26.!

'larnides also
pror.rv-acetylaniiine
rone in g0?o yietd

Reacrions of

Aqdamtnes lOAl

OH

",*{}$_L<l
L-,/ l1 No

Sulfatbiazole

NH,

)'.

V
-'o

26.4

with the aromatic ring.

26.5
robenzophenone
$O.qa)

Account for the fact that an amido substituent (_NHCOR)

is ortho- and para_direct_
ing, by drawing resonance structures that share the niirogen
lone-pair electrons

Propose syntheses of these compounds from benzene:

(a) N,N-Dimethylaniline
(c) m-Chloroaniline

(b) p-Chloroaniline
-2,a_limethylaniiine
(d)

of amino-sub_
rne that allow_.

rzied out that

ration of sulfa
tarmaceutical
have largellIa drugs were

rofthousand_.

'osulfonation
zenesulfonvl
nide, Hydro_

drolysis can
euse suifon-

DIAZONIUM SALTS: THE SANDMEYER REACTTON

Primary aromatie amines react with nitrous acid, HNo2, to yield

stabie
areaed.iazorium salts, Ar-fr=N X-. This diazotization reaction is
compatible with the presence of a wide variety of substituents
on the aromatic
ring.

/->(*''
(/

HNo, + Hzso4

,4'---.rirz*

Hso4- + 2H2o

(/"

Alkylamines also react with nitrous acid., but the products of these reactions,
alkanediazonium salts, are too reactive to isolaL since they lose
nitrogen
instantly to yield carbocations.
NH"

t"

:?:o
N&
fouilamide
tulfa drugr

ne.

* 'r

H2Soa

[n

. -HSo4]

__--., R* -HSo4 +

Arenediazonium sarts are extremely usefur in synthesis, because

the
diazonio group (N2+) can be replaced by nucleophiles:

.r'',-u;u-'*

(}"

HSon-

:Nu-

0*"

N2

Many different nucleophiles react with arenediazonium salts, and many

different substituted benzenes can be prepared with this reaction. The oveiall sequence of(L) nitration, (2) reduclion, (A) diazotization, and (4) nucleo_
phile replacement is probably the single most versatile method of aromatic
substitution (Figure 26.3). Although the details aren,t fully understood,, the

\ "'-"' ""-'''="""
1008

CHAPTER

26

*n=,,,,-J

Arylamines and Phenols

mechanism by which these substitutions occur is a radical, rather than

polar, one.

,4-'-zB'
(/

(\'
\-/

C=N

,4-"-/cl
(/+

,Z-\1oH

,4t--r'H

U
Figure

26.3

Preparation of substituted aromatic compounds by

di azonio replacement reactions.

Aryl chlorides and bromides are prepared by reaction of an

azonium salt with the corresponding cuprous halide, CuX, a process
the sandmeyer2 reaction. Aryi iodides can be prepared by direct reac:.
with sodium iodide without using a cuprous salt. Yieids generally fa-the 60-80% range.

*.-cr*'' #

1,,",(rn=NHSo4-

H,C
p-Bromotoluene

p-Methylaniline

Cr"" #

*
]

l er-=NHSoa'

-'- er'
Iodobenzene

(677o)

zTraugott Sandmeyer (L854-1922'l; b. Wettingen, Switzerland; Ph.D. Heidelberg

mann); Geigy Company, Basel, Switzerland.

,ffi

iffi

26,g

Reactions of

Arytamines

I OO9

similar treatmelt of an arenediazonium salt

with cuprous cyanide
yields the arenenitrile, ArcN. This
re-ac-tion is partic,rruriy .r"-"r,rr,
because
it altows the replacement of a,ritrogenl-ub"s;,il;;
;;;;i#i
substituent.
The nitrite can then be further .;";;;;J
into orher i"il;;;i
groups such
as carboxvl, -coo*. For example, hvdroivsi.
;-*;;;il;;;onitriie, pro_
duced by sandmeyer reac'ion oi r--"tirytbenzenediazonium
"f
bisurfate with
cuprous cyanide, yierds. o-methyrbenzoic
acid. This product could not be
prepared from o-xyrene by the usuai
side-chain oxidaiion.""r", since both
methyl groups would be oxidized

ffij

Y=N

CH,

Hso4-

C=N

COOH

o_Methylbenzonitrile

o-Methyltrenzoic

CH,
HNO,

KCN

H2SOl

,,-Methylaniline

CUCN

o-Methylbenzenediazonium bisulfate

acid

The diazonio group can arso be replaced

-oH to yierd phenols and

-H to yield ,..nuJ. phenors u.r.r'.rruitv by
prepared by addition of the
arenediazonium salt to hot aqueous
u.ia. mo ,";;i;; ['"riiiurry impor_
tant, since few other general methods
exist ro. i.riroir.irrg-'"" -orr group
onto an aromatic ring.
by

NI{"

OH

2',

\A*o,

-t
Hso' (' \

HNO,
H2SOI

NO,

7x-f{if,1'6*nilins

Vwo,
m.Nitrophenol

(86Va)

Arenes are oroduced by reduction

of the diazonium salt with hypophosphorous acid' H3po2. rlir
."r.iirn i. ro, particularry usefu], however,
uniess there's u .r""ifo, i"*p*;;iylri.oor.,"*
an amino substituenr onto
a ring to take advantage of it" *"iirrutlng
etrect. The preparation of B,sdibromotoluene from p-methylanili"e
[-161,ridine) i1]usiraies how this can
be done. Dibromination ofp-ioluiJi*
ot"r.
ortho to the strongry directing
amino substituent, and diazotization
f;r;*;d
i,rpoprro._
phorous acid vields 8,5-dibromot"r"""".-irri. il';r;;,#;i,itr,
p"oa,r.t .;;;;ilJ p""pared by
of toluene, h";";;;, since reaction woutd
oecur at posi_
f,r#:LT:Tination

CHB

p.Methytaniline
l:

-lll

2Brz.'"$"'

Br

Y=N Eso4Br

}INO,

II3PO2

H2SOI

CHs

CH,

CH,
3,5-Dibromotoluene