Carbanions

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C:
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The conjugate bases of weak acids,
strong bases, excellent
nucleophiles.

1. Alpha-halogenation of ketones
OH- or H+

O
C C
H

+ X2

O
C C
X

+ HX

-haloketone
X2 = Cl2, Br2, I2

H3C

O
C

CH3

acetone

+ Br2, NaOH

H3C

O
C

CH2Br

-bromoacetone

NaBr

O
Cl

+ Cl2, H
cyclohexanone

O
C CH3

acetophenone

+ HCl
2-chlorocyclohexanone

+ Br2, NaOH

O
C CH2Br + NaBr

-bromoacetophenone

Alpha-hydrogens: 1o > 2o > 3o

O
CH3CH2CH2CCH3 + Br2, NaOH

O
CH3CH2CH2CCH2Br + NaBr
1-bromo-2-pentanone

2-pentanone

Hydrogens that are alpha to a carbonyl group are weakly acidic:

H3C

O
C

CH3

+ OH

H3C

O
C

CH2

+ H2O

Hydrogens that are alpha to a carbonyl are weakly

acidic due to resonance stabilization of the carbanion.

O
C

CH2

O
C

CH2

"enolate" anion
The enolate anion is a strong base and a good nucleophile

Mechanism for base promoted alpha-bromination of acetone:

1)

2)

H3C

H3C

O
C

O
C

CH3

CH2

+ OH

RDS
H3C

Br Br

Rate = k [acetone] [base]

H3C

O
C

O
C

CH2

CH2Br

+ H2O

+ Br

Mechanism for acid catalyzed halogenation of ketones. Enolization.

1)

2)

3)

4)

H3C

O
C

CH3

H+

OH
+ :B
C
H3C
CH3
OH
+ Br Br
C
H3C
CH2

OH
C
H3C
CH2Br

OH
C
H3C
CH3

enol

OH
+ H:B
C
H3C
CH2
OH
+ :Br
C
H3C
CH2Br

H3C

O
C

+ H
CH2Br

Oxidation of "methyl" ketones. Iodoform test.

O
C

CH3

O
R C
O

+ (xs) OI

CHI3

NaOH + I2

O
C

O
C

O
R C CI3
OH

CH2I

CHI2

O
C

CI3

+ OH

good
leaving
group

Carbanions. The conjugate bases of weak acids;

strong bases, good nucleophiles.
1. enolate anions
2. organometallic compounds
3. ylides
4. cyanide
5. acetylides

Aldehydes and ketones: nucleophilic addition

O
C

+ YZ

OY
C
Z

Esters and acid chlorides: nucleophilic acyl substitution

O
C
W

+ Z

O
C
Z

+ W

Alkyl halides: SN2

R X

+ Z

R Z + X

Carbanions as the nucleophiles in the above reactions.

2. Carbanions as the nucleophiles in nucleophilic

addition to aldehydes and ketones:
a) aldol condensation
crossed aldol condensation
b) aldol related reactions (see problem 21.18
on page 811)
c) addition of Grignard reagents
d) Wittig reaction

Carbanions as the nucleophiles in nucleophilic addition to

aldehydes and ketones:
c) addition of Grignard reagents
Grignard reagents are examples of organo metallic
carbanions.

O
C

+ RMgX

OMgX
C
R

a) Aldol condensation. The reaction of an aldehyde or ketone

with dilute base or acid to form a beta-hydroxycarbonyl product.

CH3CH=O
acetaldehyde

OH
CH3CHCH2CH O
3-hydroxybutanal

O
CH3CCH3
acetone

OH O
CH3CCH2CCH3
CH3

dil. NaOH

dil. NaOH

4-hydroxy-4-methyl-2-pentanone

dil. NaOH

CH3CH=O
acetaldehyde

OH
CH3CHCH2CH O
3-hydroxybutanal
+ H2O

OH
CH2CH=O + CH3CH O

O
CH3CHCH2CH O

+ H2O
nucleophilic addition by enolate ion.

H3C

O
C

dil. NaOH
CH3

H3C

O
C

OH

H3C

O
C

CH2

+ H2O

OH
CH3
C
C
CH3
H2
+ H2O

H3C

O
C

CH3

H3C

O
C

O
CH3
C
C
CH3
H2

CH3CH2CH=O + dil. NaOH

CH3CHCH O
alpha!
CH3CH2CH O

OH
CH3CH2CHCH2CH2CHO

OH
CH3CH2CHCHCHO
CH3

O
dil. OH-

OH

OH

O
O

HOH

O
dil. H+

+ H2O

With dilute acid the final product is the ,unsaturated carbonyl compound!

CH2CH O

dil NaOH

OH
CH2 C CH CH=O
H

phenylacetaldehyde

dilute H+

CH2 C C CH=O
H

+ H2O

note: double bond is conjugated

with the carbonyl group!

NB: An aldehyde without alpha-hydrogens

undergoes the Cannizzaro reaction with conc. base.

CHO

benzaldehyde

conc. NaOH

COO+

CH2OH

Crossed aldol condensation:

If you react two aldehydes or ketones together in an
aldol condensation, you will get four products. However, if
one of the reactants doesnt have any alpha hydrogens it can be
condensed with another compound that does have alpha
hydrogens to give only one organic product in a crossed
aldol.
NaOH

CH3CH2CH O + H2C O

CH O
CH3CHCH2 OH

N.B. If the product of the aldol condensation under basic

conditions is a benzyl alcohol, then it will spontaneously
dehydrate to the ,-unsaturated carbonyl.

CH=O + CH3CH2CH2CH=O

OH
CHCHCH=O
CH2
CH3

dil OH-

-H2O

CH=CCH=O
CH2
CH3

A crossed aldol can also be done between an aldehyde and a

ketone to yield one product. The enolate carbanion from the
ketone adds to the more reactive aldehyde.

O
C CH3
acetophenone

+ CH3CH=O
acetaldehyde

dil

OH-

O
OH
C CH2 C CH3
H

b) Aldol related reactions: (see problem 21.18 page 811

of your textbook).
KOH

CH=O + CH3NO2

CH=CHNO2

+ H2O

CH2NO2
NaOEt
CH=O +

CH2C N

CHC

CH=C CN

+ H2O

Perkin condensation

CH=O

+ (CH3CO)2O

CH3COONa

CH=CHCOOH
+ CH3COOH

O
H2C C
O
CH3 C
O
OH
O
CHCH2 C
O
CH3 C
O

hydrolysis of
anhydride

O
H
C C C
H O
CH3 C
O

+ H2O

d) Wittig reaction (synthesis of alkenes)

1975 Nobel Prize in Chemistry to Georg Wittig

R
C O + Ph3P=C R'
ylide

CH2CH=O

Ph = phenyl

O R
C C R'
PPh3

+ Ph3P=CH2

R
C C R'

+ Ph3PO

CH2CH=CH2 + Ph3PO

Ph R
Ph P C R'
Ph
ylide

O
C

O R
C C R'
PPh3

R
C C R'

+ Ph3PO

nuclephilic addition by ylide carbanion, followed by loss of

Ph3PO (triphenylphosphine oxide)

O + Ph3PCHCH=CH2

CHCH CH2 + Ph3PO

3. Carbanions as the nucleophiles in nucleophilic acyl

substitution of esters and acid chlorides.
a) Claisen condensation
a reaction of esters that have alpha-hydrogens in basic
solution to condense into beta-keto esters

CH3COOEt
ethyl acetate

NaOEt

O
CH3CCH2COOEt + EtOH
ethyl acetoacetate

Mechanism for the Claisen condensation:

CH3COOEt

NaOEt

O
CH3CCH2COOEt + EtOH

OEt

CH2COOEt

CH3

O
C
OEt

CH3

O
C OEt
CH2COOEt

nucleophilic acyl substitution by enolate anion

ethyl propionate

CH3CH2COOEt

ethyl 2-methyl-3-oxopentanoate
OEt

O
CH3CH2CCHCOOEt
CH3

OEt
CH3CHCOOEt

O
CH3CH2C
OEt

O
CH3CH2C OEt
CHCOOEt
CH3

ethyl phenylacetate

NaOEt

CH2COOEt

O
CH2C CHCOOEt

OEt

CHCOOEt

O
CH2C
OEt

O
CH2C OEt
CHCOOEt

Crossed Claisen condensation:

COOEt + CH3COOEt

NaOEt

O
C CH2COOEt

ethyl benzoate
OEt
HCOOEt + CH3CH2COOEt
ethyl formate

O
H C CHCOOEt
CH3

COOEt

OC2H5
+

COOEt
ethyl oxalate

COOEt
COOEt

CH3CH2COOEt

NaOC2H5
+ 2 CH3CH2COOEt

O CH3
C CHCOOEt
C OEt
O
O
C
C
O

CH3
CHCOOEt
CHCOOEt
CH3

COOEt

O
+
EtOCOEt
ethyl carbonate

CH2
COOEt

O COOEt
EtO C CH
COOEt

NaOEt

ethyl malonate
O
CH3CH2COOEt
ethyl propionate

NaOEt

O
CH3CH2C

cyclohexanone

enolate from ketone in nucleophilic acyl substitution on ester

b) Coupling of lithium dialkyl cuprate with acid chloride

O
R C
Cl

+ R'2CuLi

nucleophile = R'

O
R C
R'

4. Carbanions as nucleophiles in SN2 reactions with RX:

a) Corey-House synthesis of alkanes
R2CuLi + RX R-R
b) metal acetylide synthesis of alkynes
RCC-M+ + RX RCCR
c) Malonate synthesis of carboxylic acids

d) Acetoacetate synthesis of ketones

5. Michael Addition to ,-unsaturated carbonyl

compounds

Carbanions are the conjugate bases of weak acids and

are therefore strong bases and excellent nucleophiles
that can react with aldehydes/ketones (nucleophilic
addition), esters/acid chlorides (nucleophilic acyl
substitution), and alkyl halides (SN2), etc.

Reactions involving carbanions as nucleophiles:

1. Alpha-halogenation of ketones
2. Nucleophilic addition to aldehydes/ketones
a) aldol and crossed aldol
b) aldol related reactions
c) Grignard synthesis of alcohols
d) Wittig synthesis of alkenes
3. Nucleophilic acyl substitution with esters and acid
chlorides
a) Claisen and crossed Claisen
b) R2CuLi + RCOCl
(next slide)

4. SN2 with alkyl halides

a) Corey-House
b) metal acetylide
c) Malonate synthesis
d) Acetoacetate synthesis
5. Michael Addition to ,-unsaturated carbonyl
compounds