1. 17.5 Reactions of Aldehydes and Ketones: A Review and a Preview

2. Reactions of Aldehydes and Ketones
Already covered in earlier chapters:
reduction of C=O to CH2
Clemmensen reduction
Wolff-Kishner reduction
reduction of C=O to CHOH
addition of Grignard and organolithium reagents 2

3. 17.6 Principles of Nucleophilic Addition to Carbonyl Groups: Hydration of Aldehydes and Ketones4

4. Hydration of Aldehydes and KetonesC •• O
• •
H2O HO C O H •• 5

5. Substituent Effects on Hydration EquilibriaOH R R' +
H2O C O
compared to H
electronic: alkyl groups stabilize reactants
steric: alkyl groups crowd product 6

6. Equilibrium Constants for Hydration
C=O hydrate K %
CH2=O CH2(OH)
CH3CH=O CH3CH(OH)
(CH3)3CCH=O (CH3)3CCH(OH)
(CH3)2C=O (CH3)2C(OH) 7

7. When does equilibrium favor hydrate?
when carbonyl group is destabilized
alkyl groups stabilize C=O
electron-withdrawing groups destabilize C=O 8

8. Substituent Effects on Hydration EquilibriaOH O +
H2O R C R C R R OH
R = CH3: K =
R = CF3: K = 22,000 9

9. Mechanism of Hydration (base)
Step 1:
• • O H •• – C •• O
• • •• HO C O
• • – + 10

10. Mechanism of Hydration (base)
Step 2: •• HO C O
• • –
• • O H •• ••
• • O H – •• HO C OH + 10

11. Mechanism of Hydration (acid)
Step 1:
• • H O + C •• O
• • +
• • H O C •• OH + + H 10

12. Mechanism of Hydration (acid)
Step 2:
• • H O
• • H O + •• + C OH C OH •• + •• 10

13. Mechanism of Hydration (acid)
Step 3: + H O •• H O •• + +
• • H O •• C OH
• • O H •• C OH 10

14. 17.7 Cyanohydrin Formation

15. Cyanohydrin Formation••
• • C O H C O N
• • •• +
HCN 18

16. Cyanohydrin Formation– N
• • ••
• • C O 18

17. Cyanohydrin Formation– O N C ••
• • 18

18. Cyanohydrin Formation+ O
• • – O N C ••
• • 18

19. Cyanohydrin Formation+ O
• • – O N C ••
• • H O
• • O N C ••
• • H 18

20. 2,4-Dichlorobenzaldehyde
Example Cl CH O Cl
CHCN OH
NaCN, water
then H2SO4
2,4-Dichlorobenzaldehyde
cyanohydrin (100%) 20

21. Example CH3CCH3 O CH3CCH3 OH CN NaCN, water then H2SO4 (77-78%)
Acetone cyanohydrin is used in the synthesis of methacrylonitrile (see problem 17.6). 21