18.9 The Aldol Condensation
Some thoughts... O
O
– •• RCH2CH + •• OH ••
RCHCH •• –
pKa = 16-20
••
+
HOH ••
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 •• – RCHCH ••
••
••
O ••
O ••
RCHCH
RCHCH
RCH2CH
RCH2CH
RCH2CH
O ••
•• O •• •• –
•• OH ••
••
••
O ••
••
– RCHCH ••
••
O ••
O ••
RCHCH
RCHCH
RCH2CH
RCH2CH
RCH2CH
O ••
•• O •• •• –
•• OH ••
••
O
O NaOH
2RCH2CH
RCH2CH OH
CHCH R
Aldol Addition
O RCH2CH OH
CHCH R
product is called an "aldol" because it is both an aldehyde and an alcohol
Aldol Addition of Acetaldehyde
O 2CH3CH
O NaOH, H2O
5°C
CH3CH
CH2CH
OH Acetaldol (50%)
Aldol Addition of Butanal O 2CH3CH2CH2CH
KOH, H2O
6°C O
CH3CH2CH2CH OH (75%)
CHCH CH2CH3
Aldol Condensation O
O NaOH
2RCH2CH
RCH2CH OH
CHCH R
Aldol Condensation O
O NaOH
2RCH2CH
RCH2CH OH
CHCH R
Aldol Condensation O
O NaOH
2RCH2CH
RCH2CH OH
CHCH R heat O
RCH2CH
CCH
R
Aldol Condensation O
O NaOH
2RCH2CH
RCH2CH OH
CHCH R heat
NaOH heat
O RCH2CH
CCH
R
Aldol Condensation of Butanal O 2CH3CH2CH2CH
NaOH, H2O
80-100°C
Aldol Condensation of Butanal O 2CH3CH2CH2CH
NaOH, H2O
80-100°C O
CH3CH2CH2CH
CCH CH2CH3
(86%)
Dehydration of Aldol Addition Product
C
H
C
O
C
C C
OH
C
dehydration of b-hydroxy aldehyde can be catalyzed by either acids or bases
O
Dehydration of Aldol Addition Product
C
H
O
NaOH
C C
OH
in base, the enolate is formed
C
O
C
OH
– C ••
Dehydration of Aldol Addition Product
C
H
O
C C
NaOH
C
O
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 O
Na2CO3, H2O
heat O
(96%)
via: OH
Intramolecular Aldol Condensation
O
O O
Na2CO3, H2O
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
O
–
•• CH CH 2
O – CH3CHCH ••
OH
CH2CH
What is the product?
O
O
CH3CH + CH3CH2CH
O CH3CH2CH
O
–
•• CH CH 2
O – CH3CHCH ••
OH
CHCH CH3
What is the product?
O
O
CH3CH + CH3CH2CH
O CH3CH
O
–
•• CH CH 2
O – CH3CHCH ••
OH
CHCH
CH3
What is the product?
O
O
CH3CH + CH3CH2CH
O CH3CH2CH
O
–
•• CH CH 2
O – CH3CHCH ••
OH
CH2CH
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
O HCH formaldehyde cannot form an enolate formaldehyde is extremely reactive toward nucleophilic addition
Formaldehyde
O
O
HCH + (CH3)2CHCH2CH
O K2CO3 waterether
(CH3)2CHCHCH CH2OH
(52%)
Aromatic Aldehydes
O CH3O
CH
aromatic aldehydes cannot form an enolate
Aromatic Aldehydes
O
O CH3O
+
CH NaOH, H2O
CH3CCH3 30°C
O CH3O
CH
CHCCH3 (83%)