Reagent Function Notes

-OH Good Nuc, Strong Base SN2 conditions, normal 2 R-L leads to E2
(use synth. eq. acetate)
Converts R-L to R-OH for 1
and activated 2 R-L

-OR Good Nuc, Strong Base SN2 conditions, normal 2 R-L leads to
Converts R-L to R-OR for 1 E2. Known as Williamson Ether
and activated 2 R-L Synthesis

CH3CO2 Fair Nuc, Weak Base SN2 conditions, will work fine for any 1
Is a synth. eq. for OH or 2 R-L
(unmasked with KOH/H2O)

Na (also Na) Sodium metal acts as a base, Harsh conditions that require p/p alcohol
removing H+ from ROH to as the solvent (the CA of RO)
create RO (alkoxide)

K2CO3 Weak base used to Will not work for normal alcohols, only
deprotonate (remove H+) from phenols
phenols

H2SO4 Strong acid which can The CB of H2SO4 is not a Nuc or a

protonate alcohols, allowing strong base
SN1 ether formation

RCO2- Fair Nuc, Weak Base (E2 SN2 conditions, will work well for 1 and
competition minimized) any/all 2 R-L

HBr, HI Strong acids which convert OH Can be used on 1 (SN2), or 2 and 3

into X (Br or I) (both SN1) alcohols

HCl Strong acid which converts OH Can be used only on 3 alcohols. Must
into Cl add ZnCl2 for 1 or 2 ROH

SOCl2 Converts OH into Cl All three work well for 1 and 2 alcohol
conversion. If 3 ROH, H-X is the best
PBr3 Converts OH into Br reagent.

PI3 Converts OH into I

Converts a leaving group into Known as the Gabriel Synthesis. Avoids

an NH2. This reagent is a the problem of multiple alkylations.
synthetic equivalent for NH3,
used to make 1 amines.
 Reagent Function Notes

LiAlH4 Gives an H which replaces a Very reactive, cannot be used around

leaving group with H water or alcohols

NaBH4 Gives an H which replaces a Less reactive, compatible with water or

leaving group with H alcohols

-CN Fair nucleophile, weak base SN2 reagent, works well with both 1 and
2 R-L

-C=CH Good nucleophile, strong base SN2 reagent, works with 1 only, if 2, E2
Acetylide is the major product

NaNH2 or -NH2 Very strong base Can remove H from R--C=C--H

SR or Ph3P Fair nucleophiles, weak bases SN2 reagents, works well with both 1
and 2 R-L

HBr or HI Strong acids that cleave ethers 1 (SN2) and 2 & 3 (SN1)

-OH or -OR Strong bases, Good Nuc Lead to SN2 when 1 or 2 (aprotic); but
E2 when 2 (p/p solvent) or 3
(regardless of solvent)

t-BuO- or LDA Sterically hindered base Poor Nuc, leads to E2 for 1, 2, 3

(Hofmann product)

-OH, or NaNH2 Very strong basic conditions Used to prepare alkynes (E2 twice)

H2SO4, or H3PO4, Dehydration reaction E1 mechanism (Zaitsev product), Watch

out for rearrangements

Na2Cr2O7 1 ROH --> carboxylic acid Strong Oxidizing Agent

K2Cr2O7 in H2SO4 2 ROH --> ketone
CrO3

H2CrO4 (Jones Reagent)

KMnO4 (often hot with H+ or OH-)

1 ROH --> aldehyde Sensitive Oxidizing Agent

2 ROH --> ketone
 Reagent Function Notes

Ag2O aldehyde-->carboxylic acid Incompetent Oxidizing Agent

NaOCl Only does 2 ROH --> ketone Environmentally friendly Oxidizing Agent

HF, HCl, HBr, or HI Acids that add H-X to alkenes Markovnikov addition via carbocation, so
(or alkynes) watch out for rearrangements!

H2O with H2SO4 Adds H2O to alkenes to yield Markovnikov addition via carbocation, so
alcohols (hydration) watch out for rearrangements!

Cl2 or Br2 Halogens that add X2 to Use inert solvents; Follows the
alkenes (or alkynes) borderline SN2 mechanism, results in
anti addition

Br2/H2O or Cl2/H2O Adds 1 X and 1 OH to a C=C Anti addition (inversion) occurs through
(produces a product called a the bromonium (or chloronium) ion, the
halohydrin) water attacks 3>2>1 (borderline SN2)

1) Hg(O2CCH3)2, Adds H and OH to a C=C Markovnikov addition, with NO

H2O rearrangements
2) NaBH4, NaOH

H2O, H2SO4, Hg2+(often Adds H and OH to an alkyne-- Markovnikov addition, an enol initially is
HgSO4 or HgO) > results in the formation of a formed, but spontaneously tautomerizes
ketone to the keto form as the product

1) BH3, THF Adds an H and OH to alkenes Anti-Markovnikov addition, with syn

2) H2O2, NaOH or internal alkynes (same side) addition; watch out for enol-
keto tautomerization with the internal
alkynes

1) disiamylborane Adds H and OH to a terminal Anti-Markovnikov addition, the enol

2) H2O2, NaOH alkyne --> results in the final forms first, then tautomerizes the keto
formation of an aldehyde form (forms aldehyde)

Cu2+ Adds a CH2 (carbene) to a Adds with syn addition, which is

CH2N2 ----------> C=C --> forms a cyclopropane important when product is chiral
or or hv

Ch2I2 with Zn(Cu) alloy Adds a CH2 (carbene) to a Simmons-Smith reaction; adds with syn
C=C --> forms a cyclopropane addition

CHX3 with strong bases Adds a CX2 (carbene) to a Adds with syn addition; make sure to
C=C --> forms a cyclopropane add CX2, NOT CH2
 Reagent Function Notes

RCO3H or MCPBA Adds the 3rd (extra) oxygen to Adds with syn addition, which is
a C=C --> forms an epoxide important when product is chiral

1) OsO4 Adds 1 OH group to each Addition occurs with syn (same side)
KMnO4 carbon of a C=C --> forms diol addition
----------> or --------->
2)Na2SO3 H2O
NaOH

1) O3 Breaks a C=C, adds a =O to Understand the retrosynthetic technique

--------> each carbon, called ozonolysis to know what alkene underwent
2) (CH3)2S ozonolysis (turn the two C=O back into a
C=C)

H2 Breaks a C=C, adds an H to Under normal conditions, H2 does not

--------> each carbon (will convert add to C=C in a phenyl (aromatic) ring.
Pd, or Pt alkynes to alkanes when > Addition is primarily syn
moles of H2 are used)

H2 Adds only one H to each Addition is syn, giving a cis-alkene.

--------> carbon of a C=C (alkyne), Without a Lindlar catalyst, the reaction
Lindlar Catalyst converting it to an cis-alkene cannot stop at the alkene

HNO3 + H2SO4 Substitutes -NO2 on aromatic No limitations; heat reaction or use more
(Nitration) rings vigorous conditions to get disubstituted
product

O Protects amines (and alcohols) Remove group with KOH/H2O

||
CH3CCl
------------>
pyridine

Br2 or Cl2 + Lewis Acid Substitutes -Br or -Cl on Requires Lewis acid unless ring is
(AlX3, FeX3) aromatic rings strongly activated (e.g. phenol and
(Halogenation) aniline, in which case, beware of
disubstitution)

H2SO4 Substitutes -SO3H on aromatic Reaction is reversible, heat in the

(Sulfonation) rings (mainly para if already presence of H2SO4 and H2O remove the
substituted -SO3H group
 Reagent Function Notes

R-Cl Substitutes an (-R) on an 1. Product of alkylation is more

-------> aromatic ring reactive than starting material, often
AlCl3 leading to disubstitution.
2. Rings with moderately or
Carbocation (usually strongly deactivating groups will not
formed by alkyl chloride - undergo alkylation
AlCl3 or alcohol losing 3. Watch out for carbocation
water when acid is added) rearrangements

Friedel-Crafts Alkylation

O Substitutes a 1. Very sensitive to sterics, major

|| / product is always para
R--C--Cl O=C 2. Rings with moderately or
------------> \
R strongly deactivating groups will not
AlCl3 on an aromatic ring undergo alkylation

Acyl cation (usually

formed by acetyl chloride
+ AlCl3)

Friedel-Crafts Acylation

NaNO2/H+ Converts NH2 to N2, which can N2 is a good leaving group and can be
be replaced by nucleophile replaced with a variety of reagents
 Reagent Function Notes

Nucleophile + aromatic Nucleophile replaces halide in The ring must have an electron
halide (Nucleophilic a 2-step process; Nuc attacks, withdrawing group o- or p- to the halide.
Aromatic Substitution: and then halide leaves Leaving group ability:
Addition-Elimination) F > Cl > Br > I

Very strong base (e.g. Eliminates H-X on an aromatic Results in 2 different products if the ring
NaNH2) or base and high ring, creating a reactive is asymmetric because both carbons of
heat (NaOH, ) benzyne intermediate which the intermediate alkyne will be attacked.
(Nucleophilic Aromatic then is attacked by anion
Substitution: Elimination-
Addition)

H2/metal catalyst or Metal Converts NO2 --> NH2 Important synthetic step as a diazonium
(Fe, Sn, SnCl2) + HCl ion precursor
 Reagent Function Notes

Clemmensen: Zn(Hg) + Converts C=O --> CH2 H2/metal catalyst will work only if the
HCl or C=O is attached directly to the aromatic
Wolf-Kishner: NH2NH2 + ring
KOH, or H2/metal
catalyst

1)KMnO4, NaOH, Converts an R on an aromatic Reaction will not work if the substituent
2) H3O+ ring --> CO2H C is quaternary (4)

[CN]
-
Adds a CN to the C and an H Only catalytic amounts of -CN are
HCN -------------> to the O of a C=O, forming a needed; follows the basic mechanism
H2O cyanohydrin

Mg or Li Converts a R-X into a R-M; X=Cl, Br, I; solvent must be aprotic,

which acts like a R- usually ether or THF is used

NH4Cl A weak acid (H+ donor) used to Avoids the E1 result for 3 alcohols
protonate the Td of carbonyl
addition reactions

+ - Ylide attacks C=O, resulting in Witting reaction; BuLi is usually the base
Ph3P--CR2 its eventual conversion to C=C used to make the ylide from its
(P loves O!) phosphonium salt precursor

NR2 N attacks C=O, resulting in its 1 amines --> imines

final conversion to C=N NH2OH --> oximes
2 amines --> enamines

H2/metal or NaBH3CN C=N reacts more easily than Either reagent can be used in the initial
C=O, allowing conversion of reaction mixture, so the imine is never
imines to amines isolated

LiAlH4 Reacts with all C=O Has 4 H- available, converts C=O to CH2-
compounds from table 19.1 OH (except for ketones)

NaBH4 Reacts only with ketones and Has 4 H- available, can use in presence
higher on table 19.1 of H2O, ROH, etc.

LiAlH(Ot-Bu)3 Converts acyl chlorides to Doesnt over-reduce to R-OH

aldehydes at -78 C

Diisobutylaluminum Converts esters to aldehydes Work up with H3O+ to complete reaction

hydride (DIBAH) at -78 C
 Reagent Function Notes

2 mol Grignard + acyl Reacts twice (cannot stop at Use NH4Cl as workup acid to avoid E1
chloride, anhydride, or ketone) to yield alcohol. elimination if 3 ROH
ester

(R)2CuLi Adds only 1 R group to an acyl Same reagent that gave conjugate
chloride, yielding a ketone. addition (Sec. 18.10)

Grignard + nitrile Grignard adds to the nitrile Hydrolysis is exact reverse of imine
once, and the resulting imine is formation (Fig. 18.3)
hydrolyzed back to a ketone by
H3O+.

TsCl or MsCl Converts -OH into -OTs or Reaction proceeds just like acyl
-OMs, which are much better chlorides, but attack is at S
leaving groups.

X2 w/ acid a-halogenation of aldehydes or reaction useful for adding only 1 halogen

ketones

x2 w/ base a-halogenation of aldehydes or Excess (>3 mol) of X2 will convert

ketones methyl groups a to the carbonyl to
carboxylates (haloform/iodoform
reaction)

BuLi Strongest base pKa = 50 Also acts like a nucleophile, so must

avoid using when C=O present

LDA, NaNH2, NaH Very strong bases Used to deprotonate Hs a to the C=O.
pKa=35-38 LDA is used most often because it is
totally non-nucleophilic (steric hindrance)

NaOR Moderate bases Can be used to completely deprotonate

NaOH pKa~16 1,3-dicarbonyl compounds

Both reagents attack R-X as Nuc- in

typical Sn2 reactions. The final step
involves loss of CO2 gas via a 6-member
transition state (make & break bonds
around the ring). The enol which results
Reagent Function Notes

then tautomerizes to the more stable

keto form

1,3-dithiane attacks R-X in typical SN2

reactions or C=O carbonyl reactions.
The dithiane ring can be removed
(regenerating the C=O by adding Hg2+
in H2O

Carboxylates are oxidized at Known as Kolbe electrolysis. Because a

the anode, resulting in a high concentration of Ro forms at the
fragmentation reaction where anode, the coupling reaction is
CO2 is lost prevalent, resulting in a new R-R bond.

Replaces H with a Br at the Cl2 is too reactive (not selective enough)

location of the most stable to be synthetically useful.
radical.

Known as NBS. Replaces H NBS is especially useful when

with a Br at the location of the attempting to brominate allylic systems
most stable radical. because it will not add (addition reaction)
to the C=C

Replaces X with H

Autoxidation - adds an OOH Not often synthetically useful, but

group to the most stable important in food spoilage and chemical
radical position decomposition

Anti-markovnikov addition of HF, HCl, HI do NOT work well. Anti-

HBr to a C=C markovnikov regio-chemistry is followed
because a more stable radical is formed

Each group adds to one side

of the C=C. The larger group
(boxed) adds first, the smaller
group adds second and goes
to the carbon which would
have the more stable radical.
Reagent Function Notes

Reduces benzene into 1,4- Known as Birch reduction. Also useful in

butadiene (not conjugated), or alkylating a to the carbonyl in a,B-
reduces the C=C of an a,B- unsaturated carbonyl systems.
unsaturated carbonyl, or
reduces an alkyne into a trans-
alkene