dr. wolf's chm 201 & 202 16-51 16.10 conversion of vicinal halohydrins to epoxides

Dr. Wolf's CHM 201 & 202 16-51

16.1016.10

Conversion of Vicinal HalohydrinsConversion of Vicinal Halohydrins

to Epoxidesto Epoxides

Dr. Wolf's CHM 201 & 202 16-52

HHOOHH

BrBrHH

NaOHNaOH

HH22OO

(81%)(81%)

HH

HH

OO

ExampleExampleExampleExample

Dr. Wolf's CHM 201 & 202 16-53

OO BrBr

HHHH

••••

••••••••

•••• ••••••••––

HHOOHH

BrBrHH

NaOHNaOH

HH22OO

(81%)(81%)

HH

HH

OO


via:via:

Dr. Wolf's CHM 201 & 202 16-54

antianti

additionaddition

Epoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal Halohydrins

BrBr22

HH22OO

OOHH

BrBr

Dr. Wolf's CHM 201 & 202 16-55

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

Dr. Wolf's CHM 201 & 202 16-56

antianti



BrBr22

HH22OO

OOHH

NaOHNaOH


BrBr

HHHH33CCCHCH33

OOHH

HH

CHCH33

HH33CC

HH

Dr. Wolf's CHM 201 & 202 16-57

antianti



BrBr22

HH22OO

OOHH

NaOHNaOH


BrBr

HHHH33CCCHCH33

OO

HHHHHH33CC

CHCH33

HH

HH

CHCH33

HH33CC

HH

Dr. Wolf's CHM 201 & 202 16-58

16.1116.11Reactions of Epoxides:Reactions of Epoxides:

A Review and a PreviewA Review and a Preview

Dr. Wolf's CHM 201 & 202 16-59

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 EpoxidesReactions of EpoxidesReactions of Epoxides

Dr. Wolf's CHM 201 & 202 16-60

Reaction of Grignard ReagentsReaction of Grignard Reagentswith Epoxideswith Epoxides

Reaction of Grignard ReagentsReaction of Grignard Reagentswith Epoxideswith Epoxides

CHCH22 CHCH22 OMgXOMgX

HH33OO++

HH22CC CHCH22

OO

RR MgXMgX RR

RRCHCH22CHCH22OHOH

Dr. Wolf's CHM 201 & 202 16-61

HH22CC CHCH22

OO

++

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

(71%)(71%)

Example Example Example Example

CHCH22MgClMgCl

CHCH22CHCH22CHCH22OOHH

Dr. Wolf's CHM 201 & 202 16-62

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...In general...In general...

Dr. Wolf's CHM 201 & 202 16-63

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...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:

Dr. Wolf's CHM 201 & 202 16-64

16.1216.12

Nucleophilic Ring-OpeningNucleophilic Ring-Opening

Reactions of EpoxidesReactions of Epoxides

Dr. Wolf's CHM 201 & 202 16-65

NaOCHNaOCH22CHCH33

CHCH33CHCH22OHOH

(50%)(50%)


OO

HH22CC CHCH22

CHCH33CHCH22OO CHCH22CHCH22OOHH

Dr. Wolf's CHM 201 & 202 16-66

••••••••OO

HH22CC CHCH22

CHCH33CHCH22 OO••••

•••• ••••–– MechanismMechanism

Dr. Wolf's CHM 201 & 202 16-67

••••••••OO

HH22CC CHCH22


•••• ••••––

––CHCH33CHCH22 OO

••••

•••• ••••CHCH22CHCH22 OO••••

MechanismMechanism ••••

Dr. Wolf's CHM 201 & 202 16-68

••••••••OO

HH22CC CHCH22


•••• ••••––


••••

•••• ••••CHCH22CHCH22 OO

OO CHCH22CHCH33••••

HH


••••

••••

Dr. Wolf's CHM 201 & 202 16-69

••••••••OO

HH22CC CHCH22


•••• ••••––


••••

•••• ••••CHCH22CHCH22 OO••••


••••CHCH22CHCH22 OO

••••HH OO CHCH22CHCH33

••••––

OO CHCH22CHCH33••••

HH


••••

•••• ••••

••••

Dr. Wolf's CHM 201 & 202 16-70

(99%)(99%)


OO

HH22CC CHCH22

KSCHKSCH22CHCH22CHCH22CHCH33

ethanol-water, 0°Cethanol-water, 0°C

CHCH22CHCH22OOHHCHCH33CHCH22CHCH22CHCH22SS

Dr. Wolf's CHM 201 & 202 16-71

StereochemistryStereochemistryStereochemistryStereochemistry

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

HH

HH HH

OOHH

HH

OCHOCH22CHCH33

(67%)(67%)

Dr. Wolf's CHM 201 & 202 16-72

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

Dr. Wolf's CHM 201 & 202 16-73

NHNH33

HH22OO

(70%)(70%)

++ --

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHHH22NN

HH33NN OO

HH33CCHH

HH33CCHH

Dr. Wolf's CHM 201 & 202 16-74

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

Dr. Wolf's CHM 201 & 202 16-75

Anionic nucleophile attacks less-crowded carbonAnionic nucleophile attacks less-crowded carbonAnionic 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%)

Dr. Wolf's CHM 201 & 202 16-76

(90%)(90%)

Hydride attacksHydride attacksless-crowdedless-crowded

carboncarbon

Lithium aluminum hydride reduces epoxidesLithium aluminum hydride reduces epoxidesLithium 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

Dr. Wolf's CHM 201 & 202 16-77

16.13Acid-Catalyzed Ring-Opening

Reactions of Epoxides

Dr. Wolf's CHM 201 & 202 16-78


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

Dr. Wolf's CHM 201 & 202 16-79


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

Dr. Wolf's CHM 201 & 202 16-80

MechanismMechanism

••••OO

HH22CC CHCH22++

HHBrBr••••

••••••••

––••••

••••OO

HH22CC CHCH22

••••HHBrBr

••••••••

••••

Dr. Wolf's CHM 201 & 202 16-81

MechanismMechanism ••••OO

HH22CC CHCH22++

HH

••••

OO••••

BrBr

CHCH22CHCH22 HH

••••••••

BrBr••••

••••••••

––••••

••••OO

HH22CC CHCH22

••••HHBrBr

••••••••

••••

••••

Dr. Wolf's CHM 201 & 202 16-82

Figure 16.6 Figure 16.6

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

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

Dr. Wolf's CHM 201 & 202 16-83



••••OO

HH22CC CHCH22

OO••••

••••

++

HHHH

HH


••••++

OO

OO

CHCH22CHCH22

HH

HH

HH

••••

••••

Dr. Wolf's CHM 201 & 202 16-84



OO••••

••••

HH

HH


••••++

OO

OO

CHCH22CHCH22

HH

HH

HH

OO ••••

HH

HH++

HH

••••

OO

OO

CHCH22CHCH22

HH

HH

••••

••••

••••

••••

••••

Dr. Wolf's CHM 201 & 202 16-85

Acid-Catalyzed Ring Opening of EpoxidesAcid-Catalyzed Ring Opening of EpoxidesAcid-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:

Dr. Wolf's CHM 201 & 202 16-86

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 carbonNucleophile attacks more-substituted carbonNucleophile attacks more-substituted carbon

HH22SOSO44

Dr. Wolf's CHM 201 & 202 16-86b

CHCH33OHOHCHCH33CHCH CCCHCH33

CHCH33OOHH

OCHOCH33

(76%)(76%)

CC

HH

HH33CC CHCH33

CHCH33OOHH

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

Nucleophile attacks more-substituted carbonNucleophile attacks more-substituted carbonNucleophile attacks more-substituted carbonNucleophile attacks more-substituted carbon

HH22SOSO44C

+

++

Dr. Wolf's CHM 201 & 202 16-87



(73%)(73%)

HH

HH

OO HBrHBr

HHOOHH

BrBrHH

Dr. Wolf's CHM 201 & 202 16-88

(57%)(57%)

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHCHCH33OO


CHCH33OHOH

HH22SOSO44

Dr. Wolf's CHM 201 & 202 16-89

RR

SS

RR

RR


HH33CC CHCH33

HH33CC CHCH33

OOHH

HHHH

HH OHOHCHCH33OOCHCH33OHOH

HH22SOSO44

++ ++CHCH33OO OO

HH33CCHH

HH33CCHH

HH++

HH

Dr. Wolf's CHM 201 & 202 16-90

HH22OO

HClOHClO44

(80%)(80%)

anti-Hydroxylation of Alkenesanti-Hydroxylation of Alkenesanti-Hydroxylation of Alkenesanti-Hydroxylation of Alkenes HH

HH

CHCH33COCOOOHH

OO

HH

HH

OO HHOOHH

OHOHHH

Dr. Wolf's CHM 201 & 202 16-91

16.1416.14

Epoxides in Biological ProcessesEpoxides in Biological Processes

Dr. Wolf's CHM 201 & 202 16-92

are commonare common

are involved in numerous biological processesare involved in numerous biological processes

Naturally Occurring EpoxidesNaturally Occurring EpoxidesNaturally Occurring EpoxidesNaturally Occurring Epoxides

Dr. Wolf's CHM 201 & 202 16-93

enzyme-catalyzed oxygen transfer from Oenzyme-catalyzed oxygen transfer from O22 to alkene to alkene

enzymes are referred to as monooxygenasesenzymes are referred to as monooxygenases

Biosynthesis of EpoxidesBiosynthesis of EpoxidesBiosynthesis of EpoxidesBiosynthesis of Epoxides

++

++

CC CC ++ ++OO22 HH++

CC CC

OO

NADHNADH

HH22OO ++ NADNAD++

enzymeenzyme

Dr. Wolf's CHM 201 & 202 16-94

this reaction is an important step in the biosynthesisthis reaction is an important step in the biosynthesis

of cholesterolof cholesterol

Example: biological epoxidation of squaleneExample: biological epoxidation of squaleneExample: biological epoxidation of squaleneExample: biological epoxidation of squalene

OO22, NADH, NADHmonoxygenasemonoxygenase

OO

Dr. Wolf's CHM 201 & 202 16-95

16.1516.15

Preparation of SulfidesPreparation of Sulfides

Dr. Wolf's CHM 201 & 202 16-96

prepared by nucleophilic substitution (Sprepared by nucleophilic substitution (SNN2)2)

Preparation of RSR'Preparation of RSR'Preparation of RSR'Preparation of RSR'

++ R'R' XXSSRR––

••••••••

••••

••••RR SS R'R'

••••

CHCH33CHCHCHCH CHCH22

ClCl

NaSCHNaSCH33

methanolmethanolCHCH33CHCHCHCH CHCH22

SCHSCH33

Dr. Wolf's CHM 201 & 202 16-97

16.1616.16

Oxidation of Sulfides:Oxidation of Sulfides:

Sulfoxides and SulfonesSulfoxides and Sulfones

Dr. Wolf's CHM 201 & 202 16-98

either the sulfoxide or the sulfone can be isolated either the sulfoxide or the sulfone can be isolated

depending on the oxidizing agent and reactiondepending on the oxidizing agent and reaction

conditionsconditions

Oxidation of RSR'Oxidation of RSR'Oxidation of RSR'Oxidation of RSR'


••••


OO ••••••••••••

––

++RR SS R'R'

OO ••••••••••••

––

++++

OO •••••••••••• ––

sulfidesulfide sulfoxidesulfoxide sulfonesulfone

Dr. Wolf's CHM 201 & 202 16-99


••••SCHSCH33••••

NaIONaIO44

••••SCHSCH33

OO ••••••••••••

––

++

Sodium metaperiodate oxidizes sulfides to sulfoxides and no Sodium metaperiodate oxidizes sulfides to sulfoxides and no further.further.

(91%)(91%)

waterwater

Dr. Wolf's CHM 201 & 202 16-100


HH22OO22

1 equiv of H1 equiv of H22OO2 2 or a peroxy acid or a peroxy acid

gives a sulfoxide, 2 equiv give a gives a sulfoxide, 2 equiv give a sulfone sulfone

(74-78%)(74-78%)

(2 equiv)(2 equiv)

••••SCHSCH••••

CHCH22

SCHSCH

OO ••••••••••••

––

++++

CHCH22

OO •••••••••••• ––

Dr. Wolf's CHM 201 & 202 16-101

16.1716.17

Alkylation of Sulfides:Alkylation of Sulfides:

Sulfonium SaltsSulfonium Salts

Dr. Wolf's CHM 201 & 202 16-102

product is a sulfonium saltproduct is a sulfonium salt

Sulfides can act as nucleophilesSulfides can act as nucleophilesSulfides can act as nucleophilesSulfides can act as nucleophiles

++ R"R" XXSSRR ••••••••

RR SS R"R"••••

R'R' R'R'

++XX––

Dr. Wolf's CHM 201 & 202 16-103


CHCH33(CH(CH22))1010CHCH22SCHSCH33

CHCH33IICHCH33(CH(CH22))1010CHCH22SCHSCH33

CHCH33

++II––

Dr. Wolf's CHM 201 & 202 16-104

Section 16.18Section 16.18

Spectroscopic Analysis of EthersSpectroscopic Analysis of Ethers

Dr. Wolf's CHM 201 & 202 16-105

C—O stretching: 1070 and 1150 cmC—O stretching: 1070 and 1150 cm-1-1 (strong) (strong)

Infrared SpectroscopyInfrared SpectroscopyInfrared SpectroscopyInfrared Spectroscopy

Dr. Wolf's CHM 201 & 202 16-106

2000200035003500 30003000 25002500 1000100015001500 500500

Wave number, cmWave number, cm-1-1

Figure 16.8 Infrared Spectrum of Dipropyl Ether Figure 16.8 Infrared Spectrum of Dipropyl Ether Figure 16.8 Infrared Spectrum of Dipropyl Ether Figure 16.8 Infrared Spectrum of Dipropyl Ether

C—O—CC—O—C

CHCH33CHCH22CHCH22OCHOCH22CHCH22CHCH33

Dr. Wolf's CHM 201 & 202 16-107

HH—C—O proton is deshielded by O; range is—C—O proton is deshielded by O; range is

ca. ca. 3.3-4.0 ppm. 3.3-4.0 ppm.

11H NMRH NMR11H NMRH NMR

CHCH3 3 CCHH22 CHCH2 2 OCHOCH2 2 CCHH22 CHCH33

0.8 ppm0.8 ppm 0.8 ppm0.8 ppm 1.4 ppm1.4 ppm

3.2 ppm3.2 ppm

Dr. Wolf's CHM 201 & 202 16-108

01.02.03.04.05.06.07.08.09.010.0

Chemical shift (Chemical shift (, ppm), ppm)

CHCH3 3 CCHH22 CCHH22 OCOCHH22 CCHH22 CHCH33

Dr. Wolf's CHM 201 & 202 16-109

68.0 ppm68.0 ppm

Carbons of C—O—C appearCarbons of C—O—C appearin the range in the range 57-87 ppm. 57-87 ppm.

26.0 ppm26.0 ppm

1313C NMRC NMR1313C NMRC NMR

OO

Dr. Wolf's CHM 201 & 202 16-110

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

UV-VISUV-VISUV-VISUV-VIS

Dr. Wolf's CHM 201 & 202 16-111

Molecular ion fragments to give oxygen-stabilizedMolecular ion fragments to give oxygen-stabilizedcarbocation.carbocation.

m/z m/z 102102CHCH33CHCH22OO CHCHCHCH22CHCH33

CHCH33

CHCH33CHCH22OO++

CHCH

CHCH33

CHCH33CHCH22OO++

CHCHCHCH22CHCH33

m/z m/z 8787m/z m/z 7373

Mass SpectrometryMass SpectrometryMass SpectrometryMass Spectrometry

••++

••••

•••• ••••

End of Chapter 16

dr. wolf's chm 201 & 202 16-51 16.10 conversion of vicinal halohydrins to epoxides

Documents

reactions of epoxidesdr

overall syn addition

reaction of ethylene

nucleophilic attack

diethyl ether2

anionic nucleophiles

hydride attacks

nucleophilesuggests