16.9 Preparation of Epoxides: A Review and a Preview

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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(Section
  6.18)
• conversion of alkenes to vicinalhalohydrins,
  followed by treatmentwith base (Section 16.10)

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16.10Conversion of Vicinal Halohydrinsto
Epoxides
4
Example
H
NaOH
O
H2O
H
(81)
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Example
H
NaOH
O
H2O
H
(81)


O
via


H
H
Br



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Epoxidation via Vicinal Halohydrins
Br
Br2
H2O
OH
antiaddition
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Epoxidation via Vicinal Halohydrins
Br
Br2
NaOH
H2O
O
OH
antiaddition
inversion

• corresponds to overall syn addition ofoxygen to
  the double bond

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Epoxidation via Vicinal Halohydrins
Br
H3C
Br2
H
NaOH
H3C
H
CH3
H
H2O
H
O
CH3
OH
antiaddition
inversion

• corresponds to overall syn addition ofoxygen to
  the double bond

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Epoxidation via Vicinal Halohydrins
Br
H3C
Br2
H3C
H
H
NaOH
H3C
H
H
CH3
CH3
H
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 Section
  15.4 as a method for the synthesis of alcohols).

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Reaction of Grignard Reagentswith Epoxides
R
CH2
CH2
OMgX

H3O
RCH2CH2OH
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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
NuCH2CH2OH
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In general...
For epoxides where the two carbons of thering
are differently substituted
Nucleophiles attack herewhen the reaction
iscatalyzed by acids
Anionic nucleophilesattack here
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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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Mechanism



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Mechanism



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Mechanism





CH3CH2
O
O
CH2CH2
H


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Example
KSCH2CH2CH2CH3
ethanol-water, 0C
(99)
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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
d
d-
O
H3N
H
H3C
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Anionic nucleophile attacks less-crowded carbon
NaOCH3
CH3OH
(53)

• consistent with SN2-like transition state

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Anionic nucleophile attacks less-crowded carbon

1. diethyl ether 2. H3O
(60)
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Lithium aluminum hydride reduces epoxides
Hydride attacksless-crowdedcarbon
1. LiAlH4, diethyl ether 2. H2O
(90)
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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

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Mechanism

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Mechanism

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Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 1
H2C
CH2
H2C
CH2


O
O


H

H
O


H
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Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 2

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Figure 16.6 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
OCH3
CH3OH
CH3CH
CCH3
H2SO4
CH3
OH
(76)

• consistent with carbocation character at
  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
d
d
d
H
O
CH3O
H
H
H3C
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anti-Hydroxylation of Alkenes
H2O
HClO4
H
OH
H
OH
(80)