1. Alcohols, phenols, and ethers

2. R = alkyl group (substituted or unsubstituted)
Structure
R-OH alcohol
R = alkyl group (substituted or unsubstituted)

3. Nomenclature of alcohols
Add the suffix ol to the name of longest, linear, carbon chain which includes the carbon bearing the OH and any double or triple C-C bond.
The OH group has a higher priority than a multiple C-C bond, a halogen, and an alkyl group in determining the carbon chain numbering.
5-phenyl-2-hexanol

4. Nomenclature of alcohols
CH3CH=CHCH2CH2OH
3-penten-1-ol
2-phenylethanol
trans-3-fluorocyclohexanol

5. Nomenclature of alcohols
2-hydroxypropanoic acid

6. Nomenclature of alcohols
3-hexanol?

7. Cahn - Prelog - Ingold rules
Step 1: assign a priority to the 4 atoms or groups of atoms bonded to the stereogenic carbon:
1. If the 4 atoms are all different, priority is determined by atomic number. The atom of higher atomic number has the higher priority.

8. Determination of priority
2. If priority cannot be determined by (1), it is determined by a similar comparison of atoms working out from the stereogenic carbon.
In the methyl group, the second atoms are H, H, H whereas in the ethyl group, they are C, H, H.
The priority sequence is therefore Cl, C2H5, CH3, H.

9. Cahn - Prelog - Ingold rules
3. A double or triple bond to an atom, A, is considered as equivalent to two or three single bonds to A:
The sequence is therefore -OH, -CHO, -CH2OH, -H.

10. Step 2
Arrange the molecule so that the group of lowest priority is pointing away from you and observe the arrangement of the remaining groups: R
If, on going from the group of highest priority to that of second priority and then to the group of third priority, we go in a clockwise direction, the enantiomer is designated (R).

11. Step 2
(S)
If the direction is counterclockwise, the enantiomer is designated (S).
Thus the complete name for one of the enantiomers of 2-chlorobutane is (S)-2-chlorobutane which is, by chance, the dextrorotatory enantiomer. There is no correlation between (+)/(-) and (R)/(S).

12. R or S?

13. Nomenclature of alcohols
3-bromo-3-chloro-2-methyl-2-propen-1-ol?

14. E-Z designations (Z)- 3-bromo-3-chloro-2-methyl-2-propen-1-ol
use the Cahn-Ingold-Prelog system to assign priorities to the two groups on each carbon of the double bond.
then compare the relative positions of the groups of higher priority on these two carbons.
if the two groups are on the same side, the compound has the Z configuration (zusammen, German, together).
if the two groups are on opposite sides, the compound has the E configuration (entgegen, German, across).

15. E-Z designations

16. Sterols - the steroid ring system

17. Physical properties of alcohols
Alcohols are noticeably less volatile; their melting points are greater and they are more water soluble than the corresponding hydrocarbons having similar molecular weights.
These differences are due to the OH group which renders a certain polarity to the molecule. The result is an important intermolecular attraction:

18. Solubility of alcohols
Low molecular weight alcohols are water soluble:

19. Spectroscopic properties
IR:
Unassociated alcohols show a fairly sharp absorption near 3600 cm-1 due to O-H stretching. Associated alcohols (hydrogen bonded) show a broad absorption in the cm-1 range.
1H NMR:
Absorption occurs in the range  = 3.5 to Coupling is not oberved due to rapid H - H exchange.

20. Fermentation Fermentation of sugar by yeast gives C2H5OH.
Methanol is added to denature it.

21. Azeotropic mixtures
The bp of ethanol is 78.3C whereas that of water is 100C (at least on Vancouver’s waterfront!). Can we separate a mixture by distillation?
No! An azeotropic mixture forms!
An azeotropic mixture is one whose liquid and vapor forms have identical compositions. The mixture cannot be separated by distillation.
eg C2H5OH (95%) and H2O (5%) - bp 78.13C
H2O (7.5%), C2H5OH (18.5%) and C6H6 (74%) - bp 64.9C

22. Oxymercuration

23. Oxymercuration An anti addition via a mercurinium ion: Dissociation:
Electrophilic attack:
Nucleophilic opening:

24. Oxymercuration Why do we observe Markovnikov addition?
In the mercurinium ion, the positive charge is shared between the more substituted carbon and the mercury atom.
Only a small portion of the charge resides on this carbon but it is sufficient to account for the orientation of the addition but is insufficient to allow a rearrangement to occur.

25. Hydroboration
H.C. Brown and G. Zweifel, J. Am. Chem. Soc., 83, 2544 (1961)

26. Hydroboration
syn
addition
no rearrangement
no carbocation!

27. Hydroboration - the mechanism

28. Hydroboration - the mechanism

29. Hydroboration - the mechanism

30. Reduction of carbonyls

31. Reduction of carbonyls+
LiAlH H H 4 O OH H
/Ni 2 CH CH CH CH OH CH
CH=CHCHO 3 2 2 2 3
CH=CHCHO +
NaBH H 4
cinnamaldehyde

32. Reduction of carbonyls
hydride transfer

33. Reduction of acids
1o alcohol

34. Reduction of esters

35. Reactivity of the carbonyl group

36. Nucleophilic addition

37. Preparation of alcohols - Grignard synthesis

38. Grignard synthesis primary alcohol formaldehyde aldehyde
secondary alcohol

39. Grignard synthesis ketone tertiary alcohol primary alcohol
ethylene oxide

40. Planning a Grignard synthesis

41. Limitations CH4 + Mg(OH)I
Any hydrogen bonded to an electronegative element (including an acetylenic hydrogen) is sufficiently acidic to react with a Grignard reagent.
CH4 + Mg(OH)I
CH3MgI + H2O
Grignard reagents react with O2, CO2 and with almost all organic compounds which contain multiply bonded C-O or C-N units.

42. Reactions of alcohols
The reactions of alcohols involve one of two processes:
breaking of the O-H bond
breaking of the C-O bond

43. Reactions involving O-H bond breaking
R-OH + M
RO- + M /2 H2

44. Phenols
Ka ~ 10-10

45. Acidity of phenols

46. Acidity

47. Substituent effects + H+
An electron attracting substituent stabilizes the conjugate base. The equilibrium is shifted to the right.

48. Substituent effects + H+
Electron donating substituents reduce the acidity of phenols.

49. Substituent effects

50. Reaction with hydrogen halides

51. Experimental facts 1. The reaction is acid catalyzed
2. Rearrangements are possible
3. Alcohol reactivity is 3o > 2o > 1o < CH3OH

52. The mechanism

53. Reaction of primary alcohols with HX
SN2
This reflects nucleophile strength in a protic solvent.

54. Reactions with phosphorus halides and with thionyl chloride
ROH + PX3
RX + H3PO3
Creates a good leaving group from 1o and 2o alcohols.

55. Tosylates

56. Why form tosylates?
Sulfonate ions are excellent leaving groups:

57. Dehydration

58. Dehydration
E1 mechanism

59. Oxidation of primary alcohols
C5H5NHCrO3Cl - pyridinium chlorochromate in CH2Cl2 - PCC

60. Oxidation of secondary alcohols
3-cholestanol
3-cholestanone

61. Synthesis of alcohols

62. Synthesis of alcohols

63. Alcohols in synthesis
Problems: carbocations form and rearrangements can occur in the E1 reaction
Problems: carbocations form and rearrangements can occur in the SN1 reaction. HX
alcohol
alkyl halide
SN2 reaction - no rearrangements
E2 reaction - no rearrangements

64. Synthesis of 3-methyl-1-butene

65. Synthesis of 3-methyl-1-butene

66. Synthesis of 3-methyl-1-butene
SN2 E2

67. Ethers Structure: R-O-R, Ar-O-R, or Ar-O-Ar nomenclature
Name the two groups bonded to the oxygen and add the word ether.
CH3CH2OCH2CH3 - diethyl ether

68. Nomenclature of ethers
diphenyl ether
CH3OCH=CH2
methyl vinyl ether
isopropyl phenyl ether
3-methoxyhexane
CH3CH2CH2CHCH2CH3 |
OCH3

69. Nomenclature of cyclic ethers
Use the prefix oxa- to indicate that an O replaces a CH2 in the ring.
oxacyclopropane
ethylene oxide
oxacyclopentane
tetrahydrofuran
1,4-dioxacyclohexane
1,4-dioxane

70. Williamson synthesis
A primary halide is necessary to ensure an SN2 reaction and not an E2 elimination.

71. Reaction of ethers
What is the mechanism?

72. Epoxides
syn addition

73. Mechanism

74. Reactions
What is the mechanism?

76. Problems
Solomons and Fryhle, 11.26, 11.27, 11.30, 11.33, 11.36, 11.46, 12.11, 12.12, 12.14, 12.16, 12.17, and 12.20