View
225
Download
0
Category
Tags:
Preview:
Citation preview
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
ExampleExampleExampleExample
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
Epoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal Halohydrins
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
additionadditioninversioninversion
Epoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal Halohydrins
BrBr22
HH22OO
OOHH
NaOHNaOH
corresponds to overall syn addition ofcorresponds to overall syn addition ofoxygen to the double bondoxygen to the double bond
BrBr
HHHH33CCCHCH33
OOHH
HH
CHCH33
HH33CC
HH
Dr. Wolf's CHM 201 & 202 16-57
antianti
additionadditioninversioninversion
Epoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal HalohydrinsEpoxidation via Vicinal Halohydrins
BrBr22
HH22OO
OOHH
NaOHNaOH
corresponds to overall syn addition ofcorresponds to overall syn addition ofoxygen to the double bondoxygen to the double bond
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%)
ExampleExampleExampleExample
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••••
•••• ••••––
––CHCH33CHCH22 OO
••••
•••• ••••CHCH22CHCH22 OO••••
MechanismMechanism ••••
Dr. Wolf's CHM 201 & 202 16-68
••••••••OO
HH22CC CHCH22
CHCH33CHCH22 OO••••
•••• ••••––
––CHCH33CHCH22 OO
••••
•••• ••••CHCH22CHCH22 OO
OO CHCH22CHCH33••••
HH
MechanismMechanism ••••
••••
••••
Dr. Wolf's CHM 201 & 202 16-69
••••••••OO
HH22CC CHCH22
CHCH33CHCH22 OO••••
•••• ••••––
––CHCH33CHCH22 OO
••••
•••• ••••CHCH22CHCH22 OO••••
CHCH33CHCH22 OO••••
••••CHCH22CHCH22 OO
••••HH OO CHCH22CHCH33
••••––
OO CHCH22CHCH33••••
HH
MechanismMechanism ••••
••••
•••• ••••
••••
Dr. Wolf's CHM 201 & 202 16-70
(99%)(99%)
ExampleExampleExampleExample
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
StereochemistryStereochemistryStereochemistryStereochemistry
HH33CC CHCH33
HH33CC CHCH33
OOHH
HHHH
HH OHOHHH22NN
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
Dr. Wolf's CHM 201 & 202 16-73
NHNH33
HH22OO
(70%)(70%)
++ --
RR
SS
RR
RR
StereochemistryStereochemistryStereochemistryStereochemistry
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
ExampleExampleExampleExample
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
ExampleExampleExampleExample
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
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
OO••••
••••
++
HHHH
HH
Step 2Step 2Step 2Step 2
••••++
OO
OO
CHCH22CHCH22
HH
HH
HH
••••
••••
Dr. Wolf's CHM 201 & 202 16-84
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••••
••••
HH
HH
Step 3Step 3Step 3Step 3
••••++
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
StereochemistryStereochemistryStereochemistryStereochemistry
Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophileattacked by nucleophile
(73%)(73%)
HH
HH
OO HBrHBr
HHOOHH
BrBrHH
Dr. Wolf's CHM 201 & 202 16-88
(57%)(57%)
RR
SS
RR
RR
StereochemistryStereochemistryStereochemistryStereochemistry
HH33CC CHCH33
HH33CC CHCH33
OOHH
HHHH
HH OHOHCHCH33OO
Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophileattacked by nucleophile
CHCH33OHOH
HH22SOSO44
Dr. Wolf's CHM 201 & 202 16-89
RR
SS
RR
RR
StereochemistryStereochemistryStereochemistryStereochemistry
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'
••••RR SS R'R'
••••
••••RR SS R'R'
OO ••••••••••••
––
++RR SS R'R'
OO ••••••••••••
––
++++
OO •••••••••••• ––
sulfidesulfide sulfoxidesulfoxide sulfonesulfone
Dr. Wolf's CHM 201 & 202 16-99
ExampleExampleExampleExample
••••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
ExampleExampleExampleExample
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
ExampleExampleExampleExample
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
Recommended