,
2-bromo-3-methylbutane,
only
a minor
component
of the
reaction
mixture;
expected.
However,
exposure
of
the
more
highly
substituted
3-methylexpected
2-butanol
to the
the same
same
reaction
conditions
produces
asecondary
surprising
result.
The
expected
2-butanol
to
the
same
reaction
conditions
produces
surprising
result.
The
expected
expected.
However,
exposure
of
the
more
highly
substituted
alcohol
3-methylthe major product
is
2-bromo-2-methylbutane.
stable. This species is finally
trapped by bromide
ion to giveofthethe
rearranged SN1mixture;
product.
S
product,
2-bromo-3-methylbutane,
is
component
mixture;
product,
2-bromo-3-methylbutane,
only aaaaminor
component
ofthe
thereaction
reaction
mixture;
SNNN111same
product,
2-bromo-3-methylbutane,
isis only
only
minor
component
of
reaction
mixture;
the major product
is
2-bromo-2-methylbutane.
2-butanol
to
reaction
conditions
surprising
result.
The
2-butanol
to the
the
same
reaction
conditions produces
produces
aminor
surprising
result.
The expected
expected
the
major
product
is
2-bromo-2-methylbutane.
the
the major
major product
productNis
is 2-bromo-2-methylbutane.
2-bromo-2-methylbutane.
SNN11 product,
S
product, 2-bromo-3-methylbutane,
2-bromo-3-methylbutane, isis only
only aa minor
minor component
componentofofthe
thereaction
reactionmixture;
mixture;

rbocation Rearrangements

MATION
AN I

shifts give new S 1 products

Normal SN1 Reaction

of an Alcohol
(No Rearrangement)
OH
A
CH3CHCH3  HBr
0C

Br
A
CH CHCH  HO OH

Br
A
CH3CHCH3  HO OH

ATION
N IM

ANIMATED MECHANISM:
Carbocation rearrangeme

major product is 2-bromo-2-methylbutane.

major
2-bromo-2-methylbutane.
major product is 2-bromo-2-methylbutane.
Hydride
Shift
in
the
Reaction
of
an
Alcohol
with
HBr
the
Reaction
of
an
Alcohol
with
HBr
Shift
in
Reaction
of
an
Alcohol
with
HBr
Hydride
in
the
SS
Reaction
Alcohol
with
Shift
inthe
theSS
SNNNN1NN1111Reaction
Reaction
of
an
Alcohol
with
HBr
Hydride Shift
Shift in
ofof
anan
Alcohol
with
HBrHBr
H
H
Br
Br
H
Br
H
H
Br
Br
H
HH OH
OH
H
Br
Br
H
H BrBr
H
OH
HA
Br Br
A
AAH A
AA A
AA
HBr,
HBr, 0C
0C
A AAAAA
A
AAA
A AAA
A AAA
HBr,
0C
HBr, 0C
0C
O
O
O
CCO
CCH
CH
CCH
CH
CCH

O
O
O
CH
CCH

CH
C
CCH

H
OH
C
CH
3
3
33C
3333 
33O
33
O
O

CH
C
CCH

H
OH
33C
33C
O
O
O
CCH
CH
C
CCH

CH
C
CCH

H
OH
CH
3
333
O
O
CH
CCH
CCH
CH
C
CCH
HOH
OH
CH
33C
33
O
O
O
OOH
CH
C
CCH
CH
C
CCH

CH
C
CCH

HO
OH
3
3
3
3
3
3
3
3A
3
3A
3
AA A
A
A
A
A
A
A
A
A
A
A
A
A
A
AA A A
A AA A
A AA
A
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
3
3
3
H
C
H
3
3
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C
H
3 H333
H33C3 H
H3333C H
H
3C
Minor
product
Minor
product
Minor
product
Minor
product
Minor
product

3-Methyl-23-Methyl-23-Methyl-23-Methyl-2butanol
butanol
butanol
butanol

Major
product
Major
product
Major
product
Major
product
Major
product
Major
product

Minor product
2-Bromo-32-Bromo-32-Bromo-32-Bromo-32-Bromo-32-Bromo-3methylbutane
methylbutane
methylbutane
methylbutane
methylbutane

Major product
2-Bromo-22-Bromo-22-Bromo-22-Bromo-22-Bromo-22-Bromo-2methylbutane
methylbutane
methylbutane
methylbutane
methylbutane

(Normal
product)
(Normal
product)
(Normal
product)
(Normal
product)
(Normal
product)

(Rearranged
product)
(Rearranged
product)
(Rearranged
product)
(Rearranged
product)
(Rearranged
product)

methylbutane

(Normal
(Normalproduct)
product)

methylbutane

(Rearranged
(Rearrangedproduct)
product)

Whatisisthe
themechanism
mechanism of
of this
transformation?
The
answer
is that
carbocations
can undergo
What
transformation?
The
answer
is
that
carbocations
can
unde
transformation?
The
answer
is
that
und
carbocations
can
carbocations
can
is
of
this
The
is
can
What
of this
this
The
answer
is
that
und
und
What
is the
the mechanism
mechanism
this transformation?
transformation?
Theanswer
answer
isthat
thatcarbocations
carbocations
canunde
und
rrangement
byhydride
hydride of
shifts,
in
which
the
hydrogen
(yellow)
moves
withwith
bothboth
electrons
by
shifts,
in
which
the
hydrogen
(yellow)
moves
electr
angement
(yellow)
moves
with
both
elec
by
hydride
shifts,
in
which
the
hydrogen
(yellow)
moves
with
both
elect
both
electr
the
angement
byposition
hydrideto shifts,
in which
whichcarbon
the hydrogen
hydrogen
(yellow)
moveswith
with
both
elec
m
itsoriginal
original
the
neighboring
atom.
Initially,
protonation
of
the
alcohol
position
to
the
neighboring
carbon
atom.
Initially,
protonation
of
the
its
carbon
atom.
Initially,
protonation
of
the
alc
neighboring
the
atom.
Initially,
ofof
the
alco
alc
the neighboring
atom.
Initially, protonation
protonation
oftertiary
thealco
alc
its original
original
position
togives
the
neighboring
carbon
atom.
Initially,
protonation
the
alc
lowed
by lossposition
of waterto
the expectedcarbon
secondary
carbocation.
A
shift of the
wed
by
loss
of
water
gives
the
expected
secondary
carbocation.
A
shift
of
the
tert
secondary
carbocation.
A
ter
the
expected
shift
of
the
shift
of
the
by
loss
of
water
gives
the
expected
secondary
carbocation.
A
shift
of
the
tert
ter
wed
gives
secondary
carbocation.
A
te
drogen
the of
electron-defi
cientthe
neighbor
thensecondary
generates acarbocation.
tertiary cation,
whichofis the
more
wed bytoloss
water gives
expected
A shift
te
to
the electron-defi
cient
neighbor
then
generates
a tertiary
cation,
which
is
m
ogen
then
generates
tertiary
neighbor
cation,
which
is
m
cation,
which
is
m
to
electron-defi
cient
then
tertiary
which
ogen
electron-defi
cient
then
generates
tertiary
ble. This
species
is finally trapped
by bromide
iongenerates
to give theaaaa rearranged
SN1 product.
ogen
to the
the
electron-defi
cient neighbor
neighbor
then
generates
tertiary cation,
cation,
which is
is m
This
species
is
fi
nally
trapped
by
bromide
ion
to
give
the
rearranged
S
1
product.
e.
bromide
ion
to
give
the
rearranged
product
N
trapped
by
S
1
S
1
product.
This
species
is
fi
nally
trapped
by
bromide
ion
to
give
the
rearranged
S
1
product.
N
e.
nally
bromide
ion
to
give
the
rearranged
product
N
e. This species is finally trapped by bromide ion to give the rearranged SNNNN1 product

MATIIOONN
AN I

ANIMATED
ANIMATEDMECHANISM:
MECHANISM:
Carbocation
Carbocationrearrangement
rearrangement

What
is is
that
carbocations
cancan
undergo
Whatisisthe
themechanism
mechanismofofthis
thistransformation?
transformation?The
Theanswer
answer
that
carbocations
undergo
rearrangement
with
both
electrons
rearrangementby
byhydride
hydrideshifts,
shifts,ininwhich
whichthe
thehydrogen
hydrogen(yellow)
(yellow)moves
moves
with
both
electrons
of of
thethe
alcohol
from
fromits
itsoriginal
originalposition
positiontotothe
theneighboring
neighboringcarbon
carbonatom.
atom.Initially,
Initially,protonation
protonation
alcohol
followed
thethe
tertiary
followed by
byloss
lossofofwater
watergives
givesthe
theexpected
expectedsecondary
secondarycarbocation.
carbocation.A Ashift
shiftof of
tertiary
hydrogen
cient
is is
more
hydrogen toto the
theelectron-defi
electron-defi
cientneighbor
neighborthen
thengenerates
generatesa atertiary
tertiarycation,
cation,which
which
more
stable.
SNS1Nproduct.
stable.This
Thisspecies
speciesisisfifinally
nallytrapped
trappedbybybromide
bromideion
iontotogive
givethetherearranged
rearranged
1 product.

9-3 Carbocation Rearr

9-3 Carbocation Rearra

Carbocation Rearrangem
arrbboR
occae
attiaioornnr R
9 - 3 C a r b o c a9999---t-33339i -oCCCC3aan
aReenaargrrraeannm
emmmeeeneennnnntttttstsssss
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R
a rr bb ooo cccaaatttiiiooonnn R
Reeeaaarrrrrraaannngggeeem
r
rb
em
99----33
33 CC
CCaaaarrrb
bbooooccccaaaatttitiioiooonn
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RR
mm
99
eeeaeaararrrrraraananngnggegeem
eeenenntnttssst s

Mechanism
of Carbocation
Rearrangement
Mechanism
of Carbocation
Rearrangement
Mechanism
of
Carbocation
Rearrangement
Mechanism
of Carbocation
Carbocation
Rearrangement
Mechanism
of
Carbocation
Rearrangement
Mechanism
Rearrangement
of
Rearrangement
Carbocation
Rearrangement
Mechanism
of
Carbocation
Rearrangement
Mechanismof
ofCarbocation
CarbocationRearrangement
Rearrangement
Mechanism
of
Carbocation
Rearrangement
Mechanism
Step 1.
1.
Protonation
Step
2. of
Loss
of
water
Step
Step
2.
Loss
ofwater
water
Step
1.
Protonation
Step
2.
Loss
of water
Protonation
Step
2.
Loss
of
water
1.
2.
Loss
of
water
Step
2.
Loss
Step
Step
2.
Loss
of
water
ation
Step
2.
Loss
of wate
sm
Carbocation Rearrangement
1. Protonation
Protonation
Step
2.
Loss
of
water
Protonation
Step2.
2.Loss
Lossof
ofwater
water
Step of
Step
2.
Loss
of
water
1.
Protonation
Step
H
H H H
H H H HH H H
H
H
H
H
H
H
H
H
H
H
H
H

D
G
G
D
GG
G
DH
HG
HH
HStep
HD  D Loss
H
H
H
H

G
D
H
H
H

of
water
G
D
DD
D


D
GG

DOG2.
G

H
H
OH
O
HGG
O

DD


D
DD
H
H
OH
D
D O GO
H
OH
H HHHHHAHHHA HA H
H HHHHAHHA GGGHGAOOOOOAOOADH

 O H
H
O
H
O

H
OH
H
OH

O
H
O
H
AAA
AH
AH
AAA
A O
A H

H
OH

A
A
A

A
A
A
A
AAAAA 
AAOAAAA GA DA
 A
G33ACACAO
DACCH

A A 33 ACH
ACCH
ACC
A3C

AAAO CCH
AA A 3  H



O
O
O
OCCH
O
CH
CCH
CH
CCH

H
O
CH333A3C
CH
CH
CCH
CH3A33C
CO
CCH
H
H
O




3C
33
3 3
2




O
O
O
O
O33CCH
O
OCCH
H
CH
CCH
CH
C
CCH

H
O

 
CH
C
CCH
CH
CCH
O
CH
CH
CCH
H
H
CH
CCCH
CCH
C
CH
CCH

33 3
33O 3 CH
O
O
O

333C
33 
CH
CH
CCH
C
CCH
CH
C
CCH
H
H
O
C
CCH

H
CH
O
O
O
3O
3CH
3CCH

CH
CCH

H
O


3C
3C
23
O
O

CH
CH
C
CCH
C
CCH
O
CCH

H
CH
C
CCH
C
CCH
CH
C
H
O
333C
3333 CCH
3C
3C
222
H
H
O
AAC
A
A
A
A
A
O
O
O
A
A
A
A
AO
A3C

CH
CH33H
C
CCH
CH
CCH
CH
CCH
O
O
O
3
3
3
3
3
3333
22
3
3
3
3
3
3 
2
O
O
O
O
33
3
3
3
3
3
3
2H
CH
CH
C
CCH

H
CH
C
C
CCH
C

3
3
3
3
3


A
A
A
A
A
AAAAAO
AAAAACCH
3AA AAA 3 A
3A
A
A3CH
A3HC
H
AAA AAAA H3
AA AAAAA3 H
A
A
A
A
A
A
A
A
A
A
H
H
C
H
H
CC AH
HH AA A H
H
H
H
H333G
CAH
H
H3333C
H333C
C H
H
A
A
A
A
A
A
3C
A
A
3C
H
C
H
C
H
H
H
C
H
3

3
G
D
D
H3333C
H
C
H
H
H
H
CH3H
H
C
H
HH
HH
3C
3C
3C
H
H
H
H
H
H3333C
C 3CH
H H
H
H H
H3C
C H
H
HH
H
CC H
H
H
3C
3C H
3333C
H3H
C OH
H3C H CH
H3CCCH
H H333C3 H CH
H3CC O
H
H
O
H
O3 CCH
O

CH3CH
3
3C
3
3


Step
3.
Hydride
shift
Step
4.
Trapping
by
bromide
Step4.
Trappingby
bybromide
bromide
Step
shift
4.
by
bromide
Step
Trapping
Step
Hydride
Step
4.
Trapping
by
bromide
shift
Step
4.
Trapping
by
bromide
A 3.3.3.3. Hydride
AHydrideshift
ATrapping
AStep
A4.4.Trapping
A
Step
shift AA AA
Step
4. Trapping
by bromide
Step
Hydride
shift
Step4.
Trapping
bybromide
bromide
Hydride
Step
4.
Trapping
by
bromide
by

3. CCH
Hydride shift
Step 4. Trapping
by
O
CH
HStep

H
Obr
H3C3CHHHHOHCCH3 H3CHHHHHCHH
>
>H
)
Br)
H
3CH
3
3C O CCH3)
2
3C
)
Br)
H
>
>
Br)
H
)
Br)
H
>
>
>
)
Br)
H
)
Br)
H
>
>
H
)
Br)
H
H
A
A
A
H
)
Br)
H
>
A
H
H
)
Br)
H
H
A
A
A
A
H
)
Br)
H
AHHHAAAAH A
A
A
A
A


A
A
A
A
A
A




AA A  )Br
AA A


AACAAO
ACCH
AAA A


AAACCH

OA

>





O
>
CH
C
)
CH
AHO
CCH
CH
C
O

O



OACCH
O
O
CH33333C
C
CCH
)
)
Br
)
CH3A33C
CO
CCH
CH333
C
CCH3333H
>
33

33C
3

>
p
O
3C

 CCH
CH
C
CCH

)
Br
)
CH
C
CCH
CCH
O
O

)
Br
)
CH
CCH
CH
CH
C
p
H
 CH
>
33333
>
33
O
O CCH
O
3C
3
CCH
CH

Br
)
CCH
p
O
O
>
CH
C
CH
C
CCH
)
Br
)
CH
C
CCH
CH
p
>
3C
CH
))
Br
)
CCH
CH
3C
33A
OCCH
O
HCH
H
CCCH
C
O
O
O
O
AAC
AH
ACO
AACCH
CH

)
Br
)H
CH
C
CH
CCH
Br
)
CH
CCH
CH
CCH
CH
p
C
CCH
333C
3333CCH
333C
333
33333C
3333H
p
AO
AO
AOH
A C33333O
A CCH
p
>
3CH
3
3
3
3C3333C
3
AAAO
AAAC
AAACCH
AAAAACCH
OCCH
ACCH
C

)Br
)CH
CH
CH
3AA
3Ap
3
3
AAAA33C AO
A
A
A
p
A
A
A
A
A
A
A
A
A
A
A
eCH
shift
Step
4.
Trapping
A
A
A
A3 by
A
A
A




H CC H
H
H
C
H
H
H
C H
H A
H333C
C AH
H
H
3C
H
HH333C
HH A
HA
H333C
CA H
H
C
HH3333C
C HAH A
H
C
H
H
3333C
H
H
CH
CO
HSecondary
HCCH3
33C
Secondary
HSecondary
Secondary
3C
Secondary
A HA
Secondary
Secondary
carbocation
carbocation
carbocation
carbocation
Secondary
carbocation
carbocation
carbocation
carbocation
H
H
C
(Less
3 stable)
(Less
stable)
(Less
stable)
(Less
stable)
(Less
carbocation

H
C
H
H
H
C
CH
CO
CCH3
H
H33333Tertiary
C C3H
3H
Tertiary
H
Tertiary
3
Tertiary
A A
Tertiary
Tertiary
Tertiary
Tertiary
carbocation
carbocation
carbocation
carbocation
Tertiary
carbocation
carbocation
carbocation
carbocation
H
H
(More
stable)
3C
(More
stable)
(More
stable)
carbocation

H
C H
H C O CCH3
H
H
3C
CH
3C
3333
H
3CHH
CH 3H
3

H
HH
>
H
C H
33C
 )HH
Br)
3C
33C
3H
HC C
3C HH
p
3

Step 4. Trapping
bromide
H3C by
(Less stable)
stable)
(More stable)
stable)
H H
H(More
(Less
stable)
(Less
stable)
(More
stable)
(Morestable)
stable)
Secondary
Tertiary
(Less
stable)
(More
stable)
Ashift are shown schematically
A carbocation

 the transition
carbocation

The
details
of
state
of the
the
observed
hydride
transition
stateof
theobserved
observedhydride
hydrideshift
shiftare
areshown
shown
schematically
state
observed
hydride
shift
are
shown
schematically
The
details
of the
the
transition
hydride
shift
are
shown
schematically
shown
schematically
details
of
state
schematically
transition
state
the
observed
hydride
shift
shown
schematically
The
the
transition
state
the
observed
hydride
shift
are
shown
schematically
>
>
Hofofofof
)
H isisisis
The stable)
details
ofsimple
the transition
transition
state
ofthe
thewhen
observed
hydride
shiftare
are
shown
schematically
Ohydride
Hin
O
CH
CCH

)Br)
Br)
CH
C
CCH
(Less
(More
stable)
in
Figure
9-2.
rule
to
executing
hydride
shifts
in
carbocations
3C
3shifts
3A
3 remember
p
rule
to
remember
when
executing
hydride
in
carbocations
remember
when
executing
shifts
in
carbocations
Figure
9-2.
A
simple
rule
to
hydride
shifts
in
carbocations
in
remember
when
executing
hydride
shifts
in
carbocations
isis
9-2.
A
simple
rule
to
remember
executing
hydride
shifts
in
carbocations
isis
shifts
in
carbocations
The details
of
theAtransition
state
ofwhen
the observed
hydride
shift
are
shown
schema
in
Figure
to
remember
when
executing
hydride
shifts
in
carbocations
9-2.
A
simple
rule
to
remember
when
executing
hydride
in
Figure
A
simple
rule
to
remember
when
executing
hydride
shifts
in
carbocations
is
A
A
AneighAthat
A
A
A
that
the
hydrogen
and
the
positive
charge
formally
exchange
places
between
the
two
neigh
positive
charge
formally
exchange
places
between
the
two
neighthe
positive
charge
formally
exchange
places
between
the
two
neigh
the
hydrogen
and
exchange
places
between
the
two
neighthat
the
positive
charge
formally
exchange
places
between
the
two
the
positive
charge
formally
exchange
places
between
the
two
neighand
the
hydrogen
charge
formally
exchange
places
between
the
two
neighin
Figure
9-2.
A
simple
rule
to
remember
when
executing
hydride
shifts
in
carbocati
the
positive
charge
formally
exchange
places
between
the
two
neighthat
the
hydrogen
and
the
positive
charge
formally
exchange
places
between
the
two
neigh>
boring
carbon
atoms
participating
in
the
reaction.
O
O
CH
C
CCH

)
Br
)
CH
C
CCH
atoms
participating
in
the
reaction.
CCH
boring
participating
in
the
reaction.
H
C
H
H
H
C
carbon
The
details
of
the
transition
state
of
the
observed
hydride
shift
are
shown
atoms
3
3
3
3s
3
boring
atoms
participating
in
the
reaction.
3
participating
in
the
reaction.
3
p
participating
in
the
reaction.
atoms
that
thecarbon
hydrogen
and
the positive
formally
exchange
places
between
boring
carbon
atoms
participating
in charge
the
reaction.
Hydride
shifts
of
carbocations
are
generally
very
fast

faster
than
or
E1
reactions.
N
of
carbocations
are
generally
very
fast

faster
than
or
E1
reactions.
shifts
carbocations
are
generallyvery
very
fast

fasterthan
thanShydride
or
E1
reactions.
AE1
Arule are
A in
Athe intwoca
A in
Hydride
faster
than
SNSS
or
E1
reactions.
N
of
than
SS
111111or
or
E1
reactions.
shifts
shifts
carbocations
generally
fast

faster
1N1N1
reactions.
carbocations
are
generally
very
fast

faster
than
SS
or
E1
reactions.
N
Hydride
carbocations
are
generally
very
fast

faster
than
or
E1
reactions.
Figure
9-2.
Aof
to
remember
when
executing
shifts
N
shifts
of
Tertiary
NN
Hydride
shifts
ofsimple
carbocations
are
generally
very
fast

faster
than
S
or
E1
reactions.
boring
carbon
atoms
participating
the
reaction.
N
In
part,
this
rapidity
is
due
to
hyperconjugation,
which
weakens
the
C

H
bond
(Section
7-5
is
due to
to
hyperconjugation,
which
weakens
the
C
H
bond
(Section
7-5
rapidity
toC
hyperconjugation,
whichweakens
weakensthe
theCC
CH
H
bond
(Section
7-5
weakens
the
C
H
bond
(Section
7-5
isand
H
bond
(Section
7-5
In part,
due
to
rapidity
rapidity
is
hyperconjugation,
which
C
bond
(Section
7-5
hyperconjugation,
which
weakens
bond
7-5
In
part,
this
rapidity
hyperconjugation,
which
weakens
the
C
H
H
bond
(Section
7-5
is
due
to
H
Harecharge
H
Hstable
HIn
that
thethis
hydrogen
the
positive
formally
exchange
places
between
th
In
part,
this
rapidity
is due
due
toparticularly
hyperconjugation,
which
weakens
the
H
bond
(Section
7-5
3C
Hydride
shiftsThey
of
carbocations
generally
very
the
faster
than
Sis(Section
1more
or
E1
reac
carbocation
and
Figure
are
favored
when
the
new
carbocation
is
more
stable
Nmore
They
are
favored
when
the
new
carbocation
is
and
Figure 9-2B).
9-2B).
are3 particularly
particularly
favored
when
thefast
new
carbocation
stable
9-2B). They
and Figure 9-2B).
They are
when the
thenew
newcarbocation
carbocationisisismore
morestable
stable
are particularly
particularly favored
favored when
when
the
new
carbocation
more
stable

They
are
particularly
favored
when
the
isis
and
Figure
9-2B).
particularly
favored
when
the
new
carbocation
more
stable
andpart,
Figure
9-2B).
They
are
particularly
favored
when
thenew
newcarbocation
carbocation
ismore
morestable
stable
boring
carbon
atoms
participating
in
the in
reaction.
In
this
rapidity
is in
due
toexample
hyperconjugation,
which
weakens
the C H
bond
(Sectio
than
the
original
one,
as
in
the
example
depicted
in
Figure
9-2.
ythan
one,
as
in
the
example
depicted
in
Figure
9-2.
the
example
depicted
inFigure
Figure9-2.
9-2.
(More
the
original
9-2.
one,stable)
one,
as
the
depicted
as
in
the
in
9-2.
than
the
the
example
depicted
in
Figure
9-2.
one,
as
the
than Hydride
the original
original
one,They
as in
in
the example
example depicted
depicted
inFigure
Figure
9-2.
and
Figure
9-2B).
are
particularly
favored
when
the
new
carbocation
is
shifts
of
carbocations
are
generally
very
fast

faster
than
S
1 or
ion
Nmore
Migrating
hydride
thanpart,
the this
original
one, as
in thetoexample
depicted
in Figure
9-2.
Migrating
hydride
In
rapidity
is due
hyperconjugation,
which
weakens
Migrating
hydride
the C H bond
Migrating
hydride
Migrating
hydride
Migrating
hydride
Migrating
hydride

Migrating
hydride
Migrating
hydride
ble)

Migrating hydride
andthe
Figure
9-2B). They
areof
particularly
favored hydride
when the new
carbocation
H
of
state
the observed
shift
are showis
H transition
H
H
Migrating
hydride
H
H

H
H
H
than
the
original
one,
as
in
the
example
depicted
in
Figure
9-2.
H
HH
H
H CCin
+
+hydride shifts
H
H
A simple rule +to remember
when executing
H

+
+
HH
C
H
3C
C
HH
CC
++
++++
3H
H
H
++
++
H
3H
+++++
333C
H
333C
C the observed
C
C
H
C
+C
+C
stateH of
hydride shift
+
C
C
C
CC
C
C + schematically
Care shown
C
C
C
C
C
C
C
C
C
en
and CCCCthe positive
charge
formally
places
between
C
C
Cexchange
H
H
H
CH
C
H
Migrating
hydride
C
H
H
H
333C
C
H
3
3
C
H
H
H
3
CH

C
H
C
H
H
C
H
H
H
C
H
C
H
3
3
CH
CH3H
C
33
CC
H
3H
HH
H
remember
when
hydride
shifts
inCHcarbocations
is
3333
CH
3H
HH
H
H
CH
+ executing
333C
333C
C
C
H +
H333C
H33333CC
CHin
C
H
+
3
H
atoms
the reaction.
C
CH
H
C participating
H3333C
CH
H
CH
C
CC
CH
H
CH
H
C
CH
H
33
3333333
C sp
Csp
C
C
33C
sp
CH
H
sp
CH
H
3C
33
sp
sp formally
Ccarbons
CH
H33333CC
sp
sp
veHHHcharge
exchange
places
between
the
two
neigh3CH
3
sp
are
rehybridizing
sp
Both
are
rehybridizing
Both
carbons
rehybridizing
carbons
are
rehybridizing
sp
Both
carbons
are
rehybridizing
sp
Both
carbons
are
rehybridizing
Both
carbonsare
are
rehybridizing
C
Hthan SN1 o
H
H3very
Both
carbons
are
rehybridizing
H
fts
are3 generally
fast
faster
Both
carbons
A
3Cof carbocations CH
A
Both
carbons are
are rehybridizing
rehybridizing
A
A in the reaction.
H
ng
+
+
A
+
33
3333
3
3

H
H
H

2
2222
222
2

H 3C

than the original one, as in the example depicted in Figure 9-2.

H33C
C
HH
H
3C
H

A
H3C
H3C
H3C
A
A

C
+
C

C
C

H3C C
H3CH3C C
3
H3CH3C

+
C
+

Migrating hydride

Both carbons are rehybridizing

H33CC
H
+

H
H

C+
C

C
C

sp2
sp2

sp3
sp3

H
CH3H
CH3

Hyperconjugation

B
B

H
Both carbons
are rehybridizing
rehybridizing
are
H3C
HBoth carbons
+
C +
H3C

C
C
H
H3C
H3C
C3C
H
H3H
H3C
CH3
CH3
H3C carbons are rehybridizing
Both
Migrating
hydride

H
H
CH3
CH3

Hyperconjugation

H
H

H 3C

H
H
CH33
CH

C
H33C
H

sp22
sp

sp3
sp2
Hyperconjugation
sp3
sp2

H3C

H
H

H33Chydride
Migrating
Migrating hydride

CH33
sp33
sp

+
+
C
C

H
H

Migrating hydride

Migrating hydride

H
H

H
H
CH3
CH3

CH3

C
+
H3C C
C3C
H3H

+
+

p back lobe
increasing
p back lobe
increasing

Hyperconjugation

C
C

H33C C +
+
H33CC

H3C

Hyperconjugation

H
CH3H

CH3

back lobe
lobe
pp back

p back
p back
lobe lobe
increasing
increasing
decreasing
p back lobe
decreasing

C
C

+
+
H3C
H
H3CH
HCH
CH
3C 33
H3C

back lobe
lobe
pp back
decreasing
decreasing

H3H3CC
H

+
+
C
C

C
C

H33CC
H
H
CH3H
CH3

Figure
TheThe
rearrangement
of a carbocation
by a hydride shift:
dotted-line
notation;
Figure9-2
hydride
shift:
(A) dotted-line
dotted-line notation;
notation;
9-2
rearrangement
of a carbocation
by aa(A)hydride
shift:
(A)
(B) orbital picture. Note that the migrating hydrogen and the positive charge exchange places. In
Figure
9-2 The
rearrangement
of athe
carbocation
by a hydride shift:
(A) the
dotted-line
notation;
(B) orbital
and
the
positive
charge exchange
exchange places.
places. In
In
Note
that
migrating
and
positive
charge
addition,
you picture.
can see how
hyperconjugation
weakens hydrogen
the CH bond
by effecting
some electron
(B) orbital picture. Note that the migrating hydrogen and the positive charge exchange places. In
addition,
the
CH
bond
by
effecting
some
electron
can
see
how
hyperconjugation
weakens
the
CH
bond
by
effecting
some
electron
transfer
intoyou
the empty
neighboring
p orbital.
addition, you can see how hyperconjugation weakens the CH bond by effecting some electron
transfer
into
empty
neighboring
transfer
into
the the
empty
neighboring
p orbital. p orbital.

Chapter 9

339
339

Chapter 9

339

MECHANISM

MECHANISM
Color is used to indicate
the electrophilic (blue),
nucleophilic (red), and
leaving-group (green)
character of the reacting
centers. Therefore, a color
may switch from one group
or atom to another as the
reaction proceeds.

Further Reactions of Alcohols and the Chemistry of Ethers

340

Further Reactions of Alcohols and the Chemistry of Ethers

Chapter 9

Exercise 9-4

Exercise 9-4

with the Concepts: Formulating a Carbocation Rearrangement

Working with the Concepts: Working
Formulating
a Carbocation Rearrangement
2-Methylcyclohexanol, on treatment with HBr, gives 1-bromo-1-methylcyclohexane. Explain by a
mechanism.
2-Methylcyclohexanol, on treatment
with HBr, gives 1-bromo-1-methylcyclohexane. Explain by a
Strategy
Let us dissect the problem along the lines of taking an inventory.
mechanism.
What topological/connectivity changes are taking place? Answer: The six-membered ring stays
Strategy
intact, but the functionality has migrated from a secondary to a tertiary carbon.
What
is theof
change
in molecular
formula? Answer: We start with C7H14O and wind up with
Let us dissect the problem along the
lines
taking
an inventory.
C7H13Br. The net change is that OH is being replaced by Br; no carbons are added or subtracted
What topological/connectivity changes
are taking place? Answer: The six-membered ring stays
from the starting material.
What thoughts
to mind when considering
the functional
group and the reagent to which it
intact, but the functionality has migrated
fromcome
a secondary
to a tertiary
carbon.
is exposed? Answer: We have an alcohol that is treated with HBr, a strong acid. The hydroxy
What is the change in molecular
formula? Answer: We start with C7Hgroup,
andhence
wind
up with
14O and
function will be protonated, turning it into a good leaving
we have to consider
substitution
and elimination
pathways. are added or subtracted
C7H13Br. The net change is that OH
is being
replacedas possible
by Br;reaction
no carbons
Solution
from the starting material.
The answer to point 1 (rearrangement) and consideration of point 3 (alcohol and acid) strongly
What thoughts come to mind when
considering
therearrangement
functionalviagroup
and the reagent to which it
implicate
an acid-catalyzed
a carbocation.
To arrive at the required carbocation, we need to protonate the alcohol and dissociate the leaving
is exposed? Answer: We have angroup.
alcohol
that is treated with HBr, a strong acid. The hydroxy
The result is a secondary carbocation.
function will be protonated, turning it into a good leaving group, and hence we have to consider
CH3
3
H 3C
H
substitution and elimination as possible reactionCHpathways.


OH
OH2


Solution
H
O
H

The answer to point 1 (rearrangement) and consideration of point 3 (alcohol and acid) strongly
implicate an acid-catalyzed rearrangement via a carbocation.
Secondary
carbocation
To arrive at the required carbocation, we need to protonate the alcohol and dissociate
the leaving
group. The result is a secondary carbocation.
We know that the product contains the functional substituent Br at the neighboring tertiary


center. Thus, to transfer functionality, we have to invoke a hydride shift.

The ensuing tertiary carbocation is then trapped by bromide to give the product.

CH3

CH3

OH


H3C H

OH2


H

CH3


H2
O

H 3C

Tertiary
carbocation

Br


H3C

H


Br


Secondary
carbocation

Exercise 9-5

We know that the product contains

the functional substituent Br at the neighboring tertiary
Try It Yourself
center. Thus, to transfer functionality,
we have to invoke a hydride shift.
Predict the major product from the following reactions.
The ensuing tertiary carbocation is then trapped by bromide to give the product.
OH
H

H 3C

CH3
H3C
(a) 2-Methyl-3-pentanol
H1 H2SO4, CH3OH solvent


H



(b)Br

 HCl


Br


Primary carbocations are too unstable to be formed by rearrangement. However, carbo

cations of comparable stability for example, the pairs secondary secondary or tertiary
tertiary equilibrate readily. In this case, any added nucleophile will trap all carbocation
Tertiary
present, furnishing mixtures of products.

carbocation

Exercise 9-5

Try It Yourself
Predict the major product
product from
from the
the following
following reactions.
reactions.
OH
OH
HH
(a) 2-Methyl-3-pentanol
2-Methyl-3-pentanol 1
1H
H22SO
SO44,, CH
CH33OH
OH solvent
solvent

(b)
(b)

HCl
HCl

Primary carbocations
carbocations are
are too
too unstable
unstable to
to be
be formed
formed by
byrearrangement.
rearrangement.However,
However,carbocarbocations of comparable
comparable stability
stability
for
for example,
example, the
the pairs
pairs secondary
secondarysecondary
secondary oror tertiary
tertiary
tertiary equilibrate
equilibrate readily.
readily. In
In this
this case,
case, any
any added
added nucleophile
nucleophile will
willtrap
trapall
allcarbocations
carbocations
present, furnishing mixtures
mixtures of
of products.
products.

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OH
Br
Br
Br
Br Br
Br
OH
Br
Br
OH
Br
Br
AA Br
A
OH
Br
AAA
AA OH
AAAAA
HBr,
0C
HBr,
0C
HBr,
0C
HBr,
0C
HBr,
0C
Br A
Br
Br
Br
OH
Br
Br
A22CCH

CH
CCH
CH
CH
CH
CCH
CH
CH
CH
CH
CCH
CH
A
HBr,
0C
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CH
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CH
CH
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CH33 3 CH
BrA333CCH
3
2
2
3
3
2
Br
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2CH
3 
3CH
2A
2CCH
3OH
2
2
3
3
2
A
A 3CCHOH
A
A
Br
Br
CH
CH
CH
CH
CH
CH

CH
CH
CCH
CH
CH
CH
CH33
Br
A
Br
A
2ACH2CH3
33CCH
22CH22CH33  ACH33ACH
22CCH
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HBr,
0C
A
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0C
A
A
CH
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3
2
2
3
3
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2
3
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2
2 33
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CH
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A
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3
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2 23A

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3
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2
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3
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2
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H rearrangements
H
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of
Carbocation
rearrangements take
take place
place regardless
regardless
of the
the nature
natureof
ofthe
the
precursortotothe
thecarcarsection),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
rearrangements
take
place
regardless
of
the
nature
of
the
precursor
to
cation
place
regardless
of
the
nature
ofprecursor
thetoto
precursor
to th
th
gardless
of alcohols
therearrangements
nature(this
of the
precursor
to
the
carbocation:
(this
section),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
6-7).
Carbocation
rearrangements
take
place
regardless
the
nature
of
the
precursor
to
the
car-6-7).
Carbocation
rearrangements
take
place
regardless
of
the
nature
of
the
to
the
carCarbocation
the
cartake
place
regardless
ofof
the
nature
of
the
precursor
the
carcation
rearrangements
take
place
regardless
of
the
nature
of
the
precursor
to
th
rearrangements
take
place
regardless
of
the
nature
of
the
precursor
the
carcation
rearrangements
take
place
regardless
of
the
nature
of
the
precursor
to
the
Carbocation
regardless
of
the
nature
of
the
precursor
to
the
carrearrangements
take
place
example,
solvolysis
of
inin
ethanol
(ethanolysis)
gives
esbocation:
(Chapter
7), (this
and
alkyl
sulfonates
(Section(Chapter
6-7).
For
solvolysis
of 2-bromo-3-ethyl-2-methylpentane
2-bromo-3-ethyl-2-methylpentane
ethanol
(ethanolysis)
gives
alcohols
(this
section),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
6-7).
alcohols
section),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
bocation:
alcohols
(this
section),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
6-7).
alcohols
(this
section),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
6-7).
on:
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
bocation:
(Section
6-7).
alcohols
(this
section),
haloalkanes
7),
and
alkyl
sulfonates
(Section
6-7).
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
6-7).
bocation:
alcohols
(this
section),
on:
alcohols
(this
section),
haloalkanes
(Chapter
7),
and
alkyl
sulfonates
(Section
on:
alcohols
(this
haloalkanes
(Chapter 7),inand
alkyl
sulfonates
(Section
two
possible
tertiary
ethers.
yl-2-methylpentane
insection),
ethanol
(ethanolysis)
gives
For
example,
solvolysis
of2-bromo-3-ethyl-2-methylpentane
2-bromo-3-ethyl-2-methylpentane
in
ethanol
(ethanolysis)
gives
the
tertiary
ethers.
(ethanolysis)
gives
example,
solvolysis
of
2-bromo-3-ethyl-2-methylpentane
in ethanol
(ethanolysis)
gives
For example,
For
example,
solvolysis
of
2-bromo-3-ethyl-2-methylpentane
ethanol
(ethanolysis)
gives
solvolysis
2-bromo-3-ethyl-2-methylpentane
in
gives
solvolysis
of
in
ethanol
(ethanolysis)
xample,
2-bromo-3-ethyl-2-methylpentane
in(ethanolysis)
ethanol
(ethanolysis)
solvolysis
of
2-bromo-3-ethyl-2-methylpentane
in ethanol
ethanol
gives
For
xample,
solvolysis
ofof
2-bromo-3-ethyl-2-methylpentane
ethanol
(ethanolysis)
of
2-bromo-3-ethyl-2-methylpentane
inin(ethanolysis)
ethanol
(ethanolysis)
g
the
possible
tertiary
ethers.
two
possible
tertiary
ethers.
the
two possible
possible
tertiary
ethers.
the
two
tertiary
ethers.
two
possible
tertiary
ethers.
possible
tertiary
ethers.
oothe
ethers.
Rearrangement
possible tertiary ethers.
Rearrangement in
inSolvolysis
Solvolysisof
ofaaHaloalkane
Haloalkane
Rearrangement
Solvolysis
aHaloalkane
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in Solvolysis of a Haloalkane
Rearrangement
inin
Solvolysis
Rearrangement
in
Solvolysis
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Solvolysis
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Rearrangement
Solvolysis
Br
H
HH OOCH
CH
CH
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33
Br H
H
H of a Haloalkane
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CH
OSolvolysis
CH22CH
2
3
2CH
Rearrangement
in
of
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Rearrangement
in
Solvolysis
ofaaaaHaloalkane
Haloalkane
AACH
AA
AAH H
AA
AH
AA CH
AH
Rearrangement
in
Solvolysis
of
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CH
Br
H
HH
HO
CH
CH
O 2CH
H222O
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CH
H
CH
CH
CH
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O
CH
Rearrangement
in
Solvolysis
of
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3
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233333 3CH
3
CH
CH
O
3323CH
22
H
2O
2
Br
H
H
HH
CH
CH
O
CH
CH333CH
CH
OH
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Br
H
CH
CH
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CH
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3
2
2
3
ACH
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A
A
A
AH
O
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CH
CH
C
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33
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2
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CH
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ACH
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Br33B
rr CH
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CH
CH
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O
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O
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CH
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33
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3
2
3
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3333 3
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3
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CH
CCH
CC
CCH
CH
C
CCH
CH
Br


3
3CH
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2CH
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CH
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2
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H

CH
CH
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3
2
2
2
3
3
2
3
3
2
3
3
2
3 3H
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
H
C
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C
CH
CH
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C
CH
CH
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CH
A 222ACH
A 222CH333
AA AACH
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A
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2
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CH
2 CH3
33 CH33CH22O
A
A
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CH
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CH33CH
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O
H CH2CHH
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C
H
C
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CH
CH
H
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CH
H
C
CH
CH
CH
CH
3
3
2
3
3
2
3
3
2
3
3
2
3
CH
H
2O
C
HO
CH
CH
2
3
3
2
3
3
2
3
H
C
H
C
CH
CH
H
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CH
CH
CH
CH
3
2
3
3
2
3
3
2
3
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2
CCH
CH
CH
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CCH
CH
C
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CH
CH

2-Bromo-3-ethyl2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl3C
2
3
3
3
3
2
3
3
2
3
3
2
3
OCH
3 H
2 33
3 O
CH
CO
CCH
CH
C
CCH
CH333
CH333 
2CH2CH
3 3
333C
223CH
22CH
2-Bromo-3-ethyl2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl2-Bromo-3-ethylC
C
H
CH
CH
CH
2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl3
2
3
2
3
OH
O
O
CH
C
CCH
CH
C
CCH

O
CCH
CH
CH
C
CCH
CH
C
CCH
CH
CH
2
3
3
2
3
2
3
2
3 3-Ethoxy-3-ethyl3
2
3
2-Bromo-3-ethyl3-Ethoxy-3-ethyl2-Ethoxy-3-ethyl2-Bromo-3-ethyl2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl3
3

2
2

333 3 222 2
3
2
2
3
2

A
2-methylpentane
2-Bromo-3-ethyl2-Bromo-3-ethylthoxy-3-ethyl2-methylpentane
2-methylpentane
2-Bromo-3-ethylA
2-methylpentane
2-methylpentane
2-methylpentane
2-methylpentane
methylpentane
CH
2CH3
2-methylpentane
CH
2CH3
ormal
product)

2-Ethoxy-3-ethylA A
2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl2-methylpentane
2-methylpentane
2-Ethoxy-3-ethylAAA AAA
2-methylpentane
2-methylpentane
2-methylpentane
2-methylpentane

H
CH
CH
HCC
C CH
CHCH
CH
H
C
CH
CH
H

2-methylpentane (Normal
product)
(Normal
product)
(Normal
product)2
3
33
2-methylpentane
3
(Normal
product)
(Normal
product)
(Normal
product) 222
(Normal
product)
33
33
(Rearranged product)
(Normal product)
2-Ethoxy-3-ethyl2-Ethoxy-3-ethyl-

AAA AAA
H
CH
CH
HCC
C CH
CHCH
CH333
C
CH
CH
HH
3

2-methylpentane
3-Ethoxy-3-ethyl3-Ethoxy-3-ethyl2-methylpentane
2-methylpentane
3-Ethoxy-3-ethylA A
2-methylpentane
2-methylpentane
2-methylpentane
2-methylpentane
2-methylpentane
(Rearranged
(Rearranged product)
product)

(Rearranged
33 product)22
2-methylpentane
(Rearranged
product)
(Rearranged
product)
(Rearranged
product)
(Rearranged
(Rearranged
product)
(Rearranged
product)
3
3product)
22

(Rearranged
product)
3-Ethoxy-3-ethylomo-3-ethyl3-Ethoxy-3-ethylomo-3-ethyl2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl2-Ethoxy-3-ethyl3-Ethoxy-3-ethyl2-methylpentane
2-methylpentane
ethylpentane
2-methylpentane
2-methylpentane
ethylpentane
2-methylpentane
2-methylpentane
2-methylpentane
2-methylpentane
Exercise
9-6
Exercise
(Normal
product)
(Rearranged
product)
Exercise9-6
9-6
(Normalproduct)
product)
(Rearranged
product)
Exercise
9-6
Exercise
9-6
(Normal
product)
(Rearranged
product)
(Normal
(Rearranged
product)
Exercise 9-6
Give
mechanism
for
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-chloroGive
aaaaamechanism
for
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-chloroGive
mechanism
for
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-chloromechanism
reaction
of
2-chlorofor
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-chloroGive
mechanism
for
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-chloroGive
mechanism
for
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-chloroGivepredict
a mechanism
for the
preceding
reaction.
Then predict the outcome of the reaction of 2-chloroThen
the outcome
of
the reaction
ofTry
2-chloro4-methylpentane
with
methanol.
(Hint:
Try
two
successive
hydride
shifts
to
the
most
stable
4-methylpentane
with
(Hint:
two
successive
hydride
shifts
to
the
most
stable
4-methylpentane
with
methanol.
(Hint:
Try
two
successive
hydride
shifts
to
the
most
stable
4-methylpentane
the
most
stable
with
methanol.
(Hint:
Try
two
successive
hydride
shifts
to
most
stable
4-methylpentane
with
methanol.
(Hint:
Try
two
successive
hydride
shifts
toshifts
the
most
stable
Give
a mechanism
formethanol.
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
ofmost
2-chloro4-methylpentane
with
methanol.
(Hint:
Try
two
successive
hydride
to
the
stable
4-methylpentane
with
methanol.
Try
two
successive
hydride
shifts
tothe
the
most
stable
y two
successive hydride
shifts to (Hint:
the most
stable
carbocation.)
carbocation.)
carbocation.)
carbocation.)
9-6
4-methylpentane
with
methanol.
(Hint:
Try
two successive hydride shifts to the most stable
carbocation.)
carbocation.)
cise
cise 9-6

carbocation.)

mechanism
for
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
2-ch
aaaCarbocation
mechanism for
for
the preceding
precedingreaction.
reaction.
Then
predict
theoutcome
outcomeof
ofthe
thereaction
reactionofof
of2-chlo
2-ch
mechanism
the
Then
predict
the
rearrangements
also
give
new
E1
products
the
preceding
reaction.
Then
predict
the
outcome
of
the
reaction
of
2-ch
Carbocation
rearrangements
also
give
new
E1
products
rearrangements
also
give
new
E1
Carbocation
rearrangements
also
give
new
E1
products
Carbocation
new
E1products
products
thylpentane
with
methanol.
(Hint:
Try
two
successive
hydride
shifts
the
most
ss
Carbocation
rearrangements
also
give
new
E1
products
with
methanol. (Hint:
(Hint:also
Trygive
two
successive
hydride
shiftstoto
tothe
themost
moststa
othylpentane
give
new
E1rearrangements
products
with
methanol.
Try
two
successive
hydride
shifts
thylpentane
methanol.
(Hint:
Try
two
successive
hydride
shifts
to
the
most
s
How
does
the
rearrangement
of
intermediates
affect
the
outcome
of
reactions
under
conditions
Carbocation
rearrangements
also
give
new
E1
products
How
conditions
does
the
rearrangement
of
intermediates
affect
the
of
reactions
under
conditions
rearrangement
of
intermediates
affect
theoutcome
outcome
ofof
reactions
under
conditions
cation.)
How
does
the
rearrangement
intermediates
affect
the
outcome
of
under
conditions
cation.)
How
does
the
rearrangement
ofof
affect
outcome
reactions
under
conditions
cation.)
How
does
the
rearrangement
ofintermediates
intermediates
affect
the
outcome
ofreactions
reactions
under
conditions
that
favor
elimination?
elevated
temperatures
and
inthe
relatively
nonnucleophilic
media,
reares
affect
the
outcome
ofAtreactions
under
conditions

that
media,media,
rear- rearfavor
elimination?
At
elevated
temperatures
and
in
nonnucleophilic
media,
rearelimination?
AtAt
elevated
temperatures
andand
inrelatively
relatively
nonnucleophilic
media,
rearthat
favor
elimination?
elevated
temperatures
in
nonnucleophilic
that
AtAt
elevated
temperatures
andand
in(Section
relatively
nonnucleophilic
media,
rear- rearHowfavor
does
the
rearrangement
ofby
intermediates
affect
the
outcome
of
reactions
under
conditions
that
favor
elimination?
elevated
temperatures
inrelatively
relatively
nonnucleophilic
media,
ranged
carbocations
yield
alkenes
the
E1
9-2).
example,
treatment
tures
and
inelimination?
relatively
nonnucleophilic
media,
rearcarbocations
yield
alkenes
by
the
E1
mechanism
(Section
9-2).
For
example,
treatment
ranged
carbocations
treatment
yield
alkenes
byby
the
E1mechanism
mechanism
(Section
9-2).For
For
example,
treatment
ranged
carbocations
yield
alkenes
the
mechanism
(Section
9-2).
For
example,
treatment
carbocations
bysulfuric
the
E1E1
mechanism
9-2).
For
example,
treatment
that
favor
elimination?
Atalkenes
elevated
temperatures
in(Section
relatively
nonnucleophilic
media,
rearof
2-methyl-2-pentanol
with
aqueous
acid
at
808C
gives
the
same
major
alkene
prodranged
carbocations
yield
alkenes
by
the
E1
mechanism
(Section
9-2).
For
example,
treatment
1 ranged
mechanism
(Sectionyield
9-2).
For
example,
treatment
2-methyl-2-pentanol
with
aqueous
sulfuric
acid
atatand
808C
gives
the
same
major
alkene
prodof
alkene
prod2-methyl-2-pentanol
with
aqueous
sulfuric
acid
808C
gives
the
same
major
alkene
prod2-methyl-2-pentanol
with
aqueous
sulfuric
acid
gives
same
major
alkene
prodof
2-methyl-2-pentanol
with
aqueous
sulfuric
acid
at at
808C
gives
thethe
same
major
alkene
product
as
formed
when
the
starting
material
4-methyl-2-pentanol.
The
conversion
of
the
ranged
yield
alkenes
by
the
E1is
(Section
9-2).
For
example,
treatment
of
2-methyl-2-pentanol
with
aqueous
sulfuric
acid
at 808C
808C
gives
the
same
major
alkene
prodicuct
acid
atcarbocations
808C
gives
the
same
major
alkene
prodas that
that
formed
when
the
starting
material
isismechanism
4-methyl-2-pentanol.
The
conversion
ofof
the
formed
of
the
when
the
starting
material
4-methyl-2-pentanol.
The
conversion
the
rearrangements
also
give
new
E1
products
ocation
give
new
E1
products
rearrangements
also
give
E1
products
asalcohol
that formed
formed
when
thestarting
starting
material
is4-methyl-2-pentanol.
4-methyl-2-pentanol.
The
conversion
of
the
rearrangements
also
E1the
products
uct
as
that
when
the
material
is
The
conversion
of the
latter
includes
aaa hydride
shift
of
initial
carbocation
by
deprotonation.
of is
2-methyl-2-pentanol
with
aqueous
sulfuric
acid
at new
808Cfollowed
gives
same
major
alkene
product
asalcohol
that formed
the
starting
material
is
4-methyl-2-pentanol.
The
conversion
of the
includes
hydride
shift
of
the
initial
carbocation
followed
by
deprotonation.
latter
deprotonation.
rial
4-methyl-2-pentanol.
The
conversion
of the
includeswhen
hydride
shift
of the
the
initial
carbocation
followed
by
deprotonation.
latter
alcohol
includes
hydride
shiftofof
initial
carbocation
followed
by
deprotonation.
latter
alcohol
includes
aahydride
shift
thetheinitial
carbocation
followed
byThe
deprotonation.
uct
as
that
formed
when
the
starting
material
is
4-methyl-2-pentanol.
conversion
of
the
does
the
rearrangement
of
intermediates
affect
the
outcome
of
reactions
under
cond
alcohol
includes
a hydride
shift of the initial
carbocation
followed
by deprotonation.
e latter
initial
carbocation
followed
by
deprotonation.
does
rearrangement
ofRearrangement
intermediates
affect
the
outcome
of
reactions
under
con
the
rearrangement
of
intermediates
affect
the
outcome
of
reactions
under
condi
does
rearrangement
of
intermediates
affect
the
outcome
of
reactions
under
cond
E1 Elimination
latter
alcohol includes
aelevated
hydride
shift
of thein
initial
carbocation
followed
by deprotonation.
Rearrangement
in
Elimination
Rearrangement
inE1
E1and
Elimination
vor
elimination?
At
temperatures
in
relatively
nonnucleophilic
media
vor
elimination?
At
elevated
temperatures
and
in
relatively
nonnucleophilic
media
elimination?
At
elevated
temperatures
and
in
relatively
nonnucleophilic
media,
Rearrangement
in
E1
Elimination
Rearrangement
E1
Elimination
vor in
elevated
temperaturesin
and
in
relatively nonnucleophilic
media
Rearrangement
in
E1
Elimination
OH
H
OH
ment
E1
Elimination
Rearrangement
in
E1
Elimination
OH
H
C E1
CH
carbocations
yield
alkenes
by
the
E1
mechanism
(Section
9-2).
For
example,
OH trea
H example,
OH
2CH
3 (Section
AA
AH
AOH
ddd carbocations
yield alkenes
alkenes
by the
the
E1mechanism
mechanism
(Section
9-2).For
For
example,
tre
yield
by
H
CH
H333CCG
CH
22CH
333 (Section
alkenes
by
the
E1
mechanism
9-2).
For
example,
trea
Rearrangement
in
E1
Elimination
D
H SO , 80C
H SO , 80C9-2).
2CH
AA H
AAA OHtreat
OH
H
OH
G
DD
,, 80C
HH
OH
H
OH
GCCP Cacid
HSO
SO, ,80C
, 80C
80C
SO
80C
SO
H
CH
O
CH COH
CH2CH
CCH
3C
2CH
3
HH
OH
methyl-2-pentanol
withHH SO
aqueous
sulfuric
at
808C
gives
the
same
major
alkene
3C
3
OH
2
ACH
Aalkene
O CH
OO
CH
Cacid
CH
CH
2CH
methyl-2-pentanol
aqueous
sulfuric
808C
same
major
alkene
methyl-2-pentanol
acid
atCH
808C
gives
theCH
same
major
AAO
AA22H
H
O ,the
Pacid
CH333CA
CH
CCH
33C
33 33 A
CH33with
C
C
CH
CH
CH22CH
CH222CH
G
SO O, 80C
H SO
80C
2CCH
D33C
G D at
AOHp
aqueous
sulfuric
at
808C
gives
the
same
major
alkene
3withHH
33C O
22CCH
H
CP
CH33gives
CH
2
222

4
444

24

2
4
22 22 44 44

22

OH
OH
A
A O CH CH CH
CH33C
CH3CA O CH222CH222CH333
A
CH
CH 33
3

2-Methyl-2-pentanol
2-Methyl-2-pentanol
2-Methyl-2-pentanol

H
H22SO
SO44,, 80C
80C
H2SO4, 80C
H
H2O
O
H2O2

H
CH
H3CC
CH33
CH22CH
H3C3 G
CH2CH
D
3
G GCCP
DCD
C
P
P C GG
C
D
D
D
G H
H
33C
C
H
H
H
HC
3

Major
Majorproduct
product
Major product

2-Methyl-2-pentene
2-Methyl-2-pentene
2-Methyl-2-pentene

HH

OH
OH
OH

AA
AA
HH2SO
4,4,80C
80C
2SO
A C O CH
A CCH
80C
H22SO44, 80C
CH
33C O CH
2 2CC
H
CHCH
H2OO
33C O
AACH22CCH
A 33
H22O 2
A CH A HA
With
With
33
With
CHCH
H H
rearrangement
33
rearrangement
rearrangement
rearrangement
H

4-Methyl-2-pentano
4-Methyl-2-pentan
4-Methyl-2-pentanol
4-Methyl-2-pentanol

Exercise
9-7
Exercise 9-7
9-7
Exercise
(a)
Give
mechanisms
for
the
preceding
E1
reactions.
(b)
Treatment
with
(a) Give
Give mechanisms
mechanismsfor
forthe
thepreceding
precedingE1
E1reactions.
reactions.
(b)
Treatment
of4-methylcyclohexanol
4-methylcyclohexanol
with
(a)
(b)
Treatment
of of
4-methylcyclohexanol
with
hot
acid
gives
1-methylcyclohexene.
Explain
(Hint:
Consider
several
sequential
hot acid
acid gives
gives 1-methylcyclohexene.
1-methylcyclohexene.Explain
Explainbyby
bya amechanism.
a mechanism.
mechanism.
(Hint:
Consider
several
sequential
hot
(Hint:
Consider
several
sequential
H
shifts.)
H shifts.)
shifts.)

carbocation
rearrangements
are
due
alkyl
shifts
Other
shifts
Other carbocation
carbocationrearrangements
rearrangementsare
aredue
duetoto
toalkyl
alkyl
shifts
Carbocations,
particularly
when
lacking
suitable
(secondary
and
tertiary)
hydrogens
next
and
tertiary)
hydrogens
next
to toto
Carbocations,
Carbocations, particularly
particularlywhen
whenlacking
lackingsuitable
suitable(secondary
(secondary
and
tertiary)
hydrogens
next
positively
charged
carbon,
can
undergo
another
mode
rearrangement,
known
mode
ofof
rearrangement,
known
as as
alkyl
the
the positively
positively charged
chargedcarbon,
carbon,can
canundergo
undergoanother
another
mode
of
rearrangement,
known
asalkyl
alkyl
migration
or
alkyl
shift.
group
group migration
migration or
oralkyl
alkylshift.
shift.

342

Chapter 9

Further

342

Chapter 9

Further

REACTION
REACTION

MECHANISM
MECHANISM

As in the h
to the neig
As in the h
charge form
to the neig
charge form

H3C CH3
A A

H33C
CO COH
CH
CH
3
A A
H3C O COH
H
CH

A A
H3The
C rates
H o
stability. H
The rates o
relative to t

n ss oo ff A
A ll cc oo h
h oo ll ss aa n
nd
d tt h
h ee C
Ch
h ee m
m ii ss tt rr yy oo ff
cc tt ii oo n
Reactions of Alcohols and the Chemistry of Ethers

Rearrangement
Reaction
Rearrangement by
by Alkyl
Alkyl Shift
Shift in
in S
SNN11 Reaction
Rearrangement by Alkyl Shift in SN1 Reaction

H33C
C CH
CH33
H
H C CH
AA 3 A AA A 3
O
CH
O COH
CH
O
CH33C
C
COH
3CCOH
AA A AA A
H
H
C
H
H33C
H
C 3 H

Br CH3

CH3
Br Br
CH
A 3 AA 3
A AA
C
CH3CH
C O33CCH
O3 CCH
CH
CO
CCH3
A AA
A AA 3
H3CH H
H33C
H
C H
94%

HBr

HBr
HBr
HOH
HOH
HOH

94%
94%

3,3-Dimethyl-2-butanol

2-Bromo-2,3-dimethylbutane

3,3-Dimethyl-2-butanol
2-Bromo-2,3-dimethylbutane
3,3-Dimethyl-2-butanol
2-Bromo-2,3-dimethylbutane
ydride shift, the migrating group takes its electron pair with it to form a bon
hboring positively charged carbon. The moving alkyl group and the positiv
shift,
the
group
shift,
the migrating
migrating
group takes
takes its
its electron
electron pair
pair with
with it
it to
to
mally
exchange
places.

gg positively
positively charged
charged carbon.
carbon. The
The moving
moving alkyl
alkyl group
group and
and
Mechanism of Alkyl Shift
xchange
places.
xchange places.
O
H2


 Br

CH3
Br
A A
CH3C O CCH
A A
H3C H


 Br


CH3

H3C

A 
A

CH
Mechanism
of shift
Alkyl
Shift
Mechanism
of
Alkyl
CH
CHShift
3C O CCH3
3C O CCH3

O
H2


 H





2
2

3
3



2
2




H
CH
H3C H
H3C H
H33C
C
CH33


O
H

A
A


 
O
H 
 Br
Br
A 
A


CH


CH shift
shiftwhen leading
alkyl and hydride
shifts
are
comparable
to
carbocations
of
simila
O CCH
O CCH
CH33C
CO
CCH33
CO
CCH33
CH
CH33C
CH
CH
CH
owever,
either
type
of
migration
is
faster
when
furnishing
tertiary
carbocation

A
A
A
A


O
H
A
A
A
A

Br



O
H 
 Br

hose ending inH
counterparts. This
Hwhy, in the precedinH
C secondary
H
Hexplains
C H
H
Htheir
H
H
33C
33C

of hydride shifts, alkyl group rearrangement was not observed: The less subst
would have been the result. Exceptions to this observation are found only
and
hydride shifts
shifts are comparable
comparable when leading
leading to
to carbocatio
carbocatio
and
hydride
her
compelling
reasons are
for the preference ofwhen
alkyl migration, such
as electroni
either
type(see
of Chapter
migration
is faster
faster
when
furnishing
tertiary
,, oreither
type
of
migration
is
when
steric relief
Integration
Problem
9-26furnishing
and Problem tertiary
9-61).

nding in
in their
their secondary
secondary counterparts.
counterparts. This
This explains
explains why,
why, in
in tt
nding
-8 shifts,
ide
shifts, alkyl
alkyl group
group rearrangement
rearrangement was
was not
not observed:
observed: The
The
ide
this
have
been
the
result.
Exceptions
to
observation
are
ddwith
have
been
the
result.
Exceptions
to
this
observation
are
ff
the Concepts: Formulating a More Complex
mpelling
reasons for
for the
the preference
preference of
of alkyl
alkyl migration,
migration, such
such
ion Rearrangement
mpelling
reasons
rictherelief
relief
(see
Chapter
Integration
Problem
9-26
and Problem
Problem
ric
Chapter
Problem
and
of
type A(see
have been
shown Integration
to dehydrate to B.
Formulate 9-26
a mechanism.

3,3-Dimethyl-2-butanol
3,3-Dimethyl-2-butanol
3,3-Dimethyl-2-butanol

2-Bromo-2,3-dimethylbutane
2-Bromo-2,3-dimethylbutane
2-Bromo-2,3-dimethylbutane

to
to the
the neighboring
neighboring positively
positively charged
charged carbon.
carbon. The
The moving
moving alkyl
alkyl group
group and
and the
the positive
positive
As in
in the
the hydride
hydride shift,
shift, the
the migrating
migrating
group
takes
its
electron
pair
with
form
bond
migratinggroup
grouptakes
takesits
itselectron
electronpair
pairwith
withititittoto
toform
forma aabond
bond
As
charge
places.
charge formally
formally exchange
exchange
places.
to the
the neighboring
neighboring positively
positively charged
charged
carbon.
The
moving
alkyl
group
and
the
positive
chargedcarbon.
carbon.The
Themoving
movingalkyl
alkylgroup
groupand
andthe
thepositive
positive
to
charge formally
formally
exchange places.
places.
charge
exchange
Mechanism
of Alkyl Shift














 













3
3
3

22 22

33 33

22 22

 










2
2
2






2
2
2








Mechanism of Alkyl Shift

Mechanism
Alkyl
Shift
Mechanismofof
ofAlkyl
AlkylShift
Shift
Mechanism
MECHANISM

H
H
CH
Br
CH
33C
H33C
C CH
H
C
CH33
CH33
Br
CH33




O

A
A
AA
AABr

Br
A
O 33
HCH
3 33Br
Br
H33C
CH
H33C
CH
CH
CH


H
H
CH
CH
Br
CH
A AA
A 
ACH

3 33

3C shift

CH


CH
shift


O
H

Br
A
A
A
A
O
H


Br
A
A
A
A
A AA CCH
A AA 3
O
H

Br
A







O
O
O


H
CH
C
CCH
C
CCH
CH
C
CH

3
CH
shift
CH

CHshift
shift
33
33
3
3
O COH
O
O
O
H33C
CO
COH
 HCH
CH
C
CCH
C
CCH
CH
C
CCH
CH


3
3
3
3


 
O
O
O
O
CH33C
C OCOH
COH
H
HA
CH33C
CCH
CCH
CH
CCH
CH

CH
CCH
CH
CCH
CH
O
O
CCH333
CO
CCH
CH
CO
CCH
CH
33C
33 
33C
3C
3
3C
3 33
3C OCCH


A
A
A
A
A



A A
O
H

Br
A
A
A
A
A
A

O


AAH AA
AA AAA
AAA AAA Br
A AA A AA

 Br

O
H
O
H
O
H
Br



Br
 H C
H
H
H33C H
H
H33C
C H
H
H33C
C H
H HH33C3C HHH
H33C
C H
HHH3C33CC HHH
H33HCHH
HHHH
CH
3C
33C
The
and
shifts
when
toto
The rates
rates of
of alkyl
alkyl
and hydride
hydride
shiftsare
are
comparable
when
leading
carbocations
similar
arecomparable
comparable
whenleading
leading
tocarbocations
carbocations
ofsimilar
similar
The
hydride
shifts
are
comparable
when
to
of
similar
The rates
rates of
of alkyl
alkyl and
and
hydride
shifts
are
comparable
when leading
leading
to carbocations
carbocations
ofofof
similar
stability.
isis
tertiary
carbocations
stability. However,
However, either
either type
type of
of migration
migration
faster
when
furnishing
tertiary
carbocations
migrationwhen
isfaster
fasterwhen
whenfurnishing
furnishing
tertiary
carbocations
stability.
either
of
migration
is
tertiary
carbocations
stability. However,
However,relative
eithertototype
type
migration
is faster
fastercounterparts.
when furnishing
furnishing
tertiary
those
ending
in
This
why,
relative
thoseof
ending
in their
theirsecondary
secondary
counterparts.
This
explains
why,
in
the
preceding
secondary
counterparts.
Thisexplains
explains
why,incarbocations
inthe
thepreceding
preceding
relative
in
secondary
counterparts.
This
in
preceding
relative to
to those
those ending
ending
in their
their
secondary
counterparts.
This explains
explains
why,
in the
the
preceding
discussion
of
shifts,
group
was
observed:
The
less
discussion
of hydride
hydride
shifts, alkyl
alkyl
group
rearrangement
was
not
observed:
The
less
substigrouprearrangement
rearrangement
wasnot
notwhy,
observed:
The
lesssubstisubstituted
cation
been
the
toto
observation
are
only
discussion
alkyl
group
rearrangement
was
observed:
The
less
substitutedshifts,
cation would
would have
have
been
the result.
result.
Exceptions
this
observation
are
found
only
result.Exceptions
Exceptions
tothis
this
observation
arefound
found
onlyififif
discussion of
of hydride
hydride
shifts,
alkyl
group
rearrangement
was not
not
observed:
The
less
substithere
are
other
compelling
reasons
for
the
preference
of
alkyl
migration,
such
as
electronic
there
are
other
compelling
reasons
for
the
preference
of
alkyl
migration,
such
as
electronic
for the preference
of alkyl migration,
such as only
electronic
tuted
have
the
Exceptions
to
observation
are
if
tuted cation
cation would
wouldstabilization
have been
been steric
the result.
result.(see
Exceptions
to this
thisProblem
observation
are found
found
only
if
9-61).
stabilization or
or steric relief
relief (see Chapter
Chapter
Integration
Problem
9-26
and
Problem
9-61).
ChapterIntegration
Integration
Problem9-26
9-26and
andProblem
Problem
9-61).
there
there are
are other
other compelling
compelling reasons
reasons for
for the
the preference
preference of
of alkyl
alkyl migration,
migration, such
such as
as electronic
electronic
stabilization
relief
(see
stabilization or
or steric
stericExercise
relief 9-8
(see Chapter
Chapter Integration
Integration Problem
Problem 9-26
9-26 and
and Problem
Problem 9-61).
9-61).
Exercise
9-8

Working
Working with
with the
the Concepts:
Concepts:Formulating
Formulating
More
Complex
FormulatingaaaMore
MoreComplex
Complex
Carbocation
Carbocation Rearrangement
Rearrangement

Exercise
Exercise 9-8
9-8

of
type
toto
toto
Working
Concepts:
aashown
More
Complex
Molecules
of the
the Formulating
type AA have
have been
been
dehydrate
Formulate
mechanism.
beenshown
shown
todehydrate
dehydrate
toB.B.
B.Formulate
Formulatea aamechanism.
mechanism.
Working with
with the
theMolecules
Concepts:
Formulating
More
Complex
Carbocation
Carbocation Rearrangement
Rearrangement
HH3CC

H3C
HHSO
Molecules
to
B.
SO

Molecules of
of the
the type
type A
A have
have been
been shown
shown 3%to
to
dehydrate
toH SO
B. Formulate
Formulate aa mechanism.
mechanism.
% dehydrate
H O

H
H33C
C

%
%

22

22

44

44

22
H
H22O
O

HH
H

000

OH
OH
OH
A SO
H222SO444
A
A
H
H222O
O

CH
33
CH
CH
3
B
BB

Strategy
H
Strategy
H
Strategy
First
we need
to
look carefully
at the
function(s) ininAAand
B, asaswell
as the
reagent: We
recognize
First
to
First we
we need
need
to look
look carefully
carefully at
at the
the function(s)
function(s) in A0and
and B,
B, as well
well as
as the
the reagent:
reagent: We
We recognize
recognize

the
presence
of
aa tertiary
alcohol that
is being
treated0with
acid. These
conditions are
suggestive

the
presence
of
the presence of a tertiary
tertiary alcohol
alcohol that
that is
is being
being treated
treated with
with acid.
acid. These
These conditions
conditions are
are suggestive
suggestive
of
the
formation
of
a
carbocation.
Moreover,
the
net
reaction
is
dehydration,
indicating
E1E1
OH
CH
3
OH of aa carbocation.
CHreaction
of
Moreover,
the
is dehydration,
indicatinganan
3
of the
the formation
formation
carbocation.
Moreover,
the net
net
reaction
dehydration,
process.
Second, it of
is important
to inspect
the carbon
skeleton
in Aisand
compare it indicating
with that inanB:E1
process.
in
A
B
A itit is
B
process. Second,
Second,
is important
important to
to inspect
inspect the
the carbon
carbon skeleton
skeleton
in A
A and
and compare
compare itit with
with that
that in
in B:
B:
We
can
see
that
the
methyl
group
has
migrated
totoits
neighboring
carbon.
Conclusion:
We
are
We
can
see
that
the
methyl
group
has
migrated
its
neighboring
carbon.
Conclusion:
We
We canwith
see athat
the methyl
group has migrated
its neighboring
carbon. Conclusion: We are
are
dealing
rearrangement
featuring to
a methyl
shift.
dealing
with
aa carbocation
carbocation
rearrangement
featuring
aa methyl
shift.
dealing
with
carbocation
rearrangement
featuring
methyl
shift.
Solution
Solution
lookSolution
carefully
at are
theprotonation
function(s)
in A
A by
and
B,ofas
aswater
wellto as
as
the reagent:
reagent:
We recognize
recognize
The
first steps
followed
loss
generate
the carbocation.
look
at
the
function(s)
in
and
B,
well
the
We
carefully
The
The fifirst
rst steps
steps are
are protonation
protonation followed
followed by
by loss
loss of
of water
water to
to generate
generate the
the carbocation.
carbocation.

Strategy
Strategy
First
First we
we need
need to
to
the
the presence
presence of
of aa tertiary
tertiary alcohol
alcohol that
that is
is being
being treated
treated with
with acid.
acid. These
These conditions
conditions are
are suggestive
suggestive
of
the
formation
of the formation of
of aa carbocation.
carbocation. Moreover,
Moreover, the
the net
net reaction
reaction is
is dehydration,
dehydration, indicating
indicating an
an E1
E1
H3C
H3C
H3C
process.
to
inspect
the
carbon
skeleton
in
A
and
compare
it
with

H
C
H
C
H
C
process. Second,
Second, it
it is
is important
important
to
inspect
the
carbon
skeleton
in
A
and
compare
it
with
that in
in B:
B:
3
3
3
H3%C
H%3C
H%3C that
 H

%
%
%
H

H O Conclusion:
% H
% HWe
 H
We
migrated
to
its
neighboring
carbon.
are
H has
We can
can see
see that
that the
the methyl
methyl %group
group
has
migrated
to
its
neighboring
carbon.
Conclusion:
We
are
H
O
H O
H
H
H
H
H
H
dealing
featuring
dealing with
with aa carbocation
carbocation rearrangement
rearrangement
featuring aa methyl
methyl shift.
shift.




OH
OH
Solution
2
Solution

OH

OH

OH
OH22


The
The fi
first
rst steps
steps are
are protonation
protonation followed
followed by
by loss
loss of
of water
water to
togenerate
generate the
the carbocation.
carbocation.
22

22
2

H
H33C
C

%
%

H
H



H
 H

H
H33C
C

%
%

H
H

H
H33C
C
H
H222O
O

%%

H
H




Exercise 9-8

Working with the Concepts: Formulating a More Complex

Carbocation Rearrangement
Molecules of the type A have been shown to dehydrate to B. Formulate a mechanism.

H3C

%
H

H2SO4
H2O

OH

CH3

Strategy
First we need to look carefully at the function(s) in A and B, as well as the reagent: We recognize
the presence of a tertiary alcohol that is being treated with acid. These conditions are suggestive
of the formation of a carbocation. Moreover, the net reaction is dehydration, indicating an E1
process. Second, it is important to inspect the carbon skeleton in A and compare it with that in B:
We can see that the methyl group has migrated to its neighboring carbon. Conclusion: We are
dealing with a carbocation rearrangement featuring a methyl shift.
Solution
The first steps are protonation followed by loss of water to generate the carbocation.

H 3C


OH

 H

H3C

OH2


H3C
H2O

H3C

9
99 --- 3
33
CC
bbbooooccccaaaattttiiiioooon
nnn R
RR
nnnggggeeeem
m
nnnttttssss
3 C
Caaaarrrrb
Reeeeaaaarrrrrrrraaaan
meeeen
m
9-3 Carbocation Rearrangements


B
m e n t s
H9 - 3 C a r b o c a t i o n R eHa r r a n g eH

2 as a
This
cation
in principle,
various options.
For example,
it could be
trapped by
HSO442
 has,
has,
options.
as
For example,
example, itititcould
couldbe
betrapped
trappedby
byHSO
HSO4422
asaaa
This
This cation
cation
has, in
in principle,
principle, various
various
options. For
For
example,
could
be
trapped
by
HSO
as
2
2 is very
nucleophile
1).
However,
HSO
weak
in
this
respect
(it
is
aabepoor
base;
Section
This cation(S
has,
in
principle,
various
options.
For
example,
it
could
trapped
by
HSO426-8).
as a
2 is very
N
4
2
nucleophile
(S
1).
However,
HSO
weak
in
this
respect
(it
is
poor
base;
Section
6-8).
N
4
in this
this respect
respect
(it is
is aa poor
poor base;
base; Section
Section
6-8).
nucleophile (SN1). However, HSO442 is very weak in
(it
6-8).
2
CH
2
3
Moreover,
if it
did form
aHSO
bond4 to
cationic
would
readily
(HSO
nucleophileeven
(S 1).
However,
isthe
very
weak center,
in this this
respect
(itbe
is
areadily
poor reversible
base;
Section
6-8).
2
2
4
Moreover,
this
be
(HSO
4 2
center,
thiswould
would
bereadily
reversible
(HSO
Moreover, even
evenN if
if itit did
did form
form aa bond
bond to
to the
the cationic
cationic center,
center,
this
would
be
readilyreversible
reversible
(HSO
4442
is
an
excellent
leaving
group;
Section
6-7).
It
could
also
lose
a
proton
in
two
possible
ways.
This
Moreover,
even
if
it
did
form
a
bond
to
the
cationic
center,
this
would
be
readily
reversible
(HSO
is
4
could also
alsolose
loseaaaproton
protonin
intwo
twopossible
possibleways.
ways.This
This
is an
an excellent
excellent leaving
leaving group;
group; Section
Section 6-7).
6-7). ItIt could
could
also
lose
proton
in
two
possible
ways.
This
is
also
reversible
and
not
observed.
Instead,
cation
provides
an
opportunity
to
move
the
methyl
an excellent
leaving
group;
Section
6-7).this
It could
also
lose
a
proton
in
two
possible
ways.
This
is
also
reversible
and
not
observed.
Instead,
this
cation
provides
an
opportunity
to
move
the
methyl
cation provides
provides an
an opportunity
opportunity to
to move
move the
the
methyl
is also reversible and not observed. Instead, this cation
2 methyl
group
the
neighboring
position,
as
in
B,it
by
rearrangement.
is also to
reversible
andFor
not observed.
Instead,
thiscould
cation provides
an opportunity
to move the
methyl
group
the
position,
as
in
arious
example,
be trapped
by HSO
rearrangement.
4 as a
group to
tooptions.
the neighboring
neighboring
position,
in B,
B, by
by rearrangement.
rearrangement.
2
2 as
group
deprotonation
HSO
(written
proton
loss)
provides
the
product.
to the
neighboringby
position,
in B, as
by
rearrangement.
2 as
4
Finally,
deprotonation
by
HSO
(written
as
proton
loss)
provides
the
product.
42
2Finally,

Finally,
deprotonation
by
HSO
(written
as
proton
loss)
provides
the
product.
loss)
provides
the product.
442 respect proton
O4 Finally,
is very
weak
in
this
(it
is
a
poor
base;
Section
6-8).
deprotonation by HSO4 (written as proton loss) provides the product.
ond to the cationic center, this would be readily reversible (HSO42
H
H33C
C
H3C
ction 6-7). It could
also
lose a proton intwo possible
ways. This

B
H3%
C

BB
% H

H

H
B
% H provides an opportunity
HH
 H
H
H

Bthe methyl
d. Instead, this cation
to move
H
H
H
H
H

0


00
n, as in B, by rearrangement.
CH
CH
 gives three products
0 33 of E1 reaction: one derive
dimethyl-2-butanol
CH
CH
33
2
3 product.
the
4 (written as proton loss) provides CH

lf

nt prior to rearrangement, the other two from that formed after an

veExercise
the structures
of these elimination products.
9-9
Exercise 9-9
Exercise 9-9

Try It Yourself
Try It Yourself
Try It Yourself

gives
At
At 1008C, 3,3-dimethyl-2-butanol
3,3-dimethyl-2-butanol
gives three
three products
products of
of E1
E1 reaction:
reaction:Bone
one derived
derived from
from the
the carcarAt 1008C, 3,3-dimethyl-2-butanol gives three products
products of
of E1
E1 reaction:
reaction: one
one derived
derived from
from the
the carcar-

H
bocation
prior
the
two
formed
after
an
bocation
present
prior to
to rearrangement,
rearrangement,
the other
other
two from
from
that
formedone
after
an alkyl
alkyl
shift
has
At 1008C,present
3,3-dimethyl-2-butanol
gives
three
products
of
E1that
reaction:
derived
fromshift
the has
carH rearrangement
ohols
may
undergo
bocation
present
prior
to rearrangement,
the other
two
from
that
formed
an
shift
has
two
from
that
formed after
after
an alkyl
alkyl
shift
has
taken
place.
Give
the
of
products.
taken
place.
Give prior
the structures
structures
of these
these elimination
elimination
products.
bocation
present
to rearrangement,
the other two
from that formed after an alkyl shift has
taken place. Give the structures of these elimination
elimination products.
products.

taken place. Give the structures of these elimination products.

primary alcohol with0 HBr or HI normally produces the corre
CH3
alcohols
rearrangement
SPrimary
ofmay
the undergo
alkyloxonium
ion (Section 9-2). Howeve
N2 reaction
alcohols
may
undergo
rearrangement
Primary
Primary
alcohols
may
undergo
Treatment
of
a primary
alcohol
withhydride
HBrrearrangement
or HI normally
produces
the corresponding
halo- b
to
observe
alkyl
and
shifts
to primary
carbons
of a S
primary
alcohol
with
HBr or HI normally
produces
haloTreatment
normally
produces
the corresponding
corresponding
haloalkane
through
2 reaction
of the
alkyloxonium
ion (Section
9-2). the
However,
it is possible
N
Treatment
of a primary
alcohol
with
HBr or HI normally
produces
the
corresponding
haloN
through
S
2
reaction
of
the
alkyloxonium
ion
(Section
9-2).
However,
it
is
possible
alkane
ion
(Section
9-2).
However,
it
is
possible
ough
primary
carbocations
are
not
formed
in
solution.
For
ex
in
somethrough
cases S
toN 2observe
alkyl
and
hydride shifts
to
primary
carbons
bearing
leaving
alkane
reaction
of
the
alkyloxonium
ion
(Section
9-2).
However,
it
is
possible
N observe alkyl and hydride shifts to primary carbons bearing leaving
some
cases
to
in
shifts
to
primary
carbons
bearing
leaving
groups,
even
though
primaryalkyl
carbocations
arewith
not
formed
in solution.
For
example,
treating
in
some
cases
to
observe
and
hydride
shifts
to
primary
carbons
bearing
leaving
propanol
(neopentyl
alcohol)
strong
acid
causes
rearran
carbocations
not strong
formed
in
For
groups, even though primary
formedacid
in solution.
solution.
For example,
example, treating
treating
2,2-dimethyl-1-propanol
(neopentyl
alcohol)are
with
causes rearrangement,
groups, even though primary
carbocations
are
not strong
formedacid
in solution.
For example, despite
treating
(neopentyl
alcohol)
2,2-dimethyl-1-propanol
strong
acid causes
causes rearrangement,
rearrangement, despite
despite
primary
cannot
be
anintermediate.
intermediate.
the
fact thatcarbocation
a primary carbocation
cannot
bewith
an
2,2-dimethyl-1-propanol
(neopentyl
alcohol)
with
strong
acid causes rearrangement, despite

the fact that a primary carbocation cannot be an intermediate.

intermediate.
the fact that a primary carbocation cannot be an intermediate.
Rearrangement
Rearrangement in
in aa Primary
Primary Substrate
Substrate
Rearrangement in a Primary
Substrate
Substrate
Rearrangement
inin aa Primary
Primary
Substrate
Rearrangement
Primary
Substrate
CH
Br
CH33of E1 reaction:
Br
l gives three
products
one
derived
from the carAA 3
AABr
CH
Br
HBr,

HBr,

CH
A 3from
ABr
A 22CH
CH
CH
CCH
gement, the other
two
that
formed
after
an
alkyl
shift has
HBr,

33CCH
22OH
3
3
CH
CCH
OH
CH
CCH
CH
HBr,
3
3
O
H
CH3CH3CCH
Br
A 2CH
O OH
HHBr,
OH
AAA 2OH
CH

CH33AACCH
CCH
2CH33
H
OOH
HO
OH
CCH
OH
CH3CH
CCH
Aproducts.
AA 33 2CH
of these elimination
3
A CH3CH
A
3 2
CH
CH
3
O
H
OH
HBr,
A 3
A 3
CH
CH
CH
2,2-Dimethyl-1-propanol
2-Bromo-2-methylbutane
3
2,2-Dimethyl-1-propanol
2-Bromo-2-methylbutane
CH3CCH
CH
CH3
CH
3 3CCH2CH3
2OH

in
Substrate
Rearrangement
Substrate
in
Primary
A Rearrangement
RearrangementHBr,
inaaaaPrimary
Primary
Substrate A
Rearrangement
in
Primary
Substrate
HBr,

CH33
Br
CH
CH33CCH22OH
CH33CCH22CH33
CH
Br
CH
Br
3
Br
3
OOH
HHBr,
OH
ACH
O
HBr,

H
AAAA 3
AAAA
HBr,

A CH
A
HBr,

HBr,

CH
CCH22OH
OH
CHCCH
3CCH
3CCH
2CH
CH
CH
CCH
CH
3
3
2
3
22CH
O
CH
CCH
OH
CH
CCH
CH33333
H
OH
CH ACCH
OH
CH33CCH
CH
H
O
H
OH
OOH
HO
OH
CH
O
H
OH
AAAA 22
AAAA 22 CH
CH33 33CH
CH
33
CH3
CH3
CH
CH

CH
CH3333
CH
2,2-Dimethyl-1-propanol
2,2-Dimethyl-1-propanol
2,2-Dimethyl-1-propanol
2,2-Dimethyl-1-propanol
2,2-Dimethyl-1-propanol
2,2-Dimethyl-1-propanol
2,2-Dimethyl-1-propanol
(Neopentyl
alcohol)
(Neopentyl
alcohol)
(Neopentyl
alcohol)
(Neopentyl
alcohol)
(Neopentyl
alcohol)
alcohol)
(Neopentyl(Neopentyl
alcohol)

CH
CH3333
CH

3
2-Bromo-2-methylbutane
2-Bromo-2-methylbutane
2-Bromo-2-methylbutane
2-Bromo-2-methylbutane
2-Bromo-2-methylbutane
2-Bromo-2-methylbutane
2-Bromo-2-methylbutane

In
protonation
to
form
the
alkyloxonium
ion,steric
sterichindrance
hindranceinterferes
interfereswith
with
hindrance
interferes
with
In
this
case,
after
protonation
to
Inthis
protonationto
toform
formthe
thealkyloxonium
alkyloxoniumion,
ion,
steric
hindrance
interferes
with
this case,
case, after
after protonation
protonation
to
form
the
alkyloxonium
ion,
steric
hindrance
interferes
with

direct
displacement
by
bromide
(Section
6-9).
Instead,water
waterleaves
leavesat
atthe
thesame
same
timeas
asaaaaa
displacement
bromide
(Section
6-9).
leaves
at
the
same
time
as
direct
displacement
time
direct
by
bromide
(Section
6-9). Instead,
Instead,
water
leaves
at
the
same
time
as
displacement by
by
bromide
(Section
6-9).
Instead,
water
leaves
at
the
same
time
as
er
protonation
to
form
the
ion,
steric
hindrance
er
protonation
tofrom
form
the alkyloxonium
alkyloxonium
ion,
steric
hindrance
methyl
migrates
the
neighboring
carbon,
thusbypassing
bypassing
formationof
ofaaaaaprimary
primary
methyl
group
migrates
formation
bypassing
formation
of
primary
group migrates
migrates
from
the
neighboring
carbon,
thus
bypassing
formation
of
primary
methyl group
migratesfrom
fromthe
theneighboring
neighboring carbon,
carbon,thus
thus
bypassing
formation
of
primary
ment
by
carbocation.
carbocation.
ment
by bromide
bromide (Section
(Section 6-9).
6-9). Instead,
Instead, water
water leaves
leaves at
at the
the
carbocation.
migrates
from
the
neighboring
carbon,
thus
bypassing
formati
migrates from the neighboring carbon, thus bypassing formati
Mechanism
Mechanism
of
Concerted
AlkylShift
Shift
Mechanism
Mechanism
of
Concerted
Alkyl
Shift
Mechanismof
ofConcerted
ConcertedAlkyl
Alkyl
Shift

CH
CH
CH33
AAA 3

CH
CCH
OH
CH

CCH
OH
3

CH33CCH222
OH


AAA
CH
CH
3
CH33
3

CH
CH
CH
CH333






HH
O

AAAA 33

O
H


2

H
H

O



HH
O
H

H



O
C
CH
CH
O
CH
CH
OH
CH3333CCH
CCH22CH
CH
C
OH

3
33 3

O
CH
CCH
CH
O
3CCH
2CH
CH
CH
OCH
O
OH
CH3333C
CO
CH22222O
OH22222
CH
A
AAAA 22CH33
AAA
Mechanism
of
Concerted
Alkyl
Mechanism
of
Concerted
Alkyl
CH
CH
CH
3
3
CH
CH
CH
CH33
CH3 3




222
2

33

33

Br

Br
Br

Br

AABr
AAA
CH
CCH
CH
CCH
CH
CH
CCH
CH
3
222CH
333 3
CH
CH
CH33CCH
3A3CCH
22CH
3



Br


AAAA
Br


Br



Br



Br

Shift

Shift
CH
CH
3
CH
CH
CH3333
 




Br


Br


Br



Br


Br





CHofof
Rearrangements
of3
primary
substrates

3primary
Rearrangements
are
processes,
usually
requiring
relativelydiffi
difficult

Rearrangements
primary
substrates
arerelatively
cultprocesses,
processes,usually
usuallyrequiring
requiring
Rearrangements
substrates
diffi
cult
processes,
usually
requiring

primarysubstrates
relatively
diffi
cult
processes,
usually
requiring



Br



Br


O

A ofand
elevated
temperatures
and
long
reaction
times.
H temperatures
H
H222
O



H
elevated
temperatures
long
reaction
temperatures
and
reaction times.
times.


elevated
temperatures
and long
long reaction

OH22
CH33CCH22CH33
CH33C O CH22 O

A
CH
CH33

A
CH
CH33




Br

Br




ments
ments of
of primary
primary substrates
substrates are
are relatively
relatively diffi
difficult
cult processes,
processes, uu
ratures
and
long
reaction
times.
ratures and long reaction times.

REACTION

REACTION
Chapter 9

REACTION
Nucleophile: red
Electrophile: blue
Leaving
group:
Nucleophile:
redgreen
Electrophile: blue
Leaving group: green

MECHANISM
Nucleophile: red
Electrophile: blue
MECHANISM
Leaving group: green

343

migrating group delivers its bonding electron pair to a positiv

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xchanging
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Rearrangement
may
lead
Further Reactions of Alcohols and the Chemistry of Ethers
n the conversion of a secondary cation into a tertiary one
ndergo
rearrangement,
but they
do dsot h ininby
concerted
pathwa
In
Another
mode
of
reactivity
of
carbocations,
in
addition
regular
1and
and
Summary
Another
mode
of
reactivity
of
carbocations,
addition
totto
regular
S
Summary
reactivity
addition
regular
StS
of
carbocations,
in
addition
regular
InSummary
Another
mode
ofIn
reactivity
of
carbocations,
toto
SNNhNN11SS
reactivity
carbocations,
incarbocations,
addition
to
regular
S1eNNand
an
F u r tAnother
hAnother
e r R emode
amode
c t i oof
nof
s reactivity
o f A l cAnother
oof
h ocarbocations,
lmode
s aofnreactivity
ein
Caddition
h e m i sto
rto
yregular
o f to Eregular
rand
s1an
Summary
of
in
addition
S1
and
nn E1
Summary
Another
mode
of
reactivity
of
carbocations,
in
addition
regular
11the
an
Nthe
rearrangement
by
hydride
or
alkylbyshifts.
shifts.
In
such
rearrangements,
processes,
is
rearrangement
by
hydride
or
such
rearrangements,
E1processes,
E1by
processes,
is rearrangement
hydride In
or
shifts.
In such rearrangements,
th
processes,
isprimary
rearrangement
by
hydride
or
alkyl
In
such
rearrangements,
the
rearrangement
by
hydride
or alkyl
shifts.
In
such
rearrangements,
the
is
rearrangement
hydride
or
alkyl
shifts.
In
such
rearrangements,
th
hydride
alkylshifts.
shifts.
Inalkyl
such
rearrangements,
th
mediacy
of
cations.
In
Summary
Another
mode
of
reactivity
of
carbocations,
in
addition
to
regular
S
1
and
11E1
N
processes,
is
rearrangement
by
hydride
or
alkyl
shifts.
In
such
rearrangements,
N
migrating
group
delivers
its
bonding
electron
pair
to
a
positively
charged
carbon
neighbor
migrating
delivers its
its bonding
bonding electron
electron pair
pair to
to aa positively
positivelycharged
chargedcarbon
carbonneighbor,
neighbor,th
migrating group delivers
344

Further Reactions of Alcohols and the Chemistry of Ethers

Chapter 9

groupdelivers
delivers
its
bonding
electron
pair
to
positively
charged
carbon
neighbor,
migrating
delivers
itsbonding
bonding
electron
pair
positively
charged
carbon
neighbor,
igrating
group
its
electron
pair
to
positively
charged
neighbor
electron
pair
toaaaashifts.
positively
charged
carbon
neighbo
exchanging
places with
the
charge.
Rearrangement
lead
to acarbon
more stable
cation
a
E1 processes,
is
rearrangement
by hydride
or
alkyl
Intosuch
rearrangements,
theas
igrating
group
delivers
its
bonding
electron
pair
to
positively
charged
carbon
neighbo
exchanging
with
the
charge.
Rearrangement
may
lead
aamay
more
stable
cation

places
with
the
charge.
Rearrangement
may
lead
cation

as
places
with
the
charge.
Rearrangement
may
lead
toto
acharged
more
stable
cation

as
in the Rearrangement
conversion
of a secondary
cation
intoto
a a
tertiary
one.stable
Primary
alcohols
also
exchanging
withthe
the
charge.
Rearrangement
may
lead
more
stable
cation

ascan
xchanging
places
with
charge.
lead
to
aaamore
more
stable
cation

aa
Rearrangement
may
lead
to
more
stable
cation

migrating
group
delivers
its
bonding
electron
pair
to
a
positively
carbon
neighbor,
xchanging
places
with
the
charge.
Rearrangement
may
lead
to
more
stable
cation

undergo
rearrangement,
but
they
do
so
by
concerted
pathways
and
not
through
intera
in
the
conversion
of
a
secondary
cation
into
a
tertiary
one.
Primary
alcohols
also
can
In Summary
Another
mode cation
of
reactivity
carbocations,
in
additionalcohols
to regular
SN1the
and
of
aaa secondary
into
aaof
tertiary
one.
Primary
also
can
in
the
conversion
of
secondary
cation
into
tertiary
one.
Primary
alcohols
also
can
in
the
conversion
of
secondary
cation
into
a
tertiary
one.
Primary
alcohols
also
can
n exchanging
the
conversion
aaissecondary
cation
into
aaa or
tertiary
one.
alcohols
also
ca
placesof
with
the
charge.
Rearrangement
may
lead
to Primary
aIn
more
stable
cation

as
mediacy
of primary
cations.
cation
into
tertiary
one.
Primary
alcohols
also
ca
E1
processes,
rearrangement
by
hydride
alkyl
shifts.
such
rearrangements,
the
the
conversion
of
secondary
cation
into
tertiary
one.
Primary
alcohols
also
ca
undergo
rearrangement,
but
they
do
so
by
concerted
pathways
and
not
through
the
interbut
they
do
so
by
concerted
pathways
and
not
through
the
interundergo rearrangement,
undergo
rearrangement,
butthey
they do
docation
so by
byinto
concerted
pathways
and
not
through
the
so
concerted
pathways
and
not
through
the
inter
in the rearrangement,
conversion
ofcations.
a but
secondary
a tertiary
Primary
alcohols
can
ndergo
so
by
concerted
pathways
and
not
through
theinterinte
migrating
group
delivers
itsdo
bonding
electron
pair to
aone.
positively
charged
carbonalso
neighbor,
mediacy
primary
ndergo
rearrangement,
but
they9-4
so
by
concerted
pathways
and
not
through
the
inte
of
primary
cations.
mediacy
ofprimary
primary
cations.
Esters
from
Alcoholspathways
and Haloalkane
Synthesis
mediacy
primarycations.
cations.
undergoofexchanging
rearrangement,
they
so byRearrangement
concerted
through
interplacesbut
with
the do
charge.
may leadand
to anot
more
stable the
cation
as
ediacy
ediacy
of primary cations.

9-4 Esters from Alcohols and Haloalkane Sy

Reaction of alcohols with carboxylic acids converts them to organic esters, also called
mediacyinofthe
primary
cations.
of a secondary
cation into a tertiary
one. Primary
alcohols
also canto
eaction
ofconversion
alcohols
with carboxylic
acids
converts
them
carboxylates or alkanoates (Table 2-3). They are formally derived from the carboxyli
9-4
Alcohols
and
Haloalkane
Synthesis
Esters
Alcohols
and
Synthesis
undergo from
rearrangement,
but
doHaloalkane
so by
concerted
pathways
and
througha the
interacidsthey
by
replacement
of the
hydroxy group
with alkoxy.
Onenot
can formulate
corresponding
9-4
Esters
from
Alcohols
and
Haloalkane
Synthesis
arboxylates
or
alkanoates
(Table
2-3).
They
are
formally
Esters
from
Alcohols
Haloalkane
Synthesis
set of and
inorganic
esters derived from
inorganic
acids, such as
those based
on phosphoru
9-4
Haloalkane
Synthesis
mediacy
of
primary
cations.
9-4
Esters
from
Alcohols
and
Haloalkane
Synthesis
Reaction
alcohols
with
carboxylic
acids
converts
them
to
organic
esters,
also
called
of
alcohols
with
carboxylic
acids
converts
them
to
organic
esters,
also
called
and
sulfur
in
various
oxidation
states.
In
such
inorganic
esters,
the
attachment
of th
9-4
Esters
from
Alcohols
and
Haloalkane
Synthesis
Reaction
Reaction of alcohols
alcohols with
with carboxylic
carboxylic acids
acids converts
converts them
them toto organic
organic esters,
esters, also
alsocalled
called
cids
byof
replacement
of the
hydroxy
group
with
alkoxy.
One
c
alcohols
with carboxylic
acids
converts
them
organic
esters,
also
calle
or
(Table
They
are
formally
derived
from
the
carboxylic
carboxylates
alkanoates
(Table
2-3).
They
are
formally
derived
from
the
carboxylic
eaction
carboxylic
acids
converts
them to
to
organic
esters,
also
calle
carboxylates
or
alkanoates
(Table
2-3).
They
are
formally
derived
from
the
carboxylic
eaction
ofofalcohols
with
carboxylic
acids
converts
them
to
organic
esters,
also
calle
carboxylates
or alkanoates
alkanoates
(Table 2-3).
2-3).
They
areOrganic
formally
derived
from
thealso
carboxylic
andto
Inorganic
Esters
Reaction
alcohols
with
carboxylic
acids
converts
them
organic
esters,
called
9-4
from
Alcohols
and
Haloalkane
Synthesis
arboxylates
or
alkanoates
(Table
2-3).
They
are
derived
from
the
by
replacement
of
group
with
alkoxy.
One
can
formulate
aaacorresponding
acids
replacement
of
the
hydroxy
group
with
alkoxy.
One
can
formulate
corresponding
arboxylates
or Esters
alkanoates
(Table
2-3).
They
are formally
formally
derived
from
the carboxyli
carboxyla
acids
by
replacement
of
the
hydroxy
group
with
alkoxy.
One
can
formulate
corresponding
et
of
esters
inorganic
acids,
such
acids
byinorganic
replacement
of the
the hydroxy
hydroxy
groupThey
withfrom
alkoxy.
One
canderived
formulate
corresponding
arboxylates
or
(Table
2-3).
They
are
formally
from
the
carboxyl
carboxylates
oralkanoates
alkanoates
(Tablederived
2-3).
are
carboxylic
O athe
O
O formally
HO derived from
O
cids
by
replacement
of
hydroxy
group
with
alkoxy.
One
formulate
aa correspondin
set
esters
derived
from
inorganic
acids,
such
as
those
based
on
phosphorus
of
inorganic
esters
derived
acids,
such
as
those
based
on
B inorganic
B
Besters,
Gcan
cids
by
replacement
ofofthe
the
hydroxy
group
with
alkoxy.
One
can
formulate
correspondin
Reaction
of
alcohols
withfrom
carboxylic
acidsalkoxy.
converts
them
to
organic
alsoM called
set
ofby
inorganic
esters
derived
from
inorganic
acids,
such
as
those
based
on
phosphorus
cids
by
replacement
of
the
hydroxy
group
with
alkoxy.
One
can
formulate
a phosphorus
correspondin
acids
replacement
the
hydroxy
group
with
can
Ocorresponding
S O OH e
P Oformulate
OH
C
HO O
P O OH One
R O Sainorganic
OH
nd
sulfur
in
various
oxidation
states.
In
such
sulfur
in
states.
such
inorganic
esters,
the
attachment
of
et
of
inorganic
esters
derived
from
inorganic
acids,
as
based
on
phosphoru
and
various
oxidation
states.
In
such
esters,
the
attachment
the
carboxylates
or oxidation
alkanoates
(Table
2-3).
They
aresuch
formally
derived
from
the
carboxylic
Ainorganic
B
R
OHIn
sulfur
in
various
states.
In
such
inorganic
esters,
the
attachment
ofDof
the
et
of of
inorganic
esters
derived
from
inorganic
acids,
such
those
based
on
phosphoru
Das those
sulfur
in various
various
oxidation
states.
In
such
inorganic
esters,
the
attachment
of the
the
etand
of
inorganic
esters
derived
inorganic
acids,
such
asthose
those
based
phosphoru
set
inorganic
estersoxidation
derived from
from
inorganic
acids,
such
as
based
on on
phosphorus

set of inorganic esters derived from inorganic acids, such as those based on phosphorus

of inorganic
esters derived
inorganic
acids,
suchHO
as those
basedO ona corresponding
phosphorus
HO
OH
acids
by replacement
of thefrom
hydroxy
group
with
alkoxy.
One
can
formulate
ndsetsulfur
in
oxidation
states.
In
such
inorganic
esters,
the
attachment
of
nd
sulfur
ininvarious
various
oxidation
states.
In
such
inorganic
esters,
the
attachment
ofacidth
th
carboxylic acid
Phosphoric
acid
Phosphorous
acidthe
A attachment
sulfonic
acid
Sulfurous
sulfurin
various oxidation
oxidation Astates.
In
such
inorganic
esters,
of the
ndandsulfur
In
such
inorganic
esters,
the
attachment
of
th
set ofvarious
inorganic
esters derived
from
those
based
on phosphorus
(An organic
acid) inorganic acids, such as
(Inorganic
acids)
Organic
Organic and
andInorganic
InorganicEsters
Esters
Organic
and
Inorganic
Esters

Organic and
Esters esters, the attachment of the
and sulfur in various Ooxidation
states.Inorganic
In such inorganic
O
O
HO
O
Organic and Inorganic Esters

Organic
Inorganic
Esters
Organic
and
Inorganic
Esters
B
B
BOrganic and
G
and
Inorganic
Esters
M
O
O
OOrganic
HO
O
and
Inorganic
Esters
OO
O
HO
HO
OO
O P O O O R
PO O O
HO
R O S OO O R
R
SO O O R
C
HO
O
BO
BBO
B
B
M
G
AG
B
MM
OR Organic G
RB
DEsters
D
and
Inorganic
B
BO
G
M
O
HO
O
HO R
HO
O
O
O
OH
O
O
O
O
O
O
O
O
S
OH
P
OH
HO
P
OH
S
OH
HO
O
O
O
O
O
O
O
HO
O
S
OH
P
OH
HO
P
OH
R
S
OH
O
SOM
OH
PP OOH
HO
PP OOH
RR OSSBO
OH
HO
O
O
S
OH
OH
HO OO
OH
OH
B
O
G
HO
B
B
A
G
BOA sulfonate ester M
GDHO
D
D
M
A carboxylate
ester
A phosphate
A phosphite esterBBB
A sulfite ester
D
DO
D
BBAAAO OHO
G
M
BS
D
DPPPester
O
O
O
O
S
OH
OH
HO
PP
R
OH
HO
HO
(Inorganic
esters)
O
O
O(An
O
O
O
organic
ester)
S
OH
OH
HOO
P
OH
R
S
OH
B
OH
O
HO
HO
O
O
O
O
O
O
G
B
B
S
OH
OH
HO
OH
R
S
OH
HO
HO
OH
O
G
M
OOBS O OH
O
O
O OH
O
HO
S
OH
P
OH
HO OAPAOH
R
HOD
OH
A
B
D
D
D D
O OH A
O
O
SO
OH
Pacid
P O OH
RO
OH Sulfurous
D
Phosphoric
acid
Phosphorous
acid
DOH
Phosphoric
acid
Phosphorous
acid
sulfonic
acid
Sulfurous
acid
Phosphoric
acid
Phosphorous
acid
AAsulfonic
sulfonic
acid
Sulfurous
acid
AHOHO
BBOHSBacid
O
O
O
P
OH
C
P
RO
HO
heteroatom
turns
theD
normally
poor leaving
group
in
alcohols
into
aHO
good
leaving
group
HO
HO
A carboxylic
acid OHPhosphoric
acid
Phosphorous
acid
A
sulfonic
acid
Sulfurous
acid
OH
O
A
R
D
D
OH
O
HO
OH
O
(An
(Inorganic
HO
(An organic
organic acid)
acid)
(Inorganic acids)
acids)
HO

O
O
O
BB
B
O
O
O
C
C
O
C
B
OOHO
R
R
BB B OH
RC
OH
B
C CB
C
R
OH
R
OH
RA
OH
C
acid
acid
A carboxylic
carboxylic
acid
R
OH

OH

acid)
(An organic acid)
R
OH

A
OH
G

D
HO

acids)
acids)
O in the synthesis of haloalkanes (se
(Inorganic
(highlighted in the green (Inorganic
boxes),
which
can be used

HO acidacid
HO (Inorganic
OH Phosphorous
Oacid
organicacid
acid)
acids)
A(An
carboxylic
acid
Phosphoricacid
acid
acid
AA
sulfonic
A carboxylic
Phosphoric
acid
sulfonic
Sulfurous
also SectionPhosphorous
9-2). We have already
the good acid
leaving-group
ability of sulfate
A
carboxylic
acid
Phosphoric
acid
Phosphorous
acid mentioned
A
sulfonic
acid Sulfurous
Sulfurous
acidand
A
carboxylic
Phosphoric
acid
acid
A
sulfonic
acid
Sulfurous
acid
A acid
carboxylic
acid
Phosphoric
acidPhosphorous
Phosphorous
acid
Sulfurous
acid
(An organic
acid)
(Inorganic
acids) A sulfonic acid
organic
acid)
(An
organic
acid)
O
(An(An
organic
acid)
O
(An
organic
acid)
(An organicO
O
Bacid)

(Inorganic
acids)
sulfonate
groups in SN2 reactions
(Section
6-7). Here, we shall see how specific phosphoru
(Inorganic
acids)
O
HO
(Inorganic
acids)
O
OO
HO
HO
OO
(Inorganic
(Inorganic
and sulfur
this
task:acids)
HOGreagents accomplish
O
BOacids)

BB
M
BB
GG
MM
BOO O R
O
O

R
S
SO
OO
R
OM
acid
AR
s
OO
O
O
O
OO
OR
O
RR
SS
SO
SO
R
Reagent
X
O
O
OR
OPhosphorous
OO
RO
SOOO
OO
R
OM
O
B
BBS
OO
GD
R O OH
R
L O R
R O XM
A
OR
O
O
D
HO
AA
O
B
B
B
G
OR
D
D
DD
B
B
B
G
B
B
GDPO O O
AO O O R
BOO
MM
OR
M OO
Alcohol
Inorganic
Haloalkane
D
HO
B
B
HO
(An organic
acid)
(Inorganic
acids)
O
O
O
G
HO
P
R
S
R
SO
R
R
O
HO
HO
HO
HO
OH
OO
OH
O
O
O
O
OO
O
HO
SO
O
R
SO
O O O RHODPO
O
HO
R
S OO
SO
RRR
C
R HO
OP
O
OPR
POO
OO
O
O
OO
OOR
HO O
P
RO
Sester
OO
R
OPO
RO R R
SOOOO
O
R
AO
BO
OR
DD
O
O
PO
O
O
O
OO
O
HO
P
R
O
O
R
SO
R
R
AAOH
BS
AR
OR
Rester OR
D
D
DDester
B Bester
ylate
A
phosphate
A
phosphite
A
A
OR
Dreact
HO
HO
ester
A
phosphate
ester
A
phosphite
ester
AAsulfonate
sulfonate
A
sulfite
OOB
ylate
phosphate
ester
AHO
phosphite
ester
sulfonate
ester
Asulfite
sulfite
ester
AOH ester
OR
ester
A
D
HO ester
Dester
HO
with carboxylic
acids
to give organic
esters
OH Alcohols
Oester
ylate
ester
A phosphate
ester
A phosphite
ester
A sulfonate
ester
AHO
sulfite
ester
OH

BO O O R
O
O
HO
P
O
R
HOGPO
A carboxylic
acid
Phosphoric
acid
O
O
O
PO
O
O
HO
PP
OOO
R
O
R
R
HO
O
O R
O
O
OO
O
PO
O
HO PO
HOO
PO
OO
R
R
HO O

HO
HO
(Inorganic
O
(Inorganic
esters)
HO
(Inorganicesters)
esters)
O
O A HO
O
HO
phosphite
ester
sulfonate
ester
sulfite
ester
inorganic
acid, such
as H SOesters)
or A
HCl,
to give organic
esters and A
water,
a process
A
phosphite
ester
A
sulfonate
ester
A
sulfite
estercalled
(Inorganic
B
B
(Inorganic
esters)
(Inorganic
esters)
A phosphite
estermaterials
AG
sulfonate
ester
A form
sulfite
ester
esterifi
cation.
Starting
and
products
in
this
transformation
an
equilibrium
(Inorganic
esters)
ester)
heteroatom turns
the
normally
poor
leaving
group
OHesters)
ininalcohols
into aagood
leaving group
turns
the
(Inorganic
ester)
heteroatom
the
normally
poor
leaving
alcohols
good
group
turns
that can
be shifted group
in either OH
direction.
The
formationinto
and
reactions
ofleaving
organic esters
will bO
(Inorganic
esters)
ester)
heteroatom
turns
the
normally
poor
leaving
group
OH
in
alcohols
into
a
good
leaving
group
O
O
O
PO
O
O
HO
P
R
S
O
R
O
R
(highlighted in
the
green
boxes),
which
can
used
in
the
ofofhaloalkanes
(see
presented
in detail
inbe
Chapters
and
20. synthesis
in
the
green
which
can
be
used
in
the
synthesis
(see
(highlighted
green
boxes),
which
can
be
used
in
the
synthesis
haloalkanes
(see
in
heteroatom
theboxes),
poor
leaving
group
OH
in alcohols
a haloalkanes
good
leaving
group
heteroatom
turns
theturns
normally
poor
leaving
group
OH19in
alcohols
intointo
a of
good
leaving
group
(highlighted
in the
the
green
boxes),
which
can
be
used
inleaving-group
the
synthesis
of
haloalkanes
(see
Anormally
B
OR
Dthe
also Section
9-2).
We
have
already
mentioned
the
good
ability
of
sulfate
and
Section
9-2).
We
already
mentioned
the
good
leaving-group
ofofleaving
sulfate
and
eteroatom
turns
normally
poor
leaving
OH
in
alcohols
into
aa good
grou
also
We
have
already
mentioned
the
good
leaving-group
ability
sulfate
and
Section
9-2).
(highlighted
in have
the boxes),
green
boxes),
which
can
be
used
in the
synthesis
of
haloalkanes
(see
Esterification
(highlighted
in the
the
green
which
cangroup
be
used
in
synthesis
of
haloalkanes
eteroatom
turns
normally
poor
leaving
group
OH
in
alcohols
intoability
good
leaving
grou
also
Section
9-2).
We
have
already
mentioned
the
good
leaving-group
ability
ofphosphorus
sulfate(see
and
eteroatom
turns
the
normally
poor
leaving
group
OH
in
alcohols
into
a
good
leaving
grou
sulfonate
groups
in
S
2
reactions
(Section
6-7).
Here,
we
shall
see
how
specifi
c
HO
N
groups
in
SS9-2).
2have
reactions
(Section
6-7).
Here,
we
shall
see
how
specifi
ccphosphorus
OH
O
highlighted
in
the
green
boxes),
which
can
be
used
in
the
synthesis
of
haloalkanes
(se
N
sulfonate
2
reactions
(Section
6-7).
Here,
we
shall
see
how
specifi
phosphorus
also
Section
We
have
already
mentioned
the
good
leaving-group
ability
of
sulfate
and
groups
in
N
O
O
also
Section
9-2).
We
already
mentioned
the
good
leaving-group
ability
of
sulfate
and
highlighted
in theingreen
boxes), (Section
which can
beHere,
usedwe
in shall
the synthesis
of haloalkanes
(se
sulfonate groups
SN2 reactions
6-7).
see how specifi
c phosphorus

nic
nic ester)
ester)
nic
ester)

OH
OH

(Inorganic
esters)
OH ester
O ester of catalytic
nic
ester)
(Inorganic
nic
Alcohols
react
with
carboxylic
acids
the presence
of a strong
ylate
ester
A phosphate
A phosphite
ester
A
sulfonate
A sulfite
ester
A ester)
carboxylate
ester
A phosphate ester
A phosphite
esteresters)
Ainsulfonate
ester
Aamounts
sulfite
ester

e ester

A phosphate ester

ee ester
ester
A phosphate
phosphate ester
ester
nic
ester)
nic
ester)
(An
organic ester)
A

highlighted
in theWe
green
boxes),
which
can
be
used
inleaving-group
theshall
of
haloalkanes
(se
B
B
andSection
sulfur
reagents
accomplish
this
task:
H synthesis
sulfur
reagents
this
task:
sulfonate
groups
Salready
(Section
6-7).
Here,
we
see
how
specifi
c phosphorus
and
accomplish
this
task:
so
9-2).
have
mentioned
good
ability
of
sulfate
N2 reactions
sulfur
reagents

CH
HOH
sulfonate
groups
in
Saccomplish
2 in
reactions
(Section
6-7).the
Here,
we2OH
shall
see CH
how
specifi
phosphorus
CH
3CH
2CH3 c
3COH
3COCH
and
sulfur
reagents
accomplish
this
task:
N
so
Section
9-2).
We
have
already
mentioned
the
good
leaving-group
ability
of
sulfate an
an
N
Section
9-2).
We
have
already
mentioned
good
leaving-group
ability
of
sulfate
an
so
andreagents
sulfur
reagents
accomplish
this
task:
Acetic
acid the
Ethanol
Ethyl
acetate
te
ester
A
phosphate
ester
A
phosphite
ester
A
sulfona
ulfonate
groups
in
S
2
reactions
(Section
6-7).
Here,
we
shall
see
how
specifi
c
phosphoru
and
sulfur
accomplish
this
task:

N

solvent
ulfonate groups
groups in
in S
SN22 reactions
reactions
(Section 6-7).
6-7). Here,
Here,
we shall
shall see
see how
how specifi
specificc phosphoru
phosphoru

Reagent
X
(Section
we
ulfonate
Reagent
X
N

Reagent
X
nd
sulfur
reagents
accomplish
this
task:
O
O
O
R
OH
R
L
R
X

(Inorganic
esters)
ester)
Reagent
X
R
OH this
R O LL
RRO
X
nd
sulfur reagents
reagents accomplish
accomplish
this
task:
O
O
RO
Reagent R O
X
sulfur
task:
nd

O OH
O
OX








OH




sulfonate
reactions
(Section 6-7).
Here,we
weshall
shall
seehow
howspecifi
specificcphosphorus
phosphorus
Reagent
X
SSNN22 reactions
(Section
Here,
Reagent
X see
sulfonate groups
O in
OL
OX
RO
OH
R6-7).
L
RO
Xester
O
OH
RR
O
O
R
L
X
and sulfur R
accomplish
this task:
task: R
reagents
accomplish
this



Alcohol

O OH
RAlcohol




O OH
RO

Inorganic
Reagent Inorganic
Inorganic
R O LXX
ester
Reagent
Reagent
ester
ester



OL
RO

Haloalkane
XHaloalkane
Haloalkane

OX
RO

R OX

R O OH
R OL
R OX
Alcohol
Inorganic
Haloalkane
Alcohols
react with
carboxylic
acids
to g
Alcohol
Alcohol

Inorganic
Inorganic

Haloalkane
Haloalkane

ester ester
ester
ss react
react with
with carboxylic
carboxylic acids
acids
to give
give organic
organic esters
esters
to
acids
to
give
organic
esters
Alcohols
react with
carboxylic
acids
in the
presen

react
with carboxylic
to
esters
Alcohols
carboxylic
acids
to give
give organic
organic
estersamounts
with
carboxylic
acids
inacids
the
presence
of HCl,
catalytic
amounts
o
eact
carboxylic
acids
in
the
presence
of
catalytic
eact with
in
the
presence
of
catalytic
amounts
inorganic
acid,
such
as
H2SOto
to give
organ
4 or
react
with
carboxylic
acids
give
organic
esofo
react
with
carboxylic
acids
in
the
presence
of
catalytic
amounts
ofof aa strong
Alcohols
with
carboxylic
acids
in
the
presence
of
catalytic
amounts
acid,
such as
as H
H22SO
SO44 or
or HCl,
HCl, to
to give
give organic
organic esters
esters and
and
water,
astrong
pro
such
water,
a
proc
acid,
HCl,
to
give
organic
esters
and
water,
a
pro
4 SO
products
thi
acid, such
as
HCl,
organic
and
aaprocess
inorganic esterifi
such cation.
as H
H
orStarting
HCl, to
to give
givematerials
organic esters
estersand
and water,
water,
processin
called
22SO44 or
on.
Starting
materials
and
products
in
this
transformation
formcalled
an eee
Starting
materials
and
products
in
this
transformation
an
on.
products
in
this
transformation
form
an
cation.
Starting
materials
and
products
in
this
transformation
form
an
equilibrium
esterifi
Starting
materials
and
products
in
this
transformation
form
anform
equilibrium
eact
with
carboxylic
acids
ineither
the
presence
of
catalytic
am
that
can
be
shifted
in
direction.
The
formation
direction.
The
formation
and
reactions
ofesters
organic
est
can beinshifted
in
direction.
The
formation
reactions
of
will
shifted
either
direction.
The
and
reactions
of
organic
este
that
in either
either
direction.
Theformation
formation and
and
reactions
oforganic
organic
esters
willbe
be
The
formation
and
reactions
of
organic
est
cid,
such
as
H
SO
or
HCl,
to
give
organic
esters
and
wate
in19
in Chapters 19 and 20.
4 detail
in
in
19
20.
in2Chapters
Chapters
19 and
and
20.
nnpresented
detail presented
indetail
Chapters
19
and
20.
and
20.
detail
in
Chapters
20.

on. Starting materials and products in this transformation fo

Esterification
Esterification
Esterification
shifted in either direction.
The formation
and Esterification
reactions of or
Esterification
Esterification
OO
O
B
BB
HH
n detail
in
Chapters
19
and
20.
O CH33COH
O 22CH
CH
O
 CH
CH33CH
OH
CH33  HOH
HOH
CH
COH 
CH33COCH
COCH
O
O
O22OH
B
H
BB Acetic
BBacetate
Ethanol
Ethyl
H
Acetic acid
acid
Ethanol
Ethylacetate
H
B
H HOH
solvent
solvent
OH
CH

CH
CH
COCH
CH
COH

CH
OH
CH
HOH
CH
CH
2
3
3
22
33
2CH33
3 
3COCH

HOH
CH2222OH
CH33COH  CH3333CH
CH
COCH
Esterification

CH
OH
CH
COH
CH
3
2
3
Acetic acid
Ethanol
Ethyl acetate







Acetic
Acetic acid
acid

O
B
CH3COH

Acetic acid

Ethanol
Ethanol
Ethanol
Acetic acid
solvent
solvent
solvent

Ethyl
Ethylacetate
acetate
Ethyl
acetate

H

CH3CH2OH
Ethanol
solvent

Ethanol
O
solventB

CH3COCH 2CH3
Ethyl acetate

sters

9 -- 4
4 E
m A
h oo ll ss aa n
nd
d H
E ss tt ee rr ss ff rr oo m
A ll cc oo h
H aa ll oo aa ll kk aa nn eee S
S
9
S yyy nn
n ttt hh
h eee sss iii sss

Haloalkanes
can
from
alcohols
E
rbe
s Amade
fmade
rl oc m
l lcso h aoalcohols
l sd a n
aathrough
l lo ka lakna en e SSyynn tt h ee ssi iss
9
- 4 E s t e9 r- s4 can
f rs ot em
o hAofrom
n
Hda lHothrough
Haloalkanes
be
9-4
E s complications
tmade
e r s f r from
o m A lalcohols
c o hthat
o l s acan
nthrough
d H
a l oencountered
e s ithe
s
diffi
culties
and
be
oalkanes
through
can
be
inorganic
esters
oalkanes
inorganiccan be made from alcohols through a l k a n e S y n t hin
oalkanes
Haloalkanes
can
be made from
alcohols9-2),
through
Haloalkanes
alcohols
into
haloalkanes
(Section
several
alternatives
h
ganic
esters
ganic
Because
of esters
the diffi
difficulties
culties and
and complications
complicationsthat
thatcan
canbe
beencountered
encounteredinin
inthe
theacid
ac
ganic
esters
Because
the
diffi
culties
and
complications
that
can
be
encountered
the
ac
of
the
inorganic
inorganic
esters
Haloalkanes
can
beand
made
from
alcohols
through
ethods
rely
on
a
number
of
inorganic
reagents
that
are
capab
conversions
of
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
use
can
be
encountered
in
the
acid-catal
of
the
diffi
culties
complications
that
can
be
encountered
in
the
acid-catal
of
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
conversions
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
use
of the
the
diffi
culties
and
complications
that
can
beencountered
encountered
theacid-cataly
acid-catalb
es
can
made
from
alcohols
through
use
of
diffi
culties
and
complications
that
can
be
encountered
ininthe
Haloalkanes
can
be
made
alcohols
through
Because
ofbe
the
diffi
culties
and
complications
that
can
be
in the
the
acid-catalyzed
inorganic
esters
of
the
diffi
culties
and
complications
that
can
be
encountered
in
Because
acid-catalyzed
oped.
methods
rely
on from
number
ofunder
inorganic
reagents
thatacid-catalyzed
are
capable
ersions
9-2),
several
alternatives
have
been
of
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
been
de
These
methods
rely
on
aaa number
of
inorganic
reagents
that
are
capable
oped.
methods
rely
on
number
of
inorganic
reagents
that
are
capable
nction
into
a
good
leaving
group
milder
conditions.
Th
ersions
of
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
been
ddo
conversions
of
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
been
develersions
of
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
dev
of
alcohols into
haloalkanes
(Sectiongroup
9-2), several
alternatives
have been
develinorganic
esters
conversions
beenbeen
develthe
function
into
aacomplications
good
leaving
under
milder
conditions.
Thus,
Because
of the
diffirely
culties
and
that
canreagents
be
encountered
in
the
acid-catalyzed
hydroxy
function
into
anumber
good
leaving
group
under
milder
conditions.
Thus,
...esters
These
methods
rely
on
a number
number
of
inorganic
reagents
that
are
capable
of
chan
inorganic
reagents
that
are
capable
of
chan
the
function
into
good
leaving
group
under
milder
conditions.
Thus,
These
methods
on
a
of
inorganic
reagents
that
are
capable
of
chan
oped.
These
methods
rely
on
a
number
of
inorganic
that
are
capable
of
changing
These
methods
rely
on
a
of
inorganic
reagents
that
are
capable
of
chang
oped.
These
methods
rely
on
a
number
of
inorganic
reagents
that
are
capable
of
changing
hols
react
with
phosphorus
tribromide,
a alternatives
readily
available
cop
changing
conversions
of
alcohols
into
haloalkanes
(Section
9-2),
several
have
been
develBecause
of the
diffi
culties
and
complications
that
can
be
encountered
in
the
acid-catalyzed
secondary
alcohols
react
with
phosphorus
tribromide,
aconditions.
readily
available
comm
ydroxy
under
milder
conditions.
Thus,
primary
function
into
a
good
leaving
group
under
milder
conditions.
Thus,
primary
alcohols
react
with
phosphorus
tribromide,
a
readily
available
comme
secondary
alcohols
react
with
phosphorus
tribromide,
a
readily
available
comm
the
hydroxy
function
into
a
good
leaving
group
under
milder
conditions.
Thus,
primary
and
he
diffi
culties
and
complications
that
can
be
encountered
in
the
acid-catalyzed
ydroxy
function
into
a
good
leaving
group
under
milder
Thus,
primary
hydroxy
function
into
a
good
leaving
group
under
milder
conditions.
Thus,
primary
and
the
primary
and
ydroxy
function
intorely
ainto
good
leaving
group
under
milder alternatives
conditions.
Thus,
primary
a
oped.
These
methods
on
aphosphorus
number
of
inorganic
that
are
capable
of
changing
conversions
of
alcohols
haloalkanes
(Section
9-2),reagents
several
have
been
develbromoalkanes
and
phosphorous
acid.
This
method
constitute
pound,
bromoalkanes
and phosphorous
phosphorous
acid.
This
method
constitutes
ndary
tribromide,
areadily
readily
available
commercial
secondary
alcohols
react
with
tribromide,
available
commercial
comalcohols
react
with
phosphorus
tribromide,
aareadily
readily
available
commercial
toalcohols
give
bromoalkanes
and
This
method
constitutes
a aagc
pound,
bromoalkanes
and
phosphorous
This
method
constitutes
react
with
phosphorus
tribromide,
aaacid.
available
commercial
comsecondary
commercial
comof
alcohols
into
haloalkanes
(Section
9-2),
several
alternatives
have
been
develndary
alcohols
react
with
phosphorus
tribromide,
readily
available
commercial
react
with
phosphorus
tribromide,
aacid.
readily
available
commercial
the
hydroxy
function
into
aon
good
leaving
under
milder
conditions.
Thus,
primary
andcoc
oped.
These
methods
rely
a number
ofgroup
inorganic
reagents
thatconstitutes
are capable
of changing
pound,
to
give
bromoalkanes
and
phosphorous
acid.
This
method
a
general
way
of
bromoalkanes
from
alcohols.
All
three
bromine
atoms
are
transferred
d,
acid.
This
method
constitutes
a
general
to
give
bromoalkanes
and
phosphorous
acid.
This
method
constitutes
a
general
to
give
bromoalkanes
and
phosphorous
acid.
This
method
constitutes
a
general
way
making
bromoalkanes
from
alcohols.
All
three
bromine
atoms
are
transferred
pound,
general
way
of
bromoalkanes
from
alcohols.
All
three
bromine
atoms
are
moalkanes
from
alcohols.
Allgroup
three
bromine
atoms
are
d,the
bromoalkanes
and
phosphorous
acid.
This
method
constitutes
atransfe
general
methods
on areact
number
of
inorganic
reagents
that
are
capable
of
changing
tohydroxy
giverely
bromoalkanes
phosphorous
acid.
This
method
constitutes
atransferred
general
secondary
alcohols
with
phosphorus
a readily
available
commercial
comfunction
into
a and
good
leaving
under
milder
conditions.
Thus,
primary
and w
of
making
bromoalkanes
from
alcohols.
Alltribromide,
three
bromine
atoms
are are
transferred
from
phosmaking
bromoalkanes
from
alcohols.
All
three
bromine
atoms
are
transferred
from
of
from phosphosphorus
groups.
aking
bromine
atoms
are
transferred
from
bromoalkanes
from
alcohols.
All
three
bromine
atoms
transferred
from
ppp
to
alkyl
groups.
phorus
togive
alkyl
groups.
aking
bromoalkanes
from
alcohols.
All
three
bromine
atoms
are
transferred
from
unction
abromoalkanes
good
leaving
group
under
milder
conditions.
Thus,
and
pound,
to
and
phosphorous
acid.
This
method
constitutes
aprimary
general
way
bromoalkanes
from
All
three
bromine
atoms
are
transferred
from
ph
secondary
alcohols
react
withalcohols.
phosphorus
tribromide,
a readily
available
commercial
comgroups.
phorus
tointo
alkyl
groups.
to
alkyl
groups.
phorus
us to alkyl groups.

of to
making
bromoalkanes
fromand
alcohols.
All three
atoms
are
transferred
from phosuspound,
groups.
to give
bromoalkanes
phosphorous
acid.
This method
constitutes
a general
way
alkyl
groups.
cohols
react
with
phosphorus
tribromide,
abromine
readily
available
commercial
comBromoalkane
Synthesis
by
Using
PBr
Bromoalkane
Synthesis
by
Using
PBr
Bromoalkane
Synthesis
by
Using
PBr33a33 general
phorus
to alkyl
groups.
making
bromoalkanes
from
alcohols. acid.
All
three
bromine
atoms
are transferred
from phosBromoalkane
Synthesis
bymethod
Using
PBr
Bromoalkane
Synthesis
by
Using
PBr
eof
bromoalkanes
and phosphorous
This
constitutes
way
333
Bromoalkane
Synthesis
by
Using
PBr
Synthesisby
byby
Using
PBr3333 PBr3
phorus to alkylBromoalkane
groups.Bromoalkane
Synthesis
Using
Bromoalkane
Synthesis
by
Using
PBr
Synthesis
Using
PBr
omoalkanes from alcohols.
All three
bromine
are
transferred from phosBromoalkane
Synthesis
by atoms
Using PBr
3
(CH
CH
)
O
(CH
CH
)
O
(CH
CH
)
O
(CH CH ) (CH
O
CHUsing
) O PBr
yl groups.
Bromoalkane
Synthesis
by
 
PBr33 PBr
3
 H
H333PO
PO333
AA
A
A
AA AA
3AA3
PBr
PBr(CH
3 3
 HH
H

333
33
33P
33

PBr
3
CH
(CH
CH))))OO
O 3
3 CH
(CH
CH
O
(CH
OH
Br AA
Br
(CH CH ) O
OH
Br
OH 
Br 
A OH

PBr
3
33
3
 HH
H
PO
OH
Br
A
3
333PO

PBr
3

H
PO
PBr
3
)2O 3 PBr
A
A AA
33 3 (CH3CH
33 PO
3 333
2Using
 PBr
3 OH Bromoalkane

H
PO
3
47%
Synthesis
by
(CH CH ) O
3 Br
Br 47%
Br
47%
A  Phosphorous
OH
Br
PBr
3 47%
47%
A
ABr
 Phosphorus
3 OH
3 3-Bromopentane
H3PO3 
3 PBr3
Phosphorous
3-Pentanol
Phosphorus
3-Bromopentane
3-Pentanol
Phosphorous
3-Bromopentane
47%
Phosph
47%
Phosph
3-Pentanol
Phosphorus
3-Bromopentane
Phosp
3-Pentanol
Phosphorus
3-Bromopentane
OH
Br
47%
47%
47%
acid
tribromide
Phosp
3-Pentanol
Phosphorus
3-Bromopentane
OH
Br
acid
tribromide
3
333

33
33
3

2 2
222 222

33 3
3
3

2
22 2
222 2
2
2

22 22
2 22 2
2 2

2 2

tribromide
acid
aca
ac
tribromide
Phosphorous
a
3-Pentanol
Phosphorus
tribromide
Phosphorous
3-Bromopentane
Phosphorous
3-Pentanol
Phosphorus
3-Bromopentane
3-Bromopentane
(CH
47%
Phosphorous
3-Pentanol
Phosphorus
tribromide
Phosphorous
3-Bromopentane
3-Pentanol
Phosphorus
3CH2)2O
3-Bromopentane
acid 3acid
A What is
Afirst step, the
tribromide
acid
tribromide
 mechanism
PBr3 tribromide
333? In the
 alcohol
H3PO
acidthe
Phosphorous
3-Pentanol
Phosphorus
acid
3-Bromopentane
tribromide
the
of action of PBr
attacks
attacks
the
OHWhat isreagent
BrInIninorganic
acid
tribromide
mechanism
of
PBr
the
step,
the
alcohol
phosphorus
the
mechanism
of
action
PBr
the
rst
step,
the
alcohol
33??
as a nucleophile
to
form of
aofprotonated
ester,
a derivative
of
phosphorus
derivative
of Pa
Whatisisthethe
the
mechanism
of action
action
PBr
In3-Bromopentane
the fifi
first
rst
step,
the
alcohol
tanol
Phosphorus
3?first
What
mechanism
ofaction
action
of PBr
PBrof
step,
the
alcohol
attacks
the
3?? In
mechanism
of
In
the
rst
step,
the
alcohol
attacks
phosphorous
What
Inthe
the
first
rst
step,
the
alcohol
attack
phosphorus
is the mechanism
action
the
fifi
step,
the
alcohol
attacks
33?
reagent
aof
to
a47%
inorganic
ester,
a aaded
acid.
3form
What
mechanism
of
action of
of PBr
PBr
? In
In
the
fi
rst
step,
the
alcohol
attacks
phosphorous
reagent as
as of
nucleophile
to3form
form
protonated
inorganic
ester,
d
phosphorus
reagent
as
aa nucleophile
nucleophile
to
aa protonated
protonated
inorganic
ester,

47%

phosphorus
a nucleophile
form
a derivativethe
of
tribromide
What is reagent
the mechanism
of action
PBra3a?protonated
In the firstinorganic
step,
theester,
alcohol
aas
nucleophile
totoof
form
protonated
inorganic
ester,
aaaderivative
derivativ
phorus
reagent
as
protonated
inorganic
ester,aattacks
derivativ
Phosphorous
entanol
Phosphorus
reagent
as
aas
to
form
a 3-Bromopentane
protonated
inorganic
ester,
phosphorous
acid.
phorus
as
a nucleophile
nucleophile
protonated
inorganic
derivativ
acid.
phosphorous
acid.
phosphorous
acid.
phosphorus
reagent
a nucleophile to
to form
form aa protonated
inorganic
ester,ester,
a derivative
of
Step
1
acid
tribromide
Step
acid.
phorous
phorous
acid.acid.
phosphorous
Br
A
A
eStep
mechanism
of action
of PBr3? In the first step, the alco
Step
Step
11
1
Step
1

Br
Br

Br
the
mechanism
of
action
first
step,
Br
RCH
OH

PofOPBr
PBr222the alcohol
2
2
22O
Br 3? In theRCH
 attacks the

1Step 1
Br

A
AA
 inorganic ester,
A to
gent
nucleophile
form
a protonated
AA
Br
Br
Br
 ester,
eagent as
as aaRCH
nucleophile
to
form
a
protonated
inorganic
aderivative
of
Br
A



Br
OH

P
O
RCH
O
O
PBr

Br


H

Br

2
2 
2

Br
AAAA


A

RCH
OH
PP
RCH
Br


22
2O
22 

Br
RCH
OH
O
RCH
O
O
PBr




A
2
Br

Br
RCH
OH

PO
OBr
RCH
OO
OPBr
PBr




id.
acid. RCHRCH


2
 Br



O
Br
OH

PO
O
RCH
O
PBr


AA

Br

2
2O
22AA

Br

RCH
O
O
PBr

2


Br
OH
PP
RCH
O
O
PBr

Br

2
2


222
2
2

Br
RCH
OH

P
O
RCH
O
O
PBr

Br
H
2
2


Br


A
2 AN
2
Next, HOPBr222, a good leaving
group, is displaced A(S
N
generated in
in
AAA A 
A
N2) byHthe bromide generated
A
Br
H
Br
HH
Br Br
step
1,
the haloalkane.
stepNext,
1, producing
producing
haloalkane.
Br
HHN2) by Hthe bromide generated in
Br
HOPBr2,the
a good
leaving
group, is displaced (S
Br
Br
Next,
HOPBr
,
a
good
leaving
group,
is
displaced
(S
bromide
gg
step
1,2 producing
haloalkane.
Next,
HOPBr
a22,,good
leaving
group, group,
is displaced
(SN2) by the
bromide
generated
in ge
Next,
HOPBr
good
leaving
group,
is displaced
displaced
(SNNN2)
2)by
bythe
the
bromide
2,the
Step
HOPBr
aa leaving
good
leaving
(S
2)
by
the
bromide
is
A2the
StepNext,
2
Br
good
leaving
group,
displaced
(S
2)
by
the
bromide
generate
HOPBr
good
group,
(S
the
bromide
generated
Next,
displaced
(SNNNN2)
2)by
by
the
bromide
generateg
222,, aa the

1,
producing
haloalkane.
step
HOPBr
good
leaving
group, isis
is displaced
step
1,
producing
haloalkane.



step
1,
producing
the
haloalkane.

1, producing
haloalkane.


Br
RCH
OH

Pthe
O
PBr2 >)  Br
A RCH

2
producing
the
haloalkane.
>

O>
)
)
O O PBrRCH2O ORCH
>

Step
2
1,step
)Br
) haloalkane.
producing
haloalkane.
Br
 RCH
Br
HOPBr
222 O O O PBr222
222
p )  HOPBr
p
pthe
A
A RCH222 Br
A

Step
22

Br
Br
CH
OH

P
O
RCH
O
O
PBr
 Br
Step
2
2
2 2



>
>
>
>

H
H
O
)  HOPBr
RCH2 Br
 O PBr2
Step 2
2 )Br
H
p
p
p )  A RCH2 O
Step

A
2

A

>
>
>
>


)Br
)
)  >
O O PBr
RCH2 Br
HOPBr

 RCH2 O
2
2

p
p
p

>
>
>

H

 
)Br
)
)) 
RCH
O
O
PBr
RCH
HOPBr
A2isO
2 Br
method
of
synthesis
effiby
cient
because
pBr
p>
p
>
>

>
>
H
continues

O
)
Br

RCH
O
O
PBr
RCH

HOPBr

OPBrThis
a Br
good
displaced
the
bromide
generated
>

>
)
)Br
)haloalkane
)
2, )
Br
group,
RCH
Ois
Oespecially
PBr22(SN2)
RCH
Br
222 continues
HOPBr
>
>

>
>
pHOPBr
p in22 22
pleaving
>

>
)
))

RCH
O
PBr
RCH
HOPBr
O
A>
22 O
22

RCH
O
O
PBr
RCH
Br
HOPBr
p
p
222O
222Br
2 22 p
)successively
)
)
Br
RCH
Br

HOPBr
>
>
HO
>
>
p>
p
p
p
to
 with
RCH
O
PBr
two
more
molecules
converting
them
into
A2222 of 2alcohol,
to react
2O
2p
2
haloalkane
p
p haloalkane
p
A
AO
A
cing
the
haloalkane.
This
method
of
haloalkane
synthesis
is
especially
effi
cient
because
HOPBr
continues
H
2
A
as
well.
H
as
H
H
H molecules
to react
with two more
of alcohol,
converting
them
into haloalkane
This successively
method of haloalkane
synthesis
is especially
efficient
because
HOPBr
continues

H
of haloalkane
haloalkane
synthesis
especially
effi
because
HOPBr
method
H is is
method
of
synthesis
especially
cient
because
HOPBr
>
>
>
2 cont
)
CH
OH
ofof
HOPBr
2 cient
RCH

H2
of haloalkane
haloalkane
synthesis
especiallyeffi
effi
cient
because
HOPBr
continues
method
synthesis
isis especially
effi
cient
because
HOPBr
2 2continues
2This
2 molecules
2Br
p
p
p
especially
effi
cient
because
HOPBr
continu
haloalkane
synthesis
especially
effi
cient
because
HOPBr
continues
This
method
haloalkane
synthesis
is
especially
effi
cient
because
HOPBr
This
method
of
haloalkane
synthesis
effi
cient
because
HOPBr
2continues
with
two
more
of
alcohol,
converting
them
into 3
ccessively
isis especially
22 continu
22 into
ccessively
withoftwo
more
molecules
alcohol,
converting
them
haloa
with
two
molecules
of
alcohol,
converting
them
into
haloalkane
to react
successively
with
two more
more
molecules
of
alcohol,
converting
them
into
haloalkane
Thissuccessively
method
haloalkane
synthesis
is of
especially
effi
cient because
HOPBr
continue

2haloalkan
successivelywith
withtwo
twomore
moremolecules
molecules of
alcohol,
converting
them
into
haloalkane
react
molecules
ofalcohol,
alcohol,converting
converting
them
into
haloalka
to react
successively
with
two
more
molecules
them
into
haloalkane
successively
of
alcohol,
converting
them
into
as well.

to
with two more molecules of alcohol, converting them into haloalkan
as react
well.
well.
tead
ofsuccessively
a bromoalkane,
we want the corresponding iodoalkan
as well.
>
>Br
>
>
>
))  HH3PO
2 RCH22>
OH

22RCH
OH
> HOPBr
HOPBr
RCH22Br
PO3 3
22
3PO
p
p
p
p
p
pBr
>
>
>
>
>
>
>
>
>
>
>
OH

HOPBr
RCH

))
2
RCH
OH

HOPBr
PO
odide,
,
is
best
generated
in the reaction
mixture
in
which
)HH33H
>
>
>
2 RCH
RCH2PI
OH

HOPBr
2 RCH
Br

H
)
OH

22222RCH
RCH

HPO
3H
>
p HOPBr
p
pBr
)
RCH
Br

2
2
3
p
p
3 2p
2p
2
RCH
OH
 pHOPBr
RCH
2>2 22222
2Br
33PO
33PO3
22p
22Br
3PO
p
p
p
p
>
>))
2 RCH
OH p
 p
HOPBr
2 RCH222p
Br
 H333PO333
2p
2
p
p
What if,species.
instead
bromoalkane,
we
want
the
iodoalkane?
required
instead of
of aaWe
bromoalkane,
weby
wantadding
thecorresponding
corresponding
iodoalkane?The
The
required
eactive
do
this
red
elemental
phosphor
of aa bromoalkane,
bromoalkane, we
we want
want the
the
corresponding
iodoalkane?
The
required
What
insteadofof
corresponding
iodoalkane?
The
required
want
the
corresponding
iodoalkane?
The
requir
What
if, if,
instead
aPI
we
want
the
corresponding
iodoalkane?
The
require
triiodide,
,, is
in
the
reaction
mixture
which
ititwill
be
used,
triiodide,
PIbromoalkane,
is best
best generated
generated
inthe
the
reaction
mixtureinin
which
will
be
used,
instead
aabromoalkane,
wewe
want
corresponding
iodoalkane?
The
req
instead
of
bromoalkane,
want
corresponding
iodoalkane?
Th
f,phosphorus
What
if,of
instead
of
we
want
the
corresponding
The
require
triiodide,
PIa33333,,bromoalkane,
is best
best
generated
in the
thethe
reaction
mixtureininiodoalkane?
which
will
beused,
used,
phosphorus
triiodide,
PI
is
generated
in
reaction
mixture
which
ititwill
be
esosphorus
alcohol
(margin).
The
reagent
is
consumed
as
soon
as
ituse
is
inin
the
reaction
mixture
in
which
will
be
use
ittriiodide,
is aPI
reactive
species.
We
do
this
by
adding
red
phosphorus
and
elemenPIbest
, is, is
best
generated
in
the
reaction
mixture
in
which
itititand
will
be
use
because
reactive
species.
We
do
this
by
adding
redelemental
elemental
phosphorus
elemen3
triiodide,
,
is
generated
in
the
reaction
mixture
in
which
it
will
be
phosphorus
triiodide,
PI
best
generated
the
reaction
mixture
in
which
will
be
3 3, is species.
reactive
species.
We do
do this
this by
by
adding
redelemental
elemental
phosphorus
andelemenelementriiodide,
best
generated
in
the
reaction
mixture
in
which
it
wi
because
it is a PI
reactive
We
adding
red
phosphorus
and
scause
3
to
the alcohol
(margin).
The
reagent
isis consumed
as
as
byby
adding
red
elemental
phosphorus
and eleme
eleme
tal iodine
alcohol
(margin).
The
reagent
consumed
assoon
soonphosphorus
asit
itisisformed.
formed.
it
is
a
reactive
species.
We
do
this
by
adding
red
elemental
and
ing
agent
commonly
used
to
convert
alcohols
into
chloroalk
because
it
is
a
reactive
species.
We
do
this
adding
red
elemental
phosphorus
and
elemen
alcohol (margin).
(margin).
The
reagent
consumed
assoon
soonas
asititis
isformed.
formed.and ele
to the
alcohol
The
reagent
isis consumed
as
istalaaiodine
reactive
species.
We
by
adding
red
elemental
phosphorus
species.
Wedodothis
this
by
adding
red
elemental
phosphorus
an
is
Areactive
chlorinating
agent
commonly
used
to
alcohols
into
chloroalkanes
isisthionyl
agent
commonly
used
to convert
convert
alcohols
into
chloroalkanes
thionyl
reagent
isisconsumed
consumed
as
soon
as
it
is formed.
formed.
iodine
to the
alcohol
(margin).
The
reagent
is
as
as
it
iodine
to the
alcohol
(margin).
The
reagent
consumed
assoon
soon
as
ititis
is
agent
commonly
used
to convert
convert
alcoholsas
into
chloroalkanes
isthionyl
thionyl
A chlorinating
agent
commonly
used
to
alcohols
into
chloroalkanes
isformed.
to
the
alcohol
(margin).
The
reagent
is
consumed
soon
asevolution
isformed.
chloride,
SOClwarming
warming
an
alcohol
in
presence
results
inin
the
of
.tal
Simply
an
alcohol
in
its
presence
results
in
the
Simply
warming
an
alcohol
in its
its
presence
results
the
evolution
ofSO
SO2ev
22. Simply
the
alcohol
(margin).
The
reagent
is
consumed
as
soon
as
it
is
form
to
convert
alcohols
into
chloroalkanes
is
thion
A
chlorinating
agent
commonly
used
to
convert
alcohols
into
chloroalkanes
is
thion
A
chlorinating
agent
commonly
used
to
convert
alcohols
into
chloroalkanes
is
thion
Simply warming
warming an
an alcohol
alcohol in
in its
its presence
presenceresults
resultsininthe
theevolution
evolutionofofSO
SO22 22
chloride,
SOCl
2
22. Simply
and
HCl
and
the
formation
of
chloroalkane.
rinating
agent
commonly
used
to
convert
alcohols
into chloroalkanes
is
th
formation
of the
the
chloroalkane.
loride,
alcohol
ininits
itsitspresence
presence
results
in
the
evolution of
of SO
S
SOCl
Simply
warming
in
results
in
evolution
of
SO
2.the
agent
commonly
used
to
convert
alcohols
chloroalkanes
and
HCl
and
of
the
chloroalkane.
erinating
formation
of
the
formation
ofchloroalkane.
thean
chloroalkane.
chloride,
SOCl
Simply
warming
analcohol
alcohol
presence
resultsinto
in the
the
evolution
2. formation

SOCl . Simply warming an alcohol in its presence results in the evolution o

dand
chloroalkane.
HClHCl
thethe
formation
of
the
2 andand
formation
of
thechloroalkane.
chloroalkane.
Chloroalkane
Synthesis
SOCl
an
alcohol
in itswith
presence
Chloroalkane
Synthesis
with
SOCl2 results in the evolut
SOCl
2. Simply warming
Synthesis
Chloroalkane
Synthesiswith
withSOCl
SOCl2222
nd the
formation of theChloroalkane
chloroalkane.
P
P
the33CH
formation
of Chloroalkane
the
chloroalkane.

SOCl
CH

 HCl
nd CH
Chloroalkane
Synthesis
with
Synthesis
with
SOCl
Synthesis
with
SOCl
PS
P
22CH
22OH
22
33CH
22CH
22Cl
CH
CH
CH
OH

SOCl
CH
CH
CH
Cl
 SOCl
HCl
Chloroalkane
Synthesis
with
2O
222O
CH CH CH OH  SOCl
CH CH CH Cl SOCl

OOP
SSP
OO  HCl
CH33CH22CH222OH 
 SOCl
SOCl222

PSSP
POO  HCl
CH
CH333CH
CH222CH
CH222Cl
Cl 
 OOP
HCl

91%
91%
Chloroalkane Synthesis
with SOCl2
91%
91%

P P

CHCH
CH
CH
CH

O
 HCl
HCl
91%
CH
O
PSSP
SOCl
CH
Cl 
 O
OP
O 
3CH
2CH
2OH
22 2
33CH
22CH
22Cl
3CH
2OH   SOCl
3CH
2CH
2Cl
Chloroalkane
Synthesis
with
2CH
SOCl
CH
CH
Cl
 PRCH
O 2P
SP O
2ester,
Mechanistically,
the
fifirst
forms
O
2OH
2 RCH
3CH
2SOCl
2SCl.
Mechanistically,
the alcohol
alcohol
RCH22OH
OH again
again
rst
forms
an inorganic
inorganic
ester,
RCH
91%
91%2 an
2O
2SCl.
alcohol
RCH
rst
forms
an
theSOCl
alcohol
RCH222OH
OH again
again
rst91%
forms
an inorganic
inorganic
ester,
RCH
SCl. H
22SCl.
P SRCH
P
2O
2
H2Mechanistically,
CH2OH  the
CH3fifiCH
 Oester,
O22O
2
2CH2Cl
91%
CH2OH 
SOCl
CH
CH
 ester,
O PRCH
S P22O
O

Hechanistically,
alcohol
again
first
forms
an
inorganic
RCH
again
forms
an
inorganic
ester,
RCH
O22SCl.
SCl.
thethe
alcohol
RCH
again
fifirst
forms
an
inorganic
2 RCH
3rst
2CH
2Cl
2Mechanistically,
2OH
22OH

91%

91%

, the the
alcohol
againfirstfirst
forms
an inorganic
ester,
ically,
alcoholRCH
RCH22OH
OH again
forms
an inorganic
ester, RCH
2O2S

ically, the alcohol RCH2OH again first forms an inorganic ester, RCH

REACTION
Chapter 9

REACTION

MECHANISM

MECHANISM
CH3(CH2)14CH2OH
P, I2,

REACTION

345

CH3(CH
2)14CH2I
85%
CH3(CH
2)14CH2I
85%
85%


H3
PO3
H3PO3
H3PO3

REACTION
REACTION
REACTION

F u r t1h e r R e a c t i o n s o f A l c o h o l s a n d t h e C h e m i s t r y o f E t h e r s
Step
Further Reactions of Alcohols and the Chemistry of Ethers
Fu
eeO
r acR teiaocnt si o o
n fs A
o fl c Ao lhcoolh
lasknd
aOn
Furth
e rr t hR
soO
td h et h eC hCehme ims itsr tyr y o fo f E Et ht he er rs s
B
B
F u r t h e r R e a c t i o n s o fBA l c o h o l s a n d t h e C h 
e m i s t r y o f E t h
ers
346
Chapter 9

RCH2 O 
OH
 
RCH2 O 
O O S O
Cl  H

Cl
Cl O S O 
Cl

 CC1Step
R
AAllllccccoooohhhhoooollllssss aaaan
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O
MECHANISM
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O O
ANISM
MECHANISM B
B
O B then acts
B process
BOB and
O
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The chloride
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in this
as
a nucleophile
the ester,
an

B
B H 
O



Step
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B O S O
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RCH2 RCH
OH
OO
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S
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 RCH

1O

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2O
OS
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RCH
OSO
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SO
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RCH
O
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of







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O
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molecule
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SO
HCl.
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one






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MECHANISM
O OH
O
O
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RCH

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SO
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MECHANISM
hr a 9p t e r 9

MECHANISM 2

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RCH2222O
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 H
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 ion created






The chloride

 in this process

then 
acts
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nucleophile
and
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ester,
an

Step 2
The chloride
ion
created inbetter
this process
then
acts
as apresence
nucleophile
and attacks
the ester,
an
The
reaction
works
in
the
ofthethe
an
ami
ion
created
in created
this
then
acts
as
aasnucleophile
attacks
ester,
The chloride
The
chloride
ion created
inSprocess
this
process
then
acts
aeach
and
attacks
ester,
an
yielding
one
molecule
SO2 andand
HCl.
N2 reaction
The
chloride
ion
inone
thismolecule
process
then
as2nucleophile
a ofnucleophile
and
attacks
the
ester,anan
SN2 reaction
each acts
of SO
and
HCl.
Oyielding
k molecule
SNchloride
2 reaction
yielding
one
each
of
SO
and
HCl.
SN2 reaction
one
molecule
each
of
SO
and
HCl.
2
2
Syielding
2
reaction
yielding
one
molecule
each
of
SO
and
HCl.
generated.
One
such
reagent
is
N,N-diethyletha
N
2 acts
chloride
ion
created
in
this
process
then
as
nucleophile
and
attacks
the
ester,
an
ion2created
The chloride
created in
in this
this process
processthen
then
actsas
asaaaanucleophile
nucleophileand
andattacks
attacksthe
theester,
ester,an
an
B Step
The
ion
acts
process
then
acts
as
nucleophile
and
attacks
the
ester,
an
StepO
2SSN
reaction
yielding
one
molecule
2O
yielding
one molecule
molecule
each
ofSO
SO
and
HCl.

each
  CH
N
reaction
yielding
of

each
of
and
HCl.
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one
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R2222and
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 Cl
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S O Cl
 HCl
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these
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2



con
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corresponding
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under
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  O CH2 O

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 Cl
O O S O Cl




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2

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R
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O CH2R  OPSPO  HCl
 

RO
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O OSO
kk


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 OPSPO
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an
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O


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works
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presence
of
neutralizes
2R
(CH

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SSO

HCl

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 which
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presence





A
N,N-Diethylethanamine
chloride
generated.
One such reagent is N,N-diethylethanamine
(triethylamine),
form
AAA is
A One
chloride generated.
suchR reagent
N,N-diethylethanamine
(triethylamine),
which which
forms
(Triethylamine) R
R
R
R
the
corresponding
ammonium
chloride
under
these
conditions.
reaction works
betterunder
in the these
presence
of an amine, which neutralizes the hydrogen
N
RThe
3CH

the2)3corresponding
ammonium
chloride
conditions.
hylethanamine
chloride
generated.
One
such
reagent
is
N,N-diethylethanamine
(triethylamine),
which
forms
HCl
reaction
works
better
in
the
hydrogen
works
better
in better
the presence
of anof
amine,
which
neutralizes
N
The
reaction
works
in
an
which
neutralizes
the
hydrogen
(CH3CH2)3NThe reaction
The
better
in the
the presence
presence
of
an amine,
amine,
which
neutralizesthe
thehydrogen
hydrogen
works
of
an
amine,
neutralizes
the
hydrogen
reaction
Alkyl
sulfonates
are
versatile
substrates
for
thylamine)
The reactionthe
works
better
inammonium
the
presence
ofpresence
anN,N-diethylethanamine
amine,
whichwhich
neutralizes
the
hydrogen
corresponding
chloride
these
conditions.
generated.
One
such
reagent
forms
N,N-Diethylethanamine
chloride
One
such
reagent
is
(triethylamine),
which
N,N-Diethylethanamine
is
(triethylamine),
which
forms
chloride
One
such
reagent
isN,N-diethylethanamine
N,N-diethylethanamine
(triethylamine),
whichforms
forms
generated.
amine
The
reactionchloride
works generated.
better
ingenerated.
the
presence
of
an under
amine,
which
neutralizes
the which
hydrogen
One
such
reagent
is
N,N-diethylethanamine
(triethylamine),
forms
 (Triethylamine)
substitution
chloride
generated.
One
such
reagent
isreactions
N,N-diethylethanamine
(triethylamine), which forms
corresponding
ammonium
e)Alkyl
the
corresponding
ammonium
chloride
under
these
conditions.
chloride
under
these
conditions.
the
ammonium
chloride
under
these
conditions.
corresponding
sulfonates
are
versatile
substrates
for
One
the
corresponding
ammonium
chloride
under
these
conditions.
HCl
chloride
generated.
such
reagent
is
N,N-diethylethanamine
(triethylamine),
which
forms

The
(CH3CH
The
inorganic
esters
in
the
reactions
of SOCl2 are special
examples
of 2
leaving
groups
inorganic
esters
in
the
reactions
of
SOCl
are
2)3NH Cl ammonium
the
corresponding
chloride
under
these
conditions.
Alkyl
sulfonates
are under
versatile
for
HCl
derived from
sulfur-based
acids.
They are related to the sulfonates (Section 6-7). Alky
substitution
reactions
the corresponding
ammonium
chloride
thesesubstrates
conditions.
are versatile
versatile
substrates
Alkyl
are
substrates
for
for
Alkyl sulfonates
sulfonates
versatile
substrates
forcan be are
sulfonates contain
excellentacids.
leaving
groupsThey
and
readily prepared
from the to
corre
substitution
reactions
derived
from
sulfur-based
related
Alkyl
sulfonates
are
versatile
substrates
for
sponding
sulfonyl
chloridesare
and anspecial
alcohol. Aexamples
mild base suchof
as pyridine
or a tertiary
amin
reactions
 inorganic
substitution
reactions
The
esters in
the
of SOCl
leaving
groups
substitution
reactions

2
Alkyl
sulfonates
arereactions
versatile
substrates
for
H2)3NH Cl
The inorganic
esters
the toreactions
SOCl
is
ofteninadded
remove theofHCl
formed.
2 are special examples of leaving groups

substitution
reactions

sulfur-based
sulfonates
contain
excellent
leaving
groups
and
can
Alkyl
are
versatile
substrates
for
derived
acids.
They
are
related
to
the
sulfonates
(Section
6-7).
Alkyl
inorganic
esters
in
the
groups
(CH33CH22)sulfonates
NH Cl
The
inorganic
esters
in
the
reactions
of
SOCl
are
special
examples
of
leaving
groups
reactions
of
SOCl
are
special
examples
of
leaving
groups
2
33from
The
inorganic
esters
in
the
reactions
of
SOCl
are
special
examples
of
leaving
groups
2
derived
from sulfur-based acids. They are related22 to the sulfonates (Section 6-7). Alkylb
substitution
reactions

from
sulfur-based
acids.
Alkyl
derived
from
acids.
are
related
to
sulfonates
(Section
6-7).
Alkyl
Synthesis
of
an
Alkyl
Sulfonate
They
are
related
to
the
sulfonates
(Section
6-7).
Alkyl
Cl
derived
from
sulfur-based
acids.
They
are
related
to
the
sulfonates
(Section
6-7).
Alkyl
The reactions
inorganic
esters
insulfur-based
the groups
reactions
ofThey
SOCl
are
special
examples
of
leaving
groups
sulfonates
contain
excellent
leaving
and
can
be
readily
prepared
from
the
corre2and
sulfonates
contain
excellent
leaving
groups
can
bethe
readily
prepared
from
the
corresubstitution
sponding
sulfonyl
chlorides
and
an
alcohol.
A
mild
base
contain
excellent
leaving
corresulfonates
contain
excellent
leaving
and
can
be
readily
prepared
from
the
corregroups
and
can
be
readily
prepared
from
the
corresulfonates
contain
excellent
leaving
groups
and
can
be
readily
prepared
from
thegroups
correderivedsponding
from
sulfur-based
acids.
They
are groups
related
to base
the
sulfonates
6-7).
Alkyl
sulfonyl
chlorides
and
an
alcohol.
A mild
such
as pyridine
or
a tertiary
amine
Thesulfonyl
inorganic
esters
inand
the
reactions
of
SOCl
special
examples
of
leaving
sponding
chlorides
an
alcohol.
A
mild
base
such
as
pyridine
or(Section
a tertiary
amine
2 are
sponding
sulfonyl
chlorides
and
an
alcohol.
A
mild
base
such
as
pyridine
or
tertiary
amine
amine
sulfonyl
chlorides
and
an
A
mild
base
such
pyridine
or
aaatertiary
amine
sponding
sulfonyl
chlorides
and
analcohol.
alcohol.
A
mild
base
suchas
as
pyridine
or
tertiary
amine
sulfonates
contain
excellent
leaving
groups
and
can
be
readily
prepared
from
the
correThe
inorganic
esters
in
the
reactions
of
SOCl
are
special
examples
of
leaving
groups
is
often
added
to
remove
the
HCl
formed.
2related
CH
O are
derived
from
sulfur-based
Theythe
to the formed.
sulfonates
6-7). Alkyl
CH3 (Section
O
3 added
is often
to remove
the
HCl
formed.
added
to
remove
HCl
isadded
often
added
toacids.
remove
HCl
is
to
remove
HCl
formed.
formed.
is often
often
added
to
remove the
the
HClthe
formed.
Balcohol.
A chlorides
A
Bor a tertiary amine
sulfonyl
and are
angroups
A mild
such as prepared
pyridine
derived
fromsponding
sulfur-based
acids. leaving
They
related
thebase
(Section
6-7).
sulfonates
contain
and
besulfonates
readily
from
correCHexcellent

CH
 tocan
N
theAlkyl
CH3CHCH
NCl
3CHCH2OH
3SCl
2OSCH3

Synthesis
Alkyl
Sulfonate
B of an
A
is often
added
to remove
the
HCl
formed.
B
Synthesis
of
Synthesis
of
an
Alkyl
Sulfonate
an
Alkyl
Sulfonate
Synthesis
of
an
Alkyl
Sulfonate
sulfonates
contain
excellent
leaving
groups
and
can
be
readily
prepared
from
the
corresponding
sulfonyl
chlorides
and
an
alcohol.
A
mild
base
such
as
pyridine
or
a
tertiary
amine
Synthesis of an AlkylOSulfonate
H
O
Pyridinium
Methanesulfonyl
Pyridine
2-Methylpropyl
sponding
sulfonyl
chlorides
andthe
anHCl
alcohol.
A mild base
such
asan
pyridine
or a Sulfonate
tertiary amine
is often
added
to2-Methyl-1-propanol
remove
formed.
of
Alkyl
Synthesis chloride
ofSynthesis
an Alkyl Sulfonate
hydrochlorid
methanesulfonate
is often added
remove
the HCl
(2-Methylpropyl
O
O
CH
CH3 toCH
O formed.
CH
O
CH
OO mesylate)
3
CH
O (Mesyl chloride)
CH
3333
AA 3
B BBBof an Alkyl Sulfonate
A
AAAA 3
BBB
Synthesis



CH
SCl

N
CH
CH
N

CH
CHCH
OSCH333and
Cl

CH
OSCH
NN
Cl
O 22OH
O
the inorganic
from3phosphorus
tribromide
alky
333CHCH
33 thionyl


CH3CHCH
OH
 
 
N
 chloride,
CH
N
Cl
CH33CHCH
OH
CHUnlike
CH333SCl
SCl
 esters
Nderived CH
CH
N
Cl

2CHCH
3SCl
3CHCH
2222OSCH

3CHCH
2OSCH
Cl


B
B
AAAA
B
B Synthesis
A that can
B Alkyl
Bof an
BBB purified before further
are oftenSulfonate
crystalline solids
reac
CH3
O sulfonates
CHbe3Bisolated
O and
O
H
O
O
Hthe

OO
H
O then can be used CH
B
A
B
H
tion.
They
in
reactions
with
a
variety
of
nucleophiles
to
give
corre
O
O
OH A
CH
SCl

N

CHCH
OSCH
N
Cl
3
3
2 2-Methylpropyl
3

 products
Pyridinium
Pyridinium
2-Methyl-1-propanol
Methanesulfonyl
Pyridine
2-Methylpropyl
Pyridinium
Methanesulfonyl
Pyridine
2-Methylpropyl
Pyridinium
2-Methyl-1-propanol
Pyridine
2-Methylpropyl
sponding
of nucleophilic
substitution.
NPyridine
 hydrochloride
CH
OSCH3
Pyridinium
B OCHMethanesulfonyl
A NCl
2-Methyl-1-propanol
2-Methylpropyl
B 2O
2OH
3SClMethanesulfonyl
3CHCH

CH
hydrochloride
chloride
H CH3CHCH
chloride
methanesulfonate
hydrochloride
methanesulfonate
3 methanesulfonate
hydrochloride
chloride
methanesulfonate
B chloride
A
Ochloride)
hydrochloride
methanesulfonate
33
(Mesyl
mesylate)
(Mesyl chloride)
(2-Methylpropyl
mesylate)
B
A(2-Methylpropyl
(2-Methylpropyl
mesylate)
HH
O
O B B mesylate)
chloride)
(2-Methylpropyl
mesylate)
(Mesyl
chloride)
(2-Methylpropyl
O (Mesyl
O
Sulfonate
Intermediates
in
Nucleophilic
Displacement
O
CH

OOSCH

3
B NPyridine of the2-Methylpropyl


 Pyridinium
CH
N
HCH
2OH Methanesulfonyl
3SCl
3CHCH
2 in Alcohols
3
anol
Pyridine
Cl
Hydroxy
Group
BCHMethanesulfonyl
A
Pyridinium
B
2-Methyl-1-propanol
2-Methylpropyl
Unlike
the
inorganic
esters
derived
from
phosphorus
tribromide
and
thionyl
chloride,
alkyl
inorganic
esters
derived
alkyl
B
A
from
phosphorus
tribromide
and
thionyl
chloride,
alkyl
B
Unlike the inorganic esters derived frommethanesulfonate
phosphorus tribromide and thionyl
chloride,
alkyl
hydrochloride
chloride

hydrochloride
chloride
methanesulfonate
Unlike
the
inorganic
esters
derivedsolids
from
phosphorus
and ed
thionyl
chloride,
alkyl
OH

CH
SCl

N

CH
CHCH
N
are
crystalline
that
be
and
reacCH2OH

CH
SCl

Ntribromide
CH
are
often
crystalline
reacthat
can
be
isolated
and
purifi
before
further
reac2OSCH
3purifi
HCl
Omesylate)
Osulfonates

O
sulfonates
are3often
often
crystalline solids
solids
that3can
can
beisolated
isolated
and
purified
edbefore
beforefurther
further
reac
(Mesyl 3chloride)
(2-Methylpropyl
(Mesyl
chloride)
(2-Methylpropyl
mesylate)
B Bof
Bsulfonates
Athecorreare
crystalline
that can
beaaaisolated
and
purified before
further
reaction.
then
can
be
in
with
variety
nucleophiles
to
the
then
can
be
used
in
correreactions
with
variety
of
nucleophiles
totogive
give
the
corretion. They
Theyoften
thenB
can
be used
usedsolids
inRreactions
reactions
with
of
nucleophiles
give
correPyridinium
Methanesulfonyl
Pyridine
Pyridinium
l-1-propanol
Osubstitution.
O OSR
R variety
R O Nu to
OH with a2-Methylpropyl
sponding
nucleophilic
They
thenproducts
can be of
used
in reactions
variety
of nucleophiles
give
products
of
nucleophilic
Hthe correOtion.
substitution.
BO
sponding
products
of
nucleophilic
substitution.
hydrochloride
chloride
methanesulfonate
hydrochloride
Unlike
the
inorganic
esters
derived
from
phosphorus
tribromide
and thionyl
chloride,
alkyl
Unlike theMethanesulfonyl
inorganic
esters
derived
from
phosphorus
tribromide
thionyl
chloride,
alkyl
sponding
products
of
nucleophilic
substitution.
Oand
O
Pyridinium
(Mesyl
chloride)
(2-Methylpropyl
mesylate)
anol
Pyridine
2-Methylpropyl
are often crystalline
solids
that
bein
isolated
and purifi
ed before
further
reacSulfonate
Intermediates
Displacement
Sulfonate
hydrochloride
Intermediates
in
Nucleophilic
Displacement
chloride
methanesulfonate
sulfonates aresulfonates
often crystalline
solids
that
can
be can
isolated
and purifi
ed
before
further
reacSulfonate
Intermediates
inNucleophilic
Nucleophilic
Displacement
Theused
displacement
of the
sulfonate
groups
by halide
ions
(Cl2, Br2, I2to
) readily
the cor2
of
Group
in
Alcohols
tion.chloride)
They then
can be
in reactions
with
a variety
of
nucleophiles
give yields
correof
-propanol
Pyridine
Hydroxy
Group
in
Alcohols
(Mesyl
(2-Methylpropyl
Sulfonate
Intermediates
in
Nucleophilic
Displacement
of the
the
Hydroxy
Group
inmesylate)
Alcohols
tion. They
then
can
be Methanesulfonyl
used
in responding
reactions
with
a Hydroxy
variety
of
nucleophiles
to give
thethe
correUnlike
the
inorganic
esters
derived
from
phosphorus
tribromide
and
thionyl
chloride,
alkyl
haloalkanes,
particularly
with
primary
and
secondary
systems,
in
which
SN2
sponding products of nucleophilic
substitution.
of the
Group
in sulfonates
Alcoholsallow replacement of the hydroxy
O
chloride
m
reactivity
is good.
In Hydroxy
addition,
Oalkyl
sponding
products
nucleophilic
substitution.
sulfonates
areof
often
crystalline
solids
that
can behowever,
isolated
and
purified before further reacBBO
B
Unliketion.
the They
inorganic
esters
derived
from
phosphorus
tribromide
and
thionyl
chloride,
alkyl
then can
be used chloride)
in reactions
with a variety
of nucleophiles
to give the(2-Me
corre(Mesyl
R
R
OSR
R
O
R
OH
O
ONu
RRO
OSR
RO
Nu
OOH
OO
RO
Nu
OH
Sulfonate
in Nucleophilic
Displacement
BBand purifi
BOSR
sulfonates are often crystalline
solidsIntermediates
that
can
be isolated
edR O
before
further reac-

Alkyl sulfonates are versatile substrates fo

substitution reactions

Unlike the inorganic esters derived from phosphorus tribromide and thionyl chloride, alkyl
sulfonates are often crystalline solids that can be isolated and purified before further reaction.
They Sulfonate
then canIntermediates
be usedIntermediates
in reactions with
variety
of nucleophiles
to give
the correSulfonate
in aNucleophilic
in Nucleophilic
Displacement
Displacem
sponding products of nucleophilic substitution.

of theofHydroxy
the Hydroxy
Group
Group
in Alcohols
in Alcohols

Sulfonate Intermediates in Nucleophilic Displacement

of the Hydroxy Group
Oin Alcohols
O

R O OH
R O OH
R O OH

B
B
O
R O BOSR
R O OSR
R O Nu
R O Nu
R O OSRB
B R O Nu
B
OO
O

The displacement of sulfonate groups by halide ions (Cl2, Br2, I2) readily yields the cor-

2 systems,
2which
responding haloalkanes, particularly with primary and secondary
lacement
ent
of sulfonate
of sulfonate
groups
groups
by halide
by halide
ions (Cl
ions
, (Cl
Br2, inIBr
)2readil
, IS2N)2 r
reactivity is good. In addition, however, alkyl sulfonates allow replacement of the hydroxy
ng
loalkanes,
haloalkanes,
particularly
particularly
with with
primary
primary
and secondary
and secondary
system
sy
ood.
is good.
In addition,
In addition,
however,
however,
alkyl alkyl
sulfonates
sulfonates
allowallow
replacemen
replac

Naaaam
meeeessss aaaann
opp
eerertrtitieiesessoofof fEEtEththeherers rs s
99
99---555 N
N
m
nnddd PPPhhhyyysssi iciccaaal l l PPPr rorop
N
m
9 -- 55 N
e s a n dd PPhhyyssiiccaall PPrrooppeerrtti ieess ooff EEt thheer rss
am

-- 5
5
N
aa m
m
o
E
h
5d N
N aaP
m
offff t E
Etttte
heere
errsrrssss
5
N
m
Eh
hh
9 - 5 N a m e s a9999 --n
heeeeysssss aaiaa nncnn dddda lPPPPhhhhPyyyyssrssiiiioccccaapaalllle PPrPPrrtrrooiooppeppeeeesrrrrttttiioiieeeessfss ooE

ood nucleophile:
They arearenot
limitedhalides
to halides
alone,
as i
with
group
any good
nucleophile:They
They are
arenot
notlimited
limitedto
halidesalone,
alone,as
thecase
case
with
good nucleophile:
nucleophile:
They
are
not
limited
totohalides
halides
alone,
asasisis
isisthe
the
case
with
group by
by any
any
good
nucleophile:
They
not
limited
to
alone,
as
the
case
with
group
by
any
good
nucleophile:
They
are not
limited
to
halides alone,
as
is the
case
with
phorus,
and
thionyl
halides.
hydrogen,
phosphorus,
and
thionyl
halides.
phosphorus,
and thionyl
thionyl
halides.
by any
good nucleophile:
They
are
phosphorus,
and
thionyl
halides.
group
nucleophile:
They
are not
not limited
limited to
to halides
halides alone,
alone, as
as isis the
the case
casewith
with
hydrogen,
phosphorus,
and
halides.
hydrogen, phosphorus, and thionyl halides.
hydrogen, phosphorus, and
and thionyl
thionyl halides.
halides.

hydrogen, phosphorus, and

and thionyl
thionyl halides.
halides.
cleophile:
They are
not
limited
to halides
alone,
as is the case with
Substitution
Reactions
of
Sulfonates
Substitution
Reactions
ofAlkyl
Alkyl
Sulfonates
Substitution
Reactions
of
Alkyl
Sulfonates
Substitution
Reactions
of
Alkyl
Sulfonates
Substitution
Reactions
of
Alkyl
Sulfonates
Substitution
Reactions
Alkyl
Sulfonates
Substitution
Reactions of
ofof
Alkyl
Sulfonates
and thionyl
halides.
Substitution
Reactions
Alkyl
Sulfonates

O
BBB
O


BO



O
O

CH
CH
CH
I
O
S

Substitution
Reactions
of
Alkyl
O
O
O
33CH
22CH
22 O
OCH

O
S

CH
CH
CH
I



CH
CH3333 
I

B
O
O

O
S
CH
CH

B

O
O
O
3
2
2
S

CH
CH
II

2 OOOO
O2CH
BBB CH
3  



O
CH333CH
II
BSS
OCH

OO


CH
CHB22CH
CH22 O
CH3333 





O
O

O
BO

O
B

O O S O CH OO
I

B

O I

O
O

O
BO
B
B
BOBO



O
O
O

CH
CH
CH
CH
I

O
S


Sulfonates
O
O
O
333CH
22CH
222O
333
O
O
O

CH
CH
CH
CH
I

O
S




CH
CH
CH
CH
I

O
S

B
O
O

CH
CH
I

O
S
2


B



O
O
O
3
2
2
CH3CH2CH2 
I
 

O S
BBBB CH
333

O
CH
I

O
BSS
O
O
OCH
 
CH3333
CH3333CH
CH2222CH
CH2222O
I 
OO





B
O
90%
90%

90%CH CH O
90%
CH
IOOO 
90%
3
2
2 
90%
B
90%

CH3CH2CH2 O
I 


O CH3

H
O
O

O
H
B
A
B

O
H
B

AA O
H
CH3 O
O
O
S
O
C

OC
O
OO
OS
S
B
C
A

CH
B

A
O
O
O
CH333 O
BO
AA 
CH33 O
O
S
O

C
BB
AO
O CH
O
OO
OO
S
O

C
CH
BBO

O
AA 333 
CH

O
CH
3
CH
O
O

CH33

90%
O CH3
CH3333
CH
OCH
O
O
O
CH
O
CH333
OCH
3










90%


CH
S



CH3CH
CH2
S

CH333CH
CH
S
CH
2S


CH
3CH
2S

22



CH
S

CH
CH
S


CH3333CH
CH2222
S




O O S O CH3

B
O

O


O


CH3CH O
SCH
2CH3 


CH
SCH
CH
SCH

O
22CH
O

CH
CH
SCH
O
33
3CH
2CH

ACH

333
22CH
333


ACH
AO
CH
SCH

ACH
222
CH
SCH
CH

O

CH33CH
SCH
CH3333 
2CH
O

33CH

3
AACH
3
CH
ACH
3
33 3
85%
CH
3385%
CH
CH
85%
85%
33
85%
85%
85%

OExercise
9-10
Exercise
9-10
9-10
Exercise
9-10
9-10
BExercise
Exercise
9-10
What is the
product of the reaction sequence shown in the margin?
What
is
the
product
of
the
reaction
sequence
shown
ininthe
the
margin?

of
the
reaction
sequence
shown
in
the
margin?
is the
product
of
reaction
sequence
shown
in
What
the
productO
of the
the
reaction
sequence
shown
the
margin?

CH
CH
SCH
CH
SCH2CH
CH3CH
O
CH

Smargin?

O SWhat
OO
3 
2
3CH O
of
sequence
shown
in
margin?
33CH
3CH
2

the
reaction
sequence
shown
in
the
margin?
What
is
the
product
of
the
reaction
sequence
shown
in
the
margin?
What is
is the
the product
product
of the
the reaction
reaction
sequence
shown
in the
the
margin?
A
B
A
CH3
CH3
OExercise
9-11
Exercise
9-11
Exercise
9-11
Exercise
9-11
85%
Exercise
9-11
Exercise
9-11 with which you would prepare the following haloalkanes
Supply reagents
from the corresponding
85%
with
Supply reagents
the
corresponding
which
you
would
prepare
the
following
haloalkanes
from
the
corresponding
with
Supply
reagents with
with which
whichyou
youwould
wouldprepare
preparethe
thefollowing
followinghaloalkanes
haloalkanesfrom
from
the
corresponding
alcohols.

Supply
Supply
reagents
with
which
you
would
prepare
the
following
haloalkanes
from
the
corresponding
which you
you would
would prepare
prepare the
the following
following haloalkanes
haloalkanesfrom
fromthe
thecorresponding
corresponding
alcohols.reagents
Supply
reagents with
with which
which
you
would
prepare
the
following
haloalkanes
from
the
corresponding
alcohols.
Br
alcohols.
alcohols.
Br
Br
alcohols.
Br
Br
Br
Br
Br
(a) I(CH2)6I
(b) (CH3CH2)3CCl
(c)
(a) I(CH
(b)
(c)
(b)
(CH
CH
CCl
(c)
(a)
I(CH22))6666II
(b) (CH
(CH3333CH
CH222)2)3)33CCl
(c)
3CCl
(a)
I(CH
)I
(b)
(CH
(c)
the
shown
in the margin?
33CH
(a)
I(CH
(b)
CH
CCl
(c)
(CH
CH22))))3333CCl
CCl
(c)
3
(a)reaction
I(CH222))666II sequence
(b) (CH
(CH
CCl
(c)
3CH22

In Summary
reactsequence
with carboxylic
acids byin
loss
of water
to furnish organic esters.
duct
of theAlcohols
reaction
shown
the
margin?
In Summary
Alcohols
acids
of
to
react with
with carboxylic
carboxylic
acids by
by loss
loss
ofwater
water
tofurnish
furnishorganic
organicesters.
esters.
Alcohols react

In
Summary
Alcohols
reactwith
with
carboxylic
acids
by
lossofof
water
tofurnish
furnish
organic
esters
They
also react
with inorganic
halides,
such acids
as
PBr
SOCl
and RSO
loss of
HX
3, loss
2,water
2Cl, by
In
Summary
Alcohols
react
carboxylic
by
to
organic
esters.
Alcohols
react
with
carboxylic
acids
by
of
to
furnish
organic
esters.
with inorganic
They
also
with
halides,
such
as
SOCl
RSO
by
loss
of
HX
In
Summary
reactThese
with
carboxylic
acids
by
loss
of
water
toRSO
furnish
organic
esters.
inorganic
halides,
such
as
PBr
SOCl
, and
and
RSO
by
loss
of
HX
2
333,,loss
222,water
22Cl,
Alcohols
2Cl,
They
also react
react
with esters.
inorganic
halides,
suchesters
asPBr
PBr
loss
of
HX
to produce
inorganic
inorganic
contain
good
leaving
groups
nucleo3, SOCl
2, and
2Cl, byin

They
also
react
with
inorganic
halides,
such
as
PBr
RSO
by
loss
of
HX
33,, SOCl
22,, and
2Cl,
They
also
react
with
inorganic
halides,
such
as
PBr
SOCl
RSO
Cl,
by
of
HX
inorganic
to produce
inorganic
esters.
These
inorganic
esters
contain
good
leaving
groups
in
nucleoesters.
These
inorganic
esters
contain
good
leaving
groups
inin
nucleo33,halide
22good
They
also
react
with
inorganic
halides,
such
as
PBr
SOCl
, and
and
RSO
Cl,
by loss
loss
of
HX
substitutions
that
are, for
example,
displaced
by
ions
to
give222the
corresponding
to
produce
inorganic
esters.
These
inorganic
esters
contain
leaving
groups
nucleophilic
to
produce
inorganic
esters.
These
inorganic
esters
contain
good
leaving
groups
in
to
produce
inorganic
esters.
These
inorganic
esters
contain
good
leaving
groups
ininnucleonucleophilic
substitutions
that
are,
for
example,
displaced
halide
ions
to
the
corresponding
are,
for
example,
displaced
by
halide
ions
totogive
give
the
corresponding
that
to
produce
inorganic
esters.
These
inorganic
estersby
contain
good
leaving
groups
nucleohaloalkanes.
philic
substitutions
that
are, for
for
example,
displaced
byhalide
halide
ionsto
givethe
thecorresponding
corresponding
philic
substitutions
that
are,
example,
displaced
by
ions
give
philic
substitutions
that
example, displaced
by
ions
give
the
haloalkanes.
philic
substitutions
that are,
are, for
for
displaced
by halide
halidefrom
ions to
to
give
thecorresponding
corresponding
haloalkanes.
hich
you
would prepare
theexample,
following
haloalkanes
the
corresponding
haloalkanes.
haloalkanes.

9-5
Names and
and Physical
Physical
Properties
of
Ethers
9-5 Names
Physical Properties
Properties of
of Ethers
Ethers
Ethers
Ethers may
may be
be thought
thought
of
as
derivatives
of
alcohols
inin which
which
the
hydroxy
proton
has
been
thought of
of as
as derivatives
derivatives of
of alcohols
alcohols in
whichthe
thehydroxy
hydroxyproton
protonhas
hasbeen
been
replaced
replaced by
by an
an alkyl
alkyl
group.
We
now
introduce
this
class
of
compounds
systematically.
This
alkyl group.
group. We
We now
now introduce
introduce this
thisclass
classof
ofcompounds
compoundssystematically.
systematically.This
This
section
gives
the
rules
for
naming
ethers
and
describes
some
of
their
physical
properties.
section gives the rules
rules for
for naming
naming ethers
ethers and
and describes
describes some
someofoftheir
theirphysical
physicalproperties.
properties.

In
In the
the IUPAC
IUPAC system,
system,
ethers
are
alkoxyalkanes
system, ethers
ethers are
are alkoxyalkanes
alkoxyalkanes
The
The
IUPAC
system
for
naming
ethers
treats
them
as
alkanes
that
bear
an
alkoxy
substituent

The IUPAC
IUPAC system
system for
for naming
naming ethers
ethers treats
treats them
them as
as alkanes
alkanesthat
thatbear
bearan
analkoxy
alkoxysubstituent
substituent

that
that
is,
as
alkoxyalkanes.
The
smaller
substituent
isisconsidered
considered
part
ofofthe
the
alkoxy
group
and
that is,
is, as
as alkoxyalkanes.
alkoxyalkanes. The
The smaller
smaller substituent
substituentis
consideredpart
partof
thealkoxy
alkoxygroup
groupand
and
the
larger
chain
defi
nes
the
stem.
the
larger
chain
defi
nes
the
stem.
the larger chain defines the stem.
In
In
common
names,
the
names
of
the
two
alkyl
groups
are
followed
by
the
word
ether.
In common
common names,
names, the
the names
names of
of the
the two
two alkyl
alkyl groups
groups are
arefollowed
followedby
bythe
theword
wordether.
ether.
Hence,
CH333OCH
is dimethyl
ether, CH
OCH222CH
is ethyl methyl
ether, and
so forth.
Hence,
Hence, CH
CH3OCH
OCH3333 is
is dimethyl
dimethyl ether,
ether, CH
CH3333OCH
OCH2CH
CH3333 isis ethyl
ethyl methyl
methylether,
ether,and
andsosoforth.
forth.
Ethers
are
generally
fairly
unreactive
(except
for
strained
cyclic
derivatives;
see
Section
9-9)
Ethers
are
generally
fairly
unreactive
(except
for
strained
cyclic
derivatives;
see
Section
Ethers are generally fairly unreactive (except for strained cyclic derivatives; see Section9-9)
9-9)
and
are therefore
frequently used
as solvents
in organic
reactions. Some
of these ether
soland
and are
are therefore
therefore frequently
frequently used
used as
as solvents
solvents in
in organic
organic reactions.
reactions.Some
Someofofthese
theseether
ethersolsolvents
are
cyclic;
they
may
even
contain
several
ether
functions.
All
have
common
names.
vents
are
cyclic;
they
may
even
contain
several
ether
functions.
All
have
common
names.
vents are cyclic; they may even contain several ether functions. All have common names.

Chapter 9

O

O
A




OP
O

P
S
O

AA 

OP
O
PSSP
P


AA 
A
CH
AA 3
CH
CH33
3

OH

OH
OH

% % %%

00

O
A

O P S P
O



CH33
CH3
CH33

1.
1. CH
CH33SO
SO22Cl
Cl
2.
2. NaI
NaI
1. CH3SO2Cl
1. CH
CH33SO
SO22Cl
Cl
2.1.NaI
2. NaI
NaI
2.

347

CH
OCH
CH
OCH
CH

CH
OCH
CH


CH33333
OCH22222CH
CH33333



CH
OCH
CH

Methoxyethane
Methoxyethane
Methoxyethane
Methoxyethane
Methoxyethane

CH
CH
CH3333
CH
ACH
AA 3
AA

CH
CH
OCCH

CH
CH
OCCH
33

CH
CH
OCCH

CH33333CH
CH22222
OCCH

CH
OCCH
AA

333

A
A
A
CH
CH
CH
CH333
CH

33
2-Ethoxy-2-methylpropane
2-Ethoxy-2-methylpropane
2-Ethoxy-2-methylpropane
2-Ethoxy-2-methylpropane
2-Ethoxy-2-methylpropane

OCH

33

OCH

OCH

OCH

OCH
%
33
3
%
%%
% ? OCH

2CH


OCH
CH

?
OCH
CH33333


?
OCH
OCH
CH
??
 2222CH


cis-1-Ethoxy-2cis-1-Ethoxy-2cis-1-Ethoxy-2cis-1-Ethoxy-2cis-1-Ethoxy-2methoxycyclopentane
methoxycyclopentane
methoxycyclopentane
methoxycyclopentane
methoxycyclopentane

348

Further Reactions

Chapter 9

CH3CH2OCH2CH3
Ethoxyethane
(Diethyl ether)

Cyclic ethers are memb

been replaced by a hetero
CH3CH
CH3hy
2OCH2and
atom except
carbon

O
O

Ethoxyethane
discussed (Diethyl
more fully
in Ch
ether)
The simplest system fo
which the prefix oxa indica
membered
cyclic are
ethers
are
Cyclic ethers
memb
ethylene
oxides),
been replaced
by four-mem
a hetero
homologs
arecarbon
oxacyclopent
atom except
and hy
The
compounds
are numbe
discussed
more fully
in Ch
Cyclic
polyethers
that fo
co
The simplest
system
unit
arethe
called
ether
which
preficrown
x oxa indica
tion
in thecyclic
crystalline
membered
ethers stat
are
shown
Figure 9-3.
The n
ethylenein oxides),
four-mem
to
the number
of oxygens.
homologs
are oxacyclopent
that
inside ofare
thenumbe
ring
The the
compounds
oxygens.
Cyclic polyethers that co
unit are called crown ether
tion in the crystalline stat
shown in Figure 9-3. The n
to the number of oxygens.
that the inside of the ring
oxygens.
O

of Alcohols and the Chemistry of Ethers

Ether Solvents and Their Names

O
Ether Solvents and Their Names
O

CH3OCH2CH2OCH3

1,4-Dioxacyclohexane
(1,4-Dioxane)

1,2-Dimethoxyethane
(Glycol dimethyl ether,
glyme)
CH OCH
CH OCH

Oxacyclopentane
Oxacyclopentane
(Tetrahydrofuran,
(Tetrahydrofuran,
THF)
THF)
O

1,4-Dioxacyclohexane
Oxacyclopentane
1,2-Dimethoxyethane
of a class of cycloalkanes
in which
one (Tetrahydrofuran,
or more carbons hav
ers (1,4-Dioxane)
(Glycol dimethyl
ether,
glyme)
(A heteroatom isTHF)
defined as an
atom in this case, oxygen.

drogen.) Cyclic compounds of this type, called heterocycles, ar

ers
of 25.
a class of cycloalkanes in which one or more carbons hav
apter
atom

in cyclic
this case,
oxygen.
(Aonheteroatom
is definedstem,
as ani
ethers
is based
the oxacycloalkane
r naming
drogen.)
Cyclic
compounds
of
this
type,
called
heterocycles,
ar
es the replacement of carbon by oxygen in the ring. Thus, three
apter
25.
oxacyclopropanes
(other names used are oxiranes, epoxides, an
r naming
cyclic are
ethers
is based on the and
oxacycloalkane
systems
oxacyclobutanes,
the next twostem,
highei
mbered
es the(tetrahydrofurans)
replacement of carbon
by oxygen in the(tetrahydropyrans
ring. Thus, three
and oxacyclohexanes
anes
oxacyclopropanes
(other
names
used
are oxiranes,
epoxides,
an
by starting at the
oxygen
and
proceeding
around
the ring.
red
mbered
systemsether
are functional
oxacyclobutanes,
and the
next
two highe
groups based
on the
1,2-ethanedio
ontain multiple
1,2-ethanedi
anes
oxacyclohexanes
(tetrahydropyrans
named because theand
molecules
adopt a crownlike
conforma
s, so (tetrahydrofurans)
red
by
starting
at
the
oxygen
and
proceeding
around
the ring.
18-crown-6
e and, presumably, in solution. The polyether
ontain
multiple
ether
functional
groups
based
on
the
1,2-ethanedi
umber 18 refers to the total number of atoms in the ring, and
s, soelectrostatic
named because
the molecules
adopt
a crownlike
conforma
potential
map on the
right
of Figure 9-3
show
The
es quite
and, presumably,
in
solution.
The
polyether
18-crown-6
electron rich due to the core electron pairs on the ethe
umber 18 refers to the total number of atoms in the ring, and
The electrostatic potential map on the right of Figure 9-3 show
s quite electron rich due to the core electron pairs on the ethe

O
2CH
3 222CH
CH
CH
OCH
CH3
O
CH3333CH
CH2 2222OCH
OCH
O
2CH333
1,4-Dioxacyclohexane
Ethoxyethane
1,4-Dioxacyclohexane
Ethoxyethane
1,4-Dioxacyclohexane
Ethoxyethane
1,4-Dioxacyclohexane
Ethoxyethane
1,4-Dioxacyclohexane
Ethoxyethane
(1,4-Dioxane)
(Diethyl
ether)
(1,4-Dioxane)
(Diethyl
ether)
(1,4-Dioxane)
(Diethyl ether)
(1,4-Dioxane)
(Diethyl
(1,4-Dioxane)
(Diethyl ether)
ether)
3

O
CH
O
2 222OCH
2
3
3
CH
OCH
CH
OCH
O
CH33333OCH
OCH2222CH
CH
O
2OCH333
Oxacyclopentane
1,2-Dimethoxyethane
Oxacyclopentane
1,2-Dimethoxyethane
Oxacyclopentane
1,2-Dimethoxyethane
Oxacyclopentane
1,2-Dimethoxyethane
Oxacyclopentane
1,2-Dimethoxyethane
(Tetrahydrofuran,
(Glycol
dimethyl
ether,
(Tetrahydrofuran,
(Glycol
dimethyl
ether,
(Tetrahydrofuran,
(Glycol
dimethyl
ether,(Tetrahydrofuran,
(Glycol
ether,
(Tetrahydrofuran,
(Glycol dimethyl
dimethyl
ether,
THF)
glyme)
THF)
glyme)
THF)
glyme)
glyme)
THF) THF)
glyme)

Cyclic
Cyclic
ethers
are
members
of
class
of
cycloalkanes
in
which
one
or
more
carbons
have
Cyclic ethers
ethers are
are members
members of
of aaa class
class of
of cycloalkanes
cycloalkanes in
in which
which one
one or
or more
more carbons
carbons have
have

Cyclic ethers are members of a class of cycloalkanes in which one or more carbons have
cbeen
ethers
are members
of a class
of cycloalkanes
in heteroatom
which one is
ordefi
more
carbons
been
replaced
by
heteroatom

in
this
case,
oxygen.
(A
ned
as
any
been replaced
replaced by
by aaa heteroatom
heteroatom
in
in this
this case,
case, oxygen.
oxygen. (A
(A heteroatom
heteroatom is
is defi
defined
ned as
as any
any
atom
and
Cyclic
compounds
of
called
are
laced
by a carbon
heteroatom
in this
case,
oxygen.
(A type,
heteroatom
is defined
atom
except
carbon
and
hydrogen.)
Cyclic
compounds
of
this
type,
called
heterocycles,
are
atom except
except
carbon
and hydrogen.)
hydrogen.)
Cyclic
compounds
of this
this
type,
called heterocycles,
heterocycles,
are a
discussed
more
fully
in
Chapter
25.
discussed
more
fully
in
Chapter
25.
ept
carbon
andfully
hydrogen.)
compounds of this type, called heterocycle
discussed
more
in ChapterCyclic
25.
The
simplest
system
for
naming
The
simplest
for
naming
cyclic
ethers
is
based
on
the
oxacycloalkane
stem,
in
The fully
simplest
system
for 25.
naming cyclic
cyclic ethers
ethers is
is based
based on
on the
the oxacycloalkane
oxacycloalkane stem,
stem, in
in
d more
in system
Chapter
which
which the
the prefi
prefix
x oxa
oxa indicates
indicates the
the replacement
replacement of
of carbon
carbon by
by oxygen
oxygen in
in the
the ring.
ring. Thus,
Thus, threethreesimplest
system
for
naming
cyclic
ethers
is
based
on
the
oxacycloalkane
membered cyclic
cyclic ethers
ethers are
are oxacyclopropanes
oxacyclopropanes (other
(other names
names used
used are
are oxiranes,
oxiranes, epoxides,
epoxides, and
andste
membered
oxides),
four-membered
systems
and
next
two
eethylene
prefix oxa
indicates
the replacement
carbon by oxygen
in the
Thus,
ethylene
oxides),
four-membered
systems
are
oxacyclobutanes,
and
the
next
two
higher
ethylene
oxides),
four-membered
systems are
areofoxacyclobutanes,
oxacyclobutanes,
and the
the
next ring.
two higher
higher
are
(tetrahydrofurans)
oxacyclohexanes
(tetrahydropyrans).
homologs
are
oxacyclopentanes
(tetrahydrofurans)
and
oxacyclohexanes
(tetrahydropyrans).
dhomologs
cyclic ethers
are oxacyclopropanes
(otherand
names
used are oxiranes,
epoxide
homologs
are oxacyclopentanes
oxacyclopentanes
(tetrahydrofurans)
and
oxacyclohexanes
(tetrahydropyrans).
The
are
by
at
oxygen
the
The
compounds
are
numbered
by
starting
at
the
oxygen
and
proceeding
around
the
ring.
The compounds
compounds
are numbered
numbered systems
by starting
startingare
at the
the
oxygen and
and proceeding
proceeding
around
the ring.
ring.
oxides),
four-membered
oxacyclobutanes,
andaround
the next
two h
Cyclic
multiple
groups
1,2-ethanediol
Cyclic polyethers
polyethers
that
contain
multiple
ether
functional
groups
based
on
the
1,2-ethanediol
polyethers that
that contain
contain
multiple ether
ether functional
functional
groups based
based on
on the
the (tetrahydropy
1,2-ethanediol
sunit
areCyclic
oxacyclopentanes
(tetrahydrofurans)
and
oxacyclohexanes
are
called
crown
ethers,
so
named
because
the
molecules
adopt
a
crownlike
conformaunit
molecules
unit are
are called
called crown
crown ethers,
ethers, so
so named
named because
because the
molecules adopt
adopt aa crownlike
crownlike conformaconformapounds
arecrystalline
numbered
byand,
starting
at the the
oxygen
and
proceeding
around
the
r
tion
tion
in
the
state
presumably,
in
solution.
The
polyether
18-crown-6
is
tion in
in the
the crystalline
crystalline state
state and,
and, presumably,
presumably, in
in solution.
solution. The
The polyether
polyether 18-crown-6
18-crown-6 is
is
shown
in
Figure
9-3.
The
number
18
refers
to
the
total
number
of
atoms
in
the
ring,
and
cshown
polyethers
that
contain
multiple
etherto
groups
basedin
1,2-ethan
in
9-3.
The
18
the
of
the
ring,
and
shown
in Figure
Figure
9-3.
The number
number
18 refers
refers
tofunctional
the total
total number
number
of atoms
atoms
inon
thethe
ring,
and 666
to
number
oxygens.
electrostatic
potential
map
right
9-3
to
the
number
of
oxygens.
The
electrostatic
potential
map
on
the
right
of
Figure
9-3
shows
to the
the crown
number of
of
oxygens.
The
electrostatic
potential
map on
on the
the adopt
right of
ofaFigure
Figure
9-3 shows
shows
called
ethers,
soThe
named
because
the molecules
crownlike
conf
that
the
the
is
electron
due
to
electron
pairs
ether
that
the
inside
of
the
ring
is
quite
electron
rich
due
to
the
core
electron
pairs
on
the
ether
thatcrystalline
the inside
inside of
of state
the ring
ring
is quite
quite
electron rich
richin
duesolution.
to the
the core
coreThe
electron
pairs on
on the
the
ether
he
and,
presumably,
polyether
18-crown
oxygens.
oxygens.
Figure 9-3. The number 18 refers to the total number of atoms in the ring,
mber of oxygens. The electrostatic potential map on the right of Figure 9-3 s
nside of the ring is quite electron rich due to the core electron pairs on the

O
O
O
O

O
O
O
O
O
O
O
O
O
O
O

O
O
O
O

e,
six
of
the
e,
six
of
the
e,
six
of
the
e,
six
of
the
en
by
the
en
by
en
by
the
en
by the
theby
(marked
(marked
(marked
by
(marked by
by

O
O
O
O

In
this
perspective,
two
of
the
O
atoms
In
this
perspective,
two
O
In
this
perspective,
two
of
the
O
atoms
In
this
perspective,
two of
of the
the
O atoms
atoms
are
masked
by
the
attached
carbons
are
masked
by
the
attached
carbons
are
masked
by
the
attached
carbons
are
masked
by
the
attached
carbons
(marked
by
arrows).
(marked
by
arrows).
(marked
by
arrows).
(marked by arrows).

O
O
O
Figure
crownlike
structural
arrangement
of
18-crown-6.
9-3
Figure
The
of
O
Figure
The
crownlike
structural
arrangement
of
18-crown-6.
9-3 The
Figure 9-3
The crownlike
crownlike structural
structural arrangement
arrangement
of 18-crown-6.
18-crown-6.

The
The
absence
of
hydrogen
bonding
affects
the
physical
properties
The absence
absence of
of hydrogen
hydrogen bonding
bonding affects
affects the
the physical
physical properties
properties

e of
of
ethers
of ethers
ethers

In this perspective, two of the O atoms

are masked by the attached carbons

oxygens.
oxygens.
oxygens.

O
O
O
O

O
O
O

O
O

O
O
O
O
O

In this
this perspective,
perspective, six
six of
of the
the
In
six
of
the
hidden
by the
the
H atoms are hidden
hidden by
by
the
(marked
by
attached carbons (marked
(marked by
by
arrows).
arrows).

O
O

In this perspective, two of the O atoms

are masked by the attached carbons
(marked by arrows).

ke structural arrangement of 18-crown-6.

ydrogen bonding affects the physical properties

a of simple alkoxyalkanes is CnH2n12O, identical with that of the

ause of the absence of hydrogen bonding, the boiling points of ethers
hose of the corresponding isomeric alcohols (Table 9-1). The two
he series are water miscible, but ethers become less water soluble as
ues increase in size. For example, methoxymethane is completely
ethoxyethane forms only an approximately 10% aqueous solution.

en
by the by
en
(marked
(marked
(marked by

are(marked
masked by
attached carbons
bythe
arrows).
(marked by arrows).

Figure
9-39-3
Thecrownlike
crownlike
structural
arrangement
ofarrangement
18-crown-6.
Figure
18-crown-6.
Figure
The crownlike
structural
of 18-crown-6.
The
structural
arrangement
of 18-crown-6.
Figure 9-3
18-crown-6.

The absence
The
absenceofofhydrogen
hydrogen
bonding
affects
the physical
properties
bonding
affects
the physical
properties

of ethers
The
absence of hydrogen bonding affects the ph
ethers
The molecular
identical
with that
that
of that
the o
alkoxyalkanes
is C is
HC H
O, identical
with
of
the
The
molecularformula
formulaof ofsimple
simple
alkoxyalkanes
O, identical
with
of
ethers
alkanols. However, because of the absence of hydrogen bonding, the
the boiling
boiling points
points of
of ethers
ethers
2n12
nn
n 2n12
2n12
n 2n12

alkanols. However, because of the absence of hydrogen bonding, the boiling points of
are
alcohols (Table
(Table 9-1).
9-1). The
The two
two
of of
thethe
corresponding
isomeric
alcohols
are much
much lower
lowerthan
thanthose
those
isomeric
alcohols (Table
9-1). Th
The
ofcorresponding
simplebutalkoxyalkanes
is C
smallestmolecular
become less
less water
water
soluble
as
nH2n12
members of theformula
series are water
miscible,
ethers become
soluble
as
smallest members of the series are water miscible, but ethers become less water solu
residues increase
in size.ofFor
example,
methoxymethane
is
the hydrocarbon
methoxymethane
is completely
completely
alkanols.
However,
because
the
absence
of hydrogen
bondin
the hydrocarbon
residues
increase
in
size.
For
example,
methoxymethane
is
comp
water soluble, whereas ethoxyethane forms only an approximately 10%
10% aqueous
aqueous solution.
solution.
watermuch
soluble, lower
whereas than
ethoxyethane
only an
approximately 10%
aqueous solu
are
thoseforms
of the
corresponding
isomeric
al

smallest members of the series are water miscible, but ethers

the hydrocarbon residues increase in size. For example, me
water soluble, whereas ethoxyethane forms only an approxim

N aa m
m ee ss aanndd PPhhyyssiiccaal l PPrrooppeer rt ti ieess oof f EEt thheer rs s
99 -- 55 N

9-5 Names and Physical Properties of Ethers

Methoxymethane
223.0
CH CH OH
9 - 5 N a m e s a n d P h y s i c a l P r o p e r3t i e s2 o f E t h e r s
(Dimethyl ether)
9-5 Names and Physical Properties of Ethers
Methoxyethane
10.8
CH3CH2CH2OH
2CH3
Boiling
Points
of Ethers
Ethers
and the
the Isomeric
Isomeric1-Alkanols
1-Alkanols
Table 9-1
9-1 Boiling
Points
of
and
Table
(Ethyl
methyl
ether)
Boiling
Points
of
Ethers
and
the
Isomeric
1-Alkanols
Table
9-1
Points of Ethers and the Isomeric
1-AlkanolsCH (CH ) OH
Table
9-1 Boiling
Boiling
Boiling
OCH
Ethoxyethane
34.5
Boiling
Boiling
Boiling
2CH3
3
2 3 Boiling
Ether
Name
point (8C)
(8C)
1-Alkanol
point(8C)
(8C)
Ether
Name
point
1-Alkanol
point
Ether
Name
point
(8C)
1-Alkanol
point
(8C)
(Diethyl ether)
Boiling
Boiling
Ether
Name
point
(8C)
1-Alkanol
point
(8C)
CHCH
OCH
Methoxymethane
223.0
CH3CH
78.5
3OCH
3O
3CH
2OH
CH
223.0
CH
OH
78.5
2
CH
Methoxymethane
223.0
CH
CH
1-Butoxybutane
142
CH
Points
of
andMethoxymethane
the Isomeric
1-Alkanols
3
2
2 333OCH
2)3332Ethers
3(CH2)7OH78.5
3CH
2OH
(Dimethyl ether)
ether)
(Dimethyl
(Dimethyl
ether)
CH3OCH3
Methoxymethane
223.0
CH3CH2OH
78.5
(Dibutyl
ether)
CH
OCH
CH
Methoxyethane
10.8
CH
CH
CH
OH
82.4
Methoxyethane
10.8
CH
CH
82.4
3
2
2
CH
2
2OH
Methoxyethane
10.8
CH333CH
CH
82.4
(DimethylBoiling
ether)
CH3333OCH
OCH2222CH
CH3333
2
2CH2
2OH Boiling
(Ethyl methyl
methyl ether)
ether)
(Ethyl
(Ethyl
methyl
CH3OCH2Name
CH3
Methoxyethane
10.81-Alkanol
CH3CH2CH2OHpoint (8C)
82.4
pointether)
(8C)
Ethoxyethane
34.5
CH (CH ) OH
117.3
CH CH OCH CH

CH
CH2222OCH
OCH2222CH
CH3333
CH3333CH
CH
3CH2OCH2CH3
Methoxymethane
O
(CH
(CH333CH
CH222CH
CH2222CH
CH2222))2222O
O
(Dimethyl
ether)
(CH3CH2CH2CH2)2O

Ethoxyethane
Ethoxyethane
(Ethyl methyl ether)
(Diethyl ether)
ether)
(Diethyl
ether)
(Diethyl
Ethoxyethane
223.0
1-Butoxybutane
1-Butoxybutane
(Diethyl
ether)
1-Butoxybutane
(Dibutyl ether)
ether)
(Dibutyl
ether)
(Dibutyl
1-Butoxybutane
10.8
(Dibutyl ether)

34.5
34.5

CH
)23OH
3
3
2
CH333(CH
(CH
2
2)3
3OH

34.5 CH OH
CH3(CH2)3OH
CH
3
2 CH
142
CH(CH
142
3(CH)2)OH
7OH

117.3
117.3

117.3
78.5
194.5
194.5

194.5
142
CH (CH
(CH )) OH
OH
194.5
ers solvate metal ions: crown142
ethersCH
and
ionophores
142
CH (CH ) OH
194.5
3
3
3

2
2
7
2 7

2 7

6
6
6
666 6
66





 





 










 
 




4
4
444






The
The
binding
binding
The

  





  
 


 


 


  

 


 

82.4
3CH2CH2OH
enMethoxyethane
in ethers, as in alcohols, is (Lewis) CH
basic
(Section 2-2); that
is, its
(Ethyl methyl ether)
ns can coordinate to electron-deficient metals, such as the magnesium in
Ethoxyethane
34.5
CH3(CH
Polyethers
metal ions:
ions:
crown
ethers
and
ionophores
metal
crown
ethers
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2)3OH
Polyethers
solvate
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crown
ethers
and
ionophores
Section
8-7).solvate
This solvating
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is particularly
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polyethers
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ether)
Polyethers
solvate
metal
ions:
crown
ethers
and
ionophores
The
ethers,
as
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is
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thatis,
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itslone
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pairs
oxygen
in
ethers,
as
in
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is
(Lewis)
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(Section
2-2);
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oxygen inatoms
ethers, may
as in alcohols,
is (Lewis)
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that
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its
lone
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ch
surround
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The structure
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ethe
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electron-defi
cient
such
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Grignard
of
coordinate
toalcohols,
electron-defi
cient metals,
metals,
such2as
the
magnesium
Grignard
142is (Lewis)
CH3(CH
)as7OH
194.5
of1-Butoxybutane
electrons
can
coordinate
to
electron-defi
cient
metals,
such
as
the
magnesium
ininlone
Grignard
The
oxygen
in ethers,
as into
basic
(Section
2-2);
thatin
is, ordinary
its
pairs
unction
as
strong
cation
binders,
including
cations
found
sa
(Section
8-7).
This
solvating
power
is
particularly
striking
in
polyethers,
in
which
reagents
8-7).
This
solvating
power
is
particularly
striking
in
polyethers,
in
which
reagents
(Section
8-7). This to
solvating
power
is particularly
polyethers,ininGrignard
which
(Dibutyl
ether)
of
electrons
can
coordinate
electron-defi
cient
metals, suchstriking
as the in
magnesium
wnreagents
ethers
can
render
the
salts
soluble
in
organic
solvents.
For
example,
such
oxygen
atoms
may
surround
metal
ions.
The
structure
of
crown
ethers
enables
several
atoms
may
surround
metal
ions.
The
structure
of
crown
ethers
enables
such
oxygen
atoms
may
surround
metal
ions.
The
structure
of
crown
ethers
enables
several (Section 8-7). This solvating power is particularly striking in polyethers, in which
to
function
as
cation
binders,
including
found
in
salts.
In
them
cation
binders,
including
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ordinary
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this
to such
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strong
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them (KMnO
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ethers
enables
4),
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ethers
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in
solvents.
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potassium
way,
can
render
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salts soluble
soluble
in organic
organic
solvents.
Forordinary
example,
potassium
crown
ethersascan
can
render
the
salts
soluble
in
organic
solvents.
example,
potassium
way,that
them
to function
strong
cation
binders,
including
cations
found For
in
salts.
In this
in
solvent
if
18-crown-6
is
added
to
it.
This
solution
is
useful
permanganate
(KMnO
), aa deep-violet
deep-violet
solid, completely
completely
insolubleFor
benzene, ispotassium
is readily
readily
(KMnO
solid,
insoluble
inin benzene,
permanganate
way,
crown ethers
can444),
render
the salts soluble
in organic solvents.
example,
idations
with
potassium
permanganate
to
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organic
solv
in
that
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if
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useful
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18-crown-6
added
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it. This
This
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18-crown-6
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itit
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e
metal
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ethers
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ionophores
4), a deep-violet
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potassium
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toto
beit.
carried
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with
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to
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ininorganic
organic
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possible
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theto
metal
ionout
by
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oxy
allows
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if 18-crown-6
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This
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useful
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ion
crown
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by effective
effective
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the to
metal
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by the
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oxygens. Disis possible
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by
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solution
allows
potassiumsolvation
permanganate
be 2-2);
carried
out
in
solvents.
as
in oxidations
alcohols,
is
(Lewis)
basic of(Section
that
is,crown
its lone
pairs
solution is possible by effective solvation of the metal ion by the six crown oxygens.
nate to electron-defi
cient metals, such as the magnesium
in Grignard


 

O
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This solvating
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polyethers,
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O
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O
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OO

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omsOmay
surround
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OO metal
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ong cation Obinders,
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CCH
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MnO
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MnO
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render the salts
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 MnO4
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O 
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is added to it. This solution


ent if 18-crown-6
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O
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[K
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18-Crown-6
18-Crown-6
[K
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18-Crown-6]
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potassium permanganate to be carried out in organic
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[K 18-Crown-6] MnO
effective
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by
 the six crown oxygens.
18-Crown-6
[K 18-Crown-6] MnO 



444 
44

size
size of
of the
the cavity
cavity
in
the
crown
ether
can
be
tailored
toto allow
allow
for
the
selective
cavity in
in the
the crown
crown ether
ether can
can be
be tailored
tailored to
allow4 for
forthe
theselective
selective
of
cations

namely,
those
whose
ionic
radius
is
accommodated
of only
only certain
certain
cations

namely,
those
whose
ionic
radius
isis best
best
accommodated
certain
cations

namely,
those
whose
ionic
radius
best
accommodated
size of the cavity in the crown ether can be tailored to allow for the selective

The size of the cavity in the crown ether can be tailored to allow for the select
ndingThe
of only
cationsinthe
namely,
whose
ionic radius
is best
accommoda
size ofcertain
the cavity
crown those
ether can
be tailored
to allow
for the
selective
binding
of onlyThis
certain
cationshas
namely,
those whose
ionic radius
best dimensions
accommodated
the
polyether.
concept
been extended
successfully
intoisthree
by
by the polyether.
This ethers,
concept also
has been
extended
successfully
into Greek,
three dimensions
the
nthesis
of polycyclic
called
cryptands
(kryptos,
hidden), by
which
synthesis
of polycyclic
also metal
called cryptands
(kryptos,
Greek,
which of
arethe
ghly
selective
in alkali ethers,
and other
binding (Figure
9-4).
Thehidden),
significance
highly selective in alkali and other metal binding (Figure 9-4). The significance of these
+

OO

OO

N N
OkOk

OkOk

OkOk

OO
k k

A cryptand

A cryptand
A cryptand

O) OO

O)

++

N
N

KK

++

NN
OkOk
OkOk

A cation

A cation
A
cation

N N
Ok Ok
OkOk

A cryptate complex
A cryptate complex

Chapter 9
MODEL BUILDING

349

O
O

Space-filling model of the cation

1
[K1
18-crown-6].

Space-filling model of the cation

[K1 18-crown-6].

Figure 9-4 The binding of a cation by a polycyclic ether (cryptand)

to form a complex (cryptate). The
system shown selectively binds
the potassium ion, with a binding
constant of K 5 1010. The order of
1
selectivity is K1 . Rb1 . Na11
.
1
1
Cs
.
Li
.
The
binding
constant
Figure 9-4 The binding of a catfor lithium
is about ether
100. Thus,
the
by a polycyclic
(cryptand)
ion
total range within the series of

total range within the series of

alkali metals spans eight orders
of magnitude.

organize themselves around cations by coordination. In general, the result of this interaction is
organize themselves around cations by coordination. In general, the result of this interaction is
that the polar hydrophilic nature of the ion is masked by a hydrophobic shell, hence making
F
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the ion much more soluble in nonpolar solvents. In nature, ionophores can transport ions
through350
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F u r t h e r R e a c t i o n s o f A l c o h o l s a n d t h e C h e m i s t r y o f Eof
ers
Chapter 9
through hydrophobic
cell membranes.
The ion balance between the inside and outside oft hthe
cell is carefully regulated to ensure cell survival, and therefore any undue disruption causes
cell is carefully regulated to ensure cell survival, and therefore any undue disruption causes
cell
destruction.
This
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put
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medicinal
use
in
fi
ghting
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compounds
was This
recognized
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in
shared
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recognized
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the
award
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Nobel
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chemistry
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1987,
shared
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property
put
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Alllby
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350
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350
C
polyether
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and However,
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by
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by Cram, Lehn,
and Pedersen.*
polyether
because
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transport
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some
occurring
ionophores
are
also
deadly
neurotoxins
(see
below
and
the
cover
of
this
book).
Crown
ethers
and
cryptands
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often
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ion
transport
agents
and
are
part
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Crown
ethers
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cryptands
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ethers and
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andare
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general class of ionophores (-phoros, Greek, bearing, hence ion bearing), compounds tha
general class
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theion
Nobelbearing),
Prize
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chemistry
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1987,
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ionophores
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compounds
that
award
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Nobel
Prize
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1987,
shared
organize
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byof
In general,
thecompounds
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of1987,
this interaction
i
compounds
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Prize
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in
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33 #
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H
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H
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counterparts
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and events
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cell membranes,

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B
Brevetoxin
B
Brevetoxin
B
H
H
CH
CH
333 particularly
3
CH
CH
produce polyether
neurotoxins,
oxygen lone
pairs,
in
polyethers,
allows
efficient metal
ionO
complexation.
causing cell
death.
)

3
H
(Marine
neurotoxin
produced
by
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(Marine
neurotoxin
produced
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algae
(Marine
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produced
by
H
)
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H
CH
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O
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associated
with
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redtide)
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red
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H
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Acyclic
ethersH
can be
be named
named
as alkoxyalkanes
alkoxyalkanes
or
alkyl
ethers.
cyclic
Acyclic
ethers
can
or
asasalkyl
)
H
H
responsible
for massive
fish kills H
Oas
)) ethers.
HSummary
H
can
9-6 Williamson
CH
Ether Synthesis

3C H
H
3
CH
3
H
H
O
and poisonings
ofO
humans
who
3
named
alkoxyalkanes
or
as
alkyl
ethers.
Their
cyclic
Summary
Acyclic
ethers have
can
be named
named
alkoxyalkanes
or as
asthan
alkylH
ethers.
Theircyclic
cyclic
In
Summary
Acyclic
ethers
be
alkoxyalkanes
or
alkyl
ethers.
Their
counterparts
called
oxacycloalkanes.
Ethers
have
lowerasasasboiling
boiling
points
doalcohols
alcohols
O
areBrevetoxin
Ethers
lower
points
do
ofof

CH
H
H
)
O

H
3
O
O
))
Brevetoxin
ate affected
seafood.
called
oxacycloalkanes.
HH than
Odescribes
Alkoxides
are excellent
nucleophiles.
This
section
their
use
indo
thealcohols
most common
O
oxacycloalkanes.
Ethers
have
lower
boiling
points
than
do
alcohols
of
counterparts
are called
called
oxacycloalkanes.
Ethers
have
lower
boiling
points
than
do
alcohols
of
counterparts
are
oxacycloalkanes.
Ethers
have
lower
boiling
points
than
of
OTheLewis
B binds to sodiumsize,
channels
on
comparable
because
they
cannot
hydrogen
bond
eachbond
other.
Lewis
basicity
the
because
they
cannot
hydrogen
bond
to
other.
The
basicity
ofof
the
0
0
00toeach
method
of hydrogen
ethers.
H
00the preparation
cannot
hydrogen
bond
to
each
other.
The
Lewis
basicity
of
the
comparable
size,
because
they
to
comparable
size,for
because
they
cannot
hydrogen
bondH
toeach
eachother.
other.The
TheLewis
Lewisbasicity
basicityof
ofthe
the
)
00cannot
nerve and muscle cell membranes,
membranes,
O
)
O
OO
0 cient
H
O
oxygen
particularly
in
polyethers,
allows
effi
cient
metal
ion
complexation.
polyethers,
allows
effi
metal
ion
complexation.
)
H
H
polyethers,
allows
effi
cient
metal
ion
complexation.
CH
oxygen
lone
pairs,
particularly
in
polyethers,
allows
effi
cient
metal
ion
complexation.
causing cell lone
death. pairs, particularly
oxygenin
lone
pairs,
particularly
in
polyethers,
allows
effi
cient
metal
ion
complexation.
3
H
HH by SCH
3
0 O 0
0
H O are
H prepared
N2 3reactions
CH
000
0
~
H
O
3
~ Ethers
O H
0 O
H
H
H0 9-6~CH
O H
O H
Williamson
Ether
Synthesis
Williamson
Ether
Synthesis
The 3simplest way
to synthesize
an ether is to have an alkoxide react with a primary halo
H
CH
H
H
HEther
33 or a sulfonate ester under typical S 2 conditions (Chapter 6). This approach is known
Synthesis
9-6 Williamson
Ether
Synthesis
alkane
CH
N
3 excellent
Alkoxides
nucleophiles.
This
section
describes
nucleophiles.
This
section
describes
their
use
in
the
most
common
Alkoxides are
are
excellent
nucleophiles.
This
section
describes their
their use
use in
inthe
themost
mostcommon
common

Brevetoxin
B
Brevetoxin
as the Williamson
etherBsynthesis. The alcohol from which the alkoxide is derived can
Brevetoxin
B describes
method
for
preparation
of
ethers.
method(Marine
for the
the neurotoxin
preparation
of ethers.
ethers.
produced
by
(Marine
produced
by
algae
This
section
Alkoxides are excellent
excellent nucleophiles.
nucleophiles.
This
section
describes
theiruse
useininthe
themost
mostcommon
common
(Marine neurotoxin
neurotoxin
produced
by algae
algae their
(Marine
neurotoxin
produced
by algae
associated
with
red
tide)
associated
with
red
tide)
associated
with
red
tide)
*Professor
Donald J. Cram
(1919
reactions
2001), University of California at Los Angeles; Professor Jean-Marie
of
method for the preparation
preparationEthers
of ethers.
ethers.
are
by
are prepared
prepared
byofS
S
2tide)
reactions
with
red
N
NN2
Lehn (b. associated
1939), University
Strasbourg
and Collge de France, Paris; Dr. Charles J. Pedersen (1904 1989)
E. I. duway
Pont to
de synthesize
Nemours
& Company,
Delaware.
The
simplest
an
is
an
react
aaa primary
haloether
is
to
have
an
alkoxide
react
with
primary
haloIn
The can
simplest
to
synthesize
an ether
etherWilmington,
is to
to have
have
an
alkoxide
react with
withTheir
primary
halobe way
named
as
alkoxyalkanes
or
asalkoxide
alkyl
ethers.
cyclic
In Summary
Summary Acyclic ethers
Professor
Alexander
W.
Williamson
(1824
University
College,
London.
alkane
or
a
sulfonate
ester
under
typical
SSSNNN222 1904),
conditions
(Chapter
6).
This
approach
is
In
Summary
Acyclic
ethers
can
be
named
as
alkoxyalkanes
or as
alkyl
ethers.
Their
cyclic
typical
conditions
(Chapter
6).
This
approach
isisknown
known
Ethers
are
prepared
by
S
2
reactions
alkane
or
a
sulfonate
ester
under
typical
conditions
(Chapter
6).
Thisdo
approach
known
by SNN2 reactions
counterparts
called
have
lower
boiling
points
than
of
Ethers
counterparts are
areprepared
called oxacycloalkanes.
oxacycloalkanes.
Ethers
have
lower
boiling
than
do alcohols
alcohols
of
as
from
which
alkoxide
is
synthesis.
The
alcohol
from
which
the
alkoxide
is
derived
can
as the
the Williamson
Williamson ether
ether synthesis.
synthesis. The
The alcohol
alcohol
frompoints
which the
the
alkoxide
is derived
derived can
can

Ethers
are prepared
SN2 reactions
simplest
way to
to by
synthesize
an
ether
is
to
have
an
alkoxide
react
with
primary
haloThe simplest
synthesize
an ether
ether is
is to
to have
have an
an alkoxide
alkoxidereact
reactwith
withaaaaprimary
primaryhalohaloThe
way
synthesize
an
alkoxide
react
with
primary
haloThe
simplest
to synthesize
ether is
to haveS
react with
a primary
or aaway
sulfonate
esteranunder
under
typical
SSan
conditions
(Chapter
6).
This
approach
isisknown
known
alkane
under
typical
2alkoxide
conditions
(Chapter
6).haloThisapproach
approachis
known
N2
alkane
or
sulfonate
ester
typical
6).
This
(Chapter
6).
This
approach
is
known
N
NN2 conditions (Chapter
under typical SN2 conditions
alkane
or
a
sulfonate
ester
(Chapter
6).
This
approach
is
known
as the
the Williamson
Williamson ether synthesis.
synthesis.
The
alcohol
from
which
the
alkoxide
isisderived
derived
can
synthesis. The
The alcohol
alcohol from
from which
whichthe
thealkoxide
alkoxideis
derivedcan
can
as
which
the
alkoxide
is
derived
can
as the
Williamson ether ether
synthesis. The alcohol
from which the
alkoxide
is derived
can
*Professor
Donald
J.
Cram
(1919
2001),
University
of
California
at
Los
Angeles;
Professor
Jean-Marie
*Professor
Donald
J. Cram
(1919
California atof
Los
Angeles; Professor
*Professor
Donald
J. Cram
Cram 2001),
(1919University
2001),ofUniversity
University
of
California
atLos
LosJean-Marie
Angeles;Professor
ProfessorJean-Marie
Jean-Marie
Donald
J.
(1919
2001),
California
at
Angeles;
*Professor
California
at
Los
Angeles;
Professor
Jean-Marie
Lehn
University
of Strasbourg
and Collgeand
de France,
Paris;
Charles J.
Pedersen
1989),
Lehn(b.(b.1939),
1939),
University
of
Strasbourg
Collge
de
France,
Paris;
Dr.
Charles
J.J.Pedersen
Pedersen
(1904
1989),
University
of Strasbourg
Strasbourg
and
Collge
deDr.
France,
Paris;
Dr.(1904
Charles
Pedersen(1904
(19041989),
1989),
1989),
Lehn
1939),
University
of
and
Collge
de
France,
Paris;
Dr.
Charles
J.J.
France,
Paris;
Dr.
Charles
Pedersen
(1904
E. I. du(b.
Pont
de Nemours
& Company,
Wilmington,
Delaware.
E.
I.
du
Pont
de
Nemours
&
Company,
Wilmington,
Delaware.
de Nemours
Nemours &
& Company,
Company, Wilmington,
Wilmington, Delaware.
Delaware.

E.
I. du Pont de
Delaware.
Professor Alexander W. Williamson (1824 1904), University College, London.
Professor
Alexander
W.
Williamson
(1824

1904),
University
College,
London.
Professor
Alexander
W.
Williamson
(1824

1904),
University
College,
London.
University College,
College, London.
London.
Professor Alexander W. Williamson (1824 1904), University

9-6 Williamson Ether Synthesis

9 -W
6 i lW
illiamson Ether Synthesis
99--66 W
i l l li iaammssoonn EEt thheer r SSy ynnt thhe es si si s
9-6 Williamson Ether Synthesis

351

Chapter 9

be used
usedasasthe
thesolvent
solvent
inexpensive),
other
molecules,
such
as dimethyl
sulfoxide
solvent
(if(if
inexpensive),
but but
other
polarpolar
molecules,
suchasas
dimethyl
sulfoxide
be
(if
inexpensive),
but
other
polar
molecules,
such
dimethyl
sulfoxide
hexamethylphosphoric
triamide
(HMPA),
areoften
often
betterbetter
(Table(Table
6-5). 6-5).
(DMSO)ororhexamethylphosphoric
hexamethylphosphoric
triamide
(HMPA),
are often
(DMSO)
triamide
(HMPA),
are
better
(Table
6-5).
other
polar molecules, such as dimethyl
sulfoxide
e (HMPA), are often better (TableWilliamson
6-5).
Williamson
Ether
Syntheses
Ether
Syntheses
Williamson
Ether
Syntheses

mson Ether Syntheses

Na  
Na
O

O
Na 
CH3CH2CH
2CH
2OH, 14 h

or DMSO, 9.5 h



Cl


NaCl

CH3CH
14h h
CH
3CH
2CH
2CH
2OH,14
2CH
2CH
2OH,
CH
3CH2CH2CH2OH, 14 h
DMSO,
9.5hh
ororDMSO,
9.5




Cl

Cl


Cl

or DMSO, 9.5 h


NaClCl
Na

O
60% (butanol solvent)
95% (DMSO solvent)

NaCl

O
O

O
60%(butanol
(butanolsolvent)
solvent)
60%
60% (butanol solve
95%(DMSO
(DMSOsolvent)
solvent)
95%

95% (DMSO
1-Butoxybutane
1-Butoxybutane

solve

1-Butoxybutane

1-Butoxybutane

CH
EM
C HE
MIICAL
CA L H IG
IGHLI
H LIGH
G HTT 9-1
9- 1

C HE M I CA L H I G H L I G H T 9- 1

Chemiluminescence
Chemiluminescence of
of 1,2-Dioxacyclobutanes
1,2-Dioxacyclobutanes

Chemiluminescence of 1,2-Dioxacyclobutanes
OH
OH
OOO
OOO
D
D
cyclobutanes
AA AA
O
O

HO

Br,
HOOH

OH

AA DOH
HO
HO
(CH
OCC(CH
O
(CH33))22CCO
(CH33))22 Br ,
Br ,
O O O AAA
HOOH
HOOHHO
A(CH3A)2CBr
Br
O C(CH3)2




C O C~ A
A
2-bromohydroperoxide
A}
2-bromohydroperoxide
H3C &
( CHBr3
CH3
CH 3

A 2-bromohydroperoxide

C OC OOO
}
}C O C(~
~CHA3
HH3C
(A CH
3C &&
3
CH
CH
CH3 3
O3 3C~
}CCH

}&

~
(

OO
BB
2 2CH
CH
3CCH
3CC

H3C
CH 3

Br
B
, 3,3,4,4-Tetramethyl-1,2-dioxacyclobutane
CH3
CH 3
3,3,4,4-Tetramethyl-1,2-dioxacyclobutane
HOOH
 hv
2 CH3CCH
(A
(A31,2-dioxetane)
1,2-dioxetane)

Acetone
Acetone

3,3,4,4-Tetramethyl-1,2-dioxacyclobutane

(A 1,2-dioxetane)
An
Williamson-type
kind
Bioluminescence
An intramolecular
intramolecular
Williamson-type reaction
reaction of
of aa special
special
kind
Bioluminescenceisisextraordinaril
extraordinar
3,3,4,4-Tetramethyl-1,2-dioxacyclobutane
Acetone
is
aa 2-bromohydroperoxide
isis the
the
is that
that in
in which
which(A
2-bromohydroperoxide
the reactant.
reactant.The
The
thefifirefl
reflyyconverts
convertsabout
about40%
40%ofofthe
the
1,2-dioxetane)
product
is
(1,2-dioxetane).
cominto
product
is aa 1,2-dioxacyclobutane
1,2-dioxacyclobutane
(1,2-dioxetane).
This
com- kindchemical
chemicalprocess
process
intovisible
visiblelight.
An intramolecular
Williamson-type
reaction ofThis
a special
Bioluminescence
islight.
extrF
pound
is
unusual
because
itit decomposes
to
the
corresponding
normal
light
bulb
isisonly
10%
effi
cie
pound
is
unusual
because
decomposes
to
the
corresponding
normal
light
bulb
only
10%
effi
ci
is
that
in
which
a
2-bromohydroperoxide
is
the
reactant.
The
the
fi
refl
y
converts
about
40
n ofcarbonyl
a special
kind
Bioluminescence
is extraordinarily effi
cient. being
For example,
compounds
with
light
energy
asasheat.
carbonyl
compounds
with emission
emission of
of(1,2-dioxetane).
light (chemilumines(chemiluminesenergychemical
beingemitted
emitted
heat.
product
is
aThe
1,2-dioxacyclobutane
This
process
into visibl
s the
reactant.
the fi
reflytoconverts
about
40%
of
thecomenergy
of the
underlying
cence).
Dioxacyclobutanes
seem
be
responsible
for
the
cence).
Dioxacyclobutanes
seem
to
be
responsible
for
the
pound
is unusual
it decomposes
the corresponding
normal light
xetane).
This
com- of because
chemical
process
intoto
visible
light. For your calibration,
a bulb is only 10
bioluminescence
species
in
Terrestrial
bioluminescence
of certain
certain
species
in nature.
nature.
Terrestrial
carbonyl
compounds
emission
of islight
(chemiluminesbeing emitted as hea
theorganisms,
corresponding
light
bulb
only
efficient, most ofenergy
the (electric)
such
fiwith
and
certain
organisms,
such as
as the
thenormal
firefl
refly,
y, the
the glowworm,
glowworm,
and10%
certain
cence).
Dioxacyclobutanes
seem
to
be
responsible
for
the
t (chemiluminesenergylight
being
emittedHowever,
as heat. most
click
emitters.
click beetles,
beetles, are
are well-known
well-known
light
emitters.
However,
most
bioluminescence
of certainin species
in nature.
Terrestrial
bioluminescent
ponsible
for the species
bioluminescent
species live
live in the
the ocean;
ocean; they
they range
rangefrom
from
organisms, bacteria
such
as and
the plankton
fi
refly, the
and light
certain
microscopic
to
re. Terrestrial
microscopic
bacteria
and
plankton
to figlowworm,
fish.
sh. The
The emitted
emitted
light
many
and
to
important
inin courtclick
beetles,
are well-known
rm, serves
and certain
serves
many purposes
purposes
and seems
seemslight
to be
beemitters.
importantHowever,
court- most
ship
and
communication,
sex
differentiation,
fi
nding
prey,
bioluminescent
species
live
in
the
ocean;
they
range
s. However,
most
ship and communication, sex differentiation, finding prey,from
hiding
from
or
predators.
microscopic
bacteria
and off
plankton
to fish. The emitted light
and
hiding
from
or scaring
scaring
off
predators.
heyand
range
from
An
of
inin nature
many
and seems to molecule
be
important
in courtAn example
example
of aa chemiluminescent
chemiluminescent
molecule
nature
Theserves
emitted
lightpurposes
is
fi
refl
yy luciferin.
The
base
oxidation
of
furis
fi
refl
luciferin.
The
base
oxidation
of this
this molecule
molecule
furship
and
communication,
sex
differentiation,
finding
prey,
portant
in acourtnishes
dioxacyclobutanone
intermediate
that
decomposes
nishes
aprey,
dioxacyclobutanone
intermediate
that decomposes
and
hiding
from
or
scaring
off
predators.
n, fiin
nding
a manner analogous to that of 3,3,4,4-tetramethyl-1,2in a manner
analogous
that of 3,3,4,4-tetramethyl-1,2An example
a to
chemiluminescent
molecule
dioxacyclobutane
toofgive
a complex heterocycle,
carbonin nature
dioxacyclobutane
to give base
a complex
heterocycle,
is firefl
yand
luciferin.
oxidation
of this carbon
molecule furolecule
in nature
dioxide,
emitted The
light.
dioxide,
and
emitted
light.
nishes a dioxacyclobutanone
intermediate that decomposes
his molecule
fur-

C HEM I CA L H I G H LI G H T 9-1
Chemiluminescence of 1,2-Dioxacyclobutanes
OH
D
O
A
(CH3)2C O C(CH3)2
A
Br

OOO
A A
}C O C~CH
H3C &
(
3
CH3
CH 3

HO
Br ,
HOOH


A 2-bromohydroperoxide

3,3,4,4-Tetramethyl-1,2-dioxacyclobutane
(A 1,2-dioxetane)

An intramolecular Williamson-type reaction of a special kind

is that in which a 2-bromohydroperoxide is the reactant. The
product is a 1,2-dioxacyclobutane (1,2-dioxetane). This compound is unusual because it decomposes to the corresponding
carbonyl compounds with emission of light (chemiluminescence). Dioxacyclobutanes seem to be responsible for the
bioluminescence of certain species in nature. Terrestrial
organisms, such as the firefly, the glowworm, and certain
click beetles, are well-known light emitters. However, most
bioluminescent species live in the ocean; they range from
microscopic bacteria and plankton to fish. The emitted light
serves many purposes and seems to be important in courtship and communication, sex differentiation, finding prey,
and hiding from or scaring off predators.
An example of a chemiluminescent molecule in nature
is firefly luciferin. The base oxidation of this molecule furnishes a dioxacyclobutanone intermediate that decomposes
in a manner analogous to that of 3,3,4,4-tetramethyl-1,2dioxacyclobutane to give a complex heterocycle, carbon
dioxide, and emitted light.
N

N
COC

HO

H
?~COH
B
O

O
B
2 CH3CCH3  hv
Acetone

Bioluminescence is extraordinarily efficient. For example,

the firefly converts about 40% of the energy of the underlying
chemical process into visible light. For your calibration, a
normal light bulb is only 10% efficient, most of the (electric)
energy being emitted as heat.

Base, O2

Firefly luciferin

N
COC


OOO
A A
N AO
OC
M
O
S

1,2-Dioxacyclobutanone intermediate

N
COC

KO

 CO2  hv
Male and female reies glowing in concert.

352
352

C
Ch
ha
ap
p tt e
e rr 9
9

F
Fu
u rr tt h
he
e rr R
Re
ea
ac
c tt ii o
on
n ss o
o ff

352

Chapter 9

Further Reactions of

HA

AA

H
H AA

Nucleophile:
Nucleophile: red
red
Electrophile:
Electrophile: blue
blue
Nucleophile:
red
Leaving
Leaving group:
group: green
green
Electrophile: blue
Leaving group: green





O
Na
Na


ONa





CH
CH
CH33(CH
(CH22))15
15CH22


OSO
SO22CH
CH33


CH3(CH2)15CH2

OSO2CH3


Because
Because alkoxides
alkoxides
unhindered alkylating
alkylating
Because alkoxides
(Section
(Section 7-8).
7-8).
unhindered alkylating
(Section 7-8).

are
are stron
stron
agents;
agents;
are stron
agents;

Exercise
Exercise 9-12
9-12

Exercise
9-12ethers
The
The following
following
ethers can,
can, in
in pri
pri

Consider
Consider the
the relative
relative merits
merits of
of
Thepropoxycyclohexane;
following ethers can,(d)
in 1,4pri
(c)
propoxycyclohexane;
(d)
(c)
1,4Consider
the4-bromo-1-butanol
relative merits ofas
wrong
with
(c) propoxycyclohexane; (d) 1,4wrong with 4-bromo-1-butanol as

Cyclic
Cyclic ethers
ethers can
can be
be pre
pre
Williamson
synthesis
Williamson
synthesis
Cyclic
ethers
can be pre
The
Williamson
ether
Williamson
The
Williamsonsynthesis
ether synthes
synthes

starting
starting from
from haloalcohols.
haloalcohols. Fig
Fig
The Williamson
ether synthes
moalcohol.
moalcohol. The
The black
black curved
curved li
li
starting
from
haloalcohols.
Fig
groups.
groups. The
The mechanism
mechanism consis
consis
moalcohol.
The
black
curved
li
transfer
transfer to
to the
the base,
base, followed
followed b
b
groups.
The mechanism
consis
is
an
example
of
an
intramolec
is an example of an intramolec
transfer
to
the
base,
followed
b
faster
faster than
than the
the side
side reaction
reaction sh
sh
is
an example
of an intramolec
bromide
by hydroxide
to give

Alcohols and the Chemistry of Ethers

HA
OCH2(CH2)15CH3

91%

DMSO

(CH22))15
CH33
HA
OCH22(CH
15CH


DMSO



 Na
Na

OSO22CH
CH33


OSO


Na
OSO2CH3


Cyclopentoxyheptadecane
Cyclopentoxyheptadecane

91%
use in ether synthesis
synthesis is
is restricted
restricted to
to primary
primary
g bases, theirCyclopentoxyheptadecane
otherwise, a significant amount
of
E2
product
is
amount of E2 product is formed
formed

g bases, their use in ether synthesis is restricted to primary

otherwise, a significant amount of E2 product is formed

than one
one Williamson
Williamson ether
ether synthesis.
synthesis.
nciple, be made by more than
1-Ethoxybutane; (b)
(b) 2-methoxypentane;
2-methoxypentane;
your approaches. (a) 1-Ethoxybutane;
Alkoxides are
are strong
strong bases.
bases. What
What isis
diethoxybutane. [Cautions:
[Cautions: Alkoxides
nciple,
be made
by for
more
than one Williamson ether synthesis.
a starting
material
(d)?]
(d)?]
your approaches. (a) 1-Ethoxybutane; (b) 2-methoxypentane;
diethoxybutane. [Cautions: Alkoxides are strong bases. What is
a starting material for (d)?]

pared by intramolecular

pared
byapplicable
intramolecular
is
is
to
preparation of
of cyclic
cyclic ethers,
ethers,
is
is also
also applicable
to the
the preparation
ure 9-5
of hydroxide
hydroxide ion
ion with
with aa brobroure
9-5 depicts
depicts the
the reaction
reaction of

Because alkoxides are strong bases, their use in ether synthesis is restricted to primary

Because
alkoxides
are
strong
bases,
their
use
in cant
ether
synthesis
restricted
Cyclopentoxyheptadecane
unhindered
alkylating
agents;
otherwise,
a signifi
amount
ofis
E2
product
isprimary
formed
Nucleophile:
red
Because
alkoxides
are
strong
bases,
use
ether
synthesis
isis
restricted
to
ing
ethers
can,
in principle,
be
made
by
than
one
Williamson
ether to
synthesis.
Because
alkoxides
are
strong
bases, their
their
use in
in
ether
synthesis
restricted
toprimary
primary
unhindered
agents;
otherwise,
aaa more
signifi
cant
product
Electrophile:
bluealkylating
unhindered
alkylating
agents;
otherwise,
signifi
cant
amount
of
E2
product
is
formed
(Section
7-8).
unhindered
alkylating
agents;
otherwise, (a)
signifi
cant amount
amount of
of(b)E2
E22-methoxypentane;
product is
is formed
formed
heLeaving
relative
merits
of your
approaches.
1-Ethoxybutane;
Because
alkoxides are
bases,
use in ether
is restricted
primary
group:
green
unhindered
alkylating
agents;
otherwise,
a strong
signifi
canttheiramount
of synthesis
E2 product
is toformed
(Section
7-8).
(Section
7-8).
(Section 7-8).
unhindered alkylating
agents; otherwise,
a significant
of E2
product
is formed
ycyclohexane;
[Cautions:
Alkoxides
areamount
strong
bases.
What
is
(Section 7-8). (d) 1,4-diethoxybutane.
(Section 7-8).
4-bromo-1-butanol as a starting material for (d)?]
Exercise 9-12
Exercise
Exercise
9-12
Exercise 9-12
9-12
Exercise 9-12
Exercise
9-12ethers can, in principle, be made by more than one Williamson ether synthesis.
The following

following ethers
can, in principle,
be than
made by
more
than one Williamson
synthesis.
The
following
ethers
in
be
by
more
one
Williamson
ether
synthesis.
The
following
ethers can,
can,
inTheprinciple,
principle,
be made
made
by (a)
more
than
one
Williamson
ether ether
synthesis.
Consider
the relative
merits
of
your approaches.
1-Ethoxybutane;
(b) 2-methoxypentane;

The
principle,
be
by
more
than
Williamson
ether
synthesis.
The following
following ethers
ethers can,
can, in
inConsider
principle,
be made
made
byyour
more
than one
one
Williamson (b)
ether
synthesis.
the relative
merits of
approaches.
(a) 1-Ethoxybutane;
2-methoxypentane;
The
following
ethers
can,
in 1,4-diethoxybutane.
principle,
be made
by(a)
more
than
one
Williamson
ether
synthesis.
Consider
relative
merits
of
your
approaches.
1-Ethoxybutane;
(b)
2-methoxypentane;
hers
canthe
be
prepared
by
intramolecular
Consider
the
your
(a)
(b)
2-methoxypentane;
(c) propoxycyclohexane;
(d)
[Cautions:
Alkoxides
are
bases.
What
Consider
the
relative
merits
of
your
approaches.
(a)
1-Ethoxybutane;
(b)
2-methoxypentane;
(c) of
propoxycyclohexane;
(d) 1,4-diethoxybutane.
[Cautions: Alkoxides
are strong
bases.
Whatisis
Consider
the relative
relative merits
merits
of
your approaches.
approaches.
(a) 1-Ethoxybutane;
1-Ethoxybutane;
(b)strong
2-methoxypentane;
Consider
the4-bromo-1-butanol
relative merits
ofaswith
your
approaches.
1-Ethoxybutane;
(b)
2-methoxypentane;
(c)
propoxycyclohexane;
(d)
1,4-diethoxybutane.
[Cautions:
Alkoxides
are
strong
bases.
What
is
wrong
4-bromo-1-butanol
as (a)
a for
starting
material
for (d)?]
(c)
propoxycyclohexane;
(d)
1,4-diethoxybutane.
[Cautions:
Alkoxides
are
strong
bases.
wrong
with
a
starting
material
(d)?]
(c)
propoxycyclohexane;
(d)
1,4-diethoxybutane.
[Cautions:
Alkoxides
are
strong
bases.
What
is
(c)synthesis
propoxycyclohexane; (d) 1,4-diethoxybutane. [Cautions: Alkoxides are strong bases. What
What is
is
onwrong
(c) propoxycyclohexane;
(d) 1,4-diethoxybutane.
[Cautions:
with
as
for
wrong
with 4-bromo-1-butanol
4-bromo-1-butanol
as aa starting
starting material
material
for (d)?]
(d)?]Alkoxides are strong bases. What is
wrong
wrong with
as aa starting
starting material
material for
for (d)?]
(d)?]
with 4-bromo-1-butanol
4-bromo-1-butanol as
wrong with 4-bromo-1-butanol as a starting material for (d)?]

mson ether synthesis Cyclic

is also
applicable
to the
preparation of cyclic ethers,
ethers
can be prepared
by intramolecular
synthesis
mCyclic
haloalcohols.
Figure
9-5
depicts
reaction of hydroxide ion with a broethers can
beWilliamson
prepared
bytheintramolecular
Cyclic
ethers
can
be
prepared
by
intramolecular
Cyclic
ethers
can
be
prepared
by
intramolecular
The
Williamson
synthesis
also applicable
to the
preparation
cyclic ethers,
Cyclic
ethers
can
be
prepared
by
The
black
curved
lines
denote
theether
chain
of iscarbon
atoms
linking
theoffunctional
Williamson
synthesis
Cyclic
ethers
can
bestarting
prepared
by intramolecular
intramolecular
from haloalcohols.
Figure 9-5 depicts the reaction of hydroxide ion with a broWilliamson
synthesis
e Williamson
mechanism synthesis
consists moalcohol.
of initial
formation
a the
bromoalkoxide
fast
proton
Williamson
synthesis
The black
curved linesof
denote
chain of carbon atomsby
linking
the functional
The Williamsonsynthesis
ether synthesis
is
also
applicable
to
the
preparation
of
cyclic
ethers,
Williamson
groups. Theismechanism
consists of initial
formation
of a bromoalkoxide
by fast
proton
The
Williamson
ether
also
applicable
to
preparation
of
cyclic
ethers,
he
base,
followed
bysynthesis
ring
closure
furnish
the
cyclic
ether.
The
ring
closure
The
Williamson
ether
synthesis
is
also
applicable
to
the
cyclic
ethers,
The
Williamson
ether
synthesis
is 9-5
alsoto
applicable
to the
the
preparation
ofether.
cyclic
ethers,
starting
from
haloalcohols.
Figure
depicts
the
of hydroxide
ion
with
aclosure
brotransfer
to the
base,
followed
by
ringreaction
closure
to preparation
furnish
the cyclicof
The
ring
The
Williamson
ether
synthesis
is
also
applicable
to
the
preparation
of
cyclic
ethers,
starting
from
haloalcohols.
Figure
9-5
depicts
the
reaction
of
hydroxide
ion
with
a
brostarting
haloalcohols.
9-5
the
of
hydroxide
with
aa much
brois anFigure
example
of andepicts
intramolecular
displacement.
Cyclic
ether
formation
is functional
usually
much
ple
of anfrom
intramolecular
displacement.
formation
ision
usually
starting
from
haloalcohols.
Figure
9-5
depicts
the reaction
reaction
of
hydroxide
ion
with
bromoalcohol.
The
black curved
lines denote
theCyclic
chain
ofether
carbon
atoms
linking
the
faster
than the
side reaction
shown
in
Figure
9-5,of
namely
intermolecular
displacement
of
moalcohol.
The
black
curved
lines
denote
the
chain
of
carbon
atoms
linking
the
functional
starting
from
haloalcohols.
Figure
9-5
depicts
the
reaction
hydroxide
ion
with
a
bromoalcohol.
The
black
curved
lines
denote
the
chain
of
carbon
atoms
linking
the
functional
moalcohol.
The
black
curved
denote
the
chain
ofThe
carbon
atoms
linking
the
functional
the
side The
reaction
shown
inlines
Figure
9-5,
namely
intermolecular
displacement
of
groups.
mechanism
consists
initial
of
a bromoalkoxide
by2-1).
fast
proton
bromide
by of
hydroxide
to formation
give
a diol.
reason
is entropy
(Section
In the
intragroups.
The
mechanism
consists
of
initial
formation
of
a
bromoalkoxide
by
fast
proton
moalcohol.
The
black
curved
lines
denote
the
chain
of
carbon
atoms
linking
the
functional
groups.
The
mechanism
consists
of
initial
formation
of
a
bromoalkoxide
by
fast
proton
groups.
The
consists
of initial
formation
of the
a are
bromoalkoxide
byInfast
molecular
reaction,
the two
reacting
centers
in the same
molecule;
in the
the proton
transition
transfer
to themechanism
base,
followed
byThe
ring
closure
to furnish
cyclic
ether.
The
ring
closure
hydroxide
to
give
a
diol.
reason
is
entropy
(Section
2-1).
intragroups.
Thethe
mechanism
consists
of initial
formation
ofthe
a bromoalkoxide
byring
fast
proton
state,
one
molecule
of bromoalkoxide
turns
into
two molecules
ofThe
products,
theclosure
ether
and
transfer
to
followed
by
ring
closure
to
furnish
cyclic
ether.
transfer
to
the
base,
followed
by
ring
closure
furnish
the
cyclic
ether.
The
ring
closure
is
an example
of anreacting
intramolecular
displacement.
Cyclic
ether
formation
isthe
usually
much
transfer
tothe
the base,
base,
followed
by
ring
closure
to the
furnish
the
cyclic
ether.
The
ringtransition
closure
eaction,
centers
into
same
molecule;
the leaving
group.
Inare
the intermolecular
reaction,
theformation
alkoxide
andin
the
nucleophile
have to
is
an
example
of
an
intramolecular
displacement.
Cyclic
ether
is
usually
much
transfer
to the two
base,
followed
by ring
closure
to furnish
the
cyclic
ether.
The
ring closure
is
an
intramolecular
displacement.
ether
formation
is
usually
much
is
an
example
of
an
intramolecular
displacement.
Cyclic
ether
formation
usually
much
faster
than the of
side
shown
in Figure
9-5,Cyclic
namely
intermolecular
displacement
is an
an example
example
of
an reaction
intramolecular
displacement.
Cyclic
ether
formation
isoverall,
usually
muchof
be brought
together
at an entropic
cost
to the
transition
state, and,is
the number
of
faster
thanofthe
side
shown
in
Figure
9-5,
namely
intermolecular
of
molecule
bromoalkoxide
turns
into
two
molecules
of intermolecular
products,displacement
ethermuch
and
is
an example
of
anreaction
intramolecular
displacement.
Cyclic
ether
formation
isNthe
faster
side
shown
in
9-5,
namely
intermolecular
displacement
of
same. In
those cases
which
the(Section
S
2usually
reaction
faster than
than
the
side reaction
reaction
shown
intheFigure
Figure
9-5,
namely
intermolecular
displacement
of
bromide
bythe
hydroxide
tomolecules
give
astays
diol.
The
reason
is in
entropy
2-1).
In thecompetes
intrabromide
by
hydroxide
to
give
diol.
reason
is
entropy
(Section
2-1).
In
the
intrawith
its a
intramolecular
counterpart,
the
intermolecular
process
can
be
effectively
supfaster
than
the
side
reaction
shown
in The
Figure
9-5,
namely
intermolecular
displacement
of
group.
In
the
intermolecular
reaction,
the
alkoxide
and
the
nucleophile
have
bromide
by
hydroxide
to
give
a
diol.
The
reason
is
entropy
(Section
2-1).
In
the
intrabromide
by
hydroxide
to
give
a
diol.
The
reason
is
entropy
(Section
2-1).
In
the
intrabromide byreaction,
hydroxide
give
a using
diol.high
The
reason
entropy
(Section
2-1).
In of
the
intra-to
molecular
thetotwo
reacting
centers
are
inis the
same
molecule;
in rate
the
transition
pressed
by
dilution
conditions,
which
drastically
reduce
the
bimolecular
molecular
the
two
reacting
centers
are
in
same
in
the
bromide
byreaction,
hydroxide
to
give
atodiol.
The
reason
isthe
entropy
(Section
2-1).
In transition
the
intramolecular
reaction,
the
two
reacting
centers
are
in
the
same
molecule;
in
the
transition
together
an entropic
cost
the
transition
and,molecule;
overall,
of
molecular
reaction,
the
two
reacting
centers
are
in
the
same
molecule;
in
the
transition
processes
(Section
2-1).
molecular
reaction,
thebromoalkoxide
two
reacting
centers
are two
in state,
the
same
molecule;
inthe
the
transition
state,
one at
molecule
of
turns
into
molecules
of
products,
thenumber
ether and
state,
one
molecule
turns
into
of
products,
and
molecular
reaction, of
thebromoalkoxide
twoIntramolecular
reacting centers
aretwo
in molecules
the
same
molecule;
in the
the ether
transition
state,
one
molecule
of
bromoalkoxide
turns
into
two
molecules
of
the
ether
and
Williamson
allows
the preparation
of cyclic
of various
state,
one
molecule
of
bromoalkoxide
turns
into
two
molecules
of
products,
the
ether
and
state,
onesame.
molecule
ofthe
bromoalkoxide
turns
intosynthesis
two
molecules
ofSproducts,
products,
theethers
ether
andto
tays
the
In In
those
cases
in which
the
intermolecular
2 nucleophile
reaction
competes
the
leaving
group.
In
intermolecular
reaction,
the alkoxide
alkoxide
and
the
nucleophile
have
N
sizes,
including
small
rings.
the
leaving
group.
the
intermolecular
reaction,
the
and
the
have
to
state,
one molecule
ofthe
bromoalkoxide
turns
into two
molecules
ofthe
products,
the ether
and
the
leaving
In
reaction,
the
nucleophile
have
to
the
leaving
group.
In
intermolecular
reaction,
the
alkoxide
and
have
to
the brought
leaving group.
group.
Inatthe
theanintermolecular
intermolecular
reaction,
the alkoxide
alkoxide
and
the
nucleophile
havesuptoof
be
together
entropic
cost to
to the
the transition
transition
state,and
and,
overall,
thenumber
number
ramolecular
counterpart,
the intermolecular
canthe
benucleophile
effectively
be
brought
an
entropic
cost
state,
and,
overall,
the
the
leaving together
group.
Inat
reaction,
the process
alkoxide
and
the
nucleophile
haveof
be
together
at
an
entropic
cost
the
transition
state,
overall,
the
of
be brought
brought
together
atthe
an intermolecular
entropic
cost to
toin
the
transition
state, and,
and,
overall,
the number
number
ofto
molecules
stays
the same.
same.
In those
those cases
cases
which
theintermolecular
intermolecular
Srate
2reaction
reaction
competes
N

using
high
dilution
conditions,
which
drastically
reduce
the
of
bimolecular
molecules
stays
the
In
in
which
the
S
2
competes
O OH
Ostate, and,
be
broughtstays
together
at an In
entropic
cost in
to which
the transition
the number
N
molecules
stays
the same.
same.
In
those
cases
in
which
the intermolecular
intermolecular
Soverall,
2 reaction
reaction
competesof
Intramolecular
N2
N
molecules
the
those
cases
the
S
competes
N
OH
with
its intramolecular
intramolecular counterpart,
counterpart, the
the intermolecular
intermolecular process
process ring
can
N be effectively supclosure
with
its
can
effectively
Section
2-1).
molecules
stays the same.counterpart,
In those cases
which the intermolecular
S be
2 reaction
competes
O supBr 
with
intramolecular
the
intermolecular
process
can
be
effectively
supwith
its
intramolecular
counterpart,
the
intermolecular
process
can
effectively
supFast
with its
its by
intramolecular
counterpart,
theinH
intermolecular
process
can
be
effectively
suppressed
using high
high dilution
dilution
conditions,
which
drastically
reduce
theNbe
rate
ofbimolecular
bimolecular
O OH
pressed
by
using
conditions,
which
drastically
reduce
the
rate
of
with
itsWilliamson
intramolecular
counterpart,
the the
intermolecular
process
can
be
effectively
suppressed
by
using
dilution
conditions,
which
drastically
reduce
the
of
CHallows
CH
lecular
synthesis
ofBr cyclic
ethers
of various
Fast preparation
pressed
by
using
high
dilution
conditions,
which
drastically
reduce
the
rate
of
bimolecular
2 O Br
2O
pressed
by
using high
high
dilution
conditions,
which
drastically
reduce
the rate
rate
of bimolecular
bimolecular
processes
(Section
2-1).
ether
processes
2-1).
pressed
by(Section
using
dilution conditions, which drastically reduce the rateCyclic
of bimolecular
processes
(Section
2-1).
processes
(Section
2-1).
ding
small
rings.high
processes
(Section
2-1).
Intramolecular
Williamson
synthesis allows the preparation of cyclic ethers of various


Intramolecular
synthesis
allows
of
cyclic
ethers
of
various
processes
(Section Williamson
2-1).
Intramolecular
Williamson
synthesis
cyclic
the
preparation
Intramolecular
Williamson
allows
of
cyclic
ethers
of
various
the preparation
preparation of
Intramolecular
Williamson
synthesis allows
allows the
ofIntermolecular
cyclic ethers
ethers of
of various
various
sizes,
including small
small
rings. synthesis
sizes,
including
rings.
reaction
sizes,
including
rings.
Intramolecular
Williamson
synthesis
allowsCH
theOpreparation
ofS 2cyclic
ethers
of various
sizes,
including small
small
rings.
HO
  OH
HO
OH
2 Br
Slow
sizes, including small rings.

N

OH

O OH OH
O
OH
O
OH
O OH
OH
O OH
H O OH

H2 O Br CH2 O
Fast
O
Br
CH
Br
CH
O Br
Br
CH2222 O
Br
2
CH2 O Br

HO

HO
HO
HO
HO
HO

Intramolecular
Figure 9-5 The mechanism of
cyclic ether synthesis from a bromoalcohol and hydroxide ion

Intramolecular
(upper reactions). A competing
but slower
side
reaction, direct displacement of bromide by

ring Intramolecular
closure


Intramolecular
 reaction). The
OH
Intramolecular
is also shown (lower
curved
lines denote a chain of carbon atoms.
Intramolecular
ring
closure
Intramolecular
OH



hydroxide,






OH
OH
OH
OH
OH

OHOH
H O

O
H
OH
O
H
O
H
OH
O OH
HFast
OH
Fast
Fast
Fast
O OH
HFast
Fast

O
O
O
O
O

Br2O
CH2 O
OBr
Br
CH
CH

Fast

CH
Br
CH
O
Br
CH2222 O
O Br
CH2 O Br


OO 
Br 
 Br

O


O 
 Br
Br 

ring closure
Fast
Fast
ringFast
closure
Fast
Fast
Fast

ring
closure
ring
closure
ring
Fast
ring
closure
ring closure
closure
Intramolecular

Fast

Intermolecular
Intermolecular
Intermolecular
Intermolecular
Intermolecular
Intermolecular

O
O 
 Br
Br
O  Br

Cyclic
Cyclic
ether
Cyclic ether
ether
Cyclic ether

Intermolecular
reaction
S 2reaction
Intermolecular
S
2 reaction
SNN2

SN2 reaction
2
S
N
2
reaction
S
N
OBr
2 reaction
reaction
SN
CH2O
Br  
 
HO
 OH
N
N
Intermolecular
CH
HO
N Slow
O
CH
Br
HO
OH
Slow
CH2 O Br
OH OH
CH
Br

HO
OH Slow
O
CH2222 O
Br 

HO
Slow
reaction HO
SN2Slow
Slow
Slow

CH2 O Br

OH

Slow
Slow

Cyclic
ether
Cyclic
ether
Cyclic
Cyclic ether
ether

HO

OH
OH
OH
OH
OH
OH

Figure 9-5 The mechanism of cyclic ether synthesis from a bromoalcohol and hydroxide ion

Figure 9-5 The mechanism of cyclic

cyclic ether
ether synthesis
synthesis from
from aa bromo
bromoalcohol
alcohol and
and hydroxide
hydroxideion
ion
(upper reactions). A competing but
but slower
slower side
side reaction,
reaction, direct
direct displacement
displacement of
of bromide
bromide by
by
hydroxide, is also shown (lower reaction).
reaction). The
The curved
curved lines
lines denote
denote aa chain
chain of
of carbon
carbon atoms.
atoms.

Oxacyclopropane
9
-6 Williamson
(Oxirane, ethylene oxide)

Ether

am
9 9- 6- 6 WW
i lil li lai m
s osno nE tEhtehr e rS ySnyt nh te hs

9-6 Williamson Ether Synthesis

99--66 W
liamson Ether Synthesis
Wiiill4
9-6 W
4llliiaammsssooonnn EEEttthhheeerrr SSSyyynnntt thhheeesssii isss
9 -- 6
9
6 W
W ii ll ll ii aa m
mson Ether Synthesis

33

H22Br

 

55

Cyclic
EtherSynthesis
Synthesis
Cyclic

Ether
Synthesis
Ether

HO
 Br
 Cyclic
  
Cyclic
Ether
Synthesis
2
6
Cyclic
Ether
Synthesis
22 2 3 3 6
Cyclic Ether Synthesis

 Cyclic
22CH

Cyclic Ether
Ether Synthesis
Synthesis
HOCH

CH22Br
Br
 Synthesis
HO

Br
HOCH

HO
 Br


  HOH

2 2 O
3  3



HO

Cyclic
Ether


 HO
22 O

O
133113
HOCH


Br


HOH




2CH
2Br





Br


HO


Br

HOCH
CH
Br


HO


HOH
Br
2
HO
 Br
 HOH
 HOCH

2 O1 3



2
22   







O
O 





HOCH
CH22Br
Br

 HO
HO


Br

 HOH
HOH
Br
1O
 22CH




Oxacyclopropane
Oxacyclopropane
11 
O
Oxacyclohexane
O
2
3
 1
Oxacyclopropane
1

1 ethylene
(Oxirane,
oxide)
(Oxirane,
ethylene
oxide)
Oxacyclopropane
Oxacyclopropane


HOH
Br
(Oxirane,
ethylene
oxide)
(Tetrahydropyran)


Oxacyclopropane
Oxacyclopropane
(Oxirane,
ethyleneoxide)
oxide)
(Oxirane,
ethylene
Oxacyclopropane
(Oxirane,
O 
(Oxirane, ethylene
ethylene oxide)
oxide)
4 4
4
1
(Oxirane,44ethylene
oxide)
4
33 3 4
55 5
4

 
Oxacyclopropane

33
55



HO(CH
)
CH
Br


HO

Br
HOH
HOH
Br

HO(CH
2
4
2
)
CH
Br


HO



Br

HO(CH
)
CH
Br

HO(CH

HOH



2
2 42 4 2
3
5









 ethylene
HO

 Br
 HOH
HOH
Br

HO

232 2
65 6 6 
2)44CH
22Br










(Oxirane,
oxide)



HO(CH
)
CH
Br


HO


Br

2
6
2
6
4

2)4CH2Br

  HO


 
HO(CH
 Br
 HOH
HOH



HO(CH
22)44CH22Br

 


HO



OOO
OO 66


 Br



HOH


O
11 1
11 
the reaction of 5-bromo-3,3-dimethyl-1-pentanol
O

3 O
5
with hydroxide is
Oxacyclohexane
1
Oxacyclohexane
1
Oxacyclohexane
Oxacyclohexane
Oxacyclohexane


(Tetrahydropyran)
4

(Tetrahydropyran)
Oxacyclohexane
hanism
for
its
formation.
H2Br


HO

 Br
Oxacyclohexane
(Tetrahydropyran)
(Tetrahydropyran)
(Tetrahydropyran)


 
(Tetrahydropyran)

Exercise
9-13
 9-13
xercise
9-13

Oxercise
Exercise
9-13
Exercise
9-13

Exercise
9-13

22

(Tetrahydropyran)
2
(Tetrahydropyran)

O
 
 Br
1

HOH


2 of 5-bromo-3,3-dimethyl-1-pentanol
6
The product of the reaction
with hydroxide is a cyclic ether.
product
of
reaction
5-bromo-3,3-dimethyl-1-pentanol
with
hydroxide
isisaaiscyclic
ether.
ontrols
the
speed
ether
formation
reaction
of5-bromo-3,3-dimethyl-1-pentanol
5-bromo-3,3-dimethyl-1-pentanol
with
hydroxide
cyclic
ether.
heThe
product
thethe
reaction
ofof
with
hydroxide
a cyclic
ether
Oxacyclohexane
a of
mechanism
for its
heSuggest
The
product
of
reaction
of
5-bromo-3,3-dimethyl-1-pentanol
with
hydroxide
is
product
thethe
of
5-bromo-3,3-dimethyl-1-pentanol
hydroxide
is a ether.
cyclic e
O
formation.
 of cyclic
The
product
of
thereaction
reaction
5-bromo-3,3-dimethyl-1-pentanol
with with
hydroxide
is aa cyclic
cyclic
ether.
Suggest
a of
mechanism
for
formation.
mechanism
for its
itsof
formation.

uggest
a mechanism
forforitsitsformation.
Suggest
aa mechanism
formation.
1
a mechanism
Suggest
mechanismfor
forits
its formation.
formation.
uggest

(Tetrahydropyran)

of the relative Oxacyclohexane

rates of cyclic ether formation reveals a surpris
Ring
size
controls
the
speed
of
cyclic
ether formation
Ring
size
controls
the
speed
of
cyclic
formation
the
speed
offast
cyclic
ether
formation
sng
form
quickly,
about
asof
asether
five-membered
ng
size
controls
the
speed
cyclic
ether
formation rings. SixRing
size
controls
the
speed
of
cyclic
ether
formation
(Tetrahydropyran)
Ring
size
controls
the
speed
ofof
cyclic
ether
formation
size
controls
the
speed
cyclic
ether
formation
A
comparison
of the relative
rates
of cyclic
ether formation
reveals
a surprising fact: ThreeA comparison of the relative
rates
of
formation
relative
rates
of cyclic
cyclic ether
ether
formationreveals
revealsaasurprising
surprising
fact:ThreeThreemembered
rings,
and
the
larger
oxacycloalkanes
are fact:
generate
A
the
relative
rates
of
cyclic
ether
reveals
aa surprising
fact:
Threemembered
rings
quickly,
about
as fast
as formation
fiformation
ve-membered
rings.
Six-membered
ring
comparison
of of
theform
relative
rates
of
ether
reveals
a surprising
fact:
Thre
A comparison
comparison
of
the
relative
rates
of cyclic
cyclic
ether
reveals
surprising
fact:
Threemembered
rings
form
quickly,
about
as
as
fifive-membered
rings.
Six-membered
ring
form
quickly,
about
as fast
fast
as formation
ve-membered
rings.
ringT
comparison
of the
relative
rates
of cyclic
ether
formation reveals
aSix-membered
surprising fact:

membered
rings
form
quickly,
about
aslarger
fast
fi
rings.
Six-membered
ring
systems,
four-membered
rings, about
and
theas
oxacycloalkanes
are
generated
more slowly.
mbered
rings
form
fast
as
ve-membered
rings.
Six-membered
membered
rings
formquickly,
quickly,
about
fast as
as
fifive-membered
ve-membered
rings.
Six-membered
ring ri
systems,
four-membered
rings,
the
larger
are
generated
more
four-membered
rings, and
and
theasas
larger
oxacycloalkanes
are
generated
moreslowly.
slowly.
mbered
rings
form
quickly,
about
fastoxacycloalkanes
as fiEther
ve-membered
rings. hydroxide
Six-membered
systems,
four-membered
rings,
and
the
larger
oxacycloalkanes
are
generated
more
slowly.
the
reaction
of 5-bromo-3,3-dimethyl-1-pentanol
with
is
systems,
four-membered
rings,
and
the
larger
oxacycloalkanes
areare
generated
more
slowly.
stems,
four-membered
rings,
and
the
oxacycloalkanes
generated
more
slowl
Relative
Rates
ofoflarger
Cyclic
Formation
Relative
Rates
Cyclic
Ether Formation
Rates
of
Cyclic
Ether
Formation
rings,
and
the
larger
oxacycloalkanes
are
generated
more
slo
stems, four-memberedRelative
Relative Rates
Rates of
of Cyclic Ether
Ether Formation
Formation
Relative
hanism for its formation.
RelativekRates
Rates
of kCyclic
Cyclic
Ether
Formation
Relative
of
Cyclic
Ether
Formation
$
k
.
.
k
$
k
.
k
6
4
7
$
kk555.
.
$
kEther
k33 $ kkkkkkn333Rates
.
.
kkkkk778888 Formation
. k88is a cyclic ether.
.k
. kkkn4k
$
k77.
.size
Relative
ofk6k66rate,
Cyclic
bromo-3,3-dimethyl-1-pentanol
with
35
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kk55 .
kk$
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5
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What effects are at work
Since
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What
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here?
Since
we
with
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What
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work
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Since
we are
are concerned
concerned
with
rates,we
weneed
needto
tocompare
compare
effects
at
here?
we
concerned
with
rates,
we
to
the What
structures
andare
hence
energies
ofSince
thecyclic
transition
of size
the intramolecular
k of
5
reaction
rate,
nstates
5ether
ring
What
effects
are
at work
work
here?
Since
we are
are
concerned
with
rates,
we need
need Williamson
to compare
compare
ontrols
the
speed
formation
structures
and
hence
energies
of
the
transition
states
the
intramolecular
Williamson
the
structures
and
hence
energies
of
the
transition
states of
ofof
the
intramolecular
Williamson
What
effects
are
atshall
work
here?
Since
we
are
concerned
with
rates,
werates,
need
to we
compa
sthe
are
at work
here?
Since
we
are
concerned
with
n
the
structures
and
energies
transition
states
of
the
intramolecular
Williamson
ether
synthesis.
Wehence
find
thatof
thethe
answer
is composed
both
enthalpic
and
entropic
n

the
structures
and
hence
energies
ofthetheanswer
transition
states
of of
theboth
intramolecular
Williamson
sether
are
at work
here?
Since
we
are
concerned
with
rates,
we
n
synthesis.
We
fifind
that
enthalpic
and
entropic
ether
synthesis.
We
shall
nd
thatofthat
the
answer
is composed
composed
of both
both
enthalpic
and
entropic
What
effects
are
atshall
work
here?
Since
we is
are
concerned
with
rates,
need
to com
structures
and
hence
energies
theanswer
transition
states
ofof
intramolecular
Williams
ether
synthesis.
We
shall
fi
that
the
is
composed
enthalpic
and
entropic
contributions
(Section
2-1).
Recall
enthalpy
ects
changes
not
only
in we
bond
strengths
ether
synthesis.
We
shall
find
nd
that
the
answer
isrefl
composed
ofthe
both
enthalpic
and
entropic
contributions
(Section
2-1).
Recall
that
enthalpy
refl
ects
changes
not
only
ininintramolecu
bond
strengths
of
nd
the
hence
relative
energies
rates
of
cyclic
the
transition
ether
formation
states
of
reveals
the
a
surpris
contributions
(Section
2-1).
Recall
that
enthalpy
refl
ects
changes
not
only
bond
strengths
peed
of
cyclic
ether
formation
structures
and
hence
energies
of
the
transition
states
of
the
intramolecular
Willia
er
synthesis.
We but
shallalso
find
that
answer
isrefl
composed
both
enthalpic
and
entrop
contributions
(Section
2-1).
Recall
that
enthalpy
refl
ects changes
changes
not
only
in bond
bond
strengths
during
a reaction,
inRecall
strainthe
(Section
4-2).
Entropy,
onofthe
other
hand,
is related
to
contributions
(Section
2-1).
that
enthalpy
ects
not
only
in
strengths
aa reaction,
but
also
in
(Section
4-2).
Entropy,
on
other
hand,
isisrelated
toto
during
reaction,
but
also
in strain
strain
(Section
4-2).
Entropy,
on the
the
other
hand,
related
synthesis.
shall
fiRecall
nd
thatenergy
the
answer
isEntropy,
composed
ofWhat
both
enthalpic
and
during
aa in
reaction,
but
also
in
(Section
4-2).
on
other
hand,
related
to
changes
theWe
extent
of
order
(or
dispersal)
in
thechanges
system.
are
the
differences
ntributions
(Section
2-1).
that
enthalpy
ects
not
in is
strengt
serduring
We
form
shall
quickly,
find
that
about
the
as
answer
fast
as
isrefl
fi
composed
ve-membered
ofonly
both
rings.
enthalp
Sixduring
reaction,
but
also
in strain
strain
(Section
4-2).
Entropy,
on the
the
other
hand,
isbond
related
toent
changes
in
the
extent
of
order
(or
energy
dispersal)
in
the
system.
What
are
the
differences
changes
in
the
extent
of
order
(or
energy
dispersal)
in
the
system.
What
are
the
differences
changes
in
extent
of
(or
energy
dispersal)
in
the
system.
What
are
the
differences
between
thethe
various
transition
states
for enthalpy
ring
formation
with
respect
to
quantities?
ntributions
(Section
2-1).
Recall
that
refl
changes
notthese
only
in
bond
stre
ring
a reaction,
but
also
information
strain
(Section
4-2).
Entropy,
on the
other
hand,
is
related
es
of
cyclic
ether
reveals
a
surprising
fact:
Threechanges
in
the
extent
of order
order
(or
energy
dispersal)
in ects
the
system.
What
are
the
differences
between
the
various
transition
states
for
ring
formation
with
respect
to
these
quantities?
membered
Section
2-1).
rings,
Recall
and
that
the
enthalpy
larger
oxacycloalkanes
refl
ects
changes
are
not
generate
only
in
between
the
various
transition
states
for
ring
formation
with
respect
to
these
quantities?
between
the
various
transition
states
for
formation
with
respect
to
these
quantities?
As
we
from
larger
ring
to ring
three-membered
ring
closures,
theare
most
between
theproceed
various
transition
states
for
ring
formation
with
respect
to other
these
quantities?
anges
the
extent
order
(or
energy
dispersal)
in
the
system.
What
the obvious
differenc
ring
rela
a inreaction,
butof
also
in
strain
(Section
4-2).rings.
Entropy,
on the
hand,
is
relat
As
proceed
from
larger
ring
to
three-membered
ring
closures,
the
obvious
about
as
fast
as
fi
ve-membered
Six-membered
ring
As we
we
proceed
from
larger
ring
todominant,
three-membered
ring
closures,
the most
most
obvious
As
we
proceed
from
larger
ring
to
three-membered
ring
closures,
the
most
obvious
enthalpy
effect
is
ring
strain.
If
it
were
the
most
strained
rings
should
be
formed
Asin
we
proceed
from
larger
ring
to ring
three-membered
ringsystem.
closures,
most
obvious
on,
also
intransition
strain
(Section
4-2).
Entropy,
onWhat
the
other
han
weenbut
the
various
states
for
formation
respect
tothe
these
quantities?
anges
the
extent
of
order
(or
energy
dispersal)
in with
the
are
the
differ

enthalpy
effect
is
ring
strain.
If
it
were
dominant,
the
most
strained
rings
should
be
formed
enthalpy
enthalpy
effect
is
ring
strain.
If
it
were
dominant,
the
most
strained
rings
should
be
formed
enthalpy effect
effect is
is ring
ring strain.
strain. If
If it
it were
were dominant,
dominant, the
the most
most strained
strained rings
rings should
should be
be formed
formed
at
the lowest
rate,
even
though
the
full
effect
of
strain
may
not
be
felt
in
the
structure
of
at
rate,
even
though
the
full
effect
of
strain
may
not
be
felt
in
the
structure
of
at the
the lowest
lowest rate,
rate, even
even though
though the
the full
full effect
effect of
of strain
strain may
may not
not be
be felt
felt in
in the
the structure
structure of
of
the
respective
transition
states.
However,
this
is
not
observed,
and
we
need
to
look
for
other
the
respective
transition
states.
However,
this
is
not
observed,
and
we
need
to
look
for
other
the respective transition states.
states. However,
However, this
this is
is not
not observed,
observed, and
and we
we need
need to
to look
look for
for other
other
factors
that
complicate
this
simple
analysis.
One
such
factor
is
entropy.
factors
that
complicate
this
simple
analysis.
One
such
factor
is
entropy.
factors
factors that
that complicate
complicate this
this simple
simple analysis.
analysis. One
One such
such factor
factor is
is entropy.
entropy.
To
understand
how
entropy
comes
into
play,
put
yourself
into
the
position
of
the
nucleoTo
To
understand
how
entropy
comes
into
play,
put
yourself
into
the
position
of
the
nucleoTo understand
understand how
how entropy
entropy comes
comes into
into play,
play, put
put yourself
yourself into
into the
the position
position of
of the
the nucleonucleophilic,
negatively
charged
oxygen
in
search
of
the
backside
of
the
electrophilic
carbon
philic,
negatively
charged
oxygen
in
search
of
the
backside
of
philic,
the
electrophilic
carbon
philic, negatively
negatively charged
charged oxygen
oxygen in
in search
search of
of the
the backside
backside of
of the
the electrophilic
electrophilic carbon
carbon
bearing
the
leaving
group.
Clearly,
the
closer
you
are
to
the
target,
the
easier
it
is
to
fi
nd
bearing
the
leaving
group.
Clearly,
the
closer
you
are
to
the
target,
the
easier
it
is
bearing
to
fi
nd
bearing the
the leaving
leaving group.
group. Clearly,
Clearly, the
the closer
closer you
you are
are to
to the
the target,
target, the
the easier
easier it
it is
is to
to fi
find
nd
it.
If
the
target
is
remote,
the
intervening
chain
has
to
be
arranged
or
ordered
in
such
a
it.
If
the
target
is
remote,
the
intervening
chain
has
to
be
arranged
or
ordered
in
it.
If
the
target
is
remote,
the
intervening
chain
has
to
be
arranged
or
ordered
in
such
it. If the target is remote, the intervening chain has to be arranged or ordered in such
such aaa
way
as
to
bring
it
closer
to
you.
This
is
more
diffi
cult
when
the
chain
gets
longer.
way
as
to
bring
it
closer
to
you.
This
is
more
diffi
cult
when
the
chain
gets
longer.
way
as
to
bring
it
closer
to
you.
This
is
more
diffi
cult
when
the
chain
gets
longer.
way as to bring it closer to you. This is more difficult when the chain gets longer.
In
molecular
terms,
to
reach
the
transition
state
for
ring
formation,
the
opposite
ends
of
the
In
In
molecular
terms,
to
reach
the
transition
state
for
ring
formation,
the
opposite
ends
of
the
In molecular
molecular terms,
terms, to
to reach
reach the
the transition
transition state
state for
for ring
ring formation,
formation, the
the opposite
opposite ends
ends of
of the
the
molecule
must
approach
each
other.
In
the
ensuing
conformation,
rotation
about
the
intervening
molecule
molecule
must
approach
each
other.
In
the
ensuing
conformation,
rotation
about
the
intervening
molecule must
must approach
approach each
each other.
other. In
In the
the ensuing
ensuing conformation,
conformation, rotation
rotation about
about the
the intervening
intervening
bonds
becomes
restricted,
and
energy
dispersal
in
the
molecule
is
reduced:
The
entropy
change
bonds
bonds
becomes
restricted,
and
energy
dispersal
in
the
molecule
is
reduced:
The
entropy
change
bonds becomes
becomes restricted,
restricted, and
and energy
energy dispersal
dispersal in
in the
the molecule
molecule is
is reduced:
reduced: The
The entropy
entropy change
change
is
unfavorable
(negative).
This
effect
is
most
severe
for
long
chains,
making
the
formation
of
is
is
unfavorable
(negative).
This
effect
is
most
severe
for
long
chains,
making
the
formation
of
is unfavorable
unfavorable (negative).
(negative). This
This effect
effect is
is most
most severe
severe for
for long
long chains,
chains, making
making the
the formation
formation of
of
medium-sized
and
larger
rings
relatively
most
diffi
cult.
In
addition,
their
rates
of
formation
sufmedium-sized
medium-sized
and
larger
rings
relatively
most
diffi
cult.
In
addition,
their
rates
of
formation
sufmedium-sized and
and larger
larger rings
rings relatively
relatively most
most diffi
difficult.
cult. In
In addition,
addition, their
their rates
rates of
of formation
formation sufsuffer
from
eclipsing,
gauche,
and
transannular
strain
(Section
4-5).
In
contrast,
cyclization
of
fer
fer
from
eclipsing,
gauche,
and
transannular
strain
(Section
4-5).
In
contrast,
cyclization
of
fer from
from eclipsing,
eclipsing, gauche,
gauche, and
and transannular
transannular strain
strain (Section
(Section 4-5).
4-5). In
In contrast,
contrast, cyclization
cyclization of
of
shorter
chains
requires
less
restriction
of
bond
rotation
and
therefore
a smaller
unfavorable
reducshorter
shorter
chains
requires
less
restriction
of
bond
rotation
and
therefore
smaller
unfavorable
reducshorter chains
chains requires
requires less
less restriction
restriction of
of bond
bond rotation
rotation and
and therefore
therefore aaa smaller
smaller unfavorable
unfavorable reducreduction
in
entropy:
Threeto
six-membered
rings
are
generated
relatively
quickly.
In
fact,
on
entropy
tion
in
entropy:
Threeto
six-membered
rings
are
generated
relatively
quickly.
In
fact,
on
entropy
tion
tion in
in entropy:
entropy: ThreeThree- to
to six-membered
six-membered rings
rings are
are generated
generated relatively
relatively quickly.
quickly. In
In fact,
fact, on
on entropy
entropy
grounds
alone,
the
relative
rates
for
ring
closure
should
be
k .
k .
k .
k . Superposition
of
grounds
grounds
alone,
the
relative
rates
for
ring
closure
should
be
.
.
.
Superposition
of
grounds alone,
alone, the
the relative
relative rates
rates for
for ring
ring closure
closure should
should be
be kkk33333 .
. kkk44444 .
. kkk55555 .
. kkk66666... Superposition
Superposition of
of
ring
strain
effects
then
leads
to
the
observed
trends
listed
above
(see
also
margin
structures).
ring
strain
effects
then
leads
to
the
observed
trends
listed
above
(see
also
margin
structures).
ring
ring strain
strain effects
effects then
then leads
leads to
to the
the observed
observed trends
trends listed
listed above
above (see
(see also
also margin
margin structures).
structures).

Chapter 9
Chapter 9

353
353

Chapter 9

353

The blue dot indicates the

The blue
dot in
indicates
the
carbon
atom
the product
carbon
atom in the
that
corresponds
to product
the site of
that
thethe
site of
The corresponds
blue
dotinindicates
ring
closure
thetostarting
ring
closure
carbon
atomin
inthe
thestarting
product
material.
material.
that corresponds to the site of
ring closure in the starting
BUILDING
MODEL
material.
MODEL BUILDING
MODEL BUILDING

O
O

Br
k3

Br

Br
k4

Br
k5

O
Br

k6

F
F
u
h
e
e
a
c
o
n
h
n
d
h
h
m
h
R
A
C
E
Fu
u rrr ttt h
he
e rrr R
ea
ac
c ttt iii o
on
n sss ooo fff A
h ooo lll sss aaa n
nd
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h eee rrr sss
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Ch
E ttt h

pter 9
pter 9

354

Further Reactions of Alcohols and the Chemistry of Ethers

Chapter 9

Further Reactions of Alcohols and the Chemistry of Ethers

Further Reactions of Alcohols and the Chemistry of Ethers

Recent
entropy
alone
Recent
studies
have
shown
that
entropy
alone
cannot
explain
why
three-membered
rings
Recent studies
studies have
have shown
shown that
thatRecent
entropy
alone cannot
cannot explain
explain why
why three-membered
three-membered rings
rings
studies have shown that entropy alone cannot explain why three-membered ring
are
enthalpic
phenomenon,
which
has
called
the
proximity
are
fastest.
A
second
enthalpic
phenomenon,
which
has
been
called
the
proximity
generated fastest.
are generated
fastest. A
A second
second are
enthalpic
phenomenon,
which
has been
been
called
thecalled
proximity
generated fastest.
A second enthalpic
phenomenon,
which
has been
the proximit
Recent
studies
have
shown
that
entropy
alone
cannot
explain
why
three-membered
rings
effect,
operates,
especially
in
2-haloalkoxides.
To
understand
it,
you
need
to
remember
that
effect,
operates,
especially
in
2-haloalkoxides.
To
understand
it,
you
need
to
remember
tha
Recent studies
have shown that entropy
alone cannot it,
explain
why
three-membered
rings
effect,
in
To
you
need
to
remember
that
effect, operates,
operates,areespecially
especially
in 2-haloalkoxides.
2-haloalkoxides.
Toto aunderstand
understand
it,
you
need
tocalled
remember
that(Sec
generated
fastest.
ASsecond
enthalpic
phenomenon,
which
has
been
proximity
allA
2 reactions
suffer
varying hindrance
degreewhich
from
steric
hindrance
of the
nucleophile
Nsecond
are suffer
generated
enthalpic
has
been
called
thethe
proximity
all
to
aaa varying
degree
from
steric
of
the
nucleophile
(Secall
S
reactions
suffer
to
varying
from
steric
hindrance
of
the
nucleophile
(Secall S
SNNNN222 reactions
reactions
suffer
to fastest.
varying
degree
fromphenomenon,
steric
hindrance
of
the
nucleophile
(Section 6-9).degree
In 2-haloalkoxides.
2-haloalkoxides
(and To
related
three-membered
ringneed
precursors),
the nucleophili
effect,
operates,
especially
in
understand
it,
you
to
remember
that
effect, operates, especially
in 2-haloalkoxides.
Toto understand
it, you
need
to
remember
that
tion
(and
three-membered
ring
precursors),
the
nucleophilic
partrelated
of the
molecule
is
so close
the
electrophilic
carbon
that
part
of the strain
of th
tion
6-9).
In
2-haloalkoxides
related
three-membered
ring
precursors),
the
nucleophilic
tion 6-9).
6-9). In
In 2-haloalkoxides
2-haloalkoxides
(and
related
three-membered
ring
precursors),
the
nucleophilic
all SSN22 reactions
reactions(and
suffer
varying
degree
from
steric
hindrance
ofthe
the
nucleophile
(Secall
suffer
totoaastate
varying
degree
from
hindrance
nucleophile
(SecN
transition
is already
present
in steric
the ground
state.
In of
other
words,
the molecule
is acti
part
close
to
the
electrophilic
carbon
that
part
of
strain
of
part
of
the
molecule
is
so
close
to
the
electrophilic
carbon
that
part
of
the
strain
of
the
tion 6-9).
6-9).is
Inso
2-haloalkoxides
(and
relatedcoordinate
three-membered
ring
precursors),
thenucleophilic
nucleophilic
part of
of the
the molecule
molecule
isIn
so
close
toalong
the(and
electrophilic
carbon
that
part
of the
the
strain
of the
theThi
vated
the
reaction
of the normal
(unstrained)
substitution
process.
tion
2-haloalkoxides
related
three-membered
ring
precursors),
the
transition
is
present
ground
other
words,
the
molecule
is
part
of the
the molecule
molecule
close
tothe
thestate.
electrophilic
carbon
thatpart
part
ofthethestrain
strain
of
rate-accelerating
proximity
effect In
is dramatically
reduced
in
four-membered
ring
synthesi
transition
state
is
already
present
in
the
ground
state.
In
other
words,
the
molecule
is
actiof
isisin
close
to
electrophilic
carbon
that
of
thethe
transition state
statepart
is already
already
present
insosothe
the
ground
state.
In
other
words,
the
molecule
isofactiacti(and soof
is the
entropy
advantage),
while
strain
is still large;
therefore, ring
closur
transition
state
already
present
inthe
the
ground
state.the
other
words,
themolecule
molecule
activated
reaction
coordinate
the
normal
(unstrained)
substitution
process.
This
state
isis already
present
ground
state.
InInring
other
words,
the
is is
activated
along
the
reaction
coordinate
of
the
normal
(unstrained)
substitution
process.
This
vated along
along the
thetransition
reaction
coordinate
of
the in
normal
(unstrained)
substitution
process.
This
to oxacyclobutanes
isof
comparatively
slow.(unstrained)
As we shall
find,
the general
conclusions
reached
vated
along
the
reaction
coordinate
the
normal
substitution
process.
This
vated
along the effect
reaction
theto
normal
(unstrained)
substitution
process.
This
rate-accelerating
proximity
is
dramatically
reduced
four-membered
synthesis
in this
section
applyofalso
other ring in
closing
transformations
thatring
we
shall
encounter
in
rate-accelerating
proximity
effect
is
dramatically
reduced
in
four-membered
ring
synthesis
rate-accelerating
proximity
effect
iscoordinate
dramatically
reduced
in
four-membered
ring
synthesis
rate-accelerating
proximity
effectisisdramatically
dramatically
reduced
infour-membered
four-membered
ring
synthesis
rate-accelerating
proximity
effect
reduced
in
ring
synthesis
later
chapters.
(and
advantage),
while
ring
strain
is
still
therefore,
ring
closure
(and
so
is
the
entropy
while
the
ring
strain
still
large;
therefore,
ring
closure
(and so
so is
is the
the entropy
entropy
advantage),
while the
thewhile
ringthe
strain
is
stillisislarge;
large;
therefore,
ring
closure
(and so
so isisadvantage),
the entropy
entropyadvantage),
advantage),
while
thering
ringis
strain
stilllarge;
large;
therefore,
ring
closure
(and
the
strain
still
therefore,
ring
closure
to
is
slow.
we
shall
fi
nd,
the
general
conclusions
reached
to
oxacyclobutanes
is
comparatively
slow.
As
we
shall
fi
nd,
the
general
conclusions
to oxacyclobutanes
oxacyclobutanes
comparatively
slow.
Aswe
we
shall
find,
thegeneral
general
conclusions
reached
to oxacyclobutanes
oxacyclobutanes
is comparatively
comparatively
slow. As
Asslow.
we
shall
fishall
nd,
the
general
conclusions
reached
to
isis
comparatively
As
find,
the
conclusions
reached
The
intramolecular
Williamson
synthesis
is
stereospeci
c reached
in
apply
also
to
other
ring
closing
transformations
that
we
shall
encounter
in
in
thisMODEL
section
apply
also
other
ring
closing
transformations
that
we
shall
encounterin
in
this
section
apply
also
to
other
ring
closing
transformations
that
we
shall
encounter
in
this
section
also
totoother
ring
closing
transformations
we
shall
in this
this section
section in
apply
also
toapply
other
ring
closing
transformations
that that
we
shall
encounter
inin
BUILDING
The
Williamson
ether
synthesis
proceeds
with inversion
of
confi
guration
atencounter
the carbon bearing
later
chapters.
later
chapters.
later
the leaving group, in accord with expectations based on an SN2 mechanism. The attacking
later chapters.
chapters. later chapters.

nucleophile approaches the electrophilic carbon from the opposite side of the leaving group
Only one conformation of the haloalkoxide can undergo efficient substitution. For example

The intramolecular
intramolecular
Williamson
synthesis
stereospeci
The
Williamson
isis
stereospeci
c c and the leaving
oxacyclopropane
formationsynthesis
requires
anti
arrangement
of thec
The
Williamson
synthesis
is
The intramolecular
intramolecular
Williamson
synthesis
isanstereospeci
stereospeci
cnucleophile
group. The alternative two gauche conformations cannot give the product (Figure 9-6).
MODEL BUILDING
The Williamson
Williamsonether
ethersynthesis
synthesisproceeds
proceedswith
withinversion
inversionofofconfi
confi
gurationatatthethecarbon
carbon
bearing
The
guration
bearing

MODEL BUILDING

The
ether
synthesis
with
inversion
of
confi
at
bearing
The
Williamson
ether
synthesis
proceeds
with
inversion
of
confi
guration
at
the
carbon
bearing
the
leaving
group, inproceeds
in accord
accordwith
with
expectations
based
mechanism.
Theattacking
attacking
leaving
group,
ononguration
ananSNS2N2mechanism.
The
The Williamson
Williamsonthe
ether
synthesis
proceeds
withexpectations
inversionbased
of
confi
guration
at the
the carbon
carbon
bearing
the leaving
in
accord
with
expectations
an
S
222opposite
mechanism.
The
nucleophile
approaches
theelectrophilic
electrophilicbased
carbonon
from
the
sideofofthethe
group.
nucleophile
approaches
carbon
from
the
side
leaving
group.
leaving
group,
in
accord
with
expectations
based
on
an
S
mechanism.
The
attacking
 attacking
leaving
the
leaving group,
group,
in
with the
expectations
based
on
an
SNNNNopposite
mechanism.
The
attacking
 accord



Br
H
D
O
O
O

O

Only one
one conformation
conformation
thehaloalkoxide
haloalkoxide
can
undergo
effi
cient
substitution.
example,
Only
ofofthe
undergo
effi
cient
substitution.
example,
nucleophile
the
electrophilic
carbon
from
the
opposite
side
of
the
group.

G For
H
Br
nucleophile
approaches
the
carbon
the
opposite
side
of
the
leaving
group.
DGFor
Inversion

Dfrom

nucleophile approaches
approaches
electrophilic
carbon
fromcan
the
opposite
side
of
the leaving
leaving
group.
G C electrophilic

C the
C the
C G Can
C G SCofofthe
C
Cthe
 Br

oxacyclopropane
formation
requires
anti
arrangement
nucleophile
and
leaving
oxacyclopropane
formation
requires
an
anti
arrangement
the
nucleophile
and
leaving
Only
haloalkoxide
can
undergo
substitution.
example,
( cient
H ( of
H (
H ( For
D
Only
one
conformation
of the
the
haloalkoxide
can
undergoH effi
effi
cient
substitution.
For
example,
Only one
one conformation
conformation
the
can
effi
cient
substitution.
ForR (9-6).
example,

D haloalkoxide
H undergocannot
Br
H
H
H
H(Figure
H 9-6).
group.
alternative
two
conformations
give
the
group. The
Theof
alternative
twogauche
gauche
conformations
cannot
give
theproduct
product(Figure
nucleophile
oxacyclopropane
requires
anti
arrangement
of
oxacyclopropane
formation
requires
an
anti
arrangement
of
the
nucleophile
and
the
leaving
oxacyclopropane formation
formation
requires an
an
antiunsuitable
arrangement
of the
the
nucleophile and
and the
the leaving
leaving
Gauche: unsuitable
Gauche:
Anti: correct
conformation
for SN2 gauche
for SN2
for SNthe
2
group.
cannot
product
group.
The
alternative
two
gauche
conformations
cannot
give
the
product
(Figure
9-6).
group. The
The alternative
alternative two
two
gauche conformations
conformations
cannot give
give
the
product (Figure
(Figure 9-6).
9-6).
&

C
G

&

C
G

&

Figure 9-6 Only the anti conformation of a 2-bromoalkoxide allows for oxacyclopropane
 backside attack at the
formation. The two gauche conformers cannot undergo intramolecular

C
G



Br
DD

OO

Br
bromine-bearing
carbon.
O


HH Inversion
D
Inversion
CCGG CC D
CCGGSCC
S

((
H
HH D

H ((

Br

Br
D


HH O

Br
DH Br

HH
Br

DHH

H Inversion
Exercise 9-14
Inversion

OO
GG
DGD

GG
&&
@@

CC
GG

GG
&&
@@




CC
GG

H
H
O

Br
Br

CG C 



H (


D
H
O

O

G
&
@

C
G

Br
CC GRCRCC C Br


((
HHO
( ( DD
HO
HH
O
HG
DG
Hconformation
D
Inversion

GG
GGGAnti:Ccorrect
Inversion

D


Gauche: unsuitable

C
CDGGG C
C CC


Gauche:
unsuitable C
Gauche:unsuitable
unsuitable
conformation
C
C
C
Br
Br


CG C
C Gauche:
CAnti:
Ccorrect
SSSC

R C D  Br
with
the
of(C

for
for
for
R
H
H
S Concepts:
for SSNN22 H
forSSNN22 Working
forSN
S2N2 Stereochemistry
R (
(( the Intramolecular
H
H
H
(( D
H H(((
HH((( Ether
H
D

Williamson
Synthesis
H
Br

H
H
H
Br


H
H
H
H
H
Br

H Figure
H
9-6
Only
the
anti
conformation
of
a
2-bromoalkoxide
allows
for
oxacyclopropane
Figure 9-6 Only the anti conformation 
of a 2-bromoalkoxide allows for oxacyclopropane


CC

CCC

G
G
G
&&& @@
@

CCC
G
G
G

G
G
G
&&& @@
@

CCC
G
G
G

(1R,2R)-2-Bromocyclopentanol
reacts rapidly
with sodium hydroxide
to yield
an optically
formation.
The
conformers
cannot
intramolecular
backside
attack
at at
thetheinactive
Gauche:
unsuitable
Anti:
correct
conformation
formation.
Thetwo
twogauche
gauche
conformers
cannotundergo
undergo
intramolecular
backside
attack
Gauche:
unsuitable
Anti:
correct
conformation
Gauche:bromine-bearing
unsuitable
Anti:
correct
conformation
product.
In contrast,
the (1S,2R) isomer is much less reactive. Explain.
carbon.
bromine-bearing
carbon.
for
SN
2
for
2
S
2
for
N
Strategy for
for S
SN
for S
SN
2
N2
N2
N

N
The first thing to do is to write down the two isomeric bromocyclopentanols (even better, build

Figure
of
2-bromoalkoxide
allows
for
models!),
can visualize their differences.
How
these differences affect reactivity?
Figure
9-6
Only
the
anti
conformation
of
a
2-bromoalkoxide
allows
for
oxacyclopropane
Figure 9-6
9-6 Only
Only the
the anti
anti conformation
conformation
ofsoa
ayou
2-bromoalkoxide
allows
fordooxacyclopropane
oxacyclopropane
formation. The
The
two
gauche
conformers
cannot
undergo
intramolecular
backside
attack
at
the
formation.
The two
two gauche
gauche conformers
conformers cannot
cannot undergo
undergo intramolecular
intramolecular backside
backside attack
attack at
at the
the
bromine-bearing
carbon.
Exercise
9-14
bromine-bearing
carbon.
bromine-bearing Exercise
carbon. 9-14
S R
R R
)
H @

@) Br

)
HO @

@) Br

H
H
OH H
Working
ofofthe
Working with
with the
theConcepts:
Concepts:Stereochemistry
Stereochemistry
theIntramolecular
Intramolecular
(1R,2R)-2-Bromocyclopentanol
(1S,2R)-2-Bromocyclopentanol
Williamson
Williamson Ether
EtherSynthesis
Synthesis The nucleophilic oxygen and the
Here the nucleophile and leaving
leaving group are trans (anti)

group are cis (syn)

(1R,2R)-2-Bromocyclopentanol
Solution reacts rapidly with sodium hydroxide to yield an optically inactive
Exercise
(1R,2R)-2-Bromocyclopentanol
reacts rapidly with sodium hydroxide to yield an optically inactive
Exercise
9-14
Exercise 9-14
9-14 product.
Conformational
freedom
around
thereactive.
bond connecting
the two functional groups is restricted
In contrast, the
(1S,2R) isomer
is much
less
Explain.

product. In contrast, the

(1S,2R)
isomer
is much
less
Explain.
(unlike
the situation
shown
in Figure
9-6).reactive.
In the (1R,2R)
isomer the functional groups are arranged

Strategy
Strategy
Working
the
Stereochemistry
of
the
Working
with
the
Concepts:
the
Intramolecular
thing to do isStereochemistry
to write down the two of
isomeric
bromocyclopentanols (even better, build
Working with
withThe
thefirstConcepts:
Concepts:
Stereochemistry
of
the Intramolecular
Intramolecular
The first
thing to do is to write down the two isomeric bromocyclopentanols (even better, build
Williamson
Ether
Synthesis
models!),
so you can visualize their differences. How do these differences affect reactivity?
Williamson
Ether
Synthesis
Williamson Ether
Synthesis
models!),
so you can visualize their differences. How do these differences affect reactivity?

group.

H
O

Br

 G
H
C
C
O

Br
H ( G

HC CD
H (
Gauche:
D
H unsuitable

&
G
@
&
G

GC
G

for SN2
Gauche: unsuitable
for SN2

Figure
formati
Figure
bromin
formati

clopropane
formation
requires
an anti arrangement
nucleophile
andFor
theexample,
leaving
one
conformation
of the
haloalkoxide
can undergo of
effithe
cient
substitution.
The alternative
conformations
cannotgive
give
the
product(Figure
(Figure
9-6).
two gauche
gauche
conformations
cannot
give
the
product
(Figure
9-6).
two
cannot
the
product
9-6).
clopropane
formation
requiresconformations
an anti arrangement
of
the
nucleophile
and the
leaving
The alternative two gauche conformations cannot give the product (Figure 9-6).
DD
D
O
O

O
HH
H Inversion
Inversion
Inversion
 GG
D
O
CC
C
C GSSC
C
H
H ((( G S H Inversion

Br
H
Br
H
H C C Br


H ( S 

Anti:
Br
Anti:
correct
conformation
Anti:correct
correct
conformation
H conformation


G
&G
G
G
@
&&&
@@@

C
GCCC
G
GG

G
&G
G
@
&&
@@

C
GC
G

for
for SSNN22
Gauche: unsuitable





 
OO
O
G
GG
DGDD

GGCCCC CC

CCCO

Br

Br
Br



RRR( (( DD
HH
H ((( DG G
D


C
C
C


Br
HH
HH
H
H

R ( D
H (
H
H

C
CC C

Br
Br
O


D
D
 G

Br
OC C
C 
H ( G
D
C
C
H
H
H
H (
Gauche:
H
unsuitable
Gauche:
H unsuitable


for
for
forSSSNNN222
Anti: correct conformation

for Sthe
S N2
e 9-6
aaa2-bromoalkoxide
allows
N2 anti
anti conformation
conformation
of
2-bromoalkoxide
allows
for
oxacyclopropane
9-6 Only
Only
the
conformationof
offor
2-bromoalkoxide
allowsfor
foroxacyclopropane
oxacyclopropane
e
atat
the
on. The
gauche conformers
conformers
cannot
undergo
intramolecular
backside
attack
the
The two
two gauche
conformerscannot
cannotundergo
undergointramolecular
intramolecularbackside
backsideattack
attack
at
the
ee-bearing
9-6 Onlycarbon.
the anti conformation of a 2-bromoalkoxide allows for oxacyclopropane
carbon.
e-bearing
on. The two gauche conformers cannot undergo intramolecular backside attack at the

e-bearing carbon.

cise 9-14
9-14
cise
cise
king9-14
with the Concepts: Stereochemistry of the Intramolecular

Stereochemistry of
of the
the Intramolecular
Intramolecular
king with the Concepts: Stereochemistry
iamson
Ether
Ether
Synthesis Stereochemistry of the Intramolecular
iamson
king
with
the Synthesis
Concepts:
iamson
Ether Synthesis
R)-2-Bromocyclopentanol
reacts rapidly with sodium hydroxide to yield an optically inactive

R)-2-Bromocyclopentanol reacts
rapidly with
with sodium
sodium hydroxide
hydroxide to
to yield
yield an
an optically
optically inactive
inactive
reacts rapidly
uct. In
contrast, the
(1S,2R) isomer
isis much
less reactive.
Explain.
uct.
In
isomer
reactive.
Explain.
isomer
is much
much
less
reactive.
Explain.
uct.
In contrast,
contrast, the
the (1S,2R)
(1S,2R)reacts
R)-2-Bromocyclopentanol
rapidly
withless
sodium
hydroxide
to yield an optically inactive
egy
egy In contrast, the (1S,2R) isomer is much less reactive. Explain.
egy
uct.
first
rst thing to
do is
to write
down the
two isomeric
bromocyclopentanols (even
better, build
fi
fi
rst thing
thing to
to do
do is
is to
to write
write down
down the
the two
two isomeric
isomeric bromocyclopentanols
bromocyclopentanols (even
(even better,
better, build
build
egy
ls!), so
you can
visualize their
differences.
How
do these
differences affect
reactivity?
ls!),
so
differences.
How
these
reactivity?
so you
you
can
visualize
their
differences.
How do
dobromocyclopentanols
these differences
differences affect
affect
reactivity?
fils!),
rst thing
to can
do isvisualize
to writetheir
down
the two isomeric
(even
better, build
ls!), so you can visualize their differences. How do these differences affect reactivity?
R R
)
R R)
)
H
)@@ R R@@@)
)Br
H
Br
HOH
Br
@R R H
OH
H
)
OH
HBr
)
@
H @
(1R,2R)-2-Bromocyclopentanol
(1R,2R)-2-Bromocyclopentanol
OH
H
(1R,2R)-2-Bromocyclopentanol
The nucleophilic oxygen and the

S R
)
S RR
)
HO
@ S @)
)Br
)
HO
HOH @@S RH@@)Br
Br
H
H
)
H
HBr
)
@
HO
@
(1S,2R)-2-Bromocyclopentanol
(1S,2R)-2-Bromocyclopentanol
H
H
(1S,2R)-2-Bromocyclopentanol
Here the nucleophile and leaving

leaving
leaving group
group are
are trans
trans (anti)
(anti)

group
groupare
arecis
cis(syn)
(syn)

The
nucleophilic
oxygen
and
(1R,2R)-2-Bromocyclopentanol
The
nucleophilic
oxygen
and the
the
leaving
group are
trans (anti)

Here
nucleophile
and
(1S,2R)-2-Bromocyclopentanol
Here the
the
nucleophile
andleaving
leaving
group
are cis (syn)

The nucleophilic oxygen and the

Here the nucleophile and leaving
ion
ion
leaving group are trans (anti)
group are cis (syn)
ion
nformational
freedom around the bond connecting the two functional groups is restricted
nformational
freedom
around
the
bond
connecting
the
functional
groups
isis restricted
ion
nformational
freedom
around
the
bond
connecting
the two
two
functionalgroups
groupsare
restricted
ke the situation shown in Figure 9-6). In the (1R,2R) isomer
the functional
arranged
ke
the
shown
Figure
9-6).
In
(1R,2R)
the
functional
groups
are
arranged
nformational
around
bond
connecting
the two
ke
the situation
situationfreedom
shown in
in
Figurethe
9-6).
In the
the
(1R,2R) isomer
isomer
thefunctional
functionalgroups
groupsis
arerestricted
arranged
ke the situation shown in Figure 9-6). In the (1R,2R) isomer the functional groups are arranged

for
SSNN22
for SSthe
for
Figure 9-6 Only
a 2-bromoalkoxide
allows for oxacyclopropane
N
N22 anti conformation offor
formation. The two gauche conformers cannot undergo intramolecular backside attack at the
9-6 Only
the
Figure
Onlycarbon.
the anti
anti conformation
conformationof
ofaa2-bromoalkoxide
2-bromoalkoxideallows
allowsfor
foroxacyclopropane
oxacyclopropane
bromine-bearing
formation. The
The two
two gauche
gauche conformers
conformerscannot
cannotundergo
undergointramolecular
intramolecularbackside
backsideattack
attackatatthe
the
bromine-bearing
bromine-bearing carbon.
carbon.

Exercise 9-14
Exercise 9-14
Working9-14
with the Concepts: Stereochemistry of the Intramolecular

Williamson
Ether
Synthesis
with
the
Working
with
the Concepts:
Concepts: Stereochemistry
Stereochemistryofofthe
theIntramolecular
Intramolecular
Williamson
Ether
Williamson
Ether Synthesis
Synthesis
(1R,2R)-2-Bromocyclopentanol reacts rapidly with sodium hydroxide to yield an optically inactive
product. In contrast, the (1S,2R)reacts
isomer is much
less reactive.
Explain.
(1R,2R)-2-Bromocyclopentanol
(1R,2R)-2-Bromocyclopentanol reactsrapidly
rapidlywith
withsodium
sodiumhydroxide
hydroxidetotoyield
yieldananoptically
opticallyinactive
inactive
StrategyIn contrast, the (1S,2R) isomer is much less reactive. Explain.
product.
product. In contrast, the (1S,2R) isomer is much less reactive. Explain.
The first thing to do is to write down the two isomeric bromocyclopentanols (even better, build
Strategy
Strategy
models!),
so you can
visualize
their differences.
How do these differences affect
reactivity?
The
The fi
first
rst thing
thing to
to do
do isis to
to write
write down
down the
the two
twoisomeric
isomericbromocyclopentanols
bromocyclopentanols(even
(evenbetter,
better,build
build
models!),
models!), so
so you
you can
can visualize
visualize their
their differences.
differences.How
Howdo
dothese
thesedifferences
differencesaffect
affectreactivity?
reactivity?
R R

)
H @R R @) Br
)
OHR R@)
H
)
H
@
@)Br
HOH
Br
@ H
(1R,2R)-2-Bromocyclopentanol
OH H

The nucleophilic oxygen and the

(1R,2R)-2-Bromocyclopentanol
(1R,2R)-2-Bromocyclopentanol
leaving group are trans (anti)
The nucleophilic oxygen and the
The
nucleophilic
and the
leaving
group areoxygen
trans (anti)
leaving group are trans (anti)

S R

)
HO S@ R @) Br
))
H S R)H
HO
HOH@ @ @H@)BrBr
(1S,2R)-2-Bromocyclopentanol
H
H

Here the nucleophile and leaving

(1S,2R)-2-Bromocyclopentanol
(1S,2R)-2-Bromocyclopentanol
group are cis (syn)
Here the nucleophile and leaving

Here the
nucleophile
and leaving
group
are cis (syn)
Solution
group are cis (syn)
Conformational freedom around the bond connecting the two functional groups is restricted
Solution
Solution
(unlike
Conformational
freedom
around
bond
connecting
the twothe
functional
restricted
the situation
shown in
Figurethe
9-6).
In the
(1R,2R) isomer
functionalgroups
groupsisare
arranged
Conformational freedom around the bond connecting the two functional groups is restricted
(unlike the situation shown in Figure 9-6). In the (1R,2R) isomer the functional groups are arranged
(unlike the situation shown in Figure 9-6). In the (1R,2R) isomer the functional groups are arranged

9 -- 7
7 S
S yy n
n tt h
h ee ss ii ss oo ff E
E tt h
h ee rr ss :: A
A ll cc oo h
h oo ll ss aa n
nd
d M
M ii n
n ee rr aa ll A
A cc ii d
d ss
9
7 SS
S yyy nn
n ttt hh
h eee sss iii sss ooo fff EE
Ettthh
heeerrrsss::: AA
Alllcccooohh
hoool llsss aaann
ndd
d MM
Mi iinn
neeer rraaal ll AA
Accci iidd
ds ss
--- 7
9
7

9-7 Synthesis of Ethers: Alcohols and Mineral Acids

trans and
and hence
hence in
in perfect
perfect alignment
alignment for
for backside
backside displacement
displacement of
of bromide
bromide by
by intramolecular
intramolecular S
SNN2.
2.
trans
hence in
in perfect
perfect alignment
alignment for
for backside
backsidedisplacement
displacementof
ofbromide
bromideby
byintramolecular
intramolecularSS
SN2.
2.
and
trans
N2.
transresulting
and hence
hence
in
perfect
alignment
backside
bromide
by
intramolecular
N
The
oxacyclopropane
has aa for
mirror
planedisplacement
and is
is meso
meso of
(achiral):
The
resulting
oxacyclopropane
has
mirror
plane
and
(achiral):
resulting oxacyclopropane
oxacyclopropane has
has aaa mirror
mirror plane
plane and
and isis
is meso
meso(achiral):
(achiral):
The
The resulting
resulting
oxacyclopropane
has
mirror
plane
and
meso
(achiral):

Meso
Meso
Meso
Meso
Meso

Fast

R R

Br


)
H)
H
) @@@@)
)HH
H
H)
H
O
HH
O@ )
OO
O H

@)
H)
Br
)@ R R)
)Br
Br
Br
@@@@)
H Br
H


O

O
H
H


H


H
@
)

H
H)

O@@@

H


O












hence in perfect alignment for backside displacement of bromide

by
 intramolecular SN2.

Br




Br




Fast
Br
 Br


Fast
R

 
Br

ng oxacyclopropane has )
a RRRRmirror
meso)(achiral):
Fast
Fastand is)

)
RR
R ) plane
Fast
)

)(1S,2R)
) H on
In contrast,
contrast, H
the
isomer
contains the
the
same
functions
onthe
thesame
sameside
sideofof
of the
thefifi
five-membered
ve-membered
@functions
@)isomer
H)
Br contains
In
contrast,
the
(1S,2R)
isomer
contains
the
same
the
same
side
ve-membered
functions
@(1S,2R)
In
the
same
on
the (1S,2R)
isomer
contains the
the
same
functions
on the
the same
same side
side ofthe
the fi
five-membered
ve-membered

In contrast,
the
contains
same
on
the
O functions

O(1S,2R)

H isomer
ring.
To proceed
proceed
to (the
(the
same) product,
product,
frontside
displacement
is needed,
needed, of
which
is much
much more
more
ring.
To
to
same)
aaa frontside
frontside
displacement
is
which
is
To
proceed
to
(the
same)
product,
a
ring.
proceed
to
(the
same)
product,
frontside displacement
displacementisis
isneeded,
needed,which
whichisis
ismuch
muchmore
more
ring.cult.
To proceed
toalkoxide
(the same)
product,
a the
frontside
displacement
needed,
which
much
more
diffi
Thus,
the
derived
from
1R,2R-diastereomer
reacts
faster
than
that
generated
difficult.
cult. Thus,
Thus,
the
alkoxide
derived
from
the
1R,2R-diastereomer
reacts
faster
than
that
generated
diffi
the
alkoxide
derived
from
the
1R,2R-diastereomer
reacts
faster
than
that
Thus,
the
alkoxide
derived
from
the
1R,2R-diastereomer
reacts
faster
than
that
generated
Meso
difficult.
Thus,
the alkoxide derived from the 1R,2R-diastereomer reacts faster than thatgenerated
generated
from
the
1S,2R-isomer.
from the
the 1S,2R-isomer.
1S,2R-isomer.
from
from the 1S,2R-isomer.
1S,2R-isomer.

st, the (1S,2R) isomer contains the same functions on the same side of the five-membered
roceed to (the same) product, a frontside displacement is needed, which is much more
hus,
the alkoxide
derived from the 1R,2R-diastereomer reacts faster than that generated
Exercise
9-15
Exercise
9-15
Exercise 9-15
9-15
S,2R-isomer.

Try
It
Yourself
Try
Try It
It Yourself
Yourself
Try
It
Yourself

Bromoalcohol A
A transforms
transforms rapidly
rapidly in
in the
the presence
presenceof
ofsodium
sodiumhydroxide
hydroxidetoto
togive
givethe
thecorresponding
corresponding
the
presence
of
hydroxide
give
the
Bromoalcohol
Bromoalcohol A
A transforms
transforms rapidly
rapidly in
in the
the presence
presence of
of sodium
sodium hydroxide
hydroxide to
to give
give the
the corresponding
corresponding
Bromoalcohol
transforms
rapidly
in
oxacyclopropane,
whereas its
diastereomer
B does sodium
not. Why? [Caution:
Unlikecorresponding
the previous
substrates
are
trans-bromoalcohols.
Hint:
Draw
the
most
stable
cyclohexane
chair
problem,
both
substrates
are
trans-bromoalcohols.
Hint:
Draw
the
most
stable
cyclohexane
problem, both
both substrates
substrates are
are trans-bromoalcohols.
trans-bromoalcohols. Hint:
Hint: Draw
Draw the
the most
most stable
stable cyclohexane
cyclohexanechair
chair
problem,
conformers of
of both
both isomers
isomers (Section
(Section 4-4)
4-4) and
and picture
picture the
the respective
respective transition
transition states
statesfor
forchair
the
4-4)
and
picture
the
respective
transition
states
for
the
conformers
conformers of
of both
both isomers
isomers (Section
(Section 4-4)
4-4) and
and picture
picture the
the respective
respective transition
transition states
states for
forthe
the
urself
conformers
both
isomers
(Section
the
intramolecular Williamson
Williamson ether
ether synthesis.]
synthesis.]
Williamson
ether
synthesis.]
intramolecular
intramolecular
Williamson
ether
synthesis.]
intramolecular Williamson ether synthesis.]
Br
Brhydroxide to give the corresponding
ohol A transforms rapidly in the presence
of sodium
Br
Br
Br
Br
Br
Br
Br
%
Br

OH not. Why?
OH
ropane, whereas its diastereomer%%%% B
does
[Caution: Unlike the previous
]OH
OH
OH
OH

OH
OH
]

]
OH

]OH
Hint: Draw ]
both substrates are trans-bromoalcohols.
the
most stable cyclohexane chair

whereas
its
diastereomer
B
does
not.
Why?
[Caution:
Unlike
the
previous
oxacyclopropane,
oxacyclopropane, whereas
whereas its
its diastereomer
diastereomer BB
B does
does not.
not. Why?
Why? [Caution:
[Caution: Unlike
Unlike the
the previous
previous
9-15
oxacyclopropane,
whereas
diastereomer
does
not.
Why?
Unlike
the
previous
problem,
both substrates
areits
trans-bromoalcohols.
Hint:
Draw
the[Caution:
most stable
cyclohexane
chair

s of both isomers (Section 4-4) and picture the respective transition states for the
0
00
000
ular Williamson ether synthesis.] 0C(CH
0
00
)
)
C(CH
Br
%

C(CH
C(CH
C(CH33333))))33333
C(CH
A
AA
A
A

Br

C(CH
C(CH
C(CH33333)))3)3333
C(CH
B
BB
B
B

OH
]OH
In
Ethers
are
prepared
by
the
Williamson
synthesis,
an
S
reaction
of
an
Summary
Ethers
are
prepared
by
the
Williamson
synthesis,
In
Ethers
are
prepared
by
the
Williamson
synthesis,
an
S
reaction
of
an
In
Summary
Ethers
are
prepared
by
the
Williamson
synthesis, an
an SS
SNNNNN22222 reaction
reactionofof
ofan
an
In Summary
Ethers
are prepared
by the
Williamson
synthesis,
an
reaction
an
alkoxide
with
haloalkane.
This
reaction
works
best
with
primary
halides
or
sulfonates
that
This
best
alkoxide
with
haloalkane.
This
reaction
works
best
with
primary
halides
or
sulfonates
that
alkoxide
with aaaa haloalkane.
haloalkane.
This reaction
reaction works
works
bestwith
withprimary
primaryhalides
halidesoror
orsulfonates
sulfonatesthat
that
alkoxide
with
haloalkane.
This
reaction
works
best
with
primary
halides
sulfonates
that
0
0
do
not
undergo
ready
elimination.
Cyclic
ethers
are
formed
by
the
intramolecular
version
Cyclic
are
formed
do
not
ready
elimination.
Cyclic
ethers
are
formed
by
the
intramolecular
version
do
not undergo
undergo ready
ready elimination.
elimination.
Cyclic ethers
ethers
are
formed by
by the
theintramolecular
intramolecularversion
version
do not
undergo
ready
elimination.
Cyclic
ethers
formed
by
the
intramolecular
version
C(CH
C(CHare
3)3 of
3)in
3 this
The
relative
rates
of
ring
closure
in
this
case
are
highest
for
threeand
of
this
The
relative
rates
ring
closure
case
are
highest
for
threeand
of
this method.
method. The
The relative
relative rates
rates of
of ring
ring closure
closure in
in this
this case
case are
are highest
highest for
forthreethree-and
and
of this
method.
The
relative
rates
of
ring
closure
in
this
case
are
highest
for
threeand
rings.
fi
ve-membered
rings.
A
B
fi
ve-membered rings.
rings.
five-membered
rings.

9-7 Synthesis
Ethers: Alcohols
Alcohols and
and Mineral
Mineral Acids
Acids
Synthesis of
of Ethers:

9-7
Synthesis
of Ethers:
andsynthesis,
Mineral an
Acids
ary
Ethers
are prepared
by theAlcohols
Williamson
SN2 reaction of an
An even simpler, albeit
aastrong
albeit less
less selective,
selective, route
route to
to ethers
ethers isis the
the reaction
reactionofof
stronginorganic
inorganic
An even simpler, albeit less selective, route to ethers is the reaction of a strong inorganic

An
simpler,
less
route
to
ethers
is
the
reaction
of
strong
inorganic
An
even
simpler, albeit
albeit
less selective,
selective,
route
to with
ethersprimary
is the
the reaction
reaction
oforaaa sulfonates
strong inorganic
inorganic
Anaeven
even
simpler,
albeit
less
selective,
route
ethers
is
strong
ith
haloalkane.
This reaction
works
bestto
halidesof
that

acid (e.g.,
H2SO
withcorresponding
an alcohol. Protonation
of the OH group in one alcohol generates
then
results
in4)the
alkoxyalkane.

water as a leaving group. Nucleophilic displacement of this leaving group by a second

ive
both
and SSNN11 mechanisms
mechanisms
ethers
both
SSNN22alkoxyalkane.
and
alcohol
then resultsby
in the
corresponding

ols that
givetreating
ethers primary
by bothalcohols
SN2 andwith
SN1HBr
mechanisms
ned
orHI
HIfurnishes
furnishesthe
thec
primary
alcohols
HBr or
Alcohols give ethers
by both
SN2 andwith
SN1 mechanisms
e learnedintermediate
that treating primary
alcohols with
or HI furnishes
the corres
hrough
intermediate
alkyloxonium
ionsHBr
(Section
9-2). However,
However
alkyloxonium
ions
(Section
9-2).
We have
learned
that treating primary
alcohols with
HBr(Section
or HI furnishes
corresponding
anes
through
intermediate
alkyloxonium
ions
9-2).the
However,
when
ichaloalkanes
as sulfuric
sulfuric
acid
are
are
used atat
elevated
temperatu
acids through
such intermediate
as
acid
used
elevated
alkyloxonium
ions
(Section
9-2).
However, temperatu
when
strong
eophilic
acids
such
as as
sulfuric
acid
are
areused
used
at elevated
temperatures,
t
nonnucleophilic
acids

such
sulfuric
acid

at
elevated
temperatures,
the
main
thers.
s products
are ethers.
are ethers.
products are ethers.

Symmetrical
Ether
Synthesis
from a
aaPrimary
Alcohol
with Strong
Acid
metrical
Synthesis
from
Primary
Alcohol
with
Strong
Symmetrical
Ether
Synthesis
from
Primary
Alcohol
with
Strong
AcidA
Ether
Synthesis
from
Primary
Alcohol
with
Strong
H22SO44, 130C
H

2 CH33CH22OH H2SO
4, 130C
Relatively
high

SO4Relatively
130Chigh
4,, 130C
CH3OH
CH2OH HH22SO
temperature
2 CH2CH
Relatively
high
3

Relatively
high
Relatively
high
temperature
temperature
temperature

CH33CH22OCH22CH33

HOH

 
HOH
CH3CH
2CH
3
HOH
CH
CH22OCH
OCH
CH
HOH
CH
2OCH
33CH
22CH
33 

Chapter 9

REACTION

355

m
AAll clccooohhhoooll lsss aaannnddd ttthhheee CCChhheeem
FF
uu
r tr ht he er r RRe ea ac ct it oi on ns s oooff f A
miiiissssttttrrrryyyy ooooffff EE
m
EEtttthh
hhee
eerrrrssss
Further Reactions of Alcohols and the Chemistry of Ethers

ah pa tpet re r9 9

Chapter 9
C ahhh paaa tpppettt reee rrr9 99
9
C
CC
hC
C
hh aa pp tt ee rr 99
356

F Fu ur tr h
e r RRe ea ac ct ti ioonns s oof f AAl lccoohhool lss aanndd tthhee CChh ee m
istry of Ethers
m
m ii ss tt rr yy oo ff EE tt hh ee rr ss
F u r tt hh ee rr R
eactions of Alcohols and the Chem

F FuF urutrrhtt heh ere rr RRR

e eae aca ctctittioiioononnsnsss ooofofff AAAA
l cll coc oho hoh olosll ss a anand
hhh
e em
i siiststrtryryy oofoff EEE
t ththh
eerersrss
ndd t ththehee CCC
em
m
h e r R e a c t i o nl sc oohf o Al sl c oa hn odl s t ha en d C thheem Ci sh termy i sot fr y E ot fh eErtsh e r s
C h a p t e r F9u r t h e r FRuerat c

present
in
solution
isis is
the
unprotonated
starting
nucleophile
InInthis
reaction,
the
nucleophile
present
in
is
the
unprotonated
starting
unprotonated
starting
this
reaction,
thestrongest
strongest
nucleophile
present
in solution
solution
the
unprotonated
In
this reaction,
the strongest
nucleophile
present
in
solution
the
unprotonated
starting
nucleophile
present
in
solution
isthe
the
unprotonated
starting
In
this
reaction,
the
strongest
nucleophile
present
in
solution
is
the
unprotonated
starting
In
this
reaction,
the
strongest
nucleophile
present
in
solution
is
starting
In
this
reaction,
the
strongest
nucleophile
present
in
solution
is
the
unprotonated
starting
MECHANISM
In
this
reaction,
the
strongest
nucleophile
present
in
solution
is
the
unprotonated
starting
been
protonated,
nucleophilic
attack
begins,
molecule
has
alcohol.
As
soon
as
alcohol
molecule
has
been
protonated,
attack
begins,
MECHANISM
alcohol.
As
soon
asone
one
alcohol
molecule
has
been
protonated,
nucleophilic
nucleophilic
attack
begins,
In
this
reaction,
the
strongest
nucleophile
present
in solution
isunprotonated
the unprotonated
starting
In
this
reaction,
the
strongest
nucleophile
present
in
solution
isnucleophilic
the
unprotonated
starting
MECHANISM
alcohol.
As
soon
as
one
alcohol
molecule
has
been
protonated,
nucleophilic
attack
begins,
M
M MECHANISM
Asoon
m
MECHANISM
molecule
has
been
protonated,
nucleophilic
attack
begins,
M
M
alcohol.
As
soon
as
one
alcohol
molecule
has
been
protonated,
nucleophilic
attack
begins,
MECHANISM
MECHANISM
alcohol.
As
soon
as
one
alcohol
molecule
has
been
protonated,
nucleophilic
attack
begins,
alcohol.
As
asas
one
alcohol
molecule
has
been
protonated,
nucleophilic
attack
begins,
MECHANISM
M
M
alcohol.
As
soon
as
one
alcohol
molecule
has
been
protonated,
nucleophilic
attack
begins,
A
m
alcohol.
As
soon
as
one
alcohol
molecule
has
been protonated,
nucleophilic
attack
begins
MECHANISM
alcohol.
As
soon
one
alcohol
molecule
has
been
protonated,
nucleophilic
attack
begins,
ether
and
water.
the
products
being
an
ether
and
water.
theultimate
ultimate
products
being
an
ether
and
water.
the
ultimate
products
being
an
ether
and
water.
m
the ultimate
products being an ether and w
water.
the
ultimate
products
being
an
ether
and
water.
ultimate
products
being
an
ether
and
water.
the
ultimate
being
an
ether
and
water.
the
the
ultimate
products
being
an
ether
and water.
the
ultimate
products
being
an
ether
and
water.
m products
w
the
ultimate
products
being
an
ether
and
water.

Mechanism
ofofEther
Synthesis
from
Primary
Alcohols:
Protonation
and
S
Alcohols:
Protonation
and
Primary
Mechanism
Ether
Synthesis
from
Primary
Alcohols:
Protonation
and
Mechanism
ofofEther
Synthesis
from
Primary
Protonation
and
SSSNNand
2N222SN2
N
M
m
E
m
mAlcohols:
A
N
Mechanism
Ether
Synthesis
from
Primary
Alcohols:
Protonation
and
S22N2N
of Ether
Synthesis
from
Primary
Alcohols:
Protonation
N
Primary
Alcohols:
Protonation
and
S
Mechanism
of
Ether
Synthesis
from
Primary
Alcohols:
Protonation
and
Mechanism
ofMechanism
Ether
Synthesis
from
Primary
Alcohols:
Protonation
and
SSS
2N
Mechanism
of
Ether
Synthesis
from
Primary
Alcohols:
Protonation
and
2
M
mof Ether
E
m Alcohols:
A
Mechanism
Synthesis frommPrimary
Protonation and SNNN2N

CH
OH
>
>
OH
3
22>
>
CH
OH
OH
CH
CH
CH
OH CH3CH2>
3CH
33CH
22CH
>
HH
CH
CH
CH
CH
>
3CH
2CH
H33CH
CH
CH
3CH
2OH
OH
2
3
>
OH
CH
CH
CH
CH
CH
CH
HH
CH
CH
CH
CH
CH
OH
CH
CH
CH
CH
2 CH3CH2
33CH
3CH
2>
CH
3CH
33CH
3
23233CH
22222232222 D 2
CH
CH
CH
32
3333CH
2222>
HH
CH
3CH
3CH
CH

H
22CH

H
32
3CH

S3CH
HCH
CH
2222
D
DH
D 
D CH
2D
3333
22D
H
CH
CH
>

HH
S S

HH CH
32CH
3CH
2

SS22 22 S

H

H
H

H
H >

>
HH
SSH

H
D
D
D

>
D
D
D
D3D
D

>>  >

H 

H


H


H
2222
HHH

O
D2O
D
D

D
D
H

H


>

 H O
D
DD
D


>

H

OHH>

O
O
O

CH
O

H
SS2SS2p

H
D
D
D

O
O


>

D
DD
H
CH
O
O
O

CH

H


3CH2SO
2
3



>
3
2
2
3


p
p

>

O
O

p
>
p
p
H
CH
O
O H
O
CH
O
H

H
H
O

3O
2 2O
2O
33O

O
O

CH
O
H
>

O
O

H
O
O
O

HH
O

H
H
O
O

CH
O
H


Op
H

>
O
O
O
H
CH
O
O
O

O
H

2>

O
O


CH
O
H
HH
33CH
2H
3
2
3
O
p
p
p
O
O
OG

CH
O
H
G
G
G
Hp
H
>
2O
3CH
2CH
2H
O
O
p
33CH
2O
2>
3O
33
22O
22>
333
CH
O
O
Op

O
H


H
O
2O
3O
p
p
CH
O
O
CH
O
H

p
p
G
G
p
322CH
2O
2H

H

H
p
p
p
p
p
p
p
p
3
2
2
33O

H

H
p
p
p
>
p
p
G
G
G
H
H

H

H
G

H
>
G
G
GG GGGG
G
G2 CH3CH2
GH

HH

H

H
GG3G
G

H


H
HHH
G
H CH
CH

H

H

H CH

H
G
GG

H

G

H
32CH2
>
>
CH
CH
CH
>
CH
OH
>
>
>
3
>
>
3
2
>
CH
CH
CH
CH
H
>
3
2
3
2
>
CH
CHCH
CH
CH
CH
CH
CH
CH
CH
CH
H
32
3CH
>
CH
CH
CH
HH HHH
3
22OH
CH
CH
CH
CH
CH
33CH
33CH
CH
CH
OH
3
CH
CH
H
3CH
>
33CH
222222
3333
22222
33CH
232CH
3CH
222
332
33CH
>
CH
OH
3CH
2OH
>
OH
OH
CH
CH
OH
33CH
22CH
3CH
2>
3CH
2CH
>
3333CH
2222>
>>
>
>
>
>>
CH3CH2>
OH
CH
CH
OH
>
3
2
CH
OH
CH
>
3>
22>
>
CH
CH
OH
>
2OH
>
>
OH
3CH
CH
CH
CH
OH
33CH
2>
CH
OH
32CH
2OH
CH
OH
33CH
3CH
2>
2 33 2 2>
>
>
>
>
>
>> >
Only symmetric ethers can be prepared by this method.
 



 



 



 



 



 



N
N N
N
N

N
NN
N
N NN
NNN

 



 

 














E2 Mechanism for

Only
can
prepared
by
this
method.
even higher
temperatures
(see
footnote
on p. 337), elimination of water to generat
O
mm Atethers
m
Onlysymmetric
symmetric
ethers
canbe
be
preparedby
by
this
method.
Only
symmetric
ethers
can
be
prepared
this
method.

E2 Mechanism for

Only
symmetric
ethers
can
be
prepared
by
this
method.
Only
prepared
by
this
method.
the
Acid-Catalyzed
symmetric
ethers
can
be
prepared
by
this
method.
E2
Mechanism
for
E
M
m
Only
symmetric
ethers
can
be
prepared
by
this
method.
Only
symmetric
ethers
can
be
prepared
by
this
method.
E2
Mechanism
for
Only
symmetric
ethers
can
be
prepared
by
this
method.
O
mm
m
E2E2
Mechanism
for
Mechanism
for
E2
Mechanism
for
E
M
m
Onlysymmetric
symmetric
ethers
can
be
prepared
by
this
method.
Only
ethers
can
prepared
by
this
method.
method.
prepared
by
this
chanism
an
alkene
isbe
This
reaction
proceeds
by
anelimination
E2
mechanism
(Sections
7-7
and 11-7)
At
even
higher
temperatures
(see
footnote
on
p.
337),
elimination
of
water
to
generate
forfor
anism
A
mobserved.
m
w
Dehydration
of At
At
even
(see
footnote
onp.p.
p.
337),
elimination
of
water
to
generate
he
Acid-Catalyzed
At
even
higher
temperatures
(see
footnote
on
337),
elimination
of
water
generate
higher
temperatures
(see
footnote
on
p.
337),
elimination
of
water
to
generate
even
higher
temperatures
(see
footnote
on
337),
ofof
water
toto
generate
A
C
At
even
higher
temperatures
(see
footnote
on
337),
elimination
the
Acid-Catalyzed
At
even
higher
temperatures
(see
footnote
on
p.
337),
elimination
of
water
to
generate
the
Acid-Catalyzed
A
m
m
w
he
Acid-Catalyzed
Acid-Catalyzed
A
C
even
higher
temperatures
(see
footnote
on
p.p.
337),
elimination
water
to
generate
water
to
generate
in
which
theThis
neutral
alcohol
serveson
as
the
base
that
attacks the
alkyloxonium
ion
(margin)
AtAtan
even
higher
temperatures
(see
footnote
p.
337),
elimination
of
to
generate
p.
337),
elimination
of water
water
to
generate
(see
footnote
on
d-Catalyzed
alkene
observed.
reaction
proceeds
by
an
E2
mechanism
(Sections
7-7
and
11-7),
Catalyzed
m
m
an
alkene
is
reaction
proceeds
by
an
E2
mechanism
(Sections
7-7
an
alkene
is
observed.
This
reaction
proceeds
by
an
E2
mechanism
(Sections
7-7
and
11-7),
Dehydration
ofof
and
11-7),
observed.
This
reaction
proceeds
by
an
E2
mechanism
(Sections
7-7
and
11-7),
an
alkene
is
observed.
This
reaction
proceeds
by
an
E2
mechanism
(Sections
11-7),
alkene
isis
observed.
This
reaction
proceeds
by
an
E2
mechanism
7-7
and
D
Dehydration
of1-Propanol an
an
alkene
is
observed.
This
reaction
proceeds
by
an
E2
mechanism
(Sections
7-7
and
11-7),
m
m(Sections
Dehydration
Dehydration
of
Dehydration
of
D
an
alkene
is
observed.
This
reaction
proceeds
by
an
E2attacks
mechanism
(Sections
7-7
and
11-7),
(Sectionsm
7-7
and
11-7),
an alkene
is
observed.
This
reaction
proceeds
by
an
E2
mechanism
(Sections
7-7
and
an
E2
mechanism
(Sections
7-7
and
11-7),
dration
which
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
ion
(margin).
reaction
proceeds
by
w
m11-7),
in
which
as
the
base
that
attacks
the
alkyloxonium
in
which
the
neutral
alcohol
as
the
base
that
the
alkyloxonium
ion
(margin).
ofof
ion
(margin).
1-Propanol
serves
ation
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
ion
(margin).
in
which
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
inin
which
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
(margin).
in
which
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
ion
(margin).
w
mion
m
1-Propanol
1-Propanol
H
1-Propanol
in
which
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
ion
(margin).
alkyloxonium
ion
(margin).
Alkene
Synthesis
from
a
Primary
Alcohol
and
Strong
Acid
in
which
the
neutral
alcohol
serves
as
the
base
that
attacks
the
alkyloxonium
ion
(margin).
ropanol
that
attacks
the
alkyloxonium
ion
(margin).
O
serves
as
the
base

panol

HH
H
H
H

at Elevated Temperature: E2

O
O
OO
H HO
OO

OO

Alkene
Synthesis
Primary
Alcohol
and
Strong
Acid
A
m
m Alcohol
A
A
Alkene
from
Primary
Alcohol
and
Strong
Acid
from
Primary
Alcohol
and
Strong
Acid
Alkene
Synthesis
from
Alcohol
and
Strong
Synthesis
Alkene
Synthesis
from
aaPrimary
Primary
Alcohol
and
Strong
Acid
Alkene
Synthesis
from
aaaaaPrimary
and
Strong
Acid
Alkene
Synthesis
from
Primary
Alcohol
and
Strong
Acid
A
m
m
A
A

H
A

H
HH
H
A AA

H
AlkeneSynthesis
Synthesisfrom
from
Primary
AlcoholE2
and
StrongAcid
Acid
at
Elevated
Temperature:
E2
Acid
E
T
m
E
Elevated
Temperature:
E2
Elevated
Temperature:
E2Strong
at
Elevated
Temperature:
E2
at
Elevated
Temperature:
Elevated
Temperature:
Alkene
aaaPrimary
Alcohol
and
at
Elevated
Temperature:
E2
E
T
m
E
Primary
Alcohol
and
Strong
Acid
from
Aat
H SO , 180C
Elevated
Temperature:
E2
at3Elevated
Elevated
Temperature:
E23CHP CH2  HOH
CHCH
CH
CH
atat
E2
2OHTemperature:
Temperature:
E2
Elevated
HH
Relatively high
HH
2

H
H
AAAAA


O

 
O
O
O
O




H
 O
HH
H
OO


H
HH




1-Propanol

temperature

Propene

SO
,180C
SO
,,,,180C
180C
SO
H
SO
,180C
180C
H
SO
180C
HHH
SO
, ,180C
H
SO
180C
H
H
SO
H
HCH
P
P
P
P
CHCH
CH
CH
HOH
CH
OH
CH
CH
CH

CHCH
OH Relatively
CH
CH
CH
 HOH
HOH
CH
CHCH
CH
CH
CH
HOH
CH
P
P
333CH
CH
CH
CH
CH
333CHCH
22
P
CH
HOH
CH
22OH
33CH
3CHCH
2OH
33CH
22 222
22OH
22 
333CHCH
Relatively
high
high
Relatively
high
Relatively
high
Relatively
high
Relatively
high
Relatively
high
Relatively
H
SO
,, 180C
A AACH
H
SO
180C
H
180C
Htertiary
SO
,temperature
180C
2SO
4,temperature
1-Propanol
Propene
1-Propanol
Propene
temperature
temperature
1-Propanol
Propene
1-Propanol
Propene
temperature
temperature
P
temperature
temperature
1-Propanol
Propene
1-Propanol
Propene
Secondary
and
ethers
can
also
be
made
acid
CHCH
OH
CH
CH
CH

HOH
CH
1-Propanol
Propene
HOH of secondary and
3
2
3CH
P
CHCH
OH
CH
CH222by
 treatment
CH
3
2
P
3
2
3CH
2 
CH
CH
HOH
CH33CHCH
P
CH
CH

HOH
Relatively
high
22OH
33CH
Relativelyhigh
high
Relatively
Relatively
high

2 2 222
222224 4 444
44444

22
44
2 2 4 4

tertiary
alcohols. However,
in these cases,
a carbocation is formed initially and is then
temperature
1-Propanol
Propene
temperature
1-Propanol
Propene
temperature
temperature
1-Propanol
Propene
Propene
1-Propanol
trapped
by
an alcohol
(Scan
1), as
described
in Section
9-2.
Ncan
 H2O Secondary
Secondary
tertiary
ethers
also
be
made
by
acid
treatment
ofof
secondary
and
Secondary
and
tertiary
also
be
made
by
acid
treatment
secondary
and
m
Secondaryand
and
tertiary
ethers
can
also
be
made
by
acid
treatment
of
secondary
Secondary
and
tertiary
ethers
also
be
made
by
acid
treatment
of
secondary
and
tertiary
ethers
can
also
be
made
by
acid
treatment
secondary
and
can
also
be
made
by
secondary
and
can
Secondary
and
tertiary
ethers
can
acid
treatment
of
secondary
and
m
mm of

H
H
H
HH

tertiary
alcohols.
However,
these
cases,
isisis
formed
initially
and
isisisis
then
tertiary
alcohols.
However,
in
these
cases,
carbocation
formed
initially
and
then
Hw
w inin
tertiaryalcohols.
these
cases,
carbocation
formed
initially
tertiary
However,
cases,
aaaacarbocation
is
formed
and
is
then
tertiary
alcohols.
However,
in
these
cases,
carbocation
isis
formed
and
is
then
alcohols.
However,
inthese
these
cases,
aacarbocation
carbocation
initially
and
then
tertiary
alcohols.
However,
in
these
carbocation
formed
initially
and
then
H
mm initially
Secondary
and
tertiary
ethers
can
also
be
made
by
acid
treatment
of
secondary
and
secondary and
and
Symmetrical
Ether
Synthesis
from
Secondary
Secondary
and
tertiary
ethers
can
also
be
made
by
acidatreatment
treatmentAlcohol
of secondary
trapped
by
an
alcohol
(S
1),
described
inin
Section
9-2.
Secondary
and
tertiary
ethers
can
also
be
made
by
acid
of
trapped
by
an
alcohol
(S
1),
as
described
Section
9-2.
made
by
acid
treatment
of
secondary
and
ethers
can
also
be
trapped
by
described
in
Section
9-2.
NN
trapped
by
an
alcohol
(S
1),
asas
described
in
Section
9-2.
an
alcohol
(S
1),
as
described
in
Section
9-2.
trapped
by
an
alcohol
(S
1),
as
described
in
Section
9-2.
trapped
by
an
alcohol
(S
1),
as
described
9-2.
N
NN
N
N
2O

O

HH
O
H
OMechanism
2H
2
tertiary
for alcohols.
initially and
and is
is then
then
2S 21
tertiary
alcohols. However,
However, Nin
in these
these cases,
cases, aa carbocation
carbocation is
is formed
formed initially

 HO
H2HO22O

N
tertiary alcohols. However, OH
in these
carbocation is
is formed
formed initially
initially
these cases,
cases, aa carbocation
the Acid-Catalyzed
trapped
alcohol
(S
1),A as described
in Section
9-2.
N
trappedbyby
byanan
analcohol
alcoholSymmetrical
(S1),
described
Section
9-2.
H SO ,Synthesis
40C
N1),asasdescribed
trapped
(S
in
9-2.
Ether
from
Secondary
Alcohol
Section
9-2.
described
ininSection
Symmetrical
Ether
Synthesis
from
Alcohol
mm
E
m
A
Ether
Synthesis
from
Secondary
Alcohol
Symmetrical
Synthesis
from
aaaaSecondary
Symmetrical
Ether
Synthesis
from
Secondary
Symmetrical
Ether
Synthesis
from
Secondary
Alcohol
Ether Formation
mm
E
A
Symmetrical
Ether
Synthesis
Secondary
Alcohol
2 NN
CH
(CH
CHOCH(CH
 HOH
3CCH3 Ether
3)2m
3)2 Alcohol
from
aaaSecondary
Relatively low
A
temperature
OH
OH
H Ether Synthesis from a 75%
OH
OH
OH
OH
Symmetrical
Secondary Alcohol
2

for
SS1NN1Mechanism
from
for
1 Mechanism
Mechanism
for 2-Propanol
M
m
SN
Mechanism
for
N1N Acid-Catalyzed
the
Acid-Catalyzed
the
Acid-Catalyzed
A
C
he
Acid-Catalyzed
Ether
Formation
for
chanism
Ether
Formation
E Formation
m
for
Ether
Formation
H
for
anism
from
2-Propanol
from
2-Propanol
from
2-Propanol
from
2-Propanol
d-Catalyzed
m
O
from
2-Propanol
Catalyzed

Catalyzed
Formation
rmation
2-Propanol H
H
Propanol O H
HH

O
O
OO

O
OH
O 




H
H 





O

and
and is
is then
then


H

Synthesisfrom
fromaaaSecondary
SecondaryAlcohol
Alcohol
ASymmetrical
SO
, Ether
Symmetrical
Ether
HH
SO
,40C
40C
from
Secondary
Alcohol
2-Propanol
2-(1-Methylethoxy)propane
AAAAA
Synthesis

HH
,Ether
40C
H
SO
,40C
40C Synthesis
H
40C
2
2SO
H
SO
2SO,,4,4
4,40C
2
HSO


CH
(CH
CHOCH(CH

HOH
HHH

2SO4
4 40C
CH
CCH
(CH
CHOCH(CH
HOH
33CCH
3
3))2)2)
3)2) )) 
(Diisopropyl

CH
CH
CHOCH
CH
 HOH
HOH 
H
H
2222CH
(CH
2CH
(CH
CHOCH(CH
2OH
CH
(CH

HOH

CCH
(CH
CHOCH(CH

HOH
H

CH
CHOCH
CH
Relatively
low
3CCH
3 33333 Relatively
3)32333CHOCH(CH
3)32333)3)2ether)
3CCH
3)22CHOCH(CH
2CHOCH(CH
2
(CH
33A
H
Relatively
low

HOH

3
low
Relatively
low
Relatively
low
Relatively
low
3CCH
3
3)2
2
3 22
22
Relatively
low
OH
Relatively
low
temperature
temperature
OH
AAAA
temperature
temperature
temperature
temperature
AA AH
temperature
75%
H
75%
temperature
H
SO
,
40C
2
4
H
%
HHH H HSO
75%
22SO44, 40C
75%
75%
A
75%
%


75%
40C

22 SO44,,side
40C
The
major
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again
H
22 CH
CCH
(CH
)
CHOCH(CH
)

HOH
H

H

2-Propanol
2-(1-Methylethoxy)propane
3
3
3
2
3
2

CH CCH
(CH ) CHOCH(CH )
 HOH
22
44
2 22 4 44

332-Propanol
33
2
3
2-Propanol
2-(1-Methylethoxy)propane
2M
3 2
2
Relatively
low
M
2-(1-Methylethoxy)propane
2-(1-Methylethoxy)propane
2-(1-Methylethoxy)propane
2-Propanol
2 CH33CCH
(CH
))3322(Diisopropyl
CHOCH(CH

CHOCH(CH
 HOH
HOH 
H
 H
Relatively
low
(CH
33becomes
32-(1-Methylethoxy)propane
33))22
2-Propanol
2-(1-Methylethoxy)propane
AA2-Propanol
dominant
ether)
Relatively
low
(Diisopropyl
ether)
Relatively
low at higher3 temperatures.
temperature
(Diisopropyl
ether)
(Diisopropyl
ether)
(Diisopropyl
ether)
(Diisopropyl
ether)
AH
temperature
(Diisopropyl
ether)
75%
It temperature
is harder to synthesize ethers
containing
two different alkyl groups, because mixing
temperature
75%
HH
75%
of 75%
an acid usually results in mixtures of all three possibl
2-Propanoltwo alcohols in the presence
2-(1-Methylethoxy)propane
2-(1-Methylethoxy)propane

2-Propanol
2-(1-Methylethoxy)propane
The
major
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again,
The
major
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again,
2-Propanol
2-(1-Methylethoxy)propane
2-(1-Methylethoxy)propane
2-Propanol
The
major
side
reaction
follows
the
E1
pathway
9-2,
9-3,
and
11-7),
which,
again,
m
w
w
The
major
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again,
(Diisopropyl
ether)
The
major
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again,
products.
However,
mixed
ethers
containing
one tertiary
and
one
primary
or
secondary
alky
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again,
m
w
ww (Sections
w
(Diisopropyl
ether)
The
major
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
11-7),
which,
again,
(Diisopropyl
ether)
becomes
dominant
higher
temperatures.
ether)
becomes
dominant
atat
higher
temperatures.
substituent
can
betemperatures.
prepared
in good yield
in the presence of dilute acid. Under these condi
higher
m dominant
m atat
becomes
dominant
higher
temperatures.
becomes
dominant
higher
temperatures.
m
m
m
m (Diisopropyl
becomes
dominant
atat
higher
temperatures.
H becomes
harder
synthesize
ethers
containing
two
different
alkyl
groups,
because
mixing
is
harder
to
synthesize
ethers
containing
two
different
alkyl
groups,
because
mixing
tions,
the
much more
rapidly
formed tertiary
carbocation
isgroups,
trapped
by
the other
alcohol.
ItItItItIt
isis
harder
toto
synthesize
ethers
containing
two
alkyl
because
mixing
is
harder
to
synthesize
ethers
containing
two
different
alkyl
groups,
because
mixing
wdifferent
m
w
m
is
harder
to
synthesize
ethers
containing
two
different
alkyl
groups,
because
mixing
w
m

Italcohols
is harder
tothe
synthesize
ethers
containing
two
different
alkyland
groups,
because
mixing
The
major
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
11-7),
which,
again,
two
in
presence
of
an
acid
usually
results
inin mixtures
ofof
all
three
possible
11-7),
which,
again,
two
alcohols
in
the
presence
of
an
acid
usually
results
mixtures
all
three
possible
Themajor
major
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
two
inin
the
presence
an
acid
usually
results
in
mixtures
all
three
possible
two
alcohols
in
the
presence
of
an
acid
usually
results
in
mixtures
of
all
three
possible
w alcohols
m
w
m
m
two
alcohols
in
the
presence
of
an
acid
usually
results
in
mixtures
of
all
three
possible
The
side
reaction
follows
the
E1
pathway
(Sections
9-2,
9-3,
and
which,
again,
(Sections
9-2,
9-3,
andof11-7),
11-7),
which,
again,
theofof
E1
pathway
two
alcohols
the
presence
an
acid
usually
results
in
mixtures
of
all
three
possible
products.
However,
mixed
ethers
containing
one
tertiary
and
one
primary
or secondary
alkyl
becomes
dominant
higher
temperatures.
products.
However,
mixed
ethers
containing
one
tertiary
and
one
primary
alkyl
becomes
dominant
athigher
higher
temperatures.
Synthesis
of a Mixed
Ether
from
aone
Tertiary
products.
However,
mixed
ethers
containing
one
tertiary
and
one
primary
oror
secondary
alkyl
products.
However,
mixed
ethers
containing
one
tertiary
and
primary
or
secondary
alkyl
H
wat
mAlcohol
H
w
m
m
m
m
products.
However,
mixed
ethers
containing
one
tertiary
and
one
primary
orsecondary
secondary
alkyl
becomes
dominant
at
temperatures.
products.
However,
mixed
ethers
containing
one
tertiary
and
one
primary
or
secondary
alkyl
temperatures.
substituent
can
be
prepared
in
good
yield
ininthe
presence
of
dilute
acid.
Under
these
condiIt
is
harder
to
synthesize
ethers
containing
two
different
alkyl
groups,
because
mixing
substituent
can
be
prepared
in
good
yield
the
presence
of
dilute
acid.
Under
these
condiIt
is
harder
to
synthesize
ethers
containing
two
different
alkyl
groups,
because
mixing
substituent
can
be
prepared
inin
good
yield
inin
the
presence
ofof
dilute
acid.
Under
these
condisubstituent
can
be
prepared
in
good
yield
inin
the
presence
dilute
acid.
Under
these
condiU
U
U
substituent
can
be
prepared
in
good
yield
the
presence
of
dilute
acid.
Under
these
condiCH
CH
It
harder
to
synthesize
containing
two
different
groups,
because
mixing
3 ethers
3these
substituent
can
be
prepared
good
yield
the
presence
dilute
acid.
Under
conditwo
different
alkyl
groups,
because
mixing
tions,
the
much
more
rapidly
formed
tertiary
carbocation
isofalkyl
trapped
by
the
other
alcohol.
It is
is
harder
to
synthesize
ethers
containing
tions,
the
much
more
rapidly
formed
tertiary
carbocation
trapped
by
the
other
alcohol.
two
alcohols
in
the
presence
of
an
acid
usually
results
in
mixtures
of
all
three
possible
A rapidly
Aother
all
three
possible
tions,
the
much
more
formed
tertiary
carbocation
isisistrapped
by
the
other
alcohol.
tions,
the
much
more
rapidly
formed
tertiary
carbocation
trapped
by
the
other
alcohol.
two
alcohols
in
the
presence
of
an
acid
usually
results
in
mixtures
of
m
m
m
m
m
m
tions,
the
much
more
rapidly
formed
tertiary
carbocation
is
by
the
alcohol.
15% aqueous
Htrapped
SO , 40C
tions, the
more
rapidly
formed
tertiary
carbocation
is
trapped of
by all
the
other possible
alcohol.
two
alcohols
in
the
of
usually
results
in
three
resultsand
in mixtures
mixtures
of
all
two
alcohols
in much
the presence
presence
of
an
acid
usually
 an
CH
CHacid
CHsecondary
COCH
CHalkyl
(excess)
3COH
3CH2OH
3three
2possible
3alkyl
products.
However,
mixed
ethers
containing
one
tertiary
or
secondary
one
HOH primary
products.However,
However,mixed
mixed
ethers
containing
one
tertiaryand
andone
one
primaryor
or
A ethers
A
products.
containing
one
tertiary
primary
alkyl
tertiary
one
primary
or secondary
secondary
alkyl
Synthesis
of aayield
Mixed
Ether
from
aand
Tertiary
Alcohol
products.
However,
mixed
ethers
containing
one
substituent
can
in good
in
the
presence
of
dilute
acid.
condiSynthesis
Mixed
Ether
from
Tertiary
Alcohol
Under
these
condiCH
CHthese

O
 H
substituent
can be
be prepared
prepared
in
the
presence
of
dilute
acid. Under
3 in good
3
Synthesis
of
ayield
Mixed
Ether
from
aaof
Tertiary
Alcohol
Synthesis
ofof
a Mixed
Ether
from
aaTertiary
Alcohol
M
E
m
T
A
M
E
m
T
A
M
E
m
T
A
Synthesis
Mixed
Ether
from
Tertiary
Alcohol
substituent
can
be
prepared
in
good
in
the
presence
dilute
acid.
Under
these
condiSynthesis
ofofyield
aaMixed
Ether
from
aof
Tertiary
Alcohol
presence
dilute
acid.
Under
these
condisubstituent
can
be
prepared
in
good
yield
in
the
tions,
the
much
more
rapidly
formed
tertiary
carbocation
is
trapped
by
the
other
alcohol.
95%
CH
tions, the much
rapidly formed tertiary carbocation is trapped byCH
the
3more
3 3 other alcohol.
CH
CH
3
CH
CH
CH
tions,
more
rapidly
is
the
alcohol.
CH
CH
CH
33
3 3
3 other
AACH
Athe
carbocation
is , trapped
trapped by
by2-Ethoxy-2-methylpropane
other
alcohol.
tions, the
the much
much
more
rapidly formed
formed tertiary
tertiary carbocation
15%
15%aqueous
aqueousHHSO
SO 40C
, 40C
A 33
ACH
AAACH3




H
H

HH

O

HH
O



O
O


O

O


O

H


OH

H
H

A
15%
aqueous
HHSO
,4,40C
15%
aqueous
H SO
, 40C
 CH
CH
COH
CH
(excess)
15%
aqueous
SO
40C CH
33A
33CH
22OH
3COCH
33
2
AA 2CH
2
4
CH
COH
CH
CH
CH
(excess)
3COCH
2CH
HOH
15%
aqueous
H

CH
CH
CH
(excess)

CH
COH
CH
CH
(excess)
aqueous
H22SO
SO44,, 40C
40CAlcohol
CH
CH
COCH
CH
 CH
COH Synthesis
CH
CH
OH
CH
33A
33CH
A3COCH
3COCH
2 2CH
3 33
(excess)
of
a2aOH
Mixed
Ether
from
Tertiary
2OH
3COCH
2CH
ACOH
Synthesis
of2OH
Mixed
Ether 15%
from
aHOH
Tertiary
Alcohol

HOH
a
HOH
 CH3 33of
CH333ACOH
CH
CH
(excess)
HOH
AA Synthesis
AA33ACOCH
2
A
2CH3
3
a22OH
Mixed
Ether from aTertiary
Alcohol
CH
CH
HOH
3

15% aqueous H2 22SO4 44, 40C

2

2 4

Synthesis of a Mixed Ether from a Tertiary Alcohol

O  H

CH3
A
CH3COH
A
CH3

CH3CH2OH (excess)

15% aqueous H2SO4, 40C

 HOH

CH3
A
CH3COCH2CH3
A
CH3
95%
2-Ethoxy-2-methylpropane

99--88 RReeaacct ti ioonnss oof f EEt thheer rs s

c9 -t8i oR enasc t i oonfs oEf tEht hee rr ss

cise 9-16
cise 9-16
rcise

9 -alcoholysis
8 Rea
Ethers also form by

e mechanisms for the following two reactions. (a) 1,4-Butanediol 1 H111 y oxacyclopen
e mechanisms for the following two reactions. (a) 1,4-Butanediol
oxacyclopenta
1 H y oxacyclopenta
ahydrofuran);
(b) 5-methyl-1,5-hexanediol 1 H111 y 2,2-dimethyloxacyclohexane (
Exercise
9-16
Exercise
ahydrofuran);
2,2-dimethyloxacyclohexane
(2
(b) 5-methyl-1,5-hexanediol
1 H y 2,2-dimethyloxacyclohexane
(2
As
we 9-16
know,
tertiary and secondary
ethers may also form
ethyltetrahydropyran).
ethyltetrahydropyran).
Exercise 9-16
1 y oxacyclopentane
11
Write mechanismshaloalkanes
for the following twoor
reactions.
1,4-Butanediol 1 H
responding
alkyl(a) sulfonates
(Section
7-1). T
mechanisms for
for the
the following
following two
two reactions.
reactions.(a)
(a)1,4-Butanediol
1,4-Butanediol11HH y
yoxacyclopentane
oxacyclopentane
Write mechanisms
1 y 2,2-dimethyloxacyclohexane (2,2(tetrahydrofuran); (b) 5-methyl-1,5-hexanediol 1 H11
1

(tetrahydrofuran);
(b)the
5-methyl-1,5-hexanediol
1
y 2,2-dimethyloxacyclohexane
(2,2(tetrahydrofuran);
(b)
1
(2,2Write
mechanisms
for
following twountil
reactions.
(a)HH1,4-Butanediol
1H y
dissolved
in by
an5-methyl-1,5-hexanediol
alcohol
the
Sy
1 2,2-dimethyloxacyclohexane
process
is oxacyclopentane
complete
(s
dimethyltetrahydropyran).
dimethyltetrahydropyran).
ers
also form
form
alcoholysis
(b) 5-methyl-1,5-hexanediol
1 H N
y 2,2-dimethyloxacyclohexane (2,2ers(tetrahydrofuran);
also
by
alcoholysis
dimethyltetrahydropyran).
1

ee know,
know, tertiary
tertiary and
and secondary
secondary ethers
ethers may
may also
also form
formby
bythe
thealcoholysis
alcoholysisofofthe
the
the
Ethershaloalkanes
byalkyl
alcoholysis
also
form or
by
alcoholysis
nding
sulfonates (Section
(Section
7-1).
Theoxacyclopentane
startingmaterial
materialisissim
si
ing
two
reactions.
(a)
1,4-Butanediol
17-1).
H1 The
y
nding
sim
haloalkanes
or
alkyl
sulfonates
starting
Exercise
9-17
Ethers
also
formuntil
by
1S 1 process
by the
the
alcoholysisofofthe
thecorcorAs
tertiary
andalcoholysis
secondary
ethers may
may
also form
form by
we
tertiary
and
secondary
ethers
also
alcoholysis
lved
in know,
an
alcohol
the
is complete
complete
(see
margin).
N1
-1,5-hexanediol
1
H
y
2,2-dimethyloxacyclohexane
(2,2lved
in
an
alcohol
until
the
S
process
is
(see
margin).
N
starting material
materialisissimply
simply
responding haloalkanes
haloalkanes or
or alkyl
alkyl sulfonates
sulfonates (Section
(Section 7-1).
7-1). The
The starting

responding
haloalkanes
or
alkyl
starting
material
simply
haloalkanes
or secondary
alkyl sulfonates
sulfonates
(Section
7-1).
The
starting
material
simply
As we know,
tertiary and
ethers (Section
may
also7-1).
formThe
by the
alcoholysis
ofisisthe
cormargin).
dissolved
alcohol
until
the Ssulfonates
SNNN11ways
process
complete
(see
inhaloalkanes
an alcohol
the
process
isis complete
You now
knowuntil
of
constructing
an ether
an
responding
orseveral
alkyl
(Section
7-1).(see
Themargin).
starting
materialfrom
is simply
cise
9-17in an alcohol until the SN1 process is complete (see margin).
dissolved
rcise
9-17
cise
approach
would you choose for the preparation of (a) 2-me
Exercise 9-17
(b)know
1-methoxy-2,2-dimethylpropane?
[Hint:
Theand
product
for Whi
(a)
now
know
several ways
ways of
of constructing
constructing an
an ether
ether from
from
analcohol
alcohol
and
haloalkane.
W
now
several
an
a ahaloalkane.
haloalkane.
Wh
Exercise
9-17
oach
would
youseveral
choose
for
the
preparation
offrom
(a) 2-methyl-2-(1-methylethoxy)butan
2-methyl-2-(1-methylethoxy)but
know
andaahaloalkane.
haloalkane.Which
Which
several
ways
ofthe
constructing
an ether
ether
from
an
alcoholand
You
now know
ways
of
constructing
an
an
alcohol
would
you
choose
for
preparation
of
(a)
a neopentyl
ether.]
oach
2-methyl-2-(1-methylethoxy)buta
1-methoxy-2,2-dimethylpropane?
wouldseveral
approach
would
you
for
the
preparation
of
(a)
2-methyl-2-(1-methylethoxy)butane;
you choose
choose
forconstructing
the
preparation
of from
(a)for
2-methyl-2-(1-methylethoxy)butane;
[Hint:
The
product
for
(a)
tertiary
ether,that
that
for(b)
(b
You now know
ways of
an product
ether
an(a)
alcohol
and
a haloalkane.
Which
[Hint:
The
isisaatertiary
ether,
for
1-methoxy-2,2-dimethylpropane?
ether,
that
for
(b)
(b)
1-methoxy-2,2-dimethylpropane?
The
product
(a)
for
isis
tertiaryether,
ether,
that
for(b)
(b)
1-methoxy-2,2-dimethylpropane?
[Hint:
The
product
for
(a)isisaatertiary
opentyl
ether.]
approach
would youmay
choosealso
for the[Hint:
preparation
ofthe
(a)for
2-methyl-2-(1-methylethoxy)butane;
ndary
ethers
form
by
alcoholysis
ofthat
the
corether.]
opentyl
a neopentyl ether.]

holysis

neopentyl
ether.]
ether.]
a(b)
neopentyl
1-methoxy-2,2-dimethylpropane?
[Hint: The product for (a) is a tertiary ether, that for (b) is

ylInasulfonates
7-1).beThe
startingbymaterial
is of
simply
neopentyl
ether.] (Section
Summary
Ethers can
prepared
treatment
alcoh
ummary
Ethers
cancan
becomplete
prepared
by
treatment
ofalcohols
alcohols
with
acid
through
S
Ethers
can
be
prepared
by
treatment
of
alcohols
with
acid
through
SSand
2N22
ummary
Ethers
be
prepared
by
treatment
of
with
acid
through
SSNNNN2as
N
Nin
with
acid
through
2and
InSSummary
Ethers
can
be
prepared
by
treatment
of
alcohols
eS
1
process
is
(see
margin).
N pathways, with alkyloxonium ions or carbocations
1
N
pathways,
withEthers
alkyloxonium
ions
or
carbocations
intermediates,
and
by
pathways,
with
alkyloxonium
ions
or
carbocations
as
intermediates,
by
pathways,
alcohol
with
alkyloxonium
ions
asas
intermediates,
and
by
and
byalcoholysis
alcoholysis
S
with
alkyloxonium
ionsor
orcarbocations
carbocations
as
intermediates,
InNN11Summary
can be prepared
by
treatment
of alcohols
with acidand
through
SNalcohol
2alcoho
and
pathways,
of
secondary
or
tertiary
haloalkanes
alkyl sulfonates.
condary
or tertiary
tertiary
haloalkanes
or
alkyl
sulfonates.
or
tertiary
haloalkanes
or
alkyl
sulfonates.
orwith
of
tertiary
haloalkanes
or
alkyl
sulfonates.
or
haloalkanes
or
alkyl
sulfonates.
SN1secondary
pathways,
alkyloxonium
ions
or
carbocations
as or
intermediates,
and by alcoholysis
condary
secondary
of secondary or tertiary haloalkanes or alkyl sulfonates.

Reactions
Ethers
of
Ethers
Reactions
89-8
Reactions
of of
Ethers
Ethers
9-8 Reactions of Ethers

9-8
Reactions
Ethers
9-8
Reactions
of Ethers
As mentioned
earlier,of
ethers
are normally
rather inert. They do, however, react slowly with

As mentioned earlier, ethers are normally rather inert. They do, however, react slowly with
entioned
earlier,an
ethers
are normally
normally
rather
inert.and
They
do,
however,react
react
slowlyw
earlier,
ethers
are
rather
inert.
They
do,
however,
slowly
constructing
ether
from
anhydroperoxides
alcohol
aperoxides.
haloalkane.
Which
slowly
oxygen
by
mechanisms
form
and
peroxides
radical
peroxides.
Because
peroxides
mechanisms
to
form hydroperoxides
anddo,
As mentioned
earlier,
ethers are to
normally
rather inert. They
however,Because
react slowly
with w
oxygen
by radical
en
mechanisms
to
form
hydroperoxides
and
peroxides.
Because
pero
bydecompose
radical
mechanisms
to
hydroperoxides
and
peroxides.
Because
perox
perox
can
explosively,
care
should
taken
with
samples
ofofethers
that
have
mentioned
earlier,
ethers
arebebenormally
rather
inert.
They
rAs
the
preparation
ofextreme
(a)
2-methyl-2-(1-methylethoxy)butane;
oxygen
by radical
mechanisms
toform
form
hydroperoxides
and
peroxides.
Because
explosively,
extreme
care
should
taken
with
can
decompose
samples
ethersperoxides
that
have
ecompose
explosively,
extreme
care
should
betaken
taken
with
samples
ethers
thath
explosively,
extreme
care
be
taken
with
samples
ofofethers
that
been
exposed
to
air
several
days.
that
can decompose
explosively,
extreme
careshould
should be
with
samples
of ethers
that have
been
exposed
toThe
air for
for
several
days.
ane?
[Hint:
product
for
(a)
is
a
tertiary
ether,
that
for
(b)
is
oxygen
radical
mechanisms
to form hydroperoxides andh
exposed
air
for
several
days.
to by
air
several
days.
been exposed
to for
air for
several
days.

Peroxides
Peroxidesfrom
fromEthers
Ethers care should be taken w
can decompose explosively,
extreme
Peroxides
from
Ethers
AA
AA from
AA
AA
Peroxides
Ethers
Peroxides
from
Ethers
been22 ROCH
exposed
to air for22 ROC
several
days.

ROC
OCOR
OOOO
OOOO
OOOO
OOH
ROC
ROCH
 O
O2
ROC
OH
A
AO
AO
ACOR
A
2 ROCH
A AA

O2

AO O
2 ROC
AAAA O OH

ROC
AAA O
AAO O OO AACOR
A AA

O O O O OCOR
2 ROCH  O2
ROC O O O OH
O
O
O
O
epared
of222ROC
alcohols
with acidROC
through
2COR
and
O
OOO
ROC
OAON
O
OOH
OO
OS
2 ROCH by
O22
ROC
OH
ROC
OO
COR
COR
A treatment
AAn
AAnether
An
ether
An
peroxide
peroxide
ether
A
A
Aether
AA
Peroxides
from
Ethers
hydroperoxide
A
A peroxide
hydroperoxide
An
ether
An
ether
um ions or carbocations ashydroperoxide
intermediates,
and
by
alcoholysis
An
An
An
ether
peroxide
Anether
ether
Anether
etherperoxide
peroxide
A
useful
is
by
hydroperoxide
oxygen
ethers,like
likethat
thatinin
A ininethers,
A more
more
usefulAreaction
reaction
is cleavage
cleavage
by strong
strong acid.
acid. The
The oxygen
hydroperoxide
kanes
ormayalkyl
sulfonates.
alcohols,
be
protonated
generate
The
subsequent
A more
useful
reaction isto
cleavage
byalkyloxonium
strong acid. ions.
The
oxygen
in ethers,reactivity
like that of
inof
The
subsequent
reactivity
alcohols,
may
be
protonated
to
generate
alkyloxonium
ions.
O
O
2
ROCH

O
2
ROC
O
OH
2
these
ionsmay
depends
on the alkyl
With primary
and strong reactivity
nucleophilic
alcohols,
be protonated
to substituents.
generate alkyloxonium
ions.groups
The subsequent
of

be
to generate
alkyloxonium
ions.inThe
The
subseque
be protonated
subseque
ions.
A more useful reaction
is cleavage alkyloxonium
by strong acid. The oxygen
ethers,subsequen
like that in
alcohols,
may
be
protonated
to
generate
alkyloxonium
ions.
The
subsequent
reactivity
of
nds
on
the
alkyl
substituents.
With
primary
groups
and stron
stro
nds
stron
With primary groups and
these ions depends on the alkyl substituents. With primary groups and strong nucleophilic
2
displacement
takes
place.
HBr,
S
HBr,
place.
acids such
N
N as HBr, SN2 displacement takes place.
Primary Ether Cleavage with HBr

Primary Ether
Cleavage with
with HBr
HBr
Cleavage
HBr

CH3CH2OCH2CH3
Ethoxyethane

HBr

HBr
HBr

CH3CH2Br

 CH3CH2OH

Bromoethane

Ethanol

CH
CH33CH
OH
CH33CH22OCH2CH3
CH22Br
Br 
 CH
CH333CH
CH222OH
OH
CH
Mechanism of Primary Ether Cleavage: S 2
Ethoxyethane
Ethoxyethane

Mechanism of Primary Ether Cleavage: SN2

Bromoethane
Bromoethane

Ethanol
Ethanol
Ethanol

Br

D

CH3CH2
OCH2CH3
CH3CH2 O
CH3CH2Br  HOCH
O

 2CH
G
Cleavage:
Ether
Cleavage: SSNNN22
Mechanism of Primary
Primary
CH2CHEther
3



H

Alkyloxonium ion

H
H




Br


The alcohol
attacked
by additional HBr
D may in turn beBr
H formed as the second product
H
to 3give
bromoalkane.
CH
O
CH
CH333CH
CH222Br
Br
CH
Br
3 more of the CH
33CH22O



G
CH
CH33
CH22CH

Alkyloxonium
Alkyloxonium ion
ion

formed as the second

l formed
may in
in turn
turn be
be attacked
attacked by
by
product may
by a
second product
the bromoalkane.
ff the

CH3CH2
OCH2CH3

CH3CH2
OCH2CH3


H
H

H
D
H
CH3CH2 O
OD
G

CH3CH2 O
O CH2CH3
G
Alkyloxonium
ion
CH
2CH3

Br



Br


MECHANISM

CH3CH2Br
CH3CH2Br




HOCH
 2CH3

HOCH
 2CH3

Alkyloxonium ion

The alcohol formed as the second product may in turn be attacked by additional HBr
to give
of the
bromoalkane.
The more
alcohol
formed
as the second product may in turn be attacked by additional HBr
to give more of the bromoalkane.

Chapter 9

357

Chapter 9

357

H3C

Cl

H3C

Cl

1-Chloro-1-methyl
cyclohexane
1-Chloro-1-methyl
CH3CH2OH
cyclohexane

H3C

CH
OCHCH
2CH
3 OH

H3C

OCH2CH
3
 H  Cl

 H  Cl
86%

1-Ethoxy1-methylcyclohexane

REACTION
REACTION

MECHANISM
MECHANISM

mechanism.
rechanism.
t hu er trh eRr e R
a ec at ci ot inosn so fo f AAl cl coohhoo ll ss
F
mechanism.

em
aa nn dd t thhe e C C
h eh m
i s it sr yt r oy f oEf t hEetr hs e r s

Further Reactions of Alcohols and the Chemistry of Ethers

of methoxymethane with hot concentrated HI gives two equivalents of iod

t hhee m
C hi es m
t riys t royf oEf t Eh tehr esr s
C h a p358
t e r 9 C h a p t e Fr u9r t h e r RF eu ar tchtei ro nRse a oc ft i oAnlsc oo hf oAl lsc oahno dl s tahned C
mechanism.

Further Reactions
-19
Exercise 9-18

of Alcohols and the Chemistry of Ethers

ercise
19
-19 9-18

Exercise
Exercise
Treatment9-18
of methoxymethane with
hot 9-18
concentrated HI gives two equivalents of iodomethane.
Exercisewith
9-18 hot concentrated
oxacyclohexane
(tetrahydropyran;
shown in
with hot
eatment
HI the
givesmargin)
two equivalents
of concentra
iodomethan
Suggestofa methoxymethane
mechanism.
Treatment of methoxymethane with hot concentrated HI gives two equivalents of iodomethane.
9-19
Treatment
of methoxymethane
with
hota mechanism.
concentrated
HI gives
two
equivalents
of
iodomethane.
Suggest
oxacyclohexane
(tetrahydropyran;
shown
ininthe
margin)
with
hot
oxacyclohexane
(tetrahydropyran;
shown
the
margin)
with
hotcon
co
ggest
a
mechanism.
Treatment
of
methoxymethane
with
hot concentrated
HI
gives
two equivalents
of iodomethane.
entane.
Give
a
mechanism
for
this
reaction.
Exercise 9-18
Suggest a mechanism.

Suggest a mechanism.

ntane.
Give
for
reaction.
entane.
Giveaamechanism
mechanism
forthis
this
reaction.
of
oxacyclohexane
(tetrahydropyran;
shown
in gives
the margin)
with hot
concentrate
Treatment
of methoxymethane
with
hot 9-19
concentrated
HI
two equivalents
of iodomethane.
Exercise
Exercise
9-19
Suggest aGive
mechanism.
pentane.
a
mechanism
for
this
reaction.
Exercise
9-19
O
Reaction
of
oxacyclohexane
(tetrahydropyran; shown in the margin) with hot concentrated HI gives
ercise 9-19

m Exercise
ions
derived
from secondary
ethers
canfor this
transform
by either S 2
9-19
1,5-diiodopentane.
Give a mechanism
reaction.
Reaction of
oxacyclohexane (tetrahydropyran;
shown
in the margin)
with hot concentrated HI givesN
O
Reaction of oxacyclohexane (tetrahydropyran; shown in the margin) with hot concentrated HI gives
1,5-diiodopentane.
Give
a mechanism
for
this
reaction.
pending
on
the
system
and
conditions
(Section
7-9
and
Tables
7-2
a
1,5-diiodopentane.
Give
a mechanism
for
this
reaction.
ions
derived
from
secondary
ethers
can
transform
by
maction
ions
derived
from
secondary
ethers
can
transform
by
eithe
of
oxacyclohexane
(tetrahydropyran;
shown
in
the
margin)
with
hot
concentrated
HI
Reaction of oxacyclohexane (tetrahydropyran;
the
margin)
with
concentrated
gives
Oxonium ionsshown
derived in
from
secondary
ethers
canhot
transform
by either
SHI
2 either
or
S 1give
(E1
Exercise
9-19 Give from
reactions,
on the system
conditions
7-9
andeither
Tables 7-2 and
7-4). o
Fo
-diiodopentane.
mechanism
for
this
reaction.
um
ions derived
secondary
canand
transform
by
STable
1,5-diiodopentane.
Give
a mechanism
fordepending
thisethers
reaction.
ethoxypropane
isasystem
protonated
by
aqueous
HI
and(Section
then
converted
N2into
pending
on
the
and
conditions
(Section
7-9
and
Tables
epending
on
the
system
and
conditions
(Section
7-9
and
example,
2-ethoxypropane
is protonated
by aqueous HI and
then converted
into
2-propano
Oxonium
ions
derived from
secondary
ethers can transform
by either
S 2Sor 1S (E1)
1 (E1)
Oxonium
ionsthe
derived
fromby
secondary
ethers
transform
byless
either
STables
2 or
and
iodoethane
by
selective
attack
by iodide at
the
hindered
primary
center.
N
N gives
Reaction
of oxacyclohexane
(tetrahydropyran;
shown
incan
the
margin)
with
hot
concentrated
depending
on
system
and
conditions
(Section
7-9
an
ane
by selective
attack
iodide
ataqueous
the
less
hindered
primary
cente
reactions,
depending
on
the system
and
conditions
(Section
7-9and
and
Tables
7-2 HI
and7-2
7-4).
For
thoxypropane
is
protonated
by
then
ethoxypropane
isthe
protonated
by
aqueous
HI
and
then
conver
reactions, depending on
system and conditions
(Section 7-9HI
and and
Tables
7-2
andconverte
7-4).
For
Oxacyclohexane
(Tetrahydropyran)

Oxacyclohexane
(Tetrahydropyran)

reactions, depending on the system and conditions (Section 7-9 and Tables
7-2 and 7-4). For
N

reactions,
depending
on
system
and
conditions
(Section
7-9 HI
and
Tables
and
7-4).
For
1,5-diiodopentane.
Give
athe
mechanism
for Primary-Secondary
thisis reaction.
Ether
Cleavage
with
HI:
S 2converted
at7-2
Primary
Center
example,
2-ethoxypropane
protonated
by
aqueous
and
then
into
2-propanol
Oxonium
derived
from
secondary
ethers
can
transform
by
either
SN2SNor
(E1)
2-ethoxypropane
is
protonated
by
aqueous
HI
and
then
converted
into
N1S
Oxonium
ionsions
derived
from
secondary
can
by
either
2 Sor
N1 (E
example, 2-ethoxypropane
is protonated
by ethers
aqueous
HI transform
and
converted
intocenter.
2-propanol
and iodoethane
by selective
attack
by
at thethen
less hindered
primary
Lessiodide
hindered
ne
by
selective
attack
by
iodide
at
the
less
hindered
primary
ane
by
selective
attack
by
iodide
at
the
less
hindered
primary
reactions,
depending
on
the
system
and
conditions
(Section
7-9
and
Tables
7-2
and
7-4).
For F
Primary-Secondary
Ether
Cleavage
with
HI:
SNand
2 atTables
Primary
Cente
OH
tions,
depending
the
system
conditions
(Section
7-9
7-2 and
7-4).
hane
by selective
attack
byand
iodide
at
the
hindered
primary
center.
and iodoethane
byon
selective
attack
by
iodide
at
the
lessless
hindered
primary
center.
Primary-Secondary
Ether
Cleavage
with HI:
S 2 at Primary
Center

N either S into
example,
2-ethoxypropane
is
protonated
byethers
aqueous
and
2-propanol
Oxonium
ions derived
secondary
canHI
transform
byconverted
SN2-propa
1 (E1)

N2 or
mple,
2-ethoxypropane
is from
protonated
by
aqueous
HI
andthen
then
converted
into
O
I
HI, H2O

and iodoethane
byLess
selective
attack
by Cleavage
iodide
at the(Section
less
primary
center.
Primary-Secondary
Ether
HI: hindered
Shindered
2 atand
Primary
reactions,
depending
on the
system
and
conditions
Tables
and
7-4). For
hindered
N7-9
iodoethane
by selective
attack
by
iodide
at with
the
less
primary
center.
rimary-Secondary
Ether
Cleavage
with
HI:
SSNPrimary
2Center
at
Primary
Primary-Secondary
Ether
Cleavage
with
HI:
27-2
at
Primary
OH
Primary-Secondary
Ether
Cleavage
with
HI:
S
at
Center
N
N2converted
example, 2-ethoxypropane is protonated by aqueous HI and then
into 2-propanol
Less hindered

2-Ethoxypropane
HI, H2O

2-Propanol

Iodoethane

Less hindered
Primary-Secondary
Ether Cleavage with OH
HI: SN2 at Primary
Center

and iodoethane
by selective attack
by iodide
at the
less
hindered
O ethers
I
Primary-Secondary
Ether
with
HI:
SNprotect
2 atprimary
Primary
Center
Tertiary
function
to
alcoholscenter.
OH
Less
HI, Cleavage
Hbutyl
2O
Less
hindered
Lesshindered
hindered
Less
hindered
HI,
H
O
Ethers2-Ethoxypropane
tertiary alkyl groups2-Propanol
transform
dilute acid to give intermediat
even inIodoethane
Primary-Secondary
Ethercontaining
Cleavage
withareOH
HI:
SNtrapped
2 at Primary
Center

Less hindered
tertiary carbocations, which OH
eitherOH
by SNl processes, when good nucleophile
OH
O
O
I
I
H2Hor
O2Odeprotonated OH
are HI,
present,
in their absence:
HI,
Less butyl
hindered
Tertiary
ethers
to protect
HI,
OO
HI,HHfunction
 alcohols
Acid: SN1 and E1 at Tertiary Center
HI, H2O 2 2 2-Propanol
Primary-Tertiary
EtherOH
Cleavage with Dilute
2-Ethoxypropane
Iodoethane
O
I


2-Ethoxypropane
2-Propanol
transform
even in diluteIodoethane
acid to give intermediate
O Ethers containing tertiary alkyl groups
2
2

HO
tertiary
are either
trapped
by
SNl Iodoethane
processes, when
H SO , H
O carbocations,HI,which
I good nucleophiles
O2-Ethoxypropane
O, 50C
Oare
2-Propanol
II
O
OH
present,
or deprotonated in their absence:
O
I
2-Ethoxypropane
2-Propanol
Iodoethane
Tertiary butyl
ethers function to protect
alcohols Iodoethane
2-Ethoxypropane
2-Propanol
2

Primary-Tertiary Ether Cleavage with Dilute Acid: SN1 and E1 at Tertiary Center

2-Ethoxypropane
2-Propanol
Iodoethane
2-Ethoxypropane
2-Propanol
2-Ethoxypropane
2-Propanol
Iodoethane
Ethers containing
tertiary
alkyl
groups
even
in dilute
acid to giveIodoethane
intermediate
utyl
ethers
function
tototransform
protect
alcohols
Tertiary
butyl ethers
function
protect
alcohols

Because tertiary ethers are made under similarly mild conditions from alcohols (Section 9-7)
they act as protecting groups for the hydroxy function. A protecting group renders a spe

H SO S
, H O,
50C
tertiary carbocations, which arecifieither
trapped
processes,
when
c functionality
in a by
molecule
with respect
togood
reagentsnucleophiles
and conditions tha
Nl unreactive
O transform
OHto

Ethers
containing
tertiaryfunction
alkyl
groups
in dilute
acid
give
intermediate
normally
transform it. even
Such
protection
allows
chemistry
to be carried
out elsewher
tiary
butyl
to
protect
alcohols
are present,
or ethers
deprotonated
in would
their
absence:
Tertiary
butyl
ethers
function
to
protect
alcohols
ining
tertiary
alkyl
groups
transform
even
in
dilute
acid
give
in
a
molecule
without
interference.
Subsequently,
the
original
function
isto
restored
(depro
tertiary carbocations, which are either trapped by SNl processes, when good nucleophiles
tection). A protecting group has to be reversibly installed, readily and in high yield. Such
ers
containing
tertiary
alkyl
groups
transform
even
in
dilute
acid
to
give
intermedi
ocations,
which
are
either
trapped
by
S
l
processes,
when
good
Because
tertiary
ethers
are
made
under
similarly
mild
conditions
from
alcohols
(Section
9-7),
Primary-Tertiary
Ether
Cleavage
with
Dilute
Acid:
S
1
and
E1
at
Tertiary
Center
are
present,
or
deprotonated
in
their
absence:
Ethers
containing
tertiary
alkyl
groups
transform
even
in
dilute
acid
to
give
intermediate
is the case with
tertiary ethers, ineven
which
original
alcohol isacid
protectedto
fromgive
base,
organo
NN thein
ntaining tertiary alkyl groups
transform
dilute
in
they
actare
asare
protecting
groups
for by
theand
hydroxy
function.
Awhen
protecting
group
renders
ais spemetallic
reagents,
oxidants,
Another
method
of alcohol
protection
esteri
ary
carbocations,
which
either
trapped
by
SNNreductants.
processes,
when
good
nucleophi
tertiary
carbocations,
which
either
trapped
S
l lprocesses,
good
nucleophiles
or
deprotonated
in
their
absence:
fi
cation
(Section
9-4;
Chemical
Highlight
9-2).
rbocations,
which
are
either
trapped
by
S
l
processes,
when
good
nu
cifi
c
functionality
in
a
molecule
unreactive
with
respect
to
reagents
and
conditions
Primary-Tertiary
Ether
Cleavage
with Dilute Acid:NSN1 and E1 at Tertiary Center that
present,
or
deprotonated
in
their
are
present,
or
deprotonated
in
their
absence:
H absence:
SO
, H O, 50C
would
transform transform
it.transform
Such protection
allows
chemistry
be carried out
elsewhere
ining
tertiary
groups
even
in
acid
toto
aining
tertiaryalkyl
alkyl
groups
even
intodilute
dilute
acid
Protection
of Alcohols
asOH
Tertiary
Ethers
O normally
Butyl
t, or deprotonated
their
absence:
in ain
molecule
without
interference. Subsequently, the original function is restored (deproCarry
out1
reactions
on1
R byand
Primary-Tertiary
Ether
with
Dilute
Acid:
SS
E1
at Tertiary
Center
H2with
SO
50Cto be
y-Tertiary
Ether
Cleavage
Dilute
Acid:
S
Tertiary
4, H
2O,
Primary-Tertiary
Ether
Cleavage
with
Dilute
Acid:
1and
and
E1
at E1
Tertiary
Center
tection).
ACleavage
protecting
group
has
reversibly
installed,
readily
and inat
high
yield.
Such g
ocations,
which
are
either
trapped
by
S
l
processes,
when
bocations,
which
are
either
trapped
by
S
l
processes,
when
usingN
Grignard
reagents,
N
N
N
O
OH

(CH ) COH, ethers,
H
H , H O organooxidizing agents,
etc.
is the case with tertiary
in which the original
alcohol
is protected from base,
2

butyl ethers function to protect alcohols

utyl ethers
butyl
ethersfunction
functiontotoprotect
protectalcohols
alcohols
2
2

4
4

2
2

ROH
ROC(CH ) Acid: S 1 andROC(CH
) Tertiary
ROH
ary-Tertiary
Etherare
Cleavage
with
Dilute
E1 at(Section
C
reagents,
Another N
method
alcohol protection
is9-7),
esterior
deprotonated
inin
their
absence:
or
deprotonated
their
absence:
Because
tertiary ethersmetallic
made
under
similarly
mild conditions
from of
alcohols
Hoxidants,
SO
, H O,and
50Creductants.
H SO , H O, 50C
3 3

H2O

3 3

Protected

3 3

OH  group renders a spethey act as protecting

the
hydroxy
2SO
4, H
2O, 50Cfunction. A protecting
O groups Hfor
OH 
Because tertiary ethers are made under similarly mild conditions from alcohols (Section 9-7),
22
44 step
22
Protection

R changed into R

Deprotection

2
fication
Highlight 9-2).
O (Section 29-4;4 Chemical
alcohol

Using
protecting
groups
is aas
common
in organic
synthesis,
enable
O in a molecule
OH
 whichthat
Protection
ofwith
Alcohols
Tertiary
Butyl Ethers
cific functionality
unreactive
respect
to procedure
reagents
and conditions
H
SO
, toH
O,
50C
y-Tertiary
Ether
Cleavage
with
Dilute
Acid:
SOH
1group
E1
Te
y-Tertiary
Ether
Cleavage
with
Dilute
SNcarried
1and
and
E1at
T
chemists
carry
out many
transformations
that would
otherwise
impossible.
We
shal
they
as protecting
groups
for
the
hydroxy
function.
AAcid:
protecting
renders
aat
speN
wouldactnormally
transform
it. Such
protection
allows
chemistry
to be
elsewhere
O
beout
2

Carry out reactions

on R by with other functional groups later in th
see other protecting strategies
in conjunction

using respect
Grignard
reagents,
Because
tertiarywithout
ethers
madecourse.
under
similarlywith
mild
conditions
from alcohols
(Section
9-7),
cifi
functionality
in aare
molecule
unreactive
to reagents
and
conditions
that
in ac molecule
interference.
Subsequently,
the
original
function
is restored
(CH ) COH, H
H , H O (deprooxidizing
agents,
etc.
ause
tertiary
ethers
aregroups
made
under
similarly
mild
conditions
alcohols
(Section
9ROC(CH
ROH
ROH
ROC(CH
they
actnormally
as
fortothe
hydroxy
function.
A readily
protecting
group
aSuch
spe3)3 allows
3 renders
would
transform
it.Ohas
Such
protection
chemistry
tofrom
be
out
elsewhere
H
tection).
A protecting
protecting
group
be
reversibly
installed,
andcarried
in 3)high
yield.
Protection
stepH
Protected
Rrespect
changed intoA
R protecting
Deprotection
actc as
protectingingroups
for
the
hydroxy
function.
group
renders
as
,H
50C
HSO
SO
, HO,O,
50C
cifi
functionality
a molecule
unreactive
with
to
reagents and
conditions
that


3 3

Because tertiary
ethers
under
similarly
mild
conditions
from
alcohols
(Section
9-7),
ethers are
are made
made
under
similarly
normally
transform
it.under
Such
protection
allows
chemistry
to
tertiary
ethers
are
made
under
similarly
mild
conditions
from
alcohols
(Section
9-7),
Because
mildconditions
conditions
fromalcohols
alcohols
(Section9-7),
9-7),b
Because
tertiary
ethers
are
made
similarly
mild
from
(Section
they act
as
protecting
groups
for
hydroxy
function.
A
protecting
group
renders
aaaspeprotecting
groups
for the
the
hydroxy
act
as protecting
protecting
groups
for
the
hydroxy
function.
AAprotecting
protecting
group
renders
spethey
function.
protecting
group
renders
speBecause
tertiary
ethers
made
under
similarly
mild
conditions
from
alcohols
(Section
9-7),
are
made
under
similarly
mild
conditions
from
alcohols
(Section
9-7),
Because
tertiary
ethers
are
made
under
similarly
mild
conditions
from
alcohols
(Section
9-7),
they
act
as
groups
for
the
hydroxy
function.
A
group
renders
a
speBecause
tertiaryinethers
are madeunreactive
under similarly
mild
conditions
from
alcohols
(Section 9-7),
olecule
without
interference.
Subsequently,
the
original
func
functionality
a
molecule
with
respect
to
reagents
and
conditions
that
cificc they
a
molecule
unreactive
with
respect
to
reagents
and
conditions
that
functionality
in
molecule
unreactive
withfunction.
respect AA
to
reagents
and
conditions
that
they
act as
as protecting
protecting
forthe
thehydroxy
hydroxy
function.
Aprotecting
protectinggroup
group
renders
aspespein aa molecule
groups for
for
the
hydroxy
function.
A
protecting
group
renders
speact
as
protecting
groups
for
the
hydroxy
function.
protecting
group
renders
cific they
functionality
in
unreactive
with
respect
to
reagents
and
conditions
that
act
groups
renders
aaaspenormally
transform
it.
Such
protection
allows
chemistry
to
be
carried
out
elsewhere
would
transform
it.
Such
protection
allows
chemistry
to
be
carried
out
elsewhere
functionality
in aaait.
molecule
unreactive
withrespect
respecttoto
toreagents
reagents
andconditions
conditions
that a
normally
transform
it.
Such
protection
allows
chemistry
to
be carried
carried
out
elsewhere
.would
A cifi
protecting
group
has
to beallows
reversibly
installed,
readily
molecule
unreactive
with
respect
to
reagents
and
conditions
that
cifi
functionality
in
molecule
unreactive
with
respect
reagents
and
conditions
that
cc functionality
in
molecule
unreactive
with
and
that
normally
transform
Such
protection
chemistry
to
be
out
elsewhere
without
interference.
Subsequently,
the
original
function
is
restored
(deproin aa molecule
without
interference.
Subsequently,
thechemistry
original
function
restored
(deprowould normally
normally
transform
it.Such
Such
protectionallows
allows
chemistry
tobe
becarried
carried
out
elsewhere
Such
protection
allows
chemistry
to
be
carried
out
elsewhere
molecule
without
interference.
Subsequently,
the
original
function
isisrestored
restored
(depronormally
transform
it.
Such
protection
allows
chemistry
be
carried
out
elsewhere
would
transform
it.
protection
toto
out
elsewhere
in a with
molecule
without
interference.
Subsequently,
the
original
function
is
(deproase
tertiary
ethers,
in
which
the
original
alcohol
is
prote
A
protecting
group
has
to
be
reversibly
installed,
readily
and
in
high
yield.
Such
interference.
Subsequently,
the
original
function
is
restored
(deprotection).
protecting
group
has
to
be
reversibly
installed,
readily
and
in
high
yield.
Such
in
a
molecule
without
interference.
Subsequently,
the
original
function
is
restored
(deproA
protecting
group
has
to
be
reversibly
installed,
readily
and
in
high
yield.
Such
interference.
Subsequently,
the original
original
function
restored
(deproin a A
molecule
without
interference.
the
function
restored
(deprotection).
protecting
group
has to be Subsequently,
reversibly
installed,
readily
and inisishigh
yield.
Such
the
case
with
tertiary
ethers,
which
the
original
alcohol
is
protected
from
base,
organoprotecting
has
toreductants.
be
reversibly
installed,
readily
and
in
high
yield.
Such
groupin
has
to
be
reversibly
installed,
readily
and
in
high
yield.
Such
tertiary ethers,
ethers,
in
which
the
originalinstalled,
alcohol
is
protected
from
base,
organoA protecting
protecting
group
has
to
be
reversibly
installed,
readily
and
in
high
yield.
Such
thetection).
case with
with
tertiary
ethers,
in
which
the
original
alcohol
is
protected
from
base,
organogroup
has
to
be
reversibly
readily
and
in
high
yield.
Such
c isisreagents,
oxidants,
and
Another
method
of
alco
the
case
tertiary
in
which
the
original
alcohol
is
protected
from
base,
organoreagents,
oxidants,
and
reductants.
Another
method
alcohol
protection
is
esteriwith
tertiaryethers,
inwhich
whichthe
the
original
alcoholof
protected
from
base,
organois the
the
case with
ethers,
in
which
the
original
alcohol
protected
from
base,
organowith
tertiary
ethers,
in
which
the
original
alcohol
isisisprotected
protected
from
base,
organometallic
oxidants,
and
reductants.
Another
reagents,
oxidants,
and
reductants.
Another
method
of
alcohol
protection
is
esteriis
case
tertiary
in
original
alcohol
is
from
base,
organomethod
of
alcohol
protection
is
esterimetallic
reagents,
oxidants,
and
reductants.
Another
method
of
alcohol
protection
is
esteri(Section
9-4;
Highlight
reagents,
and
reductants.
Another9-2).
methodofof
ofalcohol
alcohol
protection
esterimetallic
oxidants, and
and
reductants.
Another
method
of
alcohol
protection
esteri(Section
9-4;
Chemical
Highlight
9-2).
reagents,
oxidants,
and
reductants.
Another
method
alcohol
protection
esterifi
cation
9-4; Chemical
Chemical
Highlight
9-2).
metallic
reagents,
oxidants,
reductants.
Another
method
protection
isisisis
esteri(Section
9-4;
Chemical
Highlight
9-2).
fication
(Section
9-4;
Chemical
Highlight
9-2).
fication
(Section
9-4; 9-4;
Chemical
Highlight
9-2).
(Section
Highlight
9-2).
cation
Chemical
Highlight
9-2).
(Section
9-4; Chemical
Chemical
Highlight
9-2).
fification
(Section
9-4;
Highlight
9-2).
Protection
of
Alcohols
as
Tertiary
Butyl
Ethers
Protection of
of Alcohols
Alcohols as
asTertiary
TertiaryButyl
ButylEthers
Ethers
Protection
Protection
of
Alcohols
as
Tertiary
Butyl
Ethers
Protection
of
Alcohols
as
Tertiary
of
Alcohols
asTertiary
Tertiary
Butyl
Ethers
Protectionof
of
Alcohols
as
Tertiary
Butyl
Ethers
Protection
of
Alcohols
as
Tertiary
Butyl
Ethers
Protection
Alcohols
as
Butyl
Ethers

Butyl Ethers

Carry
out
reactions
on
Carry
out
reactions
on
RR
by
Carry
out
reactions
onR
Rby
by
Carryout
outreactions
reactionson
on
by
Carry
R
by
using
Grignard
reagents,
Carry
out
reactions
on
by
Carry
outreactions
reactions
on
by
using
Grignard
reagents,
Carry
out
reactions
on
by
using
Grignard
reagents,
Carry
out
on
RRRR
by
using
Grignard
reagents,


using
Grignard
reagents,


(CH
)33COH,
H
,, H
O2O
H
oxidizing
agents,
etc.



3
2
using
Grignard
reagents,
using
Grignard
reagents,
using
Grignard
reagents,
(CH
COH,
H
HH
HH
oxidizing
agents,
etc.
using
Grignard
reagents,
3
2

H
oxidizing
agents,
etc.reactions on R by
3))3
2O
Carry
out

,, H
(CH
COH,
H
oxidizing
agents,
etc.
3
3
2O
(CH
)
COH,
H
O
oxidizing
agents,
etc.
ROC(CH3)3
,H
ROC(CH
ROH
H
3 3 (CH
2O
(CH
oxidizing
agents,
etc.
COH,
H
COH,H
H
H
oxidizing
agents,
etc.
oxidizingagents,
agents,
etc.
3
oxidizing
etc.
)
ROC(CH
)333)3 HHHHH,,H,H
ROH
ROC(CH
2O
2O
2O
)
H
ROC(CH
333))333COH,
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3)
3
3
H
O
3
3
ROC(CH
ROH
2
H
O
ROC(CH
ROH
H ROH H
ROC(CH
33)33 333)3))3333
33)3)333)3)33)33
H22222O
O
ROC(CH
ROH
ROC(CH
ROC(CH
ROH
ROC(CH
ROC(CH
ROH
ROC(CH
ROH
ROC(CH
using
Grignard
reagents,
H
O
H
O
H
2222O
Protection
step
Protected
R
changed
into
R
Deprotection
Protection
step
R
changed
into
R
Protected
Deprotection
Protected
R
changed
into
R
Deprotection
 step
Protection
step step
Protected
Rchanged
changed
into
RR
Deprotection
Protection
R
into
R
Deprotection
HProtection
oxidizing
agents,
etc.
Protection
step
Protected
R
changed
into
R
Deprotection
Protected
R
changed
into
R
Deprotection
Protected
R
changed
into
Deprotection
Protection
step Protected
Protected
R
changed
into
R
Deprotection
3COH,
alcohol
alcohol

alcohol
alcohol
alcohol
alcohol
alcohol
alcohol
alcohol
alcohol )
ROC(CH

ROC(CH

3 3
H2O
groups
is
common
procedure
in
organic
synthesis,
which
enables
protecting
Using
groups
is
common
procedure
in
organic
synthesis,
which
enables
protecting
Using
groups
is aaais
ais
common
procedure
protecting
in
organic
synthesis,
which
enables
Using
protecting
groups
aaaacommon
procedure
inin
organic
synthesis,
enables
protecting
groups
common
procedure
organic
synthesis,
which
enables
Using
groups
iscommon
common
procedure
in
organic
synthesis,
which
enables
Using
protecting
groups
is
procedure
in
organic
synthesis,
which
enables
protecting
common
procedure
in
organic
synthesis,which
which
enables
chemists
carry
out
many
transformations
that
would
otherwise
be
impossible.
We
shall
ection
stepto
Protected
Rthat
changed
into
R be
to
out
many
transformations
that
would
otherwise
be
impossible.
We
shall
chemists
out
many
transformations
that
chemists
to
out
many
transformations
would
otherwise
be
impossible.
We
shall
to carry
carry
would
otherwise
be
impossible.
We
shall
carry
out
many
transformations
that
would
otherwise
be
impossible.
We
shall
chemists
to carry
many
transformations
that
would
otherwise
be
impossible.
We
shall
carry
out
transformations
that
would
otherwise
be
impossible.
We
shall
chemists
out
many
transformations
that
would
otherwise
impossible.
We

chemists to carry out many transformations that would otherwise be impossible. We shall
see other
protecting
strategies
in
conjunction
with
other
functional
groups
later
in
the
protecting
strategies
in
conjunction
with
other
functional
groups
later
in
the
alcohol
see
strategies
in in
conjunction
see other
protecting
strategies
with
other
functional
groups
the
protecting
strategies
in
conjunction
with
other
functional
groups
later
inin
the
other
strategies
in
conjunction
with
other
functional
groups
the
other
protecting
with
other
functional
groups
later
in
the
protecting
in conjunction
conjunction
with
other
functionalgroups
groupslater
laterinin
in
see other
protecting
strategies
in
conjunction
with
other
functional
later
the
course.
course.
course.
course.
course.

ng protecting groups is a common procedure in organic sy

s to carry out many transformations that would otherwise b
er protecting strategies in conjunction with other function

99 -- 88 RR ee aaccttiioonnss ooff EEtthheerrss

9-8 Reactions of Ethers
9-8 Reactions of Ethers

CChhaappt teer r 99
Chapter 9
Chapter 9

CHEM
I CAL
H II GG H
H LI
LIG
HTT 99-- 22
CH
EM IC
AL H
GH
CH E M I C AL H IG H LI G H T 9-2
C HE M I CA L H IG H LI G H T 9-2
Protecting Groups
Groups in
in Synthesis
Synthesis
Protecting
Protecting Groups in Synthesis
Protecting
Groups
in Synthesis
Protecting groups,
groups,
as described
described
in the
the text,
text, are
are essential
essential parts
parts
Protecting
as
in

359
359
359
359

executed, you
you will
will note
note that
that all
allthe
theaction
actiontakes
takesplace
placeatatthe
the
executed,
Protecting
groups,syntheses.
as described
the text,is are
executed,
will note
the the
action
takes of
place
atseemthe
of many
many organic
organic
An in
example
the essential
synthesisparts
of the
the
centers of
ofyou
reactivity
C3that
andall
C17,
remainder
theseemof
syntheses.
An
example
is the
synthesis
of
centers
reactivity
C3
and
C17,
the remainder
of place
the
Protecting
groups,
as described
in the
areasynthesis
essential
parts
executed,
you will
note
thatC17,
all the
takes
at the
of
organic
syntheses.
An example
is the
of
the
centers
of reactivity
C3 molecule
and
the action
remainder
of the
seemsexmany
hormone
testosterone
(Section
4-7)text,
from
cholesterolingly complex
complex
steroid
simply
providing
scaffold.
sex
hormone
testosterone
(Section
4-7)
from
a cholesterolingly
steroid
molecule
simply
providing
aascaffold.
of
many
organic
syntheses.
An example
isofthe
synthesis
of the
centers
of reactivity
and
C17,
the
remainder
the seemsex
hormone
testosterone
(Section
4-7) from
asteroid
cholesterolingly
complex
steroid C3
molecule
simply
providing
aofscaffold.
derived
starting
material.
Natural
sources
hormones
Thus,
protection
by
formation
of
the
1,1-dimethylethyl
derived
starting
material. Natural
sources
of steroid
hormones
Thus,
protection
by formation
of theproviding
1,1-dimethylethyl
sex
hormone
testosterone
(Section
4-7)
a cholesterolingly
complex
steroid
simply
a scaffold.
derived
starting
material.
Natural
sources
of steroid
hormones
Thus,
protection
by
formation
of by
thereduction
1,1-dimethylethyl
are far
far
too
limited
to meet
meet
the needs
needs
of from
medicine
and
(tert-butyl)
ether
C3molecule
followed
C17.AA
are
too
limited
to
the
of
medicine
and
(tert-butyl)
ether
atat C3
isis followed
by the
reduction
atatC17.
derived
starting
material.
of steroid
hormones
Thus,
protection
of
1,1-dimethylethyl
are
far too
limited
to meetNatural
the needs
of medicine
(tert-butyl)
ether at step
C3byisatformation
followed
by
reduction
at C17. A
second
protection
C17 isis esterifi
esterifi
cation
(Section
9-4).
research;
these
molecules
must
besources
synthesized.
Inand
our
case,
second
protection
step
C17
cation
(Section
9-4).
research;
these
molecules
must
be
synthesized.
In
our
case,
are
far
toothese
limited
to at
meet
the
of medicine
and
(tert-butyl)
ether step
at
C3atatisC17
followed
by cation
reduction
attertiary
C17.
A
second
protection
is esterifi
(Section
9-4).
research;
molecules
must
becarbonyl
synthesized.
In our
case,of
Esters are
are stable
stable
in
dilute
acid,
which
hydrolyzes
the hydroxy
hydroxy
function
C3
andneeds
function
at C17
C17
Esters
in
dilute
acid,
which
hydrolyzes
tertiary
the
function
at
C3
and
carbonyl
function
at
of
second
protection
at acid,
C17
ishydroxy
esterifi
cation
research;
these
molecules
be
synthesized.
In atour
case,
Esters
stable
in step
dilute
hydrolyzes
tertiary
the
function
at C3must
carbonyl
function
C17
of
the hydroxy
starting
material
have
toand
trade
places
to furnish
furnish
the
ethers.are
This
strategy
allows
thewhich
group(Section
C3toto9-4).
be
the
starting
material
have
to
trade
places
to
the
ethers.
This
strategy
allows
the
hydroxy
group
atatC3
be
Esters
are oxidized
stable
in to
dilute
acid,
which
hydroxy
functionprecursor.
at C3
function
at C17
the
starting
material
have
to and
trade
places
to furnish
the of
ethers.
This
strategy
allows
the hydroxy
group
C3tertiary
to be
desired
testosterone
Incarbonyl
other
words,
selective
freed and
and
a carbonyl
carbonyl
whilehydrolyzes
thatatatat
C17
remains
desired
testosterone
precursor.
In
other
words,
selective
freed
oxidized
to
a
while
that
C17
remains
the
starting
have group
to trade
places
furnish the
ethers.
strategy
the
hydroxy
at remains
C3
to
be
desired
testosterone
precursor.
In atother
words,
selective
freed
andThis
oxidized
totoaallows
carbonyl
while
thatgroup
at C17
reduction
ofmaterial
the carbonyl
C17
andto
oxidation
of the
the
protected.
Exposure
strong
acid
nally
converts
theproduct
product
group at
C17
and
oxidation
of
protected.
Exposure
to strong
acid
fifinally
converts
the
desired
words,
selective
freed
oxidized
to
a here
carbonyl
while
that
at C17
re
ductiontestosterone
of theatcarbonyl
groupInatother
C17
and
oxidation
the
protected.
Exposure
to
strong
acid
fitestosterone.
nally converts
the remains
product
hydroxy
group
C3precursor.
are required.
required.
In the
the
scheme
thatof
was
of the
theand
sequence
shown
into testosterone.
hydroxy
group
atcarbonyl
C3
are
In
scheme
that
was
of
sequence
shown
here into
reductiongroup
of theat
group at In
C17
oxidation
of the
Exposure
to here
strong
acid
finally converts the product
hydroxy
C3 are required.
theand
scheme
that was
ofprotected.
the sequence
shown
into
testosterone.
hydroxy group at C3 are required. In the scheme
that
was
of
the
sequence
shown
here
into
testosterone.
O
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C O
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HH3CC O
H33C%% 17
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Reduces
carbonyl
Protects
C3
OH
)
CO
(CH
HO)
)
)
CO
(CH
H
H
H
H
3
3
at C17 to OH
(CH33)333CO
HO 3
Cholesterol-derived
)
) Cholesterol-derived
(CH3)3CO 3
HO 3 Cholesterol-derived
starting material
material
starting
OH
starting material
OH
H3CC %OH
Cholesterol-derived
H
%
H33C
starting material
%% % 1717
H3%C %17OH
H33CC
H %
H
H
17
Esterification
Esterification
H
C
H
3 %% %%
Esterification
% %
Protects
Protects
H3C H
H
H H H
Protects
Esterification
C17OH
OH
C17
% H % H
C17 OH
)33
)
Protects
)
(CH
)
CO
(CH33))33CO
CO 3
H
H
(CH
C17 OH
3 3
)
(CH3)3CO 3
O
O
O
O
OO
BBB
BBB
OCR
OCR
O
O
OCR
OCR
H33C
C %OCR
H
C
3C OCR
3C
% B
B
H
HHH
3 %
3C%% %%17
%%17
17
17
%
17
17
%
%
DiluteHH , ,HHOO
PCC,CH
CHCl
Cl
Dilute
PCC,
H C OCR Dilute
H3C %OCR
H ,HO
PCC, CH Cl
H
C
H
H33C
C
C
H 3 % %17
33C
17
PC(CH))
Oxidizes
OxidizesC3
C3OH
OH
CH
CHPC(CH
H
HHH
H
HHH %
3%
3C%%
PC(CH
Oxidizes
C3 OH
CH
)O
Dilute
H ,H
PCC, CH
Cl
Deprotects
C3
Deprotects
C3
%% %%%
% %%%
Deprotects C3
H3C H
H3C HH H HH
but
butnot
notC17
C17OH
OH
H
H H H
Oxidizes C3 OH
CH
but
not PC(CH
C17 OH )
H % H
% H % H
%
Deprotects C3
)33
33
)
(CH
)
CO
but
not
C17
OH
O
3
3
O
H
H
H
H
(CH333)333CO
O
Testosterone
Testosterone
)
Testosterone
(CH3)3CO 3
O 3
precursor
precursor
precursor
44

33 33
3 3

3 3




4
33

2 22 2
2 2
4

2 2

3
22




22

22

3 32 2
32 2

22 22
2

3 2

Testosterone
precursor

Exercise 9-20
9-20
Exercise
Exercise
Show how
how9-20
you would
would achieve
achieve the
the
following
interconversions
(the
dashed
arrow
indicates
that
the following
following interconversions
interconversions (the
(thedashed
dashedarrow
arrowindicates
indicatesthat
that
Show
you
several steps
steps are
are required).
required). (Hint:
(Hint:
You
need
to
protect
the
OH
function
in
each
case.)
(Hint: You
You need
need to
to protect
protectthe
theOH
OHfunction
functionin
ineach
eachcase.)
case.)
several
Show how you
would achieve
the following
interconversions
(the dashed
arrow indicates that
CH22CH
CHrequired).
OH
DCH
CH
CH
OH
(a)
BrCH
DCH2You
CH222CH
CH222OH
OH
22CH
DCH
(a)
BrCH
several
steps
(Hint:
need
to protect the OH function in each case.)
22CHare
22OH
HO
CH
O CH H
H
HO CH CH
CH333OH
HO
O
OH
DCH
CH
(a) BrCH CH
2

HO

CH3

(b)
(b)

(b)
OH
OH

OH
OH
OH

OH

OH

cleaved
by
(strong)
acids.
Protonation
of
an
ether
containing
In Summary Ethers
Ethers are
are cleaved
cleaved by
by (strong)
(strong) acids.
acids. Protonation
Protonation of
of an
an ether
ethercontaining
containing
methyl or primary alkyl groups gives
gives
an alkyloxonium
alkyloxonium
ion
that
subject
to
attack
by
an
ion
to
attack
gives
alkyloxonium
ionthat
thatisisissubject
subject
toSSSNNN222containing
attackby
by
In Summary Ethers are cleaved
by an
(strong)
acids. Protonation
of an ether

methyl or primary alkyl groups gives an alkyloxonium ion that is subject to SN2 attack by

R e a c t i o n ss ooo ff A
F uu rr tt hh ee rr R
R
AAllccoohhoollss aanndd tthhee CChheemmi isst tr ryy oof f EEt thheer rs s
F
i isiststrtryryy oofof fEEtEththeherersrs s
R eeee aaaa ccccttttiiiioooonn
emm
F u rr tt h
nnsss ooofff AAAlllcccooohhhooolllsss aaaannnddd ttththheee CCChhheem
h eee rrr R
R

ucleophiles. Carbocation formation follows protonation when secondary and tertiary group
F u r t hfollows
e r R e a c protonation
t i o n s o f A l cwhen
o h o l s secondary
a n d t h e Cand
h e mtertiary
i s t r y o fgroups
Ethers
360
C h a p t e r 9 formation
nucleophiles.
Carbocation
e present, leading to SN1 and E1 products. The hydroxy group of alcohols can be protecte
are present, leading to SN1 and E1 products. The hydroxy group of alcohols can be protected
nucleophiles.
Carbocation
formation follows
followsprotonation
protonationwhen
whensecondary
secondaryand
andtertiary
tertiarygroups
groups
the
form
of
a
tert-butyl
ether.
nucleophiles.
Carbocation
formation
in
the form ofCarbocation
a tert-butylformation
ether. follows protonation when secondary and tertiary groups
nucleophiles.

Carbocation formation
formation
follows
protonation
whenprotonation
secondary
andtertiary
tertiary
groups
nucleophiles. Carbocation
follows
protonation
when
secondary
and
groups
nucleophiles.
Carbocation
formation follows
when secondary
and
tertiary group
are present,
present, leading
leading to
to SNNN111and
and E1
E1
products.
Thehydroxy
hydroxy
groupofof
ofalcohols
alcohols
can
be
protected
are
leading
products.
The
hydroxy
group
alcohols
can
be
protected
The
group
be
protected
leading to
toSS
andE1
E1
products.
The
group
of
alcohols
can
be
protected
are present,
to
SSNNN11 and
and
E1
products.
The
group
alcohols
can
be
protected
present,
leading
are products.
present,
leading
to SNhydroxy
1hydroxy
and E1 products.
Theof
hydroxy
groupcan
of
alcohols
can
be protected
form
of
a
tert-butyl
ether.
in
the
form
of
a
tert-butyl
ether.
in
in
the
form
of
a
tert-butyl
ether.
in the
form
of
ether.
tert-butyl
ether.
in
theReactions
form
of aa tert-butyl
tert-butyl
ether.
9-9
ofofOxacyclopropanes
9-9
Reactions
Oxacyclopropanes

F u r t h e r R9-9
e a c tReactions
i o n s o f of
A lOxacyclopropanes
cohols and the Chemistry of Ethers
Chapter 9
lthough
ordinary
are
inert, the
the
strainedstructure
structure
oxacyclopropan
Although
ordinaryethers
ethers
are relatively
relatively
inert,
strained
of of
thethe
oxacyclopropanes
Reactions
of
of Oxacyclopropanes
Oxacyclopropanes
9-9
Oxacyclopropanes
Reactions
of
Although ordinary ethers are relatively inert, the strained structure of the oxacyclopropane
9-9
Oxacyclopropanes
of
Oxacyclopropanes
Reactions
of
makes
possiblenucleophilic
nucleophilic
ring-opening
reactions.
This
details
of these
akes
possible
ring-opening
reactions.
Thissection
sectionpresents
presents
details
of the
makes possible nucleophilic ring-opening reactions. This section presents details of thes
Although
ordinary
ethers
are
relatively
inert,
the
strained
structure
of
the
oxacyclopropanes
ordinary ethers
ethersare
are relatively
relatively
inert,the
the strained
strainedstructure
structureofofofthe
theoxacyclopropanes
oxacyclopropanes
Although
are
inert,
the
structure
the
processes. inert,
processes.ordinary
ocesses.
Although
ordinary
ethers
are
relatively
inert,
the
strained
structure
ofofsecondary
the
oxacyclopropanes
ordinary ethers
ethers
arerelatively
relatively
inert,
thestrained
strained
structure
theoxacyclopropanes
oxacyclopropanes
nucleophiles.
Carbocation
formation
follows
protonation
when
and tertiary groups

makes possible
nucleophilic
ring-opening
reactions.
This
section
presents
details
ofofthese
these
possible nucleophilic
nucleophilic ring-opening
ring-openingreactions.
reactions.This
Thissection
sectionpresents
presentsdetails
detailsofof
these
makes
ring-opening
reactions.
This
section
presents
details
these
makes possible
possible nucleophilic
nucleophilic
reactions.
This
presents
details
ofof
these
nucleophilic
ring-opening
reactions.
This
sectiongroup
presents
details
these
are present,ring-opening
leading to SN1 and
E1 products.
The section
hydroxy
of alcohols
can be
protected
processes.
ring opening of oxacyclopropanes by SN2 is
processes.
in the form ofNucleophilic
a tert-butyl ether.
processes.

Nucleophilicring
ringopening
opening
of oxacyclopropanes
regioselective
and stereospecic by
ucleophilic
of
oxacyclopropanes
bySNS2N2is is
Oxacyclopropane
to bimolecular ring opening by anionic nucleophiles. Becaus
regioselective
and
stereospeci
ccofis subject
9-9
Reactions
of
Oxacyclopropanes
Nucleophilic
ring
opening
of
oxacyclopropanes
by
SNNto2N2
2theisis
issame extent at either carbon
egioselective
and
stereospeci
ring
opening
of
oxacyclopropanes
by
of
the
symmetry
the
substrate,
substitution
occurs
Nucleophilic
opening
of
oxacyclopropanes
by
Nucleophilic ring
ring opening
opening of
of oxacyclopropanes
oxacyclopropanesby
bySS
SS
22
isis

Nucleophilic
ringAlthough
opening
oxacyclopropanes
by
SSNthenucleophiles.
isis
opening
of
oxacyclopropanes
by
The of
reaction
proceeds
by nucleophilic
attack,
with
ether
functioning as an
N22
ordinary
ethers
are ring
relatively
inert, the
structure
of oxygen
the oxacyclopropanes
Oxacyclopropane is subject
to
bimolecular
opening
bystrained
anionic
Because

Oxacyclopropane
subject
to bimolecular
opening by anionic nucleophiles. Because
and
regioselective
and
stereospeci
cring
regioselective
stereospeci
ccc
intramolecular
group.
and
stereospeci
cleaving
xacyclopropane
isisand
subject
to
bimolecular
ring
opening
by anionic
nucleophiles.
Becau
makes
possible
nucleophilic
ring-opening
reactions.
This section
presents details of
these
regioselective
stereospeci
and
stereospeci
of the symmetry ofand
the
substrate,
substitution
occurs to the same extent at either carbon.
processes.
>
O
the symmetry ofis
substrate,
substitution
toby
the
samenucleophiles.
extent
at either
carbo
is
pG
Oxacyclopropane
isthe
subject
tobimolecular
bimolecular
ringoccurs
opening
by
anionic
nucleophiles.
Because
Oxacyclopropane
subject
to
bimolecular
ring
opening
by
anionic
nucleophiles.
Because
subject
to
ring
opening
anionic
Because
is
D
>
O
H
OH
The
reaction
proceeds
by
nucleophilic
attack,
with
the
ether
oxygen
functioning
as
an
p


Oxacyclopropane
is
subject
to
bimolecular
ring
opening
by
anionic
nucleophiles.
Because
Oxacyclopropane
is
subject
to
bimolecular
ring
opening
by
anionic
nucleophiles.
Because
>
>
>
>
>
O
O
CH
CH
)
)
CH
OCH
CH
CH
CH
HOCH
S
SCHa
S

2
2
3
2
2
3
2
2as
p
p
p
p
p
of
the
symmetry
of
the
substrate,
substitution
occurs
to
the
same
extent
at
either
carbon.
he
reaction
proceeds
nucleophilic
attack,
withtototo
thethe
ether
functioning
>
HO
symmetry
of the
theby
substrate,
substitution
occurs
the
sameoxygen
extentatat
at
eithercarbon.
carbon.
p)
of
the
substrate,
substitution
occurs
same
extent
either
carbon.
the
of
substrate,
substitution
occurs
same
extent
either
of
intramolecular
leaving
group.
of
the symmetry
symmetry
of
the
substrate,
substitution
occurs
totothe
the
same
extent
at
either
carbon.
of
the
substrate,
substitution
occurs
the
same
extent
at
either
carbon.
Oxacyclopropane
2-Methylthioethano
Nucleophilic
ring
opening
of
oxacyclopropanes
by
S
2
is
N
The
reaction
proceeds
by
nucleophilic
attack,
with
the
ether
oxygen
functioning
as
an
tramolecular
reaction leaving
proceedsgroup.
by nucleophilic
nucleophilic attack,
attack,with
withthe
theether
etheroxygen
oxygenfunctioning
functioningasasasanan
an
The reaction
proceeds
by
nucleophilic
attack,
with
the
ether
oxygen
functioning
proceeds
by


The reaction proceeds

by
attack,
ether
oxygen
functioning
asveryanan
proceeds
by nucleophilic
nucleophilic
attack, iswith
with
the
ether
oxygen
functioning
regioselective
stereospeci
cthe
This SNand
2 transformation
unusual
for two
reasons.
First, alkoxides
are usually as
poo
intramolecular
leaving
group.
>
intramolecular
leaving
group. leaving
O
intramolecular
leaving
group.
leaving
group.
groups. Second, the leaving group does O
not>actually leave; it stays bound to th
intramolecular
leaving
group.
DpG
intramolecular
leaving
group.
H by
OHanionic nucleophiles. Because
>
Oxacyclopropane
is
subject
to
bimolecular
ring
opening
p
O


molecule. The
driving force
isO
the>
release
of strain as the ring
opens.
>
>
>
>
O
CH
CH
)
)
CH
OCH
CH
CH
CH
CH
HOCH
S
S
S

2
Dp2G>
3
2
2
3
2
2
3
psituation substitution
p occurs
p example,
O>
of thep
symmetryWhat
of the
substrate,
toH>
the
same extent
at either
carbon.o
>
OH
O
p
isthe
with unsymmetric
systems?
for
thepreaction
HO
O
pCH
p)Consider,
p
>
>
D>
O
CH2 O
G 2
OCH
CH
HOCH
S) 2,2-dimethyloxacyclopropane
Satan
SCH
>
 CH
O
>
H
OH
The3>
reaction
proceeds)
by>
nucleophilic
attack,
with
the
ether
oxygen
functioning
as>
D
p
OG
>
p
2CHwith
2O
3 HH
2 CH
2
>
>
O
O
methoxide.
There
are
two
possible
reaction
sites:
th
OH
OH

HO
OH
p
p
p
p
p
p
p
Oxacyclopropane
>
 p
2-Methylthioethanol


D
HO
G
p) and
OH
D222p
S>
S>
S>

p
GCH
>
>
>
>
>
>
>
>
>
O
O>
CH
O
O
CH2222
OH
2give
2O
33 HHO
22
2
3 3 to
)
)
CH
OCH
CH
HOCH
)
CH
OCH
CH
CH
CH
HOCH
S
S>
S



)
)
CH3333>
OCH
CH
CH
HOCH
CH
CH
S)
SCH
SCH
 intramolecular
S
S
S
leaving
group.
carbon
(a), to22
1-methoxy-2-methyl-2-propanol,
at>
the 2tertiary
carbon
p

2
2
2
3
2
33
2>
3(b),
2CH
2O
2CH
p
p
p
p
p
p
p
p
p
p
 primary

p
p
p
p
p
>
>
>
>
>
>

HO
)
O
O
CH
CH
>
>
)
)
CH
OCH
CH
CH
CH
HOCH
S
S
S
p

>
HO
)
HO
)
HO
)
2
2
>
>
>
>
>
22CH22 Op
33
2 2 CH
2p
3 3a
p>
psystem
CH2 O CH2
p
xacyclopropane
pp
)p
OCH
CH
HOCH
S) yield 2-methoxy-2-methyl-1-propanol.
SCH
SCH
 CH33p
2-Methylthioethan
Evidently,
this
transforms
solely
through
path
2p

p
p
p
HO
)
p
>
HO
p) are2-Methylthioethanol
Oxacyclopropane
2-Methylthioethanol
This SN2 transformation is
usually
very poor
Oxacyclopropane
>
2-Methylthioethanol
2-Methylthioethanol
O unusual for two reasons. First, alkoxides
Oxacyclopropane
Oxacyclopropane
2-Methylthioethanol
DpG
O>
H
OH
Oxacyclopropane
2-Methylthioethanol
p
Nucleophilic
Ring Opening
of an Unsymmetrically
Substituted
Oxacyclopropane
leaving
groups. Second,
theunusual
leaving
group
not)actually
leave;
stays
bound
to2>
>
>
O>
CHis
CH
his
SN2 transformation
reasons.
alkoxides
usually
very
po3
CHtwo
OCH
CH
HOCH
S)does
Sthe
SCH3 it are
for
2O
2
3>
2CH2
p
pFirst,
p
p 2CH
p
>
HO
)
pusually
S
2
transformation
is
unusual
for
two
reasons.
First,
alkoxides
are
usually
very
poor
This
transformation
is
unusual
for
two
reasons.
First,
alkoxides
are
very
poor
N
S
2
transformation
is
unusual
for
two
reasons.
First,
alkoxides
are
usually
very
poor
N
N2 transformation
N
molecule.
The Second,
drivingOxacyclopropane
force
isHthe
release
strain
the ring
opens.are
HO
OH twoof
O leave;
@
3
This
is
for
reasons.
alkoxides
very
poor
G
aving
the
leaving
group
does
notasFirst,
actually
it,usually
stays
bound
toCHCHth
2-Methylthioethanol
N
This S
Sgroups.
transformation
is unusual
unusual
for
two
reasons.
First,
alkoxides
are
usually
very
poor
H&
Gthe
O , not
CH OH actually
CH
N2
O stays
CH OH bound
CH
groups.
Second,
the
leaving
group
does
leave;
it
stays
to
leaving
Second,
the
leaving
group
does
not
actually
leave;
it
bound
to
the
groups.
Second,
the
leaving
group
does
not
actually
leave;
it
stays
bound
to
the
C
C
Cto C
C group does
C O Cleave;
Whatgroups.
is the
situation
withleaving
unsymmetric
systems?
Consider,
foropens.
example,
thebound
reaction
of
GC release
leaving
Second,
the
ititstays
a not actually
olecule.
The
driving
force
the
of
strain
as
the
ring
bstaysbound
MODEL
BUILDING
H (very
leaving
groups.
Second,
the
leaving
does
notas
actually
leave;
tothe
the
CH3is of
Hreasons.
CH3 alkoxides
( ring
( group
(First,
This
SN2 is
transformation
unusual
for
two
are usually
poor
molecule.
driving
force
is
the
release
of
strain
as
the
ring
opens.
The
driving
force
is
the
release
strain
the
opens.
molecule.
The
driving
force
is
the
release
of
strain
as
the
ring
opens.
molecule.
driving
force
is
the
release
of
strain
as
the
ring
opens.
The
CH
O
CH
OCH
CH
H
H
2,2-dimethyloxacyclopropane
with
There
are
two
possible
reaction
sites:
at tothethe
3 the methoxide.
3
3
molecule.
drivingleaving
force
is
release
strain
as
the
opens.
groups.
theof
leaving
group
does
leave;
it stays
bound
What
is isThe
the
situation
with
systems?
Consider,
for
example,
the
reaction
anot
b actually
molecule.
force
isunsymmetric
theSecond,
release
of
strain
as
the ring
ring
opens.
What
the
situation
with
unsymmetric
systems?
Consider,
example,
the
reaction
situation
with
unsymmetric
systems?
Consider,
for
example,
the
reaction
isThe
thedriving
situation
with
unsymmetric
systems?
Consider,
for
example,
the
reaction
What
is
the
1-Methoxy2-Methoxyprimary
carbon
(a),
tomolecule.
give
1-methoxy-2-methyl-2-propanol,
andasfor
at
the
tertiary
carbon
(b),ofof
toof
The
driving force is
the release
of strain
the
opens. the
What
with
unsymmetric
systems?
Consider,
for
example,
reaction
of
2-dimethyloxacyclopropane
with
methoxide.
There2,2-Dimethyloxacyclopropane
are
two
possible
reaction
sites:
at
What is
is the
the situation
situation
with
unsymmetric
systems?
Consider,
forring
example,
the
reaction
ofth
2-methyl-2-propanol
2-methyl-1-propanol
2,2-dimethyloxacyclopropane
with
methoxide.
There
are
two
possible
reaction
sites:
at
2,2-dimethyloxacyclopropane
with
methoxide.
There
are
two
possible
reaction
sites:
at
the
2,2-dimethyloxacyclopropane
with
methoxide.
There
are
two
possible
reaction
sites:
atthe
the
What
is
the
situation
with
unsymmetric
systems?
Consider,
for
example,
the
reaction
yield
2-methoxy-2-methyl-1-propanol.
Evidently,
this
system
transforms
solely
through
path
a.of
(Notat
formed)
2,2-dimethyloxacyclopropane
with
methoxide.
There
are
two
possible
reaction
sites:
the
2,2-dimethyloxacyclopropane
with
methoxide.
There
are
two
possible
reaction
sites:
at
the
imary
carbon
(a),
to
give
1-methoxy-2-methyl-2-propanol,
and
at
the
tertiary
carbon
(b),
(a),
2,2-dimethyloxacyclopropane
with methoxide. There
are
two
possible
reaction
sites:
at
the
carbon
(a),
to
give
1-methoxy-2-methyl-2-propanol,
and
atatatthe
tertiary
carbon
(b),
toto
primary
to
give
1-methoxy-2-methyl-2-propanol,
and
the
tertiary
carbon
(b),
carbon
(a),
carbon
(a),
to
give
1-methoxy-2-methyl-2-propanol,
and
the
tertiary
carbon
(b),
primary
carbon
give
atatthe
tertiary
carbon
toto
Is (a),
this result
surprising?
No, because, asand
we know,
if there
is more
thancarbon
one(b),
possibility
carbon
toEvidently,
give
1-methoxy-2-methyl-2-propanol,
and
at
the
tertiary
(b),
to
primary
carbon (a),
(a), to
toprimary
give 1-methoxy-2-methyl-2-propanol,
1-methoxy-2-methyl-2-propanol,
and
the
tertiary
carbon
(b),
to
eld
2-methoxy-2-methyl-1-propanol.
this
system
transforms
solely
through
path
2-methoxy-2-methyl-1-propanol.
this
transforms
solely
through
path
a.a.
yield
2-methoxy-2-methyl-1-propanol.
Evidently,
this
system
transforms
solely
through
path
2-methoxy-2-methyl-1-propanol.
Evidently,
this
system
transforms
solely
through
path
Sof
will be at the
less system
substituted
carbon
center (Section
6-9).
This selectivity
ina.th
Nucleophilic
Ringyield
Opening
anEvidently,
Unsymmetrically
Substituted
Oxacyclopropane
N2 attack
yield
Evidently,
this
system
transforms
solely
through
path
a.
2-methoxy-2-methyl-1-propanol.
Evidently,
this
system
transforms
solely
through
path
a.
yield 2-methoxy-2-methyl-1-propanol.
2-methoxy-2-methyl-1-propanol.
Evidently,
system
transforms
path
a.
nucleophilic
opening of this
substituted
oxacyclopropanes
issolely
referredthrough
to as regioselectivity
because, of two possible and similar regions, the nucleophile attacks only one.
Ring
Opening
of
an
Unsymmetrically
Substituted
Oxacyclopropane
Ring
Opening
of
an
Unsymmetrically
Substituted
Oxacyclopropane
Unsymmetrically
Oxacyclopropane
HO
CHwe
HNucleophilic
Nucleophilic
Opening
Substituted
Nucleophilic
Ring
Opening
of
an
Unsymmetrically
Substituted
Oxacyclopropane
Owhen of
@ Nucleophilic
Nucleophilic
RingOpening
Opening
ofRing
an
Unsymmetrically
Substituted
Oxacyclopropane
3 find
Inan
addition,
thean
ringUnsymmetrically
opens atSubstituted
aSubstituted
stereocenter,
inversion
isOxacyclopropane
observed. Thus,
GOH Ring
Opening
of
Unsymmetrically
Oxacyclopropane
& Nucleophilic
Nucleophilic Ring
Ring
ofthe
anrules
Unsymmetrically
Oxacyclopropane
G
, CH OH that
CH OOpening
CHapply
of nucleophilic substitution
alkyl derivatives
also
Odeveloped
, CH OH for simple
CHSubstituted
3
C
C
CH3
H
OH
CHO CCH
O
C
C
C
C
O
@
to strained cyclic
ethers.
HO
OH
HG
O
@ GOH
a G
HO
CH
3
OH
3CH
G
O
HO
&
H
@
b
HO
CH
3
OH
H
O
G
O
,
CH
OH
CH
G
O
CH
CH O , CH OH H
CH3
H ( O ( CH3C O CCH
HO
(OH
H
( GGC CH
@@
33333 3 3
O
OH
CH
,, CH
C
O
CH
OH
CHG
COH
CH
C OO
G
C
C3OH
CH
&&& MODEL
OH
HO
CH
O
,,,CH
CH
H
OH
O,,,CH
CH
OH
CH

CH
CH
CH
G
333CH
G
CH
OH
CH
O, CH
CH
OH
CH
CH
a O CCCH3
CH
33O
33OH
G
O
OCH
3O
CH
,
CH
CH
H
H
O
,
CH
OH
CH
b
O
,
CH
OH
CH
C
3O
3OH
3
BUILDING
G
O
,
CH
OH
CH
3
3
H
3
3
3
C
C
CH
O
C
C
C
C
C
C
O

C
C
CH
H
CH
C
(
(
(
(C
O ,3 CH OH
CH
G
C
C
CCethers
O
C
CCCCC H
and
organometallic
reagents
strained
OH 3Hydride C
O
C C CC
C CC CH
CaO
a, CH3CH
CH3 33
O
C&G
3O a
OH
CH
b, CH3convert
GC
bC
CHCH
CH3O
HCGCC COCH
HHH((C
3O a a
3bb
3
H
(((C
( (C CH
G
33
333 a b
CH
H
CH
aaa
H((C( C
bb b
CH
H
CH
intoH
alcohols
GC (C((((CCH
CH
( C O C((CH
333
HH
a
CH
H
CH
(
3 3333
O
OCH
CH
H
1-Methoxy2,2-Dimethyloxacyclopropane
2-Methoxyb
3
3
3
3
O
CH
OCH
CH
3
3
H
H
H
CH
HH
CH
333 3
33 3
(CH
(CH
O
CH
OCH
3
(Hof 2-MethoxyCH
H( aa bb 2,2-Dimethyloxacyclopropane
1-MethoxyOCH
CH
OCH
O
HH
3
3 333 3
H
The highly
hydride is able to open 2-methyl-1-propanol
the rings
oxacyclopropanes
ethyl-2-propanol
aaa bbb lithium
O
CH3aluminum
OCH3 3
CH
H2-methyl-1-propanol
2-methyl-2-propanol
H reactive
3
3
aa bb







O O
O
O
O
O
OO

C
G

&

33
3
3
3




33
33 
3

CC
G G
C
CCC C
G
G
& GG
& G& &&&@ &@ CG G
G
GG
@@ @ G GG
@& @G

C
G

&

C
CCCCCC

33
3
3
3

G
GGG G

1-Methoxy1-Methoxy-







O
O O
O
O
O
OO

33
3
3
3

a reaction leading to alcohols. Ordinary ethers, lacking the ring strain

oxacyclopropanes
2,2-Dimethyloxacyclopropane
2-Methoxy2,2-Dimethyloxacyclopropane
2-Methoxy(Notofformed)
a b
(Not formed)
2,2-Dimethyloxacyclopropane
2-Methoxy-

2,2-Dimethyloxacyclopropane
1-Methoxy1-Methoxy2,2-Dimethyloxacyclopropane
2-Methoxydo not react with LiAlH4. The reaction also proceeds by2-methyl-1-propanol
the S2-MethoxyThus, in
1-Methoxy2,2-Dimethyloxacyclopropane
2-MethoxyN2 mechanism.
Methoxy2,2-Dimethyloxacyclopropane
2-Methoxyethyl-2-propanol
2-methyl-1-propanol
ethyl-2-propanol
2-methyl-1-propanol
1-Methoxy2,2-Dimethyloxacyclopropane
2-Methoxyethyl-2-propanol
ethyl-2-propanol
2-methyl-1-propanol
unsymmetric
the hydride
attacks
the less
substituted
side;
when
the reacting
carbon
ethyl-2-propanol
2-methyl-1-propanol
Is thisNo,
resultbecause,
surprising? systems,
No,
asifwe
know,
there
isthan
more
than
one
possibility,
yl-2-propanol
2-methyl-1-propano
(Not
formed)
(Not
formed)
Is this result surprising?
webecause,
know,
there
isif more
one
possibility,
ethyl-2-propanol
2-methyl-1-propanol
(Not
constitutes aas
stereocenter,
inversion
is observed.
(Not
formed)
(Notformed)
formed)
S 2 attack will be at the less substituted carbon center (Section 6-9). This
(Notselectivity
formed) in the

N
(Not(Not
formed)
formed)
(Not
formed)
SN2 attack will be at nucleophilic
the
less substituted
carbon center
(Section 6-9).
This to
selectivity
in the
opening of
oxacyclopropanes
is referred
as
regioselectivity,
as
we
ifif
than
possibility,
Is this
surprising? No,
No, because,
because,
assubstituted
we know,
know,
if there
there isis
is more
more
thanone
one
possibility,
this result
result surprising?
Is
surprising?
No,
because,
as
we
know,
there
more
than
one
possibility,

S
attack will
will opening
be at
at the
the less
less
substituted carbon
carbon
center (Section
(Section6-9).
6-9).
Thisselectivity
selectivity
in
the
nucleophilic
substituted
oxacyclopropanes
referred
to as
as in
regio
of substituted
oxacyclopropanes
isis referred
to
regios
SNNN22 attack
be
substituted
center
This
the
opening
of
substituted
oxacyclopropanes
is referred
to as regioselectivity,
nucleophilic
opening
of substituted
substituted
oxacyclopropanes
referred
regioselectivity,
nucleophilic
of
oxacyclopropanes
isis referred
toto asasattacks
regioselectivity,
because,
and similar
similar
regions, the
the
nucleophile
attacks
only one
one
of opening
two possible
and
regions,
nucleophile
only
because, of
two
possible
and
similar
regions,
the
nucleophile
attacks
only
one.
because,
of
two
possible
and
similar
regions,
the
nucleophile
attacks
only
one.
and ring
similar
regions,
the nucleophileinversion
attacks only
one.
because,
of two possible
ring
opens
at aa stereocenter,
stereocenter,
inversion
observed.
Th
In addition,
addition,
when
the
opens
at
isis observed.
Thu
In
when
the
ring
opens
at
aa stereocenter,
inversion
isis observed.
Thus,
we
fifind
In
addition,
when
the
ring
opens
at
stereocenter,
inversion
observed.
Thus,
we
nd
the ring opens
at a stereocenter,
inversion
is
observed.
Thus,
we find
Inthe
addition,
when
that
nucleophilic
substitution
developed
foralkyl
simple
alkyl
derivatives
rulesof
of
nucleophilic
substitution
developed
for
simple
alkyl
derivatives
that the
rules
nucleophilic
substitution
developed
for
simple
derivatives
also
apply
that
the rules
rules of
of nucleophilic
nucleophilic substitution
substitution developed
developed for
for simple
simple alkyl
alkylderivatives
derivativesalso
alsoapply
apply
that the
to
strainedcyclic
cyclic
ethers.
ethers.
to strained
to
strained
cyclic
ethers.
to strained cyclic ethers.

Hydride and
and
organometallic
reagents
convert
strained
ethers
Hydride
organometallic
reagents
convert
strained
ethers ethers
Hydride
organometallic
reagents
convert
strained
ethers
andorganometallic
organometallic
reagents
convert
strained
reagents
convert
strained
ethers
into
alcohols
into
alcohols
into alcohols
The highly
The
highly reactive
reactive lithium
lithium aluminum
aluminum hydride
hydrideisisable
ableto
toopen
openthe
therings
ringsofofoxacyclopropanes,
oxacyclopropanes,

The
lithium
aluminum
hydride
ableis
toable
opento
theopen
ringsthe
ofoxacyclopropanes,
oxacyclopropanes,
reactive
lithium
aluminum
hydride
isis able
to
open
the
rings
of
The highly
highly
reactive
lithium
aluminum
hydride
rings
The
aluminum
hydride
is
able
to
open
the
ringsof
ofoxacyclo
oxacycl
reaction
leading
to
alcohols.
Ordinary
ethers,
lacking
the
ring
strain
of
oxacyclopropanes,
reaction leading
leading to
to alcohols.
aa reaction
alcohols. Ordinary
Ordinary ethers,
ethers, lacking
lacking the
the ring
ringstrain
strainof
ofoxacyclopropanes,
oxacyclopropanes,
leading
to
alcohols.
Ordinary
ethers,
lacking
the
ring
strain
oxacyclo
ado
alcohols.
Ordinary
ethers,
lacking
the
ring
strain of
ofThus,
oxacycl
doreaction
not
react
with
LiAlH
.
The
reaction
also
proceeds
by
the
S
2
mechanism.
inin
not react
react with
with LiAlH
LiAlH4444.. The
The reaction
reaction also
also proceeds
proceeds by
by the
the SSNNNN22 mechanism.
mechanism. Thus,
Thus, in
not
unsymmetric
systems,
the
hydride
attacks
the
less
substituted
side;
when
the
reacting
carbon
do
not reactsystems,
with LiAlH
reaction
proceeds
the
SSreacting
22 mechanism
The
reaction
also
proceeds
by
the
mechanism
44. The
NN
systems,
unsymmetric
the hydride
hydride
attacks
the less
lessalso
substituted
side;by
when
the
reacting
carbon
the
attacks
the
substituted
side;
when
the
carbon
constitutes a stereocenter,
inversion
is
observed.
systems, the
hydride
attacks
unsymmetric
hydride
attacks the
the less
less substituted
substituted side;
side;when
whenthe
thereacti
reac
constitutes
stereocenter,
inversion
is observed.
observed.
a stereocenter,
inversion
is
constitutes a stereocenter, inversion
inversion is
is observed.
observed.

opapananeneses s
999---999 RRReeeaaaccctttiiiooonnnsss ooofff OOOxxxaaacccyycyccl loloo
ppp
rrorop

9-9 Reactions of Oxacyclopropanes

Ring Opening
Openingof
ofan
anOxacyclopropane
Oxacyclopropane
Ring
Opening
of
an
Oxacyclopropane
Ring
by Lithium
LithiumAluminum
AluminumHydride
Hydride
by
Lithium
Aluminum
Hydride
by
O
O

2 2

CC

Opening of
Lithium Aluminum
Lesshindered
hinderedHydride
Less
hindered
Less

OH
HHH
GOH
@@@
GGOH
H
HH&&&
CCC CCCCCC
GGG
((( HHH
HHH
RRR
GGG

O
O

O
LiAlH44,,44(CH
,(CH
(CH33CH
)O
O
1.1.LiAlH
LiAlH
CH
33CH
22O
O
1.
222O
2))2
2

,H
HH22OO
O
HH,,,H
2.2.H
22O
2.
H
2.
OC
CCCC
CCO
O
C
an
H (( Oxacyclopropane
H
H
((( H
H
R
R
H
R
H

Inversion on
onOxacyclopropane
Oxacyclopropane
Opening
Opening
Inversion
on
Oxacyclopropane
Opening
H@
1. LiAlH4, (CHInversion
3CH2)2O
GOH

H&
2. H , H2O
OH
OH
OH

)
)
CH3333
)H CH
CH
H
H

red

GC
H

1.1.LiAlD
LiAlD
1.
LiAlD
44
44
1.
LiAlD

2.
2.2.HH
,H
22
2O
HH,,,H
HH
OO
2O

O
O
O

H
R

CC
( H
R

CH
CH
CH
33
33
HHH

DDD
99.4%
99.4%
99.4%
DDand
andOH
OHare
aretrans,
trans,not
notcis
cis

andOH
OHare
aretrans,
trans,not
notcis
cis
ion on Oxacyclopropane OpeningDDand

Exercise
Exercise 9-21
9-21

OH of an
Working
Working with
with the
the Concepts:
Concepts:
Retrosynthetic
Analysis
Oxacyclopropane
Concepts:AAARetrosynthetic
RetrosyntheticAnalysis
Analysisof
ofan
anOxacyclopropane
Oxacyclopropane
1. LiAlD4
Applying
the
principles
of
retrosynthetic
analysis,
as
described
in
Section
8-9,

Applying the
principles
of
retrosynthetic
analysis,
as
described
in
Section
8-9,
which
oxacycloprinciples
of
retrosynthetic
analysis,
as
described
in
Section
8-9,which
whichoxacyclooxacyclo2.
H
,
H
O
CH
3 with LiAlH , followed
propane would be the 2best precursor to racemic 3-hexanol after treatment
propane
44
4,4,followed
propane would
would be
be the
the best
best precursor
precursor to
to racemic
racemic 3-hexanol
3-hexanol after
after treatment
treatmentwith
withLiAlH
LiAlH
followed

acidic aqueous
work-up?
by
by
work-up?
by acidic
acidic aqueous
aqueous work-up?
Strategy
CH
Strategy
3
Strategy

The
first
thing to
do
The
is
write
the
structure
of
3-hexanol.
Then
look
see
how
many
pathways
do is
is write
write the
the structure
structureof
of3-hexanol.
3-hexanol.Then
Thenlook
looktototosee
seehow
howmany
manypathways
pathways
The fi
first
rst thing
thing to
to do
lead
lead
to
this
structure
from
oxacyclopropanes
and
examine
each
path
for
feasibility.
lead to
to this
this structure
structure from
from oxacyclopropanes
oxacyclopropanesand
andexamine
examineeach
eachpath
pathfor
forfeasibility.
feasibility.
Solution
Solution
Solution
We
recognize two
possible retrosynthetic
paths to
3-hexanol from
oxacyclopropanes: removal
of
two
two possible
possible retrosynthetic
retrosynthetic paths
paths to
to 3-hexanol
3-hexanol from
fromoxacyclopropanes:
oxacyclopropanes:removal
removalofof
We
We recognize
recognize
2 with simultaneous ring closure either to the left side or the right side. In our draw:2
2
an
anti H
an
an anti
anti H
H::2 with
with simultaneous
simultaneous ring
ring closure
closure either
either to
to the
the left
leftside
sideororthe
theright
rightside.
side.InInour
ourdrawdrawing,
these
two
pathways
are
indicated
by
aa and
b,
respectively.
D
and
OH
are
trans,
not
cis
ing,
these
two
pathways
are
indicated
by
and
b,
respectively.
ing, these two pathways are indicated by a and b, respectively.
anti
anti
anti
anti anti
anti
aa
bb
a
b

D
99.4%

H H
H
H
H
H H
H
H/ H
H/ H

O
OO

OO
O

/
/
/
/

: A Retrosynthetic
Analysis of an Oxacyclopropane
00

00
OH
OH

OH
3-Hexanol
3-Hexanol
3-Hexanol

Via a

Via b

Via a
a
Via b
b
ynthetic analysis, as described in Via
Section
8-9, Via
which
oxacycloVia
a
Via b

Exercise 9-21

Working with the Concepts: A Retrosynthetic Analysis of an Oxacyclopropane

Applying the principles of retrosynthetic analysis, as described in Section 8-9, which oxacyclopropane would be the best precursor to racemic 3-hexanol after treatment with LiAlH4, followed
by acidic aqueous work-up?
Strategy
The first thing to do is write the structure of 3-hexanol. Then look to see how many pathways
lead to this structure from oxacyclopropanes and examine each path for feasibility.
Solution
We recognize two possible retrosynthetic paths to 3-hexanol from oxacyclopropanes: removal of
an anti H:2 with simultaneous ring closure either to the left side or the right side. In our drawing, these two pathways are indicated by a and b, respectively.
anti
a

anti
b
O

H H H H
/
/

0
OH
3-Hexanol

Via a

Via b

Now that we have drawn the two possible precursors to 3-hexanol, let us see which one is better
at making the desired product when it is reacted with LiAlH4. (Caution: Remember that both carbons
of an oxacyclopropane are electrophilic, so attack by hydride can occur in two possible ways.)
Inspection of the precursor derived from retrosynthetic path a shows that it is unsymmetrical.
Because both ring carbons are equally hindered, ring opening by hydride will give the two isomers,
2- and 3-hexanol.
On the other hand, retrosynthetic path b furnishes a symmetric oxacyclopropane in which the
regiochemistry of hydride opening is immaterial. Hence this precursor is best.
O

H
Unsymmetric:
will give 2- and
3-hexanol

H
Symmetric:
will give only
3-hexanol

Chapter 9
MODEL BUILDING

361

F
u rr tt h
h e r R ee aa cc tt ii oo nn ss oo ff AA ll cc oohhoollss aanndd tthhee CChheemmi isst tr ryy oof f EEt thheer rs s
FFu
R ee aa cc tt ii oo nn ss oo ff AAllccoohhoollss aanndd tthhee CChheemmi isst tr ry y oof f EEt thhe er rs s
u r t heerr RR
362

Further Reactions of Alcohols and the Chemistry of Ethers

Chapter 9

Exercise
9-22
Exercise
9-22
Exercise 9-22
9-22

Exercise 9-22

Try
ItIt Yourself
Yourself
Try
TryIt
Yourself
Yourself

Try It Yourself
(2R)-Butanol can be made by LiAlH4 reduction of an oxacyclopropane. Which one?

(2R)-Butanol
can
be
made
by
LiAlH
reductionof
ofan
anoxacyclopropane.
oxacyclopropane.Which
Which
one?
(2R)-Butanol
reduction
of
an
oxacyclopropane.
Which
one?
(2R)-Butanol
can
be
made
one?
by
LiAlH
(2R)-Butanol can
can be
be made
made by
by LiAlH
LiAlH444444 reduction
reduction
of
an
oxacyclopropane.
Which
one?

In contrast with haloalkanes (Section 8-8), oxacyclopropanes are sufficiently reactiv

electrophiles to be attacked by organometallic compounds. Thus, Grignard reagents and

F u r t h e r alkyllithium
R e(Section
a c t i o n compounds
s o8-8),
f8-8),
A l c oundergo
hoxacyclopropanes
o l s a2-hydroxyethylation
n d t h e C h e m iare
sby
t r ether
y suffi
osuffi
f ring
E tciently
hopening,
ers
C h a p t e r with
9
In
with
haloalkanes
(Section
are
reactive
following
th
haloalkanes
oxacyclopropanes
In
contrast
with
haloalkanes
(Section
8-8),
oxacyclopropanes
are
suffi
ciently
reactive
contrast
with
haloalkanes
(Section
8-8),
oxacyclopropanes
ciently
reactive
In contrast
are
suffi
SN2 mechanism. This reaction constitutes a two-carbon homologation of an alkyl chain, a
electrophiles
attacked
by
organometallic
compounds.
Thus,
Grignard
reagents
and
organometallic
compounds.
Thus,
Grignard
reagents
and
to
be
attacked
organometallic
compounds.
Grignard
reagents
and
electrophiles
to be
be attacked
attacked by
byopposed
organometallic
compounds.
by
to the one-carbon
homologation of Thus,
alkyl
organometallic
reagents
by formaldehyd
electrophiles to
Thus,
Grignard
reagents
and
alkyllithium
compounds
undergo
2-hydroxyethylation
byether
etherring
ringopening,
opening,
following
the
(Sections
8-8 and 8-9).
2-hydroxyethylation
by
ether
ring
opening,
following
the
compounds
2-hydroxyethylation
by
following
the
alkyllithium
compounds undergo
undergo
2-hydroxyethylation
undergo
alkyllithium compounds
by
ether
ring
opening,
following
the
Exercise 9-22
SS
This
reaction
constitutes
two-carbon
homologation
ofanan
an
alkyl
chain,
two-carbon
homologation
alkyl
chain,
asas
mechanism.
aaaatwo-carbon
homologation
ofof
alkyl
chain,
asas
Oxacyclopropane
Ring Opening
by a Grignard Reagent:
2-Hydroxyethylation
reaction
This
mechanism. This
This reaction
reaction constitutes
constitutes
two-carbon
SNNN222mechanism.
homologation
of
an
alkyl
chain,
Try It Yourself
opposed
one-carbon
homologation
ofalkyl
alkylorganometallic
organometallic
reagents
by
formaldehyde
O
1. THF
to
the
of
reagents
by
formaldehyde
of
alkyl
organometallic
reagents
by
formaldehyde
opposed
one-carbon
theone-carbon
one-carbon homologation
homologation
of
alkyl
organometallic
opposedto
tothe
by
formaldehyde
,HO
2. H reagents
LiAlH
an 2oxacyclopropane.
WhichCH
one?
CH2by 
CHreduction
MgBr
3CH2CHof
2CH
3CH2 CH2 CH2 CH2 CH2OH
(Sections
8-9).
8-8
and
(Sections
and 8-9).
8-9). (2R)-Butanol Hcan2CbeOmade
8-9).
(Sections 8-8
8-8 and
62%

362

O
O
O
O
O

O
O
O
O
O

In contrast
with haloalkanes (Section
8-8), oxacyclopropanes
are suffi
ciently2-hydroxyethylated
reactive
Oxacyclopropane
Butylmagnesium
bromide
1-Hexanol:
butyl
Oxacyclopropane
Opening
by
2-Hydroxyethylation
Oxacyclopropane
Ring
Opening
Grignard
Reagent:
2-Hydroxyethylation
Oxacyclopropane
Grignard
Reagent:
2-Hydroxyethylation
electrophiles
to be attacked
organometallic Reagent:
compounds.
Thus,
Grignard reagents and
Oxacyclopropane Ring
Ring
by aaabyGrignard
Grignard
Opening
Reagent:
2-Hydroxyethylation
alkyllithium compounds undergo 2-hydroxyethylation by ether ring opening, following the
Exercise 9-23
1.
THF
SN2 mechanism. This reaction constitutes
a
two-carbon
homologation
of
an
alkyl
chain,
as
OO
1.
THF
1.
THF
1.
THF
O
1. THF





,,of
O
2.

opposed to the
one-carbon
alkyl
by formaldehyde
22
,H
H
2.H
H
H
2.
H
,,H
OO organometallic reagents
2.
H
Propose
an effihomologation
cient synthesis
of
3,3-dimethyl-1-butanol
from starting
materials containing no more
22O
H
2.
H
222O
O

CH
CH
CH
CH
CH
8-8than
8-9).
2
2MgBr
3
2
2 CH
22CH
22CH
22OH
CH
CH2222CH
CH
CH
CH
CH
CH
CH
OCH
HH
CH
MgBr
CH
CH
CH
CH
 CH
H2222CC
CO
CH22222 
CH(Sections
MgBr(Hint: Consider the product
CH
OH
retrosynthetically
a CH
2-hydroxyethylated
33CH
3333
22
2
2 CH
2OH
33
2and
22
2 CH
2tert-butyl.)
2 four22carbons.
22 2as2
22

62%
Oxacyclopropane Ring Opening by a Grignard Reagent: 2-Hydroxyethylation
62%
62%
62%

62%

O
Oxacyclopropane
Butylmagnesium
bromide
Oxacyclopropane
Butylmagnesium
bromide
Butylmagnesium
Butylmagnesium
bromide
Butylmagnesium
bromide
Oxacyclopropane
Oxacyclopropane
CHEM I CAL HIGH
LIHGH
T 9-3 bromide
C O CH  CH CH CH CH
2

2MgBr

Hydrolytic
Kinetic Resolution
of Oxacyclopropanes
Oxacyclopropane
Butylmagnesium bromide
Exercise
9-23
Exercise
9-23
Exercise
Exercise9-23
9-23
As we pointed out in Chemical Highlight 5-5, nature is

1-Hexanol:
2-hydroxyethylated
butyl
1-Hexanol:
2-hydroxyethylated
butyl
1-Hexanol:
2-hydroxyethylated
1-Hexanol:
butyl
1-Hexanol:
2-hydroxyethylated
butyl

1. THF

2. H , H2O

CH3CH2 CH2 CH2 CH2 CH2OH

62%

1-Hexanol: 2-hydroxyethylated butyl

In our example, the most obvious feature is that members of

Exercise
9-23
handed
and
shows
great,
if not
preference for
the respective
groups
are shaped
completely differently
and
Propose
an
effi
cient
synthesis
of exclusive,
3,3-dimethyl-1-butanol
from
materials
containing
no
more
Propose
an
effi
cient
synthesis
3,3-dimethyl-1-butanol
from
starting
no
more
efficient
cient
synthesis
3,3-dimethyl-1-butanol
from
no
more
Propose
an
synthesis
3,3-dimethyl-1-butanol
from
starting
materials
containing
with
only
one of twoof
enantiomers
of a chiral comcould
separatedmaterials
bymaterials
an achiralcontaining
device,
such as
ano
sieve.
cient
synthesis
of
3,3-dimethyl-1-butanol
frombestarting
starting
containing
more
Proposereactions
an effi
Propose
an effi
cient
synthesis
3,3-dimethyl-1-butanol
startingtwo
materials
no tert-butyl.)
morewould be
than
four
carbons.
(Hint:
Consider
the
product
retrosynthetically
as
pound.
This preference
of particular
signifi
cance inof
drug
From thefrom
resulting
piles, containing
the right hands
than
four
carbons.
(Hint:
Consider
the
product
retrosynthetically
as
2-hydroxyethylated
tert-butyl.)
carbons.
(Hint:isConsider
Consider
product
retrosynthetically
tert-butyl.)
than
carbons.
(Hint:
the
product
retrosynthetically
asasaaaasa2-hydroxyethylated
2-hydroxyethylated
thanfour
four
(Hint:
Consider
the
retrosynthetically
tert-butyl.)
than four carbons.
(Hint:
Consider
the product retrosynthetically
a2-hydroxyethylated
2-hydroxyethylated tert-butyl.)
product

development, because usually only one enantiomer of a

recovered and recycled, leaving the right shoes separated
chiral drug is effective (Chemical Highlight 5-4). Therefore,
from the left ones.
the preparation of single enantiomers is an important green
A much better machine would be a fishing device, in
which the hook would be shaped like a right (or left) foot.
CHEM I Cchallenge
A L H IGfor
H Lthe
IGsynthetic
H T 9-3chemist (Chemical Highlight 3-1).
The classic way of meeting this challenge has been the
This machine would pull out only right shoes from the pile,
resolution of racemates via the (readily reversible) reaction
allowing their selective tagging, for example by attaching a
Hydrolytic
Kinetic
Resolution
of Oxacyclopropanes
with
an optically
pure compound
generating diastereomers
weight. Left and right shoes could then be separated by an
that can
beChemical
separatedHighlight
by chromatography
achiral
device
on thefeature
basis of
theirmembers
differingofweights. Such a
As we pointed
out in
5-5, nature isor fractionalIncrysour example,
the most
obvious
is that
tallization
(Section
5-8).
The approach
is equivalent
totheusing
at the
molecular
level differently
is called catalytic
kinetic resohanded and
shows great,
if not
exclusive,
preference
for
respectiveprocess
groups are
shaped
completely
and
a collection
hands to separate
a collection
pairs be separated
lution.byAn
is the hydrolysis
of methyloxacycloproreactions with
only oneof
of right
two enantiomers
of a chiral
com- of could
anexample
achiral device,
such as a sieve.
ofpreference
shoes. Once
allparticular
hands aresignifi
on,
the resulting
pane two
withpiles,
basicthe
water.
starting
pound. This
is of
cance
in drug collection
From the resulting
rightNormally,
hands would
be with a racemate,
5-5,
nature
is
In
our
example,
the
most
obvious
feature
is
that
members
of
ghlight
5-5,
nature
is
In
our
example,
the
most
obvious
feature
is
that
members
ofof
is divided
into
two only
groups,
rightthe
the
result
isleaving
racemic
1,2-propanediol.
This
is to be expected,
development,
because
usually
one namely,
enantiomer
ofcombinations
a example,
recovered
and
recycled,
the
right shoes
separated
ghlight
5-5,
nature
Inthe
our
example,
the
most
members
hlight
5-5,
nature
is
In
our
most
obvious
feature
isstates
that
hlight
5-5,
isisand
In
our
example,
the
most
obvious
feature
that
members
chiral drug
is nature
effectiveshoe
(Chemical
Highlight
Therefore,
the left
ones.
preference
for
the
respective
groups
are
shaped
completely
differently
and
hand/right
right
hand/left5-4).
shoe.
These
groups from
are
not
as the
two respective
transition is
for the
reactions
ofof
xclusive,
preference
for
the
respective
groups
are
shaped
completely
differently
and
xclusive,
preference
for
the
respective
groups
are
shaped
and
xclusive,
preference
for
the
groups
completely
differently
the preparation
of by
single
enantiomers
is an
important
green
A much are
better
machine
would
beare
a fienantiomeric
shing device,
in
related
mirror
symmetry,
hence
theyrespective
are
diastereomeric.
R
andshaped
S starting
ether
(Section
5-7).
xclusive,
preference
for
the
respective
groups
are
shaped
completely
differently
and
of
aa synthetic
chiral
comcould
be
separated
by
an
achiral
device,
such
as
aa sieve.
ntiomers
of
chiral
comby
an
achiral
device,
such
asasfoot.
sieve.
challenge for
the
chemist
(Chemicalcould
Highlightbe
3-1).separated
which the
hook
would
be shaped
like a right
(or left)
ntiomers
of
a
chiral
comcould
be
separated
by
an
achiral
device,
such
a
sieve.
ntiomers
of
aa ofchiral
comcould
be
by
ntiomers
ofway
chiral
comcould
be separated
separated
by an
an achiral
achiral
device,
aspile,
abe
sieve.
Thesignifi
classic
meeting
this challenge hasFrom
been thethe
This machine
would
pullthe
out only
righthands
shoes
from
the
OH such
OH
cance
in
drug
resulting
two
piles,
right
would
ular
signifi
cance
in
drug
From
resulting
two
piles,
the
right
hands
would
be
OFrom the
O
H2O, two
HO selective
by attaching
% tagging,
ular
signifiofcance
cance
inviadrug
drug
the
resulting
piles,
the
right
hands
would
resolution
racemates
reversible)
reaction
allowing
their
for
example
a be
lar
signifi
in
From
two
the
hands
would
bebe
 the
OHright

OH
lar
signifi
cance
in
drug
From
the resulting
resulting
two piles,
piles,
the
right
hands
would
aathe (readily
recovered
and
recycled,
right
separated
one
enantiomer
of
recovered
and
recycled,
leaving
the
right
shoes
separated
withenantiomer
an optically pureof
compound
generating
weight.
Left andleaving
right shoes the
could
then
be shoes
separated
by an
)Rdiastereomers
}
the
right
shoes
S
one
enantiomer
of
a
recovered
and
recycled,
leaving
separated
S
R
H
C
H
C
one
enantiomer
of
a
recovered
and
recycled,
leaving
the
right
shoes
3
3
can be5-4).
separated
by chromatography
or fractional
crys-left
achiral
device on the
basis of their
differing
a
onethatenantiomer
of
a
recovered
and
recycled,
leaving
the
right weights.
shoesSuch
separated
Highlight
Therefore,
from
the
ones.
Highlight
5-4).
Therefore,
from
the
left
ones.
Racemic
Racemic
Highlight
5-4). Therefore,
Therefore,
fromtothe
the
left ones.
ones.
tallization 5-4).
(Section
5-8).
The approach is equivalent
usingleft
process at the molecular level is called catalytic kinetic resoHighlight
from
methyloxacyclopropane
1,2-propanediol
Highlight
5-4).
from
the
leftbetter
ones.An
an
important
green
A
much
machine
be
aaof fi
shing device,
in
ers ais
is
an
green
A
much
machine
would
be
device,
of rightTherefore,
hands
to separate a collection
of
lution.
example iswould
the hydrolysis
methyloxacycloproers
iscollection
an important
important
green
Apairs
much better
better
machine
would
be
afi
fishing
shing
device,inin
rs(Chemical
is
an
A
better
machine
would
be
fi
shing
device,
inin pure
of shoes.
Once
all hands
arepresence
on, theof
resulting
collection
pane
with
basic
water.
Normally,
starting
with
a(or
racemate,
However,
in green
the
an enantiomer
of ahook
chiral
propanediol
(ourlike
selective
leaving
behind
Highlight
3-1).
which
the
would
be
shaped
left)
foot.
rs
is
an important
important
green
A much
much
better
machine
would
beaaaaright
fitagging),
shing
device,
Highlight
3-1).
which
the
hook
would
be
shaped
like
right
(or
left)
foot.
is
divided
into
two
groups,
namely,
the
combinations
right
the
result
is
racemic
1,2-propanediol.
This
is to be
expected,
(Chemical
Highlight
3-1).
which
the
hook
would
be
shaped
likeThe
right
(or
foot.
cobalt
catalyst (the
right foot inwhich
our device
above),
water
(S)-oxacyclopropane.
reason
is(or
the left)
chiral nature
of the
Chemical
Highlight
3-1).
the
hook
would
be
shaped
like
aaashoes
right
left)
foot.
has
been
the
This
machine
would
pull
out
only
right
from
the
pile,
Chemical
Highlight
3-1).
which
the
hook
would
be
shaped
like
right
(or
left)
foot.
allenge
hand/right
shoe
and
right
hand/left
shoe.
These
groups
are
not
as
the
two
respective
transition
states
for
the
reactions
of
has
been
the
This
machine
would
pull
out
only
right
shoes
from
the
attacks the R form of starting material much more rapidly
catalyst, rendering
the twoshoes
respective
transition pile,
states of the
only
right
from
allenge
has
been
the
This
machine
would
pull
out
the
allenge
has
been
the
This
machine
would
pull
out
only
right
shoes
from
related
by than
mirrorthesymmetry,
they are diastereomeric.
Rselective
and S starting
ether are
enantiomeric
(Section
5-7).
reversible)
allowing
their
tagging,
for
by
attaching
apile,
counterpart,
it selectively
to (2R)-1,2reaction
they
are
of unequal
energy,
allenge
has
beenSreaction
the hence converting
This
machine
would
pull
outdiastereomeric.
only
rightThus,
shoes
from
thepile,
adily
reversible)
reaction
allowing
their
selective
tagging,
for example
example
by
attaching
a

93
9-3
9--3
33

n of Oxacyclopropanes
Oxacyclopropanes
nnofofOxacyclopropanes
Oxacyclopropanes

adily
reversible) reaction
reaction
dily
reversible)
diastereomers
enerating
dily
reversible)
reaction
diastereomers
eneratingdiastereomers
diastereomers O
enerating

allowing their
their selective
selective tagging,
tagging, for
for example
example by
by attaching
a
allowing
weight.
Left
and
right
could
then
be separated
by an
OH for
OH shoes
allowing
their
tagging,
example
byattaching
attaching
weight.
Left
andselective
right
shoes
could
then
an a a
O
H O, HO and right

%
weight.
Left
shoes
could
thenbe
beseparated
separatedby
by
OH
 could
OH
weight.
Left
and right
shoes
then
be
separated
by an
an
2

related by mirror symmetry, hence they are diastereomeric.

O

)
H3C R

H2O, HO

}
H3C S

Racemic
methyloxacyclopropane

However, in the presence of an enantiomer of a chiral

cobalt catalyst (the right foot in our device above), water
attacks the R form of starting material much more rapidly
than the S counterpart, converting it selectively to (2R)-1,2-

R and S starting ether are enantiomeric (Section 5-7).

OH
%
R

OH

OH

OH

S
Racemic
1,2-propanediol

propanediol (our selective tagging), leaving behind pure

(S)-oxacyclopropane. The reason is the chiral nature of the
catalyst, rendering the two respective transition states of the
reaction diastereomeric. Thus, they are of unequal energy,

9
9 -- 9
9 R
Re
ea
ac
c tt ii o
on
n ss o
o ff O
O xx a
ac
c yy c
c ll o
op
p rr o
op
pa
an
ne
e ss

C
Ch
ha
ap
p tt e
e rr 9
9

9-9 Reactions of Oxacyclopropanes

Chapter 9

363
363

363

Acids catalyze
catalyze oxacyclopropane
oxacyclopropane ring
ring opening
opening
Acids
Ring opening
of
is
catalyzed
by
opening
of oxacyclopropanes
oxacyclopropanes
is also
alsoring
catalyzed
by acids.
acids.
Acids
catalyze
oxacyclopropane
opening
Ring

The
The reaction
reaction in
in this
this case
case
proceeds through
ion formation
formation followed
through initial
initial cyclic
cyclic alkyloxonium
alkyloxonium ion
followed by
by ring
ring opening
opening as
as aa
proceeds
Ring
of oxacyclopropanes is also catalyzed by acids. The reaction in this case
result opening
of
of nucleophilic
nucleophilic attack.
attack.
result
proceeds through initial cyclic alkyloxonium ion formation followed by ring opening as a
result of nucleophilic
attack.
Acid-Catalyzed Ring
Ring Opening
Opening of
of Oxacyclopropane
Oxacyclopropane
Acid-Catalyzed

REACTION
REACTION

O
O O

O
O O

O
O
Acid-Catalyzed
Ring Opening
Oxacyclopropane
H2SOof
4
HOCH
CH  CH OH H2SO4
H22C
O
HOCH22CH
CH22OCH
OCH33
H
CO
O CH22  CH33OH
H2SO4

REACTION

2-Methoxyethanol
2-Methoxyethanol

O
O O

3
3







O
O O




O
O

O
O

HOCH2CH2OCH3
H2C O CH2  CH3OH
Mechanism
Ring
MECHANISM
2-Methoxyethanol
Mechanism of
of Acid-Catalyzed
Acid-Catalyzed
Ring Opening
Opening
MECHANISM
H
H
Mechanism
of Acid-Catalyzed Ring Opening
MECHANISM
A
A

OH

OH
O
O



O
O
H
A



H
OH
A

H ,, CH
CH 
OH

A CH

O
O
H22C
CH
H
C
CH
HOCH
CH
CH
OCH

2
2
2
2
2
2


O
O

O

OH
CO
CH22
H
C
CH
CH
HOCH
CH
CH
OCH33
H
2
2
2
2
2
2

H


O
O
A
H
 H


A
A
Cyclic
H ,H
CH3
OH

Cyclic


O

alkyloxonium
O
H2C O CH2
H2C OCH2 H
CH
HOCH
CH2 O
OCH3
alkyloxonium

 2 CH2

OCH
D
G2



H
H
OCH33
D
H
ion
AG
ion
CH
H
Cyclic
3
H OCH3
alkyloxonium
H
OCH3
DG

ion
CHis
H
The
The anionic
anionic nucleophilic
nucleophilic opening
opening of
of oxacyclopropanes
oxacyclopropanes just
just discussed
discussed
is3 regioselective
regioselective
and
and stereospecifi
stereospecific.
c. What
What about
about acid-catalyzed
acid-catalyzed ring
ring opening
opening
is
is that
that also
also regioselective
regioselective and
and
The anionic
nucleophilic
opening
oxacyclopropanes
just discussed
is regioselective
stereospecifi
c?
but
are
different.
Thus,
methanolysis
of
c? Yes,
Yes,
but the
the details
details
are of
different.
Thus, acid-catalyzed
acid-catalyzed
methanolysis
of 2,22,2stereospecifi
and
stereospecific. What about
acid-catalyzed
ring
is
also regioselective
and
dimethyloxacyclopropane
proceeds
by
ring
opening
at
the
hindered
proceeds
by exclusive
exclusive
ringopening
opening
at that
the more
more
hindered carbon.
carbon.
dimethyloxacyclopropane
stereospecific? Yes, but the details are different. Thus, acid-catalyzed methanolysis of 2,2dimethyloxacyclopropane proceeds by exclusive ring opening at the more hindered carbon.

allowing
allowing one
one enantiomer
enantiomer of
of oxacyclopropane
oxacyclopropane to
to hydrolyze
hydrolyze
faster
faster than
than the
the other.
other.
The
of
enantiomer
below.
allowing
one enantiomer
of oxacyclopropane
hydrolyze
The structure
structure
of the
the catalyst
catalyst
enantiomer is
istoshown
shown
below.
You
see
the
chiral
fastercan
than
You
can
seethe
theother.
chiral environment
environment around
around the
the metal,
metal, provided
provided
The structure of the catalyst enantiomer is shown below.
H
H22O,
O,
You can see the chiral environment around the metal, provided
chiral Co2
2
O
O
)
)
H
RO
H33C
C R




O
O
}
}S O
H
C S
H33C


Racemic
Racemic
)
}
methyloxacyclopropane
R
H3C methyloxacyclopropane
H3C S

by
by the
the substituted
substituted cyclohexane
cyclohexane scaffold.
scaffold. The
The cobalt
cobalt attacks
attacks
selectively
selectively the
the lone
lone pairs
pairs on
on the
the (R)-oxacyclopropane
(R)-oxacyclopropane subsubstrate
aa Lewis
(Section
thus
facilitating
ring
by theas
cyclohexane
scaffold.
cobalt attacks
strate
assubstituted
Lewis acid
acid
(Section 2-2),
2-2),
thus The
facilitating
ring
opening
by
water.
selectively
lone pairs on the (R)-oxacyclopropane subopening
by the
water.
strate as a Lewis acid (Section 2-2), thus facilitating ring
opening
OH by water.
OH
%
%
ROH
R
%

chiral Co
catalyst
catalyst
H2O,
chiral Co2
catalyst

OH
OH




OH

O
O

}
}
H
S O
H33C
C S

}
H3C S

Racemic
methyloxacyclopropane

R
R
R
R
)
((~
H )@@
~H
H
H
N
N
NR
RN
)
~
H @ Co
Co ( H
N
N
O
O
O
O
Co

Cobalt
Cobalt catalyst
catalyst

Using
Using the
the mirror
mirror image
image of
of the
the catalyst
catalyst shown
shown gives
gives the
the Cobalt catalystof
of medicines
medicines and
and other
other fi
fine
ne chemicals
chemicals and
and therefore
therefore in
in great
great
complementary
demand
complementary results
results to
to our
our example:
example: Only
Only (S)-methyloxa(S)-methyloxademand by
by synthetic
synthetic chemists.
chemists. As
As aa result,
result, the
the above
above kinetic
kinetic
cyclopropane
is
furnish
(S)-diol,
leaving
resolution
has
been
refi
require
11 kg
cyclopropane
is attacked
attacked
to the
furnish
(S)-diol,
leaving
behind
resolution
has and
beenother
refined
ned
tochemicals
require less
less
than
kg of
of
cataUsing the mirror
image ofto
catalyst
shown
gives behind
the
of medicines
fineto
andthan
therefore
in catagreat
unreacted
R
material.
highly
functionalized
lyst
to
11 ton
Daiso
Co.
unreacted
R starting
starting
material.
Such
highly
functionalized
lyst
to make
make
ton of
of product
product
and
isabeing
being
used
by
Daiso
Co.
complementary
results
to our Such
example:
Only
(S)-methyloxademand
by synthetic
chemists.and
Asis
result,used
the by
above
kinetic
small
chiral
blocks
of
value
in
in
Japan
aa 50-ton/year
small
chiral building
building
blocks
are
of great
great
valueleaving
in the
the synthesis
synthesis
in
Japan on
onhas
50-ton/year
scale.
cyclopropane
is attacked
to are
furnish
(S)-diol,
behind
resolution
been refinedscale.
to require less than 1 kg of cataunreacted R starting material. Such highly functionalized
lyst to make 1 ton of product and is being used by Daiso Co.
small chiral building blocks are of great value in the synthesis
in Japan on a 50-ton/year scale.

O OO

O
OO

result of nucleophilic attack.

result of nucleophilic attack.
Acid-Catalyzed Ring
Ring
Opening
of
Oxacyclopropane
Ring Opening
Opening of
of Oxacyclopropane
Oxacyclopropane
Acid-Catalyzed
Acid-Catalyzed
Ring
Opening
of
Oxacyclopropane
O
O
H2SO4
H2SO
SO4
H
O
O CH
 CH
CH3OH
OH
HOCH
CH
OCH
CH2 
H2C
CO
HOCH
OH
HOCH2CH
CH2OCH
OCH3
H
22

33

22

H2C O CH2 

CH3OH

44

H2SO4

22

222

333

2-Methoxyethanol
HOCH
2-Methoxyethanol
2-Methoxyethanol
2CH2OCH3

2-Methoxyethanol

O OO

O OO

O
OO

O
OO

Mechanism
of
Acid-Catalyzed
Ring
Opening
Mechanism
Mechanism of
of Acid-Catalyzed
Acid-Catalyzed Ring
Ring Opening
Opening
Mechanism
of Acid-Catalyzed Ring Opening
H
H
AA 

OH

O
O

OH

OH




O
O
A
AA



H,, CH
CH3
OH

A
H
OH
3

CH
OH

O
O
O
O
O
H
C
CH
H
C
CH
CH
2C O
2
2


 CH22
H
CH
CH
H22C O
OCH
CH
CH
CH
A 222O
2
2
H ,H
CH3
OH
2
2
AA 222
H 
ACH
Cyclic
O
O
Cyclic
H2C O CH2
H
C
CH
CH
2
Cyclic
2
2
2



O

alkyloxonium

O
H
O
AG

alkyloxonium
alkyloxonium
H
OCH

D
Cyclic


H
OCH
D
GCH
H
OCH333
D
ion

ion
ion
H
OG
alkyloxonium

CH3333
H
H

H
OCH
D
GCH
 3
ion
CH3
H
The anionic
anionic nucleophilic
nucleophilic opening
opening of
of
oxacyclopropanes
just
discussed
The
of oxacyclopropanes
oxacyclopropanes just
just discussed
discussed isis
is
and The
stereospecifi
c.
What about
aboutopening
acid-catalyzed
ring
opening

is
that
also
regi
stereospecifi
What
acid-catalyzed
ring
is
also
anionic c.
nucleophilic
of oxacyclopropanes
just
discussed
is
and
acid-catalyzed
ring opening
opening

is that
that
also regio
regi
stereospecifi
c? Yes,
Yes,
but the
the
details
are different.
different.
Thus,
acid-catalyzed
methan
c?
but
details
are
acid-catalyzed
methan
and stereospecifi
c. What
about
acid-catalyzed
ringThus,
opening
is that also
regi
stereospecifi
different.
Thus,
acid-catalyzed
methan
dimethyloxacyclopropane
proceeds
by
exclusive
ring
opening
at
the
more
hin
proceeds
opening
at
hind
dimethyloxacyclopropane
hin
stereospecific? Yes, but the
details by
areexclusive
different.ring
Thus,
acid-catalyzed
methan
exclusive
ring
opening
at the
the more
more
hin
dimethyloxacyclopropane proceeds by exclusive ring opening at the more hin

allowing one
one enantiomer
enantiomer of
of oxacyclopropane
oxacyclopropane
to
hydrolyze
allowing
oxacyclopropane to
to hydrolyze
hydrolyze
faster
thanone
theenantiomer
other.
faster
than
the
other.
allowing
of oxacyclopropane to hydrolyze
The
structure
of
the
catalyst
enantiomer
is
shown
below.
The
structure
of the catalyst enantiomer
enantiomer is
is shown
shown below.
below.
faster
than
the other.
YouThe
can structure
see the
the chiral
chiral
environment
around
the
metal,
provided
You
can
see
environment
around
around the
theismetal,
metal,
provided
of the
catalyst enantiomer
shownprovided
below.
You can see the chiral environment around the metal, provided
H2O,
O
O
O
O
)
)
)
H
R
H333C
C R
)
H3C R

O
O
O



O
}
}
}
S
C
H
 H
C SS
H333C
Racemic H C }S
Racemic
Racemic 3

H
H222O,
O,
2
chiral
Co2
2
chiral
Co
chiral
Co2
H
catalyst
2O,
catalyst
catalyst
chiral Co2

catalyst

methyloxacyclopropane
methyloxacyclopropane
methyloxacyclopropane
Racemic
methyloxacyclopropane

RR

by
the
subs
by
by the
the subs
subs
selectively
selectively
selectively
by the subst
strate
as
strate
strate as
as aaa L
selectively
opening
by
opening
opening
by
strate asby
a
opening by
OH
OH
OH
%%%
OH O
%
RR
R
R

RR

opening as a

REACTION
REACTION
REACTION
REACTION

MECHANISM
MECHANISM
MECHANISM
MECHANISM

H
H

HOCH
CH
OCH
HOCH
OCH
CH222
OCH333



 222CH


HOCH
OCH3
 2 CH2

regioselective

H2C O CH2

H

ion
H2C OCH
2
Cyclic
alkyloxonium
ion

CH2 O CH2
A
O
DG
CH3
H
oxacyclopropanes

HOCH
OCH
H
2
33
 2 CHCH


H

H
OCH3


The anionic nucleophilic opening of oxacyclopropanes just discussed is regioselective

and stereospecifi
c. What
about
acid-catalyzed
ring
is that also regioselective and
The anionic
nucleophilic
opening
of oxacyclopropanes
just opening
discussed is
regioselective
and stereospecifi
Whatthe
aboutdetails
acid-catalyzed
opening is
that alsoacid-catalyzed
regioselective and methanolysis of 2,2stereospecifi
c? Yes, c.but
are ring
different.
Thus,
stereospecific? Yes, but the details are different. Thus, acid-catalyzed methanolysis of 2,2dimethyloxacyclopropane
proceeds
by
exclusive
ring
opening
atcarbon.
the more hindered carbon.
dimethyloxacyclopropane proceeds by exclusive ring opening at the more hindered

allowing one enantiomer of oxacyclopropane to hydrolyze

faster than the other.
The structure of the catalyst enantiomer is shown below.
You can see the chiral environment around the metal, provided

by the substituted cyclohexane scaffold. The cobalt attacks

selectively the lone pairs on the (R)-oxacyclopropane substrate as a Lewis acid (Section 2-2), thus facilitating ring
opening by water.

allowing one enantiomer of oxacyclopropane to hydrolyze

H O,
OH
chiral Co
faster than the other.
O
O
catalyst
%

OH
The structure of the catalyst
enantiomer
is
shown below.
)
}
H3C R
H3C S
R
You can see the chiral environment
around the metal, provided
Racemic

by the substituted cyclohexa

selectively
the lone pairs on
O
strate
as a Lewis acid (Sect
}
H3C S
opening by water.

2

methyloxacyclopropane

O
)
H3C R

R
)
H @
N

O~R
( H

}
H3C SCo

O
Racemic
methyloxacyclopropane

H22O,
2
chiral Co2
catalyst

OH
%

R
O

OH


H3C

Cobalt catalyst

Using the mirror image of the catalyst shown gives the

complementary results to our example: Only (S)-methyloxacyclopropane is attacked to furnish (S)-diol, leaving behind
unreacted R starting material. Such highly functionalized
small chiral building blocks are of great value in the synthesis

R
R
of medicines and other fine chemicals and therefore in great
)
demand
chemists. As a result, the above kinetic
(~ H
H by@ synthetic
resolution
has been refined to require less than 1 kg of cataN
N
lyst to make 1 ton of product and is being used by Daiso Co.
in Japan on a 50-ton/year scale.
Co

Cobalt catalyst

Using the mirror image of the catalyst shown gives the

complementary results to our example: Only (S)-methyloxacyclopropane is attacked to furnish (S)-diol, leaving behind
unreacted R starting material. Such highly functionalized
small chiral building blocks are of great value in the synthesis

of medicines and other fine

demand by synthetic chemi
resolution has been refined
lyst to make 1 ton of produ
in Japan on a 50-ton/year sc

364

Chapter 9

Further

364

Chapter 9

Further

REACTION
REACTION

Protonated
2,2-dimethyloxacyclopropane
Protonated
2,2-dimethyloxacyclopropane

Why is
generates a
Why is
carbon bon
generates a
alkyl group
carbon bon
tertiary tha
alkyl group
map in the
tertiary tha
nucleophile
map in the
neighbor ab
nucleophile
this map w
neighbor ab
this map w

R
e a c t i o n s o Ring
f A lOpening
c o h o l sofa2,2-Dimethyloxacyclopropane
nd the Chemistry of Ethers
Acid-Catalyzed

Acid-Catalyzed Ring Opening of 2,2-Dimethyloxacyclopropane

Nucleophile attacks
Nucleophile
attacks
this carbon

&

OO

G
G

G
&G
&@
@
G

Primary
Primary
less hindered
carbocationlike:
Mechanismlessofhindered
Acid-Catalyzed
carbocationlike:
H

Tertiary
Tertiary
carbocationlike:
more hindered

Ring Opening
carbocationlike:
more hindered
H
H
A

of 2,2-Dimethyloxacyclopropane
by MethanolH
A

O
O
Primary
O
O
Tertiary
H
C
hindered
carbocationlike:
more hindered
O
O
C
C
or
C
C
C
Hcarbocationlike: less

or
H ( CO
H ( CO
H C (C CH3
H C(C CH3
HH( A (CH
CH
H
CH
CH
(
(
H
A
33
33
H O
CH3
H O
CH3
H
CH OH
H
CH OH
H

H
H
C OCH
C COH
or
C OCH
C COH
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
H (
H (
( CH3
( CH3
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
CH3
H(Not formed)CH3
H
C
C

(Not formed)







 

OO



ZZ







C
C

ZZ

OO

C
( CH3
CH3

C
(C CH3
CH
(CH
33
CH3

OO

this carbon
CH3
HO
O
CH
HO
O
Acid-Catalyzed
Ring Opening
of3OH
2,2-Dimethyloxacyclopropane
33
H2SO4, CH
CH
H2SO4, CH3OH
H2CO C ~
CH2 GG C CH3
H2CO C(~Nucleophile
CH2 C
attacks
CH3
OCH3
CH
(CH
3 carbon
3 this
OCH
CH3 3
HO
O CH3
2,2-Dimethyloxacyclopropane
2-Methoxy-2-methyl-1-propanol
2,2-Dimethyloxacyclopropane H2SO4, CH3OH 2-Methoxy-2-methyl-1-propanol
CH3
H2CO C ~
CH2 G C
the more hindered
position attacked? Protonation at the oxygen of the ethe
CH
(
3
the
moreintermediate
hindered
attacked?ionProtonation
at theOCH
oxygen
of the
ethe
CH3 position
3
reactive
alkyloxonium
with substantially
polarized
oxygen
reactive
intermediate
alkyloxonium
ion2-Methoxy-2-methyl-1-propanol
with
substantially
2,2-Dimethyloxacyclopropane
ds.
This polarization
places
partial positive
charges
on the ringpolarized
carbons. oxygen
Becaus
ds.act
This
places
partial positive
charges
on the
ring is
carbons.
ps
as polarization
electron donors
(Section
7-5), more
positive
charge
locatedBecaus
on th
more
hindered
position
attacked?
at the
the electrostatic
oxygen
of the
ps
actthe
as primary
electron
donors
(Section
7-5),
more
positive
charge
is located
onethe
th
n the
on
carbon.
You
can
see
thisProtonation
difference
in
potentia
reactive
alkyloxonium
ion difference
with
polarized
oxygen
nmargin,
on the primary
You canissee
this
in the electrostatic
potenti
inintermediate
whichcarbon.
the molecule
viewed
from substantially
the perspective
of the attackin
ds.
Thistertiary
polarization
charges
the
ring than
carbons.
Becaus
in which
theplaces
molecule
is positive
viewed
from
theon
perspective
of the
.margin,
The
carbon
at thepartial
bottom
is more
positive
(blue)
theattackin
primar
ps
act
as
electron
donors
(Section
7-5),
more
positive
charge
is
located
on tho
.
The
tertiary
carbon
at
the
bottom
is
positive
(blue)
than
the
primar
bove (green). The proton in the back is strongly blue. The color-energy scale
nasonchanged
the
primary
carbon.
can
see is
this
difference
the electrostatic
bove
(green).
proton
in the
back
strongly
blue.invisible.
The
color-energypotenti
scale o
toThe
make
this You
subtle
gradation
in shading
margin,
in which
thethis
molecule
is viewed in
from
the perspective
of the attackin
as
changed
to make
subtle gradation
shading
visible.
. The tertiary
carbon at
bottom is more
positive
(blue) than the primar
Mechanism
of the
Acid-Catalyzed
Ring
Opening
Mechanism
Ring
Opening
bove (green).
The protonofinAcid-Catalyzed
the back is strongly
blue.
The color-energy scale o
of
2,2-Dimethyloxacyclopropane
by Methanol
by Methanol
as changedofto2,2-Dimethyloxacyclopropane
make this subtle gradation in shading
visible.

3

H
CH3OH
H
CH3OH
n charge distribution counteracts
steric hindrance: Methanol
is attracted by cou
nescharge
distribution
hindrance:
Methanolthe
is result
attracted
by cou
more to
the1-Methoxy-2-methyl-2-propanol
tertiarycounteracts
than to the steric
primary
center.
Although
is clear-cu
2-Methoxy-2-methyl-1-propanol
es
more
to
the
tertiary
than
to
the
primary
center.
Although
the
resultasisdifferen
clear-cu
mple, it is less so in cases
in which the two carbons are not quite
(Not formed)
mple,
it is less
so in cases
in which
two carbons
are not quite
differeno
e, mixtures
of isomeric
products
are the
formed
by acid-catalyzed
ringasopening
ne,charge
distribution
counteracts
hindrance:
Methanol is attracted
by cou
mixtures
of isomeric
products steric
are formed
by acid-catalyzed
ring opening
o

carbon
bonds.
This
polarization
places
charges
on
the
carbon
bonds.
This
polarization
partial
on
the ring
ring carbons.
carbons.Because
Because
2,2-Dimethyloxacyclopropane
2-Methoxy-2-methyl-1-propanol
partial
carbon
bonds.
This
polarization places
places
charges
on
the
ring
carbons.
Because
positive
2,2-Dimethyloxacyclopropane
2-Methoxy-2-methyl-1-propanol
2,2-Dimethyloxacyclopropane
2-Methoxy-2-methyl-1-propanol
partial positive
carbon
bonds.act
This
places
charges
on
the
ring
carbons.
Because
positive
alkyl
groups
as
electron
donors
(Section
more
positive
charge
islocated
located
onthe
the
alkyl
groups
act
aspolarization
electron donors
donors
7-5), more
more
positive
charge
isis
located
on
the
alkyl
groups
act
as
electron
donors
(Section
7-5),
more
positive
charge
located
on
the
alkyl
act
as
electron
(Section
7-5),
positive
charge
is
on
electron
(Section
positive
charge
located
on
the
donors
alkyl
groups
act
as
electron
(Section
7-5),
more
positive
charge
is
located
on
the
donors
Why
the
morehindered
hindered
position
attacked?
Protonation
theoxygen
oxygen
the
ether
alkyl groups
groups
actthe
asprimary
electroncarbon.
(Section
7-5),
more
positive
charge
isis
located
on
the
hindered
position
attacked?
Protonation
atatthe
the
oxygen
ofof
the
ether
Why
isisthe
more
position
attacked?
Protonation
at
of
the
ether
tertiary
thanon
on
the
primary
carbon.
see
this
difference
in
the
electrostatic
potential
tertiary
than
on
You
can
difference
in
the
electrostatic
potential
tertiary
the
primary
carbon.
You
can
see
this
difference
in
the
electrostatic
potential
generates
a
reactive
intermediate
alkyloxonium
ion
with
substantially
polarized
oxygen
You
difference
in
the
electrostatic
potential
tertiary
than
on
the
primary
than
the
primary
carbon.
You
can
see
this
difference
in
the
electrostatic
potential
intermediate
alkyloxonium
ion with
withthe
substantially
polarized
oxygen
carbon.
generates
a reactive
intermediate
alkyloxonium
ion
substantially
polarized
oxygen

tertiary
than
on
the
primary
You
difference
in
electrostatic
potential
can
see this
carbon.
tertiary
than
on
the
primary
You
difference
in
the
electrostatic
potential
carbon
bonds.
Thispolarization
polarization
placespartial
partial
positive
charges
ring
carbons.
Because
map
themargin,
margin, in
in which
which
the
molecule
viewed
from
the
perspective
of
the
attacking
map
ininthe
the
margin,
in
which
the
molecule
is viewed
from
theperspective
perspective
ofcarbons.
theattacking
attacking
polarization
places
partial
positive
charges
onon
thethe
ring
carbons.
Because
carbon
bonds.
This
places
positive
charges
on
the
ring
Because
map
the
molecule
from
the
perspective
of
the
attacking
map
margin,
in
which
molecule
from
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the
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the
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electron
donors(Section
(Section
7-5),more
morepositive
positivecharge
charge
located
electron
donors
(Section
7-5),
more
positive
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located
onon
thethe
groups
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7-5),
isis is
located
on
the
nucleophile.
The tertiary
tertiary alkyl
carbon
atact
is more
more
positive
(blue)
than
the
primary
nucleophile.
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tertiary
carbon
at
the
bottom
more
positive
(blue)
than
the
primary
nucleophile.
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tertiary
at
the
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(blue)
than
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nucleophile.
carbon
the
bottom
more
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(blue)
than
the
primary
at
bottom
is
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(blue)
than
the
primary
tertiarythan
than
theprimary
primary
carbon.
You
cansee
see
thisdifference
difference
the
electrostatic
potential
carbon.
You
can
see
this
difference
inin
the
electrostatic
potential
tertiary
the
carbon.
can
this
in
the
electrostatic
potential
nucleophile. The
The tertiary
tertiary carbon
carbon
atononthe
the
bottom
isisYou
more
positive
(blue)
than
the
primary
neighbor
above(green).
(green).The
The
proton
is
strongly
blue.
The
color-energy
scale
ofof
neighbor
above
(green).
The
proton
in
the
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strongly
blue.
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color-energy
scale
mapproton
inthe
themargin,
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inwhich
which
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isviewed
viewed
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which
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the
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map
in
in
the
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of
the
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(green).
in
strongly
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color-energy
scale
of
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in
(green).
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proton
the
back
is
strongly
blue.
The
color-energy
scale
the
above
in
the
back
is
blue.
The
color-energy
scale
neighbor
above
(green).
in
strongly
blue.
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color-energy
scale
of
proton The
the
back
isatatstrongly
neighbor above (green). The
in tertiary
blue.
The
color-energy
scale
ofofof
nucleophile.
tertiary
carbon
atthe
the
bottom
more
positive
(blue)than
than
primary
carbon
the
bottom
isismore
more
positive
(blue)
than
thethe
primary
nucleophile.
carbon
bottom
is
positive
(blue)
the
primary
this
mapwas
was changed
changed to
to make
make
thisThe
in
shading
visible.
this
map
changed
to
make
subtle
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in
shading
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this
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this
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in
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this
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in
shading
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this
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this
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was
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this
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visible.
to make
make
neighbor
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(green).gradation
Theproton
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theshading
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thismap
mapwas
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changed to
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in
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The
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ininin
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makethis
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gradationin
shading
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this
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make
this
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ininshading
shading
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Protonated
Mechanism of
Ring
Opening
of Acid-Catalyzed
Mechanism
of
Acid-CatalyzedRing
RingOpening
Opening
Mechanism
Acid-Catalyzed
Mechanism
Acid-Catalyzed
Ring
Opening
Mechanism
Opening
Mechanism of
of
Acid-Catalyzed
Ring
Opening
2,2-dimethyloxacyclopropane
dimethyloxacyclopropane
Mechanismof
Acid-Catalyzed
RingOpening
Opening
Mechanism
Ring
Mechanism
ofofAcid-Catalyzed
Acid-Catalyzed
Ring
Opening
of
2,2-Dimethyloxacyclopropane
by
Methanol
of
2,2-Dimethyloxacyclopropane
by
Methanol
of
2,2-Dimethyloxacyclopropane
by
Methanol
of
2,2-Dimethyloxacyclopropane
by
of
2,2-Dimethyloxacyclopropane
byMethanol
Methanol
of
Methanol
ofof2,2-Dimethyloxacyclopropane
by
2,2-Dimethyloxacyclopropane
Methanol
2,2-Dimethyloxacyclopropane
bybyMethanol
Methanol
of 2,2-Dimethyloxacyclopropane
2,2-Dimethyloxacyclopropane
by
Methanol

O
O

O
O
O
O
O
O
O
O

Z
Z
Z
Z
Z
Z

Z
Z

O
O

Tertiary
Tertiary
Tertiary

Z
Z
Z
Z
Z
Z
Z
Z

O
O
O
O
O
O

CC

O
O
C
C
or
C
C
O
O
C
C
or
C
C
OC
O
CCC(CC CH H
orOH
C
CCCH
C CC CH
O
CC
O
O
CO
C
or
C
CC
O
O
C
or
C
CH
H
OH
H
CH
OHOH
H (((C
H
CH
CH
H
CH
H
((((((CH
3
H
CH
H
CH
CH3333333 HH CHCHOHOH
HH(((((((
CH
3 33
H
CH
HH
CH
H
CH
(((((CH
H
CH
CH
(CH
CH
H((
CH
H
H
3
3333 3
3
3
CH
CH
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
H
H
CH
CH
3
33
H
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
CH
CH
CH
H
H
H
HH
CH333 (Not
CH
33 33
(Not formed)
formed)

 

33
3

CCCCCC

CC
CCC

O
O
O
O
O
O
O
O




C CC




O
O

O
O

O
O
O
O
O
O
O
O

O
OO
O
C
O
C
O
C
C
CCO
OCC
CCC(CC CH
H
CH333
HH((((
CH
H
CH
(((CH
HH
CH333333333333
H
H
CH
CH
H
H
3

Tertiary
Tertiary
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Tertiary
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carbocationlike:
more
hindered
carbocationlike:
more
hindered
carbocationlike:
more
hindered
Tertiary
carbocationlike:
more
hindered
more
hindered
carbocationlike:
carbocationlike:
more
hindered
more
hindered
carbocationlike:
carbocationlike:
more
hindered
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carbocationlike:
more
hindered
carbocationlike:
more
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HH HAHA

HA
more
H
H
H
H
O
AAAAA
AA

 O O













C
C C
OO


or
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O
oror
CO
O
CO
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O
O
O
H
H
CH
H(( (
  (( (CH
CH
33 3
CH
CH
33 3
C OHHCH

C
C

 CH

C CC




Z
Z

Primary
Primary
Primary
Primary
Primary
Primary
Primary
Primary
Primary
carbocationlike:
less
hindered
carbocationlike:
less
hindered
carbocationlike:
less
hindered
Primary
carbocationlike:
lesshindered
hindered
carbocationlike:
less
carbocationlike:
less
hindered
carbocationlike:
less
hindered
H
HH
lesshindered
carbocationlike:
carbocationlike:
less
hindered
carbocationlike:
hindered
carbocationlike:less
less
hindered
H
AA
A 
H
H

H
H
H
OO
O
A

OO

A

A
A



AAO
A


H

H
H





C
CC C
O
CCO
C
C
C
C
CCOO
CC

O
OC
O
O
O

O
H
CH
H
(
(
(
(( (CH
H
CH
CH
H (
H((
CH
33 3
33 3
H

H

(CH
H
CH
HH
H
H
HH
CH
33 3
H
H
H
3 CCC

CH
C33O
orCH



33

(Not formed)
H CH
CHOH
H CH
CH
H
H
OH
3OH
3OH
3
H
CH
OH
H
33OH
H
CH
H
CH
OH
H CH
CH333333OH
OH
H CH
CH
3
H
CH
OH
H
CH
OH
3OH
3OH
H
H
CH
OH
33
H
CH
H
CH
3OH
33OH
This
counteracts
Methanol
isis is
attracted
by
coudistribution
counteracts
steric
hindrance:
Methanol
attracted
byby
couThisuneven
unevencharge
chargedistribution
distribution
counteractssteric
sterichindrance:
hindrance:
Methanol
attracted
cou-

C
CCC C

lombic
primary
center.
Although
the
result
isis clear-cut
tertiary
than
totothe
the
primary
center.
Although
thethe
result
clear-cut
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
2-Methoxy-2-methyl-1-propanol
1-Methoxy-2-methyl-2-propanol
lombicforces
forcesmore
moretotothe
thetertiary
tertiarythan
thanto
the
primary
center.
Although
result
is
clear-cut
2-Methoxy-2-methyl-1-propanol
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
1-Methoxy-2-methyl-2-propanol
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
1-Methoxy-2-methyl-2-propanol
2-Methoxy-2-methyl-1-propanol
in this example, it is less so
the
so in
in cases
cases in
in which
which
the two
two carbons
carbons are
are not
not quite
quite as
as different.
different.

in this example,
it is less so in cases in which the two carbons are not quite as different.
(Notformed)
formed)
(Not
(Not
formed)
(Not
formed)
For
mixtures
ofofisomeric
ring
opening
of
(Not
formed)
(Not
formed)
isomeric
products
are
formed
bybyacid-catalyzed
acid-catalyzed
ring
opening
of of
(Not
formed)
(Not
formed)
Forexample,
example,
mixtures
isomericproducts
productsare
areformed
formedby
acid-catalyzed
ring
opening
2-methyloxacyclopropane.

2-methyloxacyclopropane.
This
distribution
counteracts
steric
hindrance:
Methanol
isattracted
attracted
bycoucoucharge distribution
uneven
charge
counteracts
steric
hindrance:
Methanol
is
by
This
Why
do
write
as
in
the
acid-catalyzed
uneven
charge
distribution
counteracts
steric
hindrance:
Methanol
is
by
simply
write
free
carbocations
asasintermediates
intermediates
in
thethe
acid-catalyzed
Thisuneven
unevencharge
charge
distribution
counteracts
Methanol
isis
attracted
by
couWhycounteracts
dowe
wenot
notsimply
simply
writefree
freecarbocations
carbocations
intermediates
in
acid-catalyzed
This
charge
distribution
counteracts
steric
hindrance:
Methanol
isattracted
attracted
bycoucoudistribution
steric
hindrance:
Methanol
attracted
by
couThis
charge
distribution
counteracts
hindrance:
Methanol
is
attracted
by
uneven
ring
The
is
is
when
the
reaction
takes
place
at
aat
isisthat
that
inversion
isisobserved
observed
when
the
reaction
takes
place
atcoua a
lombic
to
the
tertiary
than
toreason
the steric
primary
center.
Although
the
result
isclear-cut
clear-cut
more
forces
more
to
the
tertiary
than
to
the
primary
center.
Although
the
result
is
ringopenings?
openings?
The
reason
thatinversion
inversion
observed
when
the
reaction
place
lombic
to
the
tertiary
than
to
the
primary
center.
Although
the
result
is
clear-cut
forces
more
lombicforces
tothe
the tertiary
than
to
center.
Although
the
result
istakes
clear-cut
lombic
more to
to
the
tertiary
than
to
the
primary
center.
Although
the
result
is
clear-cut
more
than
primary
Although
the
result
is
clear-cut
stereocenter.
Liketo
thethe
reaction
of
oxacyclopropanes
with
anionic
nucleophiles,
the
acidreaction
of
oxacyclopropanes
with
anionic
nucleophiles,
the
acidforces
more
to
the
tertiary
than
to
the
primary
center.
Although
the
result
is
clear-cut
lombic
stereocenter.
Like
reactionthe
of oxacyclopropanes
with
anionic
nucleophiles,
the acidin
is less
lesscatalyzed
so in
in cases
cases
inthewhich
which
the
two
carbons
are
not
quite
as
different.
it is
this
example,
it
so
in
two
carbons
are
not
quite
as
different.
in
this
example,
it
is
less
so
in
cases
in
which
the
two
carbons
are
not
quite
as
different.
process
includes
backside
displacement

in
this
case,
on
a
highly
polarized
cyclic
in
backside

ininthis
case,
ononaquite
highly
polarized
cyclic
this
example,
itit
in
which
the
two
are
not
asas
in
it is
is less
less so
so
in cases
cases
in
which
thedisplacement
two carbons
carbons
are
not
quite
asdifferent.
different.
catalyzed
processin
includes
backside
displacement
this
case,
aquite
highly
polarized
cyclic
thisexample,
example,
is
less
so
in
cases
in
which
the
two
carbons
are
not
different.
inFor
ion.
mixtures
isomeric
are
mixtures of
ofalkyloxonium
isomeric products
products
are formed
formed by
by acid-catalyzed
acid-catalyzedring
ringopening
openingof
of
Forexample,
example, mixtures
mixtures
of
isomeric
products
are
formed
alkyloxonium
ion.
isomeric
products
are
by
acid-catalyzed
ring
opening
For
of
isomeric
products
are formed
formedby
byacid-catalyzed
acid-catalyzedring
ringopening
openingofofof
of
example, mixtures
mixtures of
of
isomeric
products
are
formed
by
acid-catalyzed
ring
opening
For
2-methyloxacyclopropane.
2-methyloxacyclopropane.
2-methyloxacyclopropane.
2-methyloxacyclopropane. Exercise 9-24
2-methyloxacyclopropane.
2-methyloxacyclopropane.
2-methyloxacyclopropane.
Exercise
9-24
Why
do
we
not
simply
simply write
write free
free carbocations
carbocations as
as intermediates
intermediates in
in the
theacid-catalyzed
acid-catalyzed
Why
do
we
not
simply
write
free
carbocations
as
intermediates
in
the
acid-catalyzed
Why
do
we
not
simply
write
free
carbocations
as
intermediates
in
the
acid-catalyzed
Why
do
not
simply
write
carbocations
as
inin
acid-catalyzed
not reason
simplyPredict
write
free
carbocations
asofofintermediates
intermediates
inthe
the
acid-catalyzed
Why
do we
we The
not
simply
free
carbocations
as
intermediates
the
the free
major
product
of
opening
2,2-dimethyloxacyclopropane
on
treatment
with
product
of
ring
opening
2,2-dimethyloxacyclopropane
onacid-catalyzed
treatment
with
openings?
is
that
is
observed
the
takes
place
atwith
The
ring
reason
iswrite
that
inversion
isofring
observed
when
thereaction
reaction
takes
place
ataaa
Predict
theinversion
major product
ringLiAlH
opening when
of
2,2-dimethyloxacyclopropane
onthen
treatment
1
1
ringopenings?
openings? The
The
reason
is
that
inversion
is
observed
when
the
takes
place
each
of the
following
reagents.
(a)
H
(b)
CH
H
O;
reagents.
(a)
LiAlH44,, then
then
H1,,1H
H22O;
O;
(b)reaction
CH
CH22CH
CH22MgBr,
MgBr,
then
H1,, H
H2at
33CH
reason
is
that
inversion
is
when
the
reaction
takes
place
atO;
2O;
ring
The
reason
is
that
inversion
is observed
observed
when
the
reaction
takes
place
ata aa
openings?Like
The
reason
is
that
is
observed
when
takes
place
ring
each
theinversion
following
reagents.
(a) LiAlH
, then
H
,H
O;concentrated
(b)reaction
CH
then
H1acid,acidH2at
4with
2the
3CHaqueous
2CH2MgBr,
stereocenter.
the
reaction
of
oxacyclopropanes
anionic
nucleophiles,
Like
the
reaction
of
oxacyclopropanes
anionic
nucleophiles,
the
(c)
CHof
in
CH33OH;
CH
(e)
OH; (d)
(d) dilute
dilute HCl
HCl in
in with
CH
CH22OH;
OH;
(e)
concentrated
aqueous HBr.
HBr.the
33SNa
33CH
stereocenter.
Like
the
reaction
of
oxacyclopropanes
with
anionic
nucleophiles,
the
acid(c)
CH
SNa
in
CH
OH;
(d)
dilute
HCl
in
CH
CH
OH;
(e)
concentrated
aqueous
HBr.
Like
the
of
with
anionic
the
acid3of oxacyclopropanes
3
3
2anionic nucleophiles,
stereocenter.
Like includes
the reaction
reaction
oxacyclopropanes
with
nucleophiles,
the
acidLike
the
reaction
of oxacyclopropanes
with
anionic
nucleophiles,
the
acidstereocenter.
process
backside
displacement

in
this
case,
on
a
highly
polarized
cyclic
catalyzed
includes
backside
displacement

in
this
case,
on
a
highly
polarized
cyclic
catalyzedprocess
processincludes
includes backside
backside displacement
displacement
in
this
case,
on
a
highly
polarized
cyclic
in
case,
aahighly
polarized
cyclic
catalyzed
includesInbackside
backside
displacement

inthis
this
case,on
on
highly
polarized
cyclic
process
in
this
case,
on
highly
cyclic
catalyzed
Summary displacement
Although ordinary
ethers
are
inert,
the
ring
oxacyclopropanes
ion.
ordinary
ethers
are relatively
relatively
inert,a
the
ring in
inpolarized
oxacyclopropanes
ion.includes
alkyloxonium
alkyloxonium
ion.
In Summary
ordinary ethers stereospecifi
are relatively inert,
the ring innucleophiles,
oxacyclopropanes
can
be opened Although
both regioselectively
regioselectively and
and stereospecifically.
cally. For
For anionic
anionic nucleophiles, the
the
alkyloxonium ion.
ion.
alkyloxonium
can be
opened
both regioselectively
stereospecifi
cally.
For is
anionic
usual
rules
of bimolecular
nucleophilicand
substitution
hold:
Attack
at thenucleophiles,
less hinderedthe
usual rules of bimolecular nucleophilic substitution hold: Attack is at the less hindered
usual rules
bimolecular
nucleophilic Acid
substitution hold:
Attack is at the
less hindered
carbon
center,ofwhich
undergoes
undergoes inversion.
inversion. Acid catalysis,
catalysis, however,
however, changes
changes the
the regioselecregioseleccarbon
center,
which
undergoes inversion.
Acidat catalysis,
however, changes
the regioselectivity
(but
not the
stereospecifi
stereospecificity):
city): Attack
Attack is
is at the
the more
more hindered
hindered center.
center. Hydride
Hydride and
and
tivity (but not reagents
the stereospecifi
city):other
Attack
is atnucleophiles,
the more hindered
center.
Hydride
and
organometallic
behave
anionic
furnishing
alcohols
by
behave like
like
other
anionic
nucleophiles,
furnishing
alcohols
by an
an
reagents
like other anionic nucleophiles, on
furnishing
alcohols
by an
Predict
of
ring
of
2,2-dimethyloxacyclopropane
with
major product
productSorganometallic
of
ring opening
opening
ofbehave
2,2-dimethyloxacyclopropane
ontreatment
treatment
with
2 pathway.
Predict
the
major
product
of
ring
opening
of
2,2-dimethyloxacyclopropane
on
treatment
with
N
Predict the
the major
major
product
of
N ring opening of 2,2-dimethyloxacyclopropane on treatment with
1
1
S
2
pathway.
1
1
1
1
Predict
the
major
product
of
ring
opening
of
2,2-dimethyloxacyclopropane
on
treatment
with
each ofthe
the major
following
reagents.
(a) LiAlH
, then
H1
H1
Predict
product
ofN ring
opening
of 2,2-dimethyloxacyclopropane
onthen
treatment
with
1, H O; (b) CH CH CH MgBr,
1, H O;

Exercise
Exercise
9-24
Exercise 9-24
9-24
Exercise
Exercise 9-24
9-24

each
the
following
reagents.
(a)
,,, then
H
CH
MgBr,
H
4
2
2
following
reagents.
(a) LiAlH
LiAlH
then
O;(b)
(b)CH
CH3333CH
then
Predict
product
of ring
opening
of 2,2-dimethyloxacyclopropane
onthen
treatment
with
each
of
the
following
reagents.
(a)
LiAlH
then
HH1,,, H
HH222O;
O;
(b)
CH
CH
CH
MgBr,
then
H
H
O;
44
22
22
3CH
2CH
2MgBr,
2O;
each of
ofthe
the major
following
reagents.
(a)
LiAlH
O;
(b)
CH
CH
then
HH11,,, 1,H
HH2222O;
O;
44, then H11, H22
2CH
2MgBr,
each
of
reagents.
(a)
LiAlH
then
HH
O;
CH
then
1, ,H
(c)
SNa
in
(d)
in
CH
concentrated
aqueous
HBr.
2MgBr,
2O;
each
of 333the
the
following
reagents.
(a) HCl
LiAlH
then
H
H2(e)
O;(b)
(b)
CH3CH
CH2CH
CH
MgBr,
thenHH
H1, ,,HH
H
O;
3
22OH;
CH333OH;
OH;
(d) dilute
dilute
HCl
in444,CH
CH
OH;
concentrated
aqueous
HBr.
(c)
CH
SNafollowing
in CH
CH
OH;
(d)
dilute
HCl
in
CH
CH
OH;
(e)
concentrated
aqueous
HBr.
2(e)
each
of
the
following
reagents.
(a)
LiAlH
,,CH
then
,H
O;
(b)
CH
then
33
(c) CH
CH
OH;
(d)
dilute
HCl
in
CH
(e)
concentrated
aqueous
HBr.
33CH22CH
22MgBr,
22O;
3SNa in CH33
33CH22
2OH; 2
(c)
CH
SNa
in
CH
OH;
(d)
dilute
HCl
in
CH
CH
OH;
(e)
concentrated
aqueous
HBr.
3
3
3
2
(c)
CH
SNa
in
CH
OH;
(d)
dilute
HCl
in
CH
CH
OH;
(e)
concentrated
aqueous
HBr.
(c) CH33SNa in CH33OH; (d) dilute HCl in CH33CH22OH; (e) concentrated aqueous HBr.

In
Although
ordinary
ethers
are
relatively
inert,
the
ring
in
oxacyclopropanes
In
Although ordinary
ordinary ethers
ethers are
are relatively
relatively inert,
inert, the
the ring
ring in
oxacyclopropanes
Summary
Although
ordinary
ethers
are
relatively
inert,
the
ring
inin oxacyclopropanes
oxacyclopropanes
In Summary
Summary Although
Incan
Summary
Although
ordinary
relatively
inert,
the
ring
can
be
both
and
stereospecifi
nucleophiles,
be
opened
both
regioselectively
and
stereospecifi
cally.
For
anionic
nucleophiles,
the
both regioselectively
regioselectively
andare
stereospecifi
cally.
For
anionic
nucleophiles,the
the
ordinary ethers
ethers
are
relativelycally.
inert,For
theanionic
ring ininoxacyclopropanes
oxacyclopropanes
In
be opened
openedAlthough
both
regioselectively
and
stereospecifi
cally.
For
anionic
nucleophiles,
the
canSummary

can
be
opened
both
regioselectively
stereospecifi
cally.
For
nucleophiles,
usual
of
u
nu
oph and
ub
u on ho
d A
hthe
nd the
dthe
bimolecular
nucleophilic
hold:
Attack
is
less
can
rules
of
bimolecular
nucleophilic
substitution
hold:
Attack
is
at
the
less
hindered
usual
bimolecular
nucleophilic
substitution
hold:
Attack
less hhindered
hindered
be rules
opened
both
regioselectively
andsubstitution
stereospecifi
cally.
Forkanionic
anionic
nucleophiles,
can
rules
of bimol
usual
bimolecular
nucleophilic
substitution
hold:
Attack
isis at
atat the
the
less
hindered
usual
rules
nucleophilic
Attack
ischanges
less
bon
n of
wh
h und
go
nv onsubstitution
A
d catalysis,
yhold:
how
v changes
his at
ng
hthe
ghindered
ohindered
carbon
center,
which
undergoes
inversion.
Acid
however,
the
regioselecusual
center,
which
undergoes
inversion.
Acid
catalysis,
however,
changes
the
regioselecwhich
carbon
undergoes
inversion.
Acid
catalysis,
however,
regioselecrules
of bimolecular
bimolecular
nucleophilic
substitution
hold:
Attack
at the
the
less
usual
carbon
center,
which
undergoes
inversion.
Acid
catalysis,
however,
changes
the
regioseleccarbon
center,
which
undergoes
inversion.
Acid
catalysis,
however,
regioselecv y (but
bu no
h stereospecifi
o p ficity):
y A
kAcid
h mo
hhindered
nd changes
dchanges
n the
Hyd
d and
nd
tivity
not
the
Attack
is
the
more
center.
Hydride
(but
not
the
stereospecifi
city):
Attack
is
at
the
more
hindered
center.
Hydride
and
carbon
tivity
stereospecifi
city):
Attack
the
more
hindered
center.
Hydride
and
center,
undergoes
inversion.
catalysis,
however,
the
regioselec(but
notwhich
the
stereospecifi
city):
Attack
isis at
atat
the
more
hindered
center.
Hydride
and
carbon
tivity
(but not the
Attack
more
Hydride
o
g nom
gstereospecifi
n b
h v city):
k o
h anionic
nisis
onatat the
nu
oph hindered
u n hcenter.
ng alcohols
oho
by
nan
organometallic
reagents
behave
like
other
nucleophiles,
furnishing
an
by
organometallic
reagents
behave
like
other
anionic
nucleophiles,
furnishing
alcohols
an
tivity
reagents
behave
like
other
anionic
nucleophiles,
furnishing
alcohols
byand
by
organometallic
reagents
behave
like
other
anionic
nucleophiles,
furnishing
alcohols
an
(but not the
stereospecifi
city):
Attack
the
more
hindered
center.
Hydride
and
tivity
organometallic
S
hw y reagents behave like other anionic nucleophiles, furnishing alcohols by an
pathway.
SNNNN222 ppathway.
organometallic
pathway.
reagents behave like other anionic nucleophiles, furnishing alcohols by an
organometallic

99 -- 11 00 SS uu ll ff uurr AAnnaallooggss ooff AAl lccoohhool lss aanndd EEt thheer rs s

9-10 Sulfur Analogs

hers
n
Al lcllcccoooohhhhooool lsllsss aaanaannd
nddd
d EEEtE
Ethttthh
99--1100 SSuuulllfffuuurrr AAAnnnaaalllooogggsss ooooffff AAA
ehereersrrsss
9-10 Sulfur Analogs of Alcohols and Ethers

C Ch

365

Chapter 9

SulfurAnalogs
Analogs
of
Alcohols
Ethers
9-10
Analogs
of
Alcohols
and
Ethers
9-10 Sulfur
Sulfur
Analogs
of Alcohols
Alcohols
andand
Ethers
9-10
Sulfur
Analogs
of
Alcohols
and
Ethers
Ethers
of
and
Ethers
logs of Alcohols
and Ethers

locateddirectly
directly
below
oxygen
in
the
and
one
might
Sulfur is
isislocated
located
directly
below
oxygen
in the
the
periodic
table,table,
andtherefore
therefore
one
might
expect
Sulfur
directly
below
oxygen
inperiodic
the periodic
periodic
table,
andtherefore
therefore
one
mightexpect
expect
below
oxygen
therefore
onemight
might
expect
Sulfur
in
the
periodic
table,
and
therefore
one
might
expect
below
oxygen
in
table,
and
one
expect

Sulfuroxygen
is located
directly
below
oxygen
in theone
periodic
and therefore one might expect
below
in the
periodic
table,and
and ethers
therefore
mightintable,
expect
the sulfur
sulfur
analogs
ofof
alcohols
tobehave
behave
rather
similar
manner.
In
this
secsulfur
analogs
alcohols
ethers
to
in
rather
manner.
InInthis
alcohols
andand
similarsimilar
manner.
Inthis
thissecsecthe
of
alcohols
and
ethers
to behave
behave
in aasimilar
rather
similar
manner.
thissecsecthe
analogs
ethers
to
behave
inaaaarather
rather
similar
manner.
In
this
secof
alcohols
and
ethers
to
behave
in
rather
similar
manner.
In
this
secanalogs
of
alcohols
and
ethers
to
manner.
In
ohols
and ethers
to behave
in a rather
similar
manner.
Inin
this
section,
we
shall
see
whether
this
assumption
is
true.
whether
thisthis
weshall
shallsee
see
whether
assumption
isis true.
tion,
shall
see
assumption
istrue.
true.
this
assumption
isis
whether
this
assumption
true.
whether
this
assumption
true.
ertion,
this we
assumption
iswhether
true.

analogs
ofare
alcohols
andsul
des
sulfur
of
alcohols
and
ethers
are
and
des
The
ethers
arethiols
thiols
andsul
sul
des
analogs
of
alcohols
and
ethers
are
thiols
and
sul
des
of
alcohols
and
ethers
thiols and
des
sulfuranalogs
analogs
of
alcohols
and
ethers
are
and
sul
The
of
alcohols
and
ethers
are thiols
thiols
and
suldes
des

sulfur
The sulfur
analogs
ofthiols
alcohols,
R
SH,
are
called
thiolsGreek,
inthe
theIUPAC
IUPAC
system
(theion,
Greek,
ohols,
R SH,analogs
are called
in the
system
(theion,
of
alcohols,
R
are
called
thiols
inin
system
Greek,
alcohols,
RIUPAC
SH,
SH,
IUPAC
system(theion,
(theion,
Greek, Greek,
The
analogs
are
called
thiols
in
the
IUPAC
system
(theion,
Greek,
of
alcohols,
R

SH,
are
called
thiols
the
IUPAC
system
(theion,
Greek,
sulfur
analogs
of
alcohols,
R
SH,
are
called
thiols
in
IUPAC
system
(theion,
The
of
alcohols,
Rto
SH,
are
called
inthe
the
IUPAC
system
(theion,
Greek,
me
for sulfur).
ending
thiol
is added
the
stem
tothiols
yield
brimstone

an older
older
name
for
sulfur).
Thealkane
ending
thiol
isadded
added
to
the
alkane
stem
to
yield

an
name
for
sulfur).
The
ending
thiol
is
toto
yield
brimstone
an
The
ending
thiol
is
added
to
the
alkane
stem
to
yield
older
name
for
sulfur).
The
ending
thiol
is
added
the
alkane
stem
yield
The
name
for
sulfur).
tothe
thealkane
alkanestem
stemtoto
to
yield

an
older
name
for
sulfur).
The
ending
thiol
is
added
to
the
alkane
stem
brimstone
name
for
sulfur).
The
ending
thiol
is
added
to
the
alkane
stemtotoyield
yield
hethe
SHalkanethiol
group is referred
as mercapto,
the Latin
the
alkanethiol
name.toThe
The
SH
group
is
referred
tomercurium,
asmercapto,
mercapto,from
from
the
Latin
mercurium,
name.
SH
isis
to
as
name.
The
SH
group
referred
to
as
mercapto,
from
the
Latin
mercurium,
alkanethiol
referred
to
as
mercapto,
from
the
Latin
mercurium,
The
SHgroup
groupfrom
isreferred
fromthe
theLatin
Latinmercurium,
mercurium,
alkanethiol
name.
The
SH
group
isismercury
referred
to
as
from
the
Latin
mercurium,
othe
capture,
because
of
its ability
to
precipitate
(and
name.
SH
group
referred
toother
as
mercapto,
from
the
Latin
mercurium,
mercury,
and captare,
captare,
to
capture,
because
ofits
itsability
ability
tomercapto,
precipitate
mercury
(and
other
and
to
capture,
because
of
toto
precipitate
(and
other
captare,
to
capture,
because
of
its
ability
precipitate
mercury
(and
other
mercury,
and
because
of
its
ability
to
precipitate
mercury
(and
other
toThe
capture,
precipitatemercury
mercury
(and
other
ocation
indicated
byIts
numbering
the
longest
chain,
as
alkanol
mercury,
and
captare,
to
because
of
ability
to
mercury
(and
mercury,
andions.
captare,
to capture,
capture,
because
ofinits
its
ability
to precipitate
precipitate
mercury
(andother
other
location
isis
by
the
chain,
in
heavyismetal)
metal)
ions.
Its
location
is indicated
indicated
bynumbering
numbering
thelongest
longest
chain,asas
as
inalkanol
alkanol
location
indicated
by
numbering
the
longest
chain,
in
alkanol
longest
chain,
as
in
alkanol
apto
functional
precedence
than hydroxy.
heavy
metal)group
ions.hasItslower
location
is indicated
by numbering the longest chain, as in alkanol
nomenclature.
The
grouphas
hasby
lower
mercapto
functional
precedence
than
hydroxy.
nomenclature.
mercapto
functional
group
lower
precedence
hydroxy.
heavy
metal)The
ions.
Its location
is indicated
numbering
thethan
longest
chain, as in alkanol
The
mercapto
functional
group
has
lower
precedence
than
hydroxy.
nomenclature.
group
has
lower
precedence
than
hydroxy.
mercapto
functional
precedence
than
hydroxy.
nomenclature. The
group
SH

nomenclature.
The mercapto
mercapto functional
functional
group has
has lower
lower precedence
precedencethan
thanhydroxy.
hydroxy.

SH

SH

SH
SH

SH

CH3
A

SH
2CHCH2

CH
SH

CH33
SH
1-butanethiol

2

SH

A CH
CH3333
CH
CH3CH2CHCH
ACH
AA
A 2CH3

SH

SH

SH

HSCH
OH
AASH
 2CH2

AA

CH
CH
CH222CHCH
CH
SH

CHCH
SH

333
22CH
3232
CH
CHCH
SH
CH

CH333CH
CH22CHCH
CHCH
CH33333
CH
2SH
3CH
22CHCH
CHCH
SH
3-Pentanethiol
Cyclohexanethiol
2-Mercaptoethanol

3CH
2
2CH
2
2
22


444
3
2
1
ASH
33
22
4
3
2 A111

SH

SH

Methanethiol
2-Methyl-1-butanethiol
3-Pentanethiol
Cyclohexanethiol
Methanethiol
2-Methyl-1-butanethiol
2-Methyl-1-butanethiol
Cyclohexanethiol
3-Pentanethiol
Cyclohexanethiol
2-Methyl-1-butanethiol
3-Pentanethiol
Cyclohexanethiol
CH
SH
CH
CH
SH
CH

3thioethers)
33CH
22CHCH
33
fMethanethiol
ethers
(common
name,
are2
called
des,
as in
alkyl 22CH


CH33
SH
CH
CH2CHCH
CHCH
SH sulfi3-Pentanethiol
CH
CH
CHCH
CH

44 3 33 2 22 11 22
RS group is named alkylthio,
the RS group alkanethiolate.

HSCH
CH
OH

HSCH
CH
OH

2
HSCH
OH

HSCH
OH
2
2
HSCH
CH
OH
22


2CH
2


 2 22CH


2-Mercaptoethanol
2-Mercaptoethanol

2-Mercaptoethanol
2-Mercaptoethanol
2-Mercaptoethanol
HSCH
C

HSCH
 2

The
of
called
des,
Methanethiol
of
ethers
calledsulfi
sulfi
des,
as
in
alkyl
2-Methyl-1-butanethiol
3-Pentanethiol
Cyclohexanethiol
The sulfur
sulfur analogs
analogs
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,
alkyl
(commonname,
name,thioethers)
thioethers)are
are
called
sulfi
des,
as
in
alkyl
of ethers
ethers(common
des,asas
asinin
inalkyl
alkyl 2-Mercap
Methanethiol
2-Methyl-1-butanethiol
3-Pentanethiol
Cyclohexanethiol
2-Merca
222 called sulfi
2 groupalkanethiolate.
etherCH
nomenclature.
The
ether
nomenclature.
The
RS
group
is
named
alkylthio,
the
RS
alkanethiolate.
RS
group
named
alkylthio,
the
RS
group
group
alkanethiolate.
ether
nomenclature.
The RS
RS group
groupisis
isnamed
namedalkylthio,
alkylthio,the
theRS
RS2group
group alkanethiolate.
alkanethiolate.
3
A
The
sulfur
analogs
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,
as
in
alkyl
The
sulfur
analogs
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,
as
in
alkyl

CH3
S
CH3
SCH2CH
CH
OH
2
CH3CS(CH
3233
CH
2)6CH3



CH
3
ether
group
is named
alkylthio, the
ACH
A nomenclature.
ether
nomenclature. The
The RS
RS
the RS
RS2 group
groupalkanethiolate.
alkanethiolate.
AA
Agroup is named alkylthio,


CH
S
CH
SCH
SCH
OH
CH
CH

3


3 33

CH
S
CH
OH
CH
SCH22CH
CH33
CH
SCH
CH33CS(CH
CS(CH

CH
CS(CH

2)2)6)CH
CH
S
CH3
SCH2CH
CH2
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Thiols
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are
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hydrogen
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hydrogen
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methyl
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ter
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ciently.
are
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sulfidethe boiling points
heptyl
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ormally
as those
oflarge
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their
volatilities
liethe
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Sulfur,high
because
of
its
size,
its
diffuse
orbitals,
and
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nonpolarized
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because
of
its
large
size,
its
diffuse
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large
size,
its
relatively
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bond
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diffuse
orbitals,
and
the
relatively
nonpolarized
SS
H
bond
because
of
its
large
size,
its
relatively
nonpolarized
Spoints
Hbond
bond
s(Table
haloalkanes
(Table
9-2).
1-2),
does
not
enter
into
hydrogen
bonding
very
effi
ciently. Thus,
the
boiling
1-2),
does
not
enter
into
hydrogen
bonding
very
effi
Thus,
the
boiling
points
enter
into
ciently.
Thus,
the
boiling
points
(Table
hydrogen
bonding
very
efficiently.
ciently.
Thus,
the
boiling
points
1-2),
does
not
enter
into
ciently.
Thus,
the
boiling
points
Thiols
are
less
hydrogen
bonded
and
more
acidic
than
alcohols
e Thiols
relatively
weak
S

H
bond,
thiols
are
also
more
acidic
than
water,
of
thiols
are
not
as
abnormally
high
as
those
of
alcohols;
rather,
their
volatilities
lie
close
are
less
hydrogen
bonded
and
more
acidic
than
alcohols
of
thiols
are
not
as
abnormally
high
as
those
of
alcohols;
rather,
their
volatilities
lie
close
rather,
their
volatilities
lie
close
thosedeprotonated
of alcohols;byrather,
of
thiols
arethe
notanalogous
as
from
9 to of
12.
They
canabnormally
therefore
behigh
moreas
readily
abnormally
high
as
rather, their
their volatilities
volatilities lie
lie close
close
to those
haloalkanes
9-2).
Sulfur,
of its large
size, its (Table
diffuse
orbitals, and the relatively nonpolarized SH bond
of
haloalkanes
(Table
analogous
haloalkanes
ions.
to those
(Table 9-2).
9-2).
thosebecause
of the
the analogous
analogous
haloalkanes
Sulfur,
because
of its large
size, its diffuse
orbitals, and the relatively nonpolarized SH bond

Partly because of the relatively weak S H bond, thiols are also more acidic than water,

Partly
because
the
relatively
weak
SSH
bond,
thiols
areeffi
also
more
(Table
1-2),
doesof
not
into hydrogen
very
ciently.
Thus,than
the water,
boiling
points
also
more
acidic
than
water,
because
of
theenter
relatively
weak
H bonding
bond,
thiols
also
more
acidic
also
moreacidic
acidic
than
water,
(Table
does
not
enter
hydrogen
bonding
very
effi
ciently.
Thus,than
thewater,
boiling
points
Acidity
of Thiols
withPartly
pKa1-2),
values
ranging
from
9into
to 12.
They
can
therefore
beare
more
readily
by
Table
9-2deprotonated
withthiols
pK
ranging
from
99 to
can
be
readily
deprotonated
by
more
readily
deprotonated
by
of
are
not
as abnormally
highThey
as those
of alcohols;
rather,
their
volatilities
close
with
pKaaa values
values
ranging
from
to 12.
12.
They
can therefore
therefore
be more
more
readily
deprotonated
by
more
readily
deprotonated
bylie
hydroxide
and
alkoxide
ions.
 not

thiols
are
as
abnormally
high
as
those
of
alcohols;
rather,
their
volatilities
lie
close

Hof

HO

HOH

RS

hydroxide
and
alkoxide
ions.

 haloalkanes (Table 9-2).
hydroxide
and
alkoxide
ions.
Comparison of the Boiling
to
those
of
the
analogous
912
pKa  15.7 (Table 9-2).
to those of the analogous haloalkanes
Acidity
of Thiols
of Thiols,
Table 9
Partly because of the relatively
weak
SThiols
H bond, thiols Points
are also
moreHaloalkanes,
acidic than water,
Acidity
of
cidic Partly because of the relatively
Less
acidic
Acidity
of
Thiols
Table
weak S H bond,
thiolsand
areAlcohols
also more acidic than water,
Table
Table
Table



with pK values ranging

from
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They can
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RSH
 9HO
12.
HOH

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therefore







Compar


 
with pKaa values ranging
from
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therefore
be
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 They can
RS

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RSH

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pK

912
pK

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ethers
a
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Comp
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Comp
Points
o
pK

912
pK

15.7
a
a
pK

15.7
pK

912
pK

15.7
hydroxide and alkoxide
pK
 15.7
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point (8C)
aa
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Point
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Alc

2-Methyl-1-butanethiol
2-Methyl-1-butanethiol
Methanethiol
Methanethiol
2-Methyl-1-butanethiol
Methanethiol
2-Methyl-1-butanethiol
Methanethiol
2-Methyl-1-butanethiol
Methanethiol
2-Methyl-1-butanethiol
2-Methyl-1-butanethiol
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2-Methyl-1-butanethiol
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SCH
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3-Pentanethiol
3-Pentanethiol
3-Pentanethiol
3-Pentanethiol
3-Pentanethiol
3-Pentanethiol
3-Pentanethiol

Cyclohexanethiol
Cyclohexanethiol
Cyclohexanethiol

2-Mercap
2-Merca
2-Mercap
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Cyclohexanethiol
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Cyclohexanethiol
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called

analogs
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ethers
(common
name,
thioethers)
are
called
sulfi
des,
as
in
alkyl
TheThe
sulfur
analogs
ofof
ethers
(common
name,
thioethers)
are
sulfi
des,
as
inalk
al
sulfur
analogs
ethers
(common
name,
thioethers)
are
called
sulfi
des,
as
alkyl
analogs
of
ethers
name,
thioethers)
are
called
sulfi
des,
as
in
A name,
name,
thioethers)
are
called
sulfi
des,
as
in
alkyl
analogs
of
ethers(common
(common
name,thioethers)
thioethers)
are
called
sulfi
des,
asin
in
alkyl
The
sulfur
analogs
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,
as
in
alkyl
2
The
sulfur
of
ethers
(common
are
called
sulfi
des,
sulfur
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,
alkyl
2
analogs
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,
alkyl
The
2
2
2
analogs
sulfur analogs
of
ethers
(common
name,
thioethers)
are
called
sulfi
des,asasas
asininin
inalkyl
alkyl
2
ether
2
nomenclature.
The
RS
group
is
named
alkylthio,
the
RS
group
alkanethiolate.
nomenclature.
The
RS
group
named
alkylthio,
the
RS
group
alkanethiolate.
erether
alkylthio,
the
RS
group
alkanethiolate.
The
RS
group
isis
named
alkylthio,
the
RS
group
alkanethiolate.
The
RS
group
isnamed
named
alkylthio,
the
RS
group
alkanethiolate.
nomenclature.
The
RS
group
is
named
alkylthio,
the
RS
group
alkanethiolate.
2
2
CH
nomenclature.
The
RS
group
is
named
alkylthio,
the
RS
group
alkanethiolate.
22
ether
2group
3 alkylthio,
ether
nomenclature.
The
RS
group
is
the
RS
alkanethiolate.
2

ether
The
RS
group
is
named
alkylthio,
the
RS
group
alkanethiolate.
ether nomenclature. The
The RS
RS group
group is
is named
named alkylthio,
alkylthio, the
the RS
RS group
group alkanethiolate.
alkanethiolate.
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heptyl
sulfide
heptyl
sulfide
heptylsulfide
sulfide
heptyl
sulfide
heptyl
heptyl
sulfide
Sulfur,
because
of its1,1-Dimethylethyl
large
heptyl
sulfide
heptyl
sulfide
heptylsize,
sulfideits diffuse orbitals, and the relatively nonpo
heptyl
sulfide
heptyl
sulfide
(Table
1-2),
does
not
enter
into
hydrogen
bonding
very
effi
ciently.
are
less
hydrogen
bonded
and
more
acidic
than
alcohols
Thiols are
hydrogen
bonded
and
more
acidic
than
alcohols
Thiols
are less
hydrogenbonded
bondedand
andmore
moreacidic
acidicthan
than
alcohols Thus,
less hydrogen
hydrogen
bonded
and
more
acidic
than
alcohols
alcohols
are
less
hydrogen
bonded
and
more
acidic
than
alcohols
Thiols
hydrogen
bonded
and
more
acidic
than
alcohols
are
less
hydrogen
bonded
and
more
acidic
than
alcohols
of
thiols
are
not
as
abnormally
high
as
those
of
alcohols;
rather,
their
vo
iols
hydrogen
bonded
and
more
acidic
than
alcohols
because
of
its
large
size,
its
diffuse
orbitals,
and
the
relatively
nonpolarized
bond
Sulfur,
ofits
itslarge
large
size,
its
diffuse
orbitals,
and
the
relatively
nonpolarized
SSH
H
bond
Sulfur,
largesize,
size,its
itsdiffuse
diffuseorbitals,
orbitals,and
and
the
relatively
nonpolarized
H
bond
because of
of
its
large
size,
its
diffuse
orbitals,
and
the
relatively
nonpolarized
H
bond
because
the
relatively
nonpolarized
SSSS
H
bond
Sulfur,
because
of
its
large
size,
its
diffuse
orbitals,
and
the
relatively
nonpolarized
bond
large
size,
its
diffuse
orbitals,
and
the
relatively
nonpolarized
S
bond
Sulfur,
because
of
its
to
those
ofdoes
the
analogous
haloalkanes
(Table
9-2).
large
size,
its
diffuse orbitals,
orbitals,
and
the
relatively
nonpolarized
SHH
H
bond
(Table
1-2),
does
not
enter
into
hydrogen
bonding
very
effi
ciently.
Thus,
the
boiling
points
enter
into
hydrogen
bonding
very
effi
ciently.
Thus,
the
boiling
points
because
of
its
large
size,
its
diffuse
and
the
relatively
nonpolarized
S

H
bon
1-2),
does
not
enter
into
hydrogen
bonding
very
effi
ciently.
Thus,
the
boiling
points
fur,
its
large
size,
its
diffuse
orbitals,
and
the
relatively
nonpolarized
S

H
bo
1-2),
not
enter
into
hydrogen
bonding
very
effi
ciently.
Thus,
the
boiling
points
(Table
enter
into
hydrogen
bonding
very
effi
ciently.
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the
boiling
points
1-2),
does
not
enter
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hydrogen
bonding
very
effi
ciently.
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the
boiling
points
1-2),
does
not
enter
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hydrogen
bonding
very
ciently.
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the
boiling
points
(Table
enter
into
hydrogen
bonding
very
effi
ciently.
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the
boiling
points
1-2),
does
notabnormally
(Table
enter
into
hydrogen
bonding
very
effi
ciently.
Thus,
the
boiling
points
thiols
are
not
as
high
those
alcohols;
rather,
their
volatilities
lie
close
of
not
as
abnormally
highasas
asthose
those
ofalcohols;
alcohols;
rather,
their
volatilities
lie
close
Partly
because
ofinto
thehydrogen
relatively
weak
S effi
Heffi
bond,
thiols
are
more
1-2),
does
not
enter
bonding
very
ciently.
Thus,
the
boiling
poin
are
not
as
abnormally
high
ofof
rather,
their
volatilities
lie
close
ble
not
are
not
as
abnormally
high
as
those
of
alcohols;
rather,
their
volatilities
lie
close
of
thiols
abnormally
high
as
those
of
alcohols;
rather,
their
volatilities
lie
close
into
hydrogen
bonding
very
effi
ciently.
Thus,
thealso
boiling
poi
of thiols
thiols
are
not
as
abnormally
high
those
alcohols;
abnormally
high
as
those
of
alcohols;
rather,
their
volatilities
lie
close
of
thiols
arethe
notanalogous
as enter
abnormally
high as
as(Table
those of
of
alcohols; rather,
rather, their
their volatilities
volatilitieslie
lieclose
close
those
of
haloalkanes
9-2).
to
analogous
haloalkanes
(Table
9-2).
those
the
analogous
haloalkanes
9-2).
are
as
abnormally
high
those
of
alcohols;
their
lie
ofnot
the
analogous
haloalkanes
9-2).
with
pKof
values
ranging
fromas
9(Table
to 12.
canrather,
therefore
be
more readil
to
those
analogous
haloalkanes
(Table
9-2).
thiols
abnormally
high
as(Table
those
of They
alcohols;
rather,
theirvolatilities
volatilities
lieclo
cl
of
the
analogous
haloalkanes
(Table
9-2).
to
analogous
haloalkanes
(Table
9-2).
those
ofabecause
the
to those
analogous
haloalkanes
(Table
9-2).
Partly
of
the
relatively
weak
bond,
thiols
are
also
more
acidic
than
water,
because
ofthe
the
relatively
weak
S
H
H
bond,
thiols
are
also
more
acidic
than
water,
Partly
Partly
because
of
relatively
weak
SSS
SH
are
also
more
acidic
than
water,
because
of
the
relatively
weak
S
H
bond,
thiols
are
also
more
acidic
than
water,
Partly
thehaloalkanes
relatively
weak
Hbond,
bond,thiols
thiols
are
also
more
acidic
than
water,
of the
analogous
(Table
9-2).
hose
Partly
because
of
the
relatively
weak
bond,
thiols
are
also
acidic
than
analogous
(Table
9-2).
hydroxide
and
alkoxide
the
relatively
weak
S
H
bond,
thiols
are
also
more
acidic
than
water,
because
of
thehaloalkanes
relatively
weak
S
H
H
bond,
thiolsbe
are
alsomore
more
acidic
thanwater,
water,
pKa values
ranging
from
99ions.
to
can
therefore
readily
deprotonated
byby
withPartly
ranging
from
to 12.
12. They
They
can
therefore
bemore
more
readily
deprotonated

pK
values
ranging
from
to
12.
They
can
therefore
be
more
readily
deprotonated
by
with pK
ranging
from
to
12.
They
can
therefore
be
more
readily
deprotonated
by
ranging
from
therefore
be
more
readily
deprotonated
bywate
pK
values
ranging
from
to
12.
They
can
therefore
be
more
readily
deprotonated
by
aaa values
with
ranging
from99999to
to12.
12.They
They
can
therefore
be
more
readily
deprotonated
by
of
the
SScan
H
bond,
thiols
also
more
acidic
ranging
from
12.
can
therefore
be
more
readily
deprotonated
with
ranging
from
to
12.
They
can
therefore
be
more
readily
deprotonated
by
Partly
of
the relatively
relatively
weak
H
bond,
thiols
are
also
more
acidicthan
thanby
wa
aaa values
because
pKbecause
values
with
ranging
from 99
9 to
to weak
12. They
They
can
therefore
beare
more
readily
deprotonated
by
and
alkoxide
ions.
hydroxide
ions.
hydroxide
and
alkoxide
ions.
andranging
alkoxide
ions.
and
alkoxide
ions.
hydroxide
alkoxide
ions.
Acidity
of
Thiols
and
alkoxide
ions.
h
pK
values
from
9
to
12.
They
can
therefore
be
more
readily
deprotonated
hydroxide
alkoxide
ions.
and
pKaa values ranging
hhydroxide
alkoxidefrom
ions.9 to 12. They can therefore be more readily deprotonatedb
Acidity
of
Thiols
Acidity
of
Thiols
Acidity
of
Thiols
droxide and
Acidity
of
Thiols
Acidityof
ofThiols
Thiols
and alkoxide
alkoxide ions.
ions. Acidity
droxide
Acidity
of
Thiols

Acidity
of
Thiols


Acidity
of
Thiols

RSH







RSH

HO


RSH


RSH

HO

RSH

HO





RSH

HO



Acidity


pKa 


RSH
 HO
HO

RSH

HO


912
RSH

HO






RSH

HO



pK

912
pK
912


pK

912
pK

912
aaaa
pK

912
pK

912
pK
a

912
pK

912
pK
912
pK
More
912 acidic 
aaaaaa 
More
acidic
RSH
 HO

HO
 RS





RS


HOH

 
RS

HOH

RS

HOH



RS



HOH
RS



HOH
 HOH

RS
 

HOH
RS

Acidity of
ofThiols
Thiols

HOH

RS


HOH

RS


15.7
pKpK

15.7
a

pK

15.7

15.7
apK
pK
pKaaaaaa
15.7
15.7
pK

15.7
pK
pK

15.7
pKaaaaa
15.7
15.7


Less
acidic
HOH
RS

More
acidic
Less
acidic

More
acidic
Less
acidic
More
acidic
Less
acidic

RSH

HO
HOH


RS

More
acidic
Less
acidic
More
acidic
Less
acidic
More
acidic
Less
acidic
More
acidic



More acidic
Less
acidic
acidic
Less
pKMore
 912
pKacidic
 15.7

pKaa  912

HOH

pKa  15.7

Less acidic

pKa aa  15.7

Thiols and
sul
des
react
much
like
alcohols
and
ethers
sul
des
react
alcohols
and
More
acidic
Less
sul
des
Thiols
react
much
like
alcohols
and
ethers
react
much
like
alcohols
and
ethers
More
acidic
Lessacidic
acidic
sul
des
react
much
like
alcohols
and
ethers
Thiols
sul
des
reactmuch
muchlike
like
alcohols
andethers
ethers
Thiols
and
sul
des
react
much
likeand
alcohols
and ethers
react
much
like
alcohols
and
ethers
and
Thiols and
sul
des
Many reactions
reactions
of
thiols
and
sulfi
des
resemble
those
their
oxygen
analogs.
The
sulfur
their
oxygen
analogs.
The
sulfur
inin
Many
reactions of
of thiols
thiols
and
sulfi
des
resemble
those
of
their
oxygen
analogs.
The
sulfur
inin
thiolsand
andsulfi
sulfides
desresemble
resemblethose
thoseofof
of
their
oxygen
analogs.
The
sulfur

Many reactions
reactions of
of thiols
thiols
and
sulfi
des
resemble
those
of
their
oxygen
analogs.
The
sulfur
in
thiols
and
sulfi
des
resemble
those
of
their
oxygen
analogs.
The
sulfur
and
des
those
oxygen
analogs.
The
inin
Many
thiols
and sulfi
sulfi
desresemble
resemble
thoseof
oftheir
theirand
oxygen
analogs.
Thesulfur
sulfur
reactions
thiols
and
sulfi
des
resemble
those
of
their
oxygen
analogs.
The
sulfur
in
Many
reactions
ofis
thiols
and
sulfi
des
resemble
those
of
their
oxygen
analogs.
The
sulfur
inin
iols
sul
des
much
like
alcohols
ethers
Many
reactions
of react
thiols
and
sulfi
des
resemble
those
of
their
oxygen
anal
these and
compounds
is
even
more
nucleophilic
and
much
less
basic
than
the
oxygen
alcohols
compounds
more
nucleophilic
and
much
less
basic
than
the
oxygen
inin
alcohols
and
sulof
des
much
like
alcohols
and
ethers
these
compounds
is
even
more
nucleophilic
and
much
less
basic
than
the
oxygen
alcohols
iols
iseven
even
more
nucleophilic
and
much
less
basic
than
the
oxygen
alcohols
these
even
more
nucleophilic
and
much
less
basic
than
the
oxygen
in
alcohols
even
more
and
than
the
alcohols
these
evenreact
morenucleophilic
nucleophilic
andmuch
muchless
lessbasic
basic
than
theoxygen
oxygeninin
in
alcohols
compounds is
is
even
more
nucleophilic
and
much
less
basic
than
the
oxygen
inin
alcohols
these compounds
these
compounds
is even
more
nucleophilic
and
muchmade
less basic
thannucleophilic
the oxygen attack
inattack
alcohols
Therefore,
thiols
and
sulfi
readily
through
byby
and ethers.
Therefore,
thiols
and
sulfides
desare
are
readily
made
through
nucleophilic

ethers.
Therefore,
thiols
and
sulfi
des
are
readily
made
through
nucleophilic
attack
by
these
compounds
is
even
more
nucleophilic
and
much
less
basic attack
than
the
o
andreactions
Therefore,
thiols
and
sulfi
des
are
readily
made
through
nucleophilic
attack
by
thiols
and
sulfi
des
are
readily
made
through
nucleophilic
attack
by
ethers.
thiols
and
sulfi
des
are
made
through
nucleophilic
by
ny
of
thiols
and
des
resemble
those
of
their
oxygen
analogs.
The
sulfur
and
Therefore,
thiols
and
sulfi
des
arereadily
readily
made
through
nucleophilic
attack
by
2
2
2
2Therefore,
2
ethers.
Therefore,
thiols
and
sulfi
des
are
readily
made
through
nucleophilic
attack
by
and
2
2
ny
sulfu
of
thiols
and sulfi
sulfi
des
resemble
those
of
their
analogs.
The
sulfur
Therefore,
thiols
and
sulfi
des
are
readily
made
through
nucleophilic
attack
by
22
2
2 ethers.
2
or
HS
on
haloalkanes,
with
competing
elimination.
Aoxygen
large
excess
ofof
the
HS
RSreactions
on
haloalkanes,
with
little
competing
elimination.
A
large
excess
the
HS
2
22
2
or
HS22
onTherefore,
haloalkanes,
with
little
competing
elimination.
A
large
excess
of
the
HS
2
2
2
haloalkanes,
withlittle
little
competing
elimination.
A
large
excess
ofthe
the
HS
RS
haloalkanes,
with
little
competing
elimination.
A
large
excess
of
the
HS
2 or
2 on
22
HS
haloalkanes,
with
little
competing
elimination.
A
large
excess
of
HS
and
ethers.
thiols
and
sulfi
des
are
readily
made
through
nucl
RS
haloalkanes,
with
little
competing
elimination.
A
large
excess
of
the
HS
se
compounds
is
even
more
nucleophilic
and
much
less
basic
than
the
oxygen
in
alcoho
or
HS
on
haloalkanes,
with
little
competing
elimination.
A
large
excess
of
the
HS
RS
or in
HSthe
with to
little
competing
elimination.
Anot
large
excess
of
the
HS
used
preparation
of
thiols
ensure
that
the
product
does
react
with
the
startishaloalkanes,
even more
nucleophilic
and
much
less basic
than
the
oxygen
instartalcoh
seis
is compounds
the
preparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
used
in
theon
preparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
start2 in
2
preparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
startpreparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
startused
the
preparation
of
thiols
to
ensure
that
the
product
does
not
startis
preparation
ofand
thiols
todes
ensure
that
the
product
does
notreact
reactwith
withthe
the
startused
the
preparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
startethers.
thiols
sulfi
are
readily
made
nucleophilic
attack
orin
HS
on
haloalkanes,
with
competing
elimination.
A
large
is
used
inTherefore,
the
preparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
starthalide
to
the
dialkyl
sulfi
de.
ing
to
give
the
dialkyl
sulfi
de.
ethers.
Therefore,
and
sulfi
des
arelittle
readily
made through
through
nucleophilic
attackeb
dd2RS
halide
to give
give
the
dialkyl
sulfi
de.
dialkyl
sulfi
de.
ing
thethiols
halide
give
the
dialkyl
sulfi
de.
2 to
dialkyl
sulfi
de.
ing
the
dialkyl
sulfi
de.
halide
to
give
the
dialkyl
sulfi
de.
2
2is
ing
or
HS
on
haloalkanes,
with
little
competing
elimination.
A
large
excess
of
the
halide
to
give
the
dialkyl
sulfi
de.
preparation
thiols
to ensure
that
theAproduct
doesofnot
re
orused
HS in
on the
haloalkanes,
withof
little
competing
elimination.
large excess
theHS
H
CH
CH
CH
CH
33
33
CH
CH
CH
CH
used
the
of
thiols
to
ensure
that
the
product
not
react
with
the
star
CH
3
ACH
ACH
3
33
33
CH
333 does
CH
AAA give
A
333
CH
inhalide
the preparation
preparation
of
thiols
to
ensure
that
the
product
does
not
react
with
the
sta
used
st
ing in
to
the
dialkyl
sulfi
de.
CH
CH
OH
CH
CH
A
3
3
CH
CH
OH
AA 3
AA 3
AA

Br

CH
CH
OH


CH
CH
OH
CH
CH
OH
A
CH
CH
OH
CH
CHBr

SH
Na
Na
CH
CHSH

CH
CH
OH



halide
to
give
the
dialkyl
sulfi
de.
Athe dialkyl
A



SH
Br
CH

33CHBr
3 3CHSH
CHCH
CHOH
OH



CH
CH
OH
CH
CHBr
 Na
SH
Br
Na
Na
CH
 Na



give
sulfi
de. CH
halide to CH
3CHBr
SH


CH
CHBr
3CHSH

Na
Br
Na

CH CHBr
CHBr 


SH
Na
CH

SH
Na
SH
 Na
SH
Na
CH
SH
Na
Excess
CH333333CHBr
CHBr 

SH
Na
Excess

33 2 2
33
22
33
22
22
33
3
2
3
2
3
2
3
2

CHSH

Na
Br
CHCHSH
CHSH 
 Na
Na
Br
CH
CH
Br

Na
Br
Br

Na
Br
 Na

CH
33CHSH
33
CH
CHSH
CH
3
2-Propanethiol
3
CH
CHSH
2-Propanethiol
33CHSH

CH3
Excess
2-Propanethiol
CH3
Excess
2-Propanethiol
Excess
Excess
2-Propanethiol
2-Propanethiol
Excess
2-Propanethiol
CH
CH
Excess
Excess
2-Propanethiol
2-Propanethiol
Excess
3
3
2-Propanethiol
CH
A
3
AA 3 A
ACH
CH CH OH CH3CH2OH
A


Br 
CH
CH
OH
CH3CHBr

Na SH
CH
CHSH
3
22
CH
CHBr

SH
Na
CH
CHSH

3

Br

3
3
CH3CHBr  Na SH
Na
CH3CHSH  Na
3

Excess
Excess

Excess

2-Propanethiol 2-Propanethiol
2-Propanethiol

Table 9-2
Comparison of the Boiling
Points of Thiols, Haloalkanes,
and Alcohols
Compound

Boiling
point (8C)

CH3SH
CH3Br
CH3Cl
CH3OH
CH3CH2SH
CH3CH2Br

6.2
3.6
224.2
65.0
37
38.4

CH3CH2Cl
CH3CH2OH

12.3
78.5

rther Reactions of Alcohols and the Chemistry of Ethers

eeF uprepared
prepared
in an
an analogous
analogous way
way by
by alkylation
alkylation of
of thiols
thiols in
in th
t
alkylation
of
thiols
in
th
in
Further Reactions of Alcohols and the Chemistry of Ethers
366
Chapter 9
e Fprepared
in an
analogous
bytt hh ealkylation
of
thiols
in
Sulfi
des The
are
prepared
in anway
analogous
alkylation
hydroxide.
base
the
alkanethiolate,
which
reacts
alkanethiolate,
which
e CC hh eeway
m ii ss tt rrby
hreacts
hydroxide.
u r t h e r R eThe
a c t i obase
n s o generates
fgenerates
A ll cc oo hh oo ll ssthe
aa nn ddalkanethiolate,
m
yywhich
ooff EEtthreacts
eerrss
base
generates
thebygenerates
alkanethiolate,
react
se,
such
asThe
hydroxide.
The
S
2Sulfi
process.
Because
of
thebase
strong
nucleophilicity
of
thiolat
nucleophilicity
of
thiolat
des are
prepared
in an
analogous
way
alkylation
of the
thiols alkanethiolate
in which
theof
presence
of
N2
Sydroxide.
process.
Because
of
the
strong
nucleophilicity
thiolate
N
Sulfides are prepared in an analogous way by alkylation of thiols in the presence o
base,hydroxide
such
hydroxide.
The
base
the The
alkanethiolate,
reacts
with
halobase,
suchthe
as
hydroxide.
base
thewhich
alkanethiolate,
which
reacts
the halo
Som
process.
ofgenerates
strong
nucleophilicity
ofthewith
thiola
kane
byasan
SBecause
2 this
process.
Because
ofgenerates
the
strong
nucleophili
in
this
displacement.
N2 hydroxide
N
om
in
displacement.
alkane
by
an
S
2
process.
Because
of
the
strong
nucleophilicity
of
thiolates,
there
is no
alkane
SN2prepared
process.inBecause
of the way
strong
of thiolates,
there is no
Sulfiby
desanare
ancompetition
analogous
byinnucleophilicity
alkylation
of thiols
thiols
in the
the presence
presence
of
analogous
by
alkylation
of
in
of
from way
this displacement.
m
hydroxide
in hydroxide
this
displacement.
mpetition
from
inhydroxide
this
displacement.
competition
hydroxide
thisgenerates
displacement.
base,
such asfrom
hydroxide.
Theinbase
generates
the
alkanethiolate,
which
reacts
with
the
halothe alkanethiolate, which reacts with the haloSulfides by Alkylation of Thiols
alkane by an SN2 process. Because of
of the
the strong
strong nucleophilicity
nucleophilicity of
of thiolates,
thiolates, there
there isis no
no
Thiols
Sulfides
by
Alkylation
of Thiols
Thiols
Sulfides
by
Alkylation
of Thiols
competition from hydroxide
displacement.
in
this displacement.
RSH  RBr
RSR  NaBr  H O
Sulfides The
byNaOH
Alkylation
Thiols
Sulfides byofAlkylation
of Thiols
nucleophilicity of sulfur also explains the ability of sulfides to attack haloalkane
NaOH
NaOH
RSH  RBr
Thiols
NaBr  H2O
RSR
to furnishby
sulfonium
ions.
by
Alkylation
of
Thiols
Sulfides
Alkylation
of
RSH C h a 

NaBr

H
F u r t h e r R e a c t i o n s RSR
oRSR
f A l c o h o l s
a n d t NaBr
hNaBr
e C h e m i s t r
y
tH
he2
sO
366
p t e r 9 RBr
o f EH
O
22rO
NaOH
NaOH
HC
NaOH H C G
NaOH
G to attack haloalkanes
The
nucleophilicity
of
sulfur
also
explains
the
ability
of
sulfi
des
k


O
RSH  RSHRBr
 NaBr
HNaB
SRSR
 CH
SH
I
RSH
RBr

RSR
OINaBr
NaBr

H2CH
RSR
O 
 RBr


RSR
2O
2O
D 
D
to furnish sulfonium ions. Sulfides are prepared
H Cin an analogous way by alkylation
H C of thiols in the presence of
95% reacts
ophilicity
also
explains
the
ability
of
sulfi
des
to
atta
of
sulfi
des
to
attac
base,
such asexplains
hydroxide. The base
generates
the alkanethiolate,
which
with
the attac
haloof
sulfur
also
the
ability
of
sulfi
des
to
explains
the ability
ability of
of sulfi
sulfides
des to
to attack
attack haloalkanes
haloalkanes
The nucleophilicity ofalkane
sulfur
the
by also
an S 2explains
process. Because
C
H3ofC thestrong nucleophilicity of thiolates, there is no
onium
hydroxide in also
this displacement.
toThe
furnishnucleophilicity
sulfonium
ions.
G ions.competition
Gability
philicity
ofH3sulfur
also
explains
sulfi
des
toofatta
offrom
sulfur
explains
the
ability
Sulfonium
salts are subjectthe
to nucleophilic
attack atof
carbon,
the
de functioning
as ths
 sulfi

Sk  CH
I
O
S
CH
I
O


3
3

leaving 
group (see also Chapter 6 Opening).
D
Sulfides byD
Alkylation of Thiols
onium
furnishions.
sulfonium
ions.
H3C
C
H
H33C 
G
G

OG
 CHH
S(CH
) 95%
HOCH
S(CH )
H
 RBr


H3C

NaBr
RSR
O

O
O

HO
3S


Sk  CH33O
IRSH
CH
I
SC
CH 
I
33




D 
D
D G
G33 iodide
G
Trimethylsulfonium
H3C
C
H
C
H

3
k
3

The
nucleophilicity
of
sulfur
also
explains
the
ability
of
sulfi
des
to
attack

OExercise
OCH
9-25ions.

 haloalkanes
I

CH333H3
O


Isulfonium
CH
II
SSO
I
H3C S  H3CH
H3C 95%
C 33O
C






95%
GD salts are subjecttoGfurnish
DD
G
G
Sulfonium
to
nucleophilic
attack
at
carbon,
the
sulfi
de
functioning
as
the

k Sulfi
Trimethylsulfonium

Trimethylsulfonium
iodide

de
(margin)CH
is a powerful
poison
knownHas
gas, a devastating
warfare
H
C
H

Oiodide
H
chemical
Sk  CH3SO
SCmustard
CH
I
I
HA C
SO
CH
3C group
3in33C
3
3O

leaving
6I
Opening).


used inGWorld
I and again
the eight-yearGwar between Iraq and Iran in the 1980s.
The
k WarCH

O
O


S
I
S
CH
I
D  (see also Chapter
D
D  agent
D



specter of chemical
and biological weapons loomed again
the Persian Gulf war of 1990 1991,
D
D during
95%
95%
H C condition
C sulfi
H
and 
a medical
knownat
as Gulf
has 95%
been,
times,
salts are H
subject
attack
carbon,
the
de
the
nucleophilic
attack
at
carbon,
the
sulfi
deatfunctioning
functioning
the
HSulfonium
Csyndrome
H
C to theasassuspected
H3ascribed
3C
3war
3C to nucleophilic
exposure of ground troops to chemical and perhaps biological
95%agents during the campaign. The


Chapter
6
Opening).
leaving group (see
Opening).
HO
CH3 O
S(CH
chemical
)2
S(CH
3)2 of 1925 explicitlyHOCH
Geneva
protocol
bans
the 3use of
and 3biological
weapons.
The 1982
Trimethylsulfonium
iodide
Trimethylsulfonium
iodide
Trimethylsulfonium
iodide
also 


95
Biological and 1993 (ratified by the United States in 1997) 95%
Chemical Weapons Conventions ban
N

NaOH

Trimethylsulfonium iodide

NaOH
3

3 2

3 2

Soldiers wearing chemical

protective gear.

Trimethylsulfonium iodide

such materials, but there is great concern about compliance and enforcement. One of

 areofsubject
Sulfoniumpossession
salts
to nucleophilic attack at carbon, the sulfide functioning as the
the
problems is the relative ease with which such toxic chemicals can be produced, as highlighted
ClCH2CH

2SCH
2CH2Cl

O
(see
also
Chapter
HO
CH33group
S(CH
HOCH
S(CH
S(CH
HOCH
with
S(CH33))22 (Hint: Your retrosyn33))22(a)
33 
A  leaving

in this
problem.
Propose6a Opening).
synthesis
oxacyclopropane.

of A starting


Trimethylsulfonium
iodide
Trimethylsul

are subject
to nucleophilic
attack
at
sulfi
de
nucleophilic
attack
at thecarbon,
carbon,
the
sulfi
deof func
funis
carbon,
the
sulfi
de
func
thetic analysis should
proceed through
diol precursor tothe
A.)
(b) Its
mechanism
action
s Exercise
9-25
believed
to include sulfonium
salt B, which is thoughtto react with nucleophiles
CH
HO
 CH O S(CH
)
HOCH 
S(CH ) in the body. How
 B formed,
ClCHChapter
CH S OA Cl
is compound
and how would it react with 
nucleophiles? 
also
6
Opening).
(see
Opening).
CH
s are subject
nucleophilic
at carbon,
theatsulfi
de fun
ulfonium
saltstoare
subject to attack
nucleophilic
attack
carbon,
t


3 2

3 2

Sulfide A (margin)
B is a powerful poison known as mustard gas, a devastating chemical warfare
Exercise
agent used9-25
in World War I and again in the eight-year war between Iraq and Iran in the 1980s. The
expansion of sulfur accounts for the special
Exercise
9-25

Valence-shell
specter of chemical and biological
weapons loomed
again
during
the Persian Gulf war of 1990 1991,
reactivity
of thiols
and sul
des
Sulfi
A (margin)
is a known
powerful
poison
known
as
gas,
chemical
warfare
poison
known
as mustard
mustard
gas,
a devastating
devastating
chemical
warfare
Sulfias
de Gulf
A
(margin)
is syndrome
a powerful
poison
as mustard
gas,
a devastating
chemical
warfare
and ade
medical
condition
war
hasknown
been,
at atimes,
ascribed
to the
suspected
3
3
2
333Iraq
333 222
As ainin
third-row
element
with
orbitals,
sulfurs
valence
shell
can
expand
to
accommodat
agentagain
used
World
I and again
indthe
eight-year
war
between
and
in1980s.
the
1980s.
The
3 War
2perhaps
agent
usedofinground
World War
I3and
the
eight-year
war
between
Iraq
and
Iran
in
the
The
in
the
eight-year
war
between
Iraq
and
Iran
inIran
the
1980s.
The
exposure
troops
to
chemical
and
biological
agents
during
the
campaign.
The
more
 byloomed
CH3SH
specter
of chemical
and than
biological
weapons
again
during
the Persian
Gulf
war
1990 1991,
electrons
are allowed
the octet
rule
(Section
1-4).
We
haveof already
seen that
specter
of chemical
biological
weapons
loomed
again
during
the
Gulf
war
of
1991,
weapons
again
during
the Persian
Persian
war
of1990
1990
1991,
Methanethiol
and a medical
condition
known
as
Gulf
war
hasbybeen,
atGulf
times,
ascribed
to The
the
suspected
in
some
of the
itsloomed
compounds,
sulfur
issyndrome
surrounded
10 or
even
12
valence
electrons,
and thi
Geneva
ofand
1925
explicitly
bans
use of
chemical
and
biological
weapons.
1982
 protocol

and
a
medical
condition
known
as
Gulf
war
syndrome
has
been,
at
times,
ascribed
to
the
suspected
exposure
of
ground
troops
to
chemical
and
perhaps
biological
agents
during
the
campaign.
The
capacity
enables
sulfur
compounds
to
undergo
reactions
inaccessible
to
the
corresponding
Gulf
war
has been,
ascribed
to the suspected
KMn O(ratifi
3edGeneva
3 2syndrome
3 in bans
3atchemical
2times,
3biological
Biological
and 1993
by the
United
States
1997)
Chemical
Weapons
Conventions
ban 3
Soldiers
wearing chemical
protocolanalogs.
of 1925
explicitly
the useofof
and
weapons.
1982
oxygen
For
example,
oxidation
thiols with
strong
oxidizing
agents,The
suchThe
as hydro
exposure
troops to
chemical
and
perhaps
biological
agents
during
the
chemical
and
perhaps
biological
agents
during
the campaign.
campaign.
The
protective
gear.ofofground
possession
such
but
there
is1993
great
concern
aboutStates
compliance
and enforcement.
One
of way
(ratifi
ed by thepermanganate,
United
in 1997)
Chemical
Weapons
Conventions
gen and
peroxide
or
potassium
gives
the corresponding
sulfonic
acids.
In ban
this
O materials,Biological
Geneva
protocol
of
1925
explicitly
bans
the
use
of
chemical
and
biological
weapons.
The
1982
possession
of
such
materials,
but
there
is
great
concern
about
compliance
and
enforcement.
One
of
bans
the
use
of
chemical
and
biological
weapons.
The
1982
methanethiol
is
converted
into
methanesulfonic
acid.
Sulfonic
acids
react
with
PCl
the problems is the relative ease with which such toxic chemicals can be produced, as highlighted
5 to giv
CH
SOH
the
problems
is
the
relative
ease
with
which
such
toxic
chemicals
can
be
produced,
as
highlighted
ClCH
CH
SCH
CH
Cl
3
2
2 and2 1993
2
Biological
(ratifieda by
the
United
States
1997)
Weapons
Conventions
ban
sulfonyl
chlorides,
whichin
used inChemical
sulfonate synthesis,
as discussed
in Section 9-4.
United
States
inare
1997)
Chemical
Weapons
Conventions
ban
in this problem.
(a)
Propose
synthesis
of
A
starting
with
oxacyclopropane.
(Hint:
Your
retrosynA
in this problem.
(a)careful
Proposeoxidation
a synthesis
A starting
withuse
oxacyclopropane.
(Hint:inYour
retrosynMore
ofofthiols,
by the
ofand
iodine,
results
theOne
formation
o
O materials,thetic
possession
of
such
but
there
is
great
concern
about
compliance
enforcement.
of
there is
great
concern
and
of
analysis
should
proceed
throughabout
diolcompliance
precursor
A.)
(b) enforcement.
Its mechanism
of One
action is
is
thetic analysis Methaneshould proceed through
the
precursor
to
A.)
(b) toIts9-8).
mechanism
action
disulfides,
the diol
sulfur
analogs
ofthe
peroxides
(Section
Disulfi
des areof
readily
reduced
back
believed
to include
sulfonium
salt
B, which
is thoughtcan
to react
with
nucleophiles
the
body. How
the
problems
is 2theacid
relative ease
which
toxic
be
produced,
as
CH
with
which
such
toxic
chemicals
can
besodium
produced,
asinhighlighted
highlighted
toB,
thiols
by mild
reducing
agents,
suchwith
as aqueous
borohydride.
believed
to2Sinclude
saltwith
which
issuch
thought
tochemicals
react
nucleophiles
in the
body.
How
Osulfonic
A Cl sulfonium
ClCH2CH
is compound B formed, and how would it react with nucleophiles?
in
this problem.
(a) Propose
ahow
synthesis
of
with
Your
synthesis
of
A starting
starting
with oxacyclopropane.
oxacyclopropane. (Hint:
Your retrosynretrosynCH
is compound
B 2formed,
and
would
it A
react
with
nucleophiles?
isanalysis
aa Bpowerful
poison
known
as
mustard
gas,
a(Hint:
che
mustard
gas,
aa devastating
devastating
rgin)
poison
known
as
mustard
gas,
devastating
ch
powerful
thetic
should
through
the
to
Its
of
theticisanalysis
should proceed
proceed
through
the diol
diol precursor
precursor
to A.)
A.) (b)
(b)
Its mechanism
mechanism
of action
action isisch

see also
Chapter
6 Opening).
aving
group
(see also
Chapter 6 Opening).

O

CH
S(CH
))

HOCH

S(CH
HO
HOCH

S(CH
S(CH
HOCH

S(CH )))







HO
S(CH
) O
HO
 CH
S(CHHOCH
)
 HOCH
)
S(CH
  CH
O



4

Exercise 9-25
O

O
HO
CH33O
S(CH333))222

 CH


HO

S(CH

HO

CH33O
S(CH

3)2




HO
 

CH3 O
S(CH3)2

HOCH

S(CH3)332)22

 3333 

HOCH

S(CH

HOCH
S(CH

33)22



HOCH
 3


S(CH3)2


Exercise9-25
9-25
Exercise
9-25
Exercise

wearing
chemical
wearing
chemical
wearing chemical
gear.
Soldiers wearing chemical
gear.
gear.
protective gear.

CH
CH222SCH
SCH222CH
CH2Cl
CH222CH
ClCH CH22Cl
SCH CH Cl
2

A
A
A

CH222  CH

CH


ClSOA 2 Cl
H
CH22S
SClCH
AA2CHCl
H22CH
2
CH
CH
CH2
2
22

O
O
O
O

B
B

Exercise 9-25
Sulfide
de A
A (margin)
(margin)isisisaaapowerful
powerfulpoison
poisonknown
knownas
asmustard
mustardgas,
gas,aaadevastating
devastatingchemical
chemicalwarfare
warfare
Sulfi
de
A
(margin)
powerful
poison
known
as
mustard
gas,
devastating
chemical
warfare
Sulfi
agent used
used
inde
World
WarIIIis
and
againin
inthe
theeight-year
eight-year
war
between
Iraq
andIran
Iranin
the1980s.
1980s.
The
in
World
War
and
again
in
the
eight-year
war
between
Iraq
and
Iran
ininthe
the
1980s.
The
Sulfi
A (margin)
a powerful
poison
known as
mustard
gas,
aand
devastating
chemical
warfare
agent
in
World
War
and
again
war
between
Iraq
The
specter
of
chemical
and
biological
weapons
loomed
againduring
during
thePersian
Persian
Gulfwar
war
1990
1991,
1991,
used in
World
War I weapons
and
againloomed
in
the eight-year
war the
between
IraqGulf
and
Iran
in
the
1980s.
The
specter of
ofagent
chemical
and
biological
weapons
loomed
again
during
the
Persian
Gulf
war
ofof
1990
specter
chemical
and
biological
again
of
1990
1991,
andaaamedical
medical
condition
known
asGulf
Gulfwar
warsyndrome
syndrome
hasbeen,
been,
times,
ascribed
the
suspected
spectercondition
of chemical
and biological
weapons
loomedhas
again
during
the
Persian
Gulfto
war
ofsuspected
1990
1991,
and
medical
condition
known
as
Gulf
war
syndrome
has
been,
times,
ascribed
toto
the
suspected
and
known
as
atatattimes,
ascribed
the
exposureand
ofaground
ground
troops
tochemical
chemical
andperhaps
perhaps
biological
agents
during
thecampaign.
campaign.
The
medicaltroops
condition
known
as Gulf
war
syndrome
has been,
at times,
ascribed
to the suspected
exposure
of
ground
troops
to
chemical
and
perhaps
biological
agents
during
the
campaign.
The
exposure
of
to
and
biological
agents
during
the
The
exposure
of
ground
troops
to
chemical
and
perhaps
biological
agents
during
the
campaign.
The
Geneva
protocol
of
1925
explicitly
bans
the
use
of
chemical
and
biological
weapons.
The
1982
Geneva protocol
protocol of
of 1925
1925 explicitly
explicitly bans
bans the
the use
use of
of chemical
chemical and
and biological
biological weapons.
weapons. The
The 1982
1982
Geneva
Geneva
protocol
of ed
1925
explicitly
bans
the use
of
chemical
and biological
weapons.
The ban
1982
Biological
and 1993
1993
(ratifi
ed
bythe
theUnited
United
States
1997)
Chemical
WeaponsConventions
Conventions
ban
Biological
and
1993
(ratifi
by
the
United
States
inin1997)
1997)
Chemical
Weapons
Conventions
Biological
and
(ratifi
ed
by
States
in
Chemical
Weapons
ban
Biological
1993 (ratifi
ed
by the
United
States about
in 1997)
Chemical and
Weapons
Conventions
ban
possession
ofsuch
suchand
materials,
butthere
there
great
concern
compliance
enforcement.
One
possession
of
such
materials,
but
there
great
concern
about compliance
compliance
andenforcement.
enforcement.
One
possession
of
materials,
but
isisisgreat
concern
about
and
One
ofofof
possession
of
such
materials,
but
there
is
great
concern
about
compliance
and
enforcement.
One
of
the problems
problems is
isthe
therelative
relativeease
ease with
withwhich
whichsuch
suchtoxic
toxicchemicals
chemicalscan
canbe
beproduced,
produced,asasashighlighted
highlighted
the
problems
is
the
relative
ease
which
such
toxic
chemicals
can
highlighted
the
the problems
is the relativewith
ease with which
such toxic
chemicals be
canproduced,
be produced,
as highlighted
in this
this problem.
problem.(a)
(a)Propose
Proposeaaasynthesis
synthesisof
ofAAAstarting
startingwith
withoxacyclopropane.
oxacyclopropane.(Hint:
(Hint:Your
Yourretrosynretrosynthis
problem.
(a)
Propose
synthesis
of
starting
with
oxacyclopropane.
(Hint:
Your
retrosynin
in this problem. (a) Propose a synthesis of A starting with oxacyclopropane. (Hint: Your retrosynthetic
analysis
should
proceed
through
the
diol
precursor
to
A.)
(b)
Its
mechanism
of
action
thetic analysis
analysis
should proceed
proceedproceed
through
the diol
diol
precursor
A.)
(b) Its
Its mechanism
mechanism
action
thetic
should
through
the
toto A.)
ofof of
action
isisis
thetic analysis
should
through
the precursor
diol precursor
to (b)
A.)
(b)
Its
mechanism
action
is
believedbelieved
to include
include
sulfonium
saltB,
B,salt
which
thought
react
with
nucleophiles
the
body.
How
believed
to
include
sulfonium
salt
B,
which
thought
totoreact
react
with
nucleophiles
the
body.
How
believed
to
salt
which
isisisthought
to
with
nucleophiles
inininthe
body.
How
to sulfonium
include
sulfonium
B, which
is thought
to react
with
nucleophiles
in
the
body.
How
compound
B
formed,
and
how
would
it
react
with
nucleophiles?
compound
B
formed,
and
how
would
it
react
with
nucleophiles?
isis compound
B
formed,
and
how
would
it
react
with
nucleophiles?
is compound B formed, and how would it react with nucleophiles?

Valence-shell
expansion
of sulfur
accounts
the
special
Valence-shell
expansion
ofsulfur
sulfur
accounts
forfor
the
special
Valence-shell
expansion
of
sulfur
accounts
for
the
special
Valence-shell
expansion
of
accounts
for
the
special
reactivity
of thiols
and
sul
reactivity
of thiols
thiols
andsul
suldes
desdes
thiols
and
sul
des
reactivity
of
and
CH3SH CH3SH

Methanethiol

Methanethiol
Methanethiol

KMn O
O4444

O
CH33SOH
O
O

KMn O4

O
CH3SOH
O
Methane-

sulfonic acid
MethaneMethanesulfonic
sulfonic acid
acid

As a third-row
element
d orbitals,
sulfurs
valence
shell
expand
toaccommodate
accommodate
As aa third-row
third-row
element
with dddwith
orbitals,
sulfurs
valence
shell
cancan
expand
accommodate
third-row
element
with
orbitals,
sulfurs
valence
shell
can
expand
As
element
with
orbitals,
sulfurs
valence
shell
can
expand
tototoaccommodate
more electrons
than
are allowed
byoctet
the octet
rule
(Section
1-4).
have
alreadyseen
seenthat,
that,
more electrons
electrons
than are
are
allowed
bythe
the
octet
rule(Section
(Section
1-4).
WeWe
have
already
seen
that,
electrons
than
are
allowed
by
the
rule
(Section
1-4).
We
have
already
more
than
allowed
by
octet
rule
1-4).
We
have
already
seen
that,
in some of its compounds, sulfur is surrounded by 10 or even 12 valence electrons, and this
in
some
of
its
compounds,
sulfur
is
surrounded
by
10
or
even
12
valence
electrons,
andthis
this
in some
some of
of its
its compounds,
compounds, sulfur
sulfur isis surrounded
surrounded by
by 10
10 or
or even
even 12
12 valence
valenceelectrons,
electrons,and
and
this
capacity enables sulfur compounds to undergo reactions inaccessible to the corresponding
capacity enables
enables sulfur
sulfur compounds
compoundsto
toundergo
undergoreactions
reactionsinaccessible
inaccessibletototothe
thecorresponding
corresponding
capacity
capacity
enables
sulfur
compounds
to
undergo
reactions
inaccessible
the
corresponding
oxygen analogs. For example, oxidation of thiols with strong oxidizing agents, such as hydrooxygen analogs.
analogs.
For
example,
oxidation
of
thiols
with
strong
oxidizing
agents,
such
as
hydrooxygen
For
example,
oxidation
of
thiols
with
strong
oxidizing
agents,
such
as
hydrooxygen
analogs.
For
example,
oxidation
of
thiols
with
strong
oxidizing
agents,
such
as
hydrogen peroxide or potassium permanganate, gives the corresponding sulfonic acids. In this way,
gen peroxide
peroxide
orpotassium
potassium
permanganate,
givesthe
thecorresponding
corresponding
sulfonic
acids.
thisway,
way,
gen
or
permanganate,
gives
acids.
this
peroxide
or
potassium
permanganate,
gives
the
corresponding
sulfonic
acids.
InIn
this
way,
methanethiol
is converted
into methanesulfonic
acid. Sulfonicsulfonic
acids
react
withIn
PCl
5 to give
methanethiol
is converted
convertedwhich
intomethanesulfonic
methanesulfonic
acid.
Sulfonic
acids
reactinwith
with
PCl
togive
give
methanethiol
is
into
acid.
Sulfonic
react
PCl
methanethiol
is
converted
into
methanesulfonic
acid.
Sulfonic
acids
react
with
PCl
5
559-4.
5 to
sulfonyl
chlorides,
are
used in sulfonate
synthesis,
asacids
discussed
Section
5to give
sulfonyl
which
are
as
discussed
inininSection
sulfonyl chlorides,
chlorides,
whichoxidation
areused
usedin
insulfonate
sulfonate
synthesis,
asiodine,
discussed
Section
9-4.
sulfonyl
chlorides,
which
are
used
in
sulfonate
synthesis,
as
discussed
Section
9-4.
More careful
of
thiols,
bysynthesis,
the use of
results
in
the 9-4.
formation
of
More
careful
oxidation
of
thiols,
by
the
use
of
iodine,
results
in
the
formation
ofofof
More
careful
oxidation
of
thiols,
by
the
use
of
iodine,
results
in
the
formation
More
careful
oxidation
of
thiols,
by
the
use
of
iodine,
results
in
the
formation
disulfides, the sulfur analogs of peroxides (Section 9-8). Disulfides are readily reduced back
disulfi
the
analogs
of
(Section
9-8).
des
to thiols
by mild
reducing
agents, such
as aqueous
sodium
borohydride.
disulfides,
des,
thesulfur
sulfur
analogs
ofperoxides
peroxides
(Section
9-8).Disulfi
Disulfi
desare
arereadily
readilyreduced
reducedback
back
des,
the
sulfur
analogs
of
peroxides
(Section
9-8).
Disulfi
des
are
readily
reduced
back
to
thiols
by
mild
reducing
agents,
such
as
aqueous
sodium
borohydride.
to thiols
thiols by
by mild
mild reducing
reducingagents,
agents,such
suchas
asaqueous
aqueoussodium
sodiumborohydride.
borohydride.

9-11 Uses of Alcohols and

9-11 Uses of Alcohols and

9-11 Uses of Alcohols and

The
Thiol
Disulfi
de
Redox
Reaction
The Thiol
ThiolDisulfi
Disulfide
de Redox
RedoxReaction
Reaction
The
The Thiol Disulfide Redox Reaction
The Thiol Disulfide Redox Reaction

Oxidation:
Oxidation:
Oxidation:
Oxidation:
O
CH3CH
CH2CH
CH2 SSO
H

OH
H 
22 CH
 III222
3
22 CH22S
Propanethiol
1The
Thiol

Disulfi
O
CH
CH
CH
S
H
2
Propanethiol
 II2de
1Propanethiol
3
2
2
O
CH
CH CH S H 
2
3

1- Propanethiol
1- Propanethiol

O
CH
CH
CH
CH
CH2CH
CH3 

OSSSCH
CH
CH333CH
CH222CH
CH222SSSO
CH22CH
2 2CH
33 
2 CH


Dipropyl
disulfide
Redox
O
disulfide
CHReaction
CHDipropyl
CH2SSO
CH2CH
CHCH
Dipropyl
disulfide
3CH
2CH
2CH3
CH
SSCH
3

Dipropyl disulfide
Dipropyl disulfide

Reduction:
Reduction:
Reduction:
HO
HHOO
Reduction:
CH
CH2ICH
CH2S
SO
SSCH
CH
CH
CH

NaBH
CH
CH
4 SCH CH
2CH

NaBH
222CH
O
OS
H CH
CH222CH
CH
CH3333CH
2 CH
CH
NaBH
33CH
CH
22SS2S
22 CH
222CH
33CH
4
3CH
2CH
2 22SO
2 S 4O
2CH
3 2CH
HO2
HO
O
CH
CH
CH
S
S
CH
CH
CH

NaBH
2
CH
CH
CH
3
2
2
2
2
3
4
3
2
2S
CHde
SCH
 Dipropyl
NaBH
2important
CH3CH2CH
disulfide
3 CH
2 CH2 S Oby
2 CH2CHof
3 thiols
4 reverse
2S
Disulfi
formation
oxidation
and
its
are
biolo
Disulfi
de formation
formation by
by oxidation
oxidation of
of thiols
thiols and
and its
itsreverse
reverseare
areimportant
importantbiolo
biol
cesses,
although
nature
uses
much
milder
reagents
and
conditions
than
those
depict
cesses,
although
nature
much
reagents
those
Disulfi
de formation
formation
by oxidation
oxidation
of thiols
thiols
andand
itsconditions
reverse are
arethan
important
biol
nature uses
uses
much milder
milder
reagents
and
conditions
than
thosedepict
depic
Disulfi
de
by
of
and
its
reverse
important
biolo
Many
proteins
and
peptides
contain
free
SH groups
groups
that
form bridging
bridging
disulfi
de
proteins
peptides
contain
free
SH
form
disulfi
de
cesses,
althoughand
nature
uses much
much
milder
reagents
andthat
conditions
thanthose
those
depic
Many
and
peptides
contain
freereagents
SH groups
that
form bridging
disulfi
d
cesses,
although
nature
uses
milder
and
conditions
than
Nature exploits
exploits this
this mechanism
mechanism to
to link
link amino
amino acid
acid chains.
chains. By
By thus
thus helping
helpingdepict
to co
c
to
Many
proteins
and
peptides
contain
free
SH
groups
that
form
bridging
disulfi
d
Nature
this
mechanism
to
link
amino
acid
chains.
By
thus
helping
to
Many
proteins
andinpeptides
contain free
SH
groups that
formbiocatalysis
bridging disulfi
de
hape
of
enzymes
three
dimensions,
the
mechanism
makes
far
mor
hape
of
enzymes
in
three
dimensions,
the
mechanism
makes
biocatalysis
far
more
Nature
exploits
this
mechanism
to
link
amino
acid
chains.
By
thus
helping
to
hape
of
enzymes
in
three
dimensions,
the
mechanism
makes
biocatalysis
far
mo
Nature
exploits this mechanism to link amino acidH2chains.
By thus helping to c
O
and
selective.
and
selective.
of
enzymes
in
three
dimensions,
the mechanism
mechanism
makes2biocatalysis
biocatalysis
far
mo
and
selective.
SO
SCH
 NaBH
CH3CH2far
CH
hape
of
enzymes
three
the
makes
mor
2hape
2 CHin
2CH
3 dimensions,
4
2S
and
selective.
and selective.
SH
Oxidation
Oxidation
SHby oxidation of
ionSH
reverse
biolo
Oxidation
SH
SHthiols and itsSH
H S are important
SH
SSS
SH HHSS
SH
SH
SH
Oxidation
Oxidation
ure uses much milder
reagents
and
conditions
than
those
depic
SH HHSS
SH
SH
SH
SS
2
2 2

peptides contain free SH groups that form bridging disulfide

mechanism to link amino acid chains. By thus helping to c
Dis
Amino acid
acid chain
chain
Amino acid
acid chain
chain
Dis
Amino
Amino
D
Amino acid
chain
Amino acid chainthe mechanism makes
three dimensions,
biocatalysis
far mo

D
Aminoacid
acidchain
chain
Amino acid
acid chain
chain
Amino
Amino
Sulfides
des are
readily
oxidized to
to sulfones,
sulfones, aa transformation
transformation
proceeding through
throughDis
a
Sulfi
readily
oxidized
proceeding
Sulfides are
areFor
readily
oxidized
to sulfones,
a transformation
proceeding
througha
ntermediate.
example,
oxidation
of
dimethyl
sulfi
de
fi
rst
gives
dimethyl
ntermediate.
For
example,
oxidation
of
dimethyl
sulfi
de
fi
rst
gives
dimethyl
readily
oxidized
to sulfones,
sulfones,
transformation
throughha
ntermediate.
example,
oxidation
ofdimethyl
dimethyl
sulfideDimethyl
fiproceeding
rst gives
dimethyl
Sulfides
areFor
readily
oxidized
to
aa transformation
proceeding
through
a
DMSO),
which
subsequently
furnishes
sulfone.
sulfoxide
DMSO), which
subsequently
furnishes
dimethyl
sulfone.
sulfoxide
ha
ntermediate.
example,
oxidation
of
dimethyl
sulfi
deDimethyl
first
rstin
gives
dimethyl
DMSO),
which
subsequently
furnishes
dimethyl
Dimethyl
sulfoxide
Foras
example,
oxidation
of
dimethyl
sulfi
de
fiuse
gives
dimethyl
been
mentioned
a highly
highly polar
polar
nonprotic
solventsulfone.
of
great
organic
chemh
been
mentioned
as
a
nonprotic
solvent
of
great
use
in
organic
chem
DMSO),
subsequently
furnishes
dimethyl
sulfone.
Dimethyl
sulfoxide
h
been
mentioned
as
a highly
polar
nonprotic
solvent
ofand
great
use 6-5).
in organic
chem
subsequently
furnishes
sulfone.
Dimethyl
sulfoxide
ha
icularly
inwhich
nucleophilic
substitutions
(seedimethyl
Section
6-8
Table
Oxidation
icularly in
substitutions
(see
Section
6-8
Table
6-5).
been
highly
polarSH
nonprotic
solvent
ofand
great
usein
in6-5).
organicchem
chem
icularly
in nucleophilic
nucleophilic
substitutions
(seeH
Section
6-8
and
Table
mentioned
as a highly
polar
nonprotic
solvent
of
great
use
organic
S
SH
S
icularly
nucleophilic
substitutions
(see
Section
6-8
andto
6-5). used
n Summary
The naming
naming
of thiols
thiols and
and
sulfi
des is
is6-8
related
toTable
the 6-5).
system
used for
fo
in nucleophilic
substitutions
(see
Section
and
Table
The
of
sulfi
des
related
the
system
nn Summary
Summary
The naming
thiols and
sulfiacidic,
des is related
to the
system used
and
ethers. Thiols
Thiols
are more
moreofvolatile,
volatile,
more
and more
more
nucleophilic
thanfo
and ethers.
are
more
acidic, and
nucleophilic
than
n
naming
of
thiols
and
sulfi
des
is
related
to
the
system
used
and
ethers.
Thiols
are
more
volatile,
more
acidic,
and
more
nucleophilic
than
Summary
The
naming
of
thiols
and
sulfi
des
is
related
to
the
system
used
Thiols
and sulfi
sulfides
des can
can be
be oxidized,
oxidized, thiols
thiols to
to disulfi
disulfides
des or
or sulfonic
sulfonic acids
acids and
andfofo
Thiols and
ss
and
are
more
volatile, thiols
more acidic,
acidic,
and
more
nucleophilic
than
ethers.
Thiols
volatile,
more
and
nucleophilic
Thiols
andand
sulfi
des are
canmore
be oxidized,
to
disulfi
desmore
or sulfonic
acids than
and
ulfoxides
sulfones.
ulfoxides and sulfones.
Thiols
can be
be oxidized,
oxidized, thiols
thiols to
to disulfi
disulfides
des or
or sulfonic
sulfonic acids
acids and
ands
and and
sulfisulfones.
des can
ulfoxides

Ethers

Chapter 9

2 HI

2 HI
H

gical proed above.

linkages.
H
ontrol
the
e efficient
gical proed above.
linkages.
ontrol the
S
e efficient

CH3
SCH3

Dimethyl
sulfide
H 2O 2

CHO
S
CH3
3


367

OH
2 CH3CH CH SO

OSCH CH CH
CH CH CH SO

 II

The
Thiol
Disulfi
Redox
Reaction
2 CH33CH22CH22S O H
CH33CH
The 
ThiolI22 D
Disulfide
de R
Redox
Reaction
T
T
R
22CH22S O SCH22CH22CH33
ction:
O
Oxidation:
1- Propanethiol
Propanethiol
Dipropyl disulfide
disulfide
Dipropyl
1Reduction:

 22 HI
HI


Oxidation:
Oxidation:
O
CH
OH
O SCH
CH CH
CH2CH
CH S O
H 
2 CH
CH3CH
CH2CH
CH2SO
 I2
CH2CH
CH2CH
CH3 
HH22O
22OH
HI
H2O
OH
O
II22 S
CH33CH
CH
CH222S
H
22 CH
CH
S
CH
 H
22O
HI
2 CH
SO
22 CH
2S
22 CH
SO
CH332CH
CH
CH
O
HI
CHNaBH
CH22CH
CH4334 
CH
H
SCH
CH
CH
CH
SSdisulfide
NaBH
CH
Reduction:
22 SO
33 2 
3 1-3Propanethiol
22 33CH
222CH
2 22CH
2 2CH
3Dipropyl
4 4

CH CH
CH S O SCH CH CHDipropyldisulfideNaBH
Propanethiol
1- Propanethiol
Dipropyl disulfide
11- Propanethiol

Dipropyl disulfide
H222O
O
H

NaBH44
CH33CH22CH22S O SCH22CH22CH33  NaBH

R
Reduction:
Disulfide

CH2
22CH
CH
3CH
2CH
2SH
3
2
2
3CH
2CH2SH
3CH
2CH
2SH

CH33CH
CH22CH
CH22SH
SH
22 CH

formation by
by oxidation
oxidation of
of thiols
thiols and
and its
its reverse
reverse are
areimportant
importantbiological
biologicalproproformation

Disulfide formation by oxidation of thiols and its reverse are important biological proReduction:
Reduction:
R
ulfi
de
formation
by uses
oxidation
of thiols
and
its
reversethan
arethose
important
biologic
H
O
cesses,
nature
uses
much
milder
reagents
and
conditions
than
thosedepicted
depictedabove.
above.
nature
milder
reagents
and
conditions
and its
its
reverse
are
important
biological
proO
CH
CH
CH
CH
CH
CH

N
BH
CH
CH
CH
H biological
Disulfi
de
by 2oxidation
of
and
are
important
proH
O
CHalthough
CHformation
CH2SSO
SCH
CH
CH2CH
CH3much
 thiols
NaBH
CH
HO
Oreverse
3CH
2CH
4
3CHCH
2CHSH
2SH
CH
NaBH
222CH
3
2
2
2
22CH
33 
Suses
CH
CH
44
2
2
 milder
NaBH
N
BHfree
CH33CH
CH
H
although
nature
uses
much
reagents
and
conditions
than
those
depicted
3 CH
2 CH
2S O S
2 CH
2CH
2SH
reagents
and
conditions
cesses, CH
than
those
depicted
above.
although
nature
much
milder
reagents
and
conditions
than
those
depicted
above.
Many
peptides
contain
free
SH
groups
that
form
bridging
disulfi
delinkages.
linkages.
proteins
and
peptides
contain
SH
groups
that
form
bridging
disulfi
de
D
m
m
groups
that
form
Many
bridging
disulfi
de
linkages.
proteins
and
peptides
contain
free
SH
groups
that
form
bridging
disulfi
de
linkages.
Disulfide
formation
by oxidation
of thiolsto
andlink
its reverse
areimportant
important
biological
pro-thusbridging
proteins
and
contain
free
SHare
thatBy
form
Nature
this
mechanism
to
link
amino
acid chains.
chains.
By
helpingtotodisulfi
controlde
theli
exploits
this
mechanism
amino
acid
helping
control
the
Disulfi
formation
by
of
its
biological
proDisulfide
de
formation
by oxidation
oxidation
of thiols
thiols and
and
its reverse
reverse
are groups
important
biological
pro-thus
D
m peptides
m
m
m
acid
chains.
By thus
Nature
thus helping
helping
to control
control the
the
cesses,
although
nature
uses much
muchmilder
milder
reagents
and
conditions
than
those
depictedabove.
above.
exploitsnature
this mechanism
to link
amino
acid
chains.
By
to
cesses,
although
reagents
and
than
cesses,
although
nature uses
uses
much
milder
reagents
and conditions
conditions
than those
those depicted
depicted
above.
m
enzymes
in
three
dimensions,
the
mechanism
makes
biocatalysis
more
shape
inm
three
dimensions,
the
mechanism
makes
biocatalysis
far
moreeffi
effi
cient
M
H groups
m bridging
Many
proteins
and peptides
contain
free
SH
that
form
disulfi
defar
linkages.
exploits
this
to
link
amino
acid
chains.
By
thusfar
helping
tocient
con
mechanism
makes
shape proteins
biocatalysis
more
efficient
cient
ofof
enzymes
inmechanism
three
dimensions,
the
mechanism
makes
biocatalysis
more
effi
Many
and
contain
free
groups
that
bridging
disulfi
linkages.
Many
proteins
and peptides
peptides
contain
free SH
SH
groups
that form
form
bridging
disulfide
de far
linkages.
M
H
m
N
m
m
m
B
Nature
exploits this
this mechanism
mechanism to
to link amino
amino acid
acid chains.By
By thushelping
helping tocontrol
controlthe
the
selective.
and selective.
Nature
exploits
Nature
exploits
mechanism
to link
link amino
acid chains.
chains.
By thus
thus helping to
tomcontrol
the
N
m
m
B
ofand
enzymes
in
three
mechanism
makes
m this
mm dimensions,
mthe
m
shape
of enzymes
in three
dimensions,
the m
mechanism
makes
biocatalysis farmore
more
efficient biocatalysis far more e
shape
the
shape of
of enzymes
enzymes
in three
three dimensions,
dimensions,
the mechanism
mechanism
makes biocatalysis
biocatalysis far
far m
more effi
efficient
cient
m in
m
m
m makes
m
and selective.
and
ective.
and selective.
selective.

CH33
SCH
CH333
CH
S


SH
2

2
2
2

SH

SH

H
SH
SH
H

SH
H
SH
SH
SH
H

Amino acid chain

Amino acid
acidchain
chain
Amino
acid
chain
Amino

SH

SH
SH

SH
H
SH
SH
SH
H

HSS
H

HS
HHS
S
H

Oxidation
Oxidation

Oxidation HS
SH
SH
S
Oxidation
Oxidation H

SH
Amino acid
acid chain
chain
Amino
Aminoacid
acidchain
chain
Amino
chain
Amino
acid

S
SS

HS

SS Oxidation
SS
Oxidation
Oxidation
S
SS

CH
Dimethyl


CH
SCH
CH3 Dimethyl

CH

S3CH

3
CH
3
sulfide
SSCH33 sulfide
S

m
Dimethyl
m
Dimethyl
m
sulfide
sulfide
sulfide

Oxidation
Disulfide bridge
bridge
Disulfide

Disulfide
bridge
Disulfide
bridge
Disulfide
bridge

SS

HH222OO222

H O
H
H 22O
O 222 2

O
SOBB
O
O

SCH
CH333
CH333
S
CH

BB
CH
CH

S CH
CH
CH
CH
SDisulfide
3CH

3
3
CH

3
3 3 Dimethyl
Dimethyl
bridge
Disulfide
bridg

transformation proceeding
proceeding
through
sulfoxide
Sulfides are readily
oxidized
through
Amino
Amino
chain
Aminoacid
acidchain
chain aa sulfoxide
Amino acid
acid
chainto sulfones, a transformation
Amino
acid
chain
Amino
acid
chain
m sulfi
are For
readily
oxidized to
tosulfones,
sulfones,of
transformation
proceeding
throughdimethyl
sulfoxide
Sulfi
readily
oxidized
aaatransformation
proceeding
aa asulfoxide
sulfoxide
sulfoxide
Dimethyl
dimethyl
de fifirst
rst through
mm
intermediate.
gives
dimethyl
sulfoxide
example,
oxidation
dimethyl
de
gives
sulfoxide
Sulfides
des are
are
readily
oxidized
to
sulfones,
transformation
proceeding
through
sulfoxide
Dimethyl
m sulfi
Dimethyl
m
m
m
m
m
sulfoxide (DMSO)
(DMSO)
sulfoxide
For example,
example,
oxidation
of dimethyl
dimethyl
sulfi
de fi
rstgives
givesdimethyl
dimethyl
sulfoxide
intermediate.
For
oxidation
of
sulfi
de
sulfoxide
sulfoxide
intermediate.
For
example,
oxidation
of
dimethyl
sulfi
de
fifirst
rst
gives
dimethyl
sulfoxide
m
m
mdimethyl
m sulfoxide
dimethyl
sulfone.
(DMSO),
Dimethyl
sulfoxide
has
already
which
subsequently
furnishes
sulfone.
Dimethyl
has
already
(DMSO)
MMa sulfoxide
(DMSO)
DM Sulfi
O which
w
mto
D
m
(DMSO)
M
des
are
readily
oxidized
sulfones,
a
transformation
proceeding
through
which
subsequently
furnishes
dimethyl
sulfone.
Dimethyl
sulfoxide
has
already
(DMSO),
su
m
D
m
subsequently
furnishes
dimethyl
sulfone.
Dimethyl
sulfoxide
has
already
readily
oxidized
to
sulfones,
a
transformation
proceeding
through
a
sulfoxide
(DMSO),
which
DM
O
w
m
D
m
solvent of
of great
great use
use in
in organic
organic
chemistry, parparmentioned as a highly polar nonprotic solvent
been m
HH222OO222
m chemistry,
been m
mentioned as
as aaFor
highly
polar nonprotic
nonproticsolvent
solventofofgreat
greatdimethyl
use inorganic
organic
chemistry,
par-gives dimethyl
H22 O 2
m
mentioned
highly
polar
use
chemistry,
H
been
H 22O
O
m
mde
example,
sulfi
fifiparrst
sulfoxide
Sectionof
6-8 dimethyl
andinTable
Table 6-5).
in nucleophilic
substitutionsoxidation
(see Section
6-8
and
6-5).
ticularly
intermediate.
example,
oxidation
of
sulfi
de
rst
gives
dimethyl
sulfoxide
nucleophilic
substitutions (see
(see Section
Section6-8
6-8and
andTable
Table6-5).
6-5).
ticularlyAmino
in nucleophilic
substitutions
Disulf
Amino acid chain
acid chain
O

O
already
which
subsequently
furnishes
dimethyl
sulfone.
Dimethyl
sulfoxide
has
O

(DMSO),
subsequently
furnishes
dimethyl
sulfone.
Dimethyl
sulfoxide
has
already
B
B
is related
related
tosystem
the
Summary
Thenaming
naming
of
thiols
sulfi
is
the
used
for
system
used
for alcohols
alcohols
In Summary
des
mm
m of
BB
mm
m
mmsystem
The
naming
of thiols
thiols
andand
sulfides
desisdes
is
related
theto
usedfor
for
alcohols
In
The
and
sulfi
related
totothe
system
used
alcohols
mm
m
m
CH
CH
SSparCH333parCH333
CH
CH
been
mentioned
as
a
highly
polar
nonprotic
solvent
of
great
use
in
organic
chemistry,
CH
CH
CH
CH
S
been
mentioned
as
a
highly
polar
nonprotic
solvent
of
great
use
in
organic
chemistry,
acidic,
and
more
ethers.
Thiols
are
more
volatile,
more
acidic,
and
more
nucleophilic
than
alcohols.
3
3
nucleophilic
than
alcohols.
S
m
m
m
3
3
and
CH
CH
3
3
m
m
m
and ethers. Thiols
more
more
more
Thiols are
are m
more volatile,
volatile, m
more acidic,
acidic, and
and m
morenucleophilic
nucleophilicthan
thanalcohols.
alcohols.
BB
BB
fiticularly
des and
are
readily
oxidized
to
sulfones,
aorortransformation
proceeding
through
a su
disulfi
des
andsulfi
sulfi
descan
can
be
oxidized,
thiols
to disulfi
des
sulfonic
acids
and
sulfi
des
ticularly
in
nucleophilic
substitutions
(see
Section
6-8
and
Table
6-5).
sulfonic
acids
and
sulfi
des to
to
Thiols
O
Thiols
des
be
oxidized,
thiols
toto
disulfi
des
sulfonic
acids
sulfi
des
sulfi
des
can
be
oxidized,
thiols
disulfi
desoror
sulfonic
acids
and
sulfi
desto
to
O
O
O

in
nucleophilic
substitutions
(see
Section
6-8and
and
Table
6-5).
O

m
andsulfones.
sulfones.
sulfoxides
sulfoxidesand
and
sulfones.
m
Dimethyl
Dimethyl
Dimethyl
Dimethyl
Dimethyl
m

ediate. For example, oxidation of dimethyl sulfide first givessulfone

dimethyl
su
sulfone
sulfone
sulfone
sulfone
In Summary
for
In
Summary The
The naming
naming of
of thiols
thiols and
and sulfi
sulfides
des isis related
related toto the
thesystem
systemused
used
foralcohols
alcohols
O),
which
subsequently
furnishes
dimethyl
sulfone.
Dimethyl
sulfoxide
has
and
ethers.
Thiols
are
more
volatile,
more
acidic,
and
more
nucleophilic
than
alcohols.
9
11
Ph
o
og
ca
P
ope
e
and
U
e
o
A
coho
and
E
he
9-11
Physiological
Properties
Uses
of
Alcohols
Ethers
and
ethers.
Thiols
are
more
volatile,
more
acidic,
and
more
nucleophilic
than
alcohols.
Physiological
Properties
and
Uses
of
Alcohols
and
Ethers
9
11
Ph
o
og
ca
P
ope
e
and
U
e
o
A
coho
and
E
he
Alcohols and
and Ethers
Ethers
9-11 Physiological Properties and Uses of Alcohols
entioned
aoxidizing
highly
polar
nonprotic
solvent
of
great
use acids
in
organic
chemist
Thiols
and
sulfi
des
can
oxidized,
thiols
to
disulfi
or
sulfonic
and
des
m be
w
m
Thiols
andinas
sulfi
des
can
be
oxidized,
thiols
tooxygen
disulfi
des
orfound
sulfonic
acids
andsulfi
sulfi
destoto
Since w
we live
an
atmosphere,
ititisisnot
surprising
that
isisdes
found
in
abunanan
oxidizing
atmosphere,
that
oxygen
found
abunm
oxidizing
atmosphere,
itnot
is surprising
not
that
is
in
not surprising
surprising
that oxygen
oxygen
is in
found
in abunabunSince we liveininm
m sulfones.
M
w
M
mm are
w
dance
in the chemicals
of
Many
alcohols
and
with
biosulfoxides
and
of nature.
nature.
Many of
of them
them
are
alcohols
andethers
ethers6-8
withvaried
varied
biom
M
m
w
ysulfoxides
in nucleophilic
substitutions
(see
Section
and
Table
and
sulfones.
in thechemicals
chemicals
of
nature.
Many
of
them
are
alcohols
and
ethers
with
biothem
are
alcohols
and
ethers
with
varied
bio-6-5).
dance
m
m
mm
mmvaried
logical
medicinal
inin drug
m
m
logical functions,
functions, exploited
exploited by
by m
medicinal chemists
chemists
drugsynthesis.
synthesis.Industrial
Industrialchemists
chemists
exploited
by medicinal
chemists
in
Industrial
chemists
chemists
in drug
drug synthesis.
synthesis.
Industrial
chemists
logical functions,
m
produce
mm
produce alcohols
alcohols and
and ethers
ethers on
on aa large
large scale,
scale,totobe
beused
usedasassolvents
solventsand
andsynthetic
syntheticintermeinterme-

alcohols
and
ethers
onof
aof
large
scale,
touses
be
used
as
solvents
and
synthetic
be sulfi
used
asdes
solvents
and
synthetic
intermeproduce
m
m
mmis related
diates.
This
section
gives
aa glimpse
the
of
compound
classes.
m
m
mmary
The
thiols
and
tointermethe system used for a
diates.
This
sectionnaming
gives
glimpse
of
the versatile
versatile
uses
ofthese
these
compound
classes.
ThisPhysiological
section
glimpseby
ofthe
thecatalytic
versatile
uses
of
compound
classes.
versatile
uses
of these
these
compound
classes.
m
m
m
M
m
m
m
diates.
Methanol,
made
large
hydrogenation
ofofcarbon
monoxide
M
m
m
m
9-11
Properties
and
Uses
of
Alcohols
and
Methanol,
made in
ingives
largeaamounts
amounts
by
the
catalytic
hydrogenation
carbon
monoxide
9-11
Physiological
Properties
and
Uses
of
Alcohols
andEthers
Ethers
hers.
Thiols
more
more
acidic,
more
nucleophilic
than al
m
m hydrogenation
m stoves
(Section
8-4), ismade
soldare
asina large
solvent
for volatile,
paintby
and
materials,
as a fuel forand
camp
Methanol,
amounts
theother
catalytic
of
monoxide
catalytic
hydrogenation
ofmcarbon
carbon
monoxide
(Section 8-4),
materials,
m stoves
8-4), is
is sold
sold as
as aa solvent
solvent for
for paint
paintand
andother
otherm
materials,asasa afuel
fuelfor
forcamp
camp
stoves

mmand other

and
soldering
torches,
and
aa synthetic
intermediate.
ItItisit
highly
poisonous
ingestion
8-4),
is sold
as aas
solvent
for atmosphere,
paint
as
for
camp
stoves
m

other
as aa fuel
fuel
foror
camp
stoves is acids
(Section
and
soldering
torches,
and
as
synthetic
intermediate.
ismaterials,
highly
poisonous

ingestion
Since
we
live
in
an
oxidizing
is
surprising
that
oxygen
and
sulfi
des
be
oxidized,
thiols
to
disulfi
des
sulfonic
sulfi
Since
we
live
incan
an
oxidizing
atmosphere,
itmaterials,
isisnot
not
surprising
that
oxygen
isfound
foundinand
inabunabunm
D
mmingestion
m
or
exposure
may
lead
Death
from
ofofas
asas3030
mL
m
D
m
m
m
m
soldering
torches,
syntheticD
intermediate.
It
highly
poisonous

ingestion
andchronic
intermediate.
It is
highly
poisonous

ingestion
or
chronic
exposure
mayand
leadasto
toablindness.
blindness.
Death
from
ingestion
aslittle
little
mL
dance
in
the
nature.
Many
of
them
are
alcohols
and
ethers with
m
m
mm
has
been
reported.
ItIt is
sometimes
toto commercial
toto
render
itas
t tfor
mlead
mof
mm
dance
in
the chemicals
chemicals
of
nature.
Many
ofethanol
them
are
alcohols
and
withvaried
variedbiobiom
m
mm
has
been
reported.
ismay
sometimes
added
commercial
ethanol
render
itunfi
unfi
for
exposure
toadded
blindness.
Death
ingestion
of
little
as
30
mL
des
and
sulfones.
Death from
from
ingestion
of
as
little
as
30 ethers
mL
or chronic
m
consumption
(denatured alcohol). The toxicity of m
methanol
is thought to be due to m
metam
m

consumption
(denatured
The
ofof
methanol
isisthought
totoin
bebe
totom
metalogical
exploited
by
medicinal
chemists
drug
synthesis.
m functions,
consumption
(denatured
alcohol).
The toxicity
toxicity
methanol
thought
due
metareported.
It alcohol).
is
sometimes
added
tom
commercial
ethanol
render
itit unfi
has been
commercial
ethanol
todue
render
unfitt for
for Industrial
logical
functions,
exploited
by
medicinal
chemists
into
drug
synthesis.
Industrial chemists
chemists
m
CH
PO
w
w
mm probolic
oxidation
to
PO,
which
interferes
with
the
m
CH
PO
w
w
m
CH
w
w
m
bolic
oxidation
to formaldehyde,
formaldehyde,
CH222PO
PO,
which
interferes
with
thephysiochemical
physiochemical
pro-to
produce
alcohols
and
ethers
on
aaacid,
large
to
used
as
solvents
and
(denatured
alcohol).
The
of
methanol
thought
to
due
ofscale,
methanol
thought
to
be
due
to metametaconsumption
mmtoxicity
HCOOH
cesses
of
Further
oxidation
to
formic
HCOOH,
causes
acidosis,
unusual
produce
alcohols
and
ethers
on
large
scale,
toisisbe
be
usedan
asbe
solvents
andsynthetic
syntheticintermeintermeHCOOH
m
HCOOH
cesses
of vision.
vision.
Further
oxidation
toCH
formic
acid,
HCOOH,
causes
acidosis,
an
unusual
oxidation
to
formaldehyde,
PO,
which
interferes
with
the
physiochemical
probolic
which
interferes
with
the
physiochemical
pro22disrupts
diates.
This
section
gives
a
glimpse
of
the
versatile
uses
of
these
compound
classes.
w
H
lowering
of
the
blood
pH.
This
condition
oxygen
transport
ininthe
blood
and
leads
H
w
H
lowering
of
the
blood
pH.
This
condition
disrupts
oxygen
transport
the
blood
and
leads
diates.
section gives
a glimpse
of the
versatile
uses
of these
compound classes.
ofThis
vision.
oxidation
to formic acid,
HCOOH,
causes
acidosis,
an
acid,
HCOOH,
causes
acidosis,
an unusual
unusual
cesses
m
eventually
to
m Further
m
Methanol,
made
in
large
amounts
by
the
catalytic
hydrogenation
ofofcarbon
monoxide
eventually
to coma.
coma.
Methanol,
made
in
large
amounts
by
the
catalytic
hydrogenation
carbon
monoxide
lowering
of
the
blood
pH.
This
condition
disrupts
oxygen
transport
in
the
blood
and
leads
M
mmin the
disrupts
oxygen
transport
blood
and Simple
leads
Methanol
has
studied
as
possible
precursor
ofofgasoline.
For
example,
certain
zeoM
m
mm m
m
methanol
stove
used
for
m
methanol
stove
used
forfor
m
Methanol8-4),
has been
been
studied
as aaa
possible
precursor
gasoline.
For
example,
certain
zeomethanol
stove
used
(Section
is
sold
solvent
paint
as Simple
aSimple
for camp
stoves
w
m
m
mfuel
lite
catalysts to
3-3)
allow
the aconversion
methanol
intoand
am
mixture
of materials,
coma.
eventually
camping.
was
m
mother
mfuel for camp stoves
w
m
is
sold
as
solventofoffor
for
paint
and
other
materials,
am
lite
catalysts (Section
(Section
3-3)
allow
the conversion
methanol
into
ofhydrocarbons,
hydrocarbons, ascamping.
camping.
we(Section
live
in8-4),
an been
oxidizing
it
isa mixture
not
surprising
that
oxygen
isingestion
found
in
Methanol
has
studiedand
as aatmosphere,
possible
precursor
gasoline.
For
example,
certain
zeoand
soldering
torches,
as
aa synthetic
intermediate.
ItIt isis highly
poisonous

precursor of
of
gasoline.
For
example,
certain
zeoSimple
methanol
stove
Simple
methanol
stove uu
and
soldering
torches,
and
as
synthetic
intermediate.
highly
poisonous

ingestion
catalysts
(Section
3-3) allow thelead
conversion
of
into
of
hydrocarbons,
camping.
of methanol
methanol
into aa mixture
mixture
of
hydrocarbons,
camping.
litethe
or
chronic
exposure
blindness.
Death
from
ingestion
ofof asas
little
nor
chemicals
nature.
Many
of them
alcohols
ethers
vari
chronic
exposureofmay
may
lead to
to
blindness.
Deathare
from
ingestionand
littleaswith
as30
30mL
mL
has been
It
sometimes
added
to
ethanol
toto render
itit unfi
functions,
exploited
medicinal
in drug
synthesis.
has
been reported.
reported.
It is
is by
sometimes
addedchemists
to commercial
commercial
ethanol
renderIndustrial
unfit tfor
forc
consumption (denatured alcohol). The toxicity of methanol is thought to be due to meta(denatured
alcohol).
Thescale,
toxicity
ofbemethanol
issolvents
thought toand
be due
to meta-in
econsumption
alcohols
and
ethers
on
a
large
to
used
as
synthetic
bolic oxidation to formaldehyde, CH22PO, which interferes with the physiochemical probolic section
oxidationgives
to formaldehyde,
PO,versatile
which interferes
the physiochemical
proThis
a glimpse CH
of 2the
uses ofwith
these
compound classes

1 Physiological Properties and Uses of Alcohols and Ethe

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m
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Thus, simply put, the idea is to power our cars with sunlight
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practice,
Glucose Glucose
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9-11
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of
our fuel
fuel
needs.
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example,
in
2006, the
the
United
States committed
committed
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itscorn
corn
crop
o our
ou
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20%
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its
corn
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fuel
the
of
corn
of
example,
in
2006, of
the
United
States committed
committed
20%
ofits
its
corn
crop
of our
our
fuel
needs. For
For
example,
in
2006,
the
United
States
committed
20%
its
corn
crop
for
the
preparation
of 44.8
4.8
billion
gallons
ethanol.
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toou
our
daily
consumption
example,
in
2006,
the
United
States
committed
20%
of
its
corn
crop
of
example,
2006,
the
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corn
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2006,
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daily
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this
to
our
daily
consumption
of 4.8
preparation
for
4.8
billion
gallons
of
ethanol.
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this
our
daily
consumption
the
preparation
of
4.8
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ethanol.
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our
daily
consumption
for
4.8
billion
gallons
of
ethanol.
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this
to
our
daily
consumption
for
the
preparation
of
billion
gallons
of
ethanol.
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this
to
our
daily
consumption
of
almost
400 m
million
gallons
of ggasoline,
gasoline,
and
you realize
realize
scope
of
this
undertaking!
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4.8
billion
gallons
of
ethanol.
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this
our
daily
consumption
for
the
of
billion
gallons
ethanol.
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this
our
daily
consumption
of 4.8
4.8
billion
gallons
ofand
ethanol.
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toof
our
daily
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o almost
mopreparation
400
on
g
on
o
o n of
nd
you
hthescope
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oof
hthis
und
k ng The
Th
million
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of
and
the
scope
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of
almost
of
gasoline,
and
you
realize
the
scope
of
this
undertaking!
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gallons
million
400
million
gallons
of
gasoline,
you
realize
the
this
undertaking!
of
of gasoline,
gasoline,
and
yourealize
realizethe
the
scope
ofthis
undertaking!
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gallons
of
gasoline,
and
you
realize
the
scope
of
this
undertaking!
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of
almost
400
million
gallons
of
and
you
scope
of
undertaking!
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gallons
of
gasoline,
and
you
realize
the
scope
of
this
undertaking!
The
potential
negative
impact
of committing
committing
large
agricultural
areas
ofou
our
planet
tobbiofuel
biofuel
proof
400
of
and
scope
of
million
gallons
of gasoline,
gasoline,
and
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the
scope
ofthis
this
undertaking!
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po almost
n
nnegative
g million
v impact
mpgallons
o
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g realize
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pplanet
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pronegative
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ourplanet
of
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to
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areas
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our
planet
to
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on
the
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the
economy,
and
the
supply
(hence
price)
of
food
is
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matter
potential
negative
impact
of
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large
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areas
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to
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of
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our
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ood
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the
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matter
the
and
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duction
on
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economy,
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supply
(hence
price)
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is
matter
in
2006,
the
United
States
committed
20%
of
its
corn
crop
duction
on
the
environment,
the
economy,
and
the
supply
(hence
price)
of
food
is
a
matter
of
concern.
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a
more
fundamental
level,
some
critics
argue
that,
at
least
for
certain
crops,
environment,
the
economy,
and
the
supply
(hence
price)
of
food
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a
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n the
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least
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more
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at
least
for
certain
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of
concern.
level,
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for
complete
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offundamental
growing,
harvesting,
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and
distributing
biofuels
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concern.
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this
toargue
our
daily
growing,
harvesting,
fermenting,
and
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process
of
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fermenting,
and
then
biofuels
conthe
process
of growing,
then
distributing
biofuels
conthe
complete
process
of
growing,
harvesting,
fermenting,
and
then
distributing
biofuels
conprocess
of
growing,
harvesting,
fermenting,
and
then
distributing
biofuels
conthe
complete
process
of
harvesting,
fermenting,
and
then
distributing
biofuels
consumes
more
energy
than
it
returns,
dealing
a
fatal
blow
to
the
viability
of
such
efforts.
the
complete
process
of
growing,
harvesting,
fermenting,
and
then
distributing
biofuels
conum more
mo
n gy than
h n it
u n dealing
d
ng aaa fatal
bblow
ow to
o the
h viability
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u h efforts.
o
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energy
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itit returns,
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returns,
dealing
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to
the
viability
of
such
efforts.
sumes
energy
viability
of
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efforts.
blow
such
than
sumes
than
it
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dealing
a fatal
fatal
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to
the
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sumes
more
than
itthat
blow
viability
of
than
it
returns,
dealing
fatal
blow
the
viability
of
such
efforts.
Commercial
alcohol
is no
notdealing
intended
as
a bbeverage
beverage
isthis
made
industrially
byhyd
hydration
gasoline,
and
you
realize
the
scope
of
The
sumes
more energy
energy
than
ith returns,
returns,
dealing
fatal
blow
to the
the
viability
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such
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oho
n nd
daaa as
v to
gto
m
d undertaking!
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on
Commercial
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that
is
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made
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hydration
industrially
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hydration
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alcohol
that
is
not
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is
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industrially
by
that
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not intended
intended
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made
industrially
by
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made
alcohol
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that
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alcohol
Commercial
alcohol
as
by
that
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intended
as
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industrially
by
hydration
of
ethene
(Section
8-4).
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isis
used,
for
example,
as aa solvent
solvent
perfumes,
varnishes,
and
alcohol
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that
isu
notdintended
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beverage
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made
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o ethene
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4 that
o areas
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pperfumes,
um biofuel
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for
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as
in
and
of
(Section
perfumes,
varnishes,
and
8-4).
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is
used,
for
example,
as
a
solvent
in
perfumes,
varnishes,
and
is
used,
for
example,
as
a
solvent
in
perfumes,
varnishes,
and
of
mmitting
agricultural
of
our
planet
to
8-4).
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ethene
(Section
It
is
used,
for
example,
as
aaa solvent
solvent
in
perfumes,
varnishes,
and
8-4).
of
ethene
(Section
8-4).
It
is
used,
for
example,
as
a
in
perfumes,
varnishes,
and
It
is
used,
for
example,
as
solvent
in
perfumes,
varnishes,
and
8-4).
shellacs
and
as
a
synthetic
intermediate,
as
demonstrated
in
earlier
equations.
of
ethene
(Section
It
is
used,
for
example,
as
solvent
in
perfumes,
varnishes,
and
h
nd
yn
h
n
m
d
d
mon
d
n
qu
on
and as
as aa synthetic
synthetic
intermediate,
as
demonstrated
in
earlier
equations.
shellacs and
equations.
intermediate,
as
demonstrated
in
earlier
equations.
intermediate,
as
demonstrated
in
earlier
equations.
shellacs
earlier
synthetic
and
as
a
synthetic
intermediate,
as
demonstrated
in
earlier
equations.
synthetic
intermediate,
as
demonstrated
in
earlier
equations.
synthetic
intermediate,
as
demonstrated
in
earlier
equations.
and
as
aaoand
1,2-Ethanediol
(ethylene
glycol)
is
prepared
by
oxidation
of
ethene
to
oxacyclopropane,
shellacs
synthetic
intermediate,
as
demonstrated
in
earlier
equations.
and
as
e shellacs
economy,
the
supply
(hence
price)
of
food
is
a
matter
1
2
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n
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by
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preparedby
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oxidationof
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(ethylene
glycol)
is
prepared
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of
toto
oxacyclopropane,
1,2-Ethanediol
glycol)
followed
by hyd
hydrolysis,
in
quantities
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billion
pounds
million
tons)inninthe
the
glycol)
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prepared
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o ow
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n
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777 billion
bbillion
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5 to
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million
the
(3.5
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inthe
the
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in
followed
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inlow
hydrolysis,
in
quantities
exceeding
billion
pounds
(3.5
million
tons)
in
the
ental
level,
argue
that,
atonitsits
least
for
certain
by
hydrolysis,
in
quantities
exceeding
billion
pounds
(3.5
million
tons)
inin
followed
hydrolysis,
in
quantities
exceeding
77 billion
billion
pounds
(3.5
million
tons)
the
by
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in
quantities
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7777
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million
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followed
United
States
persome
year. Its
Its
melting
point
(211.5C),
high
boiling
point
(198C),
and
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incritics
quantities
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billion
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Un
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ng
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211
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nd
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and
States per
per year.
year.
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low
melting
point
(211.5C),
its
high
boiling
point
and
boiling
point
(198C),
and
melting
point
(211.5C),
its
high
boiling
point
(198C),
and
United
year.
Its
low
year.
Its
low
melting
point
(211.5C),
its
high
boiling
point
(198C),
and
United
States
Its
low
melting
point
(211.5C),
its
high
boiling
point
(198C),
and
year.
Its
low
melting
point
(211.5C),
its high
highIts
boiling
point
(198C),
and
complete
miscibility
with
water
make
useful
antifreeze.
Its
toxicity
issimilar
similar
tothat
that
United
per year.
low
melting
its
boiling
point
(198C),
and
ompStatesmiscibility
m
b fermenting,
yIts
w
h water
w
m
kpoint
u
u antifreeze.
ndistributing
ox
y is
m
hthat
its
complete
miscibility
with
water
make
ititit aaaa(211.5C),
useful
antifreeze.
toxicity
isis
tooto
g,its
harvesting,
and
then
biofuels
conits
with
complete
with
it
useful
Its
to
toxicity
issimilar
similar
tothat
that
water make
make
useful
antifreeze.
Its
toxicity
similar
its
miscibility
Itstoxicity
with water
miscibility
with
water
make
useful
antifreeze.
Its
toxicity
similar
that
its
complete
miscibility
with
water
make
it
useful
antifreeze.
Its
toxicity
is
similar
to
that
its o
complete
of
other
simple
alcohols.
miscibility
with
water make
make itit
it aaaa useful
useful antifreeze.
antifreeze. Its
Itstoxicity
toxicityisis
issimilar
similartoto
tothat
that
o
h simple
mpmiscibility
oho with
of
other
simple
alcohols.
of
other
alcohols.
of
alcohols.
alcohols.
of
other
simple
alcohols.
ns,
dealing
a
fatal
blow
to
the
viability
of
such
efforts.
of other simple alcohols.
alcohols.
O
O
Oxidation
HOO
O
HH
O
Oxidation
Oxidation
O
not intended
as
is OOOOOmade
industrially
by2OH
hydration
Oxidation
Oxidation
HO
O
H
O
Oxidation
H
O
CH22a beverage
HOCH22CH
CH
OH
Oxidation
HH
Oxidation
H
CH
CH
HOCH
OH
2
Oxidation
H
O
22P
Oxidation
HOO
O
CH
CH
HOCH
CH
OH
P
HOCH
CH
2
22
22
2
2
2
CH
CH
CH
HOCH
CH
OH
P
CH
HOCH
CH
OH
P
2
2
2
2
2
2
2
2
CH
CH
CH
HOCH
CH
OH
HOCH
CH
OH
P
2
2
22
2
2
2
2
Ethene
Oxacyclopropane
1,2-Ethanediol
2
HOCH
2
E
O
E2varnishes,
Ethene
Oxacyclopropane
1,2-Ethanediol
2CH2
2OH
2 P CH2
2
sed, for CH
example,
as a solvent
in perfumes,
and
Oxacyclopropane
1,2-Ethanediol
Ethene
Oxacyclopropane
1,2-Ethanediol
22
2
2222
22
22 2
2
2
2
2
2

Ethene
Ethene
Ethene
(Ethylene)
Ethene
EEthene
(Ethylene)
Ethene
(Ethylene)
(Ethylene)
(Ethylene)

Oxacyclopropane
Oxacyclopropane
Oxacyclopropane
Oxacyclopropane
Oxacyclopropane
Oxacyclopropane
(Ethylene
oxide)
Oxacyclopropane
E
(Ethylene
oxide)
Oxacyclopropane
(Ethylene
oxide)
(Ethylene
oxide)
(Ethylene
oxide)

1,2-Ethanediol
1,2-Ethanediol
1,2-Ethanediol
1,2-Ethanediol
1,2-Ethanediol
(Ethylene
glycol)
1,2-Ethanediol
E
(Ethylene
glycol)
1,2-Ethanediol
(Ethylene
glycol)
glycol)
(Ethylene
(Ethylene
glycol)
(Ethylene
glycol)

(Ethylene)
(Ethylene
oxide)
(Ethylene
glycol)
(Ethylene)
(Ethyleneoxide)
oxide)
(Ethylene
glycol)
(Ethylene)
(Ethylene
(Ethylene
glycol)
(Ethylene)
(Ethylene
oxide)
(Ethylene
(Ethylene)
(Ethylene
oxide)
(Ethylene
glycol)
(Ethylene)
(Ethylene
oxide)
(Ethylene glycol)
glycol)
rmediate,
as demonstrated
earlier
equations.
1,2,3-Propanetriol
(glycerol,
glycerine),
HOCH
CHOHCH
OH,is
isaaaviscous
viscous
greasy
sub1
2 3 P opan
o (glycerol,
g y o glycerine),
g
y nin HOCH
HOCH
vviscous
ou greasy
ggreasy
y subub
1,2,3-Propanetriol
(glycerol,
glycerine),
OH,
isis
sub2CHOHCH
2OH
1,2,3-Propanetriol
(glycerol,glycerine),
glycerine),HOCH
HOCH22222CHOHCH
CHOHCH22222OH,
OH,
aaviscous
viscous
greasy
subviscousgreasy
greasy
sub222CHOHCH
222OH,
1,2,3-Propanetriol
(glycerol,
glycerine),
HOCH
CHOHCH
OH,
is
a
viscous
greasy
sub1,2,3-Propanetriol
OH,
is
1,2,3-Propanetriol
(glycerol,
is
a
sub2
2
1,2,3-Propanetriol
(glycerol,
glycerine),
HOCH
CHOHCH
OH,
is
a
viscous
greasy
(glycerol,
glycerine),
HOCH
isoayviscous
greasy
substance,
water,
and
nontoxic.
It is
is obtained
obtained
byalkaline
alkaline
hydrolysis
triglycerides,
n1,2,3-Propanetriol
o ub
n water,
w
nd nontoxic.
non
ox It
ob
d22CHOHCH
by
k to
n22OH,
hyd
oofoftriglycerides,
g y subd
soluble
in
water,
and
nontoxic.
ItIt
is
obtained
alkaline
hydrolysis
triglycerides,
ycol)
is
prepared
by
oxidation
ofn ethene
oxacyclopropane,
stance,
and
soluble
in
and
by
hydrolysis
nontoxic.
isobtained
obtained
byalkaline
alkaline
hydrolysis
of
triglycerides,
hydrolysisofof
oftriglycerides,
triglycerides,
water,
and
nontoxic.
It
is
obtained
by
alkaline
hydrolysis
of
triglycerides,
stance,
water,
soluble
in
water,
and
nontoxic.
It
is
by
hydrolysis
soluble
in
and
stance,
water,
and
nontoxic.
It
is
obtained
by
alkaline
hydrolysis
of
triglycerides,
soluble
in
stance,
andy nontoxic.
It sodium
is
alkaline
hydrolysis
of
triglycerides,
in water,
the
of fatty
fatty
tissue.
The
sodium
and
potassium
salts
long-alkyl-chain
h major
m
osoluble
ompon
n of
o
u The
Th
odobtained
um and
nd by
po
um salts
oofofthe
hthelong-alkyl-chain
ong
ky h n
major
component
of
fatty
tissue.
The
and
potassium
salts
the
long-alkyl-chain
the
fatty
component
tissue.
potassium
of
tissue.
The sodium
sodium
andpotassium
potassium
salts
of
the
long-alkyl-chain
component of
ofthe
thelong-alkyl-chain
long-alkyl-chain
component
of
fatty
tissue.
The
sodium
and
potassium
salts
of
long-alkyl-chain
component
The
and
salts
the
of fatty
saltsof
fatty
major
component
of
tissue.
sodium
salts
the
long-alkyl-chain
ntities
exceeding
7 tissue.
billion
pounds
(3.5
in the
the
major
component
of
fatty
tissue.
The sodium
sodium
and
potassium
salts
ofthe
thetons)
long-alkyl-chain
thedmajor
acids
fatsfatty
(fatty
acids,
Chapter
19)potassium
are sold
sold
as
soaps.
pproduced
odu
d from
om fats
y acids,
dThe
Ch
p and
19
o d million
o pof
from
fats
(fatty
acid
acids,
Chapter
19)
are
sold
as
soaps.
produced
(fatty
Chapter
19)
are
as
soaps.
acids
(fatty
acids,
Chapter
19)
are
sold
as
soaps.
from
from
fats
(fatty
acids,
Chapter
19)
are
sold
as
soaps.
produced
from
fats
(fatty
acids,
Chapter
19)
are
sold
as
soaps.
acids
fats
(fatty
acids,
Chapter
19)
are
sold
as
soaps.
produced
from
fats
(fatty
acids,
Chapter
19)
are
sold
as
soaps.
acids
from(211.5C),
fats (fatty acids,its
Chapter
19)
are sold aspoint
soaps. (198C), and
acids produced
melting
point
high
boiling
O
O
O
O
O
O
B
O
BB
BO
B
ater make it aCH
useful
antifreeze. Its toxicity is similar to that
B
BB
CH
OCR
CH
OCR
2OCR
2
CH
OCR
OCR
2

ion

OCR
CH
CH
CH222222222OCR
OCR
OCR
CH
OCR
CH
O
O
O
O
O
BO
O
B
O
HH22O
N
OH
O,NaOH
NaOH
O,
NaOH
B
BB
H
H
O,
NaOH
H
22O,
H
O,
NaOH
H
O,
NaOH
BB
H
NaOH
2
H222222222O,
O,NaOH
NaOH
HCOCR
H
O,
NaOH
2O,
HCOCR
H
HCOCR
2O, NaOH
HCOCR
HCOCR
O
HCOCR
HCOCR
HCOCR
H2O
O
O
O
O
O
O
B
BB
BO
B
B
B
B
CH
OCR
CH
OCR
OCR
CH
CH
OCR
CH22222222222OCR
OCR
CH
OCR
Oxacyclopropane
CH
OCR
T
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Triglyceride
Foxide)
(Fat)
(Fat)
Triglyceride
(Ethylene
(Fat)
(Fat)
(Fat)
(Fat)
(Fat)
(Fat)
(Fat)
(Fat)
R

long
alkyl
chain
R
long
long
alkylchain
chain
R
alkyl
long
alkyl
chain

long
alkyl
chain

long
alkyl
chain
R
alkyl
chain
R
R
alkyl
chain

long
alkyl
chain
R
R
 long
long alkyl
alkyl chain
chain

long
alkyl
chain
R

long
alkyl
chain
R

CH
OH
CH2OH
OH
O
OO
CH
CH
OO
2OH
CH222OH
OH
CH
O
CH
O
B
OH
BBBBO
AAAAAA 2222222OH
BO
ACH
 
HCOH
BBB 

RCO
A
HCOH
N

 RCO
RCO
Na
Na





HCOH
Na

RCO

RCO
Na


HCOH

HCOH

RCO
Na
HCOH
Na

 RCO
RCO
Na
HCOH

Na
AA
HCOH

RCO
Na
A
AA
A
A
CH
OH
ACH
CH22OH
OH
2OH
CH
OH
CH
2
CH
CH22222222OH
OH 2CH2OH
CH
OH
HOCH
CH
OH
2

P 1,2-Ethanediol
1,2,3-Propanetriol
Soap
1,2,3-Propanetriol
Soap
Soap
1,2,3-Propanetriol
1,2,3-Propanetriol
Soap
Soap
1,2,3-Propanetriol
Soap
1,2,3-Propanetriol
1,2,3-Propanetriol
Soap
1,2,3-Propanetriol
Soap
1,2,3-Propanetriol
Soap
1,2,3-Propanetriol
G
Soap
(Glycerol,
glycerine)
(Glycerol,
glycerine) glycol)
1,2,3-Propanetriol
Soap
(Ethylene
(Glycerol,
glycerine)
(Glycerol,
(Glycerol,
glycerine)
(Glycerol,
glycerine)
(Glycerol,
glycerine)
(Glycerol,
glycerine)
(Glycerol,glycerine)
glycerine)
(Glycerol,
glycerine)

Pho
pho esters
o
1
2 3 p op2CHOHCH
n o (phosphoglycerides;
pho phog
y dis a
S
on 20-4)
20
4 are
pprimary
m ycomom
Phosphoric
esters of
ofHOCH
1,2,3-propanetriols
(phosphoglycerides;
Section
20-4)
are
com1,2,3-propanetriols
(phosphoglycerides;
Section
20-4)
areprimary
primary
com,Phosphoric
glycerine),
viscous
greasy
subPhosphoric
1,2,3-propanetriols
(phosphoglycerides;
Section
com2OH,
1,2,3-propanetriols
Section
1,2,3-propanetriols
(phosphoglycerides;
Section
20-4)
are
primary
comesters
of
1,2,3-propanetriols
(phosphoglycerides;
Section
20-4)
are
primary
com20-4)are
areprimary
primary
com1,2,3-propanetriols
(phosphoglycerides;
Section
20-4)
are
primary
comSection20-4)
Phosphoric
esters
of
1,2,3-propanetriols
(phosphoglycerides;
Section
20-4)
are
primary
comPhosphoric
esters
ofmb
pon
n of
oof cell
m
n
ponents
cell
membranes.
membranes.
ponents
membranes.
membranes.
membranes.
of
cell
ponents
membranes.
ntoxic.
obtained
hydrolysis
ofwwell
triglycerides,
cell
ponents
membranes.
ofPIt
cell
ponents
11,2,3-Propanetriol
2 3of
op is
nmembranes.
o is
p
n by
n lotions
oalkaline
on and
nd other
oother
h cosmetics,
om
m
d n
is
present
in
lotions
and
cosmetics,
asas
asasinin
inninmedicinal
medicinal
1,2,3-Propanetriol
is present
present
in
lotions
and
other
cosmetics,
wellasas
medicinal
1,2,3-Propanetriol
in
as
well
is
present
in
and
cosmetics,
as
well
1,2,3-Propanetriol
is
present
in
lotions
and
other
cosmetics,
as
well
as
medicinal
present
in lotions
lotions
and other
cosmetics,
as
well
as
in
medicinal
1,2,3-Propanetriol
isw
well
as in
in medicinal
medicinal
cosmetics,
asas
present
in
lotions
other
as
well
as
in
medicinal
1,2,3-Propanetriol
is
present
in
lotions
and
other
cosmetics,
as
well
as
in
medicinal
p p1,2,3-Propanetriol
on Treatment
T
m nis
h nitric
n
d gives
g
v and
nother cosmetics,
known
nnitroglycerine,
og
n used
uused
d
Treatment
with
nitric
acid
gives
trinitrate
ester
preparations.
Treatment
with
nitric
acid
gives
trinitrate
ester
known
as
nitroglycerine,
used
preparations.
ssue.
The
sodium
and
potassium
salts
of known
the
long-alkyl-chain
Treatment
with
nitric
acid
gives
trinitrate
ester
known
as
nitroglycerine,
used
with
acid
aaaaaatrinitrate
ester
as
nitroglycerine,
preparations.
nitric
acid
gives
trinitrate
ester
known
as
nitroglycerine,
used
Treatment
with
nitric
acid
gives
trinitrate
ester
known
as
nitroglycerine,
used

medicinally
medicinally
in
the
treatment
of
the
symptoms
of
angina,
especially
the
chest
pain
caused
medicinally in
in the
the treatment
treatment of
of the
the symptoms
symptoms of
of angina,
angina, especially
especially the
the chest
chest pain
pain caused
caused
by
insufficient
fl
ow
of
blood
to
the
heart.
The
drug
relaxes
the
blood
vessels,
thus
increasby
flow
ow of
of blood
blood to
to the
the heart.
heart. The
The drug
drug relaxes
relaxes the
the blood
blood vessels,
vessels, thus
thus increasincreasby insuffi
insufficient
cient fl
ing
blood
fl
ow.
A
totally
different
application
of
nitroglycerin
is
as
an
extremely
powerful
ing
ing blood
blood fl
flow.
ow. A
A totally
totally different
different application
application of
of nitroglycerin
nitroglycerin is
is as
as an
an extremely
extremely powerful
powerful
explosive.
explosive.
The
explosive
potential
of
this
substance
results
from
its
shock-induced,
highly
explosive. The
The explosive
explosive potential
potential of
of this
this substance
substance results
results from
from its
its shock-induced,
shock-induced, highly
highly
exothermic
decomposition
to
gaseous
products
(N
,
CO
,
H
O
gas,
O
),
raising
temperatures
2
2
2
2
exothermic
decomposition
to
gaseous
products
(N
,
CO
,
H
O
gas,
O
),
raising
temperatures
exothermic decomposition to gaseous products (N222, CO222, H222O gas, O222), raising temperatures
to
more
than
3000C
and
creating
pressures
higher
than
2000
atmospheres
in
a
fraction
to
more
than
3000C
and
creating
pressures
higher
than
2000
atmospheres
in
a
fraction
of
to more than 3000C and creating pressures higher than 2000 atmospheres in a fraction of
of
aaa second
second
(see
also
Chemical
Highlight
16-1).
second (see
(see also
also Chemical
Chemical Highlight
Highlight 16-1).
16-1).
Ethoxyethane
Ethoxyethane
(diethyl
ether)
was
at
one
time
employed
as
general
anesthetic
(see
Ethoxyethane (diethyl
(diethyl ether)
ether) was
was at
at one
one time
time employed
employed as
as aaa general
general anesthetic
anesthetic (see
(see
Chapter
Chapter
Opening).
It
produces
unconsciousness
by
depressing
central
nervous
system
activity.
Chapter Opening).
Opening). It
It produces
produces unconsciousness
unconsciousness by
by depressing
depressing central
central nervous
nervous system
system activity.
activity.
Because
Because
of
adverse
effects
such
as
irritation
of
the
respiratory
tract
and
extreme
nausea,
its
Because of
of adverse
adverse effects
effects such
such as
as irritation
irritation of
of the
the respiratory
respiratory tract
tract and
and extreme
extreme nausea,
nausea, its
its
use
use
has
been
discontinued,
and
1-methoxypropane
(methyl
propyl
ether,
neothyl)
and
use has
has been
been discontinued,
discontinued, and
and 1-methoxypropane
1-methoxypropane (methyl
(methyl propyl
propyl ether,
ether, neothyl)
neothyl) and
and
other
compounds
have
replaced
it
in
such
applications.
Ethoxyethane
and
other
ethers
are
other
other compounds
compounds have
have replaced
replaced it
it in
in such
such applications.
applications. Ethoxyethane
Ethoxyethane and
and other
other ethers
ethers are
are
explosive
explosive
when
they
are
mixed
with
air.
explosive when
when they
they are
are mixed
mixed with
with air.
air.
Oxacyclopropane
(oxirane,
ethylene
oxide)
is
a
large-volume
industrial
chemical
interOxacyclopropane
Oxacyclopropane (oxirane,
(oxirane, ethylene
ethylene oxide)
oxide) is
is aa large-volume
large-volume industrial
industrial chemical
chemical interintermediate
mediate
and
fumigating
agent
for
seeds
and
grains.
In
nature,
oxacyclopropane
derivatives
mediate and
and aaa fumigating
fumigating agent
agent for
for seeds
seeds and
and grains.
grains. In
In nature,
nature, oxacyclopropane
oxacyclopropane derivatives
derivatives
control
insect
metamorphosis
(see
Chemical
Highlight
12-1)
and
are
formed
in
the
course
control
insect
metamorphosis
(see
Chemical
Highlight
12-1)
and
are
formed
in
the
course
control insect metamorphosis (see Chemical Highlight 12-1) and are formed in the course

Chapter 9

369

Ethylene glycol is effective in the

deicing of airplanes.

CH
OH
CH222OH
OH
CH
A
A

HCOH
 33 HONO
HONO2222
HCOH
AA
CH22OH
OH
CH
2
CH
ONO
CH222ONO
ONO222
CH
AA
A

HCONO
H
O
 333 H
HCONO222 
H2222O
O
HCONO
A
A
A
CH
ONO
CH222ONO
ONO222
CH
Nitroglycerine
Nitroglycerine
Nitroglycerine

(cancer-causing) products (see Section 16-7).

Many natural products, some of which are quite active physiologically, contain alcohol

370
370
370
370
370

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r R e a c t imorphine
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ingredient in marijuana (cannabis), whose mood-altering effects have been known for thouof enzyme-catalyzed
of aromatic
hydrocarbons,
often leading
to highly carcinogenic
sands of years. Efforts
are ongoingoxidation
in the United
States
and worldwide
to legalize
marijuana
ofenzyme-catalyzed
enzyme-catalyzed oxidation
of
aromatic
hydrocarbons,
carcinogenic
of
oxidation
ofSection
aromatic16-7).
hydrocarbons,often
oftenleading
leadingtototohighly
highly
carcinogenic
carcinogenic
(cancer-causing)
products
(see
of
enzyme-catalyzed
oxidation
of
aromatic
hydrocarbons,
often
leading
highly
carcinogenic
of enzyme-catalyzed
oxidation
of aromatic
often
leading
to highly
carcinogeni
for medical purposes,
on
the basis
of (see
the
fi
nding
that
ithydrocarbons,
provides
relief
tohighly
patients
afflicted
aromatic
hydrocarbons,
often
leading
to
highly
carcinogenic
of
enzyme-catalyzed
oxidation
ofSection
aromatic
hydrocarbons,
often
leading
to
carcinogenic
(cancer-causing)
16-7).
(cancer-causing)
products
(see
Section
16-7).
Many
natural
products,
some
of Section
which
are
quite active physiologically, contain alcohol
(cancer-causing)
products
(see
Section
16-7).
(cancer-causing)
products
(see
16-7).
Section
16-7).
(cancer-causing)
products
(see
Section
16-7).
with cancer, AIDS,
multiple
sclerosis,
and
other
diseases
from
the
effects
of
nausea,
pain,
Many natural
natural products,
products, some
of
which
are
quite
active
physiologically,
contain
alcohol
Many
some of
of
which
are
quite
active
physiologically,
contain
alcohol
alcohol
and
ethernatural
groups.
For example,
morphine
isquite
aare
powerful
analgesic.
Its synthetic
acetate
Many
products,
some
which
are
quite
active
physiologically,
contain
alcohol
Many
natural
products,
some
of are
which
quite
active
physiologically,
contain
alcoho
which
are
active
physiologically,
contain
alcohol
some
of
which
active
physiologically,
contain
alcohol
andMany
ethernatural
groups.products,
For example,
morphine
isisquite
aa powerful
analgesic.
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acetate
and loss of appetite.
and
ether
groups.
For
example,
morphine
powerful
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synthetic
acetate
acetate
derivative,
heroin,
is aexample,
widely
abused
street
is
mainacetate
active
and
etherandgroups.
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morphine
isdrug.
a powerful
analgesic.
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ether groups.
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morphine
is Tetrahydrocannabinol
a powerful
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synthetic
acetat

morphine
isdrug.
powerful
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synthetic
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and
ether groups.
morphine
aa powerful
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acetate
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is aa example,
widely
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Tetrahydrocannabinol
main
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isthe
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active
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abused
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drug.
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is main
the
main
activ
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whose
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thouderivative,
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street
drug.
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the
main
active
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is
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abused
street
drug.
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the
active
street
drug.
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main
active
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in marijuana
marijuana
(cannabis),
whose
mood-altering
effects
have
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forfor
thouingredient
in
(cannabis),
whose
mood-altering
effects
havehave
been
known
thouin marijuana
(cannabis),
whose
mood-altering
effects
for
thou
CH
thousands ofingredient
years.
Efforts
are
ongoing
in themood-altering
United
States effects
and
worldwide
to been
legalize
marijuana
ingredient
in
marijuana
(cannabis),
whose
mood-altering
effects
have
been
known
forthouthou3 known
whose
mood-altering
effects
have
been
known
for
thouingredient
in
marijuana
(cannabis),
whose
have
been
known
for
sands of
ofsands
years.
Efforts
are
ongoing
in
the
United
States
and
worldwide
to
legalize
marijuana
sands
years.
Efforts
are
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in
the
United
States
and
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to
legalize
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ofEfforts
years. are
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United
and worldwide
topatients
legalize
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for medical
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nding
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it provides
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icted
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ongoing
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legalize
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the
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and
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toto
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sands
of
Efforts
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in
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United
States
and
worldwide
to
legalize
marijuana
for
medical
purposes,
on
the
basis
of
the
fi
nding
that
it
provides
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patients
affl
icted
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the on
basis
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nding
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itthat
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icted
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it
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icted
icted
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that
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nding
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icted
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OH
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loss of
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on the way to the gold medal at

he
Athens 2004
2004 Olympic
Games.
Olympic Games.
Games.
he Athens

P
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thiols
The lower-molecular-weight
are most notorious for their foul smell.
and sulfides
its
Ethanethiol is detectable
by
odor even when
itandissulfi
diluted
inmost
50most
million
parts
of
air.
The
The
lower-molecular-weight
thiols
and
sulfi
des
are
notorious
for
their
foul
smell
The
lower-molecular-weight
thiolsand
des
are
notorious
their
foul
smell.
The lower-molecular-weight thiols
sulfi
des
are
most
notorious
forfortheir
foul
smell.
Ethanethiol
is
detectable
by
its
odor
even
when
itdiluted
is
diluted
in
50 million
parts
of
air.
Th
major volatile components
of
the
skunks
defensive
spray
3-methyl-1-butanethiol,
transEthanethiol
detectableby
byitsitsodor
odor
even
when
itisare
isare
in5050
million
parts
of
air.
The
The lower-molecular-weight
lower-molecular-weight
thiols
andwhen
sulfi
des
most
notorious
forparts
their
foul
smell.
Ethanethiol
isisdetectable
even
it
diluted
in
million
of
air.
The
smell.
The
lower-molecular-weight
thiols
and
sulfi
des
are
most
notorious
for
their
foul
smell.
thiols
and
sulfi
des
are
most
notorious
for
their
foul
smell.
The
thiols
and
sulfi
des
are
most
notorious
for
their
foul
smell.
major
volatile
components
ofskunks
the
skunks
defensive
spray
are503-methyl-1-butanethiol,
trans
major
volatile
components
of
the
defensive
spray
are
3-methyl-1-butanethiol,
trans2-butene-1-thiol,Ethanethiol
and volatile
trans-2-butenyl
methyl
disulfi
de.
The
all-too-familiar
human
BO
Ethanethiol
is
detectable
by
its
odor
even
when
it
is
diluted
in
million
parts
of
air.
The
major
components
of
the
skunks
defensive
spray
are
3-methyl-1-butanethiol,
transThe
Ethanethiol
is
detectable
by
its
odor
even
when
it
is
diluted
in
50
million
parts
of
air.
The
even when
when
is disulfi
diluted
inThe
50 million
million parts
parts of
ofhuman
air. The
The
is detectable by
odor even
itit is
diluted
in
50
air.
2-butene-1-thiol,
anditstrans-2-butenyl
methyl
de.
all-too-familiar
BO
Mutlu
2-butene-1-thiol,
and
trans-2-butenyl
methyl
disulfi
de.
The
all-too-familiar
human
BO
major
volatile
components
of
theskunks
skunks
defensive
spray
are3-methyl-1-butanethiol,
3-methyl-1-butanethiol,
trans2-butene-1-thiol,
and
trans-2-butenyl
methyl
disulfi
de. The
all-too-familiar
BO
transmajor
volatile
components
of
the
skunks
defensive
spray
are
3-methyl-1-butanethiol,
transodor)
emanating
from
sweaty
armpits
was
analyzed
chemists
in human
thein perfume
skunks
defensive
spray
are
3-methyl-1-butanethiol,
transmajor
volatile
components
of
the
defensive
are
Turkish (body
weightlifter
Halil Mutlu
(body
odor)
emanating
from
sweaty
armpitsspray
was by
analyzed
by chemists
thetransperfum
weightlifter
Halil
Mutlu
Turkish weightlifter
Mutlu
nsive
(body odor)
emanating
fromsweaty
sweatymethyl
armpits
wasde.
analyzed
bychemists
chemistsin human
in
theperfume
perfume
2-butene-1-thiol,
and trans-2-butenyl
trans-2-butenyl
methyl
disulfi
de.
Theall-too-familiar
all-too-familiar
human
BO(body
emanating
from
armpits
was
analyzed
by
the
completesHalil
his sweat-intensive
BO
2-butene-1-thiol,
and
trans-2-butenyl
methyl
disulfi
de.
The
all-too-familiar
human
BO
methyl
disulfi
de.
The
all-too-familiar
human
BO
2-butene-1-thiol,
and
disulfi
The
BO
industry
in 2004.
The odor)
major
chemical
is
3-methyl-3-methylthio-1-hexanol,
specifi
industry
in
2004.
Theculprit
major chemical
culprit
is
3-methyl-3-methylthio-1-hexanol,
specifi
his sweat-intensive
sweat-intensive
completes
his
snatch
move
in
the 56 kg category
gTurkish
category
weightlifter
Halil Mutlu
Mutlu
industry
2004.
Themajor
major
chemical
culpritwas
is3-methyl-3-methylthio-1-hexanol,
3-methyl-3-methylthio-1-hexanol,
specifi
industry
inin 2004.
The
chemical
culprit
iswas
specifi
- (body
odor)
emanating
from
sweatyarmpits
armpits
was
analyzed
bywith
chemists
the
perfume
Turkish
Halil
perfume
(body
odor)
emanating
from
sweaty
armpits
analyzed
by
chemists
the
perfume
armpits
analyzed
by
chemists
inininthe
the
perfume
(body
odor)
from
sweaty
analyzed
by
chemists
in
perfume
move
in the
the
56
kg
category
snatchweightlifter
move
in
56
kg
category
callyemanating
the obnoxious
S-enantiomer.
It
is was
excreted
admixed
25%
of
its
mirror
image
on
the
way
to
the
gold
medal
at
completes
cally
the
obnoxious
S-enantiomer.
It
is
excreted
admixed
with
25%
of
its
mirror
image,
his
sweat-intensive
edal
completes
atway to
cally the
the
obnoxious
S-enantiomer.
Itisculprit
isculprit
excreted
admixedwith
with25%
25%ofofitsitsmirror
mirror
image,
cally
Itodor.
excreted
admixed
image,
industry
inobnoxious
2004.
TheS-enantiomer.
major
chemical
3-methyl-3-methylthio-1-hexanol,
specifi
tosweat-intensive
the gold
gold
medal
at Games.
specifi
on the
the
medal
at
industry
in
2004.
The
major
chemical
culprit
isis3-methyl-3-methylthio-1-hexanol,
3-methyl-3-methylthio-1-hexanol,
specifi
chemical
culprit
is
3-methyl-3-methylthio-1-hexanol,
specifi
industry
in
2004.
The
major
chemical
is
specifi
----the
Athens
2004
Olympic
which,
curiously,
has
a
fruity
snatch
category
move
in
the
56
kg
category
snatch
kg category
con
Games.
which,
curiously,
has
a
fruity
odor.
2004
Olympic
Games.
the
Olympic
Games.
which,
curiously,
has
a
fruity
odor.
which,
curiously,
has
a
fruity
odor.
cally
the
obnoxious
S-enantiomer.
It
is
excreted
admixed
with
25%
of
its
mirror
image,
image,
cally
the
obnoxious
S-enantiomer.
It
is
excreted
admixed
with
25%
of
its
mirror
image,
theAthens
way to2004
the gold
medal
at
is excreted
excreted admixed
admixed with
with 25%
25% of
of its
its mirror
mirror image,
image,
cally the obnoxious S-enantiomer. It is

CH2SH
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H CCH
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methyl
CH
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SH

SHSH
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SH
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OH

OH
OH
3-Methyl-3-methylthioOH
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1-hexanolOH
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3-Methyl-3-methylthioCH333CHCH
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1-hexanol
1-thiol
disulfide
1-hexanol
3-Methyl-1-butanethiol
trans-2-Butenetrans-2-Butenyl
methyl
3-Methyl-3-methylthio3-Methyl-1-butanethiol
trans-2-Butenetrans-2-Butenyl
methylsulfur compounds
3-Methyl-3-methylthio3-Methyl-1-butanethiol
trans-2-Butene3-Methyl-3-methylthiotrans-2-Butenyl
methyl
3-Methyl-3-methylthio3-Methyl-1-butanethiol
trans-2-Butenetrans-2-Butenemethyl
3-Methyl-3-methylthiotrans-2-Butenyl
methyl
3-Methyl-3-methylthioStrangely
enough, when theytrans-2-Butenyl
are highly diluted,
can have a rathe
CH3
1-thiol
disulfide sulfur compounds 1-hexanol
1-hexanol
1-thiol
1-thiol
1-hexanol
disulfide
disulfide
1-hexanol
1-thiol
1-thiol
1-hexanol
disulfide
1-hexanol
Strangely
enough,
when
they
highly
diluted,
can
have
pleasant
odor.
For
example,
the
smell
ofdisulfide
freshly
or garlic
ishave
duea torather
pres
Strangely
enough,
when
theyare
are
highly
diluted,chopped
sulfur onions
compounds
can
a the
rather
CH
CH33
pleasant
odor.
For
the
smell
of
chopped
onions
or
iscan
due
to to
theathe
presence
ofenough,
low-molecular-weight
thiols
anddiluted,
sulfi
des (Chemical
Highlight
9-4).
Dimethyl
sulfid
pleasant
odor.
Forexample,
example,
the
smell
offreshly
freshly
chopped
onions
orgarlic
garlic
is
due
presStrangely
enough,
whenhighly
they
are
highly
diluted,
sulfur
compounds
can
have
rather
rather
Strangely
when
they
are
highly
sulfur
compounds
have
rather
Strangely
enough,
when
they
are
highly
diluted,
sulfur
compounds
can
have
aaa arather
highly
diluted,
sulfur
compounds
can
have
rather
CH33 Strangely enough,
CH
when
they
are
diluted,
sulfur
compounds
can
have
rather
is
a component of the thiols
of
black
tea.(Chemical
The compound
2-(4-methyl-3-cyclohexenyl)-2
ence
low-molecular-weight
and
sulfi
des
Highlight
9-4).
Dimethyl
sulfi
dede
enceof
ofodor.
low-molecular-weight
thiols
and
sulfi
des
(Chemical
Highlight
9-4).
Dimethyl
sulfi
pleasant
odor.
Forexample,
example,the
thearoma
smell
offreshly
freshly
chopped
onions
or
garlic
due
the
presprespleasant
odor.
For
example,
the
smell
of
freshly
chopped
onions
or
garlic
due
the
prespleasant
For
smell
of
chopped
onions
or
garlic
is
to
the
presof
freshly
chopped
onions
or
garlic
isisisdue
due
tototo
the
prespropanethiol
(margin)
for
thecompound
unique
taste
of
grapefruit,
in which
it isprespresen
isis example,
aa component
ofofsmell
the
ofresponsible
tea.
The
2-(4-methyl-3-cyclohexenyl)-2pleasant odor. For
the
of isthiols
freshly
onions
or
garlic
is
due
to the
thearoma
aroma
ofblack
black
tea.
The
compound
2-(4-methyl-3-cyclohexenyl)-2ence
ofcomponent
low-molecular-weight
thiols
andchopped
sulfi
des
(Chemical
Highlight
9-4).
Dimethyl
sulfi
de
sulfi
de
ence
of
low-molecular-weight
thiols
and
sulfi
des
(Chemical
Highlight
9-4).
Dimethyl
sulfi
de
ence
of
low-molecular-weight
and
sulfi
des
(Chemical
Highlight
Dimethyl
sulfi
de
and
sulfi
des
(Chemical
Highlight
9-4).
Dimethyl
sulfi
de
99-4).
in concentrations
below
the des
parts-per-billion
(ppb;
1-in-10
)inrange.
It itcan
besulfi
tasted
propanethiol
(margin)
isisand
responsible
for
the
unique
taste
ofi.e.,
which
is
present
(margin)
responsible
for
theThe
unique
taste
ofgrapefruit,
grapefruit,
in
which
it is
present
ence of low-molecular-weight
thiols
sulfi
(Chemical
Highlight
9-4).
Dimethyl
de a
SH
ispropanethiol
component
of
thearoma
aroma
ofblack
black
tea.
The
compound
2-(4-methyl-3-cyclohexenyl)-22-(4-methyl-3-cyclohexenyl)-2is
component
of
the
aroma
of
black
tea.
The
compound
2-(4-methyl-3-cyclohexenyl)-2is
aaa component
of
the
of
2-(4-methyl-3-cyclohexenyl)-224
black
tea.
The
compound
2-(4-methyl-3-cyclohexenyl)-29other
even lower
concentrations,
at a tea.
dilution
ofcompound
10
ppb.
In
words,
you
notice
in
concentrations
below
the
parts-per-billion
(ppb;
i.e.,
1-in-10
) 9range.
It Itcan
becan
tasted
at atth
H3C
in
concentrations
below
the
parts-per-billion
(ppb;
i.e.,
1-in-10
)
range.
can
be
tasted
propanethiol
(margin)
responsible
forthe
the
unique
taste
ofgrapefruit,
grapefruit,
which
present
propanethiol
(margin)
is
for
unique
taste
of
in
itititit
is
present
present
propanethiol
(margin)
isisresponsible
responsible
for
the
unique
of
grapefruit,
which
isis
present
is aSH
component
of
the
aroma
tea.
The
compound
2-(4-methyl-3-cyclohexenyl)-2for
the
unique
taste
of
grapefruit,
inininwhich
which
is
present
2424
SH
presence
ofof1 black
mg
of at
this
compound
when
itppb.
istaste
dissolved
in
10
million
liters
of
water!
CH
even
lower
concentrations,
a
dilution
of
10
In
other
words,
you
can
notice
the
3
9
9
9
9
even
lower
concentrations,
at
a
dilution
of
10
ppb.
In
other
words,
you
can
notice
the
9
H
H33C
C propanethiol (margin)
in
below
the
parts-per-billion
(ppb;
i.e.,
1-in-10
ItItItItcan
be
tasted
at
in concentrations
concentrations
belowcial
the
parts-per-billion
(ppb;
i.e.,
1-in-10)))range.
)range.
range.
can
be
tasted
at
in
concentrations
below
the
parts-per-billion
(ppb;
i.e.,
1-in-10
range.
can
be
tasted
at
parts-per-billion
(ppb;
i.e.,
1-in-10
can
be
tasted
atat
is ofresponsible
for
the unique
grapefruit,
in
which
iswater!
present
Many
benefi
drugs
contain
sulfur
inof
their
molecular
framework.
Particularly
wel
(R,S)-2-(4-Methyl-3-cyclohexenyl)presence
11mg
when
ittaste
is24
dissolved
inin1010million
liters
ofit
water!
SH
CH
SH
24
24
presence
ofconcentrations,
mgofofthis
thiscompound
compound
when
it10
is24
dissolved
million
liters
of
33
CH
even
lower
atat
of
ppb.
words,
can
notice
the
even
lower
concentrations,
ataaadilution
dilution
of10
1024
ppb.In
Inother
words,you
you
can
notice
the
even
lower
concentrations,
dilution
of
ppb.
In
words,
you
can
notice
the
the
dilution
of
10
ppb.
In
other
words,
you
can
notice
the
9other
known
are
thedrugs
sulfonamides,
or
sulfa
drugs,
powerful
antibacterial
agents
(Section
15-10):
H33C
Many
benefi
cial
contain
ini.e.,
their1-in-10
molecular
framework.
Particularly
well
in 2-propanethiol
concentrations
below
the
parts-per-billion
(ppb;
)other
range.
Itliters
can
be
tasted
at
(R,S)-2-(4-Methyl-3-cyclohexenyl)Many
cial
drugs
containsulfur
sulfur
molecular
framework.
Particularly
well
(R,S)-2-(4-Methyl-3-cyclohexenyl)presence
of
1benefi
of
compound
when
is
dissolved
in
of
presence
of
11mg
mg
of
this
compound
when
dissolved
inin10
10
million
liters
ofofwater!
water!
presence
ofthe
mg
ofthis
this
compound
when
dissolved
10million
million
liters
water!
when
itititin
isisistheir
dissolved
in
10
million
liters
of
water!
CH
CH33
24 it
2-propanethiol
known
are
sulfonamides,
or
sulfa
drugs,
powerful
antibacterial
agents
(Section
15-10):
2-propanethiol
even lower concentrations,
a drugs
dilution
ofsulfa
10
ppb.
Inmolecular
other
words,
you
can
notice
the
known
theatcial
sulfonamides,
or
drugs,
powerful
antibacterial
agents
(Section
15-10):
O Particularly
Many
benefi
sulfur
in
framework.
well
Many
benefi
cial
drugs
contain
sulfur
in
their
molecular
framework.
Particularly
well
sulfur
in
their
molecular
framework.
Particularly
well
well
Manyare
benefi
cial
drugscontain
contain
sulfur
intheir
their
molecular
framework.
Particularly
well
(R,S)-2-(4-Methyl-3-cyclohexenyl)(R,S)-2-(4-Methyl-3-cyclohexenyl)(R,S)-2-(4-Methyl-3-cyclohexenyl)N
B
2-propanethiol
presence of 1 mg
of this
compound
when
itNH
isdrugs,
dissolved
inHantibacterial
10
million
liters
of water!
known
are
sulfonamides,
or
sulfa
powerful
(Section
15-10):
2-propanethiol
drugs,
powerful
antibacterial
agents
15-10):
known
are
the
or
sulfa
drugs,
powerful
antibacterial
agents
(Section
15-10):
15-10):
known
arethe
the
sulfonamides,
orSO
sulfa
drugs,
powerful
antibacterial
agents
(Section
15-10):
Oagents
S (Section
NH2
H2sulfonamides,
N
2N
2 N
BO
N
BParticularly well
B
Many beneficial drugs contain sulfur in their
molecular
framework.
hexenyl)N
HH
SOO O
SO2NH
O
NH
HH2NN
O
2NN
2
NH
2
2NH N
2
2
N
N
known are the sulfonamides,
or sulfaSO
drugs,
powerful
antibacterial
agents
BBBBS
B (Section 15-10):
Sulfadiazine N
Diaminodiphenylsulfone
N
O
H
N
S
SO
NH
H
HHH
N
SS
NH
SO
NH
H
N
N
SO
NH drug)
NH
H222N
N
222
222NH
22222
O
2N
2NH
(An
antibacterial
(An S
drug)
BBBantileprotic
B
Sulfadiazine
Diaminodiphenylsulfone
NN
O OOOO
Sulfadiazine
Diaminodiphenylsulfone
N
N drug)
(An antibacterial
(An antileprotic
Bantileproticdrug)
(An antibacterial drug)
(An
drug)
(An antibacterial drug)

Sulfadiazine
Sulfadiazine
Sulfadiazine
Sulfadiazine

(An antileprotic drug)

(An antileprotic drug)

Diaminodiphenylsulfone
Diaminodiphenylsulfone
Diaminodiphenylsulfone
Diaminodiphenylsulfone
Diaminodiphenylsulfone

N
H2N

H2N

SO2NH
N

O
B
S
B
O

Sulfadiazine

Diaminodiphenylsulfone

(An antibacterial drug)

(An antileprotic drug)

NH2

Garlic and
and Sulfur
Sulfur
Garlic

thetreatment
treatmentofoftyphus,
typhus,chc
What
culinary delight
delight itit is
is to
to augment
augment your
your meal
meal with
with the
the
What aa culinary
ininthe
is likely that the garlic pl
flavorful
avorful components
components of
of the
the genus
genus Allium:
Allium: garlic,
garlic, onion,
onion,
fl
ItItis likely that the garlic pla
warfare agentsaga
ag
leeks,
chives,
scallions,
and
shallots!
The
odorants
in
all
of
chemical
leeks, chives, scallions, and shallots! The odorants in all of
chemical warfare agents agai
significant reduction in ga
these foods
foods are
are based
based on
on the
the same
same element:
element: sulfur.
sulfur. What
Whatisis
these
aasignificant reduction in gas
hgiving
e B i g rise
P i c t u r e parallelC hthe
a p tconsumption
er 9
371
of
surprising is
is that, in
in many cases,
cases, the
the compounds
compoundsTgiving
surprising
the consumption of g
Th
B i g that,
Podor
i cmany
t unot
r eactually
a pintact
t erise
r 9 parallel
371
ght
the common cold
to ethe
the desirable
desirable
odor
are
not
actually present
presentCin
inhthe
the
intact
andfifight
to
are
and
the common cold,
plants
but
are
biosynthesized
upon
crushing,
frying,
or
boiltion,
and
it
may
help
to
reg
plants but are biosynthesized upon crushing, frying, or boiltion, and it may help to regu
suggestingthat
thatititlow
lo
ing
the
starting
material.
For example, a clove of garlic
studiessuggesting
the
starting
material.
studies
Cing
HEM
I CA
G H T 9-4For example, a clove of garlic
CHE
MI
L H I G H LLI
IG
NationalInstitutes
InstitutesofofHH
does
not
itself
smell,
and
uncut
onions
are
neither
fl
avorful
byaaNational
does not itself smell, and uncut onions are neither flavorful
by
Amongthe
themost
mostnotabl
notab
nor bring
bring
tears to
to your
your eyes.
eyes.
Garlic
and Sulfur
nor
tears
Among
breath, originatingfrom
fro
With
regard
to
garlic,
crushing
the
clove
releases
badbreath,
regard
crushing
releases
bad
What aWith
culinary
delight to
it isgarlic,
to augment
your mealthe
withclove
the
in the treatment of typhus, cholera,
dysentery, originating
and tuberculosis.
not,
as
you
might
hav
so-called
allinase
enzymes
that
convert
sulfoxide
precursors
and
flso-called
avorful components
of the
genus Allium:
onion,sulfoxide
It isprecursors
likely that the garlic plant
theseas
compounds
as
allinase
enzymes
thatgarlic,
convert
andusesnot,
you might
have
leeks,
chives,
scallions, and
shallots! The
odorants
in allacids
of
chemical warfare agents against
invading
organisms.
In China,
mouth.
Indeed,
inges
into
intermediate
sulfenic
acids.
These
subsequently
your
intofoods
intermediate
acids.sulfur.
These
acids
subsequently
yourcancer
mouth.
Indeed,
ingeste
these
are based on sulfenic
the same element:
What
is
a significant reduction in gastric
risk has
been noted
to
44days.
days.
Allicin
re
dimerize
with
the loss
loss
of
water
to the
the flflavorants,
avorants,
such
as
for33Garlic
dimerize
with
the
to
such
Allicin
isisread
rea
surprising
is that,
in many
cases,of
the water
compounds
giving
rise
parallel
theas
consumption of for
garlic.
is alleged
to prevent
property
itshares
shares
withdid
toallicin.
the desirable
odor generates
are not actually
present
in other
the
intact
and fight
common cold, (a
it(ainhibits
blood itplatelet
aggregaallicin.
Garlic
generates
host of
of
other
compounds
this
Garlic
aa host
compounds
ininthe
this
property
with
plants
butall
arecontaining
biosynthesized the
uponfunctional
crushing, frying,
or boil-of sulfi
tion,
and itRSR9,
may help to regulate
blood
sugar levels.
Several
way,
groups
des,
been
claimed
that
rubbing
way,
all containing
theexample,
functional
des, suggesting
RSR9, that it lowers
beencholesterol
claimed
that
ing
the starting
material. For
a clovegroups
of garlic of sulfi
studies
levels
wererubbing
refuted g
ofgarlic
garlic
themo
m
thetaste
does not itself smell, and uncut onions are neither flavorful
by a National Institutes of Health
taste
fundedof
clinical
trialin
inin2007.
the
the
O
nor bring
tears to your of
eyes.typhus,
Among
the tuberculosis.
most notablethe
negative
effects
of
garlic
is
NH222
authors
of
this
text.
O
n the
treatment
cholera,
dysentery,
and
Allinase
NH
the
authors
of
this
text.
Allinase
Allinase
With regard to garlic, crushing
BB the clove releases enzymes
enzymes bad breath, originating from the lungs by way of the blood
allinase
enzymes
convert
not, as you might have
t isso-called
likely
that
thethatgarlic
plant precursors
uses theseandcompounds
as thought, from garlic traces in
SS sulfoxide
into intermediate sulfenic acids. These acids subsequently
your mouth. Indeed, ingested garlic can persist in your urine
CO22HH
CO

2 invading
chemical
warfare
agents
China,
dimerize with
the loss of water
to the flagainst
avorants, such
as
fororganisms.
3 4 days. Allicin isIn
readily
absorbed through the skin
Component
ofintact
intact in this
allicin. Garlic generates a Component
host
of other of
(a property it shares with dimethyl sulfoxide). Thus, it has
garlic
a signifi
cant reduction
in compounds
gastric
risk
has that
been
noted
way, all containing
the functional garlic
groups
of sulfides, cancer
RSR9,
been claimed
rubbing
garlic onto
the foot soon leads to
the taste of garlic in the mouth, a claim confirmed by one of
parallel the consumption
of garlic. Garlic
isauthors
alleged
to prevent
O
NH
the
of
this
text.
O
O
B
BB blood platelet aggregaS
and fight the common
cold,
it inhibits
H
HCOH
SS
H
SS
Hregulate
OO
Component
of intactto
ion, and it may
help
blood
O
O
SSsugar levels. Several
garlic
A sulfenic
sulfenic acid
acid
Allicin
A
Allicin
tudies suggesting
that it lowers
cholesterol
levels were refuted
O
(A
flavorant)
(A flavorant)
by a National
Institutes
ofSB Healthfunded clinical trial in 2007.
S
H
O
S
O
O
Among
the
most notable
negative effects of garlic is
A sulfenic acid
Allicin
BB
sulfoxides,
RSR
,
and
disulfi
des,
RSSR9.
Interestingly,
some
RSR
sulfoxides,
,
and
disulfi
des,
Interestingly,
some
bad breath, originating fromRSSR9.
the lungs
by way
of the blood
O
are medicinally
medicinally
active. For
For
example,
ofnot,
theseas
compounds
are
active.
example,
Bcompounds
andsulfoxides,
you
might
have
thought,
from
garlic
traces in
RSR
and disulfides,
RSSR9. Interestingly,
some
powerful
antibacterial
agent.
Before modern
modern
allicin is aa ,powerful
antibacterial
agent.
Before
Theavor
avorofofgarlic,
garlic,leeks,
leeks
The
of these
compoundsIndeed,
are medicinally
active. For example,
your
mouth.
ingested
garlic
can were
persist
in your urine
extrusion
ofvolatile
volatilesulfur
sulfu
antibiotics
extrusion
antibiotics
became
available,
garlic
preparations
used
became
available,
garlic
preparations
were
used
allicin
is a powerful
antibacterial
agent. Before
modern
The avor
of garlic, leeks, and onions
is due of
to the
extrusion
of
volatile
sulfur
compounds
upon
cutting.
antibiotics
became
available,
garlic
preparations
were
used
or 3 4 days. Allicin is readily absorbed through the skin
a property it shares with dimethyl sulfoxide). Thus, it has
been
claimed
that
rubbing
garlic
on
foot
soon
to raw
In Summary
Alcohols
and ethers
haveethers
various
uses,
asthe
chemical
rawboth
materials
and
rawmaterials
materialsand
and
Summary
Alcohols
and
have
various
uses,
as
chemical
In
Alcohols
and
ethers
haveboth
various
uses,
both
asleads
chemical
as medicinal agents. Many of their derivatives can be found in nature; others are readily
as medicinal
agents.
their
be
agents. Many
othersare
arereadily
readily
he
taste of garlic
in
theof
a claimcan
confi
rmed
bynature;
one others
of
Many
ofmouth,
their derivatives
derivatives
can
be found
found inin
nature;
synthesized.
synthesized.
he authors of this text.
Allinase
enzymes

222
22

H2O

(A flavorant)

THE BIG PICTURE

We have now completed our coverage of alcohols, the second major class of functionalPICTURE
BIG PICTURE
THE
group compounds
in this text. This does not mean that we are done with them, however.
On
contrary,
alcohols
show up again
in every one of
following chapters,
often inmajor class
Wethehave
now
completed
our
alcohols,
the
now
functionalWe
completed
our coverage
coverage ofofthe
alcohols,
the second
second
major classofoffunctionalconjunction with new functional-group substituents.
group
this
This
does
done
compounds
withthem,
them,however.
however.
group
inexamined
this text.
text.
This
does not
not
mean
that we
we are
are
donewith
In thiscompounds
chapter, we alsoin
the last
complication
that mean
may
be that
encountered
in the
reactions
RX with nucleophiles/bases
carbocation
rearrangements.
We shall
see
On the ofcontrary,
alcohols
up
in
of
following
contrary,
chapters,often
ofteninin
On
alcohols show
show
up again
again
in every
every one
one
of the
thelater
followingchapters,
that skeletal rearrangements are also possible by other mechanisms, but acid catalysis is by
conjunction
with
conjunction
with new
new functional-group
functional-group substituents.
substituents.
far the most important.

In
we also
also examined
the last
last complication
complication that
that may
may be
In this
this chapter,
chapter, we
examined the
be encountered in
in the
the
reactions
of RX
RX with
with nucleophiles/bases
nucleophiles/bases
carbocation
carbocation rearrangements.
rearrangements. We
We shall
shall see
see later
later
reactions of
that
that skeletal
skeletal rearrangements
rearrangements are
are also
also possible
possible by
by other
other mechanisms,
mechanisms, but
but acid
acid catalysis
catalysis is
is by
by
far
far the
the most
most important.
important.
Before
we
go
on
to
present
other
classes
of
organic
compounds,
with
other
functional
Before we go on to present other classes of organic compounds, with other functional
groups,
groups, we
we shall
shall examine
examine some
some of
of the
the key
key analytical
analytical techniques
techniques used
used by
by organic
organic chemists
chemists
to
determine
to determine molecular
molecular structure.
structure. You
You should
should now
now have
have enough
enough experience
experience with
with the
the fundafundamentals
of
structure
and
function
to
appreciate
that
subtle
differences
in
structures
mentals of structure and function to appreciate that subtle differences in structures can
can lead
lead

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CHAPTER
INTEGRATION
PROBLEMS
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INTEGRATION
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INTEGRATION
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INTEGRATION
PROBLEMS
INTEGRATION
CHAPTER
to us:
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spectroscopy.
tool available
to
lytical
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9-26.
of alcohol
A spectroscopy.
withPROBLEMS
acidic methanethiol gives sulfide B. Explain by a mechanism.
CHAPTER
INTEGRATION
PROBLEMS
9-26. Treatment
of
alcohol
A
with
acidic
methanethiol
gives
sulfi
CHAPTER
INTEGRATION
PROBLEMS
methanethiol
gives
sulfide
deB.
B.Explain
Explainby
bya amechanism.
mechanism.
9-26.
Treatment
of
alcohol
A
with
acidic
methanethiol
gives
sulfi
de
B.
Explain
by
mechanism.
INTEGRATION
PROBLEMS
CHAPTER
INTEGRATION
PROBLEMS
Treatment
of
acidic
gives
sulfi
of alcohol
alcohol A
A with
withCHAPTER
acidic methanethiol
methanethiol
gives
sulfide
deB.
B.Explain
Explainby
byaaamechanism.
mechanism.
9-26.
Treatment
9-26.
Treatment
of alcohol A withPROBLEMS
acidic
methanethiol
gives
de3SB. gives
Explain
by
a mechanism.
INTEGRATION
CH
CHAPTER
INTEGRATION
PROBLEMS
9-26.
Treatment
of alcohol A with
acidicsulfi
methanethiol
sulfide by
B. Explain
by a mechanism.
INTEGRATION
PROBLEMS
9-26.
of
A
acidic
de
B.
Explain
aa mechanism.
CH
CH
CH
S
INTEGRATION
INTEGRATION
PROBLEMS
3S
3 PROBLEMS
9-26. Treatment
Treatment
of alcohol
alcohol
A with
with
acidic methanethiol
methanethiol gives
gives sulfi
sulfi
de
B.
Explain
by
mechanism.
CHAPTER
CH
S
3
H CH
3
CH3CHby
CH
CH
3
A with
S a mechanism.
9-26. Treatment of alcohol
acidic methanethiol gives sulfi
de3S3S
B. Explain
H A
CH

3 by a mechanism.
H A
CHmethanethiol
SH, H2SO4 (0.1
equiv.)
33
CH
9-26.
Treatment of
of alcohol
alcohol
A
with
acidic
gives sulfi
sulfi
de3S
B.Explain
Explain
3methanethiol
CH
CH
3
9-26.
Treatment
with
acidic
gives
de
B.
aamechanism.
CH
3gives sulfi
ACH
33
H CH
H
AO
H CH
9-26. Treatment
Treatment
of
alcohol
A
with
acidic
methanethiol
de
B.
Explain
by
mechanism.
CH
SH,
CH
alcohol
A
with
acidic
gives
sulfi
de
B.
Explain
by
3
of
CH
CH3 333 by
SH,HH
H2SO
SO4 (0.1
(0.1Aequiv.)
equiv.)
C
9-26.
of
alcohol
A
with
givesCH
sulfi
B.equiv.)
Explain
byaCH
amechanism.
mechanism.
3S
CH
3methanethiol
CH3methanethiol
SH,
equiv.)
SH,
Hde
SO
(0.1
3 OHacidic
22SO44 (0.1
ACH
AO
H C
CH
3S
CH
CH
CH33SH,
SH,HH2SO
SO4 44(0.1
(0.1
equiv.)
CH
3
2
3 3
O
3OH
Cequiv.)
OH
3
2
A
H
O
C
OH
CH
S
CH
CH
CH
SH,
H
SO
(0.1
equiv.)
CH3
3
3
3
3
2
4
CH
CH3S3S
H C
OOH
C
OH CH3SH, H2SO4 (0.1A equiv.) CH
AO
3 33
CH
ACH
CH
CH
CH
3
CH
A
S
3
CH
S
O
CH
3
C
OH CH3SH, H2SO4 (0.1CHequiv.)
H
CH
333
33
AAC
3
CH
CH
AO
H CH
33
3
H
OH
CH
CH
CH
CH
3333 OH
CH
SH,
HH2SO
AO
33 3
CH
H
H A
4 (0.1
A equiv.)
B
C
A
3
CH3SH,
(0.1
equiv.)
CH
CH
CH
3SH,H
2SO
B CH
3 333 3
CH
SO
AAO
3
4 4(0.1 equiv.)
ACH
CH
C
CH
3SH,H
2SO
CH333SH,
H222SO
(0.1equiv.)
equiv.)
44444(0.1
A
BB
CH
O3OH
C
OH
3
2
SOLUTION
O
B CH3 3
C
OH
A
CH
A
C
A
BB CH
O33OH
C
OH
CH3 3 In other words, to solve it, w
A
AO
problem.
SOLUTION
CH
A
3 This is an example of a mechanistic, rather than a synthetic,
CH
CH
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B
3
A
3
3
A
SOLUTION
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add any reagents as in a multistep synthetic sequence;
what3 we see is what we have to wor
A
B other
SOLUTION
CH3 cannot
CH
This is an example of a mechanistic,
rather
than
a synthetic,
problem.
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words, to solve it, we
SOLUTION
A
Bother words,
SOLUTION
CH
CH33333 with.rather
Let us take
an ainventory
of whatproblem.
we have: In
This is
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of
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toto
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it,it,we
A
SOLUTION
B
synthetic,
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we
This
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other
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solve
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A
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This
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than
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problem.
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other
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SOLUTION
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is words,
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example
of aaa mechanistic,
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thanalcohol
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problem.
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words,
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we
This
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The
(tertiary)
function disappears
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(secondary)
thioether
(from
CH
A
BIn
3SH) i
A
B
SOLUTION
cannot
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as
in
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we
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This
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than
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solve
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we
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multistep
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work
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whatwe
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see
what
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work
SOLUTION
introduced.
cannot
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isis
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This
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example
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a
mechanistic,
rather
than
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synthetic,
other
words,
to
solve
it,
we
with.
Let
us
take
an
inventory
what
we
have:
SOLUTION
cannot
add
any
reagents
as
in
multistep
synthetic
sequence;
what
we
see
is
what
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work
This
anus
example
ofinventory
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rather
than a synthetic,
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other
words,
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solve
it,
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with. isLet
take
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of
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we
have:
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cannot
add
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as
in
a
multistep
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sequence;
what
we
is
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we
to
work
with.
Let
us
take
an
inventory
of
what
we
have:
SOLUTION
2. rather
Thewe
four-membered
ring
turns intoproblem.
cyclopentyl.
This is
isLet
anus
example
of
mechanistic,
than
synthetic,
InInsee
other
words,
totohave
solve
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take
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us
This
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mechanistic,
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thanand
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solve
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aaaa mechanistic,
rather
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aaaa synthetic,
problem.
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other
words,
to
solve
it,
we
1. The
The
(tertiary)
alcohol
function
disappears
the
(secondary)
thioether
unit
(from
CHSH)
SH)
is
cannot
add
any
reagents
asfunction
in aaof
multistep
synthetic
sequence;
what
we
see
is that
what
we
to
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3it,
of
rather
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other
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This
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us
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an
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what
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have:
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a mechanistic,
mechanistic,
rather
thanand
a synthetic,
synthetic,
problem.
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other
words,
solve
it,
we
1.
alcohol
the
(secondary)
thioether
CH
turns
intounit
of(from
compound
B,to
H
3.disappears
The
molecular
formula
of compound
A, C7Hwe
This
isLet
an(tertiary)
example
tohave
solve
it,
we
cannot
add
any
as
in
synthetic
sequence;
what
see
we
work
14O,
16S.is
3C8SH)
with.
us
take
an
what
we
have:
(secondary)
thioether
unit
(from
CH
SH)
is
1.
The
(tertiary)
alcohol
disappears
and
the
(secondary)
thioether
unit
(from
CH
cannot
reagents
asfunction
in aaaof
multistep
synthetic
sequence;
what
we
seeis
what
wehave
have
to
work
add
any
reagents
as
in
synthetic
sequence;
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we
see
isiswhat
what
we
have
to
work
33SH)
1.
(tertiary)
alcohol
disappears
and
the
(secondary)
thioether
unit
CH
isis
introduced.
with.
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usany
takereagents
an
inventory
ofmultistep
what
we
have:
3SH)
1. The
The
(tertiary)
alcohol
function
disappears
and
the
(secondary)
thioether
unit(from
(from
CH
is
as
in
multistep
what
we
see
we
have
to
cannot
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asfunction
in aaof
multistep
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sequence;
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we
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Focusing
onsynthetic
the alkyl
partsequence;
attached
to the
respective
functional
group,
we
can
rewrite
these
change
introduced.
cannot
add
any
we
have
to
work
with.
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us
take
an
inventory
what
we
have:
1.
The
(tertiary)
alcohol
function
disappears
and
the
(secondary)
thioether
unit
(from
CH
SH)
is
introduced.
with.introduced.
an
inventory
of what
what
we
have:
Let (tertiary)
us take an
inventory
of
we
have:
1.
The
alcohol
function
the3. (secondary) thioether unit (from CH33SH) is
OHhave:
S C7and
H13SCH
as disappears
C7Hwe
13
introduced.
inventory
of
an
inventory
of
what
we
have:
with.
Let
us
2. The
The
four-membered
ring
turns
into
cyclopentyl.
1.
(tertiary)
alcohol
function
disappears
and
the (secondary) thioether unit (from CH3SH) is
with.
Letfour-membered
us take
take an
an
inventory
of what
what
we
have:
introduced.
2.
ring
turns
into
cyclopentyl.
1.
(tertiary)
alcohol
function
disappears
and
the
(secondary)
thioether
unit
(from
CH
SH)
is
The cyclopentyl.
reaction medium
contains
catalytic acid in
the presenceunit
of
a tertiary
alcohol.
3SH)
introduced.
2.
The
four-membered
ring
turns4.into
into
1.
alcohol
function
disappears
and the
the
(secondary)
thioether
unit
(from
CH
is
(tertiary) alcohol
alcohol
function
disappears
and
(secondary)
thioether
(from
CH
2. The
The
four-membered
ring
turns
cyclopentyl.
3SH)is
3SH)
introduced.
four-membered
ring
into
cyclopentyl.
function
disappears
and
the
(secondary)
unit
CH
1.
(tertiary)
2.
function
disappears
and
the
(secondary)
thioether
unit (from
(from
SH)isis9-3
3 33(Section
H14O,
O,
turns
intothat
thatthioether
ofhave
compound
B,
CH
3. introduced.
molecular
formula
ofturns
compound
A,we
Cconclude
1.
The
(tertiary) alcohol
(from
CH
Whatcyclopentyl.
can
from
this into
information?
We
a carbocation
rearrangement
7H
8HCH
16S.
3SH) is
2.
The molecular
four-membered
ring
turns
into
of
B,B,
3.
formula
of
compound
A,
CC
introduced.
14 O, turns
8 H
16S.
2.
four-membered
ring
turns
turns
into
thatexpansion
ofcompound
compound
B,C
C
H
S. The initia
turns
into
that
compound
C
3.
The
molecular
formula
of
compound
A,
ininto
whichcyclopentyl.
the
strained
cyclobutane
ring
undergoes
to a substituted
introduced.
14
16
14
88H
O,
turns
into
that
ofof
compound
B,B,
Ccyclopentane.
S.S.
formula
of
compound
A,
CC77777HH
14
8H
1616
2.
four-membered
ring
turns
into
cyclopentyl.
introduced.
H
O,
turns
into
that
of
compound
C
S.
The
molecular
formula
of
compound
A,
3.
14
8
16
Focusing
on
the
alkyl
part
attached
to
the
respective
functional
group,
we
can
rewrite
these
changes
2. The
The
four-membered
ring
turns
into
cyclopentyl.
carbocation
mustCderive
from
a protonation
that
water loss
sequence
(Section
H14O,
O,
turns
intogroup,
ofwecompound
compound
B,9-2),
C8as
Happlied
S. to A, an
3.
The four-membered
molecular
formula
ofturns
compound
A,
Focusing
on
the
alkyl
part
attached
to the
respective
functional
can
these
7H
16changes
ring
into
cyclopentyl.
2.
four-membered
ring
turns
into
cyclopentyl.
turns
into
thatof the
of
B,
C
S.
3.
molecular
formula
of
compound
A,
C
on
the
functional
group,
we
canrewrite
rewrite
these
changes
Focusing
alkyl
part
attached
to
the
respective
functional
group,
we
can
rewrite
changes
product
B must
be7formed
through
1 capture
rearranged
cation
by these
CH
SH.
ring
into
cyclopentyl.
83H
16changes
2.
four-membered
Ninto
on
attached
to
respective
group,
we
can
rewrite
ring
into
cyclopentyl.
four-membered
OHthe
Salkyl
Cformula
H13part
SCH
as
CThe
H14
O,functional
turnsSinto
thatofof
compound
B,
Cthese
S.
3.
molecular
ofturns
A,
C
2.
The
four-membered
Focusing
on
the
alkyl
part
attached
toWethe
the
respective
functional
group,
we
can
rewrite
these
changes
7H13
7formula
3turns
7H
14O,
8H16
OH
S
C
H
SCH
.. compound
as
turns
compound
B,
H
S.
3. C
of
A,
C
can
now
to formulate
a step-by-step
description
of these
thoughts.
7H
Focusing
on
the
alkyl
part
attached
to the
the
respective
functional
group,
we
can
rewrite
these
changes
H13
molecular
OHthe
Salkyl
C77formula
H13
SCH
as
CThe
turns
that
compound
B,
C
H
S.
The
molecular
of
compound
A,
C
H14
O,functional
turnsinto
intothat
thatof
of
compound
B,C
C88these
H16
S.
3.
molecular
of333...compound
compound
A,
C77begin
OH
S
C
H
SCH
as
C
13
7formula
13
14
1616
7H
14O,
8H
Focusing
on
part
attached
to
respective
group,
we
can
rewrite
changes
77H
13
13
H
O,
turns
into
that
of
compound
B,
C
H
S.
formula
of
compound
A,
C
H

OH
S
C
H
SCH
C
3.
The
molecular
as
H
O,
turns
into
that
of
compound
B,
C
S.
formula
of
compound
A,
C
7
14
8
16
7 13 molecular
7formula
13
Step
TheA,
hydroxy
group
is
protonated
leaves
aswe
H2O.canalcohol.
4.
reaction
medium
contains
catalytic
acid
in
the
presence
of
atertiary
Focusing
on
the
alkyl
part
attached
to1.the
the
respective
functional
group,
rewrite
turns
intoand
that
oftertiary
compound
B, these
Cthese
S.changes
3.
The
of33.compound
C77Hin
14
888H16
16
14O,
16changes
H

OH
S
C
H
SCH
as
C
4.
The
reaction
medium
contains
catalytic
acid
the
presence
of
a
alcohol.
7
13
7
13
Focusing
on
the
alkyl
part
attached
to
respective
functional
group,
we
can
rewrite
OHthe
Salkyl
C7H13part
SCH
as
CThe
reaction
presencegroup,
ofaaatertiary
tertiary
alcohol.
4.
medium
contains
catalytic
acid
in
the
presence
of
alcohol.
on
attached
to
functional
we
rewrite
7H13
3.
Focusing
alkyl
part
attached
to the
the respective
respective
functional
group,
wecan
can
rewritethese
thesechanges
changes
medium
contains
catalytic
acid
in
the
presence
of
alcohol.
reaction
OH
Salkyl
C
SCH
as
CThe
part
attached
to
the
functional
group,
we
can
rewrite
changes
Focusing
on
reaction
medium
contains
catalytic
acid
inWe
the
presence
a tertiary
tertiary
CH
4.
7H13
7H13
3. this
3
the
alkyl
part
attached
to
the
respective
functional
group,
werearrangement
canalcohol.
rewrite
these
changes
H respective
Hof CH
H these
What
canthe
we
conclude
from
information?
have
carbocation
(Section
9-3)
OH
S
C
SCH
as C
CH
Focusing
on
these
changes
3
7H
13
7H
3.. this
4.
The
reaction
medium
contains
catalytic
in the
the
presence
of Aaa 3tertiary
tertiary
alcohol.
A acid We
can
we
conclude
from
information?
have
aacarbocation
9-3)
 (Section
OH
S
C
CWhat
 rearrangement
D
C
H13
SCH
as C
7H13
77H
13
33.. thiscatalytic
13SCH
 presence
4.
The
reaction
medium
contains
acid
of
alcohol.
have
carbocation
rearrangement
(Section
9-3)
SCH
What
canstrained
we
conclude
from
information?
We
have
carbocation
rearrangement
(Section

OH
S
as
conclude
from
information?
We
have
aaaato
carbocation
9-3)
CaOtertiary
CO
OH in
 the
H
OHrearrangement
 initial
O
C(Section
H9-3)
77H
13
33. this
77H
13
2
2
SC
C
Hcyclobutane
SCH


in
which
the
cyclobutane
ring
undergoes
expansion
a
substituted
cyclopentane.
The
4.
The
reaction
medium
contains
catalytic
acid
in
presence
of
alcohol.
13
13
H
OH
as
C
What
can
we
conclude
from
this
information?
We
have
carbocation
rearrangement
(Section
9-3)
D
7
13
7
13
3
in
which
the
strained
ring
undergoes
expansion
to
a
substituted
cyclopentane.
The
initial
A
A
4. The
The
reaction
medium
contains
catalytic
acid in
inexpansion
thehave
presence
of
a tertiary
tertiary
alcohol. CH
What
can
we
conclude
from
this
information?
We
a
carbocation
rearrangement
(Section
9-3)
3The
expansion
to
a
substituted
cyclopentane.
The
initial
in
strained
cyclobutane
ring
undergoes
to
a
substituted
cyclopentane.
initial
reaction
medium
contains
catalytic
acid
the
presence
of
a
alcohol.
which
the
strained
cyclobutane
ring
undergoes
expansion
to
a
substituted
cyclopentane.
The
initial
4.
medium
contains
catalytic
acid
in
the
presence
of
a
tertiary
alcohol.
CH
CH
3
3
What
can
we medium
conclude
from
this
information?
We
have
atocarbocation
rearrangement
(Section
9-3)
carbocation
must
derive
from
a protonation
protonation
acid
water
loss
sequence
(Section
9-2),
asapplied
applied
toA,A,
and
contains
catalytic
in
the
presence
aatertiary
alcohol.
4.
The
reaction
which
the
strained
cyclobutane
ring
undergoes
expansion
a of
substituted
cyclopentane.
The
initial
in
carbocation
must
derive
from
a

water
loss
sequence
(Section
9-2),
as
to
and
4.
The
reaction
medium
contains
catalytic
acid
in
the
presence
of
tertiary
alcohol.
What
can
we
conclude
from
this
information?
We
have
a
carbocation
rearrangement
(Section
9-3)
4.
The
reaction
A
in
which
the
strained
cyclobutane
ring
undergoes
expansion
to
a (Section
substituted
cyclopentane.
The
initial
must
sequence
(Section
9-2),
as
applied
to
A,
and
What
can
we
conclude
from
this
information?
We
have
a
carbocation
rearrangement
(Section
9-3)
carbocation
derive
from
a
protonation

water
loss
sequence
(Section
9-2),
as
applied
to
A,
and
must
derive
from
a
protonation

water
loss
sequence
9-2),
as
applied
to
A,
and
in
which
the
strained
cyclobutane
ring
undergoes
expansion
to
a
substituted
cyclopentane.
The
initial
product
B
must
be
formed
through
S
1
capture
of
the
rearranged
cation
by
CH
SH.
WhatBthe
can
webeconclude
conclude
from
this
information?
We
have
carbocation
rearrangement
(Section
9-3)
must
derive
from
a this
protonation
water
loss
sequence
(Section
9-2),
to A,
and
N1undergoes
3as applied
conclude
from
this
information?
We
have
carbocation
rearrangement
(Section
9-3)
carbocation
product
must
formed
through
Sinformation?
capture
ofcarbocation
the
rearranged
cation
by
CH
N
3SH.
from
We
have
aaaaatoto
carbocation
rearrangement
(Section
9-3)
in
which
strained
cyclobutane
ring
expansion
substituted
cyclopentane.
The
initial
What
can
we
conclude
from
this
information?
We
have
carbocation
rearrangement
(Section
9-3)
Step
2. capture
The
tertiary
undergoes
ring
expansion
by
alkyl
shift
(the
migrating
carbon
carbocation
must
derive
from
protonation
water
loss
sequence
(Section
9-2),
as
applied
to initial
A,
and i
What
can
webe
in
which
the
strained
cyclobutane
ring
expansion
aaaof
substituted
cyclopentane.
The
must
bebegin
rearranged
cation
by9-2),
CH
SH.
product
formed
through
capture
of
the
rearranged
cation
by
CH
SH.
must
formed
through
SS
of
the
rearranged
cation
by
CH
What
conclude
from
this
We
have
rearrangement
(Section
9-3)
33as
carbocation
must
derive
aa protonation
water
loss
sequence
(Section
applied
to
A,
and
We B
can
now
tofrom
formulate
aNNN111undergoes
step-by-step
description
these
thoughts.
in
which
the
strained
cyclobutane
ring
undergoes
expansion
to
cyclopentane.
The
initial
product
B
must
bebegin
formed
through
SaNinformation?
capture
the
rearranged
cation
by
CH3SH.
SH.
strained
cyclobutane
ring
undergoes
expansion
tocarbocation
asubstituted
substituted
cyclopentane.
The
initial
We
can
now
to
formulate
step-by-step
description
of
these
thoughts.
represented
byawater
dot).of
3as
cyclobutane
ring
undergoes
expansion
to
a
substituted
cyclopentane.
The
initial
carbocation
must
derive
from
a
protonation
loss
sequence
(Section
9-2),
applied
to
A,
and
in
which
the
strained
product
B
must
be
formed
through
S
1
capture
of
the
rearranged
cation
by
CH
SH.
which
the
strained
cyclobutane
ring
undergoes
expansion
to
a
substituted
cyclopentane.
The
initial
carbocation
must
derive
from
a
protonation

water
loss
sequence
(Section
9-2),
as
applied
to
A,
and
in
description
of
these
thoughts.
We
can
now
begin
to
formulate
a
step-by-step
description
of
these
thoughts.
3SH.
to
formulate
description
these
whichB
the
strained
cyclobutane
ring
undergoes
to of
aof(Section
substituted
cyclopentane.
TheA,
initial
product
must
bebegin
formed
through
SaaNN1step-by-step
capture
ofexpansion
the
rearranged
cationthoughts.
by
CHas
must
derive
from
aaprotonated
protonation

sequence
9-2),
applied
can
now
begin
to
formulate
description
these
3as
carbocation
derive
from
protonation
water
loss
sequence
(Section
9-2),
appliedto
and
StepWe
1. The
The
hydroxy
group
and
leaves
asrearranged
H2HO.
from
water
water
loss
sequence
9-2),
applied
totoA,
A, and
and
H9-2),
product
B
must
bederive
formed
through
SNaN11step-by-step
capture
of loss
the
rearranged
cationthoughts.
by
CH3as
SH.
carbocation
must
2O. CH
Step
1.
hydroxy
group
isis aprotonated
and
leaves
as
H
3as
We
canmust
now
begin
to
formulate
step-by-step
description
of3(Section
these
thoughts.
carbocation
must
derive
from
aa protonation
protonation
loss
sequence
(Section
applied
product
B
be
formed
through
S
capture
of
the
cation
by
CH
SH.
carbocation
must
derive
from
protonation
water
water
loss
(Section
9-2),
as
applied to
to A,
A, and
and
CH
We
can
now
to
formulate
description
these
3
B
be
formed
through
S
capture
of
cation
by
CH
O.C D of
asrearranged
H2O.
Step
hydroxy
group
is protonated
protonated
and
leaves
as
H
1.
hydroxy
group
is
and
as
Hsequence
3SH.
product
bebegin
formed
through
SNNaaN111step-by-step
capture
of the
the
rearranged
cationthoughts.
by
CH
3SH.
 CH3SH.
product
B
must
be
formed
through
SS
capture
of
the
cation
by
We
canmust
now
begin
to formulate
formulate
step-by-step
description
ofthese
these
thoughts.
1. The
The
hydroxy
group
is protonated
and leaves
leaves
asrearranged
H22O.
Step
2O.
product
B
must
be
formed
through
1
capture
of
the
rearranged
cation
by
CH
SH.
We
can
now
begin
to
a
step-by-step
description
of
thoughts.
D
N
3
product
B
must
be
formed
through
S
1
capture
of
the
rearranged
cation
by
CH
SH.
3
N
3
O. CH
StepWe
1. The
The
hydroxy
group
is protonated
protonated
andHleaves
leaves
as H
H2O.
can
now
begin
to
formulate
aa step-by-step
step-by-step
description
ofof3 these
these
thoughts.
CH3
CH33 begin
CH
We
can
now
begin
to formulate
formulate
step-by-step
theseH
thoughts.
3as
CH
CH
H
H
Step
1.
hydroxy
group
is
and
to
a
description
of
thoughts.
3description
We
can
now
CH
H
H
2
CH3 3
We
can
now
to
aa step-by-step
thoughts.
A description
O. of
Step
1. The
The
hydroxy
group
is protonated
protonated
andHHleaves
leaves
as H22O.
CH
CH
CH
We
can
now
begin
to formulate
formulate
step-by-step
of these
theseHH
thoughts.
AA 33 begin
ACH
33as
3description
Step
group
is
and
H
H hydroxy

 H
CH
CH
DDCH
CH
3 33
3 group
Step 1.
1.
hydroxy
is
and
leaves
HH
H hydroxy
H (compared
AO
ACH
AO
2O.
Step 3. The
newH
carbocation
trapped
with water)
nucleophilic
O. by the relatively
Step
1. The
The
hydroxy
group
isprotonated
protonated
and
leaves
as
O33as
C
C
OH group
 H
H
OH
 H
O sulfu
H

C




isH
DD
CH
CH
DCH
O.
is
protonated
and
as
Step
C
OH

OH
O2



A O33
AO
22222
2
H hydroxy
Hleaves
H C
O.
Step 1.
1. The
The
group
is
protonated
leaves
as
H
CH33 
CH
CH


D
3
 loss
O.
Step
1.
The
hydroxy
group
is
and
leaves
as

of CH3SH, and
followed
by
proton
H
H
H
AO
O3
C
C
OH

OH
 HH
O
CC
D9-10).
C
OH
 H
H
OH
O
C
OH
O
C
H
CH
protonated
AA O
A
2H
2
22 2to give product B (Section
2
2
CH
CH







D

3
CH
CH
H
H
H
O
O
A
CH3 333 
C
C
OH

H
OH
 H
O
C
3 
CH
DD
2

H CH
H CH
H C

 2
AAA O333 
AACH
D
AA O
CH

CH
CH

3
3
C
C
OH

H
OH

O
H
CH

H
H
H
3
D

 2
CH
AO
33 
CH
CH



CH
CH
H CH
H CH
H C
33 3333S 
O3333
D
C
C
OH
 H
OH
O
H22
CH
HH
CH
CH
H
CH
SH H
CH3
2
A
CH
D



CH
H
H
33 3
CH
AO

C

DD
3333OH
O3
O
C
C
OH 
 H
H
OH
CHHH
O
CH
ACH

AAAA O
H
H
H

 22
D
2
333 
C
OH
O
C




CH
CH
D
AC
CH
2
CH
CH


A
3
3




3
3
3

O
C
C
OH
OH
 H
O
C


D



AO
2
D
CH
CH
O3
O3



 222

DCH
C
OH 
 H
H
OH
O 
H
A
AAA O
A
O
A
C

H
OH
O
CC
HH

2
C
OH



22

CH
CH
DD
CH3 33  
22
O
O
A
C
OH

OH
O
3

SH

CH
A
3
2
O33
OCH

22
C
C
OH carbocation
 H
H undergoes
OH
 CHcarbon
O H isis
CD


Atertiary
Aexpansion
CH3 CH
CH3 C
2 by
3H
AC
CH
CH
AAtertiary

undergoes ring
ring
by alkyl
alkylshift
shift
(the
migrating
carbon
CH
Step 2. The A
(the
migrating
A
33
D
3  carbocation
33 
CH
Aexpansion
DCH
CH
CH
CH
Atertiary
Aexpansion
33
33
33
CH
2. The A
carbocation
undergoes
ring
expansion
by
alkyl
shift
(the
migrating
carbon
isisis
CH
Step
tertiary
carbocation
undergoes
ring
by
alkyl
shift
(the
migrating
carbon
expansion
by
alkyl
shift
(the
migrating
carbon
CH
CH
3
B
3
CH
3
3
3
3
dot).carbocation undergoes ringCH
ACH
represented
a 33dot).
2. Theby
tertiary
expansion
by alkyl shift (the migrating carbon is
Step
33
CH
CH
A
Step 2.
2. The
Theby
tertiary
undergoes
ring
expansion
by alkyl
alkyl
shift (the
(the
migrating
carbon
is
aa dot).
represented
dot).carbocation undergoes
A
Visually, thering
most diffi
cult step to follow
in this sequence
is step migrating
2, because it consists
of a fairl
Step
expansion
by
shift
carbon
is
Atertiary
a dot).carbocation
represented
A
Step 2. Theby
tertiary
carbocation undergoes
undergoes
ring
expansion
by
alkyl
shift
(the
migrating
carbon
is o
extreme topological
change:
The migrating
carbon
drags
with
it
the
appended
chain,
which
is
part
tertiary
carbocation
ring
expansion
by
alkyl
shift
(the
migrating
carbon
represented
by
a
dot).
HHby alkyl shift (the migrating carbon is
H
Step 2.
The
tertiary
undergoes
expansion
represented
by
a dot).carbocation
CH
3ring
3ring
the ring. ACH
good
way of
eliminatingH
confusion
is to label
the (the
action
pieces
in yourcarbon
molecule,
asis
wa
Step
2. The
Theby
tertiary
carbocation H
undergoes
expansion
byCH
alkyl
shift
(themigrating
migrating
carbonis
undergoes
ring
expansion
by
alkyl
shift
is
tertiary
Step
2.
H
represented
dot).carbocation
H
H
CH
a
dot).
D
H
D
CH
2.
The
tertiary
carbocation
undergoes
ring
expansion
by
alkyl
shift
(the
migrating
carbon
is
3
3
CH
Step
3
33ring
2. Thebytertiary
expansion
byinCH
alkyl
(theofmigrating
done 
inD
theCH
scheme
for step
2, and to H
keep
mind
the shift
bare bones
an alkyl (or H) carbon
shift. Thus, is
onl
represented
a dot).
dot).
H

H
CH
dot).carbocation undergoes
C
333
C

CH
D
3

represented
by
a
H CC
CH
CH
represented by
D
H

3
3
D

H
represented
by aa dot).
dot).

CH
CH
H CH
 DCH
CH
CH
H
33 3
H C
CH33333
H
DCH
D
H
CH3

H C
3

Step 2. The tertiary carbocation undergoes ring expansion by alkyl shift (the migrating carbon is
carbonisis
Step
2. The
Theby
is
tertiary
carbocation undergoes
undergoes ring
ring expansion
expansion by
by alkyl
alkyl shift
shift (the
(the migrating
migratingcarbon
carbon
Step 2.
tertiary
represented
a dot).carbocation
by aa dot).
represented by
dot).
H
H
CH
3
H
H
CH3
CH3
D H
CH3
H  DCH
H
CH3

C H CH
CH333
C
D
D 3


D
CC D CH
CH3
DD 3
CH3
CH3 CH
CH333
CH3
CH
3

Step 3. The new carbocation is trapped by the relatively (compared with water) nucleophilic sulfur
Step
new carbocation
sulfur
carbocation
isloss
trapped
by the
the relatively
relatively
(compared
withwater)
water)nucleophilic
nucleophilicsulfur
sulfur
Thefollowed
new
trapped
by
(compared
CH3.3SH,
by protonis
to give
product
B (Section
9-10).with
p of
new carbocation
is trapped
by the
relatively (compared w
of3.
followed
by proton
proton loss
loss to
to give
give
product BB (Section
(Section
9-10).
CHThe
by
product
9-10).
3SH, followed



CH3SH, followed by proton loss
to give product
CH3SB (Section 9-10).
SH
CH3




CH3
CH
CH33
SH
 CH3

CH3 

SH
CH33
SH


CH
CH33  CH

CH3

SH CH
CH33SH
CH
3
CH
CH33
CH3
CH
CH33

CH3S33S
CH
 

CH3
CH
CH3 33


CH3  H

CH
CH3 33  HH




SH
CH3

B
BB

CH3

Visually,
the most difficult step to follow in this sequence is step 2, because it consists of a fairly

Visually, the most
diffi
step to
in
sequence
is step 2,2,because
ititconsists
of a fairly
most
difficult
cult
to follow
follow
in this
this
sequence
becausechain,
consists
fairly
fairly
extreme topological
change:
Thestep
migrating
carbon
drags
withisit step
the appended
whichofis apart
of

CH
SH
3

topologicalCH
change:
The
carbon
drags with
itit the
chain,
which
ofof
change:
The migrating
migrating
carbon
withaction
theappended
appended
chain,
whichisispart
part
partwas
extreme
of
the
ring. topological
A good way
of3 eliminating
confusion
is todrags
label the
pieces
in CH
your 3molecule,
as
ring. A good way
of
eliminating
confusion
isis to
label
the
action
pieces
ininyour
molecule,
asas
was
way
of
eliminating
confusion
to
label
the
action
pieces
your
molecule,
was
as
the
was
done in the scheme for step 2, and to keep in mind the bare bones of an alkyl (or H) shift. Thus, only
for step
step 2,
2, and
and to
to keep
keep in
in mind
mind the
the bare
barebones
bonesofofan
analkyl
alkyl(or
(orH)
H)shift.
shift.Thus,
Thus,only
only
done in the scheme
scheme for
only

Visually, the most difficult step to follow in this sequence is step 2

eme topological change: The migrating carbon drags with it the ap
ring. A good way of eliminating confusion is to label the action pie
e in the scheme for step 2, and to keep in mind the bare bones of a

~
(

~
(

~~
~~~
(~
~
(~
(((~
(( ~

rob
C h Cp h a p t en r I n t e g rna tPi o nb P m
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n
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Chapter Integration Problems
Chapter 9
373
m take part: the cationic center,
w which
w
m
three key atoms
will receive
the migrating group; the neig
m
w
w
m
m
w
w
m
m wwill
w
three
keywwhich
atoms
take part:
part:
the cationic
cationic
center,
which
will
receive
the
migrating
group;
the
neighboring
m the
m
m A the
mm
m m the
key
atoms
take
center,
which
will
receive
migrating
group;
neighboring
three key
cationic
center,
which
willreceive
receive
the
migrating
group;
the
neighboring t
carbon,
become
charged;center,
and w
the
migrating
A
simplegroup;
aid
remembering
w
w
m
m
m atom.
A
mmigrating
m in
mthe
three
part:
cationic
which
will
neighboring
watoms
wtake
m the
m
A the
keyw
atomsw
take
part:
the
cationic
center,
which
receive
the
group;
takebecome
part:
the
cationic
center,
which will
receive
the
migrating
group;
theneighboring
neighboring
three
m
m
mm A
mmmigrating
mmmmthe
carbon,
which
will
become
charged;
and
the
migrating
atom.
A
simple
aid
in
remembering
the
basic
m and
Twillatom.
m
which
will
charged;
the
migrating
A
simple
aid
in
the
basic
carbon, of
and
thethe
migrating
atom.
A
simple
aidthe
in remembering
remembering
thebasic
basic
carbon,
which
will
become
charged;
the
migrating
simple
aid
in
the
feature
a the
carbocation
rearrangement
is
slogan:
TheA
charge
and
migrating
center
trade
mtheand
T atom.
m
which
will
become
charged;
and
the
migrating
atom.
AA
simple
aid
ininremembering
remembering
the
basic
become
charged;
and
the
migrating
atom.
simple
aid
remembering
the
basic
carbon,
which
will
will
receive
migrating
group;
neighboring
m
T
m
feature
of
a
carbocation
rearrangement
is
the
slogan:
The
charge
and
the
migrating
center
trade
places.
F
m
the
slogan:
The
charge
and
the
migrating
center
trade
places.
of aa carbocation
carbocation rearrangement
rearrangement
is
feature
is the
the
slogan:
Thecharge
charge
andthe
themigrating
migrating
centercarbocation.
tradeT
places.
feature
of
is
slogan:
The
and
center
trade
places.
F
m
T
Finally,
note
that
rearrangement
step
2
converts
a
tertiary
into
a
secondary
T
F
m
T
2
feature
of
rearrangement
isis the
slogan:
charge
and
migrating
center
places.
carbocation
rearrangement
slogan:
The
charge
andaaathe
the
migrating
centerfitrade
trade
places.
feature
ofAaa carbocation
ng
atom.
simple
aidrearrangement
in
remembering
the
basicm The
F
m
T
Finally,
th
m
T
m
m
m
2
converts
a
tertiary
into
secondary
carbocation.
The
driv2
rearrangement
step
note
that
step
2
converts
a
tertiary
into
secondary
carbocation.
The
drivFinally,
2
converts
a
tertiary
into
secondary
carbocation.
The
driv2
21
Finally,
that
step
converts
into
aa secondary
The
drivm aaatertiary
mkcal
fi to
mThe
221
2
2 rearrangement
21
ing
force
is note
the
release
of ring
strain
in22places.
a four(26.3
molcarbocation.
strain)
am
ve-me
Finally,
note
that
rearrangement
step
converts
tertiary
into
secondary
carbocation.
21 strain)
that
rearrangement
step
2going
converts
tertiary
into
am
secondary
carbocation.
drivFinally,
note
mmfrom
fififi
mThe
The
charge
the
migrating
trade
m
mm
mfidrivmrelease
Scenter
ing
force
going
from
a
four(26.3
kcal
mol
to
a
ve-membered
21
2
strain
in
is and
the
release
of
ring
strain
in
going
from
a
four(26.3
kcal
mol
strain)
to
a
ve-membered
fi
ing force
force
going
from
a
four(26.3
kcal
mol
strain)
to
a
ve-membered
2
21
21
ing
is
the
of
ring
strain
in
going
from
a
four(26.3
kcal
mol
strain)
to
a
fi
ve-membered
m
S
21strain) to a five-membered
2
mrelease
S strain
2
21 of
ing
force
is
the
ring
in
from
aafour(26.3
kcal
mol
21
(6.5into
mol
strain;
Section
4-2).
In particular
our
particular
case,
the
secondary
is
force
iskcal
theam
release
of
ring
strain
in going
going
from
four(26.3
kcal
mol
strain)
to amficarbocation
ve-membered
ing
SSection
aring
tertiary
secondary
carbocation.
The
drivS
21
m
ring
(6.5
In
our
particular
case,
the
secondary
carbocation
trapped
Section
4-2).
kcal
mol
strain;
4-2).
In
our
case,
the
secondary
carbocation
isis
trapped
ring
(6.5 kcal
In our
our
particular
case,the
thesecondary
secondary
carbocation
istrapped
trapped
21
ring
(6.5
mol
4-2).
In
particular
case,
carbocation
m
m
21 strain; Section
m
m is
ringthe
(6.5
kcal
mol
Section
4-2).
In
particular
the
secondary
carbocation
(6.5
kcal
mol
strain;
Section
4-2).
In our
our
particular
the
secondary
carbocation
trapped
by
the
highly
nucleophilic
sulfur
of the
thiol
before
itcase,
rearranges
further
by
methyl
migratio
ring
four(26.3
kcalnucleophilic
mol21strain;
strain)
to
a of
five-membered
m
m
wcase,
P m
m isistrapped
by
highly
nucleophilic
sulfur
of
the
thiol
before
rearranges
further
by
methyl
migration
to
the
thiol
before
itit
rearranges
further
by
methyl
migration
to
the
nucleophilic
sulfur
of
the
thiol
before
itrearranges
rearranges
further
bym
methyl
migration
tothe
the
by
the
highly
sulfur
the
thiol
before
it
further
by
methyl
migration
to
w
P
m
w
P
m
by the
highly
sulfur
of
the
before
itit rearranges
further
by
migration
to
thecase,
highly
nucleophilic
sulfur
of
the
thiol
before
rearranges
further
bymethyl
methyl
migration
tothe
the
w
PProblems
mmProblems
by
tertiary
counterpart,
a potential
source
of other
products,
not
observed.
ticular
thenucleophilic
secondary
isthiol
trapped
w
P
w carbocation
mof
m
tertiary
other
products,
which
are
not
observed.
Problems
36
and
61
source
of
counterpart,
potential
source
of
other
products,
which
are
not
observed.
36
and
61
other
products,
whichwhich
arenot
notare
observed.
Problems
36and
and
6136
tertiary
counterpart,
aaa potential
source
other
products,
which
are
observed.
Problems
36
61
w
m
m
w
mof
m
tertiary
counterpart,
potential
source
products,
w
m
counterpart,
a by
potential
source
of other
other
products,which
whichare
arenot
notobserved.
observed.Problems
Problems36
36and
and6161
tertiary
w
m
m
e provide
it rearranges
further
methyl
migration
to m
the
provide
mechanisms.
further
practice
with
related
mechanisms.
related
further
practice
with
related
mechanisms.
provide
mechanisms.
practice
with
related
mechanisms.
9
27 Wfurther
m
w
m A
m B fi
provide
further
practice
with
related
mechanisms.
provide
further
practice
with
related
mechanisms.
27which
W are not observed. Problems
m
w36 and 61
m A
A
m B
B fi
fi
9
ucts,
27
W
m
w
m
9 27
W
m
w
mm
fificiently.
m that
w
m A
A
m B
9-27.
convert
enantiomer
to
enantiomer
effi
ciently.
thatthat
willwill
Write
synthetic
scheme
that
will
convert
enantiomer
A
to
enantiomer
effi
Ato
Beffi
convert
enantiomer
toenantiomer
enantiomer
effi
ciently.
9-27.
Writeaa asynthetic
synthetic
scheme
convert
enantiomer
A to m
enantiomer
B efficiently.
9-27.
scheme
will
convert
enantiomer
A
BBB
ciently.
9-27. Write
Write
enantiomer
CO
O BBeffi
Write aa synthetic
synthetic scheme
scheme that
that will
will convert
convert enantiomer
enantiomer AAtotoH
enantiomer
ciently.
Hefficiently.
9-27.
O
C
O
H
H
O
C
O
H
CH
H
O
C
OO
HH
HH
O
CH
O
C
O
H
H
O
C
~
3
CH
O
C
O
H
H
nantiomer A to enantiomer
B
effi
ciently.
O
3
C
O
H
H
O
OCH
HO~
O
O
3C O
OC
CH
O
HH333CCH
HH
CH
~
O
CH3 H CH
O
CH
O
C
~
3H
O
HO
C~
~
H
O
CH3333
~
O
3
CH
HH
~
~ O
O ~H
H
C
O
O
CH
@H
HC
C
m
3
H @ isisis
~
H
H
~
&&&&& H C ~&CH3
the
CH
O O @@@@H
3C
O~
the
O
~
~
isthe
the
~
CH
OO
H3C
m
HH333C
C
~
~
H
HH
OH
H
CCH
H
3
CH
m
@
CH
H
C
H
is
the
is
the
&
CH
3
C
~
m
CH
3
H
~
H
C
3
~
33
is
theas
m
CH3
same
as
~
HH H
H
C
~
same
as
H
&
CH
H
C
same
as
CH
(
same
H
H
C
H
~
H
H
C
3
3
&
H
C
~
&
(
3
(
H
CH
~
3
3CH
~
H
C
~
same
3
H
same as
&&C&~&H
C
H
3C
C
( H
H
H
sameasas
H3(3~
HH
CH
(33C
3 3H
3
is the
H
C
H
B
H3H
CC
B
HHA
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ACH33 3
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same as

A
A
A
A

B
BB
B
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B
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B
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~
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B
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A
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SOLUTION
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m
m
m
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m
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m of
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mwIn
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This
example
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aa synthetic,
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In
other
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In
other
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solve
SOLUTION
rather than
is
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rather
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other
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This
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tosolve
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it,we
we
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This is
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it,
we
m
w
fi
m
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m
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it, solv
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This
m
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Lspecify
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t
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t
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t
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us
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ususfrom
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us
take
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hanistic,
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we use as many steps aswwe see fit to get us from
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product.
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reagents,
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Let
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product.
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material
w
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wwhich
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see
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usring
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w
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product.
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another
ether.
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in
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isis another
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material
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theproduct,
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m us take
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oxacyclopropane
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another
ether.
T
m
m
A
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m
2 T
m
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mm
2
T
m
m
A
O
B
C
H
O
T
m isis
C
H
A
m
m
C Hincrement
S
molecular
formula
of
A,
C
H
O,
is
altered
to
that
in
B,
H
O.
The
added
increment
2.
The
is
altered
to
that
in
B,
O.
The
added
increment
is
formula
of
C
altered
that
B,
C
H
O.
added
Hring
O, is
The molecular
strained
oxacyclopropane
has
beento
product,
is
another
1.
molecular
formula
of A,
A, m
C4444H
C111111
H222222
2. The
The
is
altered
toopened
thatin
inin
B,the
O.The
Thewhich
added
increment
is
8888O,
11
22
C
H
A
m
C
H
S
2.
formula
of
A,
C
H
O,
is
altered
to
that
in
B,
C
H
O.
The
added
increment
iseth
C
H
A
m
m
C
H
S
4
8
11
22
H
A
m
mmthatis
CCCAHH
S
The
molecular
formula
of
A,
C
H
O,
is
altered
to
in
B,
C
H
O.
The
added
increment
is
ened
in
the
product,
which
is
another
ether.
2. therefore
H
A
m
H
S
4
8
11
22
obvious
component
of
this
increment
the
cyclopentyl
group,
.
Subtraction
C
H
T
w
m
w
m
.
An
component
of
this
increment
is
the
cyclopentyl
group,
.
Subtraction
C
H
.
An
obvious
component
of
this
increment
is
the
cyclopentyl
group,
C
H
.
Subtraction
C
7
14
5
9
5
9
H14
obvious component
C
An obvious
componentwof
ofthis
thisincrement
increment
isthe
thecyclopentyl
cyclopentylgroup,
group,C
.Subtraction
Subtraction
5A
9 .9w
therefore
14
5H
CC
H77H
T
w
m
m
therefore
.. An
is
H
14
5
9
T
w
m
A
w
m
C
H
T
m
A
w
m
The
molecular
formula
of
A,
C
H
O,
is
altered
to
that
in
B,
C
H
O.
The
added
incre
2. leaves
4however,
8of this comparison
11 group,
22in
therefore
C
. An
obvious
component
increment
isof
the
cyclopentyl
CA
H
. Subtraction
looks
like
ethyl;
however,
comparison
of
the
substituents
in
A
(two
methyls)
T
w
m
m
7555H
14
5(two
9w
w
B
w
w
.
This
comparison
of
the
substituents
in
(two
methyls)
C
H
.
This
looks
like
ethyl;
however,
the
substituents
A
methyls)
H
ethyl;
2
looks
like
A
2
.
This
however,
comparison
of
the
substituents
in
(two
methyls)
leaves
C
d to that
in
B,
C
H
O.
The
added
increment
is
22 looksB
w
B
w
leaves
C22HC55.11H
This
ethyl;
however,
comparison
of the
substituents
in Agroup,
(two methyls)
Blike
w carbons
wSub
w
wincrement
therefore
obvious
component
of
thistwo
is
the
cyclopentyl
Hw
.w
leaves
H5.7 This
looks
ethyl;
however,
comparison
of the
in
A (two C
methyls)
14. An
5of
9two
in
B
suggests
that
the
extra
two
are
due
to
the
introduction
of
w
w carbons
wSu
m
substituents
that
the
extra
two
carbons
are
due
to
the
introduction
two
with
in
suggests
that
the
are
due
of
suggests
in B
Blike
with
theC2substituents
substituents
that
the extra
extra
two
carbons
aresubstituents
dueto
tothe
theintroduction
introduction
oftwo
two
crement
is the
cyclopentyl
group,
C5H9. Subtraction
with
the
substituents
in
B
suggests
that
the
extra
two
carbons
are
the
introduction
two
m
m
leaves
looks
like ethyl;
comparison
ofdue
thetotosubstituents
in Aofof(two
with
theC
substituents
in the
B suggests
that however,
the extra
two
carbons are
due
the introduction
two m
to
the
added
cyclopentyl
group).
2Haddition
5. This to
m
addition
cyclopentyl
group).
cyclopentyl
methyls
(in
addition
to
the
added
cyclopentyl
group).
omparison
of (in
the
substituents
in added
A (two
methyls) group).
3 methyls
W
waddition
m
R m m
methyls
(in
to
the
added
cyclopentyl
group).
m
3 W
w
methyls
(in
addition to the
added
cyclopentyl
group).
w
m
RR
with
theR
substituents
in B
suggests
that
carbons
are
due
toproduct.
the introduction
mextra two
Rmm
mmm
m
a3
carbons
are
due
twothe
stereocenters
(both
S)
in
starting
material
and
only
one
(S)
in
the
RememW
w stereocenters
m
R
m m
have
two
(both
starting
material
m to the introduction
wonly
fiRemem3.
two
starting
material
and
only
one
(S)
the
product.
RememS) in
inof
We
haveR
stereocenters
(both S)
3.twoWe
two
starting
materialand
and
onlyone
one(S)
(S)in
inthe
theproduct.
product.
Remem3.
We
have
two
(both
S)
in
starting
material
and
one
(S)
inin
the
product.
Rememm
m
ww
fifi
m
wonly
fi
methyls
(in stereocenters
addition
to does
the
added
cyclopentyl
group).
3. ber
We
have
two
stereocenters
(both
S) correlate
in
starting
material
and
only
one (S)
in
theSproduct.
Rememroup).
R,S-nomenclature
does
not
correlate
necessarily
with
changes
in
absolute
confi
guration,
not
necessarily
with
changes
in
absolute
confi
guration,
R
m
w
fi
w R,S-nomenclature
H w
correlate
necessarily
with
changes
in
absolute
confi
guration,
ber that
that
R,S-nomenclature
does
not
correlate
necessarily
with
changes
in
absolute
confi
guration,
ber
that
R,S-nomenclature
does
not
correlate
necessarily
with
changes
in
absolute
confi
guration,
w
S
H
SS
HHww
w
w R,S-nomenclature
ber
that
does(both
not
correlate
with
absolute
guration,
the
priority
sequence
of
substituents
at
stereocenter
(Section
5-3).
How
with
changes
sequence
of
substituents
at
aaachanges
stereocenter
(Section
5-3).
w
S win confi
H
wR
monestereocenters
BRememAand
Wonly in
wHow
changes
in
sequence
of
substituents
at
stereocenter
(Section
5-3).
How
priority
Weand
have
two
S) in starting
material
one
(S)
the
product.
only
with
the
3. only
changes
ininthe
sequence
ofnecessarily
substituents
at
stereocenter
(Section
5-3).
How
material
only
(S)in
thepriority
product.
only
with
changes
in
the
priority
sequence
of
substituents
at
(Section
5-3).
m
W
m
BB
AA
W
ww
ww
m
B then
Aaaastereocenter
W get
w by
wHow
only
with
changes
in
the
priority
sequence
of
substituents
at
stereocenter
(Section
5-3).
How
stereocenter
in
B
then
relate
to
those
in
A?
We
get
the
answer
by
rewriting
does
the
remaining
stereocenter
in
B
relate
to
those
in
A?
We
the
answer
rewriting
m
A
W
w
w
B
m
B
w
m
m
remaining
then
relate
to
those
in
A?
We
get
the
answer
by
rewriting
in
B
stereocenter
does
the remaining
remaining
then
relatewto
tonecessarily
thoseininA?
A?with
Weget
get
theanswer
answer
byrewriting
rewriting
ber that
R,S-nomenclature
correlate
changes
in absolute
confi
g
does
the
in Bnot
then
relate
those
We
the
by
cessarily
with
changes
instereocenter
absolutedoes
confi
guration,
m
B
w
m
m
B
m
B
m
m
m
B
w
m
m
does
the
remaining
stereocenter
in
B then
relatewith
to those
in A?
We
get w
the answer
by
rewriting
B
in
a
conformation
B9
that
is
visually
clearer
respect
to
the
stereochemical
arrangement
B9
that
is
visually
clearer
with
respect
to
the
stereochemical
arrangement
m
B
w
m
m
w
CH
H
conformation
visually
clearer
with
respect
to
the
stereochemical
arrangement
B
in
a
B9
that
is
conformation
visually
clearer
with
respect
to
the
stereochemical
arrangement
B
in awith
conformation
B9
that
is visually
clearer
with
respect to theatstereochemical
arrangement
only
in wwthe
priority
of substituents
a stereocenter
(Section 5-3
substituents
at
a changes
stereocenter
(Section
5-3).sequence
How
5CH
CH
HH
ww
B
in a the
conformation
B9
thatthe
is visually
clearer
with respect
to the
stereochemical
arrangement
around
stereocenter,
with
CH
H
connected
to
the
chain
by
aaaaawedged
and
hashed
line,
stereocenter,
with
the
CH
and
H
connected
to
the
chain
by
wedged
and
hashed
line,
w
H
w
A
T
A
and
connected
to
the
chain
by
wedged
and
hashed
line,
3333 and
around
the
CH
stereocenter,
with
the
H
and
connected
to
the
chain
by
wedged
and
hashed
line,
around
the
stereocenter,
with
the
CH
and
H
connected
to
the
chain
by
wedged
and
hashed
line,
e to those
A?remaining
We getA
answer by rewriting
does inthe
3in B then relate to those
TTstereocenter
AA in A? We get the answer by r
Athe
around
with
the CH
connected
to
chain
by replaced
areplaced
wedgedby
and
hashed
line,
respectively,
as
A.
reveals
that
the
ether
oxygen
in
A
aaaaacyclopentyl
This
reveals
that
the
ether
oxygen
in
A
has
been
by
cyclopentyl
A
T
A
3 and
wthetostereocenter,
as
in
A.
that
the
ether
oxygen
in
has
been
replaced
by
cyclopentyl
respectively,
reveals
This
Ahas
as in
in
A. This
that
theH
ether
oxygen
inthe
hasbeen
been
replaced
by
cyclopentyl
as
in
A.
This
the
ether
oxygen
in
A
has
been
by
cyclopentyl
withrespectively,
the
stereochemical
Brespect
in aw
conformation
B9reveals
that arrangement
isthat
visually
clearer
with
toreplaced
the stereochemical
arran
group
with
inversion.
respectively,
as in A. This
reveals
that
the ether
oxygen
in Arespect
has been
replaced
by a cyclopentyl
w
inversion.
group
with
inversion.
group
with
inversion.
W
w
m
B
nnected
to
the
chain
by
a
wedged
and
hashed
line,
aroundwith
theinversion.
stereocenter,
with
wedged and hash
W
w
m
w
m the CH3 and H connected to the chain by aBB
group
hints
do
we
derive
from
this
analysis?
It
is
clear
that
the
stereocenter
in
B
can
be
derived
derive
from
this
analysis?
ItIt
is
clear
that
the
stereocenter
in
BB
can
be
derived
W
w
m
mWhat
A
w
m
do
we
analysis?
is
clear
that
the
stereocenter
in
can
be
derived
What
hints
oxygen
in
A
has
been
replaced
by
a
cyclopentyl
derive
from
this
B
do
we
analysis?
It
is
clear
that
the
stereocenter
in
can
be
derived
What
hints
do
we
derive
from
this
analysis?
It
is
clear
that
the
stereocenter
in
B
can
be
derived
respectively,
as in A. This reveals
w that the ether oxygen
m
A
ww
mm in A has been replaced by a cyc
mWhat
A byhints
do we derive
from this
analysis?
It is clear
that m
the stereocenter in B can be derived
from
ring
with
aaaaa cyclopentyl
organometallic:
ring
opening
with
cyclopentyl
organometallic:
mA
w
m
nucleophilic
cyclopentyl
organometallic:
from
A by
by nucleophilic
ring opening
opening
with
nucleophilic
cyclopentyl
organometallic:
from
A
nucleophilic
ring
opening
with
cyclopentyl
organometallic:
group
with inversion.
HO
from A by nucleophilic ring opening with a cyclopentyl organometallic:
HO
HO
HH
H
CH
HCH
is clear that the stereocenter in B can be derived
L
HO
HO
H
HO
CH
H
L
~ theH
HO
CH3
What hints do we derive
that
stereocenter
in B can be
Lanalysis? It is clear
O from thisL
CH
CH
C~
HHO
Li
~ HH
Li
CH33
O
L
entyl organometallic:
Li
O

HO

Li

CH3

~
~
( (

group with inversion.

What hints do we
be derived
O derive from this analysis? It is clear that the stereocenter
C ~& in BHcan
H3HO
H , H2O
CH3
from A by nucleophilic ring openingLi
 with a cyclopentyl organometallic: H

~
HCH33

H, H2O HOH3CH &

Li

H, H22O

H33C ~&
H

~
(~
(

~
H3CO~&
( H
CH
H
3
~
~
H 3C &
( H O
~
~
CH
H
AH33C 3&
( H

CH33

at would provide an alcohol

C, not an ether, and theCoxygen-bearing carbo
A
A
C
group.
However, that would provide an alcohol C, not an ether, and the oxygen-bearing carbon misses the
ork
retrosynthetically.
Ether
disconnection
synthesis
ld
an alcohol
C, not
an ether, by
andretro-Williamson
the oxygen-bearing
car
extraprovide
methyl group.
us work retrosynthetically.
disconnection
tiary
alcohol
D. How do Ether
we unravel
D by
to retro-Williamson
C? Answer:synthesis
We go(Section
back9-6)
to
.givesLetthe
tertiary alcohol D. How do we unravel D to C? Answer: We go back to Section 8-9,
that
complex
alcohols
can can
be bemade
from by
simpler
ones by organometallic
etrosynthetically.
retro-Williamson
synthesi
recognizing that complexEther
alcoholsdisconnection
made from simpler
ones by organometallic additions
to
mpounds:
carbonyl compounds:

alcohol D. How do we unravel D to C? Answer: We go back

OH
O
omplex alcohols can be made from simpler
OH
O ones by organometal
ds:
O
HO
@
@
@
@
O

@
H

@
H
B

@
B
H

@
H

HO

@
H
D

HO

@
DH

@
H

O
 CH33Li

@
 CH3Li H

 CH3Li

@
H

@
H

OH@H

@
H

Further Reactions of Alcohols and the Chemistry of Ether

u rr tt h
h ee rr R
R
n s oofff AAAlllcccooohhhooolllsss aaannnddd ttthhheee CCChhheeem
miisissttrtryryy oooff f EEEtththh
eer
F
R eee aaa ccc ttt iii oooo n
u
e
F
mm
E tt ththhh
u
tt h
R
nnsss o
o ff AAllccoohhoolllsss aaaannnndddd tttthhhheeee CCCChhhheeeem
ee rrr
F
miiiississsttttrrtrryyryyy ooooofffff E
u rrrsolution
h eee rrr therefore
R eee aaa ccc ttt iiilooks
The
asoofollows:
follows:
Fu
th
R
oo nn ss as
f A l c o h o l s a n d t h e C h e mm
EEE
t h e ere
The
solution
therefore
looks
The
solution
therefore
looks
as
follows:
as Lifollows:
follows:
The solution therefore looks as
Further Reactions of Alcohols and the Chemistry of Ethers
374
C h a p t e r looks
9
The solution
solution
therefore
asLi
follows:
follows:
Li
The
solution therefore
therefore looks
looks as
asLi
follows:
Li
The solution
therefore
looks
as
follows:
O
O
Li
Li
The solution
solution
therefore
looks
as
follows:
O
therefore
looks
as
follows:
O
Li
The
solution
therefore
looks
as
follows:
O
Li
The solution
1.CH
CH3Li
Li
Cr2O
O7,,
Na2Cr
as
follows: Na
1.
The
solution therefore
therefore looks
looks1.1.
as
 follows:
OO
The
looks
The solution
therefore
looks
follows:
1.as
1.CH
Cr4O
O
Na2SO
,H
H2O
Osolution therefore
ILi
2.
HLi
2.
CHLi
SO
H,7,,2O
O as follows:
H
Li
2Cr
2,O
3ILi
1.
1.
Na
,
2.
H
CH
,
H
H
1.
1.2.
Cr
Na
Li
OO @

Li
A 1.2.2.2.
C
B
,
H
O
HLi
2.
CH
SO
H
O
H
Li
2O
2SO
4,,O
2O
A
C
,Li
H
H
CH
H
H
1.H
1.
CH
Cr
,
Na
,HO
I33IILi B
CH
,2H, 7O
H SO
1.2.2.
CH
Li
Cr
Na
2 O
@
Li
O
B

1.
1.
CH
Cr
O
,
Na
A 2.
C
@
O
O
H
2 ,O
2, H
1.2.HH , ,HHO
CH
O
,7O2O
C HNaHSO
BB
I
CH
SO
@H 2.1.2.CH
ILi33Li
2O
2Cr
4H
@
O

O
2.HH , ,HHO
2.
CH
, H,O2O1.
HSO
H
A 1.
I Li
2.
CH
2O
3I
,4O
H
H
2SO
CH Li
A
CC Na
B1. B
Cr
O , 2.
Na
O
O
H
1.
1.1.
CH
Cr
Na
@
O
@
H
1.
CH
Li
Cr
O
,
1.
CH
Li
Cr
O
,
Na
2. H , H O
2. B
CH I
H SO , H O
3
A 1.2. H , H O CC Na
22
22 77
A
B
3
@
1.
CH
Li
Cr
O
,AO
Na
@
1.
CH
Li
Cr
O
,
C
B
I
2.
CH
SO
,
H
O
H
H
H

@
,
H
O
I
2.
H
2.
CH
SO
,
H
H
ILi
2. H ,HHO
2.
H
Li
CH
,O
CH
22O
Cr,,O
OH
,22O
Na
22SO
442,O
2Cr
1.1.
CH
Cr
, 7O
I33Li
CH
H 1.2.1.1.
SO
H
HNa
H B
C
BB
ILi
H , H O
SO
H
A
C
CH
A 2.
C HHNa
@@@@H
CH
H
@ 2.
O C
2.
CH
SO,4,H
,H
HO2O
O
HSO
2O
B
2SO
I 3II B
2.2.HH , ,HHO
2.2.
CH
A
HH
A
C
B
B
H
A
C
B
@
@
@H
Problem 55
55 contains
contains similar
similar synthesis
synthesis exercises.
exercises.
H
Problem
H
HH
Problem
55 contains
contains similar
similar synthesis
exercises.
Problem 55
contains similar synthesis exercises.
synthesis
exercises.
Problem 55
exercises.
Problem 55 contains
contains similar
similar synthesis
synthesis exercises.
exercises.
55 contains
exercises.
ProblemReactions
contains similar
similar synthesis
synthesis
exercises.
New Reactions
New
New
similar
synthesis
exercises.
1. Alkoxides
from Alcohols (Sections 8-3, 9-1)
ProblemReactions
55
similar
exercises.
Problem
contains
similar synthesis
synthesis
exercises.
exercises.
55 contains
contains
synthesis
exercises.
8-3, 9-1)
9-1)
Reactions
Problem
Using strong
bases
New
Reactions
1. Alkoxides
from similar
Alcohols
(Sections
8-3,
Problem
contains
similar
synthesis
exercises.
55 contains
synthesis
exercises.
Reactions
New
Reactions
1. Alkoxides
from similar
Alcohols
(Sections
8-3, 9-1)
9-1)
Strong base
9-1)
from
Alcohols
(Sections
8-3,
ROH 3:::::4 RO2
Using
strong
bases
1. Alkoxides
from
Alcohols
(Sections
8-3,
9-1)
New
Alkoxides
from
Alcohols
(Sections
8-3,
9-1) ofbase
Reactions
Using
strong
bases
New
Reactions
Examples
strong bases: Li N[CH(CH ) ] ; CH CH CH CH Li; K H
bases
Strong
1. Alkoxides
from
Alcohols
(Sections
8-3,
9-1)
Reactions
Alkoxides
from
Alcohols
(Sections
8-3,
9-1) base
Strong
New
2
strong
bases
New
Reactions
Reactions
ROH
3:::::4
RO22
Using
strong
bases
Strongbase
base RO
ROH
3:::::4
Strong
base
Strong
Using
alkali
metals
2
1.
Alkoxides
from
Alcohols
(Sections
8-3,
9-1)
2
strong
Alcohols
(Sections
8-3,
9-1)
Using
strong bases
bases
1. Alkoxides
3:::::4
RO
2 1
ROH
3:::::4
RO
Alkoxides
fromExamples
Alcohols
(Sections
8-3,
9-1) base
ROH
3:::::4
RO
Strong
9-1)
12
1.
from
Alcohols
8-3,
9-1)
1CH
M2u
u
y RO
1 12Li;
H2 K11H22
Strong
baseROH
2
of (Sections
strong
bases:
Li12
N[CH(CH
CH
CHM CH
of
strong
bases:
Li
N[CH(CH
]]22RO
;; CH
Alkoxides
Strong
base
fromExamples
Alcohols
(Sections
8-3,
9-1)
Using
1. Alkoxides
from
Alcohols
(Sections
8-3,
9-1)
33CH22CH22CH22Li; K 1H 2
ROH
3:::::4
strong
bases
9-1)
Strong
base33))22RO
12
ROH
3:::::4
2M
12
22
5CH
Li, Na,
K CH Li; K
2CH
Using
strong bases
bases
strong bases:
bases:
Li12
N[CH(CH33)3)2)2]2RO
CH
CH
H
Examples
Li
N[CH(CH
Examples of
of strong
strong
bases:
Li
N[CH(CH
]];2;;CH
CH
K11HH
2CH
2CH22Li;
2Li;K
ROH
3:::::4
Using strong
333CH22CH
22CH
ROH
3:::::4
12
2 2
Strong base
base) ] 2;2RO
Strong
Using
strong
bases
bases
12
strong
2
Examples
of
strong
bases:
Li
N[CH(CH
CH
CH
CH
CH
Li;
K1
2
Strong
base
3 32)22]2; CH
3 3CH
2 2CH
2 2CH
2 2Li;
Examples of strong
bases:
Li
N[CH(CH
KH1
H2
Strong
base
12
Strong
base
Using alkali metals Examples
Haloalkanes
from
Alcohols
ROH
3:::::4
RO
12
ROH
3:::::4
2
22
2
Li
N[CH(CH
CH2CH
K1H
2
3)32)]2RO
2RO
3CH
2Li;
strongbases:
bases:
Li12
N[CH(CH
];2RO
;CH
ROH
3:::::4
Strong
base
Strong
base
3CH
2CH
2Li; K H
Using alkali metals
metals Examples ofofstrong
3:::::4
ROH
3:::::4
Strong
base
12 2CH
2RO
1CH
2
2
1
2
1
2
12
11 2
22
2.ROH
Using
Hydrogen
Halides
(Sections
8-3,
9-2,
9-3)
M
u
u
y RO
RO
M
1
H
12
ROH
3:::::4
RO
1Li
M
u
u
y
M
1
ROH
3:::::4
3:::::4
Examples of
of strong
strong
bases:
Li
N[CH(CH
)22
]2RO
CH
CH
CH
CH22Li;
K1
H2
Using alkali
22 22CH
12
1
bases:
N[CH(CH
CH
1CH
2Li;K
22;;RO
12121H
1
12
1H
22
12
1
2
33)2
333CH
222
12
Using
alkali metals
metals Examples
12
1
2
Examples of
ofstrong
strong
bases:
Li
N[CH(CH
)2]]22M
]21
;CH
CH2CH
K
H
u
u
yHXRO
RO
M
1
bases:
Li
N[CH(CH
CH
CH
CH
Li;
K1
H
33CH
22CH
22Li;
bases:
N[CH(CH
))332
CH
K
H
ROH
1
M
u
u
y
1
Using alkali
ROH
1Li
M
u
u
y
RO
1
2;;2
2CH
3332
22]M
333CH
2H
222Li;
2H
2222 222CH
12
11
22
Conc.
Using
alkali metals
metals Examples
1
2Conc. HX
122H
12
12
1H
Mu
5u
Li,
Na,
122CH
1
Examples
bases:
N[CH(CH
)333222
]22222]];2221
H
H
Examples of
of strong
strong
bases:
N[CH(CH
)K
CH
M
5
Li,
Na,
Primary
ROH
u
u
uy
RX
Secondary
or2Li;
tertiary
32
3CH
2CH
ROH
11LiLi
M
u
y
RO
M
11
H
bases:
Li
N[CH(CH
)K
CH
CH
CH
Li;KK
KROH
H2uuuuy RX
333CH
22CH
222Li;
2222CH
21CH
ROH
M
u
u
y
RO
M1;;CH
2
11
2 2
21 H
Using
alkali
metals
M
5
Li,
Na,
K
M
5
Li,
Na,
K
ROH
1
M
u
u
y
RO
M
H
M
5
Li,
Na,
K
2
X
5
Br
or
I
(S
2
mechanism)
X
5
Cl,
Br,
or
I
(S
1
mechanism)
2
ROH 1 M
u
uyNa,
ROK
M 1 12H2
Using
alkali metals
metals
Using alkali
MM55Li,
2K 11
1
alkali
Li,RO
Na,2
Using
metals
ROH
1M
M
u
u
y
RO
M1
1
11H22
2
alkali metals
u
u
y
M
1H
2
11
2
11
MM
5
Li,
Na,
K
2
Using 1
Phosphorus
Reagents
(Section
9-4)
Haloalkanes
from Alcohols 3.ROH
5
Li,RO
Na,2
K
u
u
y
RO
M
1
1
u
u
y
M
1
ROH
1M
M
u
u
y
RO
M1
121122122H
221 H
22
11
2
2
1H
22 2
2
11
Haloalkanes from Alcohols
Alcohols ROH
ROH
1
M
u
y
RO
M
H
ROH
1
M
u
u
y
RO
M
1
Mu
5
Li,
Na,
K
2 22
u
y
RO
M
1
H
3 RBr 1 H3PO3
3 ROH
1 PBr
M
5
Li,
Na,
K
22H
3 2uy
Haloalkanes
from
Alcohols
M
5
Na,
K
M
5
Li,
Na,
KK
8-3,
9-2,
9-3)
M9-2,
56Li,
Li,9-3)
Na,
2.
Using
Hydrogen
Halides
(Sections
8-3,
Haloalkanes
from
Alcohols
ROH
1
2
P
1
3
I
uy
6 RI 1 2 H3PO3
2
Haloalkanes
from
M
5
Li,
Na,
KK
M
5
Li,
Na,
Haloalkanes
from Alcohols
Alcohols
Hydrogen
9-2,
9-3)
M
5
Li,
Na,
K
2. Using Hydrogen
Halides
(Sections
9-2,
9-3)
Halides
(Sections 8-3,
8-3,
9-2,
9-3)
S 2 mechanism with primary and secondary ROH
2.
Using
Hydrogen
Halides
(Sections
8-3,
9-2,
9-3)
Alcohols
Haloalkanes
from
Alcohols
Conc.
HX
likelihood
with HXHX
2. Using
Using Hydrogen
Hydrogen
Halides
(Sections8-3,
8-3,Less
9-2,
9-3)of carbocation rearrangements thanConc.
Conc.
HX (Sections
2.
9-3)
Haloalkanes
from Halides
Alcohols
Haloalkanes
from
Alcohols
2. Using
Hydrogen
Halides
8-3,9-2,
9-2,
9-3)
Secondary
or tertiary
tertiary ROH
ROH Conc.
u
u
u
u
y RX
RX
Conc.
HX
HX
Conc.
HX
Primary
ROH
u
uuu
y (Sections
RX
Secondary
or
u
u
u
u
y
Conc.
HX
Conc.
HX
from
Alcohols
from Conc.
Alcohols
Haloalkanes
4. Using Sulfur
(Section 9-4)or
HX
HX
Halides
(Sections
8-3,Reagents
9-2,
9-3)
Primary
ROH
u
u
u
u
y
RX
Secondary
u
u
u
u
y
2. Using
Hydrogen
Halides
8-3,
9-2,
9-3)
ROH
u
u
u
u
Secondary
ortertiary
tertiaryROH
ROHConc.
u
u
u
u
yRX
RX
y (Sections
RX
Secondary
or
tertiary
ROH
u
u
u
u
y
RX
Conc.
HX
Conc.
HX
9-2,
9-3)
X9-3)
5
Cl,
Br,
or
I (S
(SNN11ROH
mechanism)
Conc.
HX
Conc.
HX
2.
Using
Hydrogen
Halides
(Sections
8-3,
9-2,
Primary
ROH
u
u
u
u
y
RX
Secondary
or
tertiary
u
u
u
u
y
X
5
Br
or
I
(S
2
mechanism)
X
5
Cl,
I
mechanism)
Hydrogen
Halides
(Sections
8-3,
9-2,
9-3)
N(CH Br,
CH
) or
 RX
N
Conc.
HX
Conc.
HX

Primary
ROH
u
u
u
u
y(Sections
RX
Secondary
or
tertiary
ROH
uu
u
uy
u
y
RX
2.
Hydrogen
Halides
8-3,
9-3)
ROH
9-2,
SOCl
RCl

(CH
Cl
SO
Hydrogen
Halides
(Sections
8-3,
9-2,
9-3)
Primary
ROH
u
u
u
u
y
RX
Secondary
or
tertiary
ROH
u
u
RX
X
5
Br
or
I
(S
2
mechanism)
X
5
Cl,
Br,
or
I
(S
1
mechanism)
or
I
(S
2
X
Cl,
Br,
or
I
(S
1
mechanism)
25
3CH
2)3NH
2  u
mechanism)
X
5
Cl,
Br,
or
I
(S
1
mechanism)
2. Using
Using
9-2,
9-3)
N
N
N
N
N
Primary
u
uu
y RX
or Itertiary
ROHConc.
uuu
uy RX
Conc.
HX
Conc.
HX
HX
HX
X
5 Br orROH
I (SNConc.
2u
mechanism)
XSecondary
5 Cl, Br, or
(SN1 mechanism)
Conc.
HX
Conc.
HX
Conc.
HX
Nu
,
DMSO
Conc.
HX
Conc.
HX
X5
5Phosphorus
Br or
or
I (S
(SNNu
2u
mechanism)
X55
Cl,Br,
Br,
or
I(S(S
mechanism)
u
u
u
y RX
RX(Section
Secondary
or
tertiary
ROH
u
u
u
u
y
RX
Primary
ROH
u
u
y
Secondary
or
tertiary
ROH
u
u
u
u
y
RX
(Section
9-4)
N1mechanism)
X
Br
I
2
mechanism)
X
Cl,
or
I
1
3. Using
Reagents
9-4)
N
RSO
ROH

RSO
Cl
ROSO
R
RNu

Conc.
HX
Conc.
HX
Secondary
ororor
tertiary
ROH
u
u
u
u
y
RX
X
5Phosphorus
Br or
I (SNu
2u
mechanism)
X 25 Cl, Br,
I 2(SN1ROH
mechanism)
Primary
ROH
u
u
u
u
y RX
RX(Section
Secondary
tertiary
ROHu
u
yRX
RX3
Conc.
HX
Conc.
HX
Conc.
HX
Primary
ROH
u
u
y
or
tertiary
u
u
u
y
Conc.
HX
3. Using
Reagents
Phosphorus
9-4)Secondary
Reagents
(Section 9-4)
9-4)
Primary
ROH
u
u
y
tertiary
ROH
u
u
u
y
Primary
ROH
u
u
u
u
y RX
RX
Secondary
or
tertiary
ROH
u
u
u
u
y
RX
X
5Phosphorus
Br or
I (SNNu
22u
mechanism)
X
5
Br,
or
IAlkyl
(S
mechanism)
X
5 Cl,
Cl,
Br,or
or
IH
(SNNPO
mechanism)
3. Using
Reagents
(Section
9-4) Secondary
Secondary
tertiary
ROHu
u
u
u
u
yRX
RX
N11 mechanism)
sulfonate
uy
3 RBr
RBr
1
3 ROH
1 PBr
PBr
X
55Cl,
Cl,
Br,
or
(S
11mechanism)
uy
3Cl,
1
X5
Br
mechanism)
5
Br,
or
IIH
(S
Phosphorus
Reagents
(Section
9-4)
3PO
3mechanism)
N
33 X
3(S
3mechanism)
5Phosphorus
Br or
or III (S
(SNNNN222 Reagents
mechanism)
X
Br,
or
I
N
NN1
3.
Using
(Section
9-4)
N
X
5
Br
or
(S
mechanism)
X
5
Cl,
Br,
or
I
(S
1
mechanism)
uy
RBr
1
HIH
PO
3 ROH
1
PBr
3. Using
Reagents
(Section
9-4)
NPO
uy
3RI
RBr
1
PBr
uy
3Cl,
RBr
ROH
1 PBr
X 5Phosphorus
Br or I (SNNN26mechanism)
X
(S
1333mechanism)
3PO
3PO
N
X5
56633Cl,
Br,
orH
I333PO
(S
mechanism)
N
N31
uy
RI
1
2or
HH
Rearrangements
inBr,
Alcohols
ROH331Carbocation
2P1
33PBr
II223333uy
1
21
uy
RBr
1
ROH
3
3.
Using
Phosphorus
Reagents
(Section
9-4)
Reagents
(Section
9-4)
uy
3
RBr
1
H
PO
3
ROH
1
PBr
6
ROH
1
2
P
1
3
I
uy
6
RI
1
2
H
PO
uy 6633RI
RBr
1 and
1
PBr
3.
(Section
9-4)
6Reagents
1
uy
RI
1
H3H
PO
3 333 3 Shifts (Section 9-3)
9-4)
ROH31
2(Section
IRearrangements
2223 3uy
Phosphorus
Reagents
9-4)
33PO
3. Using
Using Phosphorus
5.
Carbocation
by
Alkyl
Hydride
RBr
31ROH
ROH
1
ROH
2(Section
PP 1
33PBr
I9-4)
6 secondary
RI
11
2221
HH
PO
SN 26Reagents
mechanism
with
primary
and
secondary
3.
with
primary
and
ROH
3 uy
3PO
2 uy
3ROH
3 3
3. Using
Using Phosphorus
Phosphorus
Reagents
6mechanism
ROH331
1ROH
2with
1
3PBr
uy
RI
2HH
H
PO
uy
33secondary
RBr
1
ROH
2(Section
PP 1
3PBr
I9-4)
66secondary
RI
1121
PO
uy
RBr
1
H
PO
ROH
SSNN226mechanism
primary
and
ROH
333PO
2I23OH
3ROH
3 333
primary
and
3uy
primary
and
ROH
(R)H
H(R)
(R)H
6likelihood
ROH331ROH
2with
Pcarbocation
1
3PBr
uy
63secondary
11
21ROH
H
carbocation
rearrangements
than
with HX
HX
uy
33RI
RBr
1
PO
of
rearrangements
with
uy
RBr
H
PO
1
PBr
uy
RBr
H
ROH
1
3
3
SLess
2 mechanism
with
primary
and
secondary
A I23
A
33A3
33than
33 3
33PO
3uy
3 i  HX
H 3 RBrA 1 fHthan
uy
PO
31
ROH
PBr
Less
likelihood
of
carbocation
rearrangements
ROH
2
P
1
3
I
uy
6
RI
1
2
H
PO
SNNN226
mechanism
with
primary
and
secondary
ROH
ROH
1
2
P
1
3
I
6
RI
1
2
H
PO
3
3
S
mechanism
with
primary
and
secondary
ROH
Less
carbocation
rearrangements
than
with
HX
2
3
333 3with
likelihood
of
carbocation
rearrangements
than
uy
3
RBr
1
H
3
ROH
1
PBr
CO
CH
C
C OHX
O
O
2 uy
3PO
3uy
33PO
uy
3RIRBr
H
PO
33with
ROH
1
2of2with
Pcarbocation
1
3O3CIA22IOC
666Osecondary
RI
1
2221
3O
RI
1
H
PO
Less
likelihood
rearrangements
than
with
H
SN26
mechanism
primary
and
ROH
3
3
22
3
f HX
i
A
A
A
3
33 3
6
ROH
1
P
1
uy
1
H
PO
33than
2 uy
3with
6
ROH
1
2
P
1
3
I
6
RI
1
2
H
PO
Less
likelihood
of
carbocation
rearrangements
with
Less
likelihood
of
carbocation
rearrangements
than
HX
H
4. Using Sulfur Reagents
(Section
9-4)
2
3
3
S
2
mechanism
with
primary
and
secondary
ROH
2
mechanism
with
primary
and
secondary
ROH
6
ROH
1
2
P
1
3
I
uy
6
RI
1
2
H
PO
H
N
H
N
22 uy
33than
6secondary
RI 1 2 ROH
HROH
PO333 with HX
likelihood
of
carbocation
rearrangements
HX
SLess
with
primary
and
secondary
4. Using Sulfur Reagents
(Section
9-4)
primary
and
ROH
NN22 mechanism
S
mechanism
with
primary
and
secondary
Reagents
(Section
9-4)
N
SLess
mechanism
with
primary
and
secondary
ROH
Less
likelihood
of
carbocation
rearrangements
than
with
HX
4. Using Sulfur Reagents
(Section
9-4)
likelihood
of
carbocation
rearrangements
than
with
HX
NN2
S
2
mechanism
with
primary
and
secondary
ROH
N(CH
CH
N(CH
2CH
3))3
SNN2 mechanism
with
primary
and
secondary ROH
carbocation
rearrangements
than
with
HX
Less
likelihood
of
carbocation
rearrangements
than
H with
El
Sulfur Reagents
Reagents
(Section
9-4)
4. Using Sulfur
(Section
9-4)
Less
likelihood
of
carbocation
rearrangements
than
withHX
HXS 1Nu

N(CH
CH
)))
likelihood
of
carbocation
rearrangements
than
with
HX
N(CH
N(CH
CH
RCl
 SO
than
(CH
CH
NH
Cl
SO22 
4. Using Sulfur
9-4)
ROH Reagents
Less
SOCl
RCl

(CH
2CH

 Cl
LessSOCl
likelihood
of
rearrangements
with
HX
22(Section
33CH
22))33NH
N(CH
CH
)3 3
likelihood
of carbocation
carbocation
with
HX


ROH

RCl


(CH
NH
Cl
SO
4.
Using
Sulfur
(Section
9-4)
Reagents
9-4)

2(Section
33CH
22)2)3)
ROH Reagents
LessSOCl
SOCl
RCl


(CH
Cl
RClrearrangements
 SO
than
(CH
CH
NH
Cl
SO
SO222 
N(CH
N(CHCH
2
33NH
3CH
2CH)3)3
4.
Using
Sulfur
Reagents
9-4)

 Cl
ROH

RCl

Nu H(R)
H(R) (CH3CH
2(Section
2)3NH

2

4.
Using
Sulfur
Reagents
(Section
9-4)
N(CH
CH
)
Nu
,
DMSO
2
3
3
Nu
,
DMSO
9-4)
G
D (CH
 Cl
4.
Using Sulfur
ROH

RCl
A ClA 
ROH Reagents
 SOCl
SOCl2(Section
RCl  SO
(CH
SO
3CH
2)23)NH
2,2CDMSO
2(Section
3CH
3NH
4.
Sulfur
Reagents
(Section
9-4)

N(CH
CH
)
C
P
Nu
N(CH
CH
)

4. Using
Using ROH
Sulfur
Reagents
9-4)

ROH 
 RSO
SOCl Cl N(CH
RCl R
 Nu
(CH
NH
Cl
Nu
,, DMSO
O CRSO
OC
Nu, 2DMSO
DMSO
RSO
ROSO
R
RNu

ROSO
RNu

G 
O 
DSO

))
3CH)2)
3
N(CH
CH
33

N(CHCH
ROH 
 RSO
SOCl22222Cl
RCl


(CH
CH
NH
SO
ACl
22CH)33)33

RSO
ROH
ROSO
RNu
 Cl
RCl 22222R
 SO
 (CH
(CH
CH222)))33
NH
SO
A33
3RNu
2,2DMSO
N(CH
CH
RSO
3
3
ROH

RSO
Cl
ROSO
R
RNu

RSO
ROSO
R


Nu
SOCl
RCl


CH
NH
Cl
2
3
Nu
,
DMSO
RCl


(CH
CH
NH
Cl
SO
ROH

N(CH
CH
)
RSO
Alkyl
ROH

RSO
RNu
Alkyl
33 3CH
22 23
H 
222 
3)NH

3 

22Cl
2R
N(CH2CH3)3 ROSO
ROH

SOCl
RCl

(CH
NH
Cl
SO
2
3

ROH

SOCl
RCl


(CH
CH
)
Cl

SO
Nu
,
DMSO

Alkyl

2
3
2
3
RSO
ROH

RSO
ROSO
RNu

2, DMSO
RSO
ROH

RSO
Cl 6. Concerted Alkyl
ROSO
R
RNu

Alkyl
Alkyl
3 
ROH

SOCl
RCl


(CH
CH
)
NH
Cl
222Cl
2R
SO
sulfonate
sulfonate
3
2from
Nu
3
2
3
2
ROH

SOCl
RCl


(CH
CH
)
NH
Cl
SO
3
2
3
Alkyl
Nu
,
DMSO
Shifts
Primary
Alcohols
(Section
9-3)
2
3
2
3
2
RSO
ROH  RSO2Cl
ROSO
RNu  RSO
3

sulfonate
Nu
,,DMSO
2R
Nu
DMSO
sulfonate
sulfonate
Alkyl
ROH

RSO
Cl
ROSO
R
RNu

Nu
,
DMSO
Alkyl

sulfonate
RSO333
RSO22Cl
Cl
ROSO
R R
RNuR 
 RSO
22R
Nu , DMSO
R
ROH  RSO
ROSO
RNu
RSO
ROSO
RNu

Alkyl
33

Nu , DMSO
22R
sulfonate
sulfonate
AAlcohols
RSO
ROHRearrangements
 RSO
RSO222Cl
Cl
ROSO
RNui 
 RSO
3
2R A Nu , DMSO
ROH

ROSO
RNu
Alkyl


H2R

Carbocation
in
Alkyl
3

sulfonate
ROH

R
RNu CH2 RRSO
Alkyl
C O CH2ROSO
RO Alcohols
OH
Alkyl
Carbocation
Rearrangements
in
RSO333 etc.
ROHRearrangements
 RSO
RSO22Cl
Cl
ROSO
sulfonate
Alkyl22RR O CA O CH2 O OH2 H O RNuf C O
Carbocation
Rearrangements
in
AAlcohols
sulfonate
Alkyl
Carbocation
in
Alcohols
sulfonate
Alkyl
R 9-3)
R
R
sulfonate
AlkylHydride
5. Carbocation
Rearrangements in
by
Alkyl
and
Shifts
Alkylsulfonate
and
Hydride
Shifts (Section
(Section
9-3)
Rearrangements
Alcohols
sulfonate
Carbocation
Rearrangements
in
Alcohols
5.
Carbocation
Rearrangements
by
Alkyl
and
Hydride
Shifts
(Section
9-3)
5. Carbocation
Carbocation
Rearrangements by
by
Alkyl
and
Hydride
Shifts
(Section
9-3)
Carbocation
Rearrangements
inAlcohols
Alcohols
Alkylsulfonate
andHydride
HydrideShifts
Shifts(Section
(Section9-3)
9-3)
sulfonate
5.
Rearrangements
Alkyl
and
Carbocation
Rearrangements
in
Rearrangements
in
Alcohols
5.
Rearrangements
by
Alkyl
(Section
Carbocation
Rearrangements
in
Alcohols
OH
(R)H
(R)H
H(R)
5. Carbocation
Carbocation
Rearrangements
by
Alkyland
andHydride
HydrideShifts
ShiftsH(R)
(Section9-3)
9-3)














242 772

33

22

222

244 7 22

33 3

22

42

72

2 2
22
222
22 2 22
22 2
2
2
22

42
22
242
442 22
42
4
4
4
44

72
77
7
7
7 222
7
7 272
2
2
22

222

2
22
2
2
2
22

33

12

33
33
3
3
333
3
33
3
3
3
3
3
3 3

3 2 2

3
3

3 3

3 3

22
2

33 33
3 3

3 3

22
22
2
2
2

33 33
33 3
3
33
3 3
3 33
















(R)H OH
OH
(R)H
(R)H
A
A OH
AA O
AA OC
OC
C
OC
OC
O
O
AOC
AO
A
AA AH
H
H




H
H
H
H2O
H22OO
H

(R)H
(R)H
(R)H
A
A  ff
OAC OC
OCCAO
OCCfi
O
ii H
AA
HH

H(R)
H(R)
H(R)
A
i 
A
 OAC
O
iiC
OCCAO
O
fCCO
A
ff
AH
H
H




H
H
H

H(R)
H(R)
G
DH(R)
GGC P CDD
PCC G
DCCP
GG
DD

El
El
ElEl


SN1
Nu


Nu
S1NN11 Nu
Nu
SS
N

Nu H(R)
Nu
H(R)
H(R)
Nu
A H(R)
A
AA AA
O C OC O
OCCAOC
OCAO
O
O
O
AA AA
H
HH

Concerted Alkyl
6. Concerted
Alkyl Shifts from
from Primary Alcohols
Alcohols (Section9-3)
9-3)
6.
Alkyl Shifts
Shifts from Primary
Primary Alcohols (Section
(Section 9-3)
R
R
R
R
R
R
RR


H

AA
AAA


 O CH R
iiiC
CH2OH
CH2O
CO
RO
OC
OCH
OCCO
OCH
OOH
RO
OH HH
OH2 H O
2
R
R
CH
CH22R
R
C
O
O
O
OH
OH
OCH
CH
2
2
2
2
2
2
2
2R
ffCCO
H
H
2O
H
O
22O
f
AA
AAA
R
R
R
R
R
R
R
R

etc.
etc.
etc.
etc.

Elimination Reactions of Alcohols

N
Ne
ew
w R
Re
ea
a

N
ww RR
ee aa
N ee9-3,
7. Dehydration with Strong Nonnucleophilic Acid (Sections 9-2,
9-7,
NNe9-3,
7. Dehydration with Strong Nonnucleophilic Acid (Sections 9-2,
eww R9-7,
Reeaac1

New Rea

Neeewww RRReeeaaac
Temperature required
NN
H OH
OH
Temperature required
H
Primary ROH:
170
Primary ROH:
17082
D
H2SO4, heat of Alcohols
Elimination
Reactions
G
AA AA
N
e
w
R
on100
Secondary
ROH:
N
e
w
R
Elimination
Reactions
of
Alcohols
D
H
SO
,
heat
G
N e ROH:
w R eeaeacactcti toi oin10082
sns s
2
4
PCC 
O
OCO
O Reactions
CP
 HH2OO
C OC
Elimination
of Alcohols
Alcohols
Secondary
O
C
C
Teritary
ROH:
2582
Elimination
Reactions
of
2
D
G
7.
Dehydration
with
Strong
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
11-5)
AR e aReactions
ADehydration
Teritary
7.eA
Dehydration
with
Strong
Nonnucleophilic
Acid
(Sections
9-2,ROH:
9-3,
9-7, 11-5)
11-5) 2582
Elimination
of
Alcohols
N
w
c
t
i
o
n
s
C
h
a
p
t
e
r
9
375
7.
with
Strong
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
D
G
A
7. Dehydration with Strong Nonnucleophilic Acid (Sections 9-2, 9-3, 9-7, 11-5)
7. Dehydration
withrearrangements
Strong
Nonnucleophilic
Acid (Sections 9-2, 9-3, 9-7, 11-5)
Elimination
Reactions
of
Alcohols
Carbocation
may occur
Elimination
Reactions
of Alcohols
Alcohols
7. Dehydration
with Strong
Nonnucleophilic
AcidTemperature
(Sections required
9-2, 9-3, 9-7, 11-5)
Reactions
of
Elimination
Temperature required
required
H OHCarbocation rearrangements may occur
Temperature

OH
Temperature
required
Primary
ROH:
170821808C
(E2
m
7.H
Dehydration
with Strong
Strong
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
11-5)
Elimination
Reactions
ofAlcohols
Alcohols
Reactions
of
Alcohols
Primary
ROH:
170821808C
(E2 m
m
H
OH
Elimination
Reactions
of
Nonnucleophilic
Acid
(Sections
9-2,9-3,
9-3,9-7,
9-7,
11-5) (E2
Primary
ROH:
170821808C
Temperature
required
7.
with
Nonnucleophilic
Acid
(Sections
9-2,
11-5)
Dehydration
with
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
11-5)
D
H
SO
G
AADehydration
AA
4,, heat
H
OH
H22SO
SO
heat Strong
Primary
ROH:
170821808C
(E2 m
Secondary
ROH:
100821408C
(usua
4, heat
H
G
Temperature
required 170821808C
Secondary
ROH:
100821408C
(usua
PC
O
OC
O
CP
CD
 H
H
O
C
Secondary
ROH:
100821408C
(usua
Primary
ROH:
(E2
me
H
OH
D
H2with
SO4, heat
22O
G
O
O
AADehydration
AA O
7.C
Dehydration
with
Strong
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
11-5)
Strong
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
11-5)
OC
C

Secondary
ROH:
100821408C
(usua
Teritary
ROH:
2582808C
(E1
me
7.
with
Strong
Nonnucleophilic
Acid
(Sections
9-2,
9-3,
9-7,
11-5)
D
2
H SO , heat
G
Primary
170821808C
(E2
Teritary
ROH:
2582808C (E1
(E1
mem
D
G
P
O
OC
O
A
A
C
C

H
O
C
Teritary
ROH:
2582808C
mec
Secondary
ROH:
100821408C
(usuall
Temperature
required
2
A
A
D
G
D
H SO
G
O
OC
O
H
OH
Temperature
required
C G  H2O
C
Teritary
ROH:
2582808C (E1
me
Temperature
required
Preparation
of, heat
Ethers
Temperature
required
Secondary
ROH:
100821408C
DCCP
H
OH
Teritary
ROH:
2582808C
(E1 (usua
mech
Preparation
of
Ethers
Primary
ROH:
170821808C
(E2
m
P
O
OC
O
CG
C
D
AA
AA
Carbocation
rearrangements
may
occur
Primary
ROH:
170821808C
(E2
m
Primary
ROH:
170821808C
(E2
me
Primary
ROH:
170821808C
(E2
m
Temperature
required
Temperature
required
Carbocation
rearrangements
may occur
occur
D  H2OTemperature
Teritary
ROH:
2582808C
(E1
me
H
SO
required
G may
4, heat
Carbocation
OH
D
G
H
OH
H222SO
SOrearrangements
heat
Secondary
ROH:
100821408C
(usua
AA O
AA OC
H
G
4
D
D
H
SO
heat
G
4,,,heat
Carbocation
rearrangements
may
occur
Secondary
ROH:
100821408C
(usua
Secondary
100821408C
(usually
P
Primary
ROH:
170821808C
(E2
mechanism)
O8.
Primary
ROH: ROH:
170821808C
(E2
mechanism)
C
C

H
O
C
Secondary
ROH:
100821408C
(usua
Primary
ROH:
170821808C
(E2
mechanism)
Williamson
Synthesis
(Section
9-6)
2
A
A
Carbocation
rearrangements
may
occur
O
O
P
OC
O
C
C

H
O
C
P
D
C
C

H
O
H
SO
,
heat
D G
Teritary
ROH:
2582808C
(E1
me
G
SO, ,heat
heat
222 Secondary
G D D
Williamson
Synthesis
(Section
9-6)
HHSO
G
ROH:
100821408C
(usually
E1)
Secondary
ROH:
100821408C
(usually
E1)
Teritary
ROH:
2582808C
(E1
me
A
A
Teritary
ROH:
2582808C
(E1
mech
Secondary
ROH:
100821408C
(usually
E1)
Carbocation
rearrangements
may
occur
Teritary
ROH:
2582808C
(E1
mec
7,O8.11-5)
D
G
D
G
P
CCP

PCCC 
O
 HHH
O
C
CAOCAO
2O
22O
222

2
22

4
44

444

D
D
D

GGG

Teritary
ROH:
Teritary
ROH:
Teritary
ROH:

2582808C
(E1
mechanism)
2582808C
(E1
mechanism)
2582808C
(E1
mechanism)

Carbocation rearrangements
rearrangements may
occur
NaH, DMSO
RX, DMSO
mayoccur
occur
Carbocation
NaH, DMSO
Preparation
ofrearrangements
Ethers
Carbocation
rearrangementsmay
may
occur
Preparation
of
Ethers
Carbocation
may
occur
ROH
RO Na
Na RX, DMSO
ROR
Carbocation
may
Carbocation
rearrangements
mayoccur
occur
RO
ROR
Preparation
ofrearrangements
Ethers ROH
Preparation
of
Ethers
SSNN22
8. Williamson
Williamson
Synthesis
(Section 9-6)
9-6)
Preparation
ofSynthesis
Ethers (Section
8.
70821808C
(E2 mechanism)
8.
Williamson
Synthesis
(Section
9-6)
8. Williamson
Synthesis
(Section 9-6)
R9 must
must
beof
methyl
or primary
primary
Preparation
Ethers
00821408C
(usually
E1) or
R9
be
of
Ethers
Preparation
ofmethyl
NaH,
DMSO
RX,
DMSO
Ethers
8. Williamson
Synthesis
9-6)
Ethers
Preparation
Ethers
NaH, DMSO
DMSO
RX, DMSO
DMSO
Preparation
ofbe
Ethers


NaH,
RX,
ROH canof
primary
or(Section
secondary
(tertiary alkoxides
give E2 products, unless R9

 usually



ROH
RO
Na
ROR
582808C
(E1
mechanism)
ROH
can
be primary
or secondary
(tertiaryRO
alkoxides
give E2 ROR
products,
NaH,DMSO
DMSO
RX,DMSO
RO
Na usually
ROR unless R9
ROH
Na
NaH,
RX,
SDMSO

N2
8. Williamson
Williamson
Synthesis
(Section
9-6)
%
kROR
Ease of
of intramolecular
intramolecular
version
forming
cyclic
ethers:
N22
8.
Williamson
Synthesis
(Section
9-6)
ROH
ROethers:
Na kk33%
Synthesis
(Section
9-6)
Synthesis
(Section
9-6)
4 % k7 . k8
Williamson
Synthesis
(Section
9-6) cyclic
Williamson
Synthesis
(Section
9-6)
8.
kkS5SS5NDMSO
..kk6 6..kROR
Ease
version
forming
ROH
RO
Na
NaH,
DMSO
RX,
4 % k7 . k8
SN2N2
(knmust
5 reaction
reaction
rate,
5 ring
ring size)
size)
ROH
RO Na
ROR
(k
5
rate,
nn 5
R9
be methyl
or primary
SDMSO
NaH,
DMSO
RX,
NaH,
DMSO
RX,
N2
NaH,
DMSO
RX,
DMSO
R9 nmust be methyl or primary
DMSO
RX,
DMSO
NaH,NaH,
DMSO
RX,
DMSO
NaH,
DMSO alkoxides
RX,
DMSO
 
usually
DMSO
NaH,
DMSO
RX,
DMSO

R9 must
must
bebe
methyl
or
primary
ROH
canbe
bemethyl
primary
or
secondary
(tertiary
give
E2
products,
unless
R9
5
methyl)
ROH
Na
ROH
RO
Na
ROR
ROH
RO
Na
ROR
R9
or
primary
(tertiaryRO
alkoxides
usually
E2S ROR
products,
unless
R9 5
5 methyl)
methyl)
ROH
RO
Nausually
ROR ROR
ROH
RO
Na
ROH
can
primary
or
secondary
(tertiary
alkoxides
E2
products,
unless
RO
NaSS2SNgive
RORR9
2give
ROH
RO
Na
22%
SNNS
N2k .
ROH of
can
be primary or
secondary
(tertiary
give
E2
unless R9 5 methyl)
% k N.
k2NNNNproducts,
k . kROR
Ease
intramolecular
version
forming
cyclicalkoxides
ethers:
kusually

R9 must
bebemethyl
or or
primary
33 %
422% kk77 .
88
ROH
can
primary
secondary
(tertiary
alkoxides
give
E2
R9 5 methyl)
% kk555 .
.
. SkSkproducts,
. kkunless
cyclic
ethers: kkusually
kk66 .
Ease
of
intramolecular
version
forming
cyclic
ethers:
44 %
9.R9
Mineral
Acid
Method
(Section
9-7) kk3usually
% k .kk666..E2
%k7k77..k8k88unless R9 5 methyl)
Ease
of
intramolecular
version
forming
cyclicalkoxides
ethers:
(k
5of
reaction
rate,
nMethod
5
ring
size)
9.
Mineral
Acid
(Section
9-7)
ROH
can
be
primary
or
secondary
(tertiary
products,
n
be
methyl
or
primary
kk
Ease
intramolecular
version
forming
cyclic
ethers:
methyl
or
primary
3 3% k5 5. give
4 4%
(k
5
reaction
rate,
n
5
ring
size)
nmust
R9
must
be
methyl
oror
primary
must
be
methyl
or
primary
n
R9
must
be
methyl
primary
(k
5
reaction
rate,
n
5
ring
size)
R9
must
be
methyl
or
primary
ROH
can
be
primary
or
secondary
(tertiary
alkoxides
usually
give
E2
products,
unless
5
methyl)
be
primary
or
secondary
(tertiary
alkoxides
usually
give
E2
products,
unless
R9R9
n
%
k
.
k
.
k
%
k7R9
.
k5
Ease
of
intramolecular
version
forming
cyclic
ethers:
k
(kPrimary
reaction
rate, or
n5
ring
size)
3usually
6 E2 4products,
8unless
Primary
alcohols:
ROH
bebe
primary
secondary
(tertiary
alkoxides
usually
give 5E2
products,
unless
5methyl)
methyl)
n 5can
can
be
primary
or
secondary
(tertiary
alkoxides
give
methyl)
alcohols:
ROH
can
primary
or
secondary
(tertiary
alkoxides
usually
give
E2
products,
unless
R9
ROHof can
be primary
or secondary
(tertiary
give
R955
5methyl)
methyl)
k .k %
k .E2
k products, unless R9
Ease
intramolecular
version
forming cyclic
ethers:alkoxides
k % k . usually
ROH
be primary
or
secondary
(tertiary
alkoxides
usually
(tertiary
alkoxides
usually
give
E2
products, unless
unless R9
R9 5
5 methyl)
methyl)
k6 6 ..k4 k4give
% k7 E2
. 8kproducts,
Ease
intramolecular
forming
ethers:
k3k3 %%k5k5 .
(kn 5of
reaction
rate, nversion
5 ring
size) cyclic
Ease
ofcan
intramolecular
version
forming
cyclic
ethers:
3
5. k
6
4 % 7k7 . 8k8

%
.
.k4kk%
%k7k.
of intramolecular
intramolecular
version
formingcyclic
cyclic
ethers:
Ease
of
version
forming
6.
4%
7.
9. (k
Mineral
Acid
Method
(Section
9-7)
reaction
rate,
nnnMethod
5
ring
size)
reaction
rate,
5
ring
size)
%kk5kk5555..
.kk6kk6.
.k8kkk8888
cyclicethers:
ethers:kk3kk3333%%
n5
Ease
of
intramolecular
version
forming
cyclic
ethers:
66 . k
9.
Mineral
Acid
(Section
9-7)
44
(k
rate,
5
ring
size)
4 % kk777 .
n 5 reaction

reaction
rate,
5
ring
size)
rate,
nn
size)
9. (k
Mineral
Acid
Method
(Section
9-7)
 , low temperature
(knn 5
5 reaction
reaction
rate,
n5
5 ring
ringH
size)
H
RCH2OH,
130140C
Acid
Method
(Section
9-7)
2OH,130140C

Primary
alcohols:
, low temperature
RCH
Primary
alcohols:
RCH
OH
RCH
OH
RC
9. Mineral
MineralAcid
Acid
Method
(Section
9-7)
2
2
2
RCH
OH
RCH
OH
RCH
alcohols:
9.
Method
(Section
9-7)
Primary
alcohols:
2
2
2
(Section
9-7)
H2O
2O
9. Mineral Acid
Acid Method
Method
(Section
9-7)
H

Primary
alcohols:
Acid
Method
(Section
9-7)

, low
9.
Mineral
Acid
Method
(Section
9-7)
alcohols:
H
temperature
RCH
OH,
130140C

2
alcohols:

9. Primary
Mineral
Acid
Method
(Section
9-7)
temperature
RCH22OH,
OH, 130140C
130140C

H , low temperature
RCH
PrimaryRCH
alcohols:
OH
RCH
OH
RCH
OCH

H ,,low
lowtemperature
temperature
RCHOH,
130140C
OH222 RCH
RCH222OCH
OCH222RR
R
2OH,
H
130140C
RCH
RCH222OH
RCH
Primary
alcohols:
Primary
alcohols:
O
H
22OH
O
H222O
H
Primary
alcohols:
 temperature
alcohols:
RCH
OH
RCH
OH
RCHOCH

RCH
RCH
RCH
H
, low
2OH
2OCH
2R
Secondary
alcohols:
RCH

22OH
22OH, 130140C
2R
H
, low
temperature
RCH
130140C
H
RCH
2OH,
H
O2O RCH OCH R 2
H
 2
H ,,low
lowtemperature
temperature
RCHOH,
OH,130140C
130140C
RCH
RCH
OH
22OH
2
2
2
2
OH
RCH
OH
RCH
OCH
R
RCH
OH
RCH
OH
RCH
OCH
2 OH2 2
2 OCH
2 R2
2
2R
OO

RCH
RCH
RCH
H
2OH
2
2  2 H
2
2
O
H
H
,
low
temperature
RCH
OH,
130140C

2

H
,
low
temperature
RCH
OH,
130140C
2

O 2OH,
H
Secondary alcohols:
alcohols:H , low temperature


RCH
130140C
RCH
22OH, 130140C
Secondary
RCH
RCH
RCHalcohols:
OH
RCH
OH
RCH
OCH
R
OHtemperature RCH
R
2alcohols:
22
2OCH
2R2R
2OH
2OH
2OCH
OH
RR22OH
OH
RCH
RCH
RCH
RCH
Secondary
OO R
H
H
2OH
22
22OCH
22R
2G
R9 5Secondary
methyl)
O
H2222O
alcohols:
H
HH
Secondary
G
GG
Secondary
alcohols:
Secondaryalcohols:
alcohols:
OHAA
R
R
O
O
O
CH

E1
product
CH
R
O
O
OH
R
R
O
CH

E1
products
CH

 H O G

H
G
RCHR
2
H
O
A
OH
R
R
RCHR
H
OH
R
R
2
G
G
H
Secondary
OH
R
RRCHG
Secondary alcohols:
alcohols:
DDO
DDE1
OHAA
O
O
O

E1
products
CHR
Secondary
alcohols:
GCH
HHOR
O
O
OGG
CHGG
 R
E1
products
O
O
HH H
CH

products
RG RGD
R
A
AAOH
R products
OH
RCHR
R
H222O
O G
D
RCHR
O
O
O
O
O
H H
CH
E1
products
CH
OOO
 E1
CH
O
CH
D
E1 products
CH
G
GCH
DR
D
ARCHR
O
O
OO
CH
CH
HO
G
G
H
A H
H
RCHR
RCHR
2O D CH
RD
RE1
OCH
O
DD
HOO
CH

E1products
products
D
D
RCHR
D
OH
R
R
R
R
R
OH
D
O
O
O
CH

E1
products
H
O
RCHR
R
R
R
DR
D
R
HH2OR
G
G
H
R
R
R
RCHR
AOH
R
R
G
G
alcohols:
A
Tertiary alcohols:
DCHO O O CH
D
H R
H
G
G
G
R
A

E1
products
O
O
O
CH

E1
products
CH
Tertiary alcohols:
alcohols:
RD CH O
OO
OCH
OO
CHDDR 
 E1
E1 products
products
RCHR
Tertiary
H
RCHR H
Tertiary
D OO
H
H2222O
O
RCHR
Tertiary
alcohols:
Tertiaryalcohols:
alcohols:
alcohols:
D
DR
RRD
Tertiary
alcohols:
NaHSO4,4,HH
R
NaHSO
2O
2O
R
R
R
H
O
Tertiary alcohols:
NaHSO
H222O
O
NaHSO
NaHSO
,NaHSO
HHOO 444,,, H
O
R
COH

ROH
R
C
OR
E1prp
O
R
COH

ROH
R
C
OR
 E1
3
3
NaHSO
,
3
3
O
R
COH 

ROHNaHSO
RO
C
OR

E1
products
NaHSO
O
NaHSO
O
SNR
1,
H
HR
R
COH
ROH
R
OR
 OR
E1
O
SH
1,C
CO
OR
 E1
E1 products
products
2N
R
ROH

2O
, NH1,O,4,H
2R
3O
3C
Tertiary
33COH
33
H
O
R33R
COH
E1products
products
HSS
Tertiary alcohols:
alcohols:
SNO
1, 
H
H222O
OR3CCO
1,
NO
ROH
ROR
OR
E1
O
COH 
ROH
ROHSSNSN1,1,1,NaHSO
ROR
OR
E1products
products
H
O
Tertiary
alcohols:
R3R
COH
ROH

E1
products
33COH
3C
3CO
H
4,H
2O 3
SSNHN1,1,
O
OH
R

(mainly)
primary
2O
R

(mainly)
primary
N
R R
(mainly)
primary
R

(mainly)
primary
primary
 (mainly)
primary
COH
(mainly)
primary
RCH2OCH2R R
R
primary
ROH NaHSO
R3C O OR  E1 products

R3R

primary
SN1, ,4H
HH2O
O
R(mainly)
(mainly)
(mainly)
primary
NaHSO
O
2O
,, H
NaHSO
44
R

ROH
RR3C
4, H22
2O
OOR
R333COH
COH
 primary
ROH NaHSO
CO
OR 
 E1
E1products
products
SS
O
R
 (mainly)
N1,1,HHOO
O
R
COH

ROH
R
OR
E1
products
R333C
C
OR

E1
products





22




2 2

2
22

22




2
2

2



2
2

44

22

22

SSNN
1, 
H
H2222O
O
N1,

N
Reactions of
R
Reactions
of
Ethers
R
(mainly)
(mainly)primary
primary
Reactions
ofEthers
Ethers
R
primary
ofEthers
Ethers
Reactions
R
 (mainly)
(mainly) primary
Reactions
ofof
Ethers
Reactions
Ethers
10.
Cleavage
by
Hydrogen
Halides
(Section
9-8)
10. Cleavage
bybyHydrogen
Halides
(Section
9-8) 9-8)
10.
Cleavageof
Hydrogen
Halides
(Section
Reactions
Cleavage
byEthers
Hydrogen
Halides
(Section
9-8)
10.
9-8) 9-8)
by
Hydrogen
Halides
(Section
9-8)
Cleavage
by
Hydrogen
Halides
(Section
10.Cleavage
Hydrogen
Halides
(Section
9-8)HX
10.
Cleavage
by
Hydrogen
Halides
(Section
9-8)
Hydrogen
Halides
(Section
9-8) Conc.
Conc.
HX
Reactions
of
Conc. HX
Conc. HX
Reactions
ofbyEthers
Ethers
ROR
RX  ROH
2 RX
Ethers
Conc. HX
Conc.
HX
Reactions of

Conc. HX
Conc.
HX
HX
Conc.
HX
Conc.HX
HX
Conc.
Conc.
HX

ROR
ROR
ROR
ROR
ROR

RX  ROH
ROH
ROH
RX

ROH
RX

ROH
RX 
 ROH
RX

Conc. HX
Conc.
HX
Conc.
HX
Conc.
HX
Conc.HX
HX
Conc.
HX
Conc.
Conc.
HX

X 5 Br or I
Br or
or IIII
X
5 Br
Br
or
Br
or
X
5
Primary
R: SN2 mechanism
Primary R:
R: S
SNNN2222 mechanism
mechanism
mechanism
Primary
R:
SS
Primary
R:
Primary
1 or SN2 mechanism
Secondary
R:
NSNmechanism
N
or S
SNNNN2222 mechanism
mechanism
Secondary
R: S
S 11 or
mechanism
or
SS
mechanism
Secondary
R:
mechanism
Secondary
Secondary
or
R:
Tertiary
R:R:
SNSS1NNNNNN11mechanism
N mechanism
N
N
Tertiary R:
R: S
SNNN1111 mechanism
mechanism
Tertiary
R:
SS
mechanism
Tertiary
Tertiary
mechanism
R:
N
N

Nucleophilic Opening
of
Oxacyclopropanes (Sections
9-9,
25-2)
11.
11. Nucleophilic
Opening of
of Oxacyclopropanes
(Sections 9-9,
9-9, 25-2)
25-2)
Nucleophilic Opening
Opening
of
Oxacyclopropanes
(Sections
9-9,
25-2)
Oxacyclopropanes
(Sections
9-9,
25-2)
11.
Opening
(Sections
9-9,
of
Oxacyclopropanes (Sections
25-2)
(Sections
9-9,
25-2)
Anionic nucleophiles:
nucleophiles:
nucleophiles:
Anionic
Anionic
nucleophiles:
nucleophiles:
O
O
O
O
O

H, H2O
H,,,,,,H
H2222O
O
H
H
H
2O
H
O
H
H
H
O
H
H
222O

R
R
R
R
R


R
Nu

R
R
Nu

Nu
R

R
Nu

Nu

Examples
of Nu: HO, RO, RS

OH
OH
OH
OH
OH
OH
A
AOH
AAA
A
A
NuCH
CR
2CR
NuCH
NuCH2222222CR
CR22222222
NuCH
CR
NuCH
NuCH
CR
NuCH
CR

: HO
, RO


Examples
of
Nu
Examples
of
Nu
HO
RO
RS
of
Nu
HO
RO,,,,,,RS
RS
Examples
RS
Examples
of
Nu
HO
RO
RS
Examplesof
ofNu
Nu:::::HO
HO,,,,,RO
RO
RS

Acid-catalyzed opening:
opening:
Acid-catalyzed
opening:
Acid-catalyzed
opening:
opening:
H
H
H
H
H
A
AAO
AA

O

O
O
O

Nu
Nu
Nu
Nu
Nu
Nu
AANu
AAA
A
A
HOCH
CR
2
HOCH
CR
HOCH
CR
HOCH2222222CR
CR22222222
HOCH
HOCH
CR
HOCH
CR

R
R
R
R
R
R

Nu
R
R

Nu
R

R
Nu
Nu

Nu
Examples of Nu: H2O, ROH, halide
2

Examples
of
Nu:
H
O,
ROH,
halide
Examples
of
Nu:
H
ROH,
halide
Examplesof
ofNu:
Nu:H
H22222O,
O,ROH,
ROH,halide
halide
Examples
2O,
Examples
of
Nu:
H
ROH,
halide
Nu:
H
O,
ROH,
halide
Examples
of
halide
22O,

2 RX
RX
RX
RX
RX
222222RX
RX

12.
Nucleophilic Opening
OpeningofofOxacyclopropane
Oxacyclopropane
byLithium
LithiumAluminum
Aluminum
Hydride
(Section
9-9)
12. Nucleophilic
Hydride
O
2.LiAlH
Ho
12.
by
9-9)
F
R ee aaOpening
sHOxacyclopropane
ofO
fOiCH
s,by
aLithium
n)dOd
eAluminum
st rt yr y (Section
of(Section
f E Et ht9-9)
h
er sr s
LiAlH
(CH
CH
) O t thh
u rNucleophilic
ther R
cc tt ii oo nn sof
oC
fO
AAllcco1.o1.
hh
o, lHl,s(CH
aCH
n
eAluminum
CChheemmiHydride
siHydride
o(Section
e9-9)
CH
12.
Nucleophilic
Opening
of
by
Lithium
2Oxacyclopropane
3CH2OH Hydride
CH
fO
i A l2c2.o1.1.
12.
by
2.HLiAlH
H, H
(CHaLithium
CH
)O
O t hAluminum
F
u rNucleophilic
t h e r R e Opening
aOpening
c t i o nof
sH2Oxacyclopropane
offO
fOiCH
hLiAlH
o,, HHOlOO,s, (CH
n )d
eAluminum
C2OH
hOH
e m iHydride
s t r y (Section
o(Section
f E t 9-9)
h9-9)
ers
i
H
C
CH
CH
2.
H
12.
Oxacyclopropane
by
Lithium
Aluminum
Hydride
(Section
9-9)
C
CH
CH
CH
Nucleophilic
of
Oxacyclopropane
by
Lithium
2
3
O
O
1.
LiAlH
,
(CH
CH
)
O
iCH 2 1.1.2.LiAlH
Oby CH
H , H, (CH
O
2 f
3
2
) )OO
Lithium
Aluminum
Hydride
(Section
9-9)
12. Nucleophilic Opening ofH
Oxacyclopropane
Lithium
Aluminum
Hydride
(Section
9-9)
O
O
LiAlH
,
(CH
CH
C
CH
CH
OH
3 CH2 OH
H, H, H
H22Oxacyclopropane
C
CH
13.
Nucleophilic Opening
Opening of
of
Oxacyclopropane
byCH
Organometallic
(Section
9-9)
fffO
iiCH22 2.2.1.2.HHLiAlH
12.
Lithium
Aluminum
Hydride(Section
(Section9-9)
9-9)
OO
3
2 Compounds
O
, (CH
)O
12. Nucleophilic
by
Lithium
Aluminum
Hydride
O
LiAlH
,t (CH
O
Fi
uCH
r t 2h 2e r1. R
e ,aHc O
i o n CH
s o) fO A l CH
c oCH
h3oCH
l CH
s 2OH
a 2nOH
d the Chemistry of Ethers
376
Chapter 9 H
H
C
O
C
CH
2
3
2
13.
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
(Section
9-9)
f
i
,
H
O
2.
H
O
H2C
CH2OHCompounds
LiAlH
(CH
CH
O CHAluminum
OiCH2 1.1.2.1.1.LiAlH
13.
Nucleophilic Opening of
Oxacyclopropane
by
Organometallic
(Section
9-9)
,, (CH
CH
)) O
12.
Lithium
Hydride(Section
(Section9-9)
9-9)
, H ,O
HLiAlH
O
(CH
CHOrganometallic
O
(CH
CH
)) O
O
H2C
CffO
CH3CH
13. Nucleophilic
Opening
of
Oxacyclopropane
by
Compounds
3CHOH
2OH
H, O
O(CH
2.LiAlH
HO
iCH22 2.2.1.2.1.
,, H
H
13.
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
(Section
9-9)
H
CH
2Oxacyclopropane
3Aluminum
2
OiCH
LiAlH
CH
fO
HO
O, ,(CH
H
12. Nucleophilic
Nucleophilic Opening
Openingof
of
Oxacyclopropane
byCH
Lithium
Hydride
(Section
9-9)
,, H
H
Nucleophilic
Opening
of
by
Lithium
Aluminum
Hydride
(Section
9-9)
LiAlH
) )OO CH
CH
CH
OH
13.
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
(Section
9-9)
HOxacyclopropane
C
OH
Organometallic
(Section
9-9)
2Oxacyclopropane
33CH
22Compounds
f,O,HHiOOby
fO
iCH2222 2.2.HHO
THF
H ,33H
O 22OH
CH
CH
OH
H
CH
CH
13. Nucleophilic
Opening
of
by
Organometallic
Compounds
(Section
9-9)
fO
iCH
2C
12.
Nucleophilic
Opening
of
Oxacyclopropane
by
Lithium
Aluminum
Hydride
(Section
9-9)
O
1.
LiAlH
,
(CH
CH
)
O
O
12.
Nucleophilic
Opening
Oxacyclopropane
by OH
Lithium
(Section
9-9)
RLi or of
22 H2C
RCH
CH2OHHydride
HRMgX
CfO
13.
Nucleophilic Opening
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
(Section
9-9)
fHfO
iHiCH
O
THF
HCH
,CH
H 3OCH
2 of
2Aluminum
2C
3CH
H
CH
2Oxacyclopropane
2 2OH
13. Nucleophilic
Compounds
(Section
9-9)
O
THF
H ,H
O RCH
iCH
, CH
Oby Organometallic
2.
O
H
RLi
or
RMgX

C
CH
OH
O
O
1.
LiAlH
,
(CH
CH
)
O
1.
LiAlH
,
(CH
CH
)
O
f
i
THF
H
,
H
O
2
2
2
2
13.
Oxacyclopropane
by
Organometallic
Compounds
(Section
9-9)
O
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
(Section
9-9)
H
RLi
or
RMgX

C
CH
RCH
CH
OH
O
O
OiiCH
CH
OH
fO
iCH
THF
H1.CH
, H3O
2C
2 Organometallic
2CH 2OH(Section
Organometallic
Compounds
(Section
9-9)
13. Nucleophilic Opening
ofHRMgX
Oxacyclopropane
by
Compounds
9-9)
2C
2H
2RCH
O
LiAlH
, (CH CH
)O
f
O
f
,
H
O
2.
H
RLi
or

,
H
O
2.
H
2 THF
2 CH2 OH (Section 9-9)
O  H1.22fC
LiAlH
, by
(CH
CH
iiiCH
f ) iO H H
fO
,HO
O
,2.HH, O
THF
H
RLi or of
RMgX
RCH
13. Nucleophilic
Nucleophilic Opening
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
2
2
2
O
Oxacyclopropane
Organometallic
Compounds
(Section
9-9)
f
O
O
H
C
CH
CH
CH
OH
THF
H
,
H
O
H
C
CH
CH
CH
OH
O
H
C
CH
CH
CH
OH
OO
22 f i 
3 3 RCH
2 2RCH
2
2
3 OH
RLi
RLi or
or RMgX
RMgX
22H
CO
,CH
H
O2 2 THF
2.
H
2CH
2 22OH
2C
2CH
Sulfur
Compounds
fO
iCH
, HOO RCH
HH22C
RLi
or
RMgX

2byTHF
2CH2OH
OiCH
HHCH
,H
13.
Nucleophilic
Opening
Organometallic
Compounds
(Section 9-9)
H
CO
CH
OH
2Oxacyclopropane
3CH
2Organometallic
Sulfur
Compounds
O
RLi or
or of
RMgX
2HH22CCfO
RCH
13. Nucleophilic
Opening
of THF
Oxacyclopropane
Compounds (Section 9-9)
2CH
2OH
RLi
RMgX
THF
H
H
O byRCH
fO
iCH
Sulfur
Compounds
,, H
22 THF
2CH
2OH
fO
iCH
O
H
,, H
O
THF
HH
H
OO
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
14.
Preparation
of
Thiols
and
Sulfi
desH(Section
9-10)
13.
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
(Section9-9)
9-9)
Sulfur
Compounds
CH
RCH
CH
OH (Section
O
RLi
or
RMgX

C
CH
RCH
CH
Sulfur
Compounds
2
2
2
2
2
2
22OH
O
H
RLi
or
RMgX

C
CH
RCH
CH
OH
THF HH, H
,O
HOO RCH22CH22OH
22 ff ii 229-10)
14. Preparation
of
Thiols
and
Sulfi
des
(Section
THF
Compounds
13.
Nucleophilic
Opening
of
Oxacyclopropane
by
Organometallic
Compounds
9-9)
O
Sulfur
Compounds
14.
Preparation
of
Thiols
and
Sulfi
des
(Section
9-10)
f i
THF
O OH
OCH
RLi or
or RMgX
RMgX 

CO
CH229-10)
RCH
OH2CH(Section
Sulfur
Compounds
HH2(Section
RLi
RCH
2C
2, HCH
2HCH
2 2RCH
14.
Preparation
of
des
RMgX
C,O
2OH
fOORLi
i or
THF  HH2RSH
HCH
O2
14.
Preparation
of Thiols
Thiols and
and Sulfi
Sulfi
des 
(Section
9-10)
Sulfur
Compounds
RX
HS
Compounds

Preparation
of
Thiols
Sulfi
(Section
9-10)
O
H
or and
RMgX

CH
RCH2CH2OH
14.
Preparation
ofRLi
Thiols
and
Sulfi
des
(Section
2C
29-10)
RXdes
HS
RSH
f
i
THF
H
,
H
O

14.
Preparation
of
Thiols
and
Sulfi
des
(Section
9-10)
f
i
THF
H
,
H
O
Sulfur
Compounds
OExcess
Thiol RCH CH OH
Compounds
Sulfur
RX

HS
RSH
 9-10)
Sulfur
Compounds
HH(Section
or
RMgX

CH
O
14.
Preparation
ofRLi
Thiols
and
Sulfi
des
RLi
or and
RMgX

CO
RCH
29-10)
2(Section
2 2CH
2 2OH
RX

HS
2C
2 THF
14. Preparation
of
Thiols
Sulfi
des
Thiol
fExcess
iCH
HRSH
,HO
RX

HS
RSH
Sulfur
Compounds
Compounds

Excess
Thiol
14.
Preparation
of
Thiols
and SulfidesRSH
(Section
9-10)
RX
HS
14.
(Section
9-10)
 9-10)
Preparation of
ofRLi
Thiols
and
Sulfi
des
(Section
H
or and
RMgX

CH
RCH2CH2OH
Excess
RX

HS
RSH
Thiols
Sulfi
des
(Section
Thiol
14. Preparation
Base
2C O
29-10)
RX

HS
RSH
Excess
Thiol
Sulfur
Compounds
Base
RSH

RX
RSR

Excess
Thiol
Sulfi
des
(Section
14. Preparation
Preparation of
of Thiols
Thiols and
andRSH
Sulfi
des
(Section
9-10)
RX

HS
RSH
Excess9-10)
Thiol
RX
HS

HS
RSH
Base RX RSH
Excess

RX
RSR
Thiol
Compounds
Base
Sulfur
Compounds
Alkyl
sulfide
Excess
Thiol
RSH

RX
RSR
RSH
RXdes
HSBase
RSH
Excess
Base
Thiol
RX
HS
RSH
RSH
Excess
14. Preparation of Thiols andRSH
Sulfi
(Section
9-10)
Thiol

RX
RSR
Alkyl
sulfide
 Base
Base
Sulfur
Compounds
RSH

RX
RSR
Base
Alkyl
sulfide
Excess
RX
HS
RSH
Excess
14. Preparation
Sulfi
des
(Section
9-10)

RX
RSR
RX

HS
RSH
Thiol
Excess
Thiol
Excess
Thiol
Thiol
14.
Preparation of
of Thiols
Thiols and
andRSH
Sulfi
des
(Section
9-10)
 RSR
RX
RSR
RSH 
 RX
RX Base
RSR
sulfide
RSH
BaseRSH Alkyl
Alkyl
sulfide

15.
Acidity
of Thiols
(Section
9-10)
Excess
Alkyl sulfide
Thiol
Excess
Alkyl
sulfide
Thiol
14.
Preparation
of Thiols
andRSH
Sulfi
(Section
9-10)
RXdes
HS Base
RSH
RSH

RX
RSR

RX
RSR
Alkyl
sulfide
15. Acidity
of Thiols
(Section
9-10)
Alkyl
sulfide
Base
Base
Base
RX
HS
RSH
15.
Acidity of
of Thiols
Thiols (Section
(SectionRSH
9-10)
Excess
RSR

RSR
RSH
RX
RSR
Thiol

HS(Section
RSH
RSR
Alkyl
sulfide
15.RX
Acidity
ofRX
Thiols
9-10)Alkyl
sulfide
15.
Acidity
9-10)
Base
Base


15.
Acidity of
of Thiols
Thiols
(Section
9-10)

Excess
RSH
pK (RSH)  912
HO
RS
 Alkyl
 RSH
H
O
Thiol
15. Acidity
(Section
9-10)


2RSR
RX
HS
RSH
Excess
sulfide
RSH
 RX
RX
RSR
Alkyl
sulfide
Alkyl
sulfide
Alkyl
sulfide
Thiol
RSH
HO
RS

15.
of Thiols
Thiols
(Section
9-10)
 (RSH)  912
Acidity of
(Section
9-10)
RSH Base
pK (RSH)  912
RSpK
 H2O
 HOH2O
 ROH
Acidity
of 
RSH HO
HO
RSH
pK (RSH)  912
RSBase
H
sulfide
Excess
Thiol
2O
Alkyl
sulfide
Acidity
of RSH 
H O Alkyl
ROH
15. Acidity of Thiols
Thiols
(Section
9-10)
Acidity
of RSH
H O
ROH
(Section
9-10)
RSH
 RX
RSR
RSH
pK (RSH)  912
HO
RS

H
2O

 Base
RSH
(RSH)
 912
pK
HO
RS


H
O
2
RSH
Acidity
of
RSH
H
O
ROH
(RSH)
 912
pK
HO
RS


H
O

RX
RSR
2Alkyl
(Section
9-10)


Acidity of
of Thiols
Thiols
(Section
9-10)
15. Acidity
Acidity
of
RSHRSH
H
ONucleophilicity
ROH
sulfide
RSH

RX
RSR
RSH
(RSH)

912
pK
HO
RS


H
O
RSH
(RSH)

912
pK
HO
RS

H
O
2
16.
of
Sulfi
des
(Section
9-10)
2
Acidity
RSH
HO
O
ROH9-10) Base
Acidity
ofofRSH
H
16.
Nucleophilicity
of(Section
Sulfi
desRSH
(Section
 ROH
Alkyl
sulfide
15.
Acidity
of
9-10)
of Thiols
Thiols
(Section
9-10)
16. Nucleophilicity
of
Sulfi
des
(Section
RSH
(RSH)
912
pK(RSH)
HO
RS  H

HAlkyl
9-10)
RX
RSR
RSH
912
pK
RS
Acidity
of
RSH HO
ROH
sulfide
Acidity
of
RSH
HHOO ROH
2O
2O





R
RX
R2
SR
X912
16.
Nucleophilicity
of (Section
Sulfi
desHO
(Section
9-10)RS
RSH
(RSH)

912
pK
(RSH)

912
pKpK
HH
O
Acidity
of
RSH
HHOO ROH
Acidity
of
RSH
ROH9-10)
RSH
(RSH)
HO
RS

O
2Alkyl
(RSH)

912
pK
RS 
2S H
H
O sulfide
2O
16. Nucleophilicity
of
Sulfi
des
(Section
15.
Acidity of Thiols
9-10)
22



16.
Nucleophilicity
of
Sulfi
des
(Section
9-10)
 (RSH)
Nucleophilicity
of
Sulfi
des
(Section
9-10)


Sulfonium912
salt

Acidity
ofofRSH
H
OO
ROH
15. Acidity
9-10)
RSH
RS
 RHR

 pK
ROH
R
S

RX
SR
X
Acidity
RSH
H
ROH
H
O
ROH
22O
RSH
912
pK (RSH)
HO
RS

H
O
2
16.
Nucleophilicity
of(Section
Sulfi
desRHO
(Section
9-10)
15.
Acidity of
of Thiols
Thiols
(Section
9-10)


2
Nucleophilicity
of
Sulfi
des
(Section
9-10)

S
RX
SR
X
2
2



Acidity
of
RSH
H
O
ROH


Acidity
of 
RSH
OOxidation
of
Sulfi
des
(Section
9-10)
16. Nucleophilicity
Nucleophilicity
of (Section
Sulfi
desR
(Section
9-10)
R
ROH
RX
R
SR
XpK (RSH)  912
17.
of Thiols

15.
Acidity of Thiols
9-10)
22
2H
RSH
HO
RS(Section
 9-10)
H
O X



SS
RX
R
SR
Sulfonium
 salt
 
2
2


Sulfonium
 Xsalt

R
S

RX
R
SR
X
16. Nucleophilicity
of
Sulfi
des
(Section
9-10)
R
S

RX
R
SR
(RSH)

912
pK
HO
RS


H
O


2
2
2
2
2
NucleophilicityRSH
of
Sulfi
des
(Section
9-10)
16.





SR
Acidity
RSHR
H
ROH
RSH of 
pK (RSH)  912 I
HO
 Sulfonium
H
O XXsalt

R
SOO 

RXor HRS
SR
RX
RR
KMnO
O
2H
2

2S
22


Acidity
of RSH
ROH9-10)

16. Nucleophilicity
of
des
(Section
Sulfonium
salt

RSH
RSH
RS O SR
pK (RSH)
3H
16.
Nucleophilicity
of Sulfi
Sulfi
desRRHO
(Section
9-10)

RSH
 912
RSO
H
O Xsalt
Acidity
of 
RSH
H
O
S
R
SR
Sulfonium
salt
NaBH
Sulfonium
S9-10)
ROHRX
RX RS Alkanesulfonic
R
X
2SR
22
2

2
17.
Oxidation of
of Thiols
Thiols
(Section
9-10)




acid
Dialkyl disulfide

17. Oxidation
(Section

salt

Sulfonium
salt
Sulfonium


RR2(Section
S2H
RX
R
SR
X
R
SR
X
Acidity
of RSH
O
ROH
2R
16.
Nucleophilicity
of
Sulfi
des
9-10)
2


S

RX
R
SR
X
SR
X


2
2
2
9-10)


17.
Oxidation of
of Thiols
Thiols
(Section
9-10)

Sulfonium
salt

Sulfonium
salt
16.
Nucleophilicity
of
Sulfi
des
(Section
9-10)
17.
Oxidation
(Section
18.
Oxidation
of
Sulfi
des
(Section
9-10)


S

RR2
SR
X
2
16. Oxidation
Nucleophilicity
of Sulfi
desRR(Section
9-10)
of
(Section
9-10)
17.
Oxidation
of Thiols
Thiols
(Section
S9-10)
 RX
RX
SR
Xsalt
Sulfonium
salt
2
2
Sulfonium
salt
KMnO
or HHOO (Section
I I
Sulfonium
KMnO

Sulfonium
salt
of
Thiols
9-10)
17.
Oxidation
of or
Thiols
(Section
9-10)

16. Oxidation
Nucleophilicity
of Sulfi
desRRSO
(Section
O
RSO
H 9-10)
SROX

OO
RSH
RSH
RSRS
SRSR
3
S9-10)
RX
RRSH
Sulfonium
3H
I
2
2
of
salt HNaBH
KMnO
or H
HO
O (Section
B
Bsalt

17. Oxidation
of Thiols
Thiols
(Section
9-10)
 X

HSulfonium
OI
KMnO
or
R2RSO
S

RX
RO2
SR
 NaBH
I

Alkanesulfonic
acid
Dialkyl
disulfide
I
O
KMnO
or
HHOO (Section
RSRDialkyl
RSR
RSR
RSH
H
RSH
RSdisulfide
SR
Alkanesulfonic
acid
3
KMnO
or
17.
Oxidation
of
Thiols
9-10)

X
RRSO
S9-10)

RX
RRSH
SR
O
RSH KMnO
H
2
2
RS
SR

of
Thiols
(Section
3
17. Oxidation
B
I
I
Sulfonium
salt
NaBH
O
RSH
RSO
H
or
H
O
RSH
RS
or H O
O

RSH KMnO
RSO
RSH
RS SR
SR
3 3H acid
NaBH

Alkanesulfonic
Dialkyl
disulfide
O
R
S

RX
R
SR
X
Sulfonium
salt
17.
Oxidation
of
Thiols
(Section
9-10)
NaBH
2
2
O
II
RSH KMnO
RSO
RSH
RS
SR
Alkanesulfonic
acid
Dialkyl
disulfide
9-10)

NaBH
O
RSO
Hacid
RSH
RS
SR
H
33H
17. Oxidation
of oror
Thiols
KMnO
HO
O (Section
Alkanesulfonic
Sulfonium
salt
Dialkyl
disulfide
Dialkyl
sulfoxide
Dialkyl
sulfone
Alkanesulfonic
acid
Dialkyl
disulfide
NaBH
18. Oxidation
Oxidation
of or
Sulfi
des (Section
(Section
9-10)
INaBH
Odisulfide
of
Sulfi
9-10)
RSH KMnO
RSO
RSH
RS
SR
I I
H Odes
33H
O
RSO
H acid
RSH salt NaBH
RS
SR
Alkanesulfonic
Dialkyl
Alkanesulfonic
acid
Dialkyl
disulfide
I
KMnO
H O (Section
Sulfonium
17. Oxidation
Oxidation
of or
Thiols
9-10)
O
RSH
RSO
H
RSH
RS
SR
NaBH
O
RSH
RS
SR
3
18.
of
Sulfi
des
(Section
9-10)
3
Alkanesulfonic
Dialkyl
disulfide
I
17. Oxidation
of
Thiols
(Section
9-10)
O
RSH KMnO
RSO
RSH
RS
SR
Alkanesulfonic
acid
O
Dialkyl
disulfide
or
H Odes
RSH
RS
SR
33H acid
18.
Oxidation
of
Sulfi
(Section
9-10)
NaBH
I
NaBH
18.
Oxidation
of
Sulfi
des
(Section
9-10)
KMnO
or
H
O
17. Oxidation
Thiols
9-10)
NaBH
Alkanesulfonic
acidConcepts
Dialkyl
disulfide
Important
18.
of Sulfi
des(Section
(Section
9-10)
NaBH
O
RSH
RSO
Dialkyl
disulfide
RSH
RS
SR
3H
Alkanesulfonic
Dialkyl
disulfide
O
Alkanesulfonic
acid OO
RSH
RSO
Dialkyl
disulfide
RSH OONaBH
RS
SR
Oxidation
of
des
(Section
9-10)
3H acid
18.
Oxidation
of Sulfi
Sulfi
des
(Section
9-10)
17.
Thiols
I
1. 9-10)
The reactivity
ofBB
ROH with alkali metals to give
and hydrogen
the orde
KMnO
or H O
BO
Balkoxides
(Section
(Section
NaBH
Alkanesulfonic
Dialkylfollows
disulfide
18. Oxidation
of
Sulfi
des
I
H9-10)
OO acid
HH
OO
H9-10)
O
KMnO
or
H
O
18.
Oxidation
of
Sulfi
des
(Section
Alkanesulfonic
acid
Dialkyl
disulfide
O
RSH KMnO
RSO
RSH
RS SR
O I
O . secondaryRSH
R 35HCH3 . primary
.
tertiary.RSR
ORSR
O
RSR
RSR
RSR
RSR
18. Oxidation
of Sulfi
des
9-10)
or H O
RSH
RSO
H
RS O SR
B NaBH
B
O
O


(Section

3O
B
B
H9-10)
HO
O
of Sulfi
des
(Section

18. Oxidation
O
O
B
B

O
Alkanesulfonic
acid
B
Dialkyl
disulfide
NaBH
RSH KMnO
RSO
H
RSH
RS
SR
H
O
H
B
O
O
2
reactions
2.
In
the
presence
of
acid
and
a
nucleophilic
counterion,
primary
alcohols
undergo
S
3 acid RSR
I
HH
OO
HH
OO
B
N
(Section
or H O RSR
RSR
Alkanesulfonic
Dialkyl disulfide
18. Oxidation
of
9-10)
BO
B


O
O
RSR
RSR
RSR

Secondary
andRSR
tertiary
ofRS
acid,
capable
B NaBHin the presence
B alcohols Htend
RSR
RSR
18.
Oxidation
of Sulfi
Sulfides
des
(Section
9-10)

O
O
HH
OO
O
RSH
RSO
SR of E
O
Dialkyl
disulfide


3H acid
HORSH
Oto form carbocations
B
RSR
RSR
RSR
O
O
BB
Bformation,
 Alkanesulfonic


product
before
after rearrangement.
NaBH
BO
RSR
RSR
RSR
BB sulfone
Bsulfoxide
HHand
OO SN1Dialkyl
HHOand

RSR
RSR

O
O
sulfone
O Dialkyl
Alkanesulfonic
acid
Dialkyl disulfide
O
(Section

Dialkyl
Dialkyl
18.
Oxidation of
of Sulfi
Sulfides
des
(Section
9-10)
BRSR
Bsulfoxide
O

B
B
RSR
RSR
RSR
O
H
O
H
O
18. Oxidation
9-10)
O
B
H
O
H
O


OBO
O
RSR
RSR
RSR
BBsulfoxide take
3. HCarbocation
rearrangements
place by hydride
and alkyl group shifts. They usually resul
B

O
H
O
RSR
RSR
RSR
O
H
O
H
O
Dialkyl
Dialkyl
sulfone
B
18. Oxidation of Sulfides
(Section
9-10)

B
O
BBOsulfone

secondary carbocations
orRSR
conversion
of a secondary into a tertiary carboca
Dialkyl
Dialkyl
Dialkyl
sulfoxide
RSR
RSR
RSR
HinOinterconversion
H O Dialkyl
RSR
RSR
BO
Bconcerted
Bofsulfoxide


Bsulfone
Dialkyl
sulfoxide
Dialkyl
sulfone process consisting of loss of wate

18. Oxidation of Sulfides
9-10)
O Primary
alkyloxonium
ions H
canOrearrange
by
asulfone
RSR
RSR
RSR
Dialkyl
sulfoxide
Dialkyl
O
BO
B sulfone
 (Section Htion.
O
Dialkyl
sulfoxide
Dialkyl
O
O
RSR
RSR
RSR
and simultaneous
hydride
or alkyl shift to
give O
secondary
or tertiary carbocations.
O
Bsulfone
Bsulfoxide
BO


sulfoxide
sulfone
Important Concepts
Concepts
H O Dialkyl
H O Dialkyl
O
B
B

Dialkyl
Dialkyl
O
B
HO
H O Dialkyl
Dialkyl
sulfoxide
sulfone
Dialkyl
sulfoxide
DialkylRSR
sulfone
RSR
RSR
O
Synthesis
of primary
and secondary haloalkanes
can
be achieved with less risk of rearrangemen
Bsulfone
Bsulfoxide
 with 4.alkali

O
O
RSR
RSR
RSR
Concepts
H O metals
HO
Dialkyl
Dialkyl
Important
O
Dialkyl
sulfoxide
Dialkyl
sulfone


1. The
of
to
give
alkoxides
and
hydrogen
order
Concepts
Important
Concepts
by methods
using
1.
The reactivity
reactivity
of ROH
ROH
metals
to
giveesters.
alkoxides
and
hydrogenfollows
followsthethe
ord
sulfoxide
Bsulfone
Binorganic
RSR
RSR
RSR
BB
 with alkali
Important
Concepts


H O Dialkyl
H O Dialkyl
Important
Concepts
Dialkyl
sulfoxide
Dialkyl
sulfone
R
5
CH
primary
.
secondary
..are
tertiary.
O
B
Important
Concepts
33 .
5.alkali
Ethers
prepared
by give
either the
Williamson
ether
synthesis
or by reaction
of alcohols
wit
R
5
CH
.
primary
.
secondary
tertiary.
1.
The
reactivity
of
ROH
with
metals
to
alkoxides
and
hydrogen
follows
the
ord
O
RSR
RSR
RSR
The reactivity
of
metals
alkoxides
and
hydrogen
follows
thethe
order
1.
reactivity
of ROH
ROH
with alkali
alkali
metalsto
give
alkoxides
and
hydrogen
follows
ord
 with
togive
Important
Concepts
strong
nonnucleophilic
acids.
The
fi
rst
method
is
best
when
S
2
reactivity
is
high.
In
the
latte
Important
Concepts
N
1.
The
reactivity
of ROH
ROH
with
alkali.
metals
givealkoxides
alkoxides
and
hydrogen
followsthe
theorde
ord
Bsulfone
Dialkyl
sulfoxide
Dialkyl
sulfone
O
Important
Concepts
1.
The
reactivity
of
with
alkali
metals
toto
give
and
hydrogen
follows
Dialkyl
sulfoxide
Dialkyl
R5
5
CH
. primary
primary
.and
secondary
tertiary.
CH
.
secondary
tertiary.
CH
.
primary
.
secondary
.
tertiary.
case,.
elimination
(dehydration)
is aprimary
competing
process
at
higher
temperatures.
1.
The
reactivity
of
ROH
with
alkali
metals
togive
givealkoxides
alkoxides
and
hydrogen
follows
theorder
ord
2. R
In
the
presence
of
acid
aaalkali
nucleophilic
counterion,
alcohols
undergo
SNS2 reactions.
333 .
Concepts
2
reaction
2.
In
the
presence
of
acid
and
nucleophilic
counterion,
primary
alcohols
undergo
O
1.
The
reactivity
of
ROH
with
metals
to
and
hydrogen
follows
the
Important
Dialkyl
sulfoxide
Dialkyl
sulfone
N
R
5
CH
.
primary
.
secondary
.
tertiary.
R
5
CH
.
primary
.
secondary
.
tertiary.
1.
The
reactivity
of ROH
ROH
with
alkali
togive
givealkoxides
alkoxides
and
hydrogen
follows
theorder
ord
Important
33 Concepts
1. The
reactivity
of
with
alkali
metals
tocarbocations
and
hydrogen
follows
the
R5
5
CH
.
primary
.
secondary
tertiary.
Secondary
and
tertiary
alcohols
tend
tometals
form
ininDialkyl
the
presence
ofundergo
acid,
capable
of
E1E
alkoxides
and
hydrogen
follows
order
3 Concepts
In
Dialkyl
sulfoxide
sulfone
Secondary
and
tertiary
alcohols
tend
totertiary.
form
carbocations
the
presence
of
acid,
of
2the
reaction
2.
the
presence
ofROH
acid
and
nucleophilic
counterion,
primary
alcohols
Important
R
CH
primary
.
secondary
..
2capable
reactions.
the
presence
of
acid
aaanucleophilic
counterion,
primary
alcohols
undergo
SNSS
3 .
reaction
2. In
presence
of
acid
and
nucleophilic
counterion,
primary
alcohols
undergo
The
reactivity
of
with
alkali
to
and
hydrogen
follows
the
NN2
R5
5
CH
. primary
primary
.and
secondary
tertiary.
1.
to give
give alkoxides
alkoxides
and
hydrogen
follows
the ord
ord
3.
R
CH
.
secondary
..metals
tertiary.
4

2
4 4
4

 2 4
2
24


2
4 24

4


2 24
2
4


2
2 44
 44


22

22 4 4

22
4

2
44

22
4

2

2 2

3 3
3
3
3

2 22 2
2 2
2 2
2 2

3 2 22 2
2 2

2 2
2 2

33

22 22
22 22

33

3 3

2 22 2

2 2

3 3

2 2 2

2 2

 2

22


2
24
  
 2 22
2


2
2




22
22

2 2




2 2

2 2

aa
a
a

2
2
2

a a

2 2
22

a a

22

aa aa

22 22

a
a

44

22 2 2

4
4
4
44

2 2
2
2
2 2
22 2 2

224

44

22 22

2 2

44

22 22

2 24

44
4
4

44
44

22 22
22 22

4
4

2 2
2 2

4
4

2 2
2 2

22

22

4 4
22
4
4
424

24

2 22 2

2 22

44

2 2
2
2
2 2
2 2
2 2
2 2
2 2
2

22

22

22

22

22

2 2
22
22 22
2

24

4
4

22 22
2
2 22
2 2
2 2
2 2

2. In theNpresence of acid and a

R 5 reactivity
CH3 .
.alcohol
secon
3.
rearrangements
Secondary
andprimary
tertiary
1. Carbocation
The
of ROH
with
3.
Carbocation
rearrangements
in
interconversion
of
secondar
and
SCH
be
R5
. primary
. and
secon
N1
3product
in
interconversion
ofacid
secondar
2. In
the
presence
offormation,
a
tion.
Primary
alkyloxonium
io
tion.
Primary
alkyloxonium
io
Secondary
and
tertiary
alcohol
3.
rearrangements
2. Carbocation
In
the
presence
ofhydride
acid and
aa
and
simultaneous
or
and
simultaneous
hydride
orbe
a
SN1 product
formation,
in
interconversion
of secondar
Secondary
and tertiary
alcohol
4.
Synthesis
of
primary
and
seco
tion.
Primary
alkyloxonium
io
and
S
1
product
formation,
be
N
4. Synthesis
of primary
and seco
3.
Carbocation
rearrangements
by
methods
using
inorganic
and
simultaneous
hydride
or ae
by
methods
using
inorganic
in
interconversion
of
secondar
3. Carbocation rearrangementse
tion.
Primary
alkyloxonium
io
5.
Ethers
are
4.
primary
andeither
seco
in
interconversion
of by
secondar
5. Synthesis
Ethers
areofprepared
prepared
by
either
and
simultaneous
hydride
or io
a
strong
nonnucleophilic
acids.
by
methods
using
inorganic
tion.
Primary
alkyloxonium
strong nonnucleophilic acids.e
case,simultaneous
elimination
(dehydration
and
hydride
or a
case,
elimination
(dehydration
4. Synthesis
primary
andeither
seco
5.
Ethers
areofprepared
by
by
methods
using
inorganic
strong nonnucleophilic
acids.
4. Synthesis
of primary and
secoe
case,
elimination
methods
using(dehydration
inorganic
5. by
Ethers
are prepared
by eithere

5. strong
Ethers nonnucleophilic
are prepared by acids.
either
case,
elimination
(dehydration
strong nonnucleophilic
acids.
case, elimination (dehydration

portant Concepts
Concepts
portant
The
reactivity of
of
ROH
with
alkali
metals
to
give
alkoxides
and
hydrogen
follows
the
order
The
of ROH
ROH with
with alkali
alkali metals
metals to
to give
give alkoxides
alkoxides and
andhydrogen
hydrogenfollows
followsthe
theorder
order
The reactivity
R
5
CH
.
primary
.
secondary
.
tertiary.
R
5 CH
CH3333 .
. primary
primary .
. secondary
secondary .
. tertiary.
tertiary.
R5
reactions.
In
the presence
presence of
of
acid
and
nucleophilic
counterion,
primary
alcohols
undergo
2reactions.
reactions.
In the
of acid
acid and
and aaa nucleophilic
nucleophilic counterion,
counterion, primary
primaryalcohols
alcoholsundergo
undergoSS
SNN2NNN2
Secondary and
and tertiary
tertiary
alcohols
tend
to
form
carbocations
the
presence
acid,
capable
E1
tertiary alcohols
alcohols tend
tend to
to form
form carbocations
carbocationsinin
inthe
thepresence
presenceofof
ofacid,
acid,capable
capableofof
ofE1
E1
Secondary
and
SNN11 product
product formation,
formation,
before
and
after
rearrangement.
and S
formation, before
before and
and after
after rearrangement.
rearrangement.
N
Carbocation
rearrangements
take
place
by
hydride
and
alkyl
group
shifts.
They
usually
result
Carbocation rearrangements
rearrangements take
take place
place by
by hydride
hydrideand
andalkyl
alkylgroup
groupshifts.
shifts.They
Theyusually
usuallyresult
result
in
interconversion
of
secondary
carbocations
or
conversion
secondary
into
tertiary
carbocain interconversion
of secondary
secondary carbocations
carbocations or
orconversion
conversionofof
ofaaasecondary
secondaryinto
intoaaatertiary
tertiarycarbocacarbocain
interconversion of
tion.
Primary
alkyloxonium
ions
can
rearrange
by
a
concerted
process
consisting
of
loss
of
water
tion. Primary alkyloxonium
alkyloxonium ions
ions can
can rearrange
rearrangeby
byaaconcerted
concertedprocess
processconsisting
consistingofofloss
lossofofwater
water
and
hydride
or
alkyl
shift
to
give
secondary
tertiary
carbocations.
simultaneous hydride
and simultaneous
hydride or
or alkyl
alkyl shift
shift to
to give
give secondary
secondaryoror
ortertiary
tertiarycarbocations.
carbocations.
simultaneous
Synthesis
primary
and
secondary
haloalkanes
can
be
achieved
with
less
risk
rearrangement
Synthesis of
primary and
and secondary
secondary haloalkanes
haloalkanes can
canbe
beachieved
achievedwith
withless
lessrisk
riskofof
ofrearrangement
rearrangement
of primary
by
using inorganic
inorganic esters.
esters.
by methods
by
methods using
using
inorganic
esters.
Ethers
prepared
by
either
the
Williamson
ether
synthesis
by
reaction
alcohols
with
Ethers are
prepared by
by either
either the
the Williamson
Williamson ether
ether synthesis
synthesis oror
or by
byreaction
reactionofof
ofalcohols
alcoholswith
with
are prepared
strong nonnucleophilic
nonnucleophilic
acids.
The
rst
method
best
when
reactivity
high.
the
latter
nonnucleophilic acids.
acids. The
The fifi
first
rst method
method isis
is best
best when
whenSS
SNNNNN22
2reactivity
reactivityisis
ishigh.
high.InIn
Inthe
thelatter
latter
strong
case,
elimination
(dehydration)
is
a
competing
process
at
higher
temperatures.
case, elimination
(dehydration) isis aa competing
competing process
process atathigher
highertemperatures.
temperatures.
elimination (dehydration)

P
Pr rrroooobbb
bl lell eeemm
ms sss
m
PP
P
P rr oo b
b ll ee m
m ss
PPr roobbl leemmss
PPr ro obbl el emms s
ms s
PP
r ro obbl el e
em
6. Crown
ethers
and
cryptands
are
examples
of
ionophores,
polyethers
that
coordinate
PPr ro obbl elaround
mms s
6.
Crown ethers
ethers
and
cryptands
are
examples
of
ionophores,
polyethers
that
coordinate
P r o baround
laround
ems
and
cryptands
are
examples
of
polyethers
6. Crown
ethers
and
cryptands
are
examples
of ionophores,
ionophores,
polyethersthat
thatcoordinate
coordinate
around
metal
ions,
thus
rendering
them
soluble
in
hydrophobic
media.
6.
ethers
and
cryptands
are
examples
of
polyethers
leemms s
PPr roobblaround
6. Crown
Crown
ethers
cryptands
examples
of ionophores,
ionophores,
polyethers that
that coordinate
coordinate
around
metal ions,
thus
rendering
them
soluble
in
hydrophobic
media.
metal
thus
rendering
them
soluble
in
media.
themare
thusand
rendering
soluble
in hydrophobic
hydrophobic
media.
6.
Crownions,
ethers
and
cryptands
are
examples
of ionophores,
ionophores,
polyethers that
that coordinate
coordinate around
around
thus
them
soluble
6. metal
Crown
ethers
and
cryptands
are
examples
polyethers
metal
ions,
thus
rendering
them
soluble
hydrophobic
media.
6.
Crown
ethers
and
cryptands
are
examples
ionophores,
polyethers
thatless
coordinate
around
7.
Whereas
ring
opening
of
oxacyclopropanes
anions
is
the
substituted
ring
6.
Crown
cryptands
are
examples
polyethers
that
coordinate
around
P rWhereas
o bions,
lethers
enucleophilic
m and
srendering
Coxacyclopropanes
hininininahydrophobic
pofofof
tionophores,
e r media.
9byby
377
metal
ions,
thus
rendering
them
soluble
hydrophobic
media.
7.
Whereas
nucleophilic
ring them
opening
of
oxacyclopropanes
byanions
anions
isatat
atthe
the
less
substituted
ring
nucleophilic
ring
opening
of
is
less
substituted
ring
7.
nucleophilic
ring
opening
of
oxacyclopropanes
by
anions
is
at
the
less
substituted
ring
metal
ions,
thus
rendering
soluble
hydrophobic
media.
6.
Crown
ethers
and
cryptands
are
examples
of
ionophores,
polyethers
that
coordinate
around
metal ions,
ions,
thusand
rendering
them
soluble
in
hydrophobic
media.
ethers
cryptands
are
examples
of ionophores,
polyethers
that
coordinate
around
6. Crown
carbon
according
to
the
rules
of
the
S
2
reaction,
acid-catalyzed
opening
favors
the
more
substimetal
thus
rendering
them
soluble
in
hydrophobic
media.
7.
Whereas
nucleophilic
ring
opening
of
oxacyclopropanes
by
anions
is
at
the
less
substituted
ring
N
7.
Whereas
nucleophilic
ring
opening
of
by anions
is at the
less
substituted
ring
6.
Crownions,
ethers
and
cryptands
are
examples
of ionophores,
ionophores,
polyethers
that
coordinate
around
according
to cryptands
the
rules
ofare
theexamples
SNNNoxacyclopropanes
2 reaction,
reaction,
acid-catalyzed
opening
favors
themore
morearound
substiCrown
ethers
and
of
polyethers
that
coordinate
carbon
according
to
the
rules
of
the
S
2
acid-catalyzed
opening
favors
the
substi6.
according
to
the
rules
of
the
S
2
reaction,
acid-catalyzed
opening
favors
the
more
substimetal
thus
rendering
them
soluble
in
hydrophobic
media.
7.
Whereas
nucleophilic
ring
opening
ofN2oxacyclopropanes
oxacyclopropanes
byanions
anions
isatatthe
the
less
substituted
ring
thus
rendering
them
soluble
in
hydrophobic
media.
metal
ions,
tuted
carbon,
because
of
charge
control
of
nucleophilic
attack.
Crown
ethers
and
cryptands
are
examples
of
ionophores,
polyethers
that
coordinate
around
carbon
according
to
the
rules
of
the
S
reaction,
acid-catalyzed
opening
favors
the
more
substi6.
7. metal
Whereas
nucleophilic
ring
opening
of
by
is
less
substituted
ring
carbon
according
to
the
rules
of
the
S
2
reaction,
acid-catalyzed
opening
favors
the
more
substimetal
ions,
thus
rendering
them
soluble
in
hydrophobic
media.
7.
Whereas
nucleophilic
ring
opening
of
oxacyclopropanes
by
anions
is
at
the
less
substituted
ring
carbon,
because
of charge
charge
control
of hydrophobic
nucleophilic
attack.
Noxacyclopropanes
ions,
thus
rendering
them
soluble
in
media.
carbon,
because
of
control
of
nucleophilic
attack.
7. tuted
Whereas
nucleophilic
ring
opening
of
by anions
is at the
less
substituted
ring
carbon,
because
of
charge
control
of
nucleophilic
attack.
6.
and
cryptands
are
examples
of ionophores,
ionophores,
polyethers
that
coordinate
around
Crown
ethers
and
examples
of
polyethers
that
coordinate
carbon
according
to cryptands
the
rules
ofare
the
reaction,
acid-catalyzed
opening
favors
themore
morearound
substiN22of
tuted
because
of
charge
control
nucleophilic
attack.
metal
ions,
thus
rendering
them
soluble
in
hydrophobic
media.
carbon
according
to
the
rules
of
the
SS
reaction,
acid-catalyzed
opening
favors
the
substi7.
Whereas
nucleophilic
ring
opening
byanions
anions
isat
atthe
the
less
substituted
ring
NNoxacyclopropanes
tuted
carbon,
because
ofrules
charge
control
nucleophilic
attack.
carboncarbon,
according
to the
the
rules
of the
theof
SNdoes
2of
reaction,
acid-catalyzed
opening
favors
the
moresubstisubstinucleophilic
ring
opening
by
less
substituted
ring
7. Whereas
8.
Sulfur
has
more
diffuse
orbitals
than
oxygen.
In
thiols,
the
S
is
H
bond
is
less
polarized
than
carbon
according
to
of
Sof
2oxacyclopropanes
reaction,
acid-catalyzed
opening
favors
the
more
thus
rendering
them
soluble
in
hydrophobic
media.
metal
ions,
thus
rendering
them
soluble
in
hydrophobic
media.
tuted
carbon,
because
of
charge
control
of
nucleophilic
attack.
7.
nucleophilic
ring
opening
of
oxacyclopropanes
by
anions
is
at
the
less
substituted
ring
8.
more
diffuse
orbitals
than
does
oxygen.
In
thiols,
the
S
H
bond
is
less
polarized
than
Whereas
nucleophilic
ring
opening
of
oxacyclopropanes
by
anions
is
at
the
less
substituted
ring
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
In
thiols,
the
S

H
bond
is
less
polarized
than
7.
tuted
carbon,
because
of
charge
control
of
nucleophilic
attack.
8. carbon
more
diffuse
orbitals
than
does
oxygen.
In hydrogen
thiols,
theopening
Sopening
H bond
is less
polarized
than
according
to the
the
rules
ofleading
the
Sdoes
2to
reaction,
acid-catalyzed
favors
the
more
substituted
carbon,
because
ofrules
charge
control
of
nucleophilic
attack.
according
to
of
the
Sof
reaction,
acid-catalyzed
the
more
NN2oxacyclopropanes
the
O carbon,
H
bond
in
alcohols,
thus
diminished
bonding.
Because
the
SSsubstiH
bond
tuted
because
of
charge
control
of
nucleophilic
attack.
7.
Whereas
nucleophilic
ring
opening
bythe
anions
atfavors
the
substituted
ring
8.
Sulfur
has
more
orbitals
than
oxygen.
In
thiols,
S
H
bond
is
polarized
than
8. carbon
Sulfur
has
more
diffuse
orbitals
than
oxygen.
In hydrogen
thiols,
the
S
His
is less
less
polarized
than
according
to the
the
rules
ofleading
the
Sdoes
2to
reaction,
acid-catalyzed
opening
favors
the
more
bond
indiffuse
alcohols,
thus
leading
to
diminished
hydrogen
bonding.
Because
the
Hsubstibond
according
to
of
the
Sof
reaction,
acid-catalyzed
opening
favors
the
more
the
O carbon,
H
bond
in
alcohols,
thus
to
diminished
bonding.
Because
the
SS
H
bond
N2
N
bond
in
alcohols,
thus
leading
diminished
hydrogen
bonding.
Because
the
substiH
bond
7.
nucleophilic
ring
opening
oxacyclopropanes
bygreater
anions
isbond
atthe
the
less
substituted
ring
Whereas
nucleophilic
ring
opening
of
oxacyclopropanes
by
anions
is
at
less
substituted
ring
carbon,
because
ofrules
charge
control
of
nucleophilic
attack.
because
of
charge
control
nucleophilic
attack.
8.
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
Inhydrogen
thiols,
the
H
bond
less
polarized
than
is
also
weaker
than
O
thus
H
bond,
the
acidity
of
thiols
is
than
that
of
alcohols.
the
O
H
bond
in
alcohols,
leading
diminished
Because
the
S
bond
carbon
according
to the
the
rules
of
the
Sdoes
2of
reaction,
acid-catalyzed
favors
the
more
8. tuted
Sulfur
has
more
diffuse
orbitals
than
oxygen.
In
thiols,
the
SS
H
bond
isis
less
polarized
than
Nto
the
O
carbon,
H
bond
in
alcohols,
thus
leading
to
diminished
bonding.
Because
the
S H
H substibond
carbon,
because
ofO
charge
control
of
nucleophilic
attack.
8.
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
Inhydrogen
thiols,
thebonding.
Sopening
H
bond
isof
less
polarized
than
weaker
than
the
O
H of
bond,
the
acidity
ofacid-catalyzed
thiols
isgreater
greater
than
that
of
alcohols.
tuted
because
of
charge
control
of
nucleophilic
attack.
is
also
weaker
than
the

H
bond,
the
acidity
of
thiols
is
than
that
alcohols.
8.
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
In
thiols,
the
S

H
bond
is
less
polarized
than
is
also
weaker
than
O

H
bond,
the
acidity
of
thiols
is
greater
than
that
of
alcohols.
according
to
the
rules
of
the
S
2
reaction,
acid-catalyzed
opening
favors
the
more
substicarbon
according
to
the
rules
the
S
2
reaction,
opening
favors
the
more
substiNN to
thealso
Ocarbon,
H
bondbecause
in
alcohols,
thus
leading
diminished
hydrogen
bonding.
Because
theSSHHbond
bond
rdinate
around
is
weaker
than
theofO
O
thus
H bond,
bond,
the
acidity
of thiols
thiols
is greater
greater
than
that
of
alcohols.
tuted
charge
control
ofdiminished
nucleophilic
attack.
the
O
H
bond
in
alcohols,
leading
to
hydrogen
bonding.
Because
the
8.
is
weaker
than
the

H
the
acidity
of
is
that
alcohols.
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
thiols,
thebonding.
SHthan
H
bond
less
polarized
than
more
diffuse
orbitals
than
does
oxygen.
InIntext,
thiols,
the
S
bond
isisof
less
polarized
than
thealso
Oon
H
bond
in
alcohols,
thus
leading
to
diminished
hydrogen
bonding.
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theSS
H
bond
the
O
H
bond
in
alcohols,
thus
leading
to
diminished
hydrogen
Because
the

H
bond
9.
Note
color
use:
Throughout
the
main
parts
of
the
beginning
in
Chapter
6,
reacting
species
tuted
carbon,
because
of
charge
control
of
nucleophilic
attack.
because
of
charge
control
of
nucleophilic
attack.
is
also
weaker
than
the
O

H
bond,
the
acidity
of
thiols
is
greater
than
that
of
alcohols.
8.
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
In
thiols,
the
S

H
bond
is
less
polarized
than
9. the
color
use:
Throughout
the
main
parts
ofof
the
text,
beginning
inbond
Chapter
6,alcohols.
reacting
species
moreuse:
diffuse
orbitals
thanmain
does
oxygen.
Intext,
thiols,
the bonding.
Sbonding.
H
is of
less
polarized
than
Note
color
Throughout
the
parts
of
the
beginning
in
Chapter
6,
reacting
is
weaker
than
the
O
thus
H
bond,
the
acidity
thiols
is
greater
than
that
9.
Note
on
color
use:
Throughout
the
main
parts
of
the
text,
beginning
in
Chapter
6,
reacting
species
bond
in
alcohols,
leading
to
diminished
hydrogen
Because
the
species
H
bond
O on
H
bond
in
alcohols,
leading
to
diminished
hydrogen
Because
the
SS
H
bond
is also
also
weaker
than
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O
H bond,
bond,
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acidity
of
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is
greater
than
that
of
alcohols.
weaker
than
the
thus
H
the
acidity
is
greater
than
that
alcohols.
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
9.
Note
on
color
use:
Throughout
the
main
parts
of
text,
beginning
Chapter
reacting
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
In
thiols,
the
S in
H
bond
isof6,
less
polarized
than
8.
9. the
Note
color
use:
Throughout
the
main
parts
ofofthe
thethiols
text,
beginning
in
Chapter
6,
reacting
species
bond
in
alcohols,
thus
leading
to
diminished
hydrogen
Because
the
species
Hbond
bond
mechanisms
and
most
examples
of
new
transformations
are
color
coded
for
nucleophiles,
O on
H
bond
in
alcohols,
leading
to
diminished
hydrogen
bonding.
Because
the
SS
H
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
in also
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
Sulfur
has
more
diffuse
orbitals
than
does
oxygen.
In
thiols,
the
Sbonding.
bond
isred
less
polarized
than
8.
more
diffuse
orbitals
than
does
oxygen.
Intext,
thiols,
the
SH
H
bond
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less
polarized
than
weaker
than
the O
O
Hgreen
bond,
the
acidity
of
thiols
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than
that
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alcohols.
weaker
than
the
thus
H
bond,
the
acidity
thiols
isbeginning
greater
than
that
alcohols.
9.
Note
color
use:
Throughout
the
main
parts
ofof
the
beginning
in
Chapter
6,
reacting
species
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
blue
for
electrophiles,
and
for
leaving
groups.
Color
coding
is
not
in
the
Oon
on
H
bond
in
alcohols,
thus
leading
to
diminished
hydrogen
bonding.
Because
the
Sexercises,
species
H
bond
9. is
Note
color
use:
Throughout
the
main
parts
of
the
text,
in
Chapter
6,used
reacting
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
weaker
than
the
O

H
bond,
the
acidity
of
thiols
is
greater
than
that
of
alcohols.
9.
color
use:
Throughout
the
main
parts
of
the
text,
beginning
in
Chapter
6,
reacting
species
is
also
weaker
than
the
O

H
bond,
the
acidity
of
thiols
is
greater
than
that
of
alcohols.
electrophiles,
and
green
for
leaving
groups.
Color
coding
is
not
used
in
exercises,
blue
for
electrophiles,
and
green
for
leaving
groups.
Color
coding
is
not
used
in
exercises,
Note
on
color
use:
Throughout
the
main
parts
of
the
text,
beginning
in
Chapter
6,
reacting
species
blue
for
electrophiles,
and
green
for
leaving
groups.
Color
coding
isthat
not
used
inSexercises,
the
O for
Hweaker
bond
in
alcohols,
thus
leading
to
diminished
hydrogen
bonding.
Because
the
in
alcohols,
thus
leading
to
diminished
hydrogen
bonding.
Because
the
Sexercises,
HHbond
bond
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
blue
electrophiles,
and
green
for
leaving
groups.
Color
coding
is
not
used
in
summaries
of
new
reactions,
or
chapter-end
problems.
is
also
than
the
O

H
bond,
the
acidity
of
thiols
is
greater
than
of
alcohols.
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
blue
for color
electrophiles,
and
green
for
leaving
groups.
Color
coding
is not
used
in
exercises,
9. Note
color
use:
Throughout
the
main
parts
ofof
the
text,is
beginning
in
Chapter
6,alcohols.
reacting
species
on
use:
Throughout
the
main
parts
of
the
text,
beginning
in
Chapter
6,
reacting
species
substituted
ring
mechanisms
andreactions,
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
of
new
reactions,
or
chapter-end
problems.
summaries
of
new
or
chapter-end
problems.
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
is
also
weaker
than
the
O

H
bond,
the
acidity
thiols
greater
than
that
of
summaries
of
new
reactions,
or
chapter-end
problems.
than
the
O

H
bond,
the
acidity
of
thiols
is
greater
than
that
of
alcohols.
blue
for color
electrophiles,
and
green
fornew
leaving
groups.
Color
coding
not
used
in exercises,
exercises,
9. in
color
use:
Throughout
the main
main
parts
ofgroups.
thetext,
text,beginning
beginning
incoded
Chapter
6,for
reacting
species
Note
on
use:
Throughout
the
parts
of
the
incoded
Chapter
6,
reacting
species
summaries
of
or
chapter-end
problems.
blue
for
electrophiles,
and
green
for
leaving
Color
coding
isis
not
used
in
summaries
of new
new
reactions,
or
chapter-end
problems.
mechanisms
andreactions,
mostand
examples
of
transformations
arecolor
color
red
nucleophiles,
mechanisms
and
most
examples
of
transformations
are
red
for
nucleophiles,
electrophiles,
and
green
fornew
leaving
groups.
Color
coding
isnot
not
used
inexercises,
exercises,
blue
for
electrophiles,
green
for
leaving
coding
is
used
in
Note
onsubsticolor
use:
Throughout
the
main
parts
ofgroups.
the text,Color
beginning
incoded
Chapter
6,for
reacting
species
he9.
summaries
of new
new
reactions,
orthe
chapter-end
problems.
mechanisms
andreactions,
mostand
examples
of
new
transformations
arecolor
color
red
nucleophiles,
in
mechanisms
and
most
examples
of
transformations
are
red
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summaries
of
or
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Note
on
use:
Throughout
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the
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incoded
Chapter
6,for
reacting
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9. more
use:
Throughout
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thetext,
text,Color
beginning
incoded
Chapter
6,for
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blue
for color
electrophiles,
green
for
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coding
isisnot
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in
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and
green
fornew
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coding
not
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inexercises,
exercises,
summaries
of new
new
reactions,
or chapter-end
chapter-end
problems.
of
or
problems.
in
mechanisms
andreactions,
mostand
examples
of
new
transformations
are color
red
nucleophiles,
electrophiles,
and
green
for
leaving
groups.
Color
coding
is
not
used
in
exercises,
blue
for
electrophiles,
green
for
leaving
groups.
Color
coding
is
not
used
in
exercises,
in
mechanisms
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
and
most
examples
of
new
transformations
are
color
coded
red
for
nucleophiles,
summaries
of
new
reactions,
or
chapter-end
problems.
of
new
reactions,
or
chapter-end
problems.
Problems
blue for electrophiles,
and or
green
for leaving
groups. Color coding is not used in exercises,
summaries
of
new
reactions,
chapter-end
problems.
of
new
reactions,
or
chapter-end
problems.
Problems
blue for electrophiles,
and
for
groups.
electrophiles,
and green
green
for leaving
leaving
groups. Color
Color coding
coding isis not
notused
usedininexercises,
exercises,
Problems
summaries
of new
reactions,
ordochapter-end
problems.
Problems
28.
On which
which side
side
of the
the
equationor
you expect
expectproblems.
each of
ofthe
thefollowing
followingequilibria
equilibriatotolie
lie(left
(leftororright)?
right)?
of new
reactions,
chapter-end
new
reactions,
chapter-end
problems.
On
of
equation
do
you
28. summaries
side
of the
the
equationor
do
you expect
expect each
each of
of the
the following
following equilibria
equilibria to
to lie
lie (left
(left or
or right)?
right)?
Problems
28.
On which
which side
side
of
equation
do
you
each
polarized
than
28.
On
of
the equation
equation
do
you
expect each
each
of
the following
following equilibria
equilibria to
to lie
lie (left
(left or
or right)?
right)?
12
2 of
1 the
Problems
28.
On
which
side
of
the
do
you
expect
12
2
1
)
COH
1
K
OH

(CH
)
CO
K
1
H
O
(a)
(CH
12
2
1
3) 3COH 1 K 12OH (CH 3) 3CO 2K 11 H 2O
(a)
(CH
COH
1
K
OH

(CH
)
CO
K
1
H
O
3
3
3
3
2
28.
On
which
side
of
the
equation
do
you
expect
each
of
the
following
equilibria
to
lie
(left
or
right)?
Problems
12
2
1
3
3
3
3
2
)
COH
1
K
OH

(CH
)
CO
K
1
H
O
(a)
(CH
28.
OnSwhich
which
side
of
the
equation
do
you
expect
each
the
following
equilibria
totolie
lie
(left
ororright)?
right)?
12
2K1of
3) 3side
3bond
3) 31
3CO
2followingequilibria
2
COH
1
K
OH

(CH
1
H
O
(a)
(CH
side
of
the
equation
do
you
expect
each
of
the
equilibria
lie
(left
right)?
3
3
2
On
of
the
equation
do
you
expect
each
of
the
following
to
(left
or
e 28.
the(a)

H
)
COH
1
K
OH

(CH
)
CO
K
1
H
O
(CH
1
2
Problems
(b)
CH
OH
1
NH

CH
O
1
NH
(pK
5
9.2)
1(pK
2 1 NH
3 431
2
33 3 1 NH 3
3 2
12 CH
2aaa5
1 9.2)
(b)
CH
1
NH
CH
O
1
NH
(pK
5
9.2)
33K
33O
4)41 CO
12
2
1
On
the
equation
do
expect
each
of
the
following
equilibria
(b) which
CH3333OH
OH
1of
NH

CH
O2
1
NH
(pK
5
9.2)
)side
COH
1
OHCH

(CH
K
1
O
(a)
(CH
28.
of
the
equation
do
you
expect
each
of1
the
following
equilibriatotolielie(left
(leftororright)?
right)?
2you
Problems
3K
a5
2O
COH
1

(CH
CO
HH
(a)
(CH
12
22K
1
12OH
1
(b)
CH
OH
1
NH
O
1
NH
(pK
9.2)
33) 33side
334)41
33CO
3
333O
aaK
(b)
CH
1
NH
1
NH
(pK
5
9.2)
COH
1
OH
(CH
K
1
H
O
(a)
(CH
COH
1
K
OHCH

(CH
CO
1
H22following
O HH
3OH
3K
which
of
the
equation
do
you
expect
each
ofof
the
equilibria
totolielie(left
ororright)?
Problems
28. On
of
the
equation
do
you
expect
each
the
equilibria
(left
right)?
33) 3side
33)4)331
3side
2following
lcohols.
2
12
2
1
1
2
H
12OHCH
2Ka 5
11

CH
O22you
1
NH
(pK
5
9.2)
NH
A
) COH
1

(CH
CO
HH2O
(a)
(CH
3O
(b)
CH333OH
OH
1
NH

1
NH
(pK
9.2)
On which
of
equation
expect
each
of9.2)
the
equilibria to lie (left or right)?
COH
1the
K
OH

(CH
CO
1
OH
33)4)43131
28.
33K
3do
AH
12
22aK
1of
3 33side
2following
A
12OH
1
(b)
CH
1
NH
1
NH
(pK
1of
NH
CH
O2you
1
NH
(pK
5
9.2)
 CH

28. (a)
On
the
equation
expect
each
the
equilibria
333 ) 3side
33K
3do
aK
3O
a5
A
COH
1

(CH
K
11
HH2following
O
(CH
28.
On which
which
of
the
equation
do
you
expect
each
of
the
equilibriatotolie
lie(left
(leftororright)?
right)?
COH
1
K

(CH
CO
OH
33)4)4313CO


AAN
NOH
Li
3 3side
2following
Li

12
2 5
1 9.2)
N
N
H


(b)
CH
1
NH
(pK
N
N
Li
H
OH 1
33OH
33O
1 NH
NH

CH
O22
1(CH
NH34)4131
(pK
9.2)


133K
1
H2O H
(a) CH
(CH
a 15
NOH
N
Li
12
22aK
1CO
21
 Li

3 ) 3COH
N
N
H
12
11
(b)
CH
OH
1
NH

CH
O
NH
(pK
5
9.2)
A
eacting
species


)
COH
1
K
OH

(CH
)
CO
K
H
O
(a)
(CH
N
N
Li
1
NH

CH
O
1
NH
(pK
5
9.2)
A
3
3
3
4
a
33 )33COH
33 )43CH
3K
3 2 (CH
aLi1
1
OH

K
H22O H
(a)
(CH33CH

(pK

40)
(c)
CH
CH
OH

CH
O

31CO
A

A


a
2
3
2
(pK

40)
(c)


CH
OH

CH
CH
O
Li


(b)
CH333CH
OH22OH
1 NH
CH
O22 1 CH
NH3341CH
(pK
5
9.2)
(pKa aa
 40)
40)
OH
3
CH
CH
OaLi
Li
 NH
22O
N Li
N (pK
Li
N

(pK
(c) CH
CH

Li
 3O
1 (pK
9.2)
(c)


(b)
CH
OH
1
CH
NH
5
AH
N
N
aa  40)
222O
33
3O 1
aaLi
N Li
N
Li
A (pK
(b)
CH33333CH
OH222OH
1 NH
NH

CH
1 CH
NH33434CH
(pK
5
9.2)
40)
(c)
CH
CH
OH

CH
CH
O
 H
r nucleophiles,
 3
AH
 
A

Li
(pKaa
40)
40)
CH33CH
CH
O
Li 
 N
 N
N
N
Li
(pK
(c) CH
CH3CH
CH22OH
OH 

CH
O
Li
Li
HH
Li


222O

(pK

40)
A
(c)
CH
CH

N
N
(pK

40)
OH

CH
CH
O
Li

a
3
2
3
N
N
Li




a
2 2 
NH333(pK
(pK2aa 
 35)
35) 
Na3
NH

H22(pK
(pKAaAa38)
38)
 Na

Na
(d)exercises,

NH


d in(c)
H
NH
Na

(d)

NH3CH
(pKOH

35)
Na

H
(pK
38)


Na

(d) CH

(pK

CH
CH
OO222Li

a
N
N
Li
3
2NH
 35)
35)
Na
NH

H
(pKN
38)
38)
N

Na


(pKa a40)
40)
(c)
CH
CH
 
CH
Li
2(pK

NH
NH
(pK
Na

H

Na
(d)
aa 
3CH
2O


aOH
22Li
aa a
Li
NH333333CH
(pK22OH

35)
Na
NH

H

Na
(d)
(pK
(c)
 
CH
222(pK
N
N 38)
Li
(pKa a40)
40)
33CH
(c) CH
CH
CH
CH
3CH22aOH 

22OLi 
 




35)
Na
NH

(pK
38)
38)
 Na
29.
Give
the
expected
major
product
of each
each
of
the
reactions.
 of
Na
NH
(pK
 35)
Na
NH

HH



the

(pKa40)
40)
(d)
(c)
CH
major
CH
CH
O2following
Li
(pK
a
2following
H
29. Give
the
expected
product
of
reactions.


aa
33CH
2aOH
3CH
2O
29.
GiveCH
the
expected
major
product
of each
each
of
the
following
reactions.
NH
(pK
Na
NH


(d)
(pK
(c)

CH

35)
Na3

H2222(pK
(pK
38)
 Na
 of
Na
aOH
22Li
areactions.
29.
expected
major
product
of
each
of
the
following
3333CH
22OH
2NH
a  35)
a 38)
Give
the
expected
product
reactions.
(pKa a  40)
(c)
CH
CH
major
CH
CH
Li
the

3of
2O following
29. (d)
Give
the
expected
major
product
of
each
of
the
following
reactions.

Na
NH
 H

Na
22(pK
Conc.
HI
Conc.HBr
HBr
NH33(pK
(pKaa 
 35)
35) 
Na
(pKa a
38)
38) Conc.
Conc.

NaHI
(d) NH
NH22  H


 of
NH
(pK

35)
Na
NH

H
(pK

38)
Conc.
HI
Conc.
HBr


Na
29. (d)
major
product
of
each
of
the
following
reactions.
expected
Give
the
expected
major
product
each
of
the
following
reactions.
3
a
2
2
a
(a)
(b)
CH
CH
CH
OH
(CH
)
CHCH
CH
OH
NH
(pK

35)
Na
NH

H
(pK

38)
Conc.
HI
Conc.
HBr


Na
(d)
Conc.product
HI
HBr
2CH
2 OH Conc.
(a)
(b)
aCH22OH
2following
2 2reactions.
aCH
(CH
OH
the3333CH
expected
major
of
following
222CH
333))222CHCH
HI

the
29. Give
expected
major
product
of each
each
of
the
  of
(a) CH
(b)
CH
CH
OH
(CH
CHCH
235)
2reactions.
238)
(b)
OH
(CH
)22CHCH
CHCH
OH Conc. HBr
NH
(pK
235)
Na(b)
NH
H2(pK
(pK
2238)
(a)
Conc.
Na
CH
OH
(CH
CH
OH

the
(d)
 
33CH
2CH
2
3))
2
2
aCH
233
aCH
3
2
2
(a)
(b)
CH
CH
CH
OH
(CH
CHCH
CH
OH
Give
the
expected
major
product
of
each
of
following
reactions.




NH
(pK

Na
NH
H


29.

Na
(d)
3
2
2
2
2
2
a  35)major
a 38) Conc.
Conc.
HI
Conc.HBr
HBr
29. Give
Give
the33 (pK
expected
product
of each
each
of the
the2following
following
reactions.
Conc.
HI
Naof
NH
 H22 (pK
Conc.
Na
(d) NH
a H major
2
a
HI
Conc.
HBr
the
expected
product
of
reactions.
29. (a)
Conc.product
HI
Conc. HBr
(b)
GiveCH
the
expected
major
of each(b)
of the
OH
(CHfollowing
CHCH2reactions.
CHConc.
OHHCl
(b)
CH
(CH
OH
H
2OH
2CH
3CH
22CH
33))22CHCH
22Conc.
HCl
Conc.
HI HI
(a)
H
(CH
CH
Conc.
HI
Conc.
Conc. HBr
(a) CH
(b)
33CH
22CH
33))22CHCH
2reactions.
2OH
CH
CH
OH
(CHfollowing
CHCH
OHHCl
H222OH
H
Conc.
HCl
Conc.
HIproduct
Give
the
expected
major
of each
each(d)
of the
the
2CH
2Conc.
Conc.
HI
Conc. HBr
29.
(c)
(d)
(CH
CH
) COH
H
HCl
Conc.
HI
Conc.
Conc.
HI
(c)
29. (a)
Give
the
expected
major
product
of
of
following
CHCH
CH
OH
Conc.
HI
Conc. HBr
22)3)3COH
HCl
Conc.
HI
(c) CH
(d)
3CH
2CH
2OH
33)3CH
2reactions.
CH
COH
29.
Give
the
expected
major
product
of each(b)
of (CH
the
following
Conc.
HI
(a)
(b)
CH
OH
(CH
)2CH
CHCH
CH2Conc.
2
3
(c)
(d)
(d)
(CH
CH
COH
3CH
2CH
2OH
2CHCH
2reactions.
2OH Conc. HBr
2))33)COH
3COH
33)3CH
2
(a)
(b)
(CH
CH
OH
(c)
(d)
H
OH
2
3
2
2
2
2
OH
(a) CH
(b)
CH33CH
CH22CH
CH
OH
(CH
)
CHCH
CH
OH
Conc.
HI
Conc.
HBr
Conc.
HCl
Conc. HI
HI
Conc.
HCl
Conc.
H
3 2
2
2
OH
H2OHConc.
Conc.
Conc. HBr
Conc.
HI
OH
OH
HCl
Conc.
HI HI
(a) CH
(b)
(d) (CH
CH3CH
CH2CH
(CH33CH
)CH
OHHCl
(c)
(d)
Conc.
HI
Conc. HBr
COH
(CH
CH
COH
OH
H
2CHCH
2CHOH
2Conc.
22)))33COH
(a)
(b)
(c)
(d)
HCl
3 CH2CH
3))CH
2CHCH
2CH
Conc. HI
H222OH
22
3)3COH
(c)or
(d)a (CH
(a)
(b)
CH
OH
CHCH
CH2Conc.
OH
(left
right)?
H
Conc.
HCl
Conc.
HI
3 reaction
2CH
3
2
2
2
30. (c)
reaction
in
Problem
29,
write
out
detailed
step-by-step
mechanism.
For
each
in
Problem
29,
write
out
a
detailed
step-by-step
mechanism.
OH
(d)
H inConc.
Conc. HCl
HI
3CH
2)step-by-step
3COH
30. (c)
For each
each reaction
reaction
Problem
29, write
write out
out
detailed
step-by-step
mechanism.
OH
HCl
HI
(c)
(d)aaaa(CH
(CH
Problem
29,
detailed
mechanism.
30.
reaction
inConc.
Problem
29,
write
out
detailed
mechanism.
OH
3CHstep-by-step
3COH Conc.
(d)
(CH
)23))COH
30. For
For
in
Problem
29,
write
out
detailed
step-by-step
mechanism.
H in
(c) each reaction
(d) structure
(CH33CH
CH2of
COH
H
Conc.HCl
HCl
Conc. HI
HIalcohols, write the
2 3the
Conc.
31. For
theOH
following
alkyloxonium
ionproduced
producedafter
afterproproOH
Hfollowing
the
write
the
alkyloxonium
(c) each
(d)aastructure
For
each of
reaction
in
Problem
29,
write
out
detailed
step-by-step
mechanism.
30.
inConc.
Problem
29, write
write
out
astructure
detailed
mechanism.
(CH
CHof
)the
COH
Conc.
HCl ion
Conc.
HIalcohols,
31.
of
theOH
following
alcohols,
writeout
the
structure
of
the
alkyloxonium
ionproduced
producedafter
afterpropro3CH
2)step-by-step
3COH
(c)
(d)
(CH
OH
30. For
reaction
in
Problem
29,
detailed
step-by-step
mechanism.
each
of
the
following
alcohols,
write
the
structure
of
the
alkyloxonium
ion
31.
the
following
alcohols,
write
the
of
the
alkyloxonium
ion
produced
after
pro3
2
3
30.
each
reaction
in
Problem
29,
write
out
a
detailed
step-by-step
mechanism.
31.
For
each
of
the
following
alcohols,
write
the
structure
of
the
alkyloxonium
ion
produced
after
pro(c) eachby
(d)
(CH
COH
strong
acid;
the alkyloxonium
alkyloxonium
ion
capable
oflosing
losingwater
water
readily,
writethe
the
structure
tonation
strong
acid;
ifif
the
ion
isis
capable
readily,
write
structure
3CHstep-by-step
2)3of
OH
For
reaction
in
Problem
29,
write
out
a
detailed
mechanism.
tonation
by
strong
acid;
if
the
alkyloxonium
ion
is
capable
of
losing
water
readily,
write
the
structure
30.
OH
tonation
by
strong
acid;
if
the
alkyloxonium
ion
is
capable
of
losing
water
readily,
write
the
structure
strong
acid;
if
the
alkyloxonium
ion
is
capable
of
losing
water
readily,
write
the
structure
30.
For
each
reaction
in
Problem
29,
write
out
a
detailed
step-by-step
mechanism.
each
of
the
following
alcohols,
write
the
structure
of
the
alkyloxonium
ion
produced
after
pro31.
following
alcohols,
write
the
structure
of
the
alkyloxonium
ion
produced
after
protonation
by
strong
acid;
if
the
alkyloxonium
ion
is
capable
of
losing
water
readily,
write
the
structure
OH
30.
For
reaction
in
Problem
29,
write
out
a
detailed
step-by-step
mechanism.
of
the
resulting
carbocation;
if
the
carbocation
obtained
is
likely
to
be
susceptible
to
rearrangement,
carbocation;
ifif the
carbocation
obtained
isstep-by-step
likely
totobe
susceptible
totorearrangement,
31. For
each
of
the
following
alcohols,
write
the
structure
ofof
the
alkyloxonium
ion
produced
after
pro30.
For
reaction
in
Problem
29,
write
out
a
detailed
mechanism.
31.
each
of
the
following
alcohols,
write
the
structure
the
alkyloxonium
ion
produced
after
proof
the
resulting
carbocation;
the
carbocation
obtained
is
likely
be
susceptible
rearrangement,
of
the
resulting
carbocation;
if
the
carbocation
obtained
is
likely
to
susceptible
to
resulting
carbocation;
the
carbocation
obtained
isthe
likely
be
susceptible
torearrangement,
rearrangement,
tonation
by
strong
acid;
ifif the
the
alkyloxonium
ion
isis
capable
of
losing
water
readily,
write
the
structure
of
the
resulting
carbocation;
ififalkyloxonium
the
carbocation
obtained
is
likely
totobe
be
susceptible
to
rearrangement,
acid;
the
alkyloxonium
ion
capable
of
losing
water
readily,
write
the
structure
each
of
the
alcohols,
write
the
of
alkyloxonium
ion
produced
after
pro31. For
structures
ofProblem
all
new
carbocations
that
might
be
reasonably
expected
toproduced
form.
each
reaction
inof
Problem
29,
write
out
astructure
detailed
step-by-step
mechanism.
write
the
structures
all
carbocations
that
might
be
reasonably
expected
form.
For
tonation
by
strong
acid;
if
ion
is
capable
of
losing
water
readily,
the
30.
For
reaction
in
29,
write
astructure
detailed
step-by-step
mechanism.
each
of
the following
following
alcohols,
writeout
the
of
the
alkyloxonium
ionto
after
pro31.
tonation
by
strong
acid;
if new
the
alkyloxonium
ion
is
capable
of
losing
water
readily,
write
thestructure
structure
write
the
structures
ofProblem
all
new
carbocations
that
might
be
reasonably
expected
towrite
form.
each
of
the
following
alcohols,
write
the
structure
of
alkyloxonium
ion
produced
prowrite
the
structures
all
new
carbocations
that
might
be
reasonably
expected
form.
31. For
30.
For
each
reaction
inof
29,
write
astructure
detailed
mechanism.
structures
of
all
new
carbocations
that
might
be
reasonably
expected
to
form.
of
the
resulting
carbocation;
ififalkyloxonium
the
carbocation
obtained
isstep-by-step
likely
totowater
be
susceptible
to
rearrangement,
write
the
structures
of
all
new
carbocations
that
might
be
reasonably
expected
to
form.
tonation
by
strong
acid;
if the
ion
is
capable
of
losing
readily,
write
theafter
structure
carbocation;
the
carbocation
obtained
isthe
likely
be
susceptible
to
rearrangement,
31.
For
each
of
the carbocation;
following
alcohols,
writeout
the
of
the
alkyloxonium
ionto
produced
after
proof
the
resulting
if
the
carbocation
obtained
is
likely
to
be
susceptible
to
rearrangement,
tonation
by
strong
acid;
if
the
alkyloxonium
ion
is
capable
of
losing
water
readily,
write
the
structure
of the
resulting
carbocation;
if carbocations
the carbocation
obtained
isthe
likely
towater
beexpected
susceptible
to rearrangement,
by
strong
acid;
ifif the
ion
isismight
capable
of
losing
readily,
write
the
structure
OH
OH
For
each
of
the carbocation;
following
alcohols,
write the
the
structure
of
the
alkyloxonium
ionto
produced
after
pro31. tonation
For
each
of
the
following
alcohols,
write
structure
of
alkyloxonium
ion
produced
after
prowrite
the
structures
of
all
new
that
be
reasonably
form.
the
resulting
ifalkyloxonium
the
carbocation
obtained
is
likely
to be
susceptible
to
rearrangement,
of all
all
new
carbocations
that
might
be
reasonably
expected
form.
tonation
by
strong
acid;
the
alkyloxonium
ion
capable
of
losing
water
readily,
write
the
structure
structures
OH
OH
write
the
structures
of
new
carbocations
might
be
reasonably
expected
form.
Athat
AOH
31. of
For
each
of
the carbocation;
following
alcohols,
write the
structure
of
the
alkyloxonium
iontoto
produced
proof
the
resulting
carbocation;
the
carbocation
obtained
islikely
likely
be
susceptible
to
rearrangement,
OH
write
the
structures
of all
new
carbocations
that
be
reasonably
expected
to
form.
of
the
resulting
ififalkyloxonium
the
carbocation
obtained
is
totobe
susceptible
to
rearrangement,
tonation
by
strong
acid;
if the
ismight
capable
of
losing
water
readily,
write
theafter
structure
AAion

(a) CH
CH3CH
CH2CH
CH2OH
OH
(a)
(a) CH33CH22CH22OH

OH
OH
A
AOH
A
(b)
CH
CHCH
3
(b) CH3CHCH3 3
(b) CH3CHCH3

CHCH2OH
OH
(d) (CH3))2CHCH
(d) (CH33)22CHCH22OH

(e) (CH
(CH)3)CCH
(e)
3CCHCH
2CHOH
2OH
(e) (CH33)33CCH22CH2 2OH

C
(CH33))33C
(CH3)3C
(g)
(g)

OH
OH
OH

HH33CC
H3C
(h) HH33CC
(h)
(h) H3C

OH
OH
OH CH
CH3
CH3 3
CH3 3
CH
CH3

(c)CH
CH
3CH
2CH
2CH
2OH
(c)
3CH
2CH
2CH
2OH
(c) CH
33CH22CH22CH22OH
OH
OH
%
%OH
%
(f)
(f)
(f))
(f
''
'
CH
CH
3 3
CH
33

32. Write all products

products of
of the
the reaction
reactionof
ofeach
eachofofthe
thealcohols
alcoholsininProblem
Problem3131with
withconcentrated
concentratedHH
2SO
4 4
2SO
Write elimination
all
products conditions.
of the reaction of each of the alcohols in Problem 31 with concentrated H22SO44
32. under
elimination
conditions.
under elimination conditions.
33. Write all sensible
sensible products
products of
ofthe
thereaction
reactionofofeach
eachofofthe
thealcohols
alcoholsininProblem
Problem3131with
withconcentrated
concentrated
33. aqueous
Write allHBr.
sensible products of the reaction of each of the alcohols in Problem 31 with concentrated
HBr.
aqueous HBr.

378
378
378
Reactions of Alcohols
Reactions
ReactionsofofAlcohols
Alcohols

section number
section
sectionnumber
number
section
number

O
O
OB
OO
RSOR
BBBB
B
RSOR
RSOR
RSOR
RSOR
BBBBO
O
OO
O

8-6
8-6
8-6
8-6

9-1
9-1
9-1
9-1

Cr(VI)
Cr(VI)
Cr(VI)
Cr(VI)

Metal
Metal
Metal
Metal
(M)
(M)
(M)
(M)

9-4
9-4
9-4
9-4
9-4

9-4
9-4
9-4
9-4
9-4

9-6
9-6
9-6
9-6
9-6

9-7
9-7
9-7
9-7
9-7

PX3
PX
PX
PX3333

SOCl2
SOCl
SOCl
SOCl
SOCl2222

RSO2Cl
RSO
RSO
RSO
Cl
2Cl
222Cl
RSO
Cl

RX or

RX
RX
oror
RX
or
RX
orOH
RX,


OH
RX,
RX,
RX,
OH
RX,OH
OH

H, RO



ii O OH
}CCO
orOH
}
}
or
&& ROH
ROH

 OH

OH

OH

OH

8-3,9-2,9-3
8-3,9-2,9-3
Substrate:
8-3,9-2,9-3
Substrate:
Substrate:
NC
AOH

O
O
O
BB
B
RCH(R)
RCH(R)
RCH(R)


H
,
, O
H
H
H
B
O
H,,, O
O
OBBBG
B CO
O
G
CO
G
GC
O
CO
C CCGC
C
G
C
C
C
G
C C
CG
G
G

Substrate:
NC
AOH
NC
NC AAOH
OH
C
C
EC
H
E
CH
E
EH
H

15-12
15-12
15-12
15-12

17-7
17-7
17-7
17-7

18-9
18-9
18-9
18-9
18-9

H
H

OH
OH
OH
OH
RCOR or
RCOR
RCOR
RCOR or
or
H(R)
H(R)
H(R)
OR
H(R)
OR
OR
OR
RCOR
RCOR
RCOR
RCOR
H(R)
H(R)
H(R)
H(R)

20-2
20-2
20-2
20-2
20-2

O
O
O
BB
BO
C
GCBCH
CH
G
G H
H

HH
OO
H
H
lO
H
lO
O
RO
RO CC CC CClll
RO
RO
C
C
C
RO C
C C
C C
Ciii
ii

Cr(VI)
Cr(VI)
Cr(VI)

GG GGG

AA
AA
H
GGCCCH
G
G CH
H

O
O
OOB
BBO
BB
RCCl
RCCl

RCCl
RCCl
8-6 RCCl
8-6
8-6

17-11,24-9
17-11,24-9
17-11,24-9
17-11,24-9


H

AA
AA

BBB B
B

9-4
9-4
9-4
9-4

RCOOH
RCOOH
RCOOH
RCOOH

O
O
BO
B
BO

B

RCH(R),
H
RCH(R),
H

RCH(R),
RCH(R), H
H

GG
GG
GG
GG

Base
Base
Base

XX
X
X GG
CGC CC
(C(G C
(( C C OR
OR
OR
OR

9-4,19-9
9-4,19-9
9-4,19-9
9-4,19-9

H2SO4,
H222SO
SO444,,,

H
H
SO

GGG GGG
GG GG
GGG GGG
GG GG

12-6
12-6
12-6
12-6

ROR
ROR
ROR
ROR
ROR

7-6,9-2,9-3
7-6,9-2,9-3
7-6,9-2,9-3
7-6,9-2,9-3
9-7,11-7
7-6,9-2,9-3
9-7,11-7
9-7,11-7
9-7,11-7

AA
AA

8-3,9-1
8-3,9-1
8-3,9-1


, ,HH
or
or
,, H
H or
or
Lewis
Lewisacid
acid
Lewis
Lewis acid
acid

ROR
ROR
ROR
ROR
ROR

HX
HX
HX
HX

GG GGG
GG GGG

 
M
RO
RO
M
ROM

OO O
OO
O
O
OB BO
OB
BB
BB BBB
RCOCR
RCOCR
RCOCR
RCOCR
RCOCR

HH
,,,ROH
ROH
H
ROH
H, ROH

O
OO
OB
BBO

BB
H
RCOR,

RCOR,
HH

RCOR,
RCOR,
RCOR,H
H

9-1
9-1
9-1

HIO4
HIO
44
HIO
HIO
HIO
44
Substrate:
Substrate:
Substrate:
Substrate:
Substrate:
HO
HO
OHOH
HO
HO
OH
G
GGG G OH
HO
OH
C
G
GOCCOC G
CG
GC
CC
O
(O
OC
CCCC(
( (C
(C
(((
((

OO
O
BO
B
BBO
B
RCOR
RCOR
RCOR
RCOR
RCOR

20-3
20-3
20-3
20-3
20-3

OO
BO
OB
BBO
B
RCOR
RCOR
RCOR
RCOR
RCOR

20-4
20-4
20-4
20-4
20-4

Metal
Metal
Metal
(M)
(M)
(M)
OO
BO
OB
BBO
B
RCOR
RCOR
RCOR
RCOR
RCOR

24-524-5
24-5
24-5
24-5

i i
O OO Of fifiif
O
O
O

O
O f
O

G
G
G&G
&@
& & @@
@

GG
GG
GG
GG


 or
H
H
or
,, H
or
,


HO

HO
HO

GGG GGG

O
O
O

X
X22,,, C
C
X
C
2

BBB

CC
C GC
G
GG

OH
OH
@
& @&
G
GOH
OH
&& @@ GCG G
CG CGCCC
G C
GC
CG
CC(C (
G
((
RORO
G
RO
RO

GG
G
G
XX
2, ,CC CC
X
GG
X22,, 2 C
C C
CG
G

RCl
RCl
RCl
RCl
RCl

9-2
9-2
9-2
9-2

GGG
GGGGG
GG

9-9,25-2
9-9,25-2
9-9,25-2
9-9,25-2



RO
RO
RO

G G
GG
GGG G
GG

OO
O
H

oror
O
Hor
, H

or
,, H, 
HO

HO
HO
HO

H 
H
H
H


H2
RO
RO
H22
RO
H
or
or
or

R
R
R

RX
RX
RX
RX
RX

CCC
C C

Base
Base
Base
Base

Alkene
Alkene
Alkene

B
BBB B

8-3,9-2,9-3
8-3,9-2,9-3
8-3,9-2,9-3
8-3,9-2,9-3

RX
RX
RX
RX

B
BBB B

8-3,9-1
8-3,9-1
8-3,9-1
8-3,9-1

ROM
M
RO
RO
MM
RO

O
O
OB
O
BBB
RCOR
RCOR
RCOR

BBBBB

O
O
OBO
BB B
RCH(R)
RCH(R)
RCH(R)
RCH(R)

fff
fiii f
i i

RO
 
RORO
RO

RO
H

 2
RO
orH
RO
H22H2
RO
or
R
oror
R
RR

G
G
G

C
CG
C
G
G


 or
,, H
,H
H or
or

Lewis
Lewis acid
acid
Lewis
acid

O
O
O
BB
B
RCH
RCH
RCH

P rr oo bb ll eem
m ss
P
m
CCChhhhaaaappppt tetteere
PPrrrooobbbll leeem
m sss
P
CC
h a p t e rr
PPrr oro obbbll eel em
mmss s
P
CC hCh aha pap tpt eet re
Problems
Chapter
P
r
o
b
l
e
m
s
C
P
r
o
b
l
e
m
s
P
r
o
b
l
e
m
s
C
msss
PPrrrooobbbllleeem
m
P
CCCh
hChhha
ahaaap
papppttptte
eetteerrer
P r owith
s
pte
PP
lblleeelmem
sm
CCChhChaahappa
34. Give
Give detailed
detailed mechanisms
mechanisms and
and fifinal
nal products
products for
for the
the reaction
reaction of
of 3-methyl-2-pentanol
3-methyl-2-pentanol
each
3-methyl-2-pentanol
each
Prrrooobwith
bwith
m
pt tet eer rr
b
ss
34.
with
each
34.
Give
detailed
mechanisms
and
fi
nal
products
for
the
reaction
of
3-methyl-2-pentanol
each
34. Give
detailed
mechanisms
and
fi
nal
products
for
the
reaction
of
3-methyl-2-pentanol
with
each
of the
the reagents
reagents that
that follow.
follow.
34. Give
3-methyl-2-pentanol
with
each
of
34.
Give
detailed
mechanisms
and fifinal
nal products
productsfor
forthe
thereaction
reactionofof3-methyl-2-pentanol
3-methyl-2-pentanolwith
witheach
each
of
thedetailed
reagentsmechanisms
that follow.
follow.and
the
reagents
that
34. of
Give
detailed
mechanisms
and final products for
the
reaction ofHBr
3-methyl-2-pentanol with each
of
reagents
that
(a)the
NaH
(b) the
Concentrated
HBr
of
the
reagentsmechanisms
that follow.
follow. and fifinal
(a)
NaH
(b)
Concentrated
HBr
34.
detailed
for
3-methyl-2-pentanol
thereaction
3-methyl-2-pentanolwith
witheach
each
reactionof
of
34.
nal products
(a)
NaH
(b)
Concentrated
HBr
products(b)
forConcentrated
the
reaction
of
3-methyl-2-pentanol
with
each
of
the
reagentsmechanisms
that follow.and
Give
detailed
mechanisms
and fifinal
nal
products
for
the
reaction
of
3-methyl-2-pentanol
with
each
3-methyl-2-pentanol
with
each
34. Give
mechanisms
and
products
for
the
reaction
of
3-methyl-2-pentanol
with
each
(a)
NaH
HBr
(c)
PBr
(d)
SOCl
3
2
(c)
PBr
(d)
SOCl
3
2
(a)
NaH
(b)
Concentrated
HBr
of
the
reagents
that
follow.
3
2
Give
detailed
mechanisms
andfifinal
nal products(d)
forthe
thereaction
reaction
3-methyl-2-pentanol
with each
follow.and
34. Give
detailed
mechanisms
for
ofof
3-methyl-2-pentanol
with
(c)
PBr
(d)
SOCl
(a)
NaH
(b)
Concentrated
HBr
of
the
reagents
that
follow.
of
reagents
that
(c)
PBr
33
22 H2SOof
34.
3-methyl-2-pentanol
witheach
each
Give
detailed
mechanisms
final products
products (d)
for
the
reaction
with
each
(e)the
Concentrated
H22follow.
SO44 at
atand
130C
(f) SOCl
Dilute
in3-methyl-2-pentanol
(CH33))33COH
COH
(a)
NaH
(b)
Concentrated
COH
(e)
Concentrated
H
SO
130C
(f)
Dilute
H 2SO
SO444HBr
in
(CH
(c)
PBr
SOCl
2follow.
4 at 130C
3) 3COH
the
reagents
that
follow.
333
22 2H
of
reagents
that
(e)
Concentrated
H
SO
(f)
Dilute
in
(CH
(c)the
PBr
(d)Dilute
SOCl
(a)
NaH
(b)
Concentrated
4 HBr
(e)
Concentrated
H
SO
(f)
H 22SO
in
(CH
Concentrated
HBr
22follow.
44 at 130C
33)33COH
(a)
NaH
of
the
reagents
that
(b)
Concentrated
HBr
(c)
PBr
(d)
SOCl
(b)
Concentrated
HBr
(a)
NaH
(b)
Concentrated
33
2 2H22SO44 HBr
COH
(e)
Concentrated
H
130C
(f)
Dilute
44 at
4 inin(CH
33)33)COH
(e)
Concentrated
H2222SO
SO
atconverted
130C into
(f)
Dilute
H2 SO
(CH
(c)
PBr
(d)
SOCl
35. (a)
Primary
alcohols are
are
often
converted
into
bromides
by
in
H
SO
.
Explain
how
44 at
22SOHBr
44with
33 COH
33COH
NaH333alcohols
(b)
Concentrated
HBr
2reaction
(c)
PBr
NaH
(b)
Concentrated
2
4
with
NaBr
in
H
SO
.
Explain
how
SOCl
(e)
Concentrated
H
SO
130C
(f)
Dilute
H
in
(CH
)
(d)
SOCl
35.
Primary
often
bromides
by
reaction
NaBr
in
H
SO
.
Explain
how
(d)
SOCl
2
2
4
(c)
PBr
(d)
SOCl
2 often
4 converted into bromides
4with
3 3 in H 2SO 4. Explain how
2222 2
35.
Primary
alcohols are
are
by reaction
reaction
NaBr
(a)
NaH3alcohols
(b) Dilute
Concentrated
HBr
35. Primary
often
converted
into
bromides
by
with
NaBr
in H22SO
.that
Explain
(e)
Concentrated
H
SO
130C
(f)
H
in
)method
this PBr
transformation
works
and
why itit
might
be
considered
method
to444that
usinghow
conPBr
(d)considered
SOCl
4 at
3method
3)COH
(d)
SOCl
35. (c)
in
H22SO
SO
. Explain
how
(e)
H2SO
SO
in(CH
superior
to
that
using
conDilute
atconverted
(CH
COH
130C
Concentrated
H2222works
SO
(f)
Dilute
H
SO
in
(CH
COH
at
130C
(f)
Dilute
H
in
(CH
COH
this
transformation
and
why
might
be
aa 44superior
to
using
con33alcohols are
2 2H
Primary
often
bromides
by
NaBr
H
how
COH
(e)
Concentrated
H
SO
130C
(f)
Dilute
SO
(CH
2SO
44in
33in
4. Explain
44with
444 at
333)33)33)3COH
method
to
that
using
con(c)
PBr
(d)
SOCl
35.
Primary
often
converted
into
bromides
byreaction
with
NaBr
how
3 alcohols are
2 2222a superior
this
transformation
works
and
why
itinto
might
be
considered
method
to
that
using
con2reaction
22SO
4. Explain
35. (e)
Primary
alcohols
often
converted
into
bromides
by
reaction
with
NaBr
ininHH
SO
how
centrated
aqueousare
HBr.
Concentrated
SO
atand
130C
(f)considered
Dilute
(CH
)COH
2to
4.4Explain
Concentrated
HHHBr.
130C
(f)
Dilute
HH
in
(CH
)33COH
method
to
that
using
con2SO
2aSO
4 in
3COH
2works
44 at
2SO
4superior
3method
centrated
aqueous
this
transformation
why
it
might
be
that
using
con(e)
HHBr.
SO
130C
(f)
Dilute
H22SO
in
(CH
this Concentrated
transformation
and
why ititinto
might
be considered
considered
to
usinghow
con35. Primary
Primary
alcohols
are
often
bromides
by
reaction
with
NaBr
in
H
SO
Explain
2works
4 atconverted
44superior
33)method
33COH
centrated
aqueousare
2SO
4..that
Primary
reaction
with
bromides
byreaction
often
NaBr
inH
H
SO
.Explain
Explain
how
this
transformation
works
and
why
might
be
aasuperior
method
that
using
con35.
converted
often
converted
into
bromides
by
reaction
with
NaBr
in
H
SO
Explain
how
alcohols
are
into
bromides
by
reaction
with
NaBr
in
H
SO
Explain
how
in
H
SO
how
alcohols
often
converted
into
bromides
with
NaBr
in
how
22
222to
444.4.4.Explain
NaBr, H
H22SO
SOby
centrated
aqueous
HBr.
4
NaBr,
H
SO
NaBr,
2
44
centrated
aqueousare
HBr.
this
transformation
works
and
might
be
aaaaasuperior
method
to
that
using
conNaBr,
H2considered
SO
35. Primary
alcohols
often
into
bromides
with
NaBr
in in
H SO
.that
Explain
how
4by
Primary
alcohols
are
often
converted
into
bromides
byreaction
reaction
with
NaBr
SO
. Explain
how
CH
CH
CH
CH
CHconverted
CHwhy
CH2it
OH
considered
NaBr,
H
SO
works
and
superior
method
to
that
using
concentrated
aqueous
HBr.
4that
why
it
2to
4Explain
works
and
why
might
be
considered
to
using
contransformation
might
be
considered
method
that
using
conCH
Br
method
to
that
using
con3CH
2superior
2CH
2Br
this
transformation
works
and
why
it
might
be
considered
superior
method
to
using
con2it
CH
CH
CH
CH
CH
CH
OH
2CH
2method
35. Primary
in H2H
SO
how
alcohols
are
often
converted
into
bromides
reaction
with
NaBr
how
33CH
2superior
22CH
33CH
22CH
22CH
NaBr, H
H2SO
SO4 by CH
CH
OH
22SO
44.. Explain
NaBr,
22Br in Hto
centrated
aqueous
HBr.
33 a a
22 superior
22
2method
33
22andwhy
22why22ititmight
this
transformation
works
and
be
considered
superior
that
using
contransformation
works
might
be
method
to
that
using
conNaBr,
H
SO
22considered
44
centrated
aqueous
HBr.
NaBr,
H
SO
centrated
aqueous
HBr.
CH
CH
CH
Br
CH
CH
CH
CH
CH
OH
NaBr,
SO4
method
to that
that using
using conconthis transformation works
and
why
might
beH2considered
a 22superior
to
22 CH
22method
22 CH
22 CH22itOH
CH
CH33CH
CH3333CH
CH
36. centrated
3CHCH
22reactions?
22
22Br
2
2
2 of each
What
are aqueous
the mostHBr.
likely
product(s)
the following
reactions?
CH
CH
36.
NaBr,of
H SO
centrated
aqueous
HBr.
3 3 2reactions?
2CH
2Br
3 product(s)
22CH22CH22OH
36.
NaBr,
Hthe
SO4444following
What
are aqueous
the
most HBr.
likely
of each
ofH
NaBr,
H
NaBr,
H
SO
centrated
NaBr,
22SO
22SO
CH
CH
CH
Br
CH
CH
CH
CH
CH
OH
2CH
2Br
2CH
36. What are the most CH
CH2222reactions?
CH
likely
product(s)
of
ofH HSO
the
following
CH3333CH
CH
Br
CH
CH2222CH
CH
CH22222OH
CH
CH
OH
CH
CH
CH
Br
CH
CH
CH
CH3333CH
OHeach
NaBr,
22222CH
22222Br
33CH
22CH
222CH
CH
NaBr,
SO4 following
CHthe
2the
CH
36.
What are
are
most CH
likely product(s)
product(s)
of each
of
reactions?
33the most
333 CH
NaBr,
H 2the
SO
36. What
likely
of
of
reactions?
4 following
CH
CH
CH
CH
CH
CH33CH
CH2CH
OHeach
333CH
2CH
2Br
2CH
2OH
% 33 most
3 2 reactions?
2CH
2CH
2Br
2CH
2CH
2of
Conc.
HI
CH
CH
CH
Br
CH
HI
36. What
are
likely
product(s)
the
following
CH
2Conc.
CH
22CH
2Conc.
22HI
3CH
2CH
2CH
2OH
CH
CH
OH,
H22SO
SO
% 33the
3CH
2OH,
4
333
Conc.
HI
CH
H
36.
What
mostCH
likely
product(s)
of each
eachof
of
the
following
reactions?
product(s)
of
each
of
the
following
reactions?
the
most
likely
product(s)
of
each
of
the
following
reactions?
33CH
22OH,
2SO 44
following
reactions?
Conc.
HI
CH
(b)
(a) are
CH
OH
CH
CCH
OH
CH
H
3CH
2OH,
2SO
4
$ OH
33the
33 222OH
H
3CCH
(b)
(a)
%
CH
CH
CH
3
$
3
3
Conc.
HI
3
Conc.
HI
$
OH
(b)
(a)
CH
CCH
OH
36.
most
likely
product(s)
ofofeach
following
CH
CH2OH,
OH,
H2SO
SO4
3CH
33CH 22 reactions?
H
36. What
What are
are
the
mostCH
likely
product(s)
eachof
ofthe
the
following
reactions?
CH
%% the
Conc.
3the
36.
What
are
most
likely
product(s)
of each
of
the
reactions?
(b)
(a)
Conc.HIHI
HI
$ OH
CHfollowing
3CCH
CH
H
Conc.
3CH
CH
CH
CH
CH33333322OH
CH
CH
CH2OH,
OH,
H22SO
SO444
33CH22OH, H2SO
(b) CH
(a) CH
%% 33$
OH CH
CH33CH
CCH
CH
$OH
3CCH
2OH Conc. HI
(b)
(a)
3 OH
3CH
CH
CH CH OH, H SO
3
3333332 2
CH
CH
CH
Conc.
Conc.
HI
Conc.
HI
Conc.HI
HI
Conc.
HI
(b)
(a)
CH
CH
CH
OH
CH
CH
H
CH
CCH
OH
CH333CH
CH222OH,
OH,H
H222SO
SO44444
22OH,
22SO
%% 33$
(b)
(a) CH
(b)
OH
CCH
CCH
OHConc.
OH
CH
3333 2
CH
(b) CH
CH33333CH
HI HI
OH CH 33CH
CH
CCH
OH
$
222OH
2$
OH
3CCH
2OH
2
%
OH,
H
SO
Conc.
CH
2
OH
CH
CH3CH
CHOH,
CH
Conc. HI
HI
Conc.
2OH, H2SO4
(b)
(a)
3 233OH
H 2SO 4
3CCH
3
2
(b)CH
(a) CH222$
OH CH
CH
CCH
OH
$OH
CH
I
3CH
2OH
(b)
(a)
OH
CH
CCH
CH
3 OH
33CH
OH
CH222$
CH
CH
CH3333322 II
CH
OH
CH
Conc. H
H SO
SO , 180C
180C
H22O
O
Conc.
CH3333333 I
H
CH
Conc.
H2222SO
SO444,4,, 180C
180C
HH
O2O
H
OH Conc.
2O
H
(c) CH
(d) CH
CH
I
CH3CH
C 3333 CHCH
CHCH
(c)
(d)
CH
I
3C
CH
3H
CHCH
CH222OH
OH Conc. H 2SO 4, 180C
3
3
H
O
C
3
2O
(c)
(d)
3
33
4 (c) CH
I
Conc.
SO
180C
O
3 CHCH
(d) CH333CH
Conc.HH
H222SO
SO444,,,180C
180C
C
2
H
2O
OH Conc.
CH2OH
CH
2O
33 HH
CH
CH
CH
33333 IIII
(c) CH22OH Conc. H SO , 180C
(d)
CH
C
CHCH
(c)
(d)
CH
CH
C
3
CHCH
H
O
3
3CH
3 33333 I
33 H
Conc.
CH
Conc.
H
SO
180C
H22222SO
SO444,44,,180C
Conc.H
H
180C
HH
3 3 CHCH
2O
H
O
2O
2O
(c)
(d)
2O
CH
II
CH
CCH
3CH
3
Conc. H SO , 180C
(c)
(d)
CH
3333 CHCH
(d)
CH
CHCH
(d)of
CHCH
(c) the expected
CH
C of
CH
C
CHCH
3333C
33333H O
3C
Conc.
SO4product
180C of
37. (c)
ofthe
thereaction
reaction
each
the
Problem31
31with
withPBr
PBr..333...
CH
Conc.
HH22SO
,4,180C
2O
alcohols
inProblem
Problem
31
with
PBr
Give
main
the
reaction
of
each
the
alcohols
in
Problem
31
with
PBr
CH
HH
O
(d) of
CH
CH
CHCH
2O
37.
Problem
31
with
PBr
3 33the
Give
expected
main
product
of
each
ofof
alcohols
in
3C
3 H
3
(c) the
(d)
CH
CHCH
(d)
(c)
C
CHCH
3Cof
CH
37. Give
Problem 31
31 with
with PBr
PBr333..
the expected
main
of Problem
the
reaction
ofCH
each
alcohols
in Problem
33CH
33 3
3 the
Problem
33.
Compare
the results
results
withproduct
those of
of
Problem
33.
Compare
the
with
those
33.
CH
CH
CH3of
3333 the
37.
expected
main
product
of
the
reaction
of
each
thealcohols
alcoholsininProblem
Problem3131with
withPBr
PBr
Give the expected
main
product
of
the
of
37. Compare
expected
main
product
ofProblem
the reaction
reaction
ofeach
each
CHof
3. 33..
the results
withproduct
those of
33. of
3of the alcohols in Problem 31 with PBr
CH
37.
Give
the
expected
main
of
the
reaction
each
of
the
alcohols
in
Problem
31
with
PBr
.
CH
3
3
38.
the
following
reagents.
3
Compare
the
results
with
those
of
Problem
33.
3
Give
the
expected
product(s)
of
the
reaction
of
1-pentanol
with
each
of
the
following
reagents.
the
with
those
33.
eachofof
the
following
reagents.
37. Give
the
main
product
the
reaction
in
Problem
31
PBr
Compare
the results
results
with
those
Problem
33.
Problem
31
with
PBr
of
38.
the
following
reagents.
product
of
the
reaction
of
each
of
the
alcohols
in
Problem
31
with
PBr
33.....
expected
thealcohols
37.
ofProblem
product
alcohols
in
Problem
31with
with
PBr
main
the
reaction
ofeach
each
of
the
alcohols
in
Problem
31
with
PBr
the expected
expected
product(s)
of of
the
reaction
of of
1-pentanol
with
each
the
following
reagents.
eachof
ofthe
Compare
the
results
with
those
Problem
33.
37. Give
the expected
main
product
the
reaction
each of the
alcohols
in the
Problem
31 with
PBr3. 333
38.
the
following
reagents.
expected
product(s)
of of
the
reaction
ofof
1-pentanol
with
each of
following
reagents.
Compare
the
results
with
those
of
Problem
33.
12expected
those
of
Problem
33.
expected
main
product
of
the
reaction
of
each
of
the
alcohols
in
Problem
31
with
PBr
.
12
of
Compare
the
results
with
Problem
33.
those
Give
the
main
product
the
reaction
of
each
of
the
alcohols
in
Problem
31
with
PBr
..Li
37.
Problem
31
with
PBr
3Li
12
33Li
(b)
Sodium
metalwith
(c)CH
CH
38.
expected
product(s)
of
the
reaction
of
1-pentanol
with
each
the
following
reagents.
(c)
CH
Give
expected
reaction
of
1-pentanol
reagents.
(a) K
Kthe OC(CH
OC(CH
(b)
Sodium
metal
(c)
CH
the
results
with thoseof
Problem
33.
38. Compare
expected
product(s)
ofofthe
the
reaction
of
1-pentanol
witheach
eachofof
ofthe
thefollowing
following(c)
reagents.
(c)
CH
33))333product(s)
333Li
(a)
(b)
Sodium
metal
3Li
3
3
12
Compare
the results
results
with those
those
of Problem
Problem
33.
38. Give
the
expected
product(s)
of
the
reaction
of
1-pentanol
with
each
of
the
following
reagents.
Compare
the
with
of
(c)
CH
Li
(a)
K
OC(CH
(b)
Sodium
metalHCl
(c)
CH
(e)33.
Concentrated
HCl
(f)FSO
FSO
H
3)3HI
33Li
(f)
FSO
H
(d)
Concentrated
HI
(e)
Concentrated
HCl
(f)
FSO
the
expected
product(s)
of
the
reaction
of
1-pentanol
with
each
of
the
following
reagents.
38. Give
the
following
reagents.
(f)
FSO
H
12
product(s)
of
the
reaction
of
1-pentanol
with
each
of
the
following
reagents.
333H
12
(d)
(e)
Concentrated
(f)
1-pentanol
witheach
eachof
38.
thereaction
GiveConcentrated
the
expected
reaction
of
1-pentanol
with
each
of
the
following
reagents.
product(s)of
ofthe
ofthe
the
following
reagents.
3H
12OC(CH
3Li
OC(CH
(b)
Sodium
metal
(c)
CH
Li
(a)
Kthe
(b)
Sodium
metal
(c)
CH
38. Give
expected
product(s)
of
1-pentanol
with
following
reagents.
33
33H
OC(CH
)
(b)
Sodium
metal
(c)
CH
Li
333))
3HI
3
(f)
FSO
(d)
Concentrated
(e)
Concentrated
HCl
(f)
FSO
H
12
3
130C
(h)of
Concentrated
H22SO
SO4each
180C
(i)CH
CH
SO
Cl,(CH
(CH
CH
)333N
N
at180C
180C
(i)
CH
SO
Cl,
(CH
CH
N
(g) K
Concentrated
H
SO44 at
at 130C
130C
(h)
Concentrated
180C
(i)
CH
(CH
2SO
4 at
2))N
(i)
CH
SO
Cl,
(CH
CH
(a)
(b)
Sodium
metalwith
(c)
Li
22SO
3333SO
222Cl,
333CH
expected
product(s)
of the
the reaction
reaction
of
1-pentanol
with
ofthe
thefollowing
followingreagents.
reagents.
12
(g)
Concentrated
(h)
Concentrated
HH
(i)
the
expected
product(s)
of
1-pentanol
of
38. Give
the
following
reagents.
12
3)3H
2 2 each
444at 180C
33SO
22Cl,
33CH
22))2323N
12OC(CH
Concentrated
HI
(e)
Concentrated
(f)
FSO
(d)
Concentrated
HI
(e)
HCl
(f)
FSO
H
(a)
K
(b)
Sodium
metal
(c)
CH
Li
(c)
CH
33H
Concentrated
HI2 4
(e) Concentrated
Concentrated
HCl
(f)CH
FSO
(b)
Sodium
metal
(c)
CH
33Li
180C
(i)
SO
Cl,
(CH
CH1
)1
NH
3SO
12 OC(CH
(g)
Concentrated
H
(h)
Concentrated
HHCl
(i)
(CH
CH
N
metal
K
OC(CH333)))33HI
(b)
Sodium
metal
(c)
CH
Li
(c)
CH
Li
3Li
Sodium
33Cr
2Cl,
3SO
2)1
22SO44 at 180C
32Cr
2H
3SO
33H
(k)
SOCl
(l)
K
Cr
O
1
HSO
H
O
3 2SO4 at 130C
3H
(l)
K
O
1
H
H
O
((a)
j) K
PBr
(k)
SOCl
(l)
K
O
1
2
2
71
(l)
K
Cr
O
HH
O
(a)
OC(CH
(b)
Sodium
metal
(c)
CH
Li
2
2
2
4421
Concentrated
(e)
Concentrated
HCl
(f)
FSO
3
2
2
2
771
222SO
41
222O
((d)
j)
PBr
(k)
SOCl
(l)
K
Cr
O
H
HN
O
23 322SO
3 3H
3
22
2CH
77Cl,
22SO
44CH
12
12
Concentrated
H
SO
at
130C
(h)
Concentrated
H
180C
(i)
Cl,
))3222N
(g)
(h)
H
SO
180C
(i)
CH
(CH
(d)
Concentrated
HI
(e)
HCl
(f)
FSO
H
(f)
FSO
H
22SO
21
22H
(e)
Concentrated
HCl
(f)
FSO
H
4 44atat
33SO
3CH
H222SO
SO44 at
at 130C
130C
(h)Concentrated
Concentrated
H2H
SO
at(as
180C
(i)
SO
Cl,H
N
3Li
(l)
K
Cr
O
H(CH
SO
12)3H
O
OC(CH
(b)
Sodium
metal
(c)
K
(b)
Sodium
metal
(c)
CH
Li
((a)
j) Concentrated
PBr
(k)
SOCl
(l)
K
Cr
1
O
Concentrated
HCl
(c)
CH
(d)
Concentrated
(e)
Concentrated
(f)
FSO
(f)
FSO
H
21
2CH
2SO
3HI
3OC(CH
22))33COH
2CH
233323O
727Cl,
2(CH
4433CH
(n)
(CH
COH
1
H
catalyst)
3SO
3Li
3H
(m)
PCC,
CH22Cl
SO
(as
catalyst)
Cl332)2)3HI
(n)
(CH
1
catalyst)
catalyst)
(d)
(e)
Concentrated
HCl
(f)
FSO
H
(g)
Concentrated
H
SO44 at
at 130C
130C
(h)
Concentrated
HHCl
SO
at
180C
(i)
CH
(CH
CH
)1
N23H
22SO
(m)
PCC,
CH
(n)
(CH
1
H
catalyst)
4444(as
2SO
2SO
4 4at
33SO
2O
3SO
2)
3H
333)33333COH
222SO
(k)
SOCl
(l)
K
Cr
1
H
((m)
j)
PBr
(k)
SOCl
(l)
K
Cr
O
1
H
SO
1
O22O
(g)
Concentrated
H
(h)
Concentrated
H
180C
(i)
CH
Cl,
(CH
CH
N
180C
(i)
CH
SO
Cl,
(CH
CH
)
N
77Cl,
442221
2 32233Cr
2SO
72Cl,
2 2233SO
4CH
2H
130C
(h)
Concentrated
H
180C
(i)
CH
222SO
444 44at
3)3)3)N
( j) Concentrated
PBr333 CH2Cl2 H
(k)
SOCl
(l)
K
1(CH
H
O
catalyst)
2O
Concentrated
HI
(e)
Concentrated
HCl
(f)
FSO
Concentrated
HI222SO
(e) Concentrated
Concentrated
HCl
(f)
FSO
PCC,
(n)
(CH
H
SO
(as
catalyst)
(f)
FSO
H
130C
H
at
(g)
H
SO444 atat
(h)
H
180C
(i)
CH
(CH
33CH
at130C
180C
(i)
CH
SO
Cl,
(CH
N
2SO
Concentrated
33SO
3222H
33)23322COH 1
222SO
44 at
221
2H
3H
3CH
2 33N
(g)
(h)
H
180C
(i)
CH
(CH
)3N
(((d)
j)
PBr
(k)
SOCl
(l)
K
Cr
O
H
SO
O
2
4
2SO
4 at
3SO
2Cl,
3CH
21
3
2
2
2
7
2
4
2
(m)
PCC,
CH
(n)
(CH
)33trans-3-methylcyclopentanol
HH
SO
(as
catalyst)
CH
Cl
(n)
(CH
(as
catalyst)
j)
PBr
(k)
SOCl
(l)
K
1
H
1
(l)
K
Cr
O
1
HHH
1
H
3trans-3-methylcyclopentanol
4 44
(k)
SOCl
(l)
K
Cr
OO
1
SO
1
H
OO
33COH
22SO
2223))COH
2CH
232O
727Cl,
2(CH
4434CH
23H
(m)
PCC,
CH22Cl
Cl22 Hproduct(s)
(n)
(CH
COH11
1
H
SO
(as
catalyst)
the333 expected
of the
the reaction
reaction
of trans-3-methylcyclopentanol
witheach
each
of
the
22Cr
2SO
2O
(g)
Concentrated
(h)
Concentrated
HH
180C
(i)
CH
SO
CH
)H
Concentrated
SO44 atat 130C
130C
(h)SOCl
Concentrated
at
180C
(i)
)H
N
180C
(i)
CH
SO
(CH
CH
)33H
N
trans-3-methylcyclopentanol
with
each
of
the
expected
product(s)
of
the
reaction
of
trans-3-methylcyclopentanol
with
each
of
the
(Give
j) PBr
PBr
(k)
SOCl
(l)
K
1
2SO
7Cl,
2SO
2O
(l)
K
Cr
1
H
1
O
39. (Give
with
each
of
SOCl
22SO
22SO
44 4at
323Cr
2O
22SO
2N
3SO
the
of
of
with
the
2the
727Cl,
223SO
44221
j)
(k)
(l)
Kof
H(CH
(m)
PCC,
CH22Cl
Cl22H
(n)
(CH
2)322COH 1 H2SO4 (as catalyst)
2Cr
2O272 1
2SO
4 1
2O 22
39. Give
trans-3-methylcyclopentanol
with each
each
of
the
the33in
expected
of the reaction
of 33trans-3-methylcyclopentanol
with
the
(m)
PCC,
CH
(n)
(CH
1
catalyst)
catalyst)
22 Cl22 product(s)
444 (as
(n)
(CH
COH
1
SO
(as
catalyst)
((m)
j) PBr
(k)
SOCl
(l)
K
H
H
O
reagents
333)32)2)33)323COH
(k)(CH
SOCl
(l)(l)of
K2K
Cr
O27O
H2H
SO
1
H22H
O2O
Problem
38.
PCC,
CH
(n)
(CH
1
H
catalyst)
1HHH
H222SO
SO
(ascatalyst)
catalyst)
(CH
COH1
22O
44 1
3inCH
2Cr
711
2SO
4 1
2Cr
71
2SO
reagents
Problem
38.
22SO
3COH
4 (as
(m)
PCC,
(n)
)trans-3-methylcyclopentanol
(as
22Cl22 product(s)
3trans-3-methylcyclopentanol
3COH
2SO
4 4
Give
the
expected
of
the
reaction
of
with
each
of
the
39.
expected
product(s)
of
the
reaction
of
with
each
of
the
39. Give
GivePCC,
theinexpected
expected
product(s)
of the
the reaction
reaction
of3trans-3-methylcyclopentanol
trans-3-methylcyclopentanol
witheach
eachofofthethe
reagents
Problem
38.
(m)
CH
(n)
catalyst)
PCC,
CH
Cl22 product(s)
(n) (CH
(CH
1HH
(ascatalyst)
catalyst)
22Cl
22SO
44 4(as
39.
the
of
of
with
3)333)COH
3COH1
2SO
reagents
in
Problem
38.
the
expected
product(s)
of
the
reaction
of
trans-3-methylcyclopentanol
with
each
of
the
Suggest
method
for preparing
preparing
each
ofthe
thefollowing
haloalkanes
from
the
corProblem
38.
39. Give
trans-3-methylcyclopentanol
with
each
ofof
the
good
followinghaloalkanes
haloalkanes
from
the
corsynthetic
method
for
preparing
each
of
the
following
haloalkanes
from
the
cor40.
haloalkanes
from
the
corGive
the
expected
product(s)
of
the
reaction
of
trans-3-methylcyclopentanol
with
each
the
Suggest
good
synthetic
for
each
of
from
the
correagents
in
Problem
38. method
39.
of the
the
reaction
of
trans-3-methylcyclopentanol
with
each
the
Give
theaaain
expected
product(s)
trans-3-methylcyclopentanol
with
each
of
the
39. Give
the
expected
product(s)
of
trans-3-methylcyclopentanol
with
each
ofof
the
reagents
Problem
38.
40.
haloalkanes
from
the
corSuggest
good
synthetic
method
for reaction
preparingofeach
of the following haloalkanes
from
the
correagents
Problem
38.
alcohols.
responding
alcohols.
reagents
in
Problem
38.
Give
the in
product(s)
of
reaction
trans-3-methylcyclopentanol
with
each
of
the
39. reagents
trans-3-methylcyclopentanol
with
each
ofof
the
expected
product(s)
of the
the
reaction ofof
trans-3-methylcyclopentanol
with
each
the
reagents
inexpected
Problem
38. method
Problem
38.
Suggest
good
synthetic
for
preparing
each
ofof
the
following
haloalkanes
from
the
cor40.
good
synthetic
method
for
preparing
each
the
following
haloalkanes
from
the
corSuggest aain
responding
alcohols.
40.
good
synthetic
method
for
preparing
each
of
the
following
haloalkanes
from
thecorcorCl
Cfollowing
H333C
Cl
40. reagents
Suggest
a
good
synthetic
method
for
preparing
each
of
the
haloalkanes
from
the
C
H
in
Problem
38.
Cl
H
3
I
CH
in
Problem
38.
3
I
I
CH
I
I
CH
3
3
3
responding
alcohols.
a good
synthetic
method
for
preparing
each
of
the
following
haloalkanes
from
the
cor40. Suggest
haloalkanes
from
the
coralcohols.
method
for
preparing
each
of
the
following
haloalkanes
from
the
corresponding
Cl
alcohols.
Cfollowing
Suggest
good
synthetic method
methodfor
forCH
preparing
each
of
following
haloalkanes
from
the
cor40.
following
haloalkanes
from
the
cor3the
eachof
ofH
3the
II from
Suggest
aa good
synthetic
preparing
each
the
haloalkanes
the
cor3
responding
alcohols.
responding
alcohols.
Cl
C
H
responding
alcohols.
Suggest
a
good
synthetic
method
for
preparing
each
of
the
following
haloalkanes
from
the
cor3
I
CH
Cl
C
H
40. responding
haloalkanes
from
the
cor3
I
CH
a good
for
preparing
haloalkanes
(c)of the
CH
CH
CHCH
Br each
CHCH(CH
CH
responding
Suggest
333 22Br
(b)method
(c)
(d)
(d)
CH
Cl
CH33CH
CH
CHCH
CH
CH2synthetic
CHCH(CH
CH
(a)
(b)
(c)
(d)
CH33CH
CH
Cl
CH
CH
alcohols.
3 following
I from33)the
CH
2Br
3CHCH(CH
2alcohols.
22CHCH
3CHCH(CH
3)3232)))222 cor3I3CHCH(CH
Cl
3
CH3CH22alcohols.
CH22Cl
CHCH
CHCH(CH
CH333CHCH(CH
(a)
(b) CH33 CH22CH
(c) H
(d) CH
Cl
CC
HH3333C
responding
2 Br
33))22
II
CH
responding
alcohols.
3
CH
Cl
C ClCl
H
Cl (d)
HH
33C
CH
I
3C
I IICHCH(CH
CH
(a)
(b)
(c)
CH
CH
CH
Cl
CH
CH
CHCH
CH
3333 22Br
(b)
(c)
(d)
CH
Cl
CH
CH
CHCH
Br
CH
3CHCH(CH
3)32))2
(a) CH
CH333CH
CH222CH
(b) CH
(c) HH33CC ClCl (d)
(d)CH
CH222Cl
Cl
CH333CH
CH222CHCH
CHCH
CH
2Br
3 2
(a)
(b)
(c)
I3I3CHCH(CH
Br
CHCH(CH
3CH2CH
2Cl
3CH2CH
3CHCH(CH
3))2
3
I
CH33 22Br
(a)
(b)
(c)
(d)
CH
CH
CHCH
CH
CHCH(CH
))22
CH
3
2
2
3
2
3
3
(a) CH
(b)
(c)
(d)
CH
CH
CH
Cl
CH
CH
CHCH
Br
CHCH(CH
CH
3
3
41. (a)
Name
each
of
the
following
molecules
according
to
IUPAC.
molecules
according
to(c)
IUPAC.
molecules
according
to
IUPAC.
333CHCH(CH
(b) CH
(d)
CH333CH
CH222of
CHthe
Clfollowing
CH
CH22CHCH
CH
(d)CH
(b)
(c)
(d)
CHCH(CH
CH
CH
(c)
22CHCH
22Br
222Cl
333CH
22Br
3CHCH(CH
3)3233)2)22
41. Name
each
of the
following
molecules
according
to(c)
IUPAC.
(a)
(b)
(d)
CH
CH
CH
CHCH(CH
CH
33CH
22CH
22Cl
33CH
22CHCH
2Br
33CHCH(CH
33))232)2
(a)
(b)
(c)
(d)
CH
CH
CH
Cl
CH
CH
CHCH
Br
CHCH(CH
CH
2
3
41.
Name
each
of
the
following
molecules
according
toto
41.
Name
each
of
the
following
molecules
according
IUPAC.
41. Name
Name each
each of
of the
the following
following molecules
moleculesaccording
accordingto
toIUPAC.
IUPAC.
41.
Name
each
of
the
following
molecules
according
to IUPAC.
IUPAC.
41. Name
CH33OCH
OCH
CH2222OH
OH
CH
CH
CH
(c)
(a)
(b)
(c)
(b)
(c)
CH333
CHOCH
(CH
OO
Name
each
of
the
following
molecules
according
IUPAC.
3OCH
2OH
222CH
O
222CH
33))22CHOCH
each
of
molecules
according
toto
each
of the
the following
following
molecules
according
to
IUPAC.
41.
IUPAC.
Name
toIUPAC.
CH3OCH
(a)
(b)
(c)
(CH
O
2CH22OH
3)2CHOCH2CH3
each
of
the
following
molecules
according
totoIUPAC.
41.
41. Name
Name
each
of
the
following
molecules
according
IUPAC.
CH
OCH
CH
OH
(a)
(b)
(c)
CH
CHOCH
(CH
)
OO
3
2
2
2
2
3
3
CH
OCH
CH
OH
(a)
(b)
(c)
CH
CHOCH
(CH
33OCH
22CH
22OH
CH
(a) (CH
(b) H
(c)
CH333
CHOCH222CH
(CH333)))222CHOCH
OCH
H
C
H
C
OCH
OCH
O
333C
CH
3332OH
(a)
(b)
(c)
O
3OCH
2CH
CH
OCH
OH
CH
H
(CH
) CHOCH
OCH
(a)
(b)
(c)
O
222CH
3C333OCH
3 22OH
CH
OCH
CH
OH
(a)
(b)
(c)
CH
CHOCH
(CH
(a)
(b)
CH
(b) CH
(c)
OO
CH333333
CHOCH222222CH
(CH333333)))222222CHOCH
3 33OCH
2CH
2 222OH
(c)
O
OH (c)
22CH
(a) (CH
O
H
OCH
33C
33 OH
H
OCH
!
CH
!
(a)
(b)
(c)
OO
CH
(g)
CH
OCH
Cl
H
C
(d)
(e)
(f(f
)))CH
(g)
#
!
O
CH
OCH
CH
#OO
!
(ClCH
!
3OCH
2CH
CH
CH
CH333O
O#
O
CH
(e)
(g)
CH
O22CH
(f
(g)CH
CH
OCH
Cl
O
CH
(ClCH
(g)
CH
OCH
Cl
3))22CHOCH
CH22))22O
33
H
CC
OCH
33OCH
22Cl
333OCH
222Cl
CH
33O
(a) (CH
(b) H
(c)
CH33
33C
(CH
3 3222OH
3OCH
2CH
3 22CHOCH
!O
#
!
OCH
OCH
CH33333 (g)
CH
O
(g) CH
CH33OCH
OCH
Cl
(d)
(e)
(f
)
CH
O
(ClCH
)
3
3
33
22Cl
2 2
2
C OCH
OCH
HH
H333C
OCH33333
33C
#
!
OO
CH
(d)
(e)
(f(f) ) CH
(g)
CH
CH
(ClCH
)O
3O
33
3OCH
2Cl
#
!
CH
O
CH
(d) (ClCH
(e)
(g)
CH
OCH
CH
O
(ClCH
#
!
3
3
22Cl
CH
O
O
CH
(e) HH33CC OCH
(f
)
(g)
CH
OCH
Cl
CH2222)))2222O
O
(ClCH2222CH
3
#
!
CH
O
O
CH
3
3
(d)
(e)
(f
)
(g)
CH
OCH
Cl
3
OCH3
!
(d) (ClCH CH ) O
(e)
(f ) CH33O #
(g)
!O
OCH
CH33
(g) CH
CH3OCH
OCH2Cl
Cl

Problems

Chapter 9

anol with each

2
2

2
2

3
3

2
2

O . Explain how
that using con-

2
2

2
2

4
4

4
4

4
4

2
2

2
2

379

why the
the boiling
boiling points
points of
of ethers
ethers are
arelower
lowerthan
thanthose
thoseof
ofthe
theisomeric
isomericalcohols.
alcohols.Would
Would
isomeric
alcohols.
Would
42. Explain why
boiling
points
of
ethers
are
lower
than
those
of
the
isomeric
alcohols.
Would
42. Explain
isomeric alcohols.
alcohols. Would
Would
whythe
therelative
boilingwater
points
of ethers to
are
lowerin
thoseway?
of
the isomeric
expect
the
relative
water
solubilities
todiffer
differ
inthan
similar
way?
relative
water
solubilities
to
differ
in
similar
way?
you expect
solubilities
aaasimilar
you expect the relative water solubilities to differ in a similar way?
the best
best syntheses
syntheses for
for each
each of
of
the
following
ethers.
Use
alcohols
or
haloalkanes
or
both
43. Suggest the
the
following
ethers.
Use
alcohols
or
haloalkanes
or
both
of the following ethers. Use alcohols or
or haloalkanes
haloalkanesororboth
both
43. Suggest starting
or haloalkanes
haloalkanes or
or both
both
the best materials.
syntheses for each of the following ethers. Use alcohols or
materials.
as your starting
materials.
as your starting materials.
O
O
O
O
O
(a)
(b)
(c)
(b) O
(c)
O
(b)
(c)
OO
O
O
O
(a)
(b)
(c)
O
O
O
O
O
O
OO
O
O
O
(f(f)
)
O
O
(d)
(e)
(f)
(e)
(f)
(e)
O
(f )
(d)
(e)
(f)

380

Chapter 9

Further Reactions of Alcohols and the Chemistry of Ethers

380

Chapter 9

Further Reactions of Alcohols and the Chemistry of Ethers

44. Write the expected major product(s) of each of the following attempted ether syntheses.
Cl syntheses.
44. Write the expected
O major product(s) of each of the following attempted ether
A
A
HMPA
DMSO

CHCH2CH3
(b) CH3CH2CH2O  CH3CH2Cl
(a) CH3CH2CH2Cl  CH3CH2O
CHCH
2CH3
A
A
HMPA
DMSO

CH
CH
CH
O
CH
CH
CHCH

(b)
(a) CH3CH2CH
Cl  CH3CH2CHCH2CH3
3
2
2
3
2
2CH3
H3C
O 2
(c)
(c)

(e)
(e)

H3C

O

 CH3I

DMSO

(d) (CH3)2CHO  (CH3)2CHCH2CH2Br

(CH3)2CHOH

 CH3I
H
H

H
H
O Cl

O Cl

DMSO

(d) (CH3)2CHO  (CH3)2CHCH2CH2Br

CH3
A
DMSO
(f )
C O3 O  CH3CH2I
CH
A
DMSO
(f)
C O O  CH3CH2I

(CH3)2CHOH

Cyclohexanol
Cyclohexanol

45. For each reaction in Problem 44, write out a detailed step-by-step mechanism.

45.
Problemin44,Problem
write out
detailed
mechanism.
46. For each reaction
synthesisinproposed
44 athat
is notstep-by-step
likely to give
a good yield of ether prod
uct, suggest an alternative synthesis beginning with suitable alcohols or haloalkanes that will giv
46. For each synthesis proposed in Problem 44 that is not likely to give a good yield of ether prod
a superior result. (Hint: See Problem 25 in Chapter 7.)
[OH
uct, suggest an alternative synthesis beginning with suitable alcohols or haloalkanes that will giv
OH
result. be
(Hint:
See Problem
25 in of
Chapter
7.)
47. a(a)superior
What would
the product
of reaction
trans-2-bromocyclooctanol
(margin) with NaOH
[
~ Br
(b) Compare the effect of entropy on the transition state of this reaction with its effect in th
47. (a) What would be the product of reaction of trans-2-bromocyclooctanol (margin) with NaOH
~ Br
trans-2-Bromocyclooctanol
reactions presented in Figure 9-6 and in Exercise 9-14.
(b) Compare the effect of entropy on the transition state of this reaction with its effect in th
trans-2-Bromocyclooctanol
presented
in Figurefor
9-6each
and of
in Exercise
9-14. ethers, using haloalkanes or alcohols a
48. reactions
Propose effi
cient syntheses
the following
starting materials.
48. Propose efficient syntheses for each of the following ethers, using haloalkanes or alcohols a
CH3 starting materials.
CH3
O
A
CH3
CHOCH
CHOCH
(a) CH3CH2CH
(b)
(c)
(d)
O
3
2CH3
3
2CH2CH2CH3
A
CH3
CH
3
O
OCH2CH2CH2CH3
(a) CH3CH2CHOCH2CH3
(b)
(c)
(d)
O CH3
49. Give the major product(s) of each of the following reactions.
HI following reactions.
49. Give the major product(s) of Excess
eachconc.
of the
(a) CH3CH2OCH2CH2CH3
(b) CH3OCH(CH3)2

Excess conc. HI
Excess conc. HI

Excess conc. HBr

Excess conc. HBr

(b) CHCH
3OCH(CH
3)2
H
H 3 H
Excess conc. HBr
(d) CH3 H
H
H Excess conc. HBr
(d)
O

! !

(c) CH3OCH2CH2OCH3
(c) CH3OCH2CH2OCH3

Excess conc. HI

! !

(a) CH3CH2OCH2CH2CH3

OH
] O
Excess conc. HBr
H
] O CH2
Excess conc. HBr
-CH
CH
2
2
O
H
-CH
2
H
50. Give the Oexpected major product of reaction of 2,2-dimethyloxacyclopropane
with each of th
following reagents.
50. Give the expected major product of reaction of 2,2-dimethyloxacyclopropane with each of th
(b) Na12OCH3 in CH3OH
(a) Dilutereagents.
H2SO4 in CH3OH
following
(c) Dilute, aqueous HBr
(d) Concentrated HBr
(b) Na12OCH3 in CH
(a) Dilute H2SO4 in 1CH3OH
3OH
(e) CH3MgI, then H , H2O
(f) C6H5Li, then H1, H
O
(c) Dilute,
aqueous HBr
(d) Concentrated
HBr 2
1
(e) CH3MgI, then H1, H2O
(f)2CH
C62H
5Li, then H , H2O
OH
CH2CH
beginning with cyclohexanone,
51. Propose a synthesis of
O
CH2CH2CH2OH
OH
beginning with cyclohexanone,
51. Propose a synthesis of
O
and 3-bromopropanol. [Hint: Beware
OH of a possible pitfall in planning this synthesis (reca
Section 8-9).]
and 3-bromopropanol. [Hint: Beware of a possible pitfall in planning this synthesis (recal
52. Section
Cleavage8-9).]
of tertiary butyl ethers requires the use of an aqueous acid (Chapter 7, Problem 57, an
Section 9-8). Why do strong bases not cleave ethers (other than oxacyclopropanes)?
52. Cleavage of tertiary butyl ethers requires the use of an aqueous acid (Chapter 7, Problem 57, an
Section 9-8). Why do strong bases not cleave ethers (other than oxacyclopropanes)?

H
CH3
H
CH3

! !

CH
H 3
CH
H 3
! !

(e)

(e)

Excess conc. HBr

(f )

Excess conc. HBr

(f )

O
A
(a) CH3CH2CH2Cl  CH3CH2CHCH2CH3
H3 C

(c)

O
 CH3I
H

(e)

anol

DMSO

O

DMSO

Cyclohexanol

Cl

45. For each reaction in Problem 44,

46. For each synthesis proposed in Pr

uct, suggest an alternative synthes
a superior result. (Hint: See Prob

47. (a) What would be the product o

(b) Compare the effect of entrop
reactions presented in Figure 9-6

48. Propose efficient syntheses for e

AA
HMPA
HMPA
ach of the following
attempted
ether
syntheses.
syntheses.
CHether
CHCH
CH33
(b) CH3CH2CH2O attempted
CHCH
 CH33CH
22
22CH
Cl
Cl
AA
HMPA
HMPA
CH33CH
CH22CHCH
CHCH22CH
CH33
 CH
(b) CH3CH2CH22O 

(d) (CH3)2CHO  (CH33)22CHCH

CHCH22CH
CH22Br
Br

(CH33))22CHOH
CHOH
(CH

CH3
(d) (CH3)2CHO
(CH33))22CHCH
CHCH22CH
CH
Br
A  (CH
22Br
DMSO
DMSO
C O O  CH33CH
(f)
CH22II
CH33
A
DMSO
DMSO
(f )
C O O 
(f)
 CH
CH22II
CH33CH

(CH
(CH3)3)2CHOH
2CHOH

ut a detailed step-by-step mechanism.

mechanism.

44 that is not likely to give a good

good yield
yield of
of ether
ether prodprodwith
suitable
alcohols
or
haloalkanes
that
will
give
ning
haloalkanes
that
will
give
ut
a
detailed
step-by-step
mechanism.
ut a detailed step-by-step mechanism.
in Chapter 7.)
44 that
44
that is
is not
not likely
likely to
to give
give aa good
good yield
yield of
of ether
ether prodprodon
of
trans-2-bromocyclooctanol
(margin)
with
NaOH?
trans-2-bromocyclooctanol
(margin)that
withwill
NaOH?
ning with
suitable
give
ning
with
suitable alcohols
alcohols or
or haloalkanes
haloalkanes
that
will
give
state
of
this
reaction
with
its
effect
in
the
intransition
Chapter
7.)
ein
reaction
with
its
effect
in
the
Chapter 7.)
Exercise 9-14.
on of
on
of trans-2-bromocyclooctanol
trans-2-bromocyclooctanol (margin)
(margin) with
with NaOH?
NaOH?
following
ethers,
using
haloalkanes
or
alcohols
as
ee transition
state
of
this
reaction
with
its
effect
in
the
haloalkanes
or
alcohols
as
transition state of this reaction with its effect
in the
the
Exercise
9-14.
Exercise 9-14.

the following
as
O
ethers, using
haloalkanes or
the
following ethers,
using haloalkanes
or alcohols
alcohols
as
O
CH33

45.For
Foreach
each
reaction
Problem44,44,
write
a detailed
step-by-step
mechanism.
46. For each
synthesis
proposed
ininProblem
Problem
44
that
is
likely
to give mechanism.
a good
yield
of ether prodreactions
presented
in ininFigure
9-6
and
instep-by-step
Exercise
9-14.
45.
outout
a not
detailed
45.For
Foreach
eachreaction
reactionin
inProblem
Problem44,
44,write
write
out
adetailed
detailed
step-by-step
mechanism.
45.
reaction
write
out
aaadetailed
step-by-step
mechanism.
45.
For
each
reaction
in
Problem
44,
write
out
detailed
step-by-step
mechanism.
each
reaction
Problem
44,
write
out
step-by-step
mechanism.

each
reaction
inproposed
Problem
44,Problem
writewith
out asuitable
detailed
step-by-step
mechanism.
uct, suggest45.
anFor
alternative
synthesis
beginning
alcohols
haloalkanes
that
will prodgive
46.
For
eachsynthesis
synthesis
that
is not
likely
to or
give
a good
yield
of ether
46.
proposed ininProblem
4444
that
is not
likely
to give
a good
yield
of ether
prod46.For
Foreach
eachsynthesis
synthesis
proposedin
inProblem
Problem
44
that
isnot
not
likely
to
give
agood
good
yield
of
ether
prodFor
each
proposed
44
that
isisisnot
likely
to
aa good
yield
of
ether
prod46.
For
each
synthesis
proposed
in
Problem
44
that
not
likely
give
agood
yield
ether
prodeach
synthesis
proposed
in
Problem
44
that
likely
totogive
give
yield
ofof
ether
proda superior 46.
result.
(Hint:
See Problem
25
in Chapter
7.)

uct,suggest
suggest
alternative
synthesis
beginning
with
suitable
alcohols
orgood
haloalkanes
give
uct,
ananalternative
synthesis
beginning
with
alcohols
or ahaloalkanes
willwill
give
For
each
synthesis
proposed
in Problem
44 that
issuitable
not
likely
to give
yieldthat
of that
ether
product,
suggest
an
synthesis
beginning
with
suitable
alcohols
or
haloalkanes
that
will
give
suggest
analternative
alternative
synthesis
beginning
with
suitable
alcohols
or
haloalkanes
that
will
give
uct,
suggest
an
alternative
synthesis
beginning
with
suitable
alcohols
haloalkanes
that
will
give
uct,
suggest
an
alternative
synthesis
beginning
with
suitable
alcohols
oror
haloalkanes
that
will
give
OH
48. Propose
effi46.
cient
syntheses
for
each
of
the
following
ethers,
auct,
superior
result.
(Hint:See
See
Problem
Chapter
[OH
auct,
superior
result.
(Hint:
Problem
2525
in in
Chapter
7.)7.) alcohols or haloalkanes that will give
suggest
an alternative
synthesis
beginning
with suitable
[
OH
aaasuperior
(Hint:
in
Chapter
7.)
superior
result.
(Hint:
SeeProblem
Problem
25
Chapter
7.)
superior
result.
(Hint:
See
Problem
25
Chapter
7.)
superior
result.
(Hint:
See
Problem
25
ininin
Chapter
7.)
47. (a) What would
be theresult.
product
ofSee
reaction
of25
trans-2-bromocyclooctanol
(margin) with NaOH?
[
[OH
a(a)
superior
result. (Hint:
See Problem
25 in Chapter
7.)
[OH
47.
What
would
be
the
product
of
reaction
of
trans-2-bromocyclooctanol
(margin)
with
NaOH?
47.
(a)
What
would
be
the
product
of
reaction
of
trans-2-bromocyclooctanol
(margin)
with
NaOH?
starting
materials.
(b) Compare
the
effect
of entropy
on the
transition
state
of this reaction (margin)
with
itswith
effect
in the
~Br
~
47.
(a)
What
would
be
the
product
of
reaction
of
trans-2-bromocyclooctanol
NaOH?
47.
(a)
What
would
be
the
product
of
reaction
of
trans-2-bromocyclooctanol
(margin)
with
NaOH?
47.
(a)
What
would
be
the
product
of
reaction
of
trans-2-bromocyclooctanol
(margin)
with
NaOH?
What
would
be
the
product
of
reaction
of
trans-2-bromocyclooctanol
(margin)
with
NaOH?
Br
~
(b) Compare the effect of entropy on the transition state of this reaction with its effect in the
~

nol

the be
effect
entropy
the transition
state of this reaction with
its effect
the
47. (b)
(a) Compare
What
the of
product
of on
reaction
of trans-2-bromocyclooctanol
(margin)
with in
NaOH?
(b)
the
of
on
transition
state
of
this
reaction
with
its
effect
in
the
reactions presented
in would
Figure
9-6
and
in Exercise
9-14.
(b)Compare
Compare
theeffect
effect
ofentropy
entropy
onthe
the
transition
state
this
reaction
with
its
effect
inthe
the
Compare
the
effect
ofof
entropy
on
the
transition
state
ofofof
this
reaction
with
itsits
effect
inin
the
(b)
Compare
the
effect
entropy
on
the
transition
state
this
reaction
with
effect

Br
~Br

Br
trans-2-Bromocyclooctanol
trans-2-Bromocyclooctanol
trans-2-Bromocyclooctanol
trans-2-Bromocyclooctanol
trans-2-Bromocyclooctanol
trans-2-Bromocyclooctanol

reactions
presented
Figure
9-6and
and
in
Exercise
9-14.
reactions
presented
ininFigure
9-6
Exercise
9-14.
(b)
Compare
the effect
of entropy
onin
the
transition
state of this reaction with its effect in the
reactions
in
Exercise
9-14.
reactions
presented
inin
Figure
9-6
and
ininin
Exercise
9-14.
reactionspresented
presentedin
inFigure
Figure9-6
9-6and
and
Exercise
9-14.
reactions
presented
Figure
9-6
and
Exercise
9-14.

reactions
presented
in each
Figureof
9-6the
andfollowing
in Exercise
9-14. ethers,
48. Propose effi
cient
syntheses
ethers,
using
haloalkanes
48.
Propose
effi
cientfor
syntheses
for
each
following
using
haloalkanes
oralcohols
alcohols
as
48.
Propose
effi
cient
syntheses
each
of ofthethe
following
ethers,
using
haloalkanes
ororalcohols
as as
CH3
CHfor
48.
effi
cient
for
ethers,
using
haloalkanes
or
alcohols
as
Propose
effi
cient
syntheses
for
each
ofof
the
following
ethers,
using
haloalkanes
oror
alcohols
asasas
48.
Propose
effi
cient
syntheses
for
each
the
following
ethers,
using
haloalkanes
alcohols
48.Propose
Proposematerials.
effi
cientsyntheses
syntheses
for
eachof
ofthe
thefollowing
following
ethers,
using
haloalkanes
or
alcohols
3each
starting materials.
starting
materials.
48. starting
Propose
efficient syntheses for each of the following ethers, using haloalkanes or alcohols as
starting
starting
materials.
starting
materials.
startingmaterials.
materials.
A
starting materials.
CH
CH
CH
CH
OOO
CH3
CH
CH
O
CH
ACH
CH
CH
CHOCH2CH2CH2CH
CHCH
A (b)
CHOCHCH
3
ACH
3 (d) (c) OOOO
A2CH
CH
CHCH
CH
AA
CH
CH
CH
OCH CH CH CH
(a) CH CH CHOCH
(b)
(c)
33
3333

3 3
3333

3
2 CH
3
(a) CH3 CH2 CHOCH
(a)
3
2
2
3

49.

3 33 3 3
(d)
CH3 (d)
(d)
(d)
(d)
(d)
(d)
3 3
CH
O O CH
CH
33
CH
OOO
CH
CH
33
CH
O
O O 3CH
3
49.
Give
the
major
product(s)
ofofeach
ofof
thethe
following
reactions.
49.
Give
the
major
product(s)
each
following
reactions.
49.
Give
the
major
product(s)
of
each
of
the
following
reactions.
49.
49.
Give
the
major
product(s)
of
each
ofthe
the
following
reactions.
49.Give
Givethe
themajor
majorproduct(s)
product(s)of
ofeach
eachof
thefollowing
followingreactions.
reactions.
49.
Give
the
major
product(s)
each
ofof
following
reactions.
conc.
HIthe
Give the major
product(s)
of
each ofofExcess
the
following
reactions.
Excess
conc.conc.
HBr HBr
Excess
conc.
HI
Excess
Excess
conc.
HI
Excess
conc.
HBr
(a)
(b)(b)
conc.
HIHI
CHCH
conc.
HBr
2CH
3CH
2OCH
2CH
3 3 Excess
3OCH(CH
3)2 ) Excess
Excess
conc.
Excess
conc.
HBr
(a)CH
CH
Excess
conc.
HI
Excess
conc.
HBr
2CH
(a)
(b)
3CH
2OCH
2CH
3OCH(CH
CH
CH
22CH
33CH
22OCH
22CH
33 Excess conc. HI
33OCH(CH
33))22)3 2 Excess conc. HBr
(a)
(b)
CH
OCH
CH
CH
OCH(CH
CH
(a)
(b)
CH
CH
(a) CH
(b)
CH
CH
OCH
CH
CH
CH
22CH
33CH
22OCH
22CH
33 HI
3OCH(CH
3Excess
3OCH(CH
32)2
Excess
conc.
conc. HBr
(a)
(b)
CH
CH
3CH2OCH2CH2CH3
3OCH(CH3)2
CH
(a) CH3CH2OCH2CH2CH3
(b) CH3OCH(CH
3 H H
3 )2
CH
3 H
CH
H
H
3
CH
H
3 3H
Excess conc. HI
HCH
HExcess conc. HBr

CH
H
H
3HH
Excess
conc.
HI
H
H
Excess
conc.
HI

CH
(c)
(d)

Excess
conc.
HBr
H
H

OCH
CH
OCH
CH
3
conc.
HI
conc.
H
HExcess
3 OCH
2 CH
2 OCH
3 Excess
Excess
conc.
conc.HBr
HBr
(c)CH
(d)HI
CH
Excess
conc.HI
HI
(c)
(d)
H
Excess
3
2 2OCH
2
33OCH
22CH
33 3 Excess
(c)
(d)
Excessconc.
conc.HBr
HBr
Excess
conc.
OCH
CH
conc. HI
CH
H H Excess
22OCH
(c)
(d)
CH
(c) CH
(d)3
Excess conc. HBr
OCH
CH
OCH
CH
33OCH
22CH
33
2OCH
(c)
(d)
CH
H
H
3OCH2CH2OCH3
HI
O O Excess conc. HBr
O
2 conc. 3
2 2CH2OCH
2 3 Excess
3
(c)3CH3OCH
(d)
OOO
O
H
CH3 H
H
H
O
H
CH
CH
HCH3
H
33 3H
]
HH
CH
HH
O
O

CH
H
CH
Excess
conc.
HBr
O
H
CH
Excess
conc.
HBr
3
]
CH
H
]

3
H
3
O
]
33 Excess
(e) H
(f ) O
]
CH33
HCH

Excess
conc.
HBr
Excess
conc.
HBr
H
CH
conc.
HBr
Excess
conc.
HBr
]

H
CH
Excess
conc.
HBr
OOCH
conc.
HBr
2
(e)
(f(f)(f
]
(e) H
)

Excess
conc.
HBr
Excess
conc.
HBr
(e)

CH
CH33 Excess
Excess
conc.
HBr
CH
Excessconc.
conc.HBr
HBr
22 2 Excess
(e)
(f) )
3
CH
conc.
HBr
Excess
(e)
CH
2
(e)
(f(f) ) H CH
-CH
- 2 CH
2 2
CH H
O
CH
22 2
CH
Excess conc. HI ]OHHHCH
O
H 3 CH3 O
H
OO
CH
22
CH
HHCH2 Excess conc. HBr
Excess
OO conc. HBr
H
(e)3
(f
)
50.2Give the2 expected major
of reaction of 2,2-dimethyloxacyclopropane
with each of the
CH2
3majorproduct
50.
product
of
2,2-dimethyloxacyclopropane
with
each
of
the
50.Give
Givethe
theexpected
expectedmajor
productof
ofreaction
reaction
of
2,2-dimethyloxacyclopropane
with
each
of
the
50.
Give
the
expected
major
product
ofof
reaction
ofof
2,2-dimethyloxacyclopropane
with
each
ofof
the
50.
Give
the
expected
major
product
reaction
2,2-dimethyloxacyclopropane
with
each
the
2,2-dimethyloxacyclopropane
50.following
Give
the reagents.
expected
major product
productof
ofreaction
reactionof
of2,2-dimethyloxacyclopropane
witheach
eachof
ofthe
the
50.
Give
the
expected
with
following
reagents.
following
reagents.major
following
reagents.
CH2
following
reagents.
O (a)
H 3 in CH
following
reagents.
(b) Na12
OCH
Dilute H
12
following
reagents.
2SO4 in CH3OH
3OH
1212
SO
in
CH
OH
(b)
Na
OCH
in
CH
OH
(a)
Dilute
H
2
4
3
3
3
SO4 4inin
in
CH
OH
(b)Concentrated
Na12
OCH
in
CH
(a)Dilute,
DiluteH
H2SO
CH
(b)
Na
OCH
CH
(a)
Dilute
2SO
3OH
3HBr
3OH
3OH
3 in
3OH
12
(c)
aqueous
HBr
(d)
CH
(b)
Na
OCH
in
CH
OH
(a)
Dilute
H
12
2
4
3
3
3
SO
in
CH
OH
(b)
Na
OCH
in
CH
OH
(a)
Dilute
H
(c)
Dilute,
aqueous
(d)
Concentrated
HBr
3
3
CH
(b)
Na
OCH3 3in
OH
(a)
Dilute
H
22SO44 inHBr
3OH
1
1CH
(c)CH
Dilute,
aqueous
Concentrated
(c)
Dilute,
aqueous
HBr
(d)
HBr
Give the expected
major
product
2,2-dimethyloxacyclopropane
with each of the
(e)
then
H1
,HBr
H of
O reaction of
(f
)(d)
CConcentrated
H
,HBr
H23O
(c)
Dilute,
HBr
(d)
HBr
3MgI,aqueous
6Concentrated
5Li, then H1
(c)CH
Dilute,
aqueous
Concentrated
1H22O
1
1,HBr
(e)
then
,HBr
(f
)(d)
Li,Li,
then
HHHBr
HH,2O
(c)
Dilute,
aqueous
HBr
3MgI,
6H
5H
(e)
CH
MgI,
thenH
H
then
(e)
CH
then
HH
(f(d)
) )CCConcentrated
H6H
,1
OO
1, ,HH
1
3MgI,
2O
5 then
2O
3MgI,
2O
5Li,
2H
(e)
CH
then
HH
(f(f)
C6C
then
HH
H
11
following reagents.
22O
5Li,
2 2O
(e) CH
CH333MgI,
MgI, then
thenH
H11,,,H
O
(f)
C66H
thenH
H
H
(e)
) C
,, ,H
6H
5Li,then
2O
5Li,
2O
CH2CH(f
2CH2OH
CH
2CH
2CH
2OH
12
CH
CH
OH
CH
CH
CH
OH
CH
2 2 2 2OCH
2OHbeginning
with cyclohexanone,
51.
Propose
a synthesis
of
O,
(b)CH
Na
in CH3OH
(a) Dilute
H2SO
CH2 2OH
CH
22CH
4 in aCH
3OH of
3beginning
with
cyclohexanone,
CH22CH
CH
O,
2CH
3 51.
beginning
with
cyclohexanone,
51.
Propose
aasynthesis
synthesis
ofof
2 2OH
beginning
with
cyclohexanone,
51.Propose
Propose
synthesis
O, O,
OH 2CH
beginning
with
cyclohexanone,
51.
Propose
synthesis
of
O,O,
(c) Dilute,51.
aqueous
HBr
(d)
Concentratedbeginning
HBr with
beginning
withcyclohexanone,
cyclohexanone,
51.
Propose3
synthesis of
of
OH
Propose
aaa synthesis
O,
OH
OH
OH
1
1
3-bromopropanol.
[Hint:
Beware
of Li,
a possible
pitfall
in
planning this synthesis (recall
OH
Excess
conc.
HBr
OH
(e) CH3MgI, and
then
H
,
H
O
(f)
C
H
then
H
,
H
O
and
3-bromopropanol.
[Hint:
Beware
of
a
possible
pitfall
in
planning
this
synthesis
(recall
2
6
5
2
and
[Hint:
thisthis
synthesis
(recall
and 3-bromopropanol.
3-bromopropanol.
[Hint:Beware
Bewareofof
ofaaapossible
possiblepitfall
pitfallinininplanning
planning
synthesis
(recall
Section
8-9).]
and
3-bromopropanol.
[Hint:
Beware
possible
pitfall
planning
this
synthesis
(recall
Section
8-9).]
and
3-bromopropanol.
[Hint: Beware
Bewareofofa apossible
possiblepitfall
pitfallininplanning
planningthis
thissynthesis
synthesis(recall
(recall
and
3-bromopropanol.
[Hint:
Section
8-9).]
Section
8-9).]
Section
8-9).]
Section 8-9).]
8-9).]
Section
2CH
2CH2OH
52. Cleavage
of tertiary butylCH
ethers
requires
the use of an aqueous acid (Chapter 7, Problem 57, and
Cleavage
butyl ethers
requires
the
use
of an
aqueous
acid (Chapter
7,7,Problem
57,
and
52.
Cleavage
ofoftertiary
tertiary
ethers
requires
thethe
use
an
aqueous
(Chapter
Problem
57,57,
andand
beginning
with
cyclohexanone,
Propose a 52.
synthesis
ofof
52.Section
Cleavage
tertiary
butyl
ethers
requires
useofofof
an
aqueous
acid
(Chapter
Problem
O,
9-8).
Why
dobutyl
strong
bases
not cleave
ethers
(other
thanacid
oxacyclopropanes)?
52.
Cleavage
of
tertiary
butyl
ethers
requires
the
use
an
aqueous
acid
(Chapter
7,7,
Problem
57,
and
9-8).
Why
do
strong
bases
not
cleave
ethers
(other
than
oxacyclopropanes)?
52.Section
Cleavage
of
tertiary
butyl
ethers
requires
the
use
of
an
aqueous
acid
(Chapter
7,
Problem
57,
and
52.
Cleavage
of
tertiary
butyl
ethers
requires
the
use
of
an
aqueous
acid
(Chapter
7,
Problem
57,
and
Section
9-8).
Why
do
strong
bases
not
cleave
ethers
(other
than
oxacyclopropanes)?
Section 9-8).
9-8). Why
Why do
do strong
strong
bases not
not cleave
cleaveethers
ethers(other
(otherthan
thanoxacyclopropanes)?
oxacyclopropanes)?
OH bases
Section
Section 9-8).
9-8). Why
Whydo
dostrong
strongbases
basesnot
notcleave
cleaveethers
ethers(other
(otherthan
thanoxacyclopropanes)?
oxacyclopropanes)?
Section
3
OCH
(b)
(c)
2 2CH
2 2CH
2 2CH
3 3
(b)
(c)
22CH
22CH
22CH
33 3
OCH
CH
CH
CH
(b)
(c)
CH
CH
(c)
(b)
(c)
OCH
CH
CH
CH
(b)OCH2CHOCH
(c)
232CH
2OCH
2CH
2CH
3
OCH22CH
CH 2CH
(b)
(c)

3
2A
2
3
CHOCH
(a)
333CH
33
CH
CH
CH
(a) CH3CH2CHOCH
(b) 22CH
(a) CH
CH
CH
CHOCH
CH
2CH
3 2222CHOCH
3CH
CH
CH
CHOCH 22CH 33

(b) CH OCH(C

50.

CH H
H
CH
51.

CH H
H
H
O

(e)

(d)

(c) CH OCH CH OCH

!
!
!
!
!
!!

!!
!
!
!
!
!

!!
!
!!
!!

(a) CH CH OCH CH CH

!!
!
!!
!!

49. Give the major product(s) of each of the following reactions.

(f )

H
] O

-CH
H

and 3-bromopropanol. [Hint: Beware of a possible pitfall in planning this synthesis (recall
Section 8-9).]

50. Give
the expected major product of reaction of 2,2-dimethyl
52. Cleavage of tertiary butyl ethers requires the use of an aqueous acid (Chapter 7, Problem 57, and
Section reagents.
9-8). Why do strong bases not cleave ethers (other than oxacyclopropanes)?
following

(b) Na12OCH3 in CH
(d) Concentrated HBr
(f ) C6H5Li, then H1,

(a) Dilute H2SO4 in CH3OH

(c) Dilute, aqueous HBr
(e) CH3MgI, then H1, H2O

CH2CH2CH2OH

beginning w

51. Propose a synthesis of

OH

(a) CH3CH2OCH2CH2CH3
Excess conc. HI

conc. HI
(a) CH3CH2OCH2CH2CHExcess
(c) CH3OCH2CH2OCH3 3
Excess conc. HI
(c) CH3OCH2CH2OCH3
Excess conc. HI

! ! !

! ! !

(c) CH3OCH2CH2OCH3
CH H
H 3 CH3
(e) H CH3 H CH Excess conc. HBr
3 Excess conc. HBr
(e)
CH H
H O3 CH3
Excess conc. HBr
(e)
O
Give the expected major product of reac
Oreagents.
following
Give the expected
major product of react
following
reagents.
CH3OH
(b
(a)
Dilute
H2SO4 inmajor
Give
the expected
product of reac
(c)
aqueous
HBr
(d
(b
(a) Dilute,
Dilute reagents.
H
following
2SO4 in CH3OH
1
(e)
CH3MgI,
then HHBr
, H2O
(f
(c) Dilute,
aqueous
(d
(b
(a) Dilute H2SO4 in 1CH3OH
(e) CH3MgI, then H , H2O
(f
(c) Dilute, aqueous HBr
(d
CH2CH
1
(e) CH3MgI,
then Hof, H2O
Propose
a synthesis
CH2CH(f2
OH
Propose a synthesis of
CH2CH

owing reactions.
(b) CH3OCH(CH3)2
!

(d)

CH H
H 3 H

Excess conc. HBr

Excess conc. HBr

(f )

H
] O
CH2

Excess conc. HBr

-CH
2
H

of 2,2-dimethyloxacyclopropane with

Na12OCH3 in CH3OH
oncentrated HBr

O
HH
Give the
the expected
expected major
major product
product of
of reaction
reaction of
of 2,2-dimethyloxacyclopropane
2,2-dimethyloxacyclopropanewith
witheach
eachof
the
50.
Give
the
major
product
of
reaction
of
2,2-dimethyloxacyclopropane
with
each
ofofthe
the
50. Give
product
of
reaction
of
2,2-dimethyloxacyclopropane
with
each
of
the
50.
major product
2,2-dimethyloxacyclopropanewith
witheach
eachof
ofthe
the
Give
the expected
expected
major
product
of
reaction
of
2,2-dimethyloxacyclopropane
with
each
of
the
50. following
expected
major
product of
of reaction
reaction of
of 2,2-dimethyloxacyclopropane
2,2-dimethyloxacyclopropane
with
each
of
the
following
reagents.major
Give
the
expected
following
reagents.
reagents.
following
reagents.
reagents.
12
following
12
SO44 in
in CH
CH33OH
OH
(b) Na
Na12
OCH
in
CH
OH
(a) Dilute
Dilutereagents.
H22SO
3
3
(b)
OCH
in
CH
OH
(a)
H
12
12
12
2 SO4 in CH
33 in
33 OH
12OCH
(b)
Na
OCH
in
CH
12
OH
OH
(b)
Na
CH
(a)
Dilute H
Haqueous
CH333OH
22SO44 in
3OH
CH
(b)
Na
OCH33333in
inHBr
CH333OH
(c) Dilute,
Dilute,
HBr
(d) Na
Concentrated
HBr
CH
(b)
OCH
CH
(a)
Dilute
3OH
22SO
44 inHBr
33OH
(c)
aqueous
(d)
Concentrated
1
(d)
Concentrated
HBr
(c)
Dilute,
aqueous
HBr
(d)
Concentrated
HBr
HBr
1
11, H O
1
1
aqueous
HBr
(d) C
Concentrated
HBr
(c)
Dilute,
aqueous
(d)
Concentrated
(e) CH
CH33MgI,
MgI,
then H
HHBr
,H
H22O
O
(f)
C
H55Li,
Li,then
thenHHBr
H
6H
22
1
1
6
1
1
(e)
then
,
(f)
,
H
1
6H
5 Li,
22O
(f)
C
H
Li,
then
H
H
O
(e) CH
CH33MgI,
MgI, then
then
H
H
O
(f)
C
then
H
H
O
H11,,,, H
H222O
(f ) C
2O
(e)
(f)
then H
H
H
(f)
C66666H
H55555Li,
Li, then
thenH
H11,,,,H
H222O
3
22O
2O
CH222CH
CH222OH
OH
CH222CH
CH
CH
CH
OH
CH
CH
CH
OH
CH
22CH
22CH
222OH
beginning
with
cyclohexanone,
Propose
a
synthesis
of
CH
O,
51.
CH
CH
OH
CH
22
22
22
beginning
with
cyclohexanone,
51. Propose
of
O,
beginning
with
cyclohexanone,
Propose aaa synthesis
synthesis
of
beginning
with
cyclohexanone,
51.
O,
O,
cyclohexanone,
of
O,
beginning
Propose
synthesis
beginning with
withcyclohexanone,
cyclohexanone,
51.
synthesis of
of
OH
O,
O,
OH
OH
OH
OH
OH of
3-bromopropanol. [Hint:
[Hint: Beware
Beware
of aa possible
possible pitfall
pitfall inin planning
planning this
this synthesis
synthesis(recall
(recall
and 3-bromopropanol.
and
3-bromopropanol.
[Hint:
Beware
of
a
possible
pitfall
in
planning
this
synthesis
(recall
Beware
of
a
possible
pitfall
in
planning
this
synthesis
(recall
[Hint:
3-bromopropanol.
planningthis
thissynthesis
synthesis(recall
(recall
and
3-bromopropanol.
[Hint:
3-bromopropanol.
[Hint: Beware
Beware of
of aa possible
possible pitfall
pitfall inin planning
planning
this
synthesis
(recall
Section
8-9).]
Section
Section 8-9).]
8-9).]
Section
8-9).]
Cleavage of
of tertiary
tertiary butyl
butyl ethers
ethers requires
requires the
theuse
useof
ofan
anaqueous
aqueousacid
acid(Chapter
(Chapter7,7,Problem
Problem57,
57,and
and
52. Cleavage
Cleavage
of tertiary
tertiary
butyl
ethers
requires
the
use
of
an
aqueous
acid
(Chapter
7,
Problem
57,
and
requires
the
use
of
an
aqueous
acid
(Chapter
7,
Problem
57,
and
ethers
52.
butyl
(Chapter7,
7,Problem
Problem57,
57,and
and
Cleavage
of
butyl
ethers
requires
the
of
aqueous
acid
(Chapter
52. Section
tertiary
butyl
ethers
requires
the use
use
ofan
an
aqueous
acid
(Chapter
7,
Problem
57,
and
Section 9-8).
9-8).
Why do
do
strong
bases
not cleave
cleave
ethers
(other
than
oxacyclopropanes)?
Why
strong
bases
not
ethers
(other
than
oxacyclopropanes)?
Section 9-8).
9-8). Why
Why
do
strong
bases
not
cleave
ethers
(other
than
oxacyclopropanes)?
bases
not
cleave
ethers
(other
than
oxacyclopropanes)?
strong
do
oxacyclopropanes)?
Section
do
strong
bases
not
cleave
ethers
(other
than
oxacyclopropanes)?
Why do strong bases not cleave ethers (other than oxacyclopropanes)?

PPrr o
or ob
b bll e
el em
mmss s
P

Ch
hC a
ah p
pa ttpe
et rre r9
99
C

381
381
381

Problems

Chapter 9

381

53.
an IUPAC
IUPAC name
name for
for each
each of
of the
thestructures
structurespictured
picturedbelow.
below.
Provide an
an
IUPAC
name
for
each
of
the
structures
pictured
below.
53. Provide
OO CH Cl
53. Provide an IUPAC name for each of the
below.
CH
O
CH
CH2Cl
?structures picturedCH
!! O !!
3O
!
OO ?
33O
O
!CH22Cl
O
O
(a)
(b)
(c)
(b)
(c) CH3O! O
(a)
(b)
(c)
O ?
!CH2Cl
O
(a)
(b)
(c)
OO
O
OO
OO
O
O
O
OH
O
(d) O
(e)
(f)
OOH
OH
O
(e)
(f )
O
(d)
(e)
(f)
O
O
O OH
(d) O
(e)
(f)
the major
major
product(s)
of
each
of
the
following
reactions.
(Hint:
The
strained
oxacyclobutanes
54. Give
major product(s)
product(s) of
of each
eachof
ofthe
thefollowing
followingreactions.
reactions.(Hint:
(Hint:The
Thestrained
strainedoxacyclobutanes
oxacyclobutanes
Give the
react like
like oxacyclopropanes.)
oxacyclopropanes.)
react
oxacyclopropanes.)
OO The strained oxacyclobutanes
54. Give the major product(s) of each of the following reactions. (Hint:
O
NaNa
SCH
CH
CH
CH
OH
Na
SCH
CH
,, CH
CH
OH
SCH
2CH
3, CH
3CH
2OH
Na
NH
NH
~~
react O
like oxacyclopropanes.)
Na
NaNH
NH2,,,NH
NH3
~
O
(b)
(a)
H
&
(b)
(a)
(b) HH& & O
CH
3
CH
Na SCH CH , CH CH OH
CH
33
(b) H~&
(a) O Na NH , NH
CH
OO3
O Excess
Dilute
HCl
in in
CH
OH
Excess
conc.
HBr
O
O
Dilute
HCl
in
CH
OH
Dilute
HCl
CH
Excess conc.
conc.HBr
HBr
(c)
(d)
3OH
(c)
(d)
(d)
CH
33
CH
3 Dilute HCl in CH OH
O CH
O Excess conc. HBr
(c)
(d) CH
CH
CH33 3CH






2
2

2
2

3
3

3
3

2
2

3
3





3
3

(e)
(e)
(e)

(e)

O
O
O


OCH3 in CH3OH
Na
Na
NaOCH
OCH33ininCH
CH3OH
3OH

CH3
CH
O CH33
CH
CH
CH333CH

NaOCH3 in CH3OH

1. LiAlD
LiAlD ,, (CH
(CH CH
CH )) O
O
1.
OOCH3
1. LiAlD
O
4, (CH3CH2)2O
O
2.
H
H, H
O2O
2.2.
H H,, H
(f)
CH
(f)
CH
(f )
33 3
CH
1. LiAlD4, (CH3CH2)2O
O CH
2. H, H2O
CH
CH33 CH
(f)
3 3



(g)
(g)
(g)

(g)

CH3
O
O
O

CH33
CH
CH3
O CH
CH
CH33CH
3 3

4
4
2
2

3
3

2 2
2 2

CH3
1.
(CH33))22CHMgCl,
2)
2O
1.
CHMgCl, (CH
(CH33CH
CH
2)2O
 3)2CHMgCl, (CH
1.(CH
3CH2)2O
, H
2.
H(CH
2O
2.
2.HH,,HH2O
2O

1. (CH3)2CHMgCl, (CH3CH2)2O
2. H, H2O

(h) O
O
(h)
(h) O

(h)

Li,
(CH
1.
3CH
2)2O
Li,Li,
(CH
1.1.
3CH2)2O
(CH
3CH2)2O
2. H
H, H2O
2.
2. H,H, 2HO2O
Li, (CH3CH2)2O
1.

2. H, H2O

55. For
each CH
alcohol
in Problem
Problem 51 of
of Chapter 8,
8, suggest aa synthetic
synthetic route that
that starts with
with an
55.
For
in
3
55.
For each
each alcohol
alcohol
in Problem 51
51 of Chapter
Chapter 8, suggest
suggest a syntheticroute
route thatstarts
starts withanan
oxacyclopropane (if
(if possible).
oxacyclopropane
oxacyclopropane (if possible).
possible).
55.
For each
in Problemexpected
51 of Chapter
8, suggest
starts Watch
with an
56. Give
Give
the alcohol
major product(s)
product(s)
from each
each
of thea synthetic
reactions route
shownthatbelow.
below.
56.
expected
56.
Give the
the major
major (ifproduct(s)
expected from
from each ofof the
the reactions
reactions shown
shown below.Watch
Watch
oxacyclopropane
possible).
stereochemistry.
stereochemistry.
stereochemistry.
1. LiAlD
LiAlD ,,below.
(CH CH
CH )) O
OWatch
56. Give theOmajor product(s) expected from each of the reactions
shown
1.
(CH
O
O
O
HO
O 4, (CH3CH2)2O
2. 1.
H LiAlD
Dilute H
H22 SO
SO44 in
in CH
CH33 CH
CH22 OH
OH
,, H
2.
H
Dilute
O
O
stereochemistry.
2. H , H2O
Dilute H2 SO4 in CH3 CH2 OH
~
~
~
~
~
~
(b) H
(a) H
CH33
H~
H~
CH33
(b)
(a)
CH
&&
&&
(( ~
(( CH
~
~
(b) H
(a) HCH
& 3O ~
( CH
(H
H
CH&33 O H
CH
HCH3
3 1. LiAlD , (CH CH ) O
CH
2. H , H O
Dilute H2 SO4 in CH3 CH2 OH
H
CH3
CH33
H
~
~
(b) H~&
(a) H~&
CH3
( CH3
( the
57.
Name
each
of
following
compounds
according
to
IUPAC.
57. Name each
of the following compounds according to IUPAC.CH3
H
3 ofHthe following compounds according to IUPAC.
57. NameCH
each
4
4
2
2




3
3

2 2
2 2

2 2

CH33 according to IUPAC.

CH
57. Name each of the following compounds
A
ACH3
A
(a)
(b)
(c)
(d)
CH
3
(a)
(b) CH
(c) CH
(d) CF
CH33CH
CH22CHSCH
CHSCH
CH33CH
CH22SO
SO33 H
H
CF33SO
Cl
SO22Cl
CH22CH
CH22 SH
SH
3
(a)
(b) CH3CH2CHSCH
(c) CH3CH2CH2SO3 H
(d) CF3SO2Cl
CH2 SH
CH3
3
A
58. In
In
each of
of CH
the 2following
following
pairs
of
compounds,
indicate
which
isCH
the2SO
stronger
acid
and
which
is
(a)each
(b)
(c) CH
(d) and
CHof
CF3SO
SH
58.
the
pairs
compounds,
which
is
the
stronger
acid
which
3CH
2CHSCH3 indicate
3CH2
3H
2Cl is
2indicate
2 which 1
1
58. the
In each
of the
following
pairsCH
of 3OH;
compounds,
is,, H
the
stronger acid and which is
2
2
the
stronger
base.
(a) CH
CH33SH,
SH,
CH
OH;
(b)
HS
,
HO
;
(c)
H
S
H
S.
3
2
stronger
base.
(a)
(b)
HS
,
HO
;
(c)
H
S
S.
3
3
2
the stronger base. (a) CH3SH, CH3OH; (b) HS2, HO2; (c) H3S1, H2S.
58.
In each
of the following
pairs
of of
compounds,
indicate
which is the stronger acid and which is
59. Give
Give
reasonable
products for
for
each
of
the following
following
reactions.
59.
reasonable
products
each
the
reactions.
2
base.products
(a) CH3for
SH,each
CH3OH;
HS2, HOreactions.
; (c) H3S1, H2S.
59. the
Givestronger
reasonable
of the(b)
following
H
H
Br
H KSH
59. Give reasonable products for
of Na
the2SS following reactions.
[ Br
Oneeach
equivalent
Na

[
One
equivalent
KSH
)
KSH
)
(b)
(c)
(a) ClCH
CH22 CH
CH22CH
CH22 Cl
Cl One equivalent Na2 2S
ClCH22 CH
(b)
(c)
(a)

[ Br KSH
O
O
KSH
KSH
)
[
[
(b)
(c)
(a) ClCH2 CH2 CH2CH2 Cl
O
[H

Br

H
[
One equivalent Na 2 S

KSH
KSH
)
(b) CH
(c)
(a) ClCH2 CH2 CH2CH2 Cl
H
O
33
CH
[
CH3

CH
CH33CH
CH22
H

II2
CH3AACH2 CH
Excess H
H 22O
O 22
CH33SH
SH
Excess
CH
(d) CH
(e) CH
(f)3 O
CH33CH
CHCH
CH3 2
CH33CH
CBr
CH22 CBr
S
A
(d)
(e)
(f)
S Excess H2O2
O
ACHCH3 I2
ACBr CH3SH
A
A
(d) CH3CH23CH
(e)
(f)
CH
S
3
3
O
2
SH
CH33CH
CH
A
SH
CH
A 22 CH3SH
I2
Excess H 2O 2
SHCH3
CH2
(d) CH3CH23CBr
(e) CH3CH
(f) O
S
A
A
SH
CH3CH2

(a) O
react like oxacyclopropanes.)

(a) O Na NH2, NH3
NaNH
2, NH
3
O Excess
Excess
conc.
HBr
Excess
conc.
HBr
(a)
(c) OO
O
Excess conc.
conc. HBr
HBr
(c)
(c)
O Excess conc. HBr
(c)

(c)

(e)
(e)
(e)

O
O
O

(e)

(e)

Excess conc. HBr

CH
CH3
CH
O CH333
CH333
CH
CH3CH3
O


 OCH3 in CH3OH
Na
Na
OCH33 in
in CH33OH
OH
Na
NaOCH
OCH3 inCH
CH3OH

NaOCH3 in CH3OH

NaOCH3 in CH3OH

CH3CH3
1. (CH
(CH33)))22CHMgCl,
CHMgCl,(CH
(CH3CH
CH)2))O
O
3CH
2O
1.
1.
(CH
CHMgCl,
(CH
O
O
1.
(CH
(CH3CH22)22O
3)22CHMgCl,
H
O
2. H
H,,, H
OCH3 CH 2.2.
H
O
H
2O
(g)
2. H , H O
(g)
CH
CH
(g)
CH3333 1. (CH ) 2CHMgCl, (CH CH ) O
3 2
3
2 2
O CH
2. H, H2O
CH
333
(g)
CHCH
3 3 1. (CH3)2CHMgCl, (CH3CH2)2O
O
2. H, H2O
(g)
CH
3
55.
alcohol
in Problem
Problem 51
51 of
of Chapter
Chapter 8,
8,
CH
For
each
alcohol
in
in
3
55.
55. For each alcohol
alcohol
in Problem
Problem 51
51 of
of Chapter
Chapter 8,
8,
oxacyclopropane
(if
possible).
oxacyclopropane
(if
oxacyclopropane
(if
possible).
CH3
oxacyclopropane
(if possible).
possible).
55. For each alcohol in Problem 51 of Chapter 8,
56.
Give
the major
product(s)
expected
ea
major
expected from
from
56.
oxacyclopropane
56.
Giveeach
the alcohol
major (ifproduct(s)
product(s)
from 8,ea
ea
55. stereochemistry.
For
inpossible).
Problem expected
51 of Chapter
stereochemistry.
stereochemistry.
stereochemistry.
oxacyclopropane
possible). expected from ea
56. Give
the major (ifproduct(s)
O
DiluteH
H22SO
SO44in
inCH
CH33CH
CH22OH
OH
Dilute
Dilute
H
SO
in
CH
CH
OH
56. stereochemistry.
Give ~
theOmajor product(s)
Dilute H22 SO44 expected
in CH33 CH22 OHfrom ea
~
~
(a)
H~
&
(~CH
CH
stereochemistry.
(a) HCH
CH3333 Dilute H SO in CH CH OH
& 33O ~
(H
H
H
2
4
3
2
3
CH
H
~3 ~


3 2

2 2

reactions. (Hint: The

The strained
strained oxacyclobutanes
oxacyclobutanes
O
NaSCH2CH3, CH3CH2OH
O
NaSCH
SCH2CH
CH3,, CH
CH3CH
CH2OH
OH
Na
(b) H~&
~
(b) HCH
& 3
CH3


O
O

(d)
(d)

CH3
CH33

Dilute HCl in CH3OH

Dilute HCl
HCl in
in CH
CH33OH
OH
Dilute

CH3
CH33
(f)
(f)

(h)
(h)

O
O

1. LiAlD4, (CH3CH2)2O
2. LiAlD
H, H424,O
1.
LiAlD
, (CH
(CH33CH
CH22))22OO
1.
CH3 2.2. HH


,, H
H22O
O

CH33
CH3
CH33

O
O

Li, (CH3CH2)2O
1.
Li,
1.
Li, (CH
(CH33CH
CH22))22O
O
1.
2. H, H2O

2.
H,, H
H22O
O
2. H

suggest a synthetic route that starts with an

route that
that starts
starts with
with an
an
suggest a synthetic
synthetic route

oxacyclopropane (if possible).

oxacyclopropane (if possible).
56. Give the major product(s) expected from each of the reactions shown below. Watch
56. Give
the major product(s) expected from each of the reactions shown below. Watch
stereochemistry.
stereochemistry.
1. LiAlD 4, (CH 3CH 2) 2O
O

O
, H24O
2.
H
1. LiAlD
LiAlD
(CH3CH
CH2))2O
O
,, (CH
Dilute H2 SO4 in CH3 CH2 OH
~ O ~ CH 2. H ,, HH2OO
~ O ~ CH Dilute H2SO4 in CH3CH2OH
(b)
(a) H~
H
&
&
(
(
3
3
~
~
~
(b) HCH
(a) HCH
& 3 ( HCH33
& 3 (HCH3
H
CH3
CH3
H





57. Name each of the following compounds according to IUPAC.

57. Name each of the following compounds according to IUPAC.
CH3
CH
A 3
A
(a)
(b) CH3CH2CHSCH
(c) CH3CH2CH2SO3 H
CH2 SH
3
(a)
(b) CH3CH2CHSCH3
(c) CH3CH2CH2SO3 H
CH2 SH

2 2

244

33

22 22

22

(d) CF3SO2Cl
(d) CF33SO22Cl

58. In each of the following pairs of compounds, indicate which is the stronger acid and which is
58. In
of the
following
of compounds,
indicate
2
2 which is1 the stronger acid and which is
theeach
stronger
base.
(a) CH3pairs
SH, CH
3OH; (b) HS , HO ; (c) H3S , H2S.
the stronger base. (a) CH3SH, CH3OH; (b) HS2, HO2; (c) H3S1, H2S.
59. Give reasonable products for each of the following reactions.
59. Give reasonable products for each of the following reactions.
H
H KSH
[ Br KSH
One equivalent Na 2 S
)

[ Br KSH
(b)
(c)
(a) ClCH2 CH2 CH2CH2 Cl One equivalent Na 2S
O KSH
)
(b)
(c)
(a) ClCH2 CH2 CH2CH2 Cl
[O KSH

[
H

H
3
CH
CH3
CH3CH2
CH3CH
A 2 CH3SH
I2
Excess H 2O 2
A
(d) CH3CH2 CBr
(e) CH3CHCH3 I22
(f) O
CH33SH
S Excess H22OO22
(d) CH3CH2 CBr
(e) CH3CH
(f) O
A CH3
A
S
A
A 2
SH
CH3CH
SH
CH3CH2

er Reactions of Alcohols and the Chemistry of Et

eme.
in (Hint:
the following
A is acyclic.)
scheme.To
(Hint:
what Acompound
is acyclic.)
class
To does
what the
co
F u r t h e r R ee aa cc tt ii oo nn ss oo ff AAllccoohhoollss aanndd tthhee CChheemmi isst tr ry y oof f EEt thhe er rs s
belong?
F
u rr tt h
h382
R eeCaah accpttt iei oro n
thlhceoeh C
m
uArltlc
hceoo
r hhRoo
e lals
cst i oaannsndd
o f tA
oC
lh
s he
aenm
d i tishstetr rC
yt th
oh
fe e
Er trshse r s
9n ss oo ff F A
Fu
ee rr R
y yh eomofi fs tEr E

u rthe
t h estructures
r R e a c tofi ocompounds
n s o f A l A,
coh
s aCn (with
d t h estereochemistry)
C h e m i s t r y from
o f Ethe
t h einfo
rs
B,oolland
u 60.
r t hGive
e r the
R estructures
a c t i o nof
s compounds
o f A l c oA,
sandaCCn(with
d t stereochemistry)
hstereochemistry)
e C h e m i sfrom
tH
r 3yC
o finformation
E t CH
h e r 3s
structures
of
compounds
A,hB,
B, and
(with
from
the
information
the

60. Give the structures of compounds A, B, and C (with stereochemistry) from the informatio
e following
scheme.
(Hint:
A
Towhat
what
compound
class
does
the
following
scheme.
(Hint:
Aisis
isacyclic.)
acyclic.)
To
what
compound
class
does
the
in the following
scheme.
(Hint:
acyclic.)
class
does
the
product
in A
the
following
scheme.To
(Hint:
A iscompound
acyclic.)
To what
compound
does
the produc
*class
$product
60.
Give the
the structures
structures of
of compounds
compounds
A, B,
B, and
and CC (with
(with stereochemistry)
stereochemistry)from
fromthe
theinformation
information
A,
belong?
60. Give
ng?
F
u 3rbelong?
t h 2e)3rN,RCH
e a2 Cl
c t22i oCH
n s3 SO
o Na
l cHo23O,
h oDMF
n d2 Clt 2hExcess
e C hHe2Na
m22iS,
s tHr2yO, oDMF
f E t h e r s Ex
(CH
CH
S,
(CH
CH
O
2fCl,
2A
2l)s3 N,a CH

following
scheme.
(Hint:
acyclic.)
compound
the
the
F u rint hthe
e rfollowing
R e a c tscheme.
i o n s o(Hint:
f A lA
cAoisis
h oacyclic.)
l s a n To
dTo what
twhat
h e compound
C
h e m i sclass
tclass
r y does
odoes
f E
t hproduct
eproduct
rs

HC

CH

3
3
belong?
. Give
the structures of compounds A, B, and C (with stereochemistry)
fromCH
the
* informat
$
belong?
CH
H3C
SO Cl, C
(CH CH
) N, CH Clstereochemistry)
Na S, H O, DMF H
Excess
HO
. Give the structures of compounds A, AB,2 CHand
(with
from
the
33 3informatio
3C
C class
in the following scheme. (Hint: A is acyclic.) To whatB compound
prod
3
* * H$3does
$C SS the CH
in the following
scheme.
(Hint:
ACl22 is acyclic.)
To
what Excess
compound
class
does
the
produ
*33J3M
22 CH
Na
CH33SO
SO22Cl,
Cl, (CH
(CH33CH
CH22))33N,
N,CH
CH22Cl
Na2S,
DMF
ExcessHH
2O,
22O
22 2 H
JCH
M $
2 S,HH
2O,DMF
2O
H3C
CH
belong?
3C
O
60.
C
Give theA structures of compounds A,BBB, and C (with C
stereochemistry)
from the Oinformation
belong?
3

2 3

60. Give
the3 SO
structures
of )compounds
A,
B, and
C2O,
(with
stereochemistry)
from
the
information
H
DMFstereochemistry)
ExcessCHH2O
O
2Cl, (CH3 CH
3 N, CH2 Cl2 A,
2 S,C
2* * O
$ $ information
C H B,
O Na
CH SO
S
60. Give2 CH
structures
of 2compounds
and
(with
from
the
CH333SO
SO22scheme.
Cl, (CH
(CH333CH
CH222(Hint:
N,CH
CH222Cl
Cl
Na22S,
DMFwhat Excess
ExcessHH
B Na
Ccompound
Ain thethe
S
following
A
To
class Sdoes
the product
22 CH
))333N,
2Cl,
2 S,HH
2O,DMF
2O
2
22O,
22O
22 2
22 is acyclic.)
in the following
scheme.
(Hint:
A
is
acyclic.)
To
what
compound
class
does
the
J
M
J
M
B
C
C
H
O
H
S
O
H
S
O
C
C
B
C
A
C
H
S
Cproduct
H
6
14
2
8
18
2
6
8
18
2
6
6
12
6sequence
12S wa
61. In an attempt to make 1-chloro-1-cyclobutylpentane, the O
following
reaction
CH
HO3C OO
belong?
3
S
CH
H3desired
CSS* molecule
belong?
employed. The actual product isolated, however, was not the
an isome
$ for3but
C66H14
CC88H
J
M
CC6product
H
SS and give a mechanistic
O22
H1818SS2O
6a6 structure for the
12
1212
14O
2O
6H
J
M
of it.
Suggest
explanation
its formation
J
M
*
$
O
2 CH3 SO 2Cl, (CH3 CH2)3 N, CH2(Hint:
Cl2 See Chapter
Na2S, H2O, DMF
Excess H2O2 OO
OOO
2 CH3 SO 2Cl, (CH3 CH2)3 N, CH2 Cl
Na2S, Integration
H2O, DMFProblem
Excess H2O2 H 3C
2
CH33
B
CSS9-26.)
A
3
C666H14
O222
HB
SS
O
CH
H
C6HIn
H888H18
S
C8CC
14O
18
2O
C
18
6666
6H
12
3C
3
2A
222O
14
18
1212
6H
12S
61.
ake
InO1-chloro-1-cyclobutylpentane,
an
attempt
make
1-chloro-1-cyclobutylpentane,
theCC66Hthe
following
reaction
the
seque
* sequence
$S
an
attempt
to
1-chloro-1-cyclobutylpentane,
following
reaction
was
61. 14
attempt
to make
make to
1-chloro-1-cyclobutylpentane,
the
sequence
wasfo
MgCl following reaction
*
$
Cl
2 CH33SO 22Cl, (CH33CH22)33 N, CH22Cl22
Na22S, H22O, DMF
Excess
H
O
2
2
1. CH CH2CH2CH CHO
JSbut
Mananisomer
employed.
The
actual
product
isolated,
desired
2.
H
, H2O
2 CH3 SO
NaMg,
H2CH
O,)was
DMF
Excess
H
O2 molecule
Owas not
The
actual
product
isolated,
however,
not
the
desired
molecule
but
isomer
2Cl, (CH
3 CH2)3 N, CH
2 Cl2
2 S,(CH
Bhowever,
Cthe
A isolated,
J
M
l61.product
employed.
The
actual
however,
product
was
not
isolated,
the
desired
however,
molecule
was
not
but
the
a
O
O
B
C
A
In
an
attempt
to
make
1-chloro-1-cyclobutylpentane,
the
following
reaction
sequence
was
attempt
to
make
1-chloro-1-cyclobutylpentane,
the
following
reaction
sequence
was
Oformation.
of it. Suggest
aa structure
for
and
explanation
itsits
Suggestmake
structure
for the
the product
product
and give
give aa mechanistic
mechanistic
explanationOfor
for
formation.
S but
n attempt
1-chloro-1-cyclobutylpentane,
the
following
reaction
seque
C6H14O2toThe
C8H18Showever,
C6Hthe
2O 6
12S desired
employed.
actual
product
isolated,
was
not
molecule
ananisomer
The
actual
product
isolated,
however,
was
the
desired
molecule
butfor
isomer
JSMM
Cfor
O
C
Cnot
(Hint:
See
Chapter
Integration
Problem
OH
Cl mechanis
ture
of
the
product
a
structure
and
give
for
a
mechanistic
the
product
explanation
and
give
a
its
fo
6Hit.
14O
2 Suggest
8H18S9-26.)
29-26.)
6
6H12S
(Hint:
See
Chapter
Integration
Problem
J
O
O
loyed.
The
actual
productfor
however,
not theexplanation
desired
molecule
but a
of it.
Suggest
aa structure
the
and
mechanistic
Suggest
structure
forisolated,
the product
product
and give
give aawas
mechanistic
explanation
forOitsitsformation.
formation.
O for
C H14OProblem
C H S2O6
12S
2
Conc. HCl
66H12
ntegration
(Hint:
See
Chapter
9-26.)
Integration
Problem
9-26.)
(Hint:
Integration
C66See
H
C88H1818S9-26.)
H
S following
Chapter
Integration
Problem
9-26.)
notreaction sequence
Suggest
a14Ostructure
for1-chloro-1-cyclobutylpentane,
the Problem
product
and
give
aCC6mechanistic
explanation
for its fo
2Chapter
2O
6
12
.. In
In
an
attempt
to make
the
w
MgCl
an
attempt
the
following reaction
sequence wa
Cl
MgCl 1. CH CH CH CH CHO
Clto make 1-chloro-1-cyclobutylpentane,
1. CH CH CH
CHnot
CHO the desired molecule but an isom
employed.
The actual
actual
product
isolated,9-26.)
however,
was
t:61.
See
Chapter
Integration
Problem
2.2.HH , ,HHfor
OO
Mg,
CH
employed.
The
product
however,
was
not
desired
moleculesequence
but an isome
62. Suggest better
methods
the final
stepthe
infollowing
Problem
61. reaction
Mg,
(CH
CH ))O
O isolated,
In an
an attempt
attempt
to (CH
make
1-chloro-1-cyclobutylpentane,
the
was
61.
In
to
make
1-chloro-1-cyclobutylpentane,
the
following
reaction
sequence
was
MgCl
MgCland
of it.
it. Suggest
SuggestCl
structure for
for the
the product
product
and
give
mechanistic
explanationfor
foritsitsformatio
formati
Cl
of
aa structure
give
aaCH
mechanistic
explanation
CH
CH
CH
CHO
employed. The
The
actual product
product
isolated, however,
however,
was
not
the desired
desired
molecule
butananisomer
isomer
CH
CHstudy
CH
CH
CHO
63.
In1.1.
an
early
of
the
stereochemistry
of
nucleophilicbut
displacements,
opticall
employed.
actual
isolated,
not
the
molecule
2.2.HH , ,HHOwas
Mg,
(CH
MgCl
MgCl
O was
Mg,
(CH CH
CH ))OO
(Hint:
See
Chapter
Integration
Problem
9-26.)
Cl
pure
(R)-1-deuterio-1-pentanol
treated with 4-methylphenylsulfonyl
(tosyl)formation.
chloride to mak
(Hint:
Chapter
Integration
Problem
9-26.)
of it.
it.See
Suggest
structure
for the
the
product
andtosylate.
giveCHO
a mechanistic
mechanistic
explanation
for
MgCl
of
Suggest
aa structure
for
product
and
give
explanation
for
itsits
formation.
Cl
1.OH
CH
1.
CH
the
corresponding
tosylate was then
treated
with3CH
excess
ammonia
to
convert it t
3CH2CH
2CH
2 aThe
2CH
2CH
2CHO
Cl


OH
Cl
1.
CH
CH
CH
CH
CHO
(Hint:
See
Chapter
Integration
Problem
9-26.)
1-deuterio-1-pentanamine:
3
2
2
2
2.Problem
H3CH
, H2)2O
2. H , H2O
H3CH(Hint:
Mg, (CH
O
See
Chapter Integration

2)2O
29-26.)
Mg, (CH3CH2)2O
MgCl 2. H , H2O
Cl
OH
ClCl
Cl
OHMgCl 1. CH3Conc.
CH
SO Cl
CHCH
HCl
2CH
2CH2CHO
1.2.CH
CH
3CH
Excess NH
Conc.
2
2HCl
2CHO
not
(R)-CH
CHDOH
CH3CH2CH2CH2CHDNH2
H
,
H
MgCl
Mg,
(CH
3CH2CH2CH
2
2O
Cl
3CH2)2O
not
MgCl 2.1.HCH, H
2O
ClMg, (CH3CH2)2O
3CH 2CH 2CH 2CHO
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
6

14

18 2

33
3

333

22 22
2 2

222 222

22
2

22
2

33 3



22 2

22 2

22 2

2 2

33
22

2
 3
22
2

12

22 2

33
22
22
22
1. CH3CH
2CH2CH2CHO
HConc.
22
2O HCl
2.2.HH, ,HConc.
HCl
2O
not
(a) Describe the stereochemistry that you
expect to observe at C1 of both the intermediate tosylat
not
62.
Suggest
better
methods
for
the
fi
nal
step
in
Problem
61.
and the
finalin
amine.
62. Suggest better methods for the final
step
Problem 61.
OH
(b) When the reaction sequence is actually carried out, the
expected results are not obtained
OH
ClCl
Instead,
the
finalProblem
amine is isolated
as nucleophilic
a 70 : 30 mixture ofdisplacements,
(S)- and (R)-1-deuterio-1pentanamine
OH
Cl
63. Suggest
an
of
the
stereochemistry
optically
62.
for
the
nal
step
in
61.
Cl
62.
Suggest better
betterIn
methods
forstudy
the fifiOH
nal
step
in Problem
61.of
63.
Inmethods
an early
early
study
of
the
of(Hint:
nucleophilic
displacements,
optically
Suggest
astereochemistry
mechanistic explanation.
Recall that reaction
of an alcohol with
a sulfony
Conc.
HCl
pure
(R)-1-deuterio-1-pentanol
was
treated
with
4-methylphenylsulfonyl
(tosyl)
chloride
totomake

chloride
displaces
chloride
ion,
which
is
a
nucleophile.)
pure (R)-1-deuterio-1-pentanol
was
treated
with
4-methylphenylsulfonyl
(tosyl)
chloride
make
O
Br
Conc.HCl
HCl
Conc.
63.
In
an
early
study
of
the
stereochemistry
of
nucleophilic
displacements,
optically
Conc.
HCl
Conc.
HCl
A
Aearly study
63. the
In
an
of
the
stereochemistry
of
nucleophilic
displacements,
optically
corresponding
tosylate.
The
tosylate
was
then
treated
with
excess
ammonia
to
convert
it
not
Conc.
HCl
not
Conc.
HCl
the corresponding
The
with
excess
convert ittoattoth
64. tosylate
What is the was
productthen
of the treated
reaction shown
margin?ammonia
(Pay attentionto
to stereochemistry
CC
CCH2CH2CH2tosylate.
notin the
pure
was
treated
with
4-methylphenylsulfonyl
(tosyl)
not
H (
( H
1-deuterio-1-pentanamine:
pure (R)-1-deuterio-1-pentanol
(R)-1-deuterio-1-pentanol
was
treated
with
(tosyl)chloride
chloridetotomake
make
reacting
centers.)
What4-methylphenylsulfonyl
is the kinetic order
of this reaction?
1-deuterio-1-pentanamine:
D
CH
3
the
tosylate. The tosylate
was then
treated
with excess
ammonia
totoconvert
itittoto
the corresponding
corresponding
then
treated
excess
ammonia
convert
DMSOtosylate. The
65. tosylate was
Propose
syntheses
of the with
following
molecules,
choosing reasonable
starting material
. 62.
Suggest
better
methods
for
the
nal
step
in
Problem
61.
1-deuterio-1-pentanamine:
methods
for
the
fifinal
step
Problem
61.
on the
basisin
of
the
principles
of
synthetic strategy introduced in preceding chapters, particularly i
1-deuterio-1-pentanamine:
Suggest
better
methods
for
the
fi
nal
step
in
Problem
61.
CH
SO
Cl
62. Suggest better methods for the fiCH
nal
step
in Problem
61.for carboncarbon bond formation are indicated by wavy lines.
33
2
Section
8-9. Suggested
SO2 2Clpositions
3
Excess NH33
(R)-CH3CH2CHan
CH3CH2CH
Excess
NH
2CH
2CHDOH
2CH22CHDNH22 optica
3
. 63.
early
study
of
the
stereochemistry
nucleophilic
CHDOH
CH3CH
CH
an
early
ofofnucleophilic
nucleophilic
displacements,
opticall
CH
CH3stereochemistry
CH
CH32CH2CHDNH
3CHIn
2CH
2CH
2early
2displacements,
2
In
an
earlystudy
studyof
ofthe
the
stereochemistry
of
nucleophilic
displacements,
optically
2CH SO
CH
Cl2CH2SO3H of
63. (R)-CH
In
an
study
of
the
stereochemistry
displacements,
optically
CH
SO
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
CH333
SO22Cl
2Cl
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
Excess
NH33 (b) CH CH
(R)-1-deuterio-1-pentanol
was
treated
with
4-methylphenylsulfonyl
(tosyl)
chloride
ma
pure
(R)-1-deuterio-1-pentanol
was
4-methylphenylsulfonyl
(tosyl)
chloride
totomak
Excess
(R)-1-deuterio-1-pentanol
was
treatedwith
with 4-methylphenylsulfonyl
4-methylphenylsulfonyl
(tosyl)
chloride
CHO
(a)treated
C 2CH
(R)-CH
CH
pure
(R)-1-deuterio-1-pentanol
treated
with
(tosyl)
chloride
totomake
3 3CH
2CH
22CH
ExcessNH
NH3
3CH2CH2CH2CHDOH was
2CHDNH
2make

(CH3CH
CH2))2OO
Mg, (CH
Mg,
3
2 2

OH

OH

OH

Cl

Cl

not

not

not

gest better methods for the final step in Problem 61.

62.
ds for
Suggest
the
final
better
methods
in ofProblem
the
61.final step
in Problem
61.
In an
earlystep
study
the for
stereochemistry
of nucleophilic
displacements,

(R)-1-deuterio-1-pentanol was treated with 4-methylphenylsulfonyl (tosyl) chloride

(R)-CH3 CH2 CH2 CH2 CHDOH

CH3 CH2 CH2 CH2 CHDNH2

3
2
2
2
3
2
2
2
corresponding
tosylate.
The
tosylate
was
then
treated
with
excess
ammonia
toconvert
convert
the (a)
corresponding
The
tosylate
was
treated
with
excess
ammonia
toconvert
ititt
corresponding
tosylate.
The
tosylate
was then
then
treated
with
excess
ammonia
itcon
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
corresponding
tosylate.
The
tosylate
then
treated
with
excess
toit2nuc
CHammonia
CHtotoconvert
the
corresponding
tosylate.
The
tosylate
was
then
treated
with
excess
ammonia
toto
Describeof
the tosylate.
stereochemistry
that
youwas
expect
toof
observe
at
C1
of
both
the
intermediate
tosylate
63.
arly
study
the
Instereochemistry
an
early
study
of
nucleophilic
the
stereochemistry
displacements,
of
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
1-Deuterio-1-pentanamine
(a) (R)-1-Deuterio-1-pentanol
Describe the stereochemistry that you expect to observe at C1 of both
the intermediate tosylate
1-deuterio-1-pentanamine:
1-deuterio-1-pentanamine:
1-deuterio-1-pentanamine:
1-deuterio-1-pentanamine:
and
the final amine.
66. Give efficient syntheses of each of the following compounds, beginning with the indicated start
uterio-1-pentanamine:
and
the (R)-1-deuterio-1-pentanol
final
amine.
-pentanol
pure
was
treated
with
4-methylphenylsulfonyl
was
treated
with
(tosyl)
4-methylpheny
chloride
(a)
Describe
the
stereochemistry
that
you
expect
to
observe
at
C1
of
both
the
intermediate
tosylate
ing
material.
(b)
When thethe
reaction
sequence that
is actually
carried
out, theat expected
are not obtained.
(a) Describe
stereochemistry
you expect
to observe
of bothresults
the intermediate
tosylate
(b)
When
theamine.
reaction
sequence (a)is trans-1-Bromo-2-methylcyclopentane,
actually
carried
out, the C1
expected
results
are not obtained.
from
cis-2-methylcyclopentanol
and
the
fifi
nal
Instead,
the
nal
amine is was
isolated
as a 70treated
: 30
mixture
of (S)- excess
and
(R)-1-deuterio-1pentanamine.
CH
SO
Cl
and
the
nalfifitosylate
amine.
sylate.
theWhen
The
corresponding
tosylate.
then
The
with
was
then
ammonia
treated
to with
con
CH
Cl
CH
SO
Cl tosylate
CH
SO
Cl
Instead,
the
nal
amine sequence
is isolated
a 70 : 30
mixture
of the
(S)and
(R)-1-deuterio-1pentanamine.
(b)
the
reaction
isasactually
carried
out,
expected
results
are
not
obtained.
from
3-pentanol
(b)
Excess
NH
Excess
NH
CH
SO
Cl
Excess
NH
Excess
NH
Suggest
a
mechanistic
explanation.
(Hint:
Recall
that
reaction
of
an
alcohol
with
a
sulfonyl
CH
CH
CHDOH
CH
CH
CH
CH
CHDNH
(b)
When
the
reaction
sequence
is
actually
carried
out,
the
expected
results
are
not
obtained.
(R)-CH
CH
CH
CH
CHDOH
CH
CH
CH
CH
CHDNH
22 2CH
22 2CHDNH
33 22CH
22 22CHDOH
22
3 3 3CH
2 22 2CH
2 22 2 2
(R)-CH
CH
CHDOH
CH
CH
3alcohol
22CH
22CH
2aCHDNH
3CH
22CH
Suggest
a 22mechanistic
explanation.
Recall
reaction
ofCH
an
with
sulfonyl
mine:
1-deuterio-1-pentanamine:
NH(R)-1-deuterio-1Instead,
amine
is
isolated
as (Hint:
a 70
mixturethat
of Excess
(S)and
pentanamine.
CN
chloride
displaces
chloride
ion, which
a::30
nucleophile.)
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
1-Deuterio-1-pentanamine
CH
CH2the
CHfifi2nal
CHDOH
CH3CH2CH
Instead,
the
nal
amine
is isolated
as ais70
30 mixture of (S)- and (R)-1-deuterio-1pentanamine.
3CH
2(R)-1-Deuterio-1-pentanol
2CH2CHD
2

3 333

22
22 22

3 33
33 3

(R)-1-Deuterio-1-pentanol
(R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanamine
chloride adisplaces
chloride
ion, which
is a nucleophile.)
Suggest
mechanistic
explanation.
(Hint:
Recall that reaction of an1-Deuterio-1-pentanamine
alcohol with a sulfonyl

Suggest a mechanistic explanation. (Hint: Recall that reaction of an alcohol

with a sulfonyl
R)-1-Deuterio-1-pentanol
1-Deuterio-1-pentanam
64. chloride
What is the
productchloride
of the reaction
shown
the margin? (Pay attention to stereochemistry at the
displaces
ion, which
is a innucleophile.)

Suggest a mechanistic explanation. (Hint: Recall that reaction of an alcohol with a sulfonyl
Suggest
a mechanistic
explanation.
(Hint:
Recall
that
reaction
of
an
alcohol
with
aa asulfonyl
mechanistic
explanation.
(Hint:
Recall
that
reaction
an
alcohol
with
sulfonyl
Suggest
mechanistic
explanation.
(Hint:
Recall
that
reaction
ofof
an
alcohol
with
sulfonyl
expect
to
observe
at
C1
of
both
the
intermediate
tosylate
(a)Describe
Describe
the
stereochemistry
that
you
expect
toobserve
observe
at
C1
of
both
the
intermediate
tosylate
chloride adisplaces
chloride
ion,
which
is a nucleophile.)
(a)
the
stereochemistry
that
you
expect
totoobserve
at at
C1
of
both
thethe
intermediate
tosylate
(a)
Describe
the
stereochemistry
that
you
expect
to
observe
at
C1
of
both
the
intermediate
tosylate
(a)
Describe
the
stereochemistry
that
you
expect
C1
of
both
intermediate
tosylate
chloride
ion,
which
is
and
the
nal
amine.
chloride displaces
displaces chloride
chloride
ion,
which
nucleophile.)
and
amine.
andthe
thefifinal
final
nal
amine.
and
the
fifi
nal
amine.
chloride
displaces
chloride
ion,
which
isis aaa nucleophile.)
nucleophile.)
and
the
amine.
actually
carried
out,
the
expected
results
are
not
obtained.
(b)
sequence
actually
carried
out,
thethe
expected
results
areare
not
obtained.
(b)When
Whenthe
thereaction
reaction
sequence
isactually
actually
carried
out,
the
expected
results
are
not
obtained.
(b)
When
the
reaction
sequence
actually
carried
out,
the
expected
results
are
not
obtained.
(b)
When
the
reaction
sequence
isis
carried
out,
expected
results
not
obtained.
64. What is the product of the
reaction
shown
in
theismargin?
(Pay
attention
to stereochemistry
at the
30
mixture
of
(S)and
(R)-1-deuterio-1pentanamine.
Instead,
the
amine
isin
isolated
as
aasa70
:70
30
mixture
ofof(S)and
(R)-1-deuterio-1pentanamine.
64.
is
product
of
reaction
shown
the
margin?
(Pay
attention
to
stereochemistry
at
Instead,
thefifinal
nal
amine
isisolated
isolated
30
mixture
of(S)(S)and
(R)-1-deuterio-1pentanamine.
Instead,
the
fifinal
nal
amine
is
isolated
aa70
70
:::30
mixture
of
(S)and
(R)-1-deuterio-1pentanamine.
Instead,
the
amine
is
asas
: 30
mixture
and
(R)-1-deuterio-1pentanamine.
64.
What
is the
the
product
of the
the
reaction
shown
in
the
margin?
(Pay
attention
stereochemistry
atthe
the
64. What
What
is
the
product
of
the
reaction
shown
in
the
margin?
(Pay
attention
toto
stereochemistry
at
the
reacting
centers.)
What
is
the
order
of
this
reaction?
Suggest
mechanistic
explanation.
(Hint:
Recall
that
reaction
of
an
alcohol
with
aasulfonyl
sulfonyl
Suggest
akinetic
explanation.
(Hint:
Recall
that
reaction
ofofan
with
a sulfonyl
(Hint:
Recall
that
reaction
of
an
alcohol
with
sulfonyl
Suggest
mechanistic
explanation.
(Hint:
Recall
that
reaction
ofanalcohol
analcohol
alcohol
with
sulfonyl
Suggest
mechanistic
explanation.
(Hint:
Recall
that
reaction
of
an
alcohol
with
Suggest
aaaamechanistic
mechanistic
explanation.
(Hint:
Recall
that
reaction
with
a aasulfonyl
reacting
centers.)
What
is
the
kinetic
order
of
this
reaction?
reacting
centers.)
What
is
the
kinetic
order
of
this
reaction?
centers.)
What is
the kinetic
order
of
this
reaction?

chloride
displaces
chloride
ion,
which
isisis
aisanucleophile.)

nucleophile.)
chloride
displaces
chloride
ion,
which
nucleophile.)
chloride
displaces
chloride
ion,
which
aanucleophile.)
nucleophile.)
O
Br
Br

chloride
displaces
chloride
ion,
which
Oreacting
Br
O
Br
AAA
AAA
65.CCH
Propose
syntheses
of
the
following
molecules,
choosing
reasonable
starting
materials
64.
What
product
of
the
reaction
shown
ininin
the
margin?
(Pay
attention
to to
stereochemistry
at the
65.
syntheses
of
the
molecules,
choosing
reasonable
starting
materials
in
the
margin?
(Pay
attention
to
stereochemistry
atthe
the
CH22CH
CH22222C
CCCCC Propose
CCH22CH
64.
Whatisisis
isthe
the
product
of
the
reaction
shown
inthe
the
margin?
(Pay
attention
to
stereochemistry
atthe
the
64.
What
the
product
of
the
reaction
shown
the
margin?
(Pay
attention
to
stereochemistry
64.
What
the
product
of
the
reaction
shown
margin?
(Pay
attention
stereochemistry
atat
65.
CH
CH
C
CCH
Propose
syntheses
of
the following
following
molecules,
choosing
reasonable
starting
materials
65.
Propose
syntheses
of
the
following
molecules,
choosing
reasonable
starting
materials
H ((( on 22the22 basis
((( H
of
the principles
ofcenters.)
synthetic
introduced
inreaction?
preceding
chapters,
particularly
in
reacting
What
isstrategy
the
kinetic
order
ofofof
this
reaction?
H
H the
reacting
centers.)
What
the
kinetic
order
of
this
reaction?
reacting
centers.)
What
isthe
the
kinetic
order
ofthis
this
reaction?
H
order
this
reaction?
reacting
What
isis
kinetic
order
the
of
synthetic
strategy
introduced
in
chapters,
particularly
in
D
CH
CH333on
the principles
principles
ofcenters.)
synthetic
strategy
introduced
preceding
chapters,
particularly
Dof
D
CH
on
the basis
basis
of
the
principles
of
synthetic
strategy
introduced
ininpreceding
preceding
chapters,
particularly
inin
Section
8-9.
Suggested
positions
for
carbon

carbon
bond
formation
are
indicated
by
wavy
lines.
DMSO
65.
Propose
syntheses
of
the
following
molecules,
choosing
reasonable
starting
materials
DMSO
Section
8-9.
positions
for
carbon
carbon
bond
formation
are
indicated
by
wavy
lines.
DMSO
following
molecules,
choosing
reasonable
starting
materials
DMSO
65.
Propose
syntheses
ofthe
the
following
molecules,
choosing
reasonable
starting
materials
65.
Propose
syntheses
the
following
molecules,
choosing
reasonable
starting
materials
Propose
syntheses
ofof
following
molecules,
choosing
reasonable
starting
materials
Suggested65.
positions
for
carbon
carbon
bond
formation
are
indicated
by
wavy
lines.
Section
8-9. Suggested
Suggested
positions
for
carbon
carbon
bond
formation
are
indicated
by
wavy
lines.
on
the
principles
ofofof
synthetic
strategy
introduced
in inpreceding
chapters,
particularly
in inin
strategy
introduced
in
preceding
chapters,
particularly
inin
on
the
basis
of
the
principles
synthetic
strategy
introduced
in
preceding
chapters,
particularly
onthe
thebasis
basisofof
of
the
principles
of
synthetic
strategy
introduced
in
preceding
chapters,
particularly
on
the
basis
the
principles
synthetic
strategy
introduced
preceding
chapters,
particularly
CH
HSuggested
CH3CH2CH
CH CH2CH
CH
Section
8-9.
positions for carbon
carbon
bond
formation
are are
indicated
by wavy
lines.lines.
2SO
38-9.
3formation
carbon
carbon
bond
formation
indicated
by
wavy
H
CH
CH
Section
Suggested
positions
for
carbon
bond
are
indicated
wavy
lines.
Section
carbon
are
indicated
byby
wavy
lines.
Section
8-9.
Suggestedpositions
positionsfor
forcarbon
carbon
carbon
carbonbond
bond
formation
are
indicated
by
wavy
lines.
22SO
3formation
CH222CH
CH
SO338-9.
H Suggested
CH CH
CH
CH
CH333CH
CH222CH
CH
3H
2SO
33
CH
CH
CH3CH
2CH
2SOSO
3H H
3CH
2CH
CH
CH
CH
CH
CH
CH
CH
SO
H
CH
CH
CH
CH
CH
CH
CH
222CH
222SO
333H 3CH2CH2
CH
CH
(a)
(b)
CH333CH
CH
C CHO
22CH
22SO
33H
222CH
3 3333
33CH
22CH CH
CH
(a)
(b)
C
2
CH22(b)
CH
CHO
CH333CH
(b) CH
C 2CHO
CH
CHO
CH
(a)
(b)
CCH
CH
(a)
C CCHO
2CH
2CH
3CH
2CHCH
CHO
(b)
(a)
(b)
CHO
CH
(a)
(b)
CH
CHO
CH
(a)
(b)2CH
C CHO
2CH
3CH
2CH
2 2222 CC
3333CH
222CH
CH
2CH
32CH3
CH
CH
CH
2
3
CH2CH
CH
CH
CH
CH
2CH
3CH
2CH
2CH
3 3333
222CH
3CH
66.
Give
effi
cient
syntheses
of
each
of
the
following
compounds,
beginning
withthe
the indicated
indicated start66.
Give effi
efficient syntheses
syntheses
of
each
of the
the
following
compounds,
beginning
with
startfollowing
compounds,
beginning
with
the
indicated
start66.
Give
effi
of
the
beginning
with
the
indicated
start66. Give
of
each
of
following
compounds,
beginning
with
indicated
start66.
Give
effi
cient
syntheses
of
each
the
following
compounds,
beginning
with
the
indicated
start66.ing
Give
efficient
cient
syntheses
ofeach
eachofof
of
thefollowing
followingcompounds,
compounds,
beginning
with
the
indicated
startmaterial.
66.
syntheses
of
each
of syntheses
the
following
compounds,
beginning
withthe
the
indicated
startGive
efficient
cient syntheses
of
each
of
the
following
compounds,
beginning
with
the
indicated
starting
material.
ing
material.
ing
material.
ing
material.
ing
(a) trans-1-Bromo-2-methylcyclopentane, from cis-2-methylcyclopentanol
ing material.
material.
(a)
trans-1-Bromo-2-methylcyclopentane,
from
cis-2-methylcyclopentanol
from
cis-2-methylcyclopentanol
(a)
trans-1-Bromo-2-methylcyclopentane,
from
cis-2-methylcyclopentanol
(a)
trans-1-Bromo-2-methylcyclopentane,
from
cis-2-methylcyclopentanol
(a) trans-1-Bromo-2-methylcyclopentane,
trans-1-Bromo-2-methylcyclopentane,
fromcis-2-methylcyclopentanol
cis-2-methylcyclopentanol
(a)
from
from 3-pentanol
(b)
trans-1-Bromo-2-methylcyclopentane,
from
cis-2-methylcyclopentanol
(a) trans-1-Bromo-2-methylcyclopentane,
cis-2-methylcyclopentanol
from
3-pentanol
(b)
from
3-pentanol
(b)
fromfrom
3-pentanol
(b)
CN
from 3-pentanol
3-pentanol
(b)
from
(b)
CN
CN
CN
from 3-pentanol
3-pentanol
from
(b)
CN
CN
CN
CC

-methylhexane, from 3-methyl-2-hexanol

Problems
Chapter 9
383
om
2-bromoethanol
(two
equivalents)
3-methylhexane,
from
3-methyl-2-hexanol
PPr roobbl leemms s
(c) 3-Chloro-3-methylhexane, from 3-methyl-2-hexanol
Problems

msss
m
PPPrrrooobbbllleeem
3-Chloro-3-methylhexane,
from 3-methyl-2-hexanol
3-methyl-2-hexanol
Omethods of alkene
(c) 3-Chloro-3-methylhexane,
from
ollowing
synthesis from a general primary
alc
from
2-bromoethanol
(two
equivalents)
O
disadvantages of each one.
(d)
, from 2-bromoethanol (two equivalents)
(d)

from 2-bromoethanol
2-bromoethanol
(two
equivalents)
(d)
, from
equivalents)
(c) 3-Chloro-3-methylhexane,
3-Chloro-3-methylhexane,
from(two
3-methyl-2-hexanol
(c)
3-Chloro-3-methylhexane,
from
3-methyl-2-hexanol
(c)
from
3-methyl-2-hexanol
SS
O methods of
following
alkene
synthesis
from a general primary a
CH2
RCH P
O
0C
8methods
67. Compare
following
of alkene
alkene synthesis
synthesis from a general primary alcohol. State the
the following
of
, 1methods
(d)
, from
from 2-bromoethanol
2-bromoethanol
(two equivalents)
equivalents) from a general primary alcohol. State the
4of
(two
equivalents)
(d)
nd
disadvantages
each
one.
,and
(two
O
S
Compare
following
methods
of
alkene
synthesis from a gene
advantages the
and
disadvantages
of
each
one.
disadvantages
of each one.
H2
SS

advantages
and disadvantages of each one.
RCH
2CH
2OH
PCH
P
CH22 from
RCH
RCH
ohol.
State
67.
Compare
the the
following
methods of
ofCCalkene
alkene
synthesis
from aaa general
general primary
primaryalcohol.
alcohol.State
Statethe
the
of
synthesis
from
general
primary
alcohol.
State
the
67. Compare
the
following
synthesis
8800 alkene
PBmethods
, ,11
OO each
r HHSC
RCH
advantages and
and disadvantages
disadvantages
each
one. P CH2
Sof
one.
advantages
each
one.
0 of
8
1
,
RCH
RCH22CH
CH
OH
K RCH
OC(CH
SO22OH
P)CH2
PPBB
H
02C
rr CC
PCH
CH
RCH
P
RCH

RCH P CH2
RCH
P
RCH
22
2CH
28Br
, 1CH
88000C
,,1118
O
KK OC(CH
OC(CH) )
OO,
S
O
S
S
S
RCH2CH2OH
HH
RCH
RCH
H
PCH
CH2 2
RCHP
RCH22CH
CH22Br
Br
H
PB
RCH22CH
CH222OH
OH
RCH
r
PBB
RCH
Brrr
2CH2PPOH
PB
compounds
(Chapter
reactions
characteristic
68. Sugars, being polyhydroxylic
polyhydroxylic
compounds
(Chapter
undergo
reactions
characteristic ofof
polyhydroxylic
compounds
(Chapter
24),
reactions
ch
Kundergo
)
K24),
OC(CH
) undergo
OC(CH
r KK24),
OC(CH
))OC(CH
PCH
P
CH2RCH
RCH
RCH222CH
CH22(the
BrBr
CH
RCH
RCH
CH
Br
alcohols. In one
glycolysis
metabolismRCH
ofof glucose),
gluP
RCH
2Br
one of
of the
the later
later steps
steps in
in
glycolysis
(the
glucose),
oneof
ofthe
the
glu22 one
P
CH
RCH
CH
2
2
2 metabolism
e ofcosethe
later with
steps
in glycolysis
(the
metabolism
of
glucose),
metabolites
aa remaining
OC(CHinto
) o
metabolites with
remaining hydroxy
hydroxy group,
group, 2-phosphoglyceric
2-phosphoglyceric acid,
acid,isisKconverted
converted
into
2-phosphoenolpyruvic
acid.
This
catalyzed
by
enolase
the
RCH
2-phosphoenolpyruvic
acid. hydroxy
This reaction
reaction isis
catalyzed2-phosphoglyceric
bythe
theenzyme
enzyme
enolase
thepresence
presenceof
of
es68.with
a remaining
group,
acid,
is
2CH
2Br inin
21
polyhydroxylic
compounds
(Chapter
24),
undergo
reactions
characteristic
of
compounds
(Chapter
24),
undergo
reactions
characteristic
of
Sugars,
polyhydroxylic
24),
undergo
reactions
characteristic
of
a Lewis being
acid such
as
How
you
this
reaction?
(b)
isisthe
such
as Mg
Mg21.. (a)
(a)compounds
How would
would(Chapter
you classify
classify
this
reaction?
(b)What
What
thepossible
possible
steps
in
glycolysis
(the
metabolism
of
glucose),
one
of
the
gluone
of
thereaction
later steps
steps
in
glycolysis
(the metabolism
metabolism
of glucose),
glucose),one
oneof
ofthe
thegluglualcohols.
one
of
the
later
in
glycolysis
(the
of
pyruvic
This
is
catalyzed
by
the
enzyme
enolase
in
t
role
of acid.
theInLewis
acidic
metal
ion?
Lewis acidiccompounds
metal ion?
g polyhydroxylic
(Chapter
24), undergo
reactions
remaining
hydroxy
group,
2-phosphoglyceric
acid,
converted
into
metabolites
with aa remaining
remaining hydroxy
hydroxy
group, 2-phosphoglyceric
2-phosphoglyceric
acid,isisisconverted
converted
into
with
group,
acid,
into
uch cose
as metabolites
Mg21. (a)
How
would
you
classify
this
reaction?
(b)
What
reaction
is
catalyzed
by
the
enzyme
enolase
in
the
presence
of
2-phosphoenolpyruvic
acid.
This
reaction
is
catalyzed
by
the
enzyme
enolase
in
the
presence
of
2-phosphoenolpyruvic
acid.
This
reaction
is
catalyzed
by
the
enzyme
enolase
in
the
presence
of
one
of thebeing
later polyhydroxylic
steps
in glycolysis
(the metabolism
of24),
glucose),
Sugars,
compounds
(Chapter
under
21
21
2
How
would
you
classify
this
reaction?
(b)
What
the
possible
such as
as
Mg21
(a)332
How would
would you
you classify
classify this
thisreaction?
reaction?(b)
(b)What
Whatisisisthe
thepossible
possible
a Lewis acid
such
Mg
.. (a)
How
OPO
wis
acidic
metal
ion?
OPO
OPO322
AAthe
ites
with
remaining
hydroxy
group,
2-phosphoglyceric
acid, i
ion?
DDOPO3 (the metabolism
Lewis
acidicof
metal
ion?
role
of theaIn
Lewis
acidic
metal
ion?
Enolase,
Mg
alcohols.
one
later
steps
Enolase,
Mg in glycolysis
HOCH
CH
OCH
OCOOH
PCCG
HOCH22O
CHO
COOH
CH22P
haracteristic
of
olpyruvic
acid.
Thiswith
reaction
is catalyzed
by
the
enzyme
enolase in
GCO
cose metabolites
a remaining
hydroxy
group,
2-phosphogl
2H
CO
2H
21
2
2
2
one
of
the
glu2-Phosphoglyceric
2-Phosphoenolpyruvic
acid
OPO
2
2
OPO
2
333 acid
2-Phosphoglyceric
acid
2-Phosphoenolpyruvic
acid
such
as
Mg
.
(a)
How
would
you
classify
this
reaction?
(b) enzy
Wha
2
OPO
OPO
OPO333
2-phosphoenolpyruvic
reaction is DDcatalyzed
by the
OPO3 AA acid. This
Enolase,
Mg
Enolase,
D
Enolase,Mg
Mg
OPO32
converted
into
21
P
COOH
CH
HOCH
CH
OCH
OCOOH
PCCC
HOCH
CHO
COOH
CH222P
222O
ewis
acidic
ion?
Ametal
a69.Lewis
acid
such
as
Mg
.
(a)
How
would
you
classify
this
reac
GG
G
D 5-methyl-FH
Enolase, Mg
The
formidable-looking
molecule
CO
CO
CO22H
69.
The
formidable-looking
molecule 5-methyltetrahydrofolic
5-methyltetrahydrofolicacid
acid
(abbreviated
5-methyl-FH4)4)isisthe
the
he
presence
ofO COOH
O
P
HOCH
CH
CH(abbreviated
C2HHfrom
2the
2atoms
role
of
Lewis
acidic
metal
ion?
product
of
sequences
of
biological
reactions
that
convert
carbon
a
variety
of
simple
2-Phosphoglyceric
acid
2-Phosphoenolpyruvic
acid
2-Phosphoglyceric
acid
2-Phosphoenolpyruvic
acid
2-Phosphoglyceric
acid
2-Phosphoenolpyruvic
acid
product of sequences of biological reactions that convert carbon atoms G
from a variety of simple
is the
possible
molecules,
such
molecules,
such as
as formic
formic acid
acid and
and the
the amino
amino acid
acid histidine,
histidine,into
intomethyl
methylgroups.
groups.
CO2H
2
44

22



44

3 3

22

33

222

444




3 33 3

33

333








333333

3
3 3
3



2
2

2
2
2

2

2

3 3

2-Phosphoglyceric
2-Phosphoglyceric
acid
2-Phosphoglyceric
2-Phosphoglyceric
acid acidacid
2-Phosphoglyceric acid

22

CO2H
2-Phosphoenolpyruvic
acidacid
2-Phosphoenolpyruvic
acid
2-Phosphoenolpyruvic
2-Phosphoenolpyruvic acid

2-Phosphoenolpyruvic acid

The
formidable-looking molecule
molecule 5-methyltetrahydrofolic
5-methyltetrahydrofolicacid
acid(abbreviated
(abbreviated5-methyl-FH
5-methyl-FH)4)isisthe
the
The formidable-looking
4
product
of
sequences of
ofmolecule
biological
reactions
that convert
convertacid
carbon
atomsfrom
from
avariety
variety4of
The The
formidable-looking
5-methyltetrahydrofolic
(abbreviated
5-methyl-FH
)of
is4)simple
the
formidable-looking
molecule
5-methyltetrahydrofolic
acid
(abbreviated
isthe
the
69.
formidable-looking
molecule
5-methyltetrahydrofolic
acid
(abbreviated
5-methyl-FH
is
product
of
sequences
biological
reactions
that
carbon
atoms
a5-methyl-FH
4)simple
The
formidable-looking
molecule
5-methyltetrahydrofolic
acidcarbon
(abbreviated
5-methyl-FH
thesimple
4) isof
product
of
sequences
of
biological
reactions
that
convert
atoms
from
a
variety
molecules,
such
as
formic
acid
and
the
amino
acid
histidine,
into
methyl
groups.
sequences
ofacid
biological
reactions
that convert
convert carbon
carbon
atomsfrom
from
varietyofofsimple
simple
product such
of sequences
of
biological
that
atoms
aavariety
molecules,
as formic
and
thereactions
amino
acid
histidine,
into from
methyl
groups.
product
of sequences
of biological
reactions
that convert
carbon atoms
agroups.
variety
of simple 5-met
-looking
molecule
5-methyltetrahydrofolic
acid
(abbreviated
molecules,
such
as formic
acid
and
the the
amino
acidacid
histidine,
intointo
methyl
such
as formic
formic
acid
and
the
amino
acid
histidine,
into
methyl
groups.
molecules,
such
as
acid
and
amino
histidine,
methyl
groups.
molecules, such as formic acid and the amino acid histidine, into methyl groups.

uences
O of biological reactions that convert carbon atoms from a va
O
O
BB O
h as Oformic
acid and the amino acid histidine, into methyl groups.
B B
C
C

BH
HE
OH
H
OH
ECCH
H
EC
H
E
HFormic
OH OH
H OH
Formic
acid
H
acid

E H

Four st
Fo
ur st eps

eps
Fo st
Fo
Four
urst eps
Four ur
s
stepseps step

HH
H22NNH NN H HNNHH
H
OH
NH22
OO M DDOH
NH
H
H
N
H
N
NN
N
N
N
H
N
N
2
2
2
H
N
O
N
N
OMMD
NH
NH
2
OH OO
O O
OM
OH
H
AA 2 2 22
NH
HH H
DDOH
CCOH
DO
MOO
A
ACHCOH
CAC O
CM
OO
O
B
B
O
C
HN
B
A
BO
CH22ACHCOH
HN
55 H
H
BCNHCHCH
B BCO
B A AA B CH
B
CH
55 HCH NH
B BACNHCHCH
CH22CHCOH
CHCOH
CHCOH
HN 5 5H
B
22CHCOH
HNHNHN
fCH
NNN
H CH
NH
H
2
2CH
2
2
2 CH
2COH
B
B
B
f
B
B
B
CNHCHCH
ff
N 2CH
N N CH
NH
CNHCHCH
COH
CNHCHCH
NHCH
CNHCHCH
2NH
2 22CH
2COH
2CH
2CH
2CH2COH
2NH
2CO
s
B
ep
s
B
O
B
B
st
ep
n
venepstseps stepss
Senve
OO
O ve
N
Se
NHFourOO O
stvenn step
CH33
CH
vestnSe
O O OO
Seve
N N NH
NH NH stepsSeSe
CHCH
3 CH
3CH33
C
C
C C
5-Methyltetrahydrofolic
acid
5-Methyltetrahydrofolic
acid
5-Methyltetrahydrofolic
acid acid
5-Methyltetrahydrofolic
acid
H
5-Methyltetrahydrofolic
5-Methyltetrahydrofolic
acid
(5-Methyl-FH
H
(5-Methyl-FH
4)4))
H
(5-Methyl-FH
(5-Methyl-FH
4)
H H
(5-Methyl-FH
(5-Methyl-FH
H
4) 4 4)
H
N
N
N
2
Histidine
O
Histidine
Histidine
Histidine
Histidine
Formic
acid acid
Formic
acid
Formic
acid

O
Band
The
simplest
synthesis
ofof
5-methyltetrahydrofolic
acidacid
isacid
from
tetrahydrofolic
acid (FH
)(FH
and
COH
synthesis
of
5-methyltetrahydrofolic
is
from
tetrahydrofolic
acid
(FH
and
HN
5acid
TheThe
simplest
synthesis
of
5-methyltetrahydrofolic
from
tetrahydrofolic
acid
(FH
4acid
simplest
synthesis
of
acid
isis
from
tetrahydrofolic
acid
(FH
4)44))and
The
simplest
synthesis
of 5-methyltetrahydrofolic
5-methyltetrahydrofolic
acid
from
tetrahydrofolic
(FH
The
simplest
synthesis
5-methyltetrahydrofolic
isis
from
tetrahydrofolic
acid
H
4) 4and
trimethylsulfonium
ion,
aion,
reaction
carried
out out
by microorganisms
inCH
theinsoil.
Btrimethylsulfonium
ion,
reaction
carried
byby
microorganisms
the
soil.
trimethylsulfonium
ion,
reaction
carried
by
microorganisms
the
soil.
trimethylsulfonium
aa reaction
carried
microorganisms
soil.
N
NH
CN
trimethylsulfonium
ion,
reaction
carried
out
by
microorganisms
in
the
soil.
trimethylsulfonium
ion,
aaareaction
carried
out
by
microorganisms
in in
the
soil.
2in
Boutout
O
steps
O
Seven
HH
CH3HN HHHHH
H
CH
NH H
N

N
N

H
H4
FH

CH
CH
CH
33 33
CH
A CH
3A
A
SAAA
S



C
S
D DDG
SG

SSD
H
CH
H
D
D
G
3
GG3 GCH3
CHH
2NH
H
H
H
H
N
CH
C
CH
H33C
H33CC CH
HH
33 3
2NH
3C
NH
CH22CH
N
3CH
NH
NH
CH
2NH
2CH
H
H
Trimethylsulfonium ion

N N
N
N

FH
FH
FH444 FH44

Trimethylsulfonium
ion
Trimethylsulfonium
Trimethylsulfonium
ion
Trimethylsulfonium
ion
Trimethylsulfonium
ionion

NN
NNN

 CH O SO CH  H

3
3
O

CH
O
SSS
CH
5-Methyltetrahydrofolic

CH
OCH
CH
O
O
33O

S
CH
CH
3acid
H
3O
3CH
3C
N
H
CH
NH
H
HCH2NH
NNH2H
(5-Methyl-FH
4)
CH
NNN
CH
CH
NH
2NH
2NH
2NH
2CH

CH3

CH

3
CH
CH
CH
5-Methyl-FH
343 3
3CH
5-Methyl-FH
4
5-Methyl-FH

5-Methyl-FH
5-Methyl-FH
5-Methyl-FH
5-Methyl-FH
4 4 44

st synthesis of 5-methyltetrahydrofolic acid is from tetrahydrofolic

ium ion, a reaction carried out by microorganisms in the soil.

H2NH

CH3
A


S
D G
CH3
H3C

H
N
N
CH3

H
CH2NH

rther Reactions of Alcohols and the Chemistry of Ethers

F
u rr tt h
her R
R ee aa cc tt ii oo n
ns of Alcohols and the Chemistry of Ethers
F
u
Fu
r t h ee rr R
e a c t i o n ss oo ff AAllccoohhoollss aanndd tthhee CChheemmi isst tr ry y oof f EEt thhe er rs s
uh
h
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an
Chehhem
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m
Et tth
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rrF
tu
hrrr eettt h
r eeeR
Rrrr eeR
d dexample.
t ht ehheeeeCCCC
EE
h
i isiiisstssttrttrryrryyyy ooooof ffff EE
F
R
rh
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llocchooohhloosll ssa naa dnn ddt htt h
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F u r t Fh ue rrt hRe er a R
c et iaocnt iso no sf oAfl cAol hc o h
l so l as nadn dt hteh eC hC eh m
i si ts rt yr y oof f EEtthheerr ss
em

F u rassumed
t h e r R e ato
c tproceed
i o n s o f through
Alcohola
s nucleophilic
a n d t h e C h esubstitution
m i s t r y o f Emechthers
C h a p t be
e r reasonably
9
(a)
Can384
this reaction
reaction
(a) Can
this
be reasonably
assumed to
proceed through
a nucleophilic
substitution mech(a) Write
Can this
this
reaction
be reasonably
reasonably
assumed
to proceed
proceed through
through
nucleophilic
substitution
mech(a)
Can
reaction
be
assumed
aanucleophilic
nucleophilic
substitution
mechanism?
thereaction
mechanism,
using the
theassumed
electron-pushing
arrownotation.
(b)Identify
Identify
thenucleonucleo(a)
Can
this
be
reasonably
totoproceed
through
anotation.
substitution
mechanism?
Write
the
mechanism,
using
electron-pushing
arrow
(b)
the
H
H
anism?
Write
the
mechanism,
using
the
electron-pushing
arrow
notation.
(b)
Identify
the
nucleo(a)
Can
this
reaction
be
reasonably
assumed
to
proceed
through
nucleophilic
substitution
mechanism?
Write
the mechanism,
mechanism,
using
the
electron-pushing
arrow
notation.
(b)Identify
Identify
thenucleonucleo(a)
Can
this
reaction
be
reasonably
assumed
to
proceed
through
aareaction,
nucleophilic
substitution
phile,
the
nucleophilic
and
electrophilic
atoms
participating
in
the
and
the
leaving
group.
Can
this
reaction
be
reasonably
assumed
to
proceed
through
aareaction,
substitution
mech(a) anism?
reaction
be
reasonably
assumed
to
proceed
through
nucleophilic
substitution
mech(a)
Can
this
reaction
be
reasonably
assumed
to
proceed
anucleophilic
nucleophilic
substitution
mechWrite
the
using
electron-pushing
arrow
notation.
(b)
the
NH
phile,
the
nucleophilic
and
electrophilic
atoms
participating
in
the
and
leaving
group.
(a)the
Can
thisassumed
reaction
reasonably
assumed
to
through
athe
nucleophilic
substitution
2 through
(a)
Can
this
reaction
be
reasonably
to
proceed
through
a nucleophilic
substitution
mechN
Nmech
phile,
the
nucleophilic
and
electrophilic
atoms
participating
in
the
reaction,
and
the
leaving
group.
(a)
Can
this
reaction
be using
reasonably
assumed
tobeproceed
through
aproceed
nucleophilic
substitution
mechanism?
Write
the
mechanism,
using
the
electron-pushing
arrow
notation.
(b)
Identify
the
nucleophile,
the
nucleophilic
and
electrophilic
atoms
participating
in
the
reaction,
and
the
leaving
group.
anism?
Write
the
mechanism,
using
the
electron-pushing
arrow
notation.
(b)
Identify
the
Write
the
mechanism,
the
electron-pushing
arrow
notation.
(b)
Identify
nucleo(c)
On
the
basis
of
the
concepts
presented
in
6-7,
6-8,
9-2,
and
9-9,
are
all
the
groups
anism?
Write
theSections
mechanism,
using
the
electron-pushing
arrow
notation.
(b)the
Identify
the nucleo
anism?
mechanism,
using
the
electron-pushing
arrow
notation.
(b)
Identify
the
nucleophile,
the
nucleophilic
and
electrophilic
atoms
participating
in
the
reaction,
and
the
leaving
group.
anism?
Write
the
mechanism,
using
the
electron-pushing
arrow
notation.
(b)
Identify
the
nucleoA
(c)
On
the
basis
of
the
concepts
presented
in
Sections
6-7,
6-8,
9-2,
and
9-9,
are
all
the
groups
anism?
the
mechanism,
using
theinelectron-pushing
arrow
notation.
(b)
Identify
thenucleonucleoanism?
Write
the
mechanism,
using
theatoms
electron-pushing
arrow
notation.
(b)
Identify
(c)
Onthe
the
basisWrite
ofand
the
concepts
presented
Sections
6-7,
6-8,
9-2,
andand
9-9,
are
all
groups
phile,
the
nucleophilic
and electrophilic
atoms
participating
in9-9,
the
reaction,
and the
the leaving
group
phile,
the
nucleophilic
and
electrophilic
atoms
participating
in
the
reaction,
and
the
leaving
group.
(c)
On
the
basis
of
the
concepts
presented
Sections
6-7,
6-8,
9-2,
and
are
all
the
groups
phile,
nucleophilic
and
electrophilic
participating
in
the
reaction,
and
the
leaving
phile,
nucleophilic
and
electrophilic
atoms
participating
the
reaction,
and
the
leaving
group.
the
nucleophilic
electrophilic
atoms
participating
ininin
the
reaction,
the
leaving
group.
(c)
On
the
basis
the
concepts
inin
Sections
6-8,
9-2,
and
9-9,
are
all
the
groups
phile,
the
nucleophilic
and
electrophilic
atoms
participating
the
reaction,
and
leaving
group.
that
you
identifi
edthe
inof
(b)
behaving
inpresented
aOn
reasonable
way
in6-7,
this
reaction?
Does
itand
help
to
know
that
phile,
nucleophilic
and
electrophilic
atoms
participating
in
the
reaction,
the
leaving
group.
that
you
identifi
ed
in
(b)
behaving
in
a
reasonable
way
in
this
reaction?
Does
it
help
to
know
that
(c)
the
basis
of
the
concepts
presented
in
Sections
6-7,
6-8,
9-2,
and
9-9,
are
all
the
group

C
thebasis
nucleophilic
and
electrophilic
atoms
participating
in
the
and
theDoes
leaving
group.
that
youthe
identifi
ed
in
(b)
behaving
inacids
a reasonable
reasonable
way
in
this
reaction?
Does
itare
help
to
know
that
1
1
(c) phile,
On
the
basis
ofin
the
concepts
presented
in
Sections
6-7,
6-8,
9-2,
and
9-9,
are
all
the
groups
19-2,
1
that
you
identifi
ed
in
(b)
behaving
in
way
in
this
reaction?
Does
it
help
to
know
that
(c)
On
of
the
concepts
presented
in
Sections
6-7,
6-8,
9-2,
and
9-9,
are
all
the
groups
1
1
that
you
identifi
ed
in
(b)
behaving
in
a36-8,
reasonable
way
in
this
reaction?
itknow
help
to
know
tha
species
such
asbasis
H
Sed
are
very
strong
(e.g.,
pK
of6-7,
SH
isreaction,
27)?
the
basis
of
the
concepts
presented
in
Sections
6-8,
and
9-9,
all
the
groups
(c) On
the
concepts
presented
inin
Sections
6-7,
and
9-9,
are
all
the
that
you
identifi
(b)
behaving
in
aa reasonable
inCH
this
reaction?
Does
it9-9,
help
to
that
groups
(c)
On
the
of
the
concepts
presented
Sections
6-7,
6-8,
9-2,
and
9-9,
the
groups
H
(c)
On
the
basis
of
the
concepts
presented
inway
Sections
6-8,
9-2,
and
are
all
the
groups
33S
aa of
229-2,
1
1
3 6-7,
species
such
as
H
are
very
strong
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(e.g.,
pK
CH
SH
is
27)?
1
1
1
1
3
a
3
2
(c)
On
the
basis
of
the
concepts
presented
in
Sections
6-7,
6-8,
9-2,
and
9-9,
are
all
the
groups
H
species
such
as H
H33SS
Sin
arebehaving
very strong
strong
acids
(e.g.,
pK
of
CH
SH
is27)?
27)?
such
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H3S
arepK
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pK
of CH
is help
27)? to
1
that
you
identifi
ed
in1 (b)
(b)
behaving
in
reasonable
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reaction?
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know
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( way
a 27)?
3SH2 it
aof
2 2is
CH
CH
SH
species
such
as
H
are
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of
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SH
is
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that
you
identifi
ed
in
aaacids
reasonable
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this
reaction?
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know
that
33reaction?
2acids
such
are
very
pK
CH
SH
you you
identifi
in
behaving
in
ain
this
reaction?
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itititithelp
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that
you
identifi
edbehaving
in (b)strong
behaving
in a(e.g.,
reasonable
way
this
reaction?
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toknow
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in
(b)
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a reasonable
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Does
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identifi
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aacids
reasonable
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3(b)
a ain
3in
221
N
N
1
1
that
you
identifi
ed
in
(b)
behaving
in
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reasonable
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reaction?
Does
it
help
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know
that
CH
NH
1
1
species
such
asSH
H
S
are
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pKof
of
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27)?
112SH
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13S
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27)?
species
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aCH
269)
1
The
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in biology
33role
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3SH
4SH
of
5-methyl-FH
69)
biology
serve
asaadonor
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H
very
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isserve
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3S 5-methyl-FH
ain
3SH
2is
role
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69)
inin
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isthe
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44 (Problem
groups
to
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synthesis
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role
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69)
biology
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asa aadonor
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70.
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role
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69)
biology
serve
donor
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44 (Problem
The
of
5-methyl-FH
69)
inin
biology
isis
toto
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asas
ofof
methyl
70.
groups
to small
small molecules.
molecules.
The
synthesis
of
the amino
amino
acid
methionine
from
homocysteine
is
perhaps4 the
best-known
example.
groups
to
The
synthesis
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the
acid
methionine
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isis
H
groups
to
small
molecules.
The
synthesis
of
the
amino
acid
methionine
from
homocysteine
CH
Themolecules.
roleThe
of role
5-methyl-FH
(Problem
69)
in
biology
is to
to
serve
asashomocysteine
ahomocysteine
donor
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methyl
70.
of 5-methyl-FH
69)
in biology
is
to serve
adonor
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methyl
70.to
groups
tobest-known
small
molecules.
The
synthesis
of
the
amino
acid
methionine
from
homocysteine
4 (Problem
3 The
O
The
role
of
5-methyl-FH
(Problem
69)
in
biology
is
to
serve
as
a
of
methyl
70.
4 (Problem
groups
small
The
synthesis
of
the
amino
acid
methionine
from
isis
4
The
role
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5-methyl-FH
69)
in
biology
is
serve
as
of
70.
role
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5-methyl-FH
(Problem
69)
in
biology
is
to
serve
as
a
donor
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methyl
perhaps
the
example.
role
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5-methyl-FH
(Problem
69)
in
biology
is
to
serve
as
a
donor
of
methyl
44 4
The
role
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5-methyl-FH
(Problem
69)
in
biology
is
to
serve
as
a
donor
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methyl
70.
perhaps
the
best-known
example.
4
perhaps
the
best-known
example.
groups
to
small
molecules.
The
synthesis
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the
amino
acid
methionine
from
homocysteine
groups
to
small
molecules.
The
synthesis
of
the
amino
acid
methionine
from
homocysteine
is
best-known
example.
groups
to
small
molecules.
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synthesis
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acidmethionine
methionine
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homocysteineisisis
H synthesis
H
perhaps
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best-known
example.
groups
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molecules.
The
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to
small
molecules.
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of
the
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from
molecules.
The
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methionine
from
homocysteine
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NH
NH
5-Methyl-FH
Homocysteine
2
groupsthe
to best-known
small
synthesis of Athe2 amino acid methionine
from homocysteine
is F
N The
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perhaps
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best-known
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example.
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perhaps
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perhaps
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perhaps
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best-known
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CH

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perhaps
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A
A 22 Methionine
 
CHNH

C
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For
problem,Homocysteine
answer
the same
questions
that


C
 C
C

C
2 2 5-Methyl-FH
NH
NH
NH
H
C

C
ANH
2 22 22

C
CNH
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H
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NNNN
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H NH
H
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H
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3
22
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22SCH
H
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CH
CH
SH
CH
CH
H
H
 circled
CCH
HOC
CProblem
CH
NH
2222SH
333 33th
(2222CH
(H


C
HOC
HOC
N
NNNN
CH
SHproblem,
CH
CH
SCH
2CH
2SCH
2
CH
CH
NHH HOC
NH
CH
CH
NHN
NH
2CH
2pK
For 2this
answer
the
same
that 
were
posedHin
69.2a
The
HOC
HOC

C
C
H
H
hydrogen
in
FH
is
5.
Does
this
cause
prob
2questions
2NH
2NH
22CH
2H
CH
a of 3
CH
NH
H
HOC
HOC

C

C
2
HOC
HOC
4
2
2
N
C

C
H
CH
CH
NH
NH
H
H
H
( feature
HOC
HOC
CH22CH
CH22SH
SH hydrogen in FH4 is 5. Does
CH
CHmechanism
SCH
 H
H 2
H this2cause2 a problem
HCBBBH
 2 BBH
H
H
HCH
(C
2SCH
3
CH
CH
SH
CH
CH
H
H
of222your
BH
((( CH
CH
H
H
H
H
( CH
BBany
2 SH
2 circled
222SCH
33
NH
CH
CH
SH
CH
CH
SCH
CH
CH
NH
NH require with
H
H 22NH
H
H
BCH
2SCH
(( H
(BB(( B(H
HOC
HOC
22CH
N
2NH
CH
CH
CH
NH
NH
H
H
22CH
222SHIn2fact, methyl transferH
2CH
2SCH
3 333
HOC
HOC
N
2
HH
H
CH
CH
H
CH
CH
reactions
of
5-methyl-FH
a
proton
source.
Review
the
materia
H
2
2
HOC
HOC
N
N
4
2
2
O
O
CH
CH
NH
NH
O
O
In
transferNNHHthereactions
of HOC
5-methyl-FH
HOC
HCH
2
OO
O HOC
HCH22NH
CH32
O
CH
333 22NH
HOC
O
NH
Omethyl
BBfact,
BBBOprimary alcohols 4andreq
HOC
HOC
in Section 9-2, especially
subsection
titled Haloalkanes
from
HX.
BO
B
B
B
-FH
Homocysteine
FH
Methionine
H
H
ethyl-FH
Homocysteine
FH
Methionine
4
4
Homocysteine
FH
Methionine
4
4
-FH
Homocysteine
FH
Methionine
3
B O
BO
OMethionine
OHomocysteine
HforFH
H
ethyl-FH
Homocysteine
FH
Methionine
Then suggest a useful roleH
here.
4a4 proton
Homocysteine
FH in the reaction illustrated
Methionine
O
4
44
ethyl-FH
CH
33 4 3 5-Methyl-FH
O
in
9-2,
especially
titled
Halo
HH HFH44 4the4 subsection
OOO Methionine
O
O Section
ethyl-FH
Homocysteine
Methionine
ethyl-FH4
Homocysteine
FH 4

CC C

C C
C

CCCC C
C

C CC CC
C
CCC C

ethyl-FH44 4
5-Methyl-FH

Homocysteine
FH
Methionine
Homocysteine
FH
Methionine
44 44
also
Chapter 6 Opening) is produced
in
your body in a two-ste
Methionine
Homocysteine 71. Epinephrine (adrenalin; seeFH
4

Homocysteine
FH4 4 for a proton in
Methionine
Then
suggest
athe
useful
role
the
reaction
process
that
accomplishes
the
transfer
of
a methyl
group
from methionine
(Problem
70)
to
nor
For
thisanswer
problem,
same
questions
that
were
posed
in Problem
69.
The
pK
of
the
For
this
problem,
answer
the
same
questions
that
were
posed
in
Problem
69.
The
pK
the
problem,
answer
theanswer
same
questions
that
were
posed
Problem
69.
The
pK
aof
For For
this this
problem,
the
same
questions
that
were
posed
inin
Problem
69.
The
pK
problem,
answer
the
same
questions
that
were
posed
Problem
69.
The
the
problem,
answer
the
same
questions
that
were
posed
Problem
69.
The
pK
the
inin
pK
aa aaof
(see
1 aandproblem
2 below). (a)
Explain
infeature
detail what
isyour
going mechanism?
on mechanisticall
circled
hydrogen
in
FH
isepinephrine
5. this
Does
thisreactions
with
any
of
circled
hydrogen
in FH
FH
is 5.
5.the
Does
this
cause
problem
with
any
feature
ofyour
your
mechanism?
4Does
ForFor
this
problem,
answer
the
same
circled
inproblem,
FH
is4444answer
5.
Does
this
cause
with
any
feature
of
your
mechanism?
circled
hydrogen
in
is
Does
cause
aproblem
problem
with
any
feature
of
your
mechanism?
hydrogen
in
is
5.
this
cause
aaproblem
problem
with
any
feature
of
your
mechanism?
hydrogen
in
FH
5.
Does
this
cause
aacause
with
any
feature
of
mechanism?
a of
questions
that
were
posed
in
Problem
69.
The
pK
the
44 is
in
these
two
reactions,
and
analyze
the
role
played
by
the
molecule
of
ATP.
(b)
Would
youthe
expec
4FH
For
this
problem,
answer
same
questions
that
were
posed
in
Problem
69.
The
pK
this
the
same
questions
that
were
posed
in
Problem
69.
The
pK
of
the
aaaaof
In
fact,
methyl
transfer
reactions
ofto
5-methyl-FH
require
a any
proton
source.
Review
the
material
For
this
problem,
answer
the
same
questions
that
were
posed
in
Problem
69.
The
pK
of
the
4
methionine
react
directly
with
norepinephrine?
Explain.
(c)
Propose
a
laboratory
synthesis
o
methyl
transfer
reactions
of
5-methyl-FH
require
a
proton
source.
Review
the
a
circled
hydrogen
in
FH
is
5.
Does
this
cause
a
problem
with
feature
of
your
mechanism?
For
this
problem,
answer
the
same
questions
that
were
posed
in
Problem
69.
The
pK
of
the
In
fact,
methyl
transfer
reactions
of
5-methyl-FH
require
a
proton
source.
Review
the
material
4
In fact,
methyl
transfer
reactions
of
5-methyl-FH
require
a
proton
source.
Review
the
material
methyl
transfer
of this
5-methyl-FH
require
awith
proton
source.
Review
the
4reactions
transfer
reactions
ofDoes
5-methyl-FH
a with
proton
source.
Review
a
44aproblem
4 problem
4a4
circled
hydrogen
in9-2,
FH
is4 is
5. 5.
Does
any
feature
of
mechanism?
circled
in
FH
thiscause
cause
any
feature
ofyour
yourthe
mechanism?
4 require
44especially
epinephrine
from
inhydrogen
Section
the
subsection
titled
Haloalkanes
from
primary
alcohols
and HX.
HX.
circled
hydrogen
in
FH
5.
Does
this
cause
anorepinephrine.
problem
with
any
feature
ofalcohols
your
9-2,
especially
the
subsection
titled
Haloalkanes
from
primary
alcohols
and
44 is
in
Section
9-2,
especially
the
subsection
titled
Haloalkanes
from
primary
alcohols
circled
hydrogen
intransfer
FH
isthe
5.reactions
Does
this
cause
aHaloalkanes
problem
with
any
feature
your
mechanism?
9-2,
especially
the
subsection
titled
Haloalkanes
from
primary
alcohols
in
especially
the
subsection
titled
Haloalkanes
from
primary
alcohols
and
HX.
4 require
In In
fact,
methyl
reactions
of
5-methyl-FH
proton
source.
Review
the
material
71.
Epinephrine
(adrenalin;
see
Chapter
6 mechanism?
Opening)
Section
9-2,
especially
subsection
titled
primary
and
HX.
and
fact,
methyl
transfer
of5-methyl-FH
5-methyl-FH
require
afrom
proton
source.of
Review
the
material
aaalso
proton
source.
Review
the
material
44 4require
Then
suggest
a
useful
role
for
a
proton
in
the
reaction
illustrated
here.
In
methyl
transfer
reactions
5-methyl-FH
require
aa proton
source.
Review
the
material
suggest
useful
role
for
proton
in
the
reaction
illustrated
here.
insuggest
Section
9-2,
especially
the
titled
Then
suggest
a9-2,
role
aof
the
reaction
illustrated
44Haloalkanes
suggest
aa useful
useful
role
for
aasubsection
proton
in
the
reaction
illustrated
here.
In fact,
fact,
methyl
transfer
reactions
ofproton
5-methyl-FH
require
proton
source.
Review
theand
material
here.
Haloalkanes
from
primary
alcohols
and
HX.
Then
useful
role
forfor
proton
inin
the
reaction
illustrated
here.
a9-2,
useful
role
for
aathe
proton
the
reaction
illustrated
here.
HX.
in
Section
especially
subsection
titled
Haloalkanes
from
primary
alcohols
and
Reaction
1in
in
Section
especially
the
subsection
titled
from
primary
alcohols
HX.
process
that
accomplishes
the
transfer
of
a methyl
gro
in
9-2,
especially
the
subsection
titled
Haloalkanes
from
primary
Then
suggest
useful
role
for
in
the
reaction
illustrated
here.
in Section
Section
9-2,
especially
the
subsection
titled
Haloalkanes
fromhere.
primary alcohols
alcoholsand
andHX.
HX.
Then
suggest
a useful
role
for
aproton
proton
inthe
the
reactionillustrated
illustrated
here.
Then
suggest
aa useful
role
for
aasee
proton
in
reaction
71.
Epinephrine
(adrenalin;
Chapter
6 HOpening)
is produced
in your body in a two-step
H
H illustrated
NH2 also
Then
suggest
a
useful
role
for
a
proton
in
the
reaction
here.
71.
(adrenalin;
see
also
Chapter
Opening)
is
produced
inyour
your
body
inaaaaaExplain
two-step
Then
suggestprocess
a useful
for
aalso
proton
in66reactions
the
reaction
O O Oillustrated
epinephrine
(see
and
2inmethionine
(a)
Epinephrine
(adrenalin;
Chapter
6Opening)
Opening)
is1
produced
inbelow).
your
body
in
two-step
NH
71.
(adrenalin;
see
also
Chapter
66Opening)
Opening)
is
produced
in
your
body
in
two-step
2
that role
accomplishes
the
transfer
of
a methyl
group
fromhere.
(Problem
70)
to
norEpinephrine
(adrenalin;
seesee
also
Chapter
is
produced
in
your
body
in
two-step
(adrenalin;
see
also
Chapter
is
produced
body
in
two-step
CH3
C
accomplishes
the
transfer
of
methyl
group
from
methionine
(Problem
70)
tonornorprocess
accomplishes
the
of
amethyl
group
methionine
(Problem
to
71.
Epinephrine
(adrenalin;
see
also
Chapter
CH
SCH
Htransfer
 Opening)
accomplishes
the
transfer
aa66methyl
methyl
group
from
methionine
(Problem
to
norHOPOPOPOCH
71.
Epinephrine
(adrenalin;
see
also
Chapter
isfrom
produced
your
body
in70)
two-step
Opening)
is
produced
ininCyour
your
body
in
aaRtwo-step
two-step
epinephrine
(seethe
reactions
and
2of
(a)
Explain
in
detail
what
is
going
on
mechanistically
( 1Chapter
2CH
36
2R
71.
Epinephrine
(adrenalin;
see
also
Opening)
is
produced
body
a70)
thatthat
accomplishes
transfer
of
aa2below).
methyl
group
from
methionine
(Problem
to
norprocess
accomplishes
the
transfer
of
from
methionine
(Problem
70)
to
nor- 

Hby
CH
Sin70)
CH
Hin
in
these
two
and
the
role
played
(
Bgroup
B B analyze
4P3O10t
HOC reactions,
2 CH2
2
(see
reactions
and
below).
(a)
Explain
inproduced
detail
what
is
going
onmechanistically
mechanistically
epinephrine
(see
reactions
1also
and
2transfer
below).
Explain
in
detail
what
is
going
on
Epinephrine
(adrenalin;
see
also
6the
Opening)
is
inis
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a(a)
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BChapter
in
these
two
reactions,
and
role
played
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the
molecule
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ATP.
(b)
Would
you
(see
reactions
11the
and
22analyze
below).
(a)
Explain
in
detail
what
is
going
on
mechanistically
process
that
accomplishes
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of
amethyl
methyl
group
from
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toexpect
normethyl
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(Problem
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process
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to
norEpinephrine
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see
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Opening)
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a70)
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11 and
22transfer
below).
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reactions
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below).
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B
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O
reactions,
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Would
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in
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(b)
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methionine
to
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with
norepinephrine?
Explain.
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of
epinephrine
(see
reactions
1
and
2
below).
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in
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what
is
going
on
mechanistically
process
that
accomplishes
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transfer
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methyl
group
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(Problem
70)
to
norO
methionine
to
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Exp
epinephrine
(see
reactions
1
and
2
below).
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mechanistically
reactions,
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role
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andthe
2 below).
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and
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role
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process
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70)
to
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the
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in
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Would
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epinephrine
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below).
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in
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expect
methionine
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(c)
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in
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(b)
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Would
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Explain.
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agoing
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reactions
and 2norepinephrine?
below).
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react
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with
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Propose
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laboratory
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methionine
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to
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isom
Pr ro obbl el emms s
he
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Figure
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Explain
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the
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the trans
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2-bromocyclohexanol
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(a) Only the
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oxacyclopropane-containing
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iflack
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The
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[Hint: Draw
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m ss
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the
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the
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Figure
4-12).
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models
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The
some
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72.
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Only
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of4-12).
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ifif if
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synthesis
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4-12).
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N
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Psynthesis
CHsynthesis
CHCHof
CH
CHP
SO
CH
the
success
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oxacyclopropane-forming
step?
Highlight
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a CH
short
of
allicin,
starting
with
Propose
asynthesis
short
starting
with
2
2
2
allicin,

9-4).9-4).
Propose
aa short
allicin,
starting
with
3-chloropropene.
Propose
short
synthesis
of
allicin,
starting
with
3-chloropropene.
2 synthesis
2 of
2
23-chloropropene.
}
0
Allicin
Allicin
HO
Allicin
73. Freshly
cut garlicallicin,
contains
allicin,
a compound
responsible
for the for
true garlic
odor (see
(see
Chemical
odor
Chemical
garlic
contains
a compound
responsible
the true
garlic
odo
H
Oallicin,
allicin, starting
3-chloropropene.
OofO
starting with
with 3-chloropropene.
Highlight 9-4). Propose a short synthesisO
B
B
4).
Propose
a
short
synthesis
of
allicin,
starting
with
3-chloropropen
Team
Problem
B
BO
Team Problem
O
O
O
P
P
CH
CHCH
S
CH
CH
S
CH
O
O
O
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CHCH
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S CH
CH2 2
22S
22CH




O
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S
O
O
O
PCH
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SB
CH
CH
SO
CH
22P
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22




74. There
74.
There are
are four
four diastereomers
diastereomers (A
(AD,
D, margin)
margin)
of (4S)-2-bromo-4-phenylcyclohexanol.
(4S)-2-bromo-4-phenylcyclohexanol.As
Asa a
O of
Allicin
Allicin
Allicin
team,
their
structures
draw
each
diastereomer
ininthe
stable
chair confor
Beach
OAllicin
O
O
P
r proposed
sequence
haveand
specifi
c
stereochemical
requirements
for
team, formulate
formulate
their2 P
structures
and
diastereomer
themost
most
CH
CHCH
S
CH
CH
S
CH
2 draw
2
2stable chair confor21


21).

O
S
mation
(see
Table
4-3;
the
DG8
value
for
axial
versus
equatorial
C
H
is
2.9
kcal
mol
O
O
O
P
P
P
CH
CHCH
S
CH
CH
S
CH
CH
CH
CH
2
2
2
2
21
55 is 2.9 kcal mol21
21).
2
2
 versus

O axial
mation
4-3;
equatorial
C
5
mation (see
(see Table
Table
4-3; the
the DG8
DG8 value
value for
for
axial
versus
equatorial
C66 66H
H
5 is 2.9 kcal mol ).
pane-forming
step?
Problem
Divide
your
team
into
equal
groups
to
consider
the
outcome
of
the
reaction
of
each
isomer
Team
Allicin
BAllicin the
Allicin
Divide
team
am Problem
Divide your
your2
team into
into equal
equal groups
groups to
to consider
consider
the outcome
outcome of
of the
the reaction
reaction of
of each
each isomer
isomer
2
base
((four
OH).
2
2
74. with
There
are
diastereomers
(A

D,
margin)
of
(4S)-2-bromo-4-phenylcyclohexanol.
As
with
base
OH).
four CH
diastereomers
(A D,O
margin)
(4S)-2-bromo-4-phenylcyclohexanol.
Asa a
witharebase
O
SOofof
CH2CHP CH2
Sof(4S)-2-bromo-4-phenylcyclohexanol.
There
four( OH).
diastereomers
(A
As
2 P CHCH
2margin)
diastereomers
(AD,
D, margin)
(4S)-2-bromo-4-phenylcyclohexanol.
Asa a
formulate
structures
inin the
most
stable
formulate their
theirresponsible
structures and
and draw
draw
each
diastereomer
the
most(see
stablechair
chairconforconforcin, team,
a compound
foreach
thediastereomer
true
garlic
odor
Chemical
Team
Problem their
team, formulate
and
21
their structures
structures
and draw
draw each
each diastereomer
diastereomer inin the
the most
moststable
stablechair
chairconforconfor21
?
mation
(see Table 4-3; ?the DG8 value forOH
axial versus equatorial C6H
is 2.9 kcal mol2121
).
6 55
OH
OH
OH

`
mation (see Table 4-3; ?
DG8 value for
axial versus equatorial
2.9 kcal mol ).
Allicin
?the
`O CCCHHH isisis2.9
mation
(see
Table
4-3;
the
value
for
axial
versus
equatorial
of
4-3;
DG8
value
for
axial of
versus
equatorial
kcalmol
mol
(4S)-2-bromo-4-phenylcyclohexanol.
As).a).
a
ODG8
A
mt74.
There
are
four
diastereomers
(A
D,Bto
margin)
As
synthesis
of
allicin,
starting
with
3-chloropropene.
Divide
your
team
into
equal
groups
consider
the(4S)-2-bromo-4-phenylcyclohexanol.
outcome
the reaction2.9
of kcal
each
isomer
``of
team
intothe
equal
outcome
?
O
O
A
O groups B
O the reaction of each isomer
Bto consider the
A
` of
)
)









OH
OH

OH
OH

66 55

Fast
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?
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to
consider
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ofofeach
Fast
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)into
)
eachHthe
stable
chair
confor? groups
Divide
your
team
equal
groups
todraw
consider
the
outcome
of
the reaction
reaction
eachisomer
isomer
team,
formulate
theirequal
structures
and
each
diastereomer
in
the
most
stable
chair
conforFast
Slow
diastereomer
in the
the
most
with
base
(22
OH).
H
OH).
5C
66 )
5C66 )
)into
)
2
21
21
2OH).
H
H
C
6
6
with
base
H555C
H555of
CTable
C
axial
2.9 kcal
kcal mol
mol21
6
6 (4S)-2-bromo-4-phenylcyc
4-3; (A
the DG8
for axial
versus
equatorial
).).
versus
equatorial C
C66H
H55 is
is 2.9
withmation
base (((see
OH).
our
diastereomers
D, value
margin)
consider the
reaction of
of each
each isomer
isomer
Divide your team into ?
equal groups to consider
the outcome
outcome of
of the
the reaction
?
`` Enols are unstable
O
OH
OH draw each
2 O
lateAwith
their
and
diastereomer
in
the
most
stab
OH
OH
OH structures
[Note:
with
base
(
OH).
[Note:
Enols
are
unstable
with
O
?
BB OH
O `
OH
? ?O
OH
[Note:
Enols
are
OOH
AOH Fast
``OOto
OH
`
[Note:
are unstable
unstable with
with
respect
isomerization
OH
respect
toEnols
isomerization
Slow
B) DG8
OH
? D, Bmargin)
Fast
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OH
respect
to
)
)
O
OOcorresponding
A C OH
Table
4-3;
the
axial
equatorial
C6H5 is
our
diastereomers
of
(4S)-2-bromo-4-phenylcycl
to
the
ketone
respect
to isomerization
isomerization
)versus
`
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to
the
corresponding
ketone
B for
A
Fast
?
H
HH55C
CFast
`
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55C
to
HO
C66 )O
C66
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Fast Fast
Slow
(Chapters
13
to the
the corresponding
corresponding
ketone
Fast
)
)
(Chapters
13 and
and 18).]
18).] ketone
Fast












mation (see
(see Table
4-3;
the
DG8
value
for
axial
versus
equatorial
C 6H
2.9
kcal
mol
21).
5 is
21
with
OH).4-3;
4-3; the
the DG8
DG8 value
value for
for axial
axial versus
versus equatorial
equatorial C
2.9 kcal
kcal mol
mol21
mation
).
mationbase
(see (Table
Table
4-3;
the
value
for
axial
versus
equatorial
CC6666H
HH55555 is
isis 2.9
2.9
kcal
mol
).).
Divide your team into equalDG8
groups to consider the outcome of the 6reaction
of each isomer
Divide your team
team into
equal
groups
to
consider
the
outcome
of
the
reaction
of each
isomer
into equal
equal groups
groups to
to consider
consider the
the outcome
outcome of
of the
the reaction
reaction of
eachisomer
isomer
Divide
Divide your
your2
team into
into
equal
groups
to
consider
the
outcome
of
the
reaction
ofof each
each
isomer
2OH).
with base
base
(2
2
?
2


with
`
with
base
OH).
OH
OH(( OH).
?

A
A
A
A
A

OH

Fast
OH
OH
OH
OH
Fast
Fast
Fast
Fast

C
C

C
C
C

?
? ?
?
) )?
C ??OOOO
H5H
C
)65 6 ?

Fast















)
)
H C66)
H
H55555C
C6666

C66H555

D
D
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OH
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OH

OH
OH
OH
OH
Slow
Slow
Slow
Slow
Slow

B
B
BB

)
)
)
)
C
H
C
H
Fast C
C666H
H5655 5








OH


OH
OH
OH
OH OH
Fast
Fast
Fast
Fast








OH
OH
OH
OH
OH
OH
Slow
Slow
Slow
Slow
Slow
Slow

OH

Slow
`
`
`
`
)
`OO
O
H5C`
`
6`O
)
)
)
H
C
)
H
CC66666
H55555C
H

OH
CH
C
H555555 C6H5
H
CC666666H

)
CEnol
HEnol
6Enol
Enol
Enol
Enol5

Slow

O
O
OO

`
`O

`O

H5C6

[Note: Enols are unstable with

[Note:
Enols
are
unstable
with
[Note:Enols
Enols
are
unstable
with
[Note: E
are
unstable
with
[Note:
isomerization
[Note:
Enols
are
unstable
with
[Note:
Enols
arerespect
unstableto
with
[Note:
Enols
are
unstable
with
respect
to
isomerization
respect
to
isomerization
respect
toto
isomerization
respectto
toisomerization
isomerization
to theketone
corresponding respect
ketone t
respect
isomerization
respect
tothe
thecorresponding
corresponding
to
the
corresponding
ketone
to
ketone
to
the
corresponding
ketone
tothe
thecorresponding
corresponding
ketone13 and 18).]
to(Chapters
ketone
(Chapters
13and
and
18).]
(Chapters
13
and
18).]
to the co
(Chapters
13
18).]
(Chapters
13
and
18).]
(Chapters13
13and
and18).]
18).]
(Chapters

C6H5

(Chapter

Enol

OH
D
(a)
Using the
the curved-arrow
curved-arrow
formalism
(Section
6-3),
show
the
ow
of
electrons
the
attack
(a)
curved-arrow formalism
formalism (Section
(Section 6-3),
6-3), show
show the
the fl
flow
ow of
ofelectrons
electronsin
inthe
theattack
attackof
of
Using
the
curved-arrow
formalism
(Section
6-3),
show
the
flfl
ow
of
electrons
inin
the
attack
ofof
(a) Using
Slow
(a)
Using
thevarious
curved-arrow
formalism
(Section
6-3),
flmechanisms
ow
of electrons
in
the
various
cyclohexane
conformers.
Reconvene
andshow
presentthe
your
mechanisms
toyour
your
base on
on the
the
cyclohexane
conformers.
Reconvene
and
present
your
toto
your
the
various
cyclohexane
conformers.
Reconvene
and
present
your
mechanisms
to
various
cyclohexane
conformers.
Reconvene
and
present
your
mechanisms
your
the base
teammates,
the
structural
assignments
of
D.
Find
an
explanation
for
the
qualitative
the
base onjustifying
the various
cyclohexane
conformers.
and present
your
mecha
the
assignments
of
Find
for
qualitative
teammates,
the structural
structural
assignments
of A
AD.
D.Reconvene
Find an
an explanation
explanation
forthe
the
qualitative
justifying
the
structural
assignments
of
AA
D.
Find
an
explanation
for
the
qualitative
rate
differences
and the
the
divergent
course
of
the
reactions
of
A
and
versus
and
D.
divergent
course
the
and
versus
and
teammates,
justifying
the structural
assignments
of
A
D.B
Find
anC
explanation
for
rate differences
the
divergent
course of
of
the reactions
reactions(Section
of A
A
and
B
versus
Cshow
andD.
D.the fl
and
the
divergent
course
of
the
reactions
of
A
and
BB
versus
CC
and
D.
(a)
Using
the
curved-arrow
formalism
6-3),
owt
(b)
compounds
A
D
are
exposed
to
conditions
favoring
bromide
dissociation
the
compounds
A

are
to
favoring
dissociation
in
(b) When
compounds
A
D
Ddivergent
are exposed
exposed
to conditions
conditions
favoring bromide
bromide
dissociation
in
the
When
compounds
A

D
are
exposed
to
conditions
favoring
bromide
dissociation
inin
the
rate
differences
and
the
course
of
the
reactions
of
A
and
B
versus
Cthe
and
1
1
1 salts (to accelerate heterolysis with formation of insoluble AgBr), A, C, and
1
1
presence
1
of
Ag
salts
(to
accelerate
heterolysis
with
formation
of
insoluble
AgBr),
A,
C,
and
the
base
on
the
various
cyclohexane
conformers.
Reconvene
and
pres
presence
salts (to
(to accelerate
accelerate
heterolysis
with
formation of
of insoluble
insolubleAgBr),
AgBr),
A,C,
C,
and
of Ag
salts
heterolysis
with
A,
and
(b)
When
compounds
Athose
D are
exposed
to formation
conditions
favoring
bromide
dissoc
D
products
as
obtained
on
treatment
with
base.
Discuss
the
mechanism
products
as
on
with
mechanism
as
D give
products
as those
those
obtained
on treatment
treatment
with base.
base. Discuss
Discuss
the
mechanism
ase
give the
the same
same justifying
obtained
on
treatment
with
base.
Discuss
the
mechanism
asas
1
teammates,
theobtained
structural
assignments
of Aof
the
D.
Find an
presence
of
Agproducts
salts as
(tothose
accelerate
heterolysis
with
formation
insoluble
AgB
aa group.
group.
D
give
the
same
products
as
those
obtained
on
treatment
with
base.
Discuss
the
m
(c)
compound
B
traverses
another
pathway
under
the
conditions
described
(b);
that
rate
differences
the divergent
course
ofconditions
the reactions
of(b);
Athat
and
compound
B
another
under
described
is,
Curiously,
compound
B
traverses
another
pathway
under
the
conditions
described
inin
(b);
that
is,is,
(c) Curiously,
compoundand
B traverses
traverses
another pathway
pathway
under the
the
conditions
describedin
in
(b);
that
is,
aldehyde
E.
Discuss
possible
mechanism
for
this
ring
contraction.
(Hint:
Keep
to
the
aaaa possible
mechanism
this
ring
arearrangement
group.
to
the
aldehyde
E.
Discuss
possible
mechanism
for
this
ring
contraction.
(Hint:
Keep
rearrangement
aldehyde E.
E. Discuss
Discuss
possible
mechanismfor
forto
thisconditions
ringcontraction.
contraction.(Hint:
(Hint:Keep
Keep
to compounds
the aldehyde
(b)
When
A

D
are
exposed
favoring
in
outlined
in
Section
9-3.
The
mechanism
proceeds
through
hydroxycation.
the
outlined
Section
The
through
aaaahydroxycation.
(c)
Curiously,
compound
Bin
another
pathway proceeds
under
the
conditions
described
mind
the
principles
outlined
in
Section
9-3.
The
mechanism
proceeds
through
hydroxycation.
in mind
outlined
intraverses
Section 9-3.
9-3.
The mechanism
mechanism
proceeds
through
hydroxycation.
1
mind
the principles
principles
presence
oftoAg
salts
(to
accelerate heterolysis with formation of
What
force
for
its
formation?)
the driving
force
for
its
is
force
for
its
formation?)
What is
forcealdehyde
for
its formation?)
formation?)
rearrangement
the
E. Discuss a possible mechanism for this ring contraction
is the
the driving
driving

D
givethe
theprinciples
same products
those9-3.obtained
on treatment
with bas
in mind
outlined in as
Section
The mechanism
proceeds through
ah
is the driving force for its formation?)
aWhat
group.
(c) Curiously, compound B traverses another pathway under the cond
rearrangement to the aldehyde E. Discuss a possible mechanism for this
in mind the principles outlined in Section 9-3. The mechanism proce
What is the driving force for its formation?)

Chapter 9

OH
R or S
A

R or
or SS
R

Br
E Br

S0

C66H55

AD
Diastereomers
Diastereomers AD
(4S)-2-bromo-4of (4S)-2-bromo-4phenylcyclohexanol
phenylcyclohexanol

Note: C66H55 equals

equals

385

)
&
C6H5
E

O
B
CH

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H
75.
The compound
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whose
structure
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structure is
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75.
The compound
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H
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75.
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structure isis CH
H structure
HH
OO CH3
3
CH
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H
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CH3 HHH
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O
O
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H14O)
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3,5-dimethylcyclopentane-oxo
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CH
CH
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(d) trans-3,5-dimethyloxacyclohexane
3
is
best
named
(IUPAC)
CH
CH
H
O)
(C
H
O)
(C
3
H
O)
(C
is
best
named
(IUPAC)
3
7
14
7
14
7
14
CH
O) 3,5-dimethylcyclopentane-oxo
(Cin77H
3H
is best
named (IUPAC)
(C
76. The first step
the
detailed
mechanism for the dehydration of 1-propanol with concentrate
14O)
14
(a)
3,5-dimethylcyclopentyl
ether
(b)
(C
7H
14O)
(a)
3,5-dimethylcyclopentyl
ether
(b)
be
is
named (IUPAC)
O)
7H14(d)
(a)best
3,5-dimethylcyclopentyl
etherH2SO4 would(C
(b) 3,5-dimethylcyclopentane-oxo
3,5-dimethylcyclopentane-oxo
(c)
cis-3,5-dimethyloxacyclohexane
trans-3,5-dimethyloxacyclohexane
(a)
3,5-dimethylcyclopentyl
ether
(b)
3,5-dimethylcyclopentane-oxo
is
best
named
(IUPAC)
(IUPAC)
(c)
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
(b) formation of a sulfate ester
(a) loss of OH2
is
best
named
(IUPAC)
(c) cis-3,5-dimethyloxacyclohexane
cis-3,5-dimethyloxacyclohexane
(d) 3,5-dimethylcyclopentane-oxo
trans-3,5-dimethyloxacyclohexane
named (IUPAC)
(a)
3,5-dimethylcyclopentyl
ether(c) protonation of the alcohol
(b)
loss of H1 bywith
the alcohol
(c)
trans-3,5-dimethyloxacyclohexane
best
named
76. is
The
first
step (IUPAC)
in the detailed mechanism
for the(d)
dehydration
of (d)
1-propanol
concentrated
is
best
named
(IUPAC)
3,5-dimethylcyclopentyl
3,5-dimethylcyclopentane-oxo
ether
(b)
3,5-dimethylcyclopentane-oxo
76. (a)
The
first
step in
the detailedether
mechanism
for
of 1-propanol with
3,5-dimethylcyclopentyl
ether
(b)
3,5-dimethylcyclopentane-oxo
(e) elimination
of Hthe
bydehydration
the
alcohol
CHconcentrated
2O(b)
(c)
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
3
3,5-dimethylcyclopentyl
ether
(b)
3,5-dimethylcyclopentane-oxo
76.
The
fi
rst
step
in
the
detailed
mechanism
for
the
dehydration
of
(a)
3,5-dimethylcyclopentyl
ether
(b)
3,5-dimethylcyclopentane-oxo
SO
would
be
H
2
4
76. (c)
The
fi4rst
step be
in the detailed
mechanism
for the
dehydration
of 1-propanol
1-propanol with
with concentrated
concentrated
(a)
3,5-dimethylcyclopentyl
ether
(b)
3,5-dimethylcyclopentane-oxo
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
would
H
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
2SO
77.
Identify
the
nucleophile
in
the
following
reaction:
(a)
3,5-dimethylcyclopentyl
ether
(b)
3,5-dimethylcyclopentane-oxo
cis-3,5-dimethyloxacyclohexane
(d)dehydration
trans-3,5-dimethyloxacyclohexane
SO
would
H2SO
(c)
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
76. (c)
The
fi4rst
step be
in
of 1-propanol with
concentrated
2 the detailed mechanism for the
H
(d)
trans-3,5-dimethyloxacyclohexane
(b)
formation
of a sulfate
ester(C7H14O)
(a)
loss
of OHbe
2 cis-3,5-dimethyloxacyclohexane
4 would
2
1 2
(c)
cis-3,5-dimethyloxacyclohexane
(d)
trans-3,5-dimethyloxacyclohexane
The
fi
rst
step
in
the
detailed
mechanism
for
the
dehydration
1-propanol
with
concentrated
mechanism
for
the
dehydration
of
1-propanol
with
concentrated
RX
1
H
O
uy
ROH
1
H
X
(b)
formation
of
a
sulfate
ester
(a)
loss
of
OH
76.
in
the
detailed
mechanism
for
the
dehydration
of
1-propanol
with
concentrated
2
2
would
be
H
1of
2SO
4rst
76.
step
in
the
detailed
mechanism
for
the
dehydration
1-propanol
with
concentrated
The
fi
step
in
detailed
mechanism
for
the
dehydration
1-propanol
with
concentrated
2ofthe
(b)
formation
of
a
sulfate
ester
(a)
loss
of
OH
(c)
protonation
the
alcohol
(d)
loss
of
H
by
the
alcohol
1
76. The
fi4rst
in
the
forH1the(d)
dehydration
ofof 1-propanol
with concentrated
(b)
formation
athe
sulfate
ester
(a)2SO
loss
ofstep
OHbe
(a) X2
(b)
(c)
H
(e)
RX
would
(c)
protonation
thedetailed
alcohol mechanism
loss
of(d)HROH
alcohol
2O
be
1by
2of the
76. H
The
fi4rst
in
detailed
mechanism
for the(b)
ofbya1-propanol
with concentrated
would
be
SO
would
H
1of
(c)
protonation
of
the
(d)dehydration
loss
of
the
alcohol
formation
sulfate
ester
(a)
loss
ofstep
OHbe
(e)
elimination
of
H
by the alcohol
2Oalcohol
H
(c)22SO
protonation
of H
the
alcohol
loss
of H
H1
byether
the
alcohol
4 would be
2
Which is the method of(d)
choice
for preparing
the
(CH
(e)
elimination
of
alcohol
2
3CH2)3COCH3?
2O by the 78.
SO
would
be
H
(b)
formation
of
a
sulfate
ester
(a)
loss
of
OH
(b)
formation
of
aa sulfate
ester
(b)
formation
of
sulfate
ester
OH
2
2of
4
(e)2 elimination
elimination
H
Oalcohol
bynamed
the alcohol
alcohol(IUPAC)
(c)
protonation
of best
theO
(d)
of H of
the
alcohol
2loss
(b)
sulfate
ester
(a)
loss
of OH
OH
(b) formation
formation
ofby
asulfate
sulfate
ester
OHis
(e)
by
the
2of H2
K1
(b)
1 CH3MgBr
(a) CH3Br 1 (CH3CH(b)
2
2)3COformation
3CH2)3COH
of
aa(CH
ester
(a)
loss
of
77. (c)
Identify
the
nucleophile
in the
following
reaction:
2of
protonation
the
alcohol
(d)
H
by
alcohol
(d)
loss
of
H11111
by
the
alcohol
protonation
of
the
alcohol
(d)
loss
of
by
the
alcohol
(e) elimination
H
by
the following
alcohol
(c) (CH3CHreaction:
1
CHloss
OH of
(CH
1 CH3O2K1
2)3CMgBr (d)
3formation
3CHalcohol
2)alcohol
3CBr ester
(b)
of
athe
sulfate
(a)
loss the
of OH
2Oalcohol
77. Identify
nucleophile
in the
(c)
protonation
of
the
loss
of
HH
by
the
protonation
of the
the
alcohol
(d)
loss
ofH
H1(d)
by
the
(c)
protonation
of
alcohol
(d)
loss
of
77.
Identify
the
nucleophile
in
the
following
reaction:
elimination
of
H
O
by
the
alcohol
1by the alcohol
alcohol
elimination
of
H
O
by
the
alcohol
2
2
2
77. (e)
Identify
the
nucleophile
in
the
following
reaction:
(a)
3,5-dimethylcyclopentyl
ether
(b) 3
(c) elimination
protonation of
of H
the
(d) 1
lossH1ofX2
H by the alcohol
(e)
O
by
the
alcohol
elimination
of
H
Oalcohol
by the
theRX
alcohol
22O
1 H O reaction:
uy ROH
elimination
of
H
by
alcohol
77. (e)
Identify
the nucleophile
in the
theRX
following
1 H22O u
y ROH 1 H11X22
(e)
elimination
of1H22O by
alcohol
1X2
RX
1
H
O
uy
ROH
1
H
2 the nucleophile
Identify
in
the
following
reaction:
following
reaction:
2
(c)
cis-3,5-dimethyloxacyclohexane
(d) t
77.
nucleophile
in
the
following
reaction:
1 (d)
H2Oreaction:
uy ROH
H X
(a) X
X2 the (b)
(b)
H1
(c)
H2RX
O
ROH
(e)1RX
RX
Identify
nucleophile
in
the
following
77.
nucleophile
in the
the
following
reaction:
(a)
H
(c)
H
O
ROH
(e)
77. Identify
in
following
reaction:
2RX
2 the nucleophile
1
1 (d)
H
uy ROH
1RX
H11X22
2O reaction:
2 the (b)
1
(a)
H
(c)
H
(d)
ROH
(e)
nucleophile
in the
following
77. Identify
1
2
2O
1
2
(a) X
X2
(b)
H1
(c)
HRX
(d)
ROH
(e)
RX
1
H
u
y
ROH
1
H
X
RX
1
H
O
u
y
ROH
1
H
X
2O
11
2
222O
1
H
O
u
y
ROH
1
H
X
CH
)
COCH
?
78.
Which
is
the
method
of
choice
for
preparing
the
ether
(CH
2
3CH
2 3
3
2 mechanism
RX
1
HH
ythe
ROH
11(CH
H
X
The
first
step
in
the
detailed
for the deh
RX
1preparing
Ou
uy
ROH
H1X
78. Which
the(b)
method
choice
for1
ether
2O
(a) X2 is76.
H1 of
(c)
HRX
(d)
ROH
(e)
RX
3X
2)3COCH3?
2O
H
ROH
1
H
22O uy the
1 3CH
2 2)3COCH3?
78.
Which
method
of)(c)
choice
ether
(CH
2 is the
1
2 RX
X
(b)
H
O
(d)
(e)
H
u
ythe
ROH
1RX
X
O11for
(d)
ROH
(e)
RX
uy
2
1 CHof
)3COCH
78. (a)
Which
method
for1preparing
preparing
ether
(CH
X2
(b)
H1
(c)
H
(d)
ROH
(e)
RX
Brthe
1
(CH
COH
(b)
(CH
)3COH
CH3MgBr
MgBr
(a)
CH
2 3is
222K
2OROH
3CH21
3?
2O
2 (c)
3choice
3CH
2H
X
(b)
H
H
(d)
ROH
(e)
RX
Br
1
(CH
CHof
CO
(b)
(CH
1
CH
(a)
CH
(b)
H2133SO
H
O1for preparing
(d)
ROH
(e)
RX
3is
2)4(c)
3(c)
3CH
2)3COH
3 2?1
2O
would
be
H
222K
X
(b)
H
H
(d)
ROH
(e)
RX
CH
)
COCH
78. (a)
Which
the
method
choice
the
ether
(CH
3
2
3
3
2
1
2
1
Br
1
(CH
CH
)
CO
K
(b)
(CH
CH
)
COH
1
CH
MgBr
(a)
CH
(c)
(CH
CH
CMgBr
1
CHH3OH
OH
(d)
(CH
1COCH
CH
K
33CH
2 choice
3CO
2)3(CH
33CH
22)33CBr
3O32?K
(a) (CH
X
(b)
H 33CH
Ofor
(d) ROH
(e)
RX
CH
78. Which
the
of
the
ether
(CH
(b)
(CH
CH
CHis
(c)
CH
(d)
CH
CH
COCH
?? 11
preparing
the
ether
(CH
33Br
2)(c)
3choice
3CH
333COH
2)method
3CMgBr
3 2Kfor
3CH
2)23)CBr
3O33MgBr
CH21
COCH
78.
Which
is
the1
method
of1
for preparing
preparing
the(CH
ether
(CH
2)2)3)31
3?
3CH
3COCH
32
2
1
Which
is
the
method
of
choice
for
preparing
the
ether
(CH
78.
the
method
of21
for preparing
preparing
the(CH
ether
(CH
2))21
3)COCH
(c)
CH
CMgBr
CH
OH
(d)
CBr
CH
1
)choice
CO
(b)
CH3O
(a)
CHis
3CH
3COCH
2
2)
3(CH
3K
CH
?23?K
78. Which
the
of
for
the
ether
(CH
33Br
3CH
3choice
3CH
2)333COH
333MgBr
31
2
1
(c) (CH
(CH
)method
CMgBr
1
CH
OH
(d)
(CH
1
CH
O
K1
2
1
3CH
3(CH
3CH)2)COH
3CBr2 1
23K
1
(b) f
(a)
loss
of
OH
Br
1
))333choice
CO
(b)
(CH
CH
CH
2
(b)
(CH
CH
1
CH
MgBr
2
1
)1
Which
the
of
for
preparing
the
ether
78. (a)
33CH
2221
333CH
222)3)33COH
Br
122)method
(CH
CH
CO
K
(b)
(CH
CH(CH
COH
CH3333MgBr
MgBr
(a)
CH3is
3CH21
3COCH
3?K1
23K
1
3
3
(c) (CH
CH
CMgBr
CH
OH
(d)
CBr
CH
O
2
1
Br
1
(CH
CH
)
CO
(b)
(CH
CH
)
COH
MgBr
(a)
CH
3
3
3
2
3
33Br 1
33CH
2)23)COH
3MgBr
11
1) (CH
(CH
CH221
CO
K
(b) (CH
(CH33CH
1
CH
MgBr
2
2))333CO
3CH
3COH
32
K
(b)
CH
1
CH
(a)
CH
2
3
3
2
3
3
(c)
(CH
CH
CMgBr
CH
OH
(d)
(CH
)
CBr
1
CH
O
K
OH
(d)
(CH
CH
)
CBr
1
CH
O
K
2
11
1
333CH222)333CMgBr 1 CH2
333OH
333CH
2223)33CBr 1 CH
333O 2K
(c)
(CH
(d)
(CH
2
11
(c)
(CH
CH
)
CMgBr
1
CH
OH
(d)
(CH
CH
)
CBr
1
CH
O
K
Br
1
(CH
CH
)
CO
K
(b)
(CH
CH
)
COH
1
CH
MgBr
(a)
CH
(c)
protonation
of
the
alcohol
(d)
l
3
2
3
3
3
2
3
3
(c)
(CH
CH
)
CMgBr
1
CH
OH
(d)
CBr
1
CH
O
K
3
3
2
3
3
2
3
3
3 2)23CBr
3
3 K
(c) (CH33CH22)33CMgBr 1 CH33OH
(d) (CH3CH
1 CH3O
(c) (CH3CH2)3CMgBr 1 CH3OH
(d) (CH3CH2)3CBr 1 CH3O2K1
(e) elimination of H
2O by the alcohol

77. Identify the nucleophile in the following reaction:

RX 1 H2O uy ROH 1
(a) X

(b) H

(c) H2O

(d) ROH

(e)

78. Which is the method of choice for preparing the ethe

(a) CH3Br 1 (CH3CH2)3CO2K1

(b) (CH3C