Organic Chemistry 6 th Edition Paula Yurkanis Bruice

1. Chapter 18 Carbonyl Compounds II Reactions of Aldehydes and Ketones More Reactions of Carboxylic Acid Derivatives Reactions of a,b-Unsaturated Carbonyl Compounds Organic Chemistry 6th Edition Paula Yurkanis Bruice

2. Ch. 18 Overview • Reactions of Class II Carbonyl Compounds • Nomenclature of Ketones and Aldehydes • Grignard Reactions • Reductions with NaBH4, LiAlH4 and DIBALH • Addition of Cyanide • Formation of Imines and Enamines • Reductive Amination • Acetal Formation • Protecting Groups • Wittig Reaction • Synthesis

3. Nomenclature of Aldehydes

4. If the aldehyde group is attached to a ring,

5. If a compound has two functional groups, the one with the lower priority is indicated by its prefix:

6. Nomenclature of Ketones The carbonyl is assumed to be at the 1-position in cyclic ketones:

7. If a ketone has a second functional group of higher priority… A few ketones have common names:

8. The partial positive charge on the carbonyl carbon causes that carbon to be attacked by nucleophiles: An aldehyde has a greater partial positive charge on its carbonyl carbon than does a ketone:

9. Aldehydes Are More Reactive Than Ketones • Steric factors contribute to the reactivity of an aldehyde. • The carbonyl carbon of an aldehyde is more accessible • to the nucleophile. • Ketones have greater steric crowding in their transition • states, so they have less stable transition states.

10. The reactivity of carbonyl compounds is also related to the basicity of Y–:

11. Carboxylic acid derivatives undergo nucleophilic acyl substitution reactions with nucleophiles:

12. Aldehydes and ketones undergo nucleophilic addition reactions with nucleophiles: This is an irreversible nucleophilic addition reaction if the nucleophile is a strong base

13. A reversible nucleophilic addition reaction:

14. Formation of a New Carbon–Carbon Bond Using Grignard Reagents Grignard reagents react with aldehydes, ketones, and carboxylic acid derivatives

15. Grignard reagents are used to prepare alcohols:

16. Mechanism for the reaction of an ester with a Grignard reagent:

17. Examples of Grignard Reactions

18. + + NH3 Na Reaction of Acetylide Ions with Carbonyl Compounds

19. Reactions of Carbonyl Compounds with Hydride Ion

21. Mechanism for the reaction of an acyl chloride with hydride ion:

22. Mechanism for the reaction of an ester with hydride ion: Esters and acyl chlorides undergo two successive reactions with hydride ion and Grignard reagents

23. Utilization of DIBALH to Control the Reduction Reaction

24. The reduction of a carboxylic acid with LiAlH4 forms a single primary alcohol: Acyl chloride is also reduced by LiAlH4 to yield an alcohol

25. An amide is reduced by LiAlH4 to an amine Mechanism for the reaction of an N-substituted amide with hydride ion:

26. Hydride Reducing Agents

27. Selectivity of Reductions

28. Hydrogen cyanide adds to aldehydes and ketones to form cyanohydrins:

29. Compared with Grignard reagents and hydride ion, CN– is a relatively weak base; therefore, in basic solution…

30. Aldehydes and ketones react with a primary amine to form an imine: This is a pH-dependent nucleophilic addition–elimination reaction

31. Dependence of the rate of the reaction of acetone with hydroxylamine on the pH of the reaction: a pH-rate profile Maximum rate is at pH = pKa of +NH3OH; at this pH, both [H+] and [NH2OH] have the highest values Decreasing rate: [H+] is decreasing Decreasing rate: [NH2OH] is decreasing Composition of the rate- determining step:

32. Aldehydes and ketones react with secondary amines to form enamines: An enamine undergoes an acid-catalyzed hydrolysis to form a carbonyl compound and a secondary amine

33. Enamine Reactions

34. Formation of Imine Derivatives

35. Types of Amine–Carbonyl Addition Products

36. Reductive Amination

37. Deoxygenation of the Carbonyl Group Called the Wolff–Kishner reduction

38. Water adds to an aldehyde or ketone to form a hydrate:

39. Mechanism for acid-catalyzed hydrate formation:

40. Why is there such a difference in the Keq values?

41. The equilibrium constant for the reaction depends on the relative stabilities of the reactants and products:

42. Addition of an Alcohol to an Aldehyde or a Ketone

43. Mechanism for acid-catalyzed acetal or ketal formation:

44. Utilization of Protecting Groups in Synthesis LiAlH4 will reduce the ester to yield an alcohol, but the keto group will also be reduced

45. The keto group is protected as a ketal in this synthesis: The more reactive aldehyde is protected with the diol before reaction with the Grignard reagent:

46. An OH group can be protected as a trimethylsilyl (TMS) ether:

47. Protection of an OH group in a carboxylic acid as the ester:

48. Protection of an amino group as the amide:

49. Addition of Sulfur Nucleophiles

50. Desulfurization replaces the C—S bonds with C—H bonds: