1. Alcohols Biological Activity Nomenclature Preparation Reactions

2. Some Alcohols

3. Alcohols are Found in Many Natural Products

4. Paralytic Shellfish Poisoning

6. Ethanol: the Beverage

7. Methanol: Not a Beverage

8. Oxidation levels of oxygen- halogen- and nitrogen- containing molecules

10. Acidity of Alcohols Due to the electronegativity of the O atoms, alcohols are slightly acidic (pKa 16-18). The anion dervived by the deprotonation of an alcohol is the alkoxide. Alcohols also react with Na (or K) as water does to give the alkoxide (red-ox):

11. Withdrawing Groups Enhance Acidity alcoholpKa CH 3 OH15.54 CH 3 CH 2 OH16.00 CF 3 CH 2 OH12.43 (CH 3 ) 3 COH18.00 (CF 3 ) 3 COH 5.4

12. Phenols are more acidic than alcohols

13. Physical Properties CH 3 CH 2 CH 3 -42 0.08 i CH 3 OCH 3 -251.3 ss CH 3 CH 2 OH781.7 vs b.p. o C  Dsol. in H 2 O

14. Intermolecular H-Bonding

15. Alcohol Nomenclature

16. Nomenclature

17. Preparation of Alcohols Reduction of ketones and aldehydes Reduction of esters and carboxylic acids Hydration of Alkenes Nucleophilic addition –Grignard reaction –Acetylide addition Substitution Epoxide opening

18. NaBH 4 Reduction

19. Some Examples

20. Two Alcohol Products Form in Lab

21. LiAlH 4 Reduction a Stronger Reducing Agent

22. LiAlH 4 is a much stronger reducing agent

23. NaBH 4 is More Selective

24. Oxymercuration Hydration Markovnikov

25. Hydroboration Hydration Anti-Markovnikov

26. Base Catalyzed Ring-Opening of Epoxides

27. Acid Catalyzed Ring-Opening Aqueous and in Alcohol

28. Nucleophilic addition to Carbonyl Compounds Acetylides

29. Organometallic Chemistry Grignard Reaction

30. Grignard Reagents React With Ketones to form tertiary alcohols

31. Grignard Reagents React With Aldehydes to form secondary alcohols

32. Grignard Reagents React With Formaldehyde to form primary alcohols

33. Grignard Reagents react (twice) with Esters to form 3 o Alcohols

34. Grignard Summary

36. Grignard Reagents are exceptionally strong bases

37. Synthesis

38. Retrosynthetic Analysis

39. 4-Step Synthesis

40. Synthesize Using Only 1,2, or 3-Carbon Reagents

41. Retrosynthesis

42. Reactions of Alcohols Oxidation R-X, Ether, and Ester Preparation Protection of Alcohols Synthesis The Logic of Mechanisms

43. Alcohols are Synthetically Versatile

44. Oxidation - Reduction

45. Oxidation of 2 o Alcohols with Cr(VI)

46. Mechanism

47. Oxidation of 1 o Alcohols

48. PCC oxidizes 1 o Alcohols to Aldehydes

49. Oxidation of 1 o Alcohols to Aldehydes: PCC

50. Oxidation Summary

51. Reduction Summary

52. Conversion of Alcohol into a Leaving Group Form Tosylate (p-TsCl, pyridine) Use strong acid (H 3 O + ) Convert to Alkyl Halide (HX, SOCl 2, PBr 3 )

53. Formation of p-Toluenesulfonate Esters

54. Best to use p-TsCl with pyridine

55. Reactions of Tosylates: Reduction, Substitution, Elimination

56. Alcohols to Alkyl Halides

57. Lucas Test

58. Qualitative test for Alcohol Characterization

59. Other Simple Qualitative Tests

60. 1 o and 2 o Alcohols: best to use SOCl 2, PBr 3, or P/I 2

61. Thionyl chloride mechanism in Pyridine – S N 2, Inversion

62. Dehydration of Alcohols – E1

63. Propose a Mechanism

64. Both approaches seem logical

65. Take the Blue Route

66. Problem Set: Road Map Problem

67. Ethers

68. Dimerization of Alcohols: Symmetrical Ethers

69. Mechanism

70. Williamson Ether Synthesis Preparation of Unsymmetrical Ethers

71. Mechanism, S N 2

72. Alkoxides are strong bases so there is competition with E2 reactions. Bulky alkoxides reacting with primary alkyl halides favor Williamson ether synthesis(S N 2). How would you prepare the following ethers starting from an alcohol and an alkyl halide?

73. Alkene Oxides, Oxiranes or Epoxides

74. Epoxides are Extremely Reactive

75. Cleavage of Unsymmetrical Ethers

76. Size 1, Pairwork 8.28 b,d 8.29 a,d 8.33 e,f 8.44 a-e 8.45 8.47 8.51 8.57 8.61 8.64