1. Chapter 7 Alcohols, Ethers, and Epoxides
(醇、醚、环氧化物)
Text 1: Chapter 10, 11, 14

2. I. Alcohol (醇) The origins of alcohols
Ethyl alcohol (ethanol): grain alcohol（酒精）
Methyl alcohol (methanol): wood alcohol（木醇）
Role of alcohols
Reagents
Solvents
Synthetic intermediates (合成中间体)

3. 1. Structure of alcohols sp3 sp2 sp3 sp3 ethanol 乙醇 methanol 甲醇 Phenol苯酚
sp2
tautomerism
互变异构
Enol (烯醇)
Aldehyde (醛)

4. 2. Classification of alcohols
According to the type of carbinol carbon atom alcohols can be classified as follows:
primary alcohol
(伯醇) 1°
secondary alcohol
(仲醇) 2°
tertiary alcohol
(叔醇) 3°

5. 3. Nomenclature of Alcohols
IUPAC names:
alkane
alkanol
alkyl alcohol
Common names:
中文:
XX醇
ethanol
(ethyl alcohol) 乙醇
2-propanol
propan-2-ol
(isopropyl alcohol)
2-丙醇; 异丙醇
methanol
(methyl alcohol) 甲醇

6. 1-butanol
butan-1-ol
(n-butyl alcohol)
1-丁醇; (正丁醇)
2-butanol
butan-2-ol
(sec-butyl alcohol)
2-丁醇; (仲丁醇)
2-methyl-1-propanol
2-methylpropan-1-ol
iso-butyl alcohol
2-甲基-1-丙醇; (异丁醇)
2-methyl-2-propanol
2-methylpropan-2-ol
t-butyl alcohol
2-甲基-2-丙醇; (叔丁醇)

7. The order of precedence of functional groups for assigning IUPAC names
Acids
Esters
Aldehydes
Ketones
Alcohols
Amines
Alkenes
Alkynes
Alkanes
Ethers
Halides
Decreasing priority
4-penten-2-ol
pent-4-en-2-ol
4-戊烯-2-醇
2-hydroxy-3,3-dimethylbutanal
2-羟基-3,3-二甲基丁醛

8. phenylmethanol
(benzyl alcohol)
苯甲醇
苄(基)醇
2-propenol
(allyl alcohol)
2-丙烯醇
烯丙醇
2-propynol
2-丙炔醇
炔丙醇
cyclohexanol
环已醇
trans- 2-bromocyclohexanol
(1R,2R)-2-bromocyclohexanol

9. Names of diols
ethane-1,2-diol
(ethylene glycol)
乙二醇
butane-2,3-diol
2,3-丁二醇
glycol (甘醇)= 1,2-diol = vicinal diol, 邻位二醇

10. Names of phenols
2-bromophenol
(ortho-bromophenol)
2-溴苯酚
邻溴苯酚
3-bromophenol
(meta-bromophenol)
3-溴苯酚
间溴苯酚
4-bromophenol
(para-bromophenol)
4-溴苯酚
对溴苯酚
o-, m-, p-
邻, 间, 对

11. 4. Physical properties of alcohols
hydrophobic region
疏水区
hydrophilic region
亲水区
Boiling points: Alcohols have much higher boiling points than ethers or hydrocarbons having similar molecular weight.
Solubility: C1-3, miscible with water.

12. Problem 10-34
Predict which member of each pair has the higher bp, and explain the reasons for your predictions.
1-hexanol or 3,3-dimethyl-1-butanol
2-hexanone or 2-hexanol
2-hexanol or 1,5-hexanediol
2-pentanol of 2-hexanol

13. Methanol is highly toxic,it can cause blindness or death.
Important alcohols
Methanol
Methanol is highly toxic,it can cause blindness or death.
Ethanol

14. (A) Hydration of alkenes
5. Synthesis of alcohols
1) Synthesis of alcohol from alkyl halide
SN2 reaction
2) Synthesis of alcohols from alkenes
(A) Hydration of alkenes
C+ intermediate

15. (B) oxymercuration-Demercuration(羟汞化－脱汞)
anti addtion
follow Mar’s rule

16. (C) Hydroboration-oxidation (硼氢化-氧化反应)
syn addition
anti Mar’s product

17. Problem: (10-37)
Show how you would synthesize the following alcohols from appropriate alkenes.

18. 3) Synthesis of alcohols from carbonyl compounds (由羰基化合物制醇）
carbonyl group 羰基
aldehyde 醛
ketone 酮
carboxylic acid 羧酸
carboxylic ester
羧酸酯

19. Nu:-
alkoxide ion
Nucleophilic addition
(亲核加成)

20. (A) Reaction of carbonyl compounds with organometallic reagents to give alcohols
alkynol (炔醇)

21. Organometallic compounds （有机金属化合物）
Compounds that contain carbon-metal bonds (C-M) are called organometallic compounds.
(a) great important in organic synthesis;
(b) relatively stable in ether solutions.
(a) highly reactive Nu;
(b) powerful B.

22. (a) much less reactive;
(b) often volatile (挥发性的) and are stable in air;
(c) all poisonous;
(d) generally soluble in nonpolar solvents.
Tetraethyllead has been used as an
"antiknock" compound in gasoline.

23. Preparation of organolithium and organomagnesium compounds
Organolithium compounds (有机锂化合物）
The order of reactivity of halides is:
RI > RBr > RCl

24. Grignard reagents （格利雅试剂, 格氏试剂）

25. Grignard reagents are stable in ether

26. Preparation of alcohols by the addition of Grignard reagents to carbonyl compounds
Nucleophilic addition

27. Acetaldehyde 乙醛

28. Grignard reagent
ester
ketone
tertiary alcohol

29. Organolithium reagents (RLi) react with carbonyl compounds in the same way as Grignard reagents.

30. Attention!!! Side reactions of organometallic reagents
体系中不能有活泼氢, 如 O-H, N-H, S-H, -C≡C-H;
底物中不能含有其它极性多重键,如
C=O, C=N, C≡N, S=O, N=O.

31. X

32. 2) Reduction of carbonyl compounds to give alcohols (10-11, 11-1)

33. LiAlH4
lithium aluminum hydride 氢化铝俚，四氢铝锂　
NaBH4
sodium borohydride
硼氢化钠
(A)
LiAlH4
aldehydes
ketones
acids
esters
NaBH4
hydride transfer
nucleophile addition

35. fast
LiAlH4 + H2O
H2 + LiOH + Al(OH)3
slow
NaBH3 + H2O
H2 + NaOH + B(OH)3
LiAlH4: dry Et2O, THF as solvents
NaBH4: EtOH, MeOH, etc. as solvents

36. (B) Catalytic hydrogenation of aldehydes and ketones

37. Problems: give the main products.

38. Summary for alcohols synthesis
Synthesis of alcohol from:
alkenes
acid-catalyzed hydration (酸催化的水化反应)
hydroboration-oxidation (硼氢化反应)
oxymercuration-demercuration (汞氧化反应)
hydroxylation (羟化反应) to prepare 1,2-diols
carbonyl compounds
addition of Grignard reagents
reduction with NaBH4 and LiAlH4
alkyl halides

39. Assignments
Text 1: 10-31, 33, 38, 44, 49

40. 7. Reactions of alcohols Oxidation (氧化) substitution dehydration (脱水)
Esterification （酯化）

41. 1) Oxidation of alcohols (11-1, 2, 3)
Oxidation-Reduction reactions in organic chemistry
Reduction (还原)of an organic molecule usually corresponds to increasing its hydrogen content or to decreasing its oxygen content.(加氢、去氧或去卤素, 增加Ｃ－Ｈ键数或减少Ｃ－Ｏ键数)
Oxidation (氧化): increasing the oxygen content of an organic molecule or decreasing its hydrogen content.(加氧或加卤素、去氢，减少Ｃ－Ｈ键数或增加Ｃ－Ｏ键数)

42. C-O, 3→2
C-O, 2→1
C-O, 1→0

43. Problem p 446

44. Primary alcohols
aldehydes
carboxylic acids
Secondary alcohols
ketones
Tertiary alcohols
difficult to be oxidized.

45. (A) Oxidization with Cr(VI) (11-2)
Oxidants:
K2Cr2O7 or Na2Cr2O7 / H2SO4
CrO3/ H2SO4
butyric acid

46. Mechanism of chromate oxidations （铬酸氧化机理）

47. Or

48. A Chemical test for 1°, 2°, and 3° alcohols
Reagent: CrO3 / aqueous H2SO4
or Na2Cr2O7 / aqueous H2SO4
alcohol
phenomenon 1°
greenish opaque solution Cr3+ 2° 3°
No reaction

49. PCC (Pyridinium chlorochromate, 吡啶三氧化铬)
PDC (Pyridinium dichromate, 重铬酸吡啶盐)

50. Oxidation with KMnO4, or HNO3 (11-3)
If the conditions are not controlled, KMnO4 or HNO3 will cleave the carbon-carbon bonds.

51. Catalytic dehydrgenation (11-3) DMSO/(COCl)2/Et3N/CH2Cl2
Swern oxidation:
convert alcohols to aldehyde or ketone
DMSO/(COCl)2/Et3N/CH2Cl2

52. 2) Substitution

53. (1) Acidity of alcohols and phenols (10-6)
reactivity of alcohols:
CH3OH > 1°> 2° > 3°
(CH3)3COH + KH
(CH3)3COK + H2
+ NaOH
+ H2O
pKa = 10

54. (2) Conversion of alcohols into alkyl halides
1° alcohols, SN2
3° alcohols, SN1

55. reactivity :
HI > HBr > HCl
3° > 2 ° > 1 °

56. The Lucas reagent: HCl / ZnCl2

57. To distinguish 1°, 2°, and 3° alcohols
The Lucas test:
To distinguish 1°, 2°, and 3° alcohols
alcohol
Time to react (min)
phenomenon 1°
>6
No reaction
or react very slow 2°
1~5
Emulsion (乳状) 3°
<1
The second phase to separate (分层)

58. Wagner－Meerwerin Rearrangement
当伯醇或仲醇的β-碳原子具有二个或三个烷基或芳基时, 在酸作用下都能发生分子重排反应. 亲核能力强的或能使碳正离子更稳定的基团优先迁移．

59. B.

60. Advantages to use SOCl2 as chloride reagents:
1) no rearrangement; 2) high yield; 3) easily to separate.
Stereochemistry
configuration retention
pyridine
pyridine (吡啶) is present,
configuration inversion

61. ion pair

63. Give the major product of the following reactions.

64. Neighboring group participation (邻基参与)
Br、O、N、C=C、cyclopropyl (环丙基)、aryl (芳基), etc.
configuration retention
构型保持

65. (3) Conversion of alcohols into mesylates （甲磺酸酯）and tosylates（苯磺酸酯）
R—Nu
Nu-
R—OH
R—OMs
R—Nu
Nu-
R—OH
R—OTs
OTs, OMs are good leaving groups

66. Ms
MsOR
Methanesulfonyl
甲磺酰基
Methanesulfonate esters　
甲磺酸酯 Ts
TsOR
p-Toluenesulfonyl
对甲苯磺酰基
p-Toluenesulfonate esters
对甲苯磺酸酯

67. CH3CH2—OTs
p-Toluenesulfonyl chloride
对甲苯磺酰氯
solvent: pyridine
or Et3N/CH2Cl2
Ethyl p-toluenesulfonate
(ethyl tosylate)
对甲苯磺酸乙酯

68. 3) Acid-catalyzed dehydration
Intramolecular dehydration yield alkenes.
Intermolecular dehydration yield ethers. (bimolecular dehydration, unhindered primary alcohols, 非位阻的伯醇才能反应生成醚)

69. Alcohol dehydration: An E1 reaction
rearrangement
and orientation

70. Propose a mechanism for each reaction.
H3O+
(1)
H2SO4, heat
(2)
(3)
(4)

71. 4) Esterification (酯化反应)
Carboxylic acids react with alcohols to form esters through a condensation reaction known as esterification (Fischer esterification):
Carboxylic ester

72. Phosphate esters (烷基磷酸酯)

73. phosphate ester
Linkage in DNA

74. Sulfate ions are also excellent leaving group.
Sulfate esters (硫酸酯)
(Notice!! sulfonate esters, 磺酸酯, S—C bond)
methyl sulfate
Sulfate ions are also excellent leaving group.
dimethyl sulfate
(硫酸二甲酯)
甲基化试剂, 毒！

75. methylsulfate ion
甲基硫酸离子
methylammonium ion
甲铵离子

76. Nitrate esters (硝酸酯) alkyl nitrate esters Glyceryl trinitrate 炸药
(nitroglycerine)
硝酸甘油 炸药
治心绞痛药

77. 5) Unique reaction of diols (11-11)
Pinacol(频那醇)
Pinacolone
(频那酮)
The Pinacol rearrangement
(频那醇重排, 邻二叔醇重排)

78. Propose a mechanism for each reaction.
(1)
(2)
(3)

79. Periodic acid (HIO4) cleavage of glycols
(高碘酸氧化邻位二醇)
ketones or aldehydes

80. APPLICATION:
To identify the structure of the vicinal diols.
Determining the structure of sugars.

81. Summary for reactions of alcohols
oxidation
Cr(VI), PCC (PDC); KMnO4
substitution
RO-Na+
HBr, PBr3, SOCl2 (to prepare alkyl halides)
ROTs, ROMs
dehydration
E1, yield alkenes
SN2, yield ethers (primary ROH)
esterification
unique reactions of diols
pinacol rearrangment; HIO4 cleavage

82. Outline a multistep synthesis for the following transformation.

83. Assignments
Text 1: , 46, 47, 48, 53, 54, 56

84. Structure and physical properties of ethers
II. Ethers (醚)
Structure and physical properties of ethers
R, R’ = alkyl or aryl
Having much lower bp than alcohols of similar formula weight.
Polar solvents, aprotic solvents
Lewis base: Coordination with H+, B, Mn+, etc.

85. 2. Nomenclature of ethers
Acids
Esters
Aldehydes
Ketones
Alcohols
Amines
Alkenes
Alkynes
Alkanes
Ethers
Halides
Common names
IUPAC names:
alkyl alkyl ether
alkoxy alkane
Decreasing priority
simple ethers
complex ethers
ethyl methyl ether
Common:
(甲基乙基醚)
IUPAC:
methoxyethane
(甲氧基乙烷)
The order of precedence of functional groups for assigning IUPAC names

86. Chain ethers Allyl methyl ether 甲基烯丙基醚 3-methoxypropene
Methyl phenyl ether
苯甲醚
Methoxybenzene
Ethylene glycol dimethyl ether
乙二醇二甲醚
2-Methoxypentane
2-甲氧基戊烷
1,2-Dimethoxyethane
1，2-二甲氧基乙烷

87. Cyclic ethers (环醚) Heterocyclic compounds （杂环化合物） O: Heteroatom （杂原子）
tetrahydrofuran
tetrahydropyran
(THP)
四氢吡喃
3-methyl-tetrahydropyran
四氢呋喃
THF
oxacyclopentane
氧杂环戊烷
1,4-dioxane
二噁烷
Heterocyclic compounds
（杂环化合物）
O: Heteroatom （杂原子）
1,4-dioxacyclohexane
1,4-二氧六环

88. Oxirane
(环氧乙烷)
Oxetane
1,3-epoxypropane
1,3-环氧丙烷
12-crown-4
12-冠-4
Epoxide
环氧化物
Crown ethers 冠醚

89. Ethers by bimolecular dehydration of alcohols (醇的分子间脱水制醚）
3. Synthesis of ether
Ethers by bimolecular dehydration of alcohols
(醇的分子间脱水制醚）
R: Primary alkyl group
Suitable for symmetrical ether (对称醚) synthesis

90. Can we use this method to synthesize the unsymmetrical ethers?
CH3CH2OCH2CH2CH ?

91. 2) The Williamson synthesis of ethers (醚的威廉姆逊合成）
L = Br, I, OSO2R'', or OSO2OR''
R’: Primary alkyl group
Williamson ether synthesis:
Suitable for unsymmetrical ethers (不对称醚) synthesis

92. How to synthesize ethyl propyl ether? (CH3CH2OCH2CH2CH3)
Way 1:

93. Way 2:

94. How to synthesize tert-butyl ethyl ether ?

95. a: X b:
Notice: Hindered, no reaction!!!
Elimination

96. Conclusion To convert two alcohols to an ether:
Convert the more hindered alcohol to its alkoxide.
Convert the less hindered alcohol to its tosylate (OTs, or an alkyl halide).
Make sure the tosylate or halide is a good SN2 substrate.
Propose a Williamson synthesis of
3-butoxy-1,1-dimethylcyclohexane
from 3,3-dimethyl-cyclohexanol and butanol.

97. Synthesis of phenyl ethers ( 苯醚)
Phenoxide ion
Ullmann reaction

98. 3) Alkoxymercuration-demercuration
ether
Anti addition(反式加成)
Follow Markovnikov rule(符合马氏规则)

99. 4. Reactions of ethers 1) Cleavage of ethers(醚键的断裂) by HBr and HI
Very strong conditions;
Reactivity: HI > HBr >> HCl.
The molecule must not contain any acid-sensitive functional group!!

101. The order of C-O cleavage : 3 > 2 > 1 > Ph-O

102. Phenyl ethers
No further reaction
Ethyl phenyl ether
Protonated ether
Phenol + ethyl bromide
Ether cleavage: 1°alkyl ether: SN2 3°alkyl ether: SN1 alkyl phenyl ether: give phenol and alkyl halide. ?

103. Propose a mechanism.

104. 2) Autoxidation of ethers
Add FeSO4 to remove a hydroperoxide!!
Peroxides test: KI/starch(淀粉), or FeSO4/KSCN, etc.

105. 5. Important ethers Diethyl ether: bp 35 ºC, polar solvent
THF: bp 66 ºC, strong polar solvent
Crown ethers: as PTC (相转移催化剂)

106. 使用乙醚注意事项
蒸馏时不能蒸干！
蒸馏时尾接管要通下水道！
周围不能有明火！
不能在冰箱里敞口存放！
萃取时要及时放气!

107. Crown Ethers （冠醚） Structural characteristic:
Containing more than three –OCH2CH2O- units in one molecule.
Nomenclature: x-crown-y x----total atom number in the ring y----oxygen atom number
12-crown-4
12-冠-4
15-crown-5
15-冠-5

108. 18-crown-6
Dibenzo-18-crown-6
二苯基-18-冠-6
Dicyclohexyl-18-crown-6
二环己基-18-冠-6

109. NH4+ K+
Na+
Li+
金属离子直径

110. Phase-Transfer catalysis (PTC) (相转移催化）
MnO4－
(or CN－)
Crown ethers are used as phase-transfer catalysts.

112. Summary for ethers
Nomenclature: “alkyl alkyl ether”, “alkoxy alkane”(IUPAC)
Synthesis
Ethers by intermolecular dehydration of alcohols (醇的分子间脱水制醚）
The Williamson synthesis of ethers (醚的威廉姆逊合成）
Alkoxymercuration-demercuration
Reactions
Cleavage of ethers by HBr and HI
Autoxidation of ethers
Application
Solvents: stable, low bp., diethyl ether, THF, 1,4-dioxane
Crown ethers: as PTC

113. Epoxides 环氧化物

114. an epoxide
环氧化物
IUPAC: oxirane
Common: Ethylene oxide
环氧乙烷
cyclohexene oxide
trans-1,2-epoxy-4-methylcyclohexane
trans-4-甲基-1,2-环氧环己烷
2,2-diethyl-3-isopropyloxirane
2,2-二乙基-3-异丙基环氧乙烷

115. 1. Synthesis of epoxides 1) Epoxidation of alkenes
2) Base-Promoted cyclization of halohydrins

117. 2. Reactions of epoxides 1) Acid-catalyzed ring opening (review)
Nu: H2O
ROH HX

118. Orientation of acid-catalyzed epoxides opening
SN2
酸性条件下, 亲核试剂进攻取代基多的碳，即带正电多的碳.

119. 2) Based-Catalyzed Ring Opening
Nu: OH-, RO-, NH3
Orientation of base-catalyzed epoxides opening
Less hindered
碱性条件下, 亲核试剂进攻位阻较小的碳。

120. 3) Reaction of organometalic reagents with oxiranes
Give primary alcohols
primary alcohol
Attact the less hindered carbon
secondary alcohol

121. Problem 1: Give the structures of A and B:
Problem 2: Explain the following results:

122. Sharpless不对称环氧化反应
烯丙醇及其衍生物在钛酸酯参与下的不对称环氧化反应称为Sharpless环氧化反应，简称为AE反应(asymmetric epoxidation) 。1980年，由Sharpless K.B. 等研究发现。

124. Summary for epoxides Synthesis Peroxyacid epoxidation
Base-Promoted cyclization of halohydrins
Reactions
　 acid-catalyzed ring opening
base-catalyzed ring opening
reaction with Grignard reagents

125. Assignments
T , 33, 37, 39, 41, 43
T.2(selected) 4, 8, 9, 10, 13, 15, 16, 19, 22