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

1. 17.5Reactions 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

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

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

5. OH O + C H2O R R' C R' R OH Substituent Effects on Hydration Equilibria 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. O Substituent Effects on Hydration Equilibria R = CH3: K = 0.000025 R = CF3: K = 22,000 OH + C H2O R R C R R OH

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

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

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

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

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

14. 17.7Cyanohydrin Formation

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

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

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

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

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

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

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