18.

9
The Aldol Condensation
 Some thoughts...

O O
– •• ••
RCH2CH + •• OH RCHCH + HOH
•• ••
– ••
pKa = 16-20 pKa = 16

A basic solution contains comparable amounts

of the aldehyde and its enolate.
Aldehydes undergo nucleophilic addition.
Enolate ions are nucleophiles.
What about nucleophilic addition of enolate to
aldehyde?
 ••
O ••
–
RCHCH
••

RCH2CH

O ••
••
 ••
O •• •• ••
– O •• O ••
RCHCH
•• RCHCH RCHCH
RCH2CH RCH2CH RCH2CH
O •• •• O •• •• OH
•• •• – ••
 ••
O •• •• ••
– O •• O ••
RCHCH
•• RCHCH RCHCH
RCH2CH RCH2CH RCH2CH
O •• •• O •• •• OH
•• •• – ••

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R
 Aldol Addition

RCH2CH CHCH
OH R

product is called an "aldol" because it is

both an aldehyde and an alcohol
 Aldol Addition of Acetaldehyde

O O
NaOH, H2O
2CH3CH CH3CH CH2CH
5°C
OH
Acetaldol
(50%)
Aldol Addition of Butanal

2CH3CH2CH2CH

KOH, H2O 6°C

CH3CH2CH2CH CHCH
OH CH2CH3
(75%)
 Aldol Condensation

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R
 Aldol Condensation

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R
 Aldol Condensation

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R

heat

RCH2CH CCH
R
 Aldol Condensation

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R

NaOH heat
heat
O

RCH2CH CCH
R
Aldol Condensation of Butanal

2CH3CH2CH2CH

NaOH, H2O 80-100°C

Aldol Condensation of Butanal

2CH3CH2CH2CH

NaOH, H2O 80-100°C

CH3CH2CH2CH CCH
CH2CH3
(86%)
 Dehydration of Aldol Addition Product

C O C O
H
C C

C OH C

dehydration of b-hydroxy aldehyde can be

catalyzed by either acids or bases
 Dehydration of Aldol Addition Product

C O C O
H NaOH
–
C C ••

C OH C OH

in base, the enolate is formed

 Dehydration of Aldol Addition Product

C O C O
H NaOH
–
C C ••

C OH C OH

the enolate loses hydroxide to form the

a,b-unsaturated aldehyde
 Aldol reactions of ketones

O OH O
2%
2CH3CCH3 CH3CCH2CCH3
98%
CH3

the equilibrium constant for aldol addition

reactions of ketones is usually unfavorable
 Intramolecular Aldol Condensation

O O

Na2CO3, H2O
O
heat

O (96%)

via:

OH
 Intramolecular Aldol Condensation

O O

Na2CO3, H2O
O
heat

(96%)

even ketones give good yields of aldol

condensation products when the reaction is
intramolecular
 18.10
Mixed Aldol Condensations
 What is the product?

O O
NaOH
CH3CH + CH3CH2CH

There are 4 possibilities because the

reaction mixture contains the two
aldehydes plus the enolate of each
aldehyde.
 What is the product?

O O

CH3CH + CH3CH2CH O

CH3CH CH2CH
O O OH
– –
•• CH CH CH3CHCH
2
••
 What is the product?

O O

CH3CH + CH3CH2CH O

CH3CH2CH CHCH
O O OH CH3
– –
•• CH CH CH3CHCH
2
••
 What is the product?

O O

CH3CH + CH3CH2CH O

CH3CH CHCH
O O OH CH3
– –
•• CH CH CH3CHCH
2
••
 What is the product?

O O

CH3CH + CH3CH2CH O

CH3CH2CH CH2CH
O O OH
– –
•• CH CH CH3CHCH
2
••
 In order to effectively carry out
a mixed aldol condensation:

need to minimize reaction possibilities

usually by choosing one component that cannot
form an enolate
 Formaldehyde

HCH

formaldehyde cannot form an enolate

formaldehyde is extremely reactive toward
nucleophilic addition
 Formaldehyde

O O O
K2CO3
HCH + (CH3)2CHCH2CH (CH3)2CHCHCH
water-
ether CH2OH

(52%)
 Aromatic Aldehydes

CH3O CH

aromatic aldehydes cannot form an enolate

 Aromatic Aldehydes

O O

CH3O CH + CH3CCH3

NaOH, H2O 30°C

CH3O CH CHCCH3

(83%)