16.9 preparation of epoxides: a review and a preview

16.916.9

Preparation of Epoxides:Preparation of Epoxides:

A Review and a PreviewA Review and a Preview

Epoxides are prepared by two major methods.Epoxides are prepared by two major methods.Both begin with alkenes.Both begin with alkenes.

reaction of alkenes with peroxy acidsreaction of alkenes with peroxy acids(Section 6.18)(Section 6.18)

conversion of alkenes to vicinalconversion of alkenes to vicinalhalohydrins, followed by treatmenthalohydrins, followed by treatmentwith base (Section 16.10)with base (Section 16.10)

Preparation of EpoxidesPreparation of Epoxides

16.1016.10

Conversion of Vicinal HalohydrinsConversion of Vicinal Halohydrins

to Epoxidesto Epoxides

HHOOHH

BrBrHH

NaOHNaOH

HH22OO

(81%)(81%)

HH

HH

OO

ExampleExample

OO

BrBr

HHHH

••••••••

••••

•••• ••••••••––

HHOOHH

BrBrHH

NaOHNaOH

HH22OO

(81%)(81%)

HH

HH

OO

ExampleExample

via:via:

antianti

additionaddition

Epoxidation via Vicinal HalohydrinsEpoxidation via Vicinal Halohydrins

BrBr22

HH22OO

OOHH

BrBr

antianti

additionadditioninversioninversion


BrBr22

HH22OO

OOHH

NaOHNaOH

corresponds to overall syn addition ofcorresponds to overall syn addition ofoxygen to the double bondoxygen to the double bond

BrBr

OO

antianti



BrBr22

HH22OO

OOHH

NaOHNaOH


BrBr

HHHH33CCCHCH33

OOHH

HH

CHCH33

HH33CC

HH

antianti



BrBr22

HH22OO

OOHH

NaOHNaOH


BrBr

HHHH33CCCHCH33

OO

HHHHHH33CC

CHCH33

HH

HH

CHCH33

HH33CC

HH

16.1116.11Reactions of Epoxides:Reactions of Epoxides:

A Review and a PreviewA Review and a Preview

All reactions involve nucleophilic attack All reactions involve nucleophilic attack at carbon and lead to opening of the ring.at carbon and lead to opening of the ring.

An example is the reaction of ethylene oxide An example is the reaction of ethylene oxide with a Grignard reagent (discussed in Section 15.4 with a Grignard reagent (discussed in Section 15.4 as a method for the synthesis of alcohols).as a method for the synthesis of alcohols).

Reactions of EpoxidesReactions of Epoxides

Reaction of Grignard ReagentsReaction of Grignard Reagentswith Epoxideswith Epoxides

CHCH22 CHCH22 OMgXOMgX

HH33OO++

HH22CC CHCH22

OO

RR MgXMgX RR

RRCHCH22CHCH22OHOH

HH22CC CHCH22

OO

++

1. diethyl ether1. diethyl ether2. H2. H33OO++

(71%)(71%)

Example Example

CHCH22MgClMgCl

CHCH22CHCH22CHCH22OOHH

Reactions of epoxides involve attack by aReactions of epoxides involve attack by anucleophile and proceed with ring-opening.nucleophile and proceed with ring-opening.For ethylene oxide:For ethylene oxide:

Nu—H Nu—H ++

Nu—Nu—CHCH22CHCH22O—O—HH

HH22CC CHCH22

OO

In general...In general...

For epoxides where the two carbons of theFor epoxides where the two carbons of thering are differently substituted:ring are differently substituted:

In general...In general...

CHCH22

OO

CC

RR

HH

Nucleophiles attack hereNucleophiles attack herewhen the reaction iswhen the reaction iscatalyzed by acids:catalyzed by acids:

Anionic nucleophilesAnionic nucleophilesattack here:attack here:

16.1216.12

Nucleophilic Ring-OpeningNucleophilic Ring-Opening

Reactions of EpoxidesReactions of Epoxides

NaOCHNaOCH22CHCH33

CHCH33CHCH22OHOH

(50%)(50%)

ExampleExample

OO

HH22CC CHCH22

CHCH33CHCH22OO CHCH22CHCH22OOHH

••••••••OO

HH22CC CHCH22

CHCH33CHCH22 OO••••

•••• ••••––

MechanismMechanism

••••••••OO

HH22CC CHCH22


•••• ••••––

––••

••CHCH33CHCH22 OO

••••

•••• ••••CHCH22CHCH22 OO••••

MechanismMechanism

••••••••OO

HH22CC CHCH22


•••• ••••––

––••


••••

•••• ••••CHCH22CHCH22 OO••••

OO CHCH22CHCH33••••

••

••

––

HH

MechanismMechanism

••••••••OO

HH22CC CHCH22


•••• ••••––

––••


••••

•••• ••••CHCH22CHCH22 OO••••

••


••••

••••CHCH22CHCH22 OO

••••HH OO CHCH22CHCH33

••••••

••••

••

––

OO CHCH22CHCH33••••

••

••

––

HH

MechanismMechanism

(99%)(99%)

ExampleExample

OO

HH22CC CHCH22

KSCHKSCH22CHCH22CHCH22CHCH33

ethanol-water, 0°Cethanol-water, 0°C

CHCH22CHCH22OOHHCHCH33CHCH22CHCH22CHCH22SS

StereochemistryStereochemistry

Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophileattacked by nucleophile

Suggests SSuggests SNN2-like transition state2-like transition state

NaOCHNaOCH22CHCH33

CHCH33CHCH22OHOHOO

HHHH

HHOOHH

HH

OCHOCH22CHCH33

(67%)(67%)

NHNH33

HH22OO

(70%)(70%)

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHHH22NN


Suggests SSuggests SNN2-like transition state2-like transition state

NHNH33

HH22OO

(70%)(70%)

++ --

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHHH22NN

HH33NN OO

HH33CCHH

HH33CCHH

NaNaOCHOCH33

CHCH33OHOHCHCH33CCHH CCHCCH33

CHCH33

OOHH

CHCH33OO

(53%)(53%)

CCCC

HH

HH33CC CHCH33

CHCH33OO

consistent with Sconsistent with SNN2-like transition state2-like transition state

Anionic nucleophile attacks less-crowded carbonAnionic nucleophile attacks less-crowded carbon

Anionic nucleophile attacks less-crowded carbonAnionic nucleophile attacks less-crowded carbon

1. diethyl ether1. diethyl ether2. H2. H33OO++

MgBrMgBr

++

OO

HH22CC CHCHCHCH33

CHCH22CHCHCHCH33

OOHH

(60%)(60%)

(90%)(90%)

Hydride attacksHydride attacksless-crowdedless-crowded

carboncarbon

Lithium aluminum hydride reduces epoxidesLithium aluminum hydride reduces epoxides

OO

HH22CC CH(CHCH(CH22))77CHCH33

1. LiAlH1. LiAlH44, diethyl ether, diethyl ether

2. H2. H22OO

OOHH

HH33CC CH(CHCH(CH22))77CHCH33

16.13Acid-Catalyzed Ring-Opening

Reactions of Epoxides

ExampleExample

OO

HH22CC CHCH22CHCH33CHCH22OOCHCH22CHCH22OOHH

(87-92%)(87-92%)

CHCH33CHCH22OCHOCH22CHCH22OCHOCH22CHCH33 formed only on heating formed only on heating

and/or longer reaction times and/or longer reaction times

CHCH33CHCH22OHOH

HH22SOSO44, 25°C, 25°C

ExampleExample

OO

HH22CC CHCH22 HBrHBr

10°C10°CBrBrCHCH22CHCH22OOHH

(87-92%)(87-92%)

BrCHBrCH22CHCH22Br formed only on heating and/or Br formed only on heating and/or

longer reaction timeslonger reaction times

MechanismMechanism

••••OO

HH22CC CHCH22++

HHBrBr••••

••••••••

––••••

••••OO

HH22CC CHCH22++

••••HHBrBr

••••••••

••••

MechanismMechanism

••••OO

HH22CC CHCH22++

HH

••••

••

••OO••••

BrBr

CHCH22CHCH22 HH

••••••••

BrBr••••

••••••••

––••••

••••OO

HH22CC CHCH22++

••••HHBrBr

••••••••

••••

Figure 16.6 Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene OxideAcid-Catalyzed Hydrolysis of Ethylene Oxide

••••OO

HH22CC CHCH22++

HH

••••OO

HH22CC CHCH22++

••••

OO••••

HH

HH

HH++ OO••••

HH

HH

••••

Step 1Step 1Step 1Step 1


••••OO

HH22CC CHCH22

OO••••

••••

++

HH

HH

HH


••••++

••

••OO

OO

CHCH22CHCH22

HH

HH

HH

••

••


OO••••

••••

HH

HH


••••++

••

••OO

OO

CHCH22CHCH22

HH

HH

HH

OO ••••

HH

HH++

HH

••••

••

••OO

OO

CHCH22CHCH22

HH

HH

••••

••

••

••

••

Acid-Catalyzed Ring Opening of EpoxidesAcid-Catalyzed Ring Opening of Epoxides

nucleophile attacks more substituted carbon nucleophile attacks more substituted carbon of protonated epoxideof protonated epoxide

inversion of configuration at site of nucleophilic inversion of configuration at site of nucleophilic attackattack

Characteristics:Characteristics:

CHCH33OHOHCHCH33CHCH CCCHCH33

CHCH33OOHH

OCHOCH33

(76%)(76%)

CCCC

HH

HH33CC CHCH33

CHCH33OO

consistent with carbocation character at consistent with carbocation character at transition statetransition state

Nucleophile attacks more-substituted carbonNucleophile attacks more-substituted carbon

HH22SOSO44



(73%)(73%)

HH

HH

OO HBrHBr

HHOOHH

BrBrHH

(57%)(57%)

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHCHCH33OO


CHCH33OHOH

HH22SOSO44

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHCHCH33OOCHCH33OHOH

HH22SOSO44

++ ++CHCH33OO OO

HH33CCHH

HH33CCHH

HH++

HH

HH22OO

HClOHClO44

(80%)(80%)

anti-Hydroxylation of Alkenesanti-Hydroxylation of Alkenes

HH

HH

CHCH33COCOOOHH

OO

HH

HH

OO

HHOOHH

OHOHHH

16.9 preparation of epoxides: a review and a preview

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