1. Chapter 16 Ethers, Epoxides, and Sulfides
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2. Ethers Formula is R—O—R¢where R and R¢ are alkyl or aryl.
Symmetrical or unsymmetrical

3. Nomenclature of Ethers, Epoxides, and Sulfides2

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

5. Functional Class IUPAC Names of Ethers
Name the groups attached to oxygen in alphabetical order as separate words; "ether" is last word.
CH3OCH2 CH3
CH3CH2OCH2CH2CH2Cl
ethyl methyl ether
3-chloropropyl ethyl ether
CH3CH2OCH2 CH3
diethyl ether 3

6. Structure and Bonding in Ethers and Epoxides
bent geometry at oxygen analogous to water and alcohols 8

7. Structure and Polarity
Oxygen is sp3 hybridized.
Bent molecular geometry.
Tetrahedral C—O—C angle is 110°.
Polar C—O bonds.

8. 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

9. 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

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

11. Physical Properties of Ethers11

12. 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

13. solubility in water (g/100 mL)
Table 16.1 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

14. Hydrogen Bond Acceptor
Ethers cannot hydrogen bond with other ether molecules, so they have a lower boiling point than alcohols.
Ether molecules can hydrogen bond with water and alcohol molecules.
They are hydrogen bond acceptors.

15. Ethers as Solvents Ethers are widely used as solvents because
they can dissolve nonpolar and polar substances.
they are unreactive toward strong bases.
Ethers are relatively unreactive.
Their low level of reactivity is one reason why
ethers are often used as solvents in chemical
reactions.

16. Ether Complexes
Grignard reagents: Complexation of an ether with a Grignard reagent stabilizes the reagent and helps keep it in solution.
Electrophiles: The ether’s nonbonding electrons stabilize the borane (BH3).

17. Crown Ethers
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18. structure cyclic polyethers derived from repeating —OCH2CH2— units
Crown Ethers
structure cyclic polyethers derived from repeating —OCH2CH2— units
properties form stable complexes with metal ions
applications synthetic reactions involving anions 14

19. Crown Ether Complexes
Crown ethers can complex metal cations in the center of the ring.
The size of the ether ring will determine which cation it can solvate better.
Complexation by crown ethers often allows polar inorganic salts to dissolve in nonpolar organic solvents.

20. forms stable Lewis acid/Lewis base complex with K+
18-Crown-6 O K+
forms stable Lewis acid/Lewis base complex with K+ 15

21. Ion-Complexing and Solubility
K+F–
not soluble in benzene 16

22. Ion-Complexing and Solubility
K+F–
benzene
add 18-crown-6 16

23. Ion-Complexing and SolubilityF– K+
benzene
18-crown-6 complex of K+ dissolves in benzene 16

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

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

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

27. Preparation of Ethers 21

28. Acid-Catalyzed Condensation of Alcohols*
2 CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
Method is good for primary alcohols. Diethyl ether is made on industrial scale using this method. Ethylene will form at higher temperatures. Secondary and tertiary alcohols give alkenes as main product. 10

29. Addition of Alcohols to Alkenes
(CH3)2C=CH2 + CH3OH
(CH3)3COCH3
tert-Butyl methyl ether
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

30. The Williamson Ether Synthesis24

31. Williamson Ether Synthesis
This method involves an SN2 attack of the alkoxide on an unhindered primary halide or tosylate.
The alkoxide is commonly made by adding Na, K, or NaH to the alcohol

32. Example
CH3CH2CH2CH2ONa + CH3CH2I
CH3CH2CH2CH2OCH2CH3 + NaI
(71%) 25

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

34. Origin of Reactants CH2OH HCl CH3CHCH3 OH Na CH2OCHCH3 CH3 CH2Cl +
ONa
(84%) 26

35. 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

36. Reactions of Ethers: 28

37. Acid-Catalyzed Cleavage of Ethers Ethers can be cleaved by heating with concentrated HBr and HI. Reactivity: HI > HBr 29

38. Example
CH3CHCH2CH3
HBr
CH3CHCH2CH3 +
CH3Br
heat
OCH3 Br
(81%) 31

39. Mechanism of Ether Cleavage
Step 1: Protonation of the oxygen.
Step 2: The halide will attack the carbon and displace the alcohol (SN2).

40. Mechanism of Ether Cleavage
Step 3: The alcohol reacts further with the acid to produce another mole of alkyl halide.
This does not occur with aromatic alcohols (phenols).

41. Cleavage of Cyclic EthersHI
ICH2CH2CH2CH2I
150°C
(65%) 32

42. Mechanism O ICH2CH2CH2CH2I HI HI H O + I – H O I •• •• •• • • •• • •32

43. Autoxidation of Ethers
In the presence of atmospheric oxygen, ethers slowly oxidize to hydroperoxides and dialkyl peroxides.
Both are highly explosive.
Precautions:
Do not distill to dryness.
Store in full bottles with tight caps.

44. Autoxidation of Ethers

45. Preparation of Epoxides: A Review and a Preview
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46. Preparation of Epoxides
Epoxides are prepared by two major methods. Both begin with alkenes.
Reaction of alkenes with peroxy acids (Section 6.19)
Conversion of alkenes to vicinal halohydrins, followed by treatment with base (Section 16.10, this chapter) 30

47. Synthesis of Epoxides
Peroxyacids are used to convert alkenes to epoxides.
Most commonly used peroxyacid is meta-chloroperoxybenzoic acid (MCPBA).
The reaction is carried out in an aprotic acid to prevent the opening of the epoxide.

48. Halohydrin Cyclization
If an alkoxide and a halogen are located in the same molecule, the alkoxide may displace a halide ion and form a ring.
Treatment of a halohydrin with a base leads to an epoxide through this internal SN2 attack.

49. Another look H OH Br H
NaOH O
H2O H
(81%) O Br H
• • •• –
via: 5

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

51. Reactions of Epoxides: A Review and a Preview6

52. 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

53. Example
H2C O
CH2
NaOCH2CH3
CH3CH2OH
CH3CH2O
CH2CH2OH
(50%) 11

54. 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

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

56. 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:
CH2 O C R H 10

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

58. 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

59. Acid-Catalyzed Ring-Opening Reactions of Epoxides22

60. Example O H2C CH2 CH3CH2OH CH3CH2OCH2CH2OH H2SO4, 25°C (87-92%)
CH3CH2OCH2CH2OCH2CH3 formed only on heating and/or longer reaction times. 11

61. 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

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

63. Acid-Catalyzed Hydrolysis of Ethylene Oxide
Step 1
H2C
CH2
• • O
H2C
CH2 + H O O
• • H +
• • •• 12

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

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

66. Acid-Catalyzed Ring Opening of Epoxides
Characteristics:
Nucleophile attacks more substituted carbon of protonated epoxide.
Inversion of configuration at site of nucleophilic attack. 30

67. Nucleophile Attacks More-substituted Carbon
CH3CH
CCH3
CH3 OH
OCH3
(76%) C H
H3C
CH3 O
CH3OH
H2SO4 19

68. 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

69. (57%) Stereochemistry H3C CH3 H CH3OH H OH O CH3O H H2SO4 H H3C CH3
Inversion of configuration at carbon being attacked by nucleophile 18

70. Stereochemistry H3C CH3 H CH3OH H OH O CH3O H H2SO4 H H3C CH3 H3C H +18

71. anti-Hydroxylation of Alkenes
CH3COOH O H
H2O
HClO4
(80%) H OH
+ enantiomer 35