1. Structure and Synthesis of Alcohols
Biological Activity
Nomenclature
Preparation
Reactions

2. Structure of Water and Methanol
File Name: AAAKWXK0
Oxygen is sp3 hybridized and tetrahedral.
The H—O—H angle in water is 104.5°.
The C—O—H angle in methyl alcohol is 108.9°.

3. Examples of ClassificationsH 3 2 O * C H 3 O 2 *
Primary alcohol
Secondary alcohol C H 3 O *
Tertiary alcohol
Phenol

5. Some Alcohols

6. Alcohols are Found in Many Natural Products

7. Paralytic Shellfish Poisoning

9. Ethanol: the Beverage

10. Enzymatic Oxidation of Ethanol
Ethanol oxidizes to acetaldehyde, then acetic acid, which is a normal metabolite.

11. Excess NADH can cause Metabolic Problems

12. Methanol: Not a Beverage

13. Synergistic and Metabolic Effects
In men, ethanol lowers levels of testosterone (and sperm count) due to lack of enzymes needed for the steroid biosynthesis.
The enzyme CYP2E1, which is responsible for converting acetaminophen into liver toxins, is activated by ethanol.
Ethanol has a caloric value of 7.1Cal/g (fat has a value of 9 Cal/g).
Alcohol can cause a degenerative muscle disease called alcoholic myopathy (3 times more common than cirrhosis).

14. Synergistic Effects
Women will have higher BAL’s with the consumption of an equal number of drinks due to lower ADH activity and lower % H2O in blood.
Estradiol levels increase in women (and men). This has been associated with higher incidences of heart disease and a change in bone density.
A higher than normal concentration of Cytochrome P-450 enzymes (in the liver) are activated by ethanol creating a potential dependency.

15. Antitumor Agents Often functionalized with alcohols
Designed to fit into specific geometic sites on proteins
Hydrogen bonding is crucial for binding
Water solubility is crucial for cell membrane transport

16. From the Bark of the Pacific Yew Tree Taxol (Paclitaxel)

17. How Taxol Works
A large number of microtubules are formed at the start of cell division, and as cell division comes to an end, these microtubules are normally broken down into tubulin – a protein responsible for the cell’s structural stability.
Taxol promotes tubulin polymerization then binds to the microtubules and inhibits their depolymerization back into tubulin.
The cell can't divide into daughter cells and therefore the cancer can’t spread.

18. May be More Effective than Taxol

19. DNA Cross-linker

20. Prevents DNA from Unraveling

21. IUPAC Nomenclature
Find the longest carbon chain containing the carbon with the —OH group.
Drop the -e from the alkane name; add -ol.
Number the chain, giving the —OH group the lowest number possible.
Number and name all substituents and write them in alphabetical order.

22. Alcohol Nomenclature

23. Nomenclature

24. Naming Diols Two numbers are needed to locate the two —OH groups.
Use -diol as suffix instead of -ol.
hexane-1,6-diol

25. Who am I?

27. Boiling Points of Alcohols
Alcohols have higher boiling points than ethers and alkanes because alcohols can form hydrogen bonds.
The stronger interaction between alcohol molecules will require more energy to break, resulting in a higher boiling point.
File Name: AAAKWYJ0

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

29. 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):

30. Formation of Alkoxide Ions
Ethanol reacts with sodium metal to form sodium ethoxide (NaOCH2CH3), a strong base commonly used for elimination reactions.
More hindered alcohols like 2-propanol or tert-butanol react faster with potassium than with sodium.
File Name: AAAKWYQ0

31. Withdrawing Groups Enhance Acidity
alcohol pKa
CH3OH
CH3CH2OH
CF3CH2OH
(CH3)3COH
(CF3)3COH

32. Formation of Phenoxide Ion
File Name: AAAKWYU0
The aromatic alcohol phenol is more acidic than aliphatic alcohols due to the ability of aromatic rings to delocalize the negative charge of the oxygen within the carbons of the ring.

33. Charge Delocalization on the Phenoxide Ion
File Name: AAAKWYT0
The negative charge of the oxygen can be delocalized over four atoms of the phenoxide ion.
The true structure is a hybrid between the four resonance forms.

34. Intermolecular H-Bonding

35. 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

36. Oxymercuration Hydration Markovnikov

37. Hydroboration Hydration Anti-Markovnikov

38. Oxidation and Reduction 3 hydrocarbon oxidation levels

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

40. Grignard Reagents Formula R—Mg—X (reacts like R:– +MgX).
Ethers are used as solvents to stabilize the complex.
Iodides are most reactive. Fluorides generally do not react.
May be formed from primary, secondary, or tertiary alkyl halides.
File Name: AAAKWZG0

41. Organometallic Chemistry Grignard Reaction

42. Formation of Grignard Reagents

43. Grignard Reagents React With Aldehydes to form secondary alcohols

44. Grignard Reagents React With Ketones to form tertiary alcohols

45. Grignard Reagents React With Formaldehyde to form primary alcohols

46. Grignard Reagents open Epoxides

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

48. Reaction of Grignards with Carboxylic Acid Derivatives
File Name: AAAKXAC0

49. Grignard Summary

50. Grignard Summary

51. Solved Problem 2 Solution
Show how you would synthesize the following alcohol from compounds containing no more than five carbon atoms.
Solution
This is a tertiary alcohol; any one of the three alkyl groups might be added in the form of a Grignard reagent. We can propose three combinations of Grignard reagents with ketones:
Copyright © 2006 Pearson Prentice Hall, Inc.

52. Solved Problem 2 (Continued)
Solution (Continued)
Any of these three syntheses would probably work, but only the third begins with fragments containing no more than five carbon atoms. The other two syntheses would require further steps to generate the ketones from compounds containing no more than five carbon atoms.
Copyright © 2006 Pearson Prentice Hall, Inc.

53. Grignard Reagents are exceptionally strong bases

54. An Effective Use of the Basicity Isotopic Labeling

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

56. NaBH4 Reduction

57. Some Examples

58. Two Alcohol Products Form in Lab

59. LiAlH4 Reduction a Stronger Reducing Agent

60. LiAlH4 is a much stronger reducing agent

61. NaBH4 is More Selective

62. Reducing Agents
NaBH4 can reduce aldehydes and ketones but not esters and carboxylic acids.
LiAlH4 is a stronger reducing agent and will reduce all carbonyls.

63. Synthesis

64. Retrosynthetic Analysis

65. 4-Step Synthesis

66. Gilman Reagent Lithium dialkylcuprate

67. Gilman reagents: Source of Nucleophilic R- Coupling Reaction

68. Try these

69. Coupling occurs between original alkyl halide carbons

70. Think of it as an SN2 rxn

71. Base Catalyzed Ring-Opening of Epoxides

72. Base Opens Ring from Unhindered Side

73. Acid Catalyzed Ring-Opening Aqueous and in Alcohol

74. Regiochemistry Ring Opens at More Hindered Site

75. Different Regiosomers

76. Propose a Mechanism

77. 2 SN2 steps

78. Propose a Mechanism

80. Ring-Opening is Sterically Controlled

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

82. Retrosynthesis