1. Chapter 16 Ethers, Epoxides, and Sulfides
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2

2. 16.1 Nomenclature of Ethers, Epoxides, and Sulfides2

3. Substitutive IUPAC Names of Ethers
Name as alkoxy derivatives of alkanes.
CH3OCH2 CH3
CH3CH2OCH2CH2CH2Cl
methoxyethane
1-chloro-3-ethoxypropane
CH3CH2OCH2 CH3
ethoxyethane 3

4. Functional Class IUPAC Names of Ethers
Name as "ethers" , listing the groups attached to oxygen as substituents, in alphabetical order.
CH3OCH2 CH3
CH3CH2OCH2CH2CH2Cl
ethyl methyl ether
3-chloropropyl ethyl ether
CH3CH2OCH2 CH3
diethyl ether 3

5. Substitutive IUPAC Names of Sulfides
Name as alkylthio derivatives of alkanes.
CH3SCH2CH3
SCH3
methylthioethane
(methylthio)cyclopentane
CH3CH2SCH2CH3
ethylthioethane 3

6. Functional Class IUPAC Names of Sulfides
Name as "sulfides" in a manner analogous to that when using "ether" as the parent.
CH3SCH2CH3
SCH3
ethyl methyl sulfide
cyclopentyl methyl sulfide
CH3CH2SCH2CH3
diethyl sulfide 3

7. Oxirane (Ethylene oxide) Oxetane Oxolane (tetrahydrofuran)
Names of Cyclic Ethers O O O
Oxirane (Ethylene oxide)
Oxetane
Oxolane (tetrahydrofuran)
Oxane (tetrahydropyran)
1,4-Dioxane O O O 3

8. Names of Cyclic Sulfides
Thiirane
Thietane S S
Thiolane
Thiane 3

9. 16.2 Structure and Bonding in Ethers and Epoxides
Bent geometry at oxygen analogous to water and alcohols 8

10. Bond angles at oxygen are sensitive to steric effectsH H
CH3 H
112°
105°
108.5°
132° O
(CH3)3C O
C(CH3)3
CH3
CH3 9

11. An oxygen atom affects geometry in much the same way as a CH2 group
Most stable conformation of diethyl ether resembles that of pentane. 10

12. An oxygen atom affects geometry in much the same way as a CH2 group
Most stable conformation of tetrahydropyran resembles that of cyclohexane. 10

13. 16.3 Physical Properties of Ethers11

14. solubility in water (g/100 mL)
Table Ethers resemble alcohols more than alkanes with respect to solubility in water
solubility in water (g/100 mL)
very small
7.5
Hydrogen bonding to water possible for ethers and alcohols; not possible for alkanes. O 9 OH 12

15. Table 16.1 Ethers resemble alkanes more than alcohols with respect to boiling point
Intermolecular hydrogen bonding possible in alcohols; not possible in alkanes or ethers.
36°C
35°C O
117°C OH 12

16. 16.4 Crown Ethers 11

17. Properties: They form stable complexes with metal ions.
Crown Ethers
Structure: These are cyclic polyethers derived from repeating —OCH2CH2— units.
Properties: They form stable complexes with metal ions.
Applications: They participate in synthetic reactions involving anions. 14

18. = the number of atoms in the ring. 6 = the number of oxygens.
18-Crown-6
= the number of atoms in the ring.
6 = the number of oxygens. O
A region of negative charge is concentrated in the cavity inside the molecule. 15

19. 18-Crown-6 O K+
This negative region forms a stable Lewis acid/Lewis base complex with K+. 15

20. Ion-Complexing and Solubility
K+F– alone is not soluble in benzene.
But when 18-crown-6 is added: O O F– K+
benzene
The 18-crown-6 complex of K+ dissolves in benzene. 16

21. Ion-Complexing and SolubilityK+
benzene + F–
F– is carried into benzene to preserve electroneutrality. 16

22. Application to organic synthesis
Complexation of K+ by 18-crown-6 solubilizes potassium salts in benzene.
The anion of the salt is in a relatively unsolvated state in benzene (sometimes referred to as a "naked anion").
The unsolvated anion is very reactive.
Only catalytic quantities of 18-crown-6 are needed. 20

23. Example KF
CH3(CH2)6CH2Br
CH3(CH2)6CH2F
18-crown-6
benzene
(92%) 20

24. 16.5 Preparation of Ethers 1. Acid catalyzed condensation of alcohols.
2. Williamson ether synthesis. 11

25. Acid-Catalyzed Condensation of Alcohols*
2 CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
*Best for symmetrical ethers, discussed earlier in Section 15.7. 10

26. Addition of Alcohols to Alkenes
(CH3)2C=CH2 + CH3OH
(CH3)3COCH3
tert-Butyl methyl ether
This is a commercial method of preparation.
tert-Butyl methyl ether (MTBE) was produced on a scale exceeding 15 billion pounds per year in the U.S. during the 1990s. It is an effective octane booster in gasoline, but contaminates ground water if allowed to leak from storage tanks. Further use of MTBE is unlikely. 23

27. 16.6 The Williamson Ether Synthesis
Think SN2!
primary alkyl halide + alkoxide nucleophile 11

28. Good for preparing unsymmetrical ethers.
Example
CH3CH2CH2CH2ONa + CH3CH2I
Alkyl halide (1o or Me),
SN2 substrate
Alkoxide,
Nucleophile
CH3CH2CH2CH2OCH2CH3 + NaI
(71%)
Good for preparing unsymmetrical ethers. 25

29. Another Example + CH3CHCH3 ONa CH2Cl (84%) CH2OCHCH3 CH3
Alkyl halide must be
primary or methyl
Alkoxide ion can be derived from a methyl, primary, secondary, or tertiary alcohol. +
CH3CHCH3
ONa
CH2Cl
(84%)
CH2OCHCH3
CH3 26

30. Origin of Reactants CH3CHCH3 OH Nao CH2OH SOCl2 CH2OCHCH3 CH3 CH2Cl +
ONa
(84%) 26

31. What happens if the alkyl halide is not primary ?
CH2ONa +
CH3CHCH3 Br
CH2OH +
H2C
CHCH3
Elimination by the E2 mechanism becomes the major reaction pathway. 27

32. 16.7 Reactions of Ethers: A Review and a Preview11

33. Summary of reactions of ethers
No reactions of ethers except epoxides have been encountered to this point.
Most ethers are relatively unreactive.
Their low level of reactivity is one reason why ethers are often used as solvents in chemical reactions.
Ethers oxidize in air to form explosive hydroperoxides and peroxides. 27

34. 16.8 Acid Catalyzed Cleavage of Ethers11

35. Cleavage of ethers works well with HBr or HI.
Initial cleavage is at the least hindered carbon, see mechanism.
Example
Forms CH3Br first.
CH3CHCH2CH3
HBr
CH3CHCH2CH3 +
CH3Br
heat
OCH3 Br
(81%) 31

36. Mechanism CH3 CH3CHCH2CH3 O CH3CHCH2CH3 Br CH3 CH3CHCH2CH3 O H + H Br
• • ••
CH3CHCH2CH3 Br
CH3
CH3CHCH2CH3 O H + •• •• H Br
• •
HBr (repeat) ••
• •
CH3 Br
CH3CHCH2CH3 O H •• Br –
• • 31

37. Cleavage of Cyclic EthersHI
ICH2CH2CH2CH2I ••
150°C •• HI H O •• +
• • I –
HI (repeat)
Mechanism H O ••
• • I 32

38. 16.9 Preparation of Epoxides: A Review and a Preview11

39. Preparation of Epoxides
Epoxides are prepared by two major methods. Both begin with alkenes.
1. Reaction of alkenes with peroxy acids like m-chloroperoxybenzoic acid, (Section 6.19).
2. Conversion of alkenes to vicinal halohydrins, followed by treatment with base, (Section 16.10). 30

40. 16.10 Conversion of Vicinal Halohyhdrins to Epoxides11

41. Example H H OH NaOH O H2O Br H A bromohydrin (81%) – O via: H Br • ••• –
via: 5

42. Epoxidation via Vicinal HalohydrinsBr
Br2
NaOH O
H2O OH
anti addition
inversion
Corresponds to overall syn addition of oxygen to the double bond. 3

43. Epoxidation via Vicinal HalohydrinsBr
H3C
Br2 H
H3C
CH3 H
NaOH H
H3C
CH3
H2O H O
CH3 OH
anti addition
inversion
Corresponds to overall syn addition of oxygen to the double bond. 3

44. 16.11 Reactions of Epoxides: A Review and a Preview

45. In General...
Reactions of epoxides involve attack by a nucleophile and proceed with ring-opening.
For ethylene oxide:
H2C
CH2 O
Nu—H +
Nu—CH2CH2O—H 10

46. In General...
For epoxides where the two carbons of the ring are differently substituted:
Nucleophiles attack here when the reaction is catalyzed by acids.
Anionic nucleophiles attack here (least
substituted position).
CH2 O C R H 10

47. Reactions of Epoxides
All reactions involve nucleophilic attack at carbon and lead to opening of the ring.
An example is the reaction of ethylene oxide with a Grignard or organolithium reagent (discussed in Section 15.4 as a method for the synthesis of alcohols). 7

48. Reaction of Grignard Reagents with Epoxides
MgX
CH2
OMgX R
H2C
CH2 O
H3O+
RCH2CH2OH 9

49. Example CH2 CH2MgCl H2C + O 1. diethyl ether 2. H3O+ CH2CH2CH2OH (71%)29

50. 16.12 Nucleophilic Ring-Opening Reactions of Epoxides11

51. Epoxide Ring Opening O H2C CH2 Example NaOCH2CH3 CH3CH2OH CH3CH2O
(50%) 11

52. Mechanism CH3CH2 O – – CH3CH2 O CH2CH2 O H2C CH2 O CH2CH3 H CH3CH2 O••
• • – – ••
CH3CH2 O
• •
CH2CH2 O
H2C
CH2 •• O
CH2CH3
• • •• H ••
CH3CH2 O
CH2CH2 H
• •
CH2CH3 – 12

53. Example O H2C CH2 KSCH2CH2CH2CH3 ethanol-water, 0°C (99%) CH2CH2OH
CH3CH2CH2CH2S 11

54. Inversion of configuration at carbon being attacked by nucleophile.
Stereochemistry
OCH2CH3 O H
NaOCH2CH3
CH3CH2OH H H OH
(67%)
Inversion of configuration at carbon being attacked by nucleophile.
Suggests SN2-like transition state. 11

55. Inversion of configuration at carbon being attacked by nucleophile.
Stereochemistry
CH3
H3C R R H
NH3 H OH
H2N H O
H2O R S H
H3C
CH3
(70%)
Inversion of configuration at carbon being attacked by nucleophile.
Suggests SN2-like transition state. 18

56. An SN2-like transition state.
Stereochemistry
An SN2-like transition state.
H3C
CH3 R H R
NH3
H2O H OH O
H2N H R S H
H3C
CH3
(70%)
H3C H
via: - + H
H2N O H
H3C 18

57. Anionic Nucleophile Attacks Less-crowded Carbon
CH3CH
CCH3
CH3 OH
CH3O C H
H3C
CH3 O
NaOCH3
CH3OH
(53%)
An unsymmetrical epoxide. 19

58. Anionic Nucleophile Attacks Less-crowded Carbon
MgBr + O
H2C
CHCH3
1. diethyl ether
2. H3O+
CH2CHCH3 OH
(60%) 15

59. Lithium Aluminum Hydride Reduces Epoxides
H2C
CH(CH2)7CH3
Hydride attacks less-crowded carbon.
1. LiAlH4, diethyl ether
2. H2O
(90%) OH
H3C
CH(CH2)7CH3 16

60. 16.13 Acid Catalyzed Ring-Opening Reactions of Epoxides11

61. Example O H2C CH2 CH3CH2OH CH3CH2OCH2CH2OH H2SO4, 25°C (87-92%)
CH3CH2OCH2CH2OCH2CH3 formed only on heating and/or longer reaction times. The first step is easy due to the strained three membered ring. 11

62. BrCH2CH2Br formed only on heating and/or longer reaction times.
Example O
H2C
CH2
HBr
BrCH2CH2OH
10°C
(87-92%)
BrCH2CH2Br formed only on heating and/or longer reaction times. 11

63. Mechanism Br – H2C CH2 O H2C CH2 + • • O H Br H O Br CH2CH2 H O H2C••
• • –
H2C
CH2 O
H2C
CH2 + • • O ••
• • H Br ••
• • H
• • •• O Br
CH2CH2 H O
H2C
CH2 •• 12

64. Acid-Catalyzed Hydrolysis of Ethylene Oxide
Step 1
H2C
CH2
• • O
H2C
CH2 + H
Protonateoxygen O O
• • H +
• • •• ••
• • H
Step 2 +
• • •• O
CH2CH2 H
Nucleophileattacks ring O
• • O
H2C
CH2 + H 12

65. Acid-Catalyzed Hydrolysis of Ethylene Oxide•• O
• • H +
CH2CH2
Step 3
Deprotonate O ••
• • H +
• • •• O
CH2CH2 H •• 12

66. Acid-Catalyzed Ring Opening of Epoxides
Characteristics:
Nucleophile attacks more substituted carbon of protonated epoxide. The more substituted carbon of the epoxide ring tolerates positive charge better.
Inversion of configuration at site of nucleophilic attack. 30

67. Inversion of configuration at carbon being attacked by nucleophile.
Stereochemistry
Inversion of configuration at carbon being attacked by nucleophile.
H3C
CH3 R H R
CH3OH
H2SO4 H OH O
CH3O H R S H
H3C
CH3
(57%)
H3C H
via: + + + O H
CH3O H H
H3C 18

68. Nucleophile Attacks More-substituted Carbon
CH3CH
CCH3
CH3 OH
OCH3
(76%) C H
H3C
CH3 O
CH3OH
H2SO4
Consistent with carbocation character at transition state. 19

69. Inversion of configuration at carbon being attacked by nucleophile.
Stereochemistry H O H OH
HBr H Br
(73%)
Inversion of configuration at carbon being attacked by nucleophile. 11

70. anti-Hydroxylation of Alkenes
CH3COOH O H
Goes through the epoxide.
H2O
HClO4
(80%) H OH
Note:
Dil. KMnO4 and OsO4 give syn diols.
+ enantiomer 35

71. 16.15 Preparation of Sulfides11

72. Prepared by nucleophilic substitution (SN2).
Preparation of RSR'
Prepared by nucleophilic substitution (SN2). – ••
• • •• R S R' R S + R' X
CH3CHCH
CH2 Cl
NaSCH3
methanol
SCH3
allylic carbon

73. 16.16 Oxidation of Sulfides: Sulfoxides and Sulfones11

74. Oxidation of RSR' R S R' O – ++ sulfone + R S R' O – R S R' sulfide•• R S R'
• • O – ++
sulfone + •• R S R' O
• • – •• R S R'
sulfide
sulfoxide
Either the sulfoxide or the sulfone can be isolated depending on the oxidizing agent and reaction conditions.

75. Example + SCH3 O – SCH3 NaIO4 water (91%) •• • • ••
Sodium metaperiodate oxidizes sulfides to sulfoxides and no further.

76. Example SCH CH2 SCH O – ++ CH2 H2O2 (2 equiv) (74-78%) •• •• • •
1 equiv of H2O2 or a peroxy acid gives a sulfoxide, 2 equiv give a sulfone. ••
SCH
CH2
SCH O
• • •• – ++
CH2
H2O2
(2 equiv)
(74-78%)

77. 16.17 Alkylation of Sulfides: Sulfonium Salts11

78. Sulfides Can Act as Nucleophiles+ •• •• R S +
R" X R S
R" X–
• • R' R'
Product is a sulfonium salt.
Example
CH3I +
CH3(CH2)10CH2SCH3
CH3(CH2)10CH2SCH3 I–
CH3

79. 16.18 Spectroscsopic Analysis of Ethers, Epoxides and Sulfides11

80. Figure 16.4 Infrared Spectrum of Dipropyl Ether
C—O stretching of ethers: and 1150 cm-1 (strong)
Francis A. Carey, Organic Chemistry, Fifth Edition. Copyright © 2003 The McGraw-Hill Companies, Inc. All rights reserved. 8

81. Infrared Spectroscopy
Epoxides exhibit bands for C—O stretching at: cm-1 (asymmetric stretch) and 1250 cm-1 (symmetric stretch). There is also a third band in the range cm-1. C O H
CH2(CH2)8CH3
n = 837, 917, and 1265 cm-1 6

82. Infrared Spectroscopy
Sulfoxides exhibit strong S—O absorption in the range cm-1. Sulfones have two S—O absorptions: cm-1 (symmetric stretch) and cm-1 (asymmetric stretch). ++ S O
• • •• –
H3C
CH3 O •• + S
• • –
H3C
CH3
n = 1050 cm-1
n = 1139 and 1298 cm-1 6

83. H—C—O proton is deshielded by O; range is ca.  3.3-4.0 ppm.
1H NMR
H—C—O proton is deshielded by O; range is ca.  ppm.
CH3 CH2 CH2 OCH2 CH2 CH3
 0.8 ppm
 1.4 ppm
 3.2 ppm 6

84. Fig (b) 1H NMR 1

85. H—C—S proton is less deshielded than H—C—O.
1H NMR
H—C—S proton is less deshielded than H—C—O.
CH3 CH2 CH2 S CH2 CH2 CH3
 2.5 ppm
Oxidation of sulfides to sulfoxide deshields an adjacent C—H proton by ppm. An additional ppm downfield shift occurs on oxidation of the sulfoxide to the sulfone. 6

86. 13C NMR
Carbons of C—O—C appear in the range  ppm.
But the ring carbons of epoxides are somewhat more shielded. C O H
CH2(CH2)2CH3
d 47
d 52
d 68
d 26 O

87. Fig (c) C NMR

88. UV-VIS
Simple ethers have their absorption maximum at about 185 nm and are transparent to ultraviolet radiation above about 220 nm.

89. Mass Spectrometry
The molecular ion fragments to give an oxygen-stabilized carbocation. •+
CH3CH2O
CHCH2CH3
m/z 102 ••
CH3
CH3CH2O + CH
CH3
CHCH2CH3
m/z 87
m/z 73 ••

90. End of Chapter 16 Ethers, Epoxides, and Sulfides11