1. Aldol Condensation Reaction
Mr. R. B. Gawade M. Sc. NET / GATE
Assistant Professor
Department of Chemistry
S. M. Joshi College Hadapsar Pune

2. Aldehydes undergo nucleophilic addition.
Some thoughts...
RCH2CH O
RCHCH O •• OH
• • – ••
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? 2

3. ••
RCHCH O
• • –
RCH2CH 3

4. O – RCHCH RCHCH RCHCH RCH2CH RCH2CH RCH2CH O O O H – •• • • • • •• • •3

5. RCHCH O – – RCH2CH O RCHCH RCH2CH O RCHCH H RCH2CH O 2RCH2CH O RCH2CH••
• • – –
RCH2CH O ••
• •
RCHCH
RCH2CH O ••
• •
RCHCH H ••
RCH2CH O ••
• • ••
2RCH2CH O
RCH2CH OH
CHCH O R
NaOH 3

6. Aldol Addition RCH2CH OH CHCH O R
product is called an "aldol" because it is both an aldehyde and an alcohol 5

7. Aldol Addition of Acetaldehyde
2CH3CH O
CH3CH OH
CH2CH O
NaOH, H2O
5°C
Acetaldol (50%) 6

8. Aldol Addition of Butanal
2CH3CH2CH2CH O
KOH, H2O
6°C
CH3CH2CH2CH OH
CHCH O
CH2CH3
(75%) 6

9. Aldol Condensation
2RCH2CH O
RCH2CH OH
CHCH O R
NaOH 3

10. Aldol Condensation
2RCH2CH O
RCH2CH OH
CHCH O R
NaOH 3

11. Aldol Condensation 2RCH2CH O RCH2CH OH CHCH O R NaOH heat O RCH2CH CCH3

12. Aldol Condensation 2RCH2CH O RCH2CH OH CHCH O R NaOH NaOH heat heat O
CCH R 3

13. Aldol Condensation of Butanal
2CH3CH2CH2CH O
NaOH, H2O
80-100°C 6

14. Aldol Condensation of Butanal
2CH3CH2CH2CH O
NaOH, H2O
80-100°C
CH3CH2CH2CH
CCH O
CH2CH3
(86%) 6

15. Dehydration of Aldol Addition ProductOH H C O C O
dehydration of b-hydroxy aldehyde can be catalyzed by either acids or bases 12

16. Dehydration of Aldol Addition ProductOH H C O OH C O
• • –
NaOH
in base, the enolate is formed 12

17. Dehydration of Aldol Addition ProductOH H C O OH C O
• • –
NaOH
the enolate loses hydroxide to form the a,b-unsaturated aldehyde 12

18. Aldol reactions of ketones
2CH3CCH3 O O
CH3CCH2CCH3 OH
CH3 2%
98%
the equilibrium constant for aldol addition reactions of ketones is usually unfavorable 16

19. Intramolecular Aldol Condensation
(96%)
Na2CO3, H2O
heat O OH
via: 19

20. Intramolecular Aldol Condensation
(96%)
Na2CO3, H2O
heat
even ketones give good yields of aldol condensation products when the reaction is intramolecular 19

21. 18.10 Mixed Aldol Condensations

22. What is the product? O O NaOH + CH3CH2CH CH3CH
There are 4 possibilities because the reaction mixture contains the two aldehydes plus the enolate of each aldehyde. 21

23. What is the product? CH3CH O CH3CH2CH O + CH3CH OH CH2CH O CH2CH O O –
• • – –
CH3CHCH •• 21

24. What is the product? CH3CH O CH3CH2CH O + CH3CH2CH OH CHCH O CH3 CH2CH
• • – –
CH3CHCH •• 21

25. What is the product? CH3CH O CH3CH2CH O + CH3CH OH CHCH O CH3 CH2CH O
• • – –
CH3CHCH •• 21

26. What is the product? CH3CH O CH3CH2CH O + CH3CH2CH OH CH2CH O CH2CH O
• • – –
CH3CHCH •• 21

27. 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 22

28. formaldehyde cannot form an enolate
HCH
formaldehyde cannot form an enolate
formaldehyde is extremely reactive toward nucleophilic addition 23

29. Formaldehyde O HCH (CH3)2CHCH2CH O (CH3)2CHCHCH O CH2OH + (52%) K2CO3
water- ether
(52%) 23

30. aromatic aldehydes cannot form an enolate
CH3O CH O
aromatic aldehydes cannot form an enolate 24

31. Aromatic Aldehydes CH3O CH O CH3CCH3 O + NaOH, H2O 30°C CH3O CH CHCCH3
(83%) 24

32. Thanks