Organic

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

2. 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
Table 17.2 Reactions of Aldehydes and Ketones

3. 17.6
Principles of Nucleophilic Addition:
Hydration of Aldehydes and
Ketones

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

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

6. C=O hydrate K % Relative
rate
CH2=O CH2(OH)2 2300 >99.9 2200
CH3CH=O CH3CH(OH)2 1.0 50 1.0
(CH3)3CCH=O (CH3)3CCH(OH)2 0.2 17 0.09
(CH3)2C=O (CH3)2C(OH)2 0.0014 0.14 0.0018
Table 17.3 Equilibrium Constants and Relative Rates
of Hydration

7. When carbonyl group is destabilized
• alkyl groups stabilize C=O
• electron-withdrawing groups destabilize C=O
When Does Equilibrium Favor Hydrate?

8. OH
OH
R R
+ H2O C
C
R R
O
Substituent Effects on Hydration Equilibria
R = CH3: K = 0.0014
R = CF3: K = 22,000

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

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

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

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

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

14. 17.7
Cyanohydrin Formation

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

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

17. Cyanohydrin Formation
–
O
N C C
••
••
•
•
•
•
H
H
H
+
O•
•
H
H
O•
•
•
•
O
N C C
••
••
•
• H

18. 2,4-Dichlorobenzaldehyde
cyanohydrin (100%)
Example
Cl
Cl CH
O
Cl
Cl CHCN
OH
NaCN, water
then H2SO4

19. Example
CH3CCH3
O
NaCN, water
then H2SO4
CH3CCH3
OH
CN
(77-78%)
Acetone cyanohydrin is used in the synthesis
of methacrylonitrile (see problem 17.7).