1. Biological Activity Nomenclature Preparation Reactions
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
alcohol pKa
CH3OH
CH3CH2OH
CF3CH2OH
(CH3)3COH
(CF3)3COH

12. Physical Properties b.p. oC m D sol. in H2O CH3CH2CH3 -42 0.08 i
CH3OCH ss
CH3CH2OH vs

13. Intermolecular H-Bonding

14. Alcohol Nomenclature

15. Nomenclature

16. 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

17. NaBH4 Reduction

18. Some Examples

19. Two Alcohol Products Form in Lab

20. LiAlH4 Reduction a Stronger Reducing Agent

21. LiAlH4 is a much stronger reducing agent

22. NaBH4 is More Selective

23. Oxymercuration Hydration Markovnikov

24. Hydroboration Hydration Anti-Markovnikov

25. Base Catalyzed Ring-Opening of Epoxides

26. Acid Catalyzed Ring-Opening Aqueous and in Alcohol

27. Regiochemistry Ring Opens at More Hindered Site

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 3o Alcohols

34. Grignard Reagents open Epoxides

35. Ring-Opening is Sterically Controlled

36. Grignard Summary

37. Grignard Summary

38. Grignard Reagents are exceptionally strong bases

39. Synthesis

40. Retrosynthetic Analysis

41. 4-Step Synthesis

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

43. Retrosynthesis

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

45. Alcohols are Synthetically Versatile

46. Oxidation - Reduction

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

48. Mechanism

49. Oxidation of 1o Alcohols

50. PCC oxidizes 1o Alcohols to Aldehydes

51. Oxidation of 1o Alcohols to Aldehydes: PCC

52. Oxidation Summary

53. Reduction Summary

54. Conversion of Alcohol into a Leaving Group
Form Tosylate (p-TsCl, pyridine)
Use strong acid (H3O+)
Convert to Alkyl Halide (HX, SOCl2, PBr3)

55. Formation of p-Toluenesulfonate Esters

56. Best to use p-TsCl with pyridine

57. Reactions of Tosylates: Reduction, Substitution, Elimination

58. Alcohols to Alkyl Halides

59. SN1: Carbocations can Rearrange

61. Lucas Test

62. Qualitative test for Alcohol Characterization

63. Other Simple Qualitative Tests

64. 1o and 2o Alcohols: best to use SOCl2, PBr3, or P/I2

65. Thionyl chloride mechanism in Pyridine – SN2, Inversion

66. Dehydration of Alcohols – E1

67. Methide Shift is Faster than Loss of H+

69. Provide a sequence of steps

70. 2 Approaches

71. Alternate Approach

72. Propose a Mechanism

73. Both approaches seem logical

74. Take the Blue Route

75. Problem Set: Road Map Problem