17.5 Reactions of Aldehydes and Ketones: A Review and a Preview
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
17.6 Principles of Nucleophilic Addition to Carbonyl Groups: Hydration of Aldehydes and Ketones 4
Hydration of Aldehydes and Ketones C •• O • • H2O HO C O H •• 5
Substituent Effects on Hydration Equilibria OH R R' + H2O C O compared to H electronic: alkyl groups stabilize reactants steric: alkyl groups crowd product 6
Equilibrium Constants for Hydration C=O hydrate K % CH2=O CH2(OH)2 41 99.96 CH3CH=O CH3CH(OH)2 0.018 50 (CH3)3CCH=O (CH3)3CCH(OH)2 0.0041 19 (CH3)2C=O (CH3)2C(OH)2 0.000025 0.14 7
When does equilibrium favor hydrate? when carbonyl group is destabilized alkyl groups stabilize C=O electron-withdrawing groups destabilize C=O 8
Substituent Effects on Hydration Equilibria OH O + H2O R C R C R R OH R = CH3: K = 0.000025 R = CF3: K = 22,000 9
Mechanism of Hydration (base) Step 1: • • O H •• – C •• O • • •• HO C O • • – + 10
Mechanism of Hydration (base) Step 2: •• HO C O • • – • • O H •• •• • • O H – •• HO C OH + 10
Mechanism of Hydration (acid) Step 1: • • H O + C •• O • • + • • H O C •• OH + + H 10
Mechanism of Hydration (acid) Step 2: • • H O • • H O + •• + C OH C OH •• + •• 10
Mechanism of Hydration (acid) Step 3: + H O •• H O •• + + • • H O •• C OH • • O H •• C OH 10
17.7 Cyanohydrin Formation
Cyanohydrin Formation •• • • C O H C O N • • •• + HCN 18
Cyanohydrin Formation – N • • •• • • C O 18
Cyanohydrin Formation – O N C •• • • 18
Cyanohydrin Formation + O • • – O N C •• • • 18
Cyanohydrin Formation + O • • – O N C •• • • H O • • O N C •• • • H 18
2,4-Dichlorobenzaldehyde Example Cl CH O Cl CHCN OH NaCN, water then H2SO4 2,4-Dichlorobenzaldehyde cyanohydrin (100%) 20
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