1. 18.9 The Aldol Condensation

2. 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? RCH 2 CH O+ OH – RCHCHO+HOH – pK a = 16-20 pK a = 16 Some thoughts...

3. RCHCH O – RCH 2 CH O

4. RCHCH O – RCH 2 CH O – RCH 2 CH O RCHCH O RCH 2 CH O RCHCH O H

5. RCHCH O – RCH 2 CH O – RCH 2 CH O RCHCH O RCH 2 CH O RCHCH O H 2RCH 2 CH ONaOH RCH 2 CH OH CHCHOR

6. product is called an "aldol" because it is both an aldehyde and an alcohol Aldol Addition RCH 2 CH OH CHCHOR

7. Aldol Addition of Acetaldehyde Acetaldol (50%) NaOH, H 2 O 5°C 2CH 3 CH O CH 3 CH OH CH 2 CH O

8. Aldol Addition of Butanal (75%) KOH, H 2 O 6°C 2CH 3 CH 2 CH 2 CH O CH 3 CH 2 CH 2 CH OH CHCHO CH 2 CH 3

9. 2RCH 2 CH ONaOH RCH 2 CH OH CHCHOR Aldol Condensation

10. 2RCH 2 CH ONaOH RCH 2 CH OH CHCH OR Aldol Condensation

11. 2RCH 2 CH ONaOH RCH 2 CH OH CHCH OR Aldol Condensation heat RCH 2 CH CCHOR

12. 2RCH 2 CH ONaOH RCH 2 CH OH CHCH OR Aldol Condensation heat RCH 2 CH CCHOR NaOH heat

13. Aldol Condensation of Butanal NaOH, H 2 O 80-100°C 2CH 3 CH 2 CH 2 CH O

14. Aldol Condensation of Butanal (86%) NaOH, H 2 O 80-100°C 2CH 3 CH 2 CH 2 CH O CH 3 CH 2 CH 2 CH CCHO CH 2 CH 3

15. dehydration of  -hydroxy aldehyde can be catalyzed by either acids or bases Dehydration of Aldol Addition Product C O C C OH H C O C C

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

17. the enolate loses hydroxide to form the ,  -unsaturated aldehyde Dehydration of Aldol Addition Product OH H C O C C NaOH OH C O C C –

18. Aldol reactions of ketones the equilibrium constant for aldol addition reactions of ketones is usually unfavorable 2%98% 2CH 3 CCH 3 O O CH 3 CCH 2 CCH 3 OH CH 3

19. Intramolecular Aldol Condensation Na 2 CO 3, H 2 O heatOO OOH O(96%) via:

20. Intramolecular Aldol Condensation Na 2 CO 3, H 2 O heatOO O(96%) even ketones give good yields of aldol condensation products when the reaction is intramolecular

21. 18.10 Mixed Aldol Condensations

22. What is the product? There are 4 possibilities because the reaction mixture contains the two aldehydes plus the enolate of each aldehyde. NaOH CH 3 CH O CH 3 CH 2 CH O+

23. What is the product? CH 3 CH O CH 3 CH 2 CH O+ CH 2 CH O CH 3 CHCH O – – CH 3 CH OH CH 2 CH O

24. What is the product? CH 3 CH O CH 3 CH 2 CH O+ CH 2 CH O CH 3 CHCH O – – CH 3 CH 2 CH OH CHCHO CH 3

25. What is the product? CH 3 CH O CH 3 CH 2 CH O+ CH 2 CH O CH 3 CHCH O – – CH 3 CH OH CHCHO CH 3

26. What is the product? CH 3 CH O CH 3 CH 2 CH O+ CH 2 CH O CH 3 CHCH O – – CH 3 CH 2 CH OH CH 2 CH O

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

28. Formaldehyde formaldehyde cannot form an enolate formaldehyde is extremely reactive toward nucleophilic addition OHCH

29. FormaldehydeOHCH + (CH 3 ) 2 CHCH 2 CH O (CH 3 ) 2 CHCHCH O CH 2 OH (52%) K 2 CO 3 water- ether

30. Aromatic Aldehydes CH 3 O CHO aromatic aldehydes cannot form an enolate

31. Aromatic Aldehydes CH 3 O CHO+ CH 3 CCH 3 O NaOH, H 2 O 30°C CH 3 O CH CHCCH 3 O(83%)