Organic Chemistry 6 th Edition Paula Yurkanis Bruice

1. Organic Chemistry 6th Edition Paula Yurkanis Bruice Chapter 19 Carbonyl Compounds III Reactions at the a-Carbon

2. The a-Hydrogen Is Acidic The anion is stabilized by resonance A carbon acid is a compound with a relatively acidic hydrogen bonded to an sp3-hybridized carbon

4. Esters Are Less Acidic Than Aldehydes and Ketones The electrons are not as readily delocalized because of resonance electron release by -OR (green arrows)

5. In the following compounds, the anion resulting from deprotonation can be delocalized into electronegative atoms (oxygen and nitrogen):

6. The acidity of the a-hydrogens is attributed to anion stabilization by resonance:

7. Keto–Enol Tautomerism

8. The enol tautomer can be stabilized by intramolecular hydrogen bonding: In phenol, the enol tautomer predominates because it is aromatic:

9. Mechanism for base-catalyzed keto–enol interconversion:

10. Mechanism for acid-catalyzed keto–enol interconversion:

11. An Enol Is a Better Nucleophile Than an Alkene Carbonyl compounds that form enol undergo substitution reactions at the a-carbon: an a-substitution reaction

12. Mechanism for base-catalyzed a-substitution:

13. Mechanism for acid-catalyzed a-substitution:

14. An Enolate Is an Ambident Nucleophile Reaction at the C or O site depends on the electrophile and on the reaction condition Protonation occurs preferentially on the O site Otherwise, the C site is likely the nucleophile

15. Acid-Catalyzed Halogenation Under acidic conditions, one a-hydrogen is substituted for a halogen

16. Mechanism for acid-catalyzed halogenation:

17. Base-Promoted Halogenation Under basic conditions, all the a-hydrogens are substituted for halogens

18. Mechanism for base-promoted halogenation:

19. Conversion of a Methyl Ketone to a Carboxylic Acid

20. a-Halogenated Carbonyl Compounds Are Useful in Synthesis Removing a proton from an a-carbon makes the a- carbon a nucleophile:

21. When the a-carbon is halogenated, it becomes electrophilic: An E2 elimination will occur if a bulky base is used:

22. LDA is a strong base but a poor nucleophile Why? Because the steric bulk of the isopropyl groups prevents an SN2 reaction

23. Using LDA to Form an Enolate

24. Keto–Enol Tautomerization

25. Alkylation of the a-Carbon of Carbonyl Compounds This method can be used to alkylate ketones, esters, and nitriles at the a-carbon; however, aldehydes give a poor yield

26. Enol and Enolate Reactions: Halogenation and Alkylation

27. Two different products can be formed if the ketone is not symmetrical:

28. The less substituted a-carbon can be alkylated if the hydrazone is used:

29. Alkylation and Acylation of the a-Carbon Using an Enamine Intermediate

30. The alkylation step is an SN2 reaction:

31. Direct alkylation of a carbonyl compound yields several products: In contrast, alkylation of an aldehyde or a ketone using an enamine intermediate yields the monoalkylated product

32. Aldehydes and ketones can be acylated via an enamine intermediate:

33. The a-carbon of an aldehyde or a ketone can be made to react with an electrophile: The a-carbon of an aldehyde or a ketone can also be made to react with a nucleophile:

34. The Michael Addition

35. Michael reactions form 1,5-dicarbonyl compounds:

36. Mechanism for the Michael Addition Reaction

37. The Stork Enamine Reaction Enamines are used in place of enolates in these Michael addition reactions:

38. Aldol Addition Reaction

39. One molecule of a carbonyl compound acts as a nucleophile, and the other carbonyl compound acts as an electrophile:

40. Ketones are less susceptible than aldehydes to attack by nucleophiles for steric reasons:

41. An aldol addition product loses water to form an aldol condensation product:

42. Conjugation stabilizes the dehydrated product:

43. The Mixed Aldol Addition

44. One product will be formed if one of the carbonyl compounds does not have any a-hydrogen:

45. Primarily one product can be formed by using LDA to deprotonate one of the carbonyl compounds:

46. Condensation of Two Ester Molecules: The Claisen Condensation

49. Anion formation results in an irreversible reaction The reaction can be driven to completion by removing a proton from the b-keto ester: The Claisen condensation requires an ester with two a-hydrogens and an equivalent amount of base

50. The Crossed Claisen Condensation The excess reactant has no  protons