1. Created by Professor William Tam & Dr. Phillis Chang Ch. 18 - 1 Chapter 18 Reactions at the  Carbon of Carbonyl Compounds Enols and Enolates

2.  What is a keto form ? A structure that contains a carbonyl. E.g. aldehyde, ketone, ester, acid, etc.  What is an enol ? A compound that has an alkene and an OH attached to the same carbon atom.  What is an enolate ?  An enol with the proton removed. May be formed by removing a proton from the  carbon atom of a keto form. Keto, enol and enolate structures:

3.   What is an  carbon ? A carbon atom adjacent to a carbonyl.   What is an  hydrogen ?  A hydrogen attached to an  carbon atom.  The  carbon and  hydrogens:   Hydrogens are weakly acidic (pK a = 19 – 20) due to the e-withdrawing C=O.

4. Ch. 18 - 4 Reactions at the  Carbon of Carbonyl Compounds: Enols and Enolates This shows a reaction at the carbonyl carbon atom. Tetrahedral intermediate

5. Ch. 18 - 5 1.The Acidity of the  Hydrogens of Carbonyl Compounds: Enolate Anions Comparison of pKas.

6. Ch. 18 - 6 Resonance structures for the delocalized enolates  Removal of  H forms a resonance stabilized enolate. Deprotonation:

7. Ch. 18 - 7 Protonation of oxygen.  Protonation of  carbon. Protonation:

8. Ch. 18 - 8 2.Keto and Enol Tautomers  Interconvertible keto and enol forms are called tautomers, and their interconversion is called tautomerization.  The keto and enol forms are in equilibrium (not resonance structures) because a proton transfer occurs.

9. Ch. 18 - 9 E.g.

10. Ch. 18 - 10 Resonance stabilization of the enol form E.g.

11. Ch. 18 - 11 3.Reactions via Enols & Enolates 3A. Racemization Racemization at an  carbon takes place in the presence of acids or bases

12. Ch. 18 - 12  Base-Catalyzed Enolization:

13. Ch. 18 - 13  Acid-Catalyzed Enolization:

14. Ch. 18 - 14 3B.Halogenation at the  Carbon

15. Ch. 18 - 15  Base-Promoted Halogenation:

16. Ch. 18 - 16  Acid-Promoted Halogenation:

17. Ch. 18 - 17 3C. The Haloform Reaction

18. Ch. 18 - 18  The Iodoform reaction:

19. Ch. 18 - 19  Mechanism:

20. Ch. 18 - 20 ●Acyl Substitution Step:

21. Ch. 18 - 21 3D.  -Halo Carboxylic Acids: The Hell – Volhard – Zelinski Reaction

22. Ch. 18 - 22  Example:

23. Ch. 18 - 23  Mechanism:

24. Ch. 18 - 24  Further reaction of an  halo acid:

25. Ch. 18 - 25 4.Lithium Enolates

26. Ch. 18 - 26  Prep. of lithium diisopropylamide: (LDA)

27. Ch. 18 - 27 4A.Regioselective Formation of Enolates  Formation of a Kinetic Enolate: This enolate is formed faster because the hindered strong base removes the less hindered proton faster. (Dimethoxyethane)

28. Ch. 18 - 28  Formation of a Thermodynamic Enolate: This enolate is more stable because the double bond is more highly substituted. It is the predominant enolate at equilibrium.

29. Ch. 18 - 29 4B.Direct Alkylation of Ketones via Lithium Enolates Lithium diisopropylamide = LDA or LiN(iPr) 2.

30. Ch. 18 - 30 4C.Direct Alkylation of Esters

31. Ch. 18 - 31  Examples:

32. Ch. 18 - 32 5.Enolates of  -Dicarbonyl Compounds

33. Ch. 18 - 33  Recall:   -hydrogens of  -dicarbonyl compounds are more acidic:

34. Ch. 18 - 34 Contributing resonance structures Resonance hybrid

35. Ch. 18 - 35 6.Synthesis of Methyl Ketones: The Acetoacetic Ester Synthesis

36. Ch. 18 - 36  Synthesis of monosubstituted methyl ketones:

37. Ch. 18 - 37  Synthesis of disubstituted methyl ketones:

38. Ch. 18 - 38

39. Ch. 18 - 39  Synthesis of  -keto acids and  -diketones:

40. Ch. 18 - 40 6A.Acylation  Synthesis  -diketones:

41. Ch. 18 - 41 7.Synthesis of Substituted Acetic Acids: The Malonic Ester Synthesis

42. Ch. 18 - 42  Synthesis of substituted acetic acid:

43. Ch. 18 - 43  Synthesis of monoalkylacetic acid:

44. Ch. 18 - 44  Synthesis of dialkylacetic acid:

45. Ch. 18 - 45  Example 1:

46. Ch. 18 - 46  Example 2:

47. Ch. 18 - 47 8.Further Reactions of Active Hydrogen Compounds

48. Ch. 18 - 48  Example:

49. Ch. 18 - 49 9.Synthesis of Enamines: Stork Enamine Reactions

50. Ch. 18 - 50  2° amines most commonly used to prepare enamines: ●e.g.

51. Ch. 18 - 51 (a) (b)

52. Ch. 18 - 52  Synthesis of  -diketones:

53. Ch. 18 - 53  Synthesis of  -keto esters:

54. Ch. 18 - 54  Enamines can also be used in Michael additions:

55. Ch. 18 - 55 10. Summary of Enolate Chemistry 1.Formation of an Enolate: Resonance- stabilized enolate

56. Ch. 18 - 56 2.Racemization: Enantiomers

57. Ch. 18 - 57 3.Halogenation of Aldehydes & Ketones:  Specific example: haloform reaction:

58. Ch. 18 - 58 4.Halogenation of Carboxylic Acids: The HVZ Reaction:

59. Ch. 18 - 59 5.Direct Alkylation via Lithium Enolates:  Specific example:

60. Ch. 18 - 60 6.Direct Alkylation of Esters:

61. Ch. 18 - 61 7.Acetoacetic Ester Synthesis:

62. Ch. 18 - 62 8.Malonic Ester Synthesis:

63. Ch. 18 - 63 9.Stork Enamine Reaction:

64. Ch. 18 - 64  END OF CHAPTER 18 