Chapter 16 Ethers, Epoxides, and Sulfides

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Chapter 16Ethers, Epoxides, and Sulfides
2
16.5Preparation of Ethers
3
Acid-Catalyzed Condensation of Alcohols
2CH3CH2CH2CH2OH
CH3CH2CH2CH2OCH2CH2CH2CH3
(60)
4
Addition of Alcohols to Alkenes
H
(CH3)2CCH2 CH3OH
(CH3)3COCH3
tert-Butyl methyl ether
tert-Butyl methyl ether (MTBE) was produced on
ascale exceeding 15 billion pounds per year in
the U.S.during the 1990s. It is an effective
octane rating booster ingasoline, but
contaminates ground water if allowed toleak from
storage tanks. Further use of MTBE is unlikely.
5
16.6The Williamson Ether Synthesis

• Think SN2!
• Primary alkyl halide alkoxide nucleophile.

6
Example
CH3CH2CH2CH2ONa CH3CH2I
CH3CH2CH2CH2OCH2CH3 NaI
(71)
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Williamson Ether Synthesis Has Limitations
1) Alkyl halide must be primary (RCH2X). 2)
Alkoxides can be derived from primary, secondary
or tertiary alcohols.
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Williamson Ether Synthesis Has Limitations
1) Alkyl halide must be primary (RCH2X). 2)
Alkoxides can be derived from primary, secondary
or tertiary alcohols.
The reaction works particularly well with benzyl
and allyl halides, which are excellent alkylating
agents.
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Origin of Reactants
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What Happens if the Alkyl Halide Is Not Primary?
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16.7Reactions of EthersA Review and a Preview
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Summary of Reactions of Ethers

• No reactions of ethers encountered to this
  point.
• 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.

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16.8Acid-Catalyzed Cleavage of Ethers
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Example
HBr
CH3CHCH2CH3
CH3CHCH2CH3

CH3Br
heat
OCH3
Br
(81)
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Mechanism
16
Cleavage of Cyclic Ethers
HI
ICH2CH2CH2CH2I
150C
(65)
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Mechanism


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16.9Preparation of EpoxidesA Review and a
Preview
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Preparation of Epoxides
Epoxides are prepared by two major methods.Both
begin with alkenes.

• Reaction of alkenes with peroxy acids(6.19).
• Conversion of alkenes to vicinalhalohydrins
  (6.18), followed by treatmentwith base (16.10).

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16.10Conversion of Vicinal Halohydrinsto
Epoxides
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Example
H
NaOH
O
H2O
H
(81)
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Epoxidation via Vicinal Halohydrins
Br
H3C
Br2
H
NaOH
H2O
H
O
CH3
OH
Antiaddition
Inversion
Corresponds to overall syn addition ofoxygen to
the double bond.
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16.11Reactions of EpoxidesA Review and a
Preview
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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 reagent (discussed in 15.4 as a
  method for the synthesis of alcohols).

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Reaction of Grignard Reagentswith Epoxides

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Example
CH2
H2C


O
1. diethyl ether 2. H3O
(71)
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In General...
Reactions of epoxides involve attack by
anucleophile and proceed with ring-opening.For
ethylene oxide

NuH
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In General...
For epoxides where the two carbons of thering
are differently substituted
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16.12Nucleophilic Ring-OpeningReactions of
Epoxides
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Example
NaOCH2CH3
CH3CH2OH
(50)
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Mechanism
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Example
KSCH2CH2CH2CH3
ethanol-water, 0C
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Stereochemistry
OCH2CH3
H
H
OH
(67)

• Inversion of configuration at carbon being
  attacked by nucleophile.
• Suggests SN2-like transition state.

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Stereochemistry
CH3
H3C
R
R
H
NH3
H
OH
O
H2N
H
R
H2O
S
H
H3C
CH3
(70)

• Inversion of configuration at carbon being
  attacked by nucleophile.
• Suggests SN2-like transition state.

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Stereochemistry
CH3
H3C
R
R
H
NH3
H
OH
O
H2N
H
R
H2O
S
H
H3C
CH3
(70)
H3C
H
?-
O
H3N
H
H3C
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Good Nucleophiles Attack Less-Crowded Carbon
NaOCH3
CH3OH
(53)

• Consistent with SN2-like transition state.

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Good Nucleophiles Attack Less-Crowded Carbon

1. diethyl ether 2. H3O
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Lithium Aluminum Hydride Reduces Epoxides
1. LiAlH4, diethyl ether 2. H2O
Hydride anion attacksless-crowdedcarbon.
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16.13Acid-Catalyzed Ring-OpeningReactions of
Epoxides
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Example
CH3CH2OH
CH3CH2OCH2CH2OH
H2SO4, 25C
(87-92)

• CH3CH2OCH2CH2OCH2CH3 formed only on heating
  and/or longer reaction times.

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Example
HBr
BrCH2CH2OH
10C
(87-92)

• BrCH2CH2Br formed only on heating and/or longer
  reaction times with excess HBr.

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Mechanism

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Acid-Catalyzed Hydrolysis of Ethylene Oxide
Step 1
H2C
CH2
O


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Acid-Catalyzed Hydrolysis of Ethylene Oxide
Step 2
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Acid-Catalyzed Hydrolysis of Ethylene Oxide
Step 3

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Acid-Catalyzed Ring Opening of Epoxides
Characteristics

• Nucleophile attacks more substituted carbon of
  protonated epoxide.
• Inversion of configuration at site of
  nucleophilic attack.

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Nucleophile Attacks More-Substituted Carbon
CH3OH
H2SO4

• Consistent with carbocation character of
  transition state.

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Stereochemistry
H
OH
HBr
H
Br
(73)

• Inversion of configuration at carbon being
  attacked by nucleophile.

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Stereochemistry
CH3
H3C
R
R
H
H
OH
O
CH3O
H
R
S
H
H3C
CH3
(57)

• Inversion of configuration at carbon being
  attacked by nucleophile.

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Stereochemistry
CH3
H3C
R
R
H
H
OH
O
CH3O
H
R
S
H
H3C
CH3
H3C
H
?
?
?
H
O
CH3O
H
H
H3C
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anti-Hydroxylation of Alkenes
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16.15Preparation of Sulfides
53
Preparation of RSR'

• Prepared by nucleophilic substitution (SN2).

S
R
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Section 16.18Spectroscopic AnalysisofEthers,
Epoxides, and Sulfides
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Infrared Spectroscopy

• CO stretching of ethers between 1070 and 1150
  cm-1 (strong)

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Infrared Spectrum of Dipropyl Ether
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1H NMR of Ethers

• HCO proton is deshielded by O range is?
  3.2-4.0 ppm.

? 1.4 ppm
? 0.8 ppm
? 0.8 ppm
CH3CH2CH2OCH2CH2CH3
? 3.2 ppm
Epoxide ring protons slightly more shielded ?
2.5 ppm.
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Dipropyl Ether
CH3CH2CH2OCH2CH2CH3
Chemical shift (?, ppm)
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1H NMR of Sulfides

• HCS proton is less deshielded than HCO.

CH3 CH2 CH2 SCH2 CH2 CH3
? 2.5 ppm
Oxidation of sulfides to sulfoxide deshields
anadjacent CH proton by 0.3-0.5 ppm.
Anadditional 0.3-0.5 ppm downfield shift
occurson oxidation of the sulfoxide to the
sulfone.
60
13C NMR of Ethers and Epoxides
Carbons of COC appear in the range? 57-87 ppm.