Dr. Wolf's CHM 201 & 202 16-1
Chapter 16Ethers, Epoxides, and Sulfides
Dr. Wolf's CHM 201 & 202 16-2
Nomenclature of Ethers, Epoxides, and Sulfides
Dr. Wolf's CHM 201 & 202 16-3
name as alkoxy derivatives of alkanesname as alkoxy derivatives of alkanes
CHCH33OOCHCH2 2 CHCH33
methoxymethoxyethaneethane
CHCH33CHCH22OOCHCH2 2 CHCH33
ethoxyethoxyethaneethane
CHCH33CHCH22OOCHCH22CHCH22CHCH22ClCl
1-chloro-3-1-chloro-3-ethoxyethoxypropanepropane
Substitutive IUPAC Names of EthersSubstitutive IUPAC Names of EthersSubstitutive IUPAC Names of EthersSubstitutive IUPAC Names of Ethers
Dr. Wolf's CHM 201 & 202 16-4
name the groups attached to oxygen in name the groups attached to oxygen in alphabetical order as separate words; "ether" is alphabetical order as separate words; "ether" is last wordlast word
CHCH33OOCHCH2 2 CHCH33
ethylethyl methylmethyl ether ether
CHCH33CHCH22OOCHCH2 2 CHCH33
didiethylethyl ether ether
CHCH33CHCH22OOCHCH22CHCH22CHCH22ClCl
3-chloropropyl3-chloropropyl ethylethyl ether ether
Functional Class IUPAC Names of EthersFunctional Class IUPAC Names of EthersFunctional Class IUPAC Names of EthersFunctional Class IUPAC Names of Ethers
Dr. Wolf's CHM 201 & 202 16-5
name as alkylthio derivatives of alkanesname as alkylthio derivatives of alkanes
CHCH33SSCHCH2 2 CHCH33
methylthiomethylthioethaneethane
CHCH33CHCH22SSCHCH2 2 CHCH33
ethylthioethylthioethaneethane
(methylthio)cyclopentane(methylthio)cyclopentane
Substitutive IUPAC Names of SulfidesSubstitutive IUPAC Names of SulfidesSubstitutive IUPAC Names of SulfidesSubstitutive IUPAC Names of Sulfides
SCHSCH33
Dr. Wolf's CHM 201 & 202 16-6
cyclopentyl cyclopentyl methylmethyl sulfide sulfide
analogous to ethers, but replace “ether” as lastanalogous to ethers, but replace “ether” as lastword in the name by “sulfide.”word in the name by “sulfide.”
CHCH33SSCHCH2 2 CHCH33
ethylethyl methyl sulfide methyl sulfide
CHCH33CHCH22SSCHCH2 2 CHCH33
didiethylethyl sulfide sulfide
Functional Class IUPAC Names of SulfidesFunctional Class IUPAC Names of SulfidesFunctional Class IUPAC Names of SulfidesFunctional Class IUPAC Names of Sulfides
SSCHCH33
Dr. Wolf's CHM 201 & 202 16-7
OxiraneOxirane(Ethylene oxide)(Ethylene oxide)
OxetaneOxetane OxolaneOxolane(tetrahydrofuran)(tetrahydrofuran)
OxaneOxane(tetrahydropyran)(tetrahydropyran)
1,4-Dioxane1,4-Dioxane
Names of Cyclic EthersNames of Cyclic EthersNames of Cyclic EthersNames of Cyclic Ethers OO OO OO
OO
OO
OO
Dr. Wolf's CHM 201 & 202 16-8
ThiiraneThiirane ThietaneThietane ThiolaneThiolane
ThianeThiane
Names of Cyclic SulfidesNames of Cyclic SulfidesNames of Cyclic SulfidesNames of Cyclic Sulfides SS SS SS
SS
Dr. Wolf's CHM 201 & 202 16-9
bent geometry at oxygen analogousbent geometry at oxygen analogousto water and alcohols, to water and alcohols,
i.e.i.e. spsp33 hybidizationhybidization
Structure and Bondingin
Ethers and Epoxides
Dr. Wolf's CHM 201 & 202 16-10
112°112°
HHOO
HH
105°105° 108.5°108.5°
(CH(CH33))33CCOO
C(CHC(CH33))33
132°132°
HHOO
CHCH33
CHCH33
OOCHCH33
Bond angles at oxygen are sensitiveBond angles at oxygen are sensitiveto steric effectsto steric effects
Bond angles at oxygen are sensitiveBond angles at oxygen are sensitiveto steric effectsto steric effects
Dr. Wolf's CHM 201 & 202 16-11
most stable conformation of diethyl ethermost stable conformation of diethyl etherresembles pentaneresembles pentane
An oxygen atom affects geometry in much theAn oxygen atom affects geometry in much thesame way as a CHsame way as a CH22 group group
An oxygen atom affects geometry in much theAn oxygen atom affects geometry in much thesame way as a CHsame way as a CH22 group group
Dr. Wolf's CHM 201 & 202 16-12
most stable conformation of tetrahydropyranmost stable conformation of tetrahydropyranresembles cyclohexaneresembles cyclohexane
An oxygen atom affects geometry in much theAn oxygen atom affects geometry in much thesame way as a CHsame way as a CH22 group group
An oxygen atom affects geometry in much theAn oxygen atom affects geometry in much thesame way as a CHsame way as a CH22 group group
Dr. Wolf's CHM 201 & 202 16-13
Physical Properties of Ethers
Dr. Wolf's CHM 201 & 202 16-14
boiling pointboiling point
36°C36°C
35°C35°C
117°C117°C
Ethers resemble alkanes more than alcoholsEthers resemble alkanes more than alcoholswith respect to boiling pointwith respect to boiling point
Ethers resemble alkanes more than alcoholsEthers resemble alkanes more than alcoholswith respect to boiling pointwith respect to boiling point
OO OHOH
Intermolecular hydrogenIntermolecular hydrogenbonding possible in bonding possible in alcohols; not possible alcohols; not possible in alkanes or ethers.in alkanes or ethers.
Dr. Wolf's CHM 201 & 202 16-15
solubility in water (g/100 mL)solubility in water (g/100 mL)
very smallvery small
99
7.57.5
Ethers resemble alcohols more than alkanesEthers resemble alcohols more than alkaneswith respect to solubility in waterwith respect to solubility in water
Ethers resemble alcohols more than alkanesEthers resemble alcohols more than alkaneswith respect to solubility in waterwith respect to solubility in water
OO OHOH
Hydrogen bonding toHydrogen bonding towater possible for etherswater possible for ethersand alcohols; not and alcohols; not possible for alkanes.possible for alkanes.
Dr. Wolf's CHM 201 & 202 16-16
Crown Ethers
Dr. Wolf's CHM 201 & 202 16-17
structurestructurecyclic polyethers derived from repeating cyclic polyethers derived from repeating
—OCH—OCH22CHCH22— units— units
propertiespropertiesform stable complexes with metal ions form stable complexes with metal ions
applicationsapplicationssynthetic reactions involving anions synthetic reactions involving anions
Crown EthersCrown EthersCrown EthersCrown Ethers
Dr. Wolf's CHM 201 & 202 16-18
18-Crown-618-Crown-618-Crown-618-Crown-6
negative charge concentrated in cavity inside negative charge concentrated in cavity inside the moleculethe molecule
OO
OO OO
OO
OO
OO
Dr. Wolf's CHM 201 & 202 16-19
18-Crown-618-Crown-618-Crown-618-Crown-6
negative charge concentrated in cavity inside negative charge concentrated in cavity inside the moleculethe molecule
OO
OO OO
OO
OO
OO
Dr. Wolf's CHM 201 & 202 16-20
OO
OO OO
OO
OO
OO
18-Crown-618-Crown-618-Crown-618-Crown-6
forms stable Lewis acid/Lewis base complex forms stable Lewis acid/Lewis base complex with Kwith K++
K+
Dr. Wolf's CHM 201 & 202 16-21
OO
OO OO
OO
OO
OO
18-Crown-618-Crown-618-Crown-618-Crown-6
forms stable Lewis acid/Lewis base complex forms stable Lewis acid/Lewis base complex with Kwith K++
K+
Dr. Wolf's CHM 201 & 202 16-22
not soluble in benzenenot soluble in benzene
Ion-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and Solubility
KK++FF––
Dr. Wolf's CHM 201 & 202 16-23
Ion-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and Solubility OO
OO OO
OO
OO
OO
KK++FF––
add 18-crown-6add 18-crown-6
benzenebenzene
Dr. Wolf's CHM 201 & 202 16-24
Ion-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and Solubility OO
OO OO
OO
OO
OO
OO
OO OO
OO
OO
OO
K+
18-crown-6 complex of K18-crown-6 complex of K+ + dissolves dissolves in benzenein benzene
benzenebenzene
FF––
Dr. Wolf's CHM 201 & 202 16-25
Ion-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and SolubilityIon-Complexing and Solubility OO
OO OO
OO
OO
OO
++ FF––
OO
OO OO
OO
OO
OO
K+
FF– – carried into benzene carried into benzene to preserve electroneutralityto preserve electroneutrality
benzenebenzene
Dr. Wolf's CHM 201 & 202 16-26
Application to organic synthesisApplication to organic synthesisApplication to organic synthesisApplication to organic synthesis
Complexaton of KComplexaton of K++ by 18-crown-6 "solubilizes" by 18-crown-6 "solubilizes" salt in benzenesalt in benzene
Anion of salt is in a relatively unsolvated state Anion of salt is in a relatively unsolvated state in benzene (sometimes referred to as a in benzene (sometimes referred to as a "naked anion")"naked anion")
Unsolvated anion is very reactiveUnsolvated anion is very reactive
Only catalytic quantities of 18-crown-6 are Only catalytic quantities of 18-crown-6 are neededneeded
Dr. Wolf's CHM 201 & 202 16-27
ExampleExampleExampleExample
CHCH33(CH(CH22))66CHCH22BrBrKKFF
18-crown-618-crown-6benzenebenzene
CHCH33(CH(CH22))66CHCH22FF
(92%)(92%)
Dr. Wolf's CHM 201 & 202 16-28
Preparation of EthersPreparation of Ethers
Dr. Wolf's CHM 201 & 202 16-29
Acid-Catalyzed Condensation of Alcohols*Acid-Catalyzed Condensation of Alcohols*Acid-Catalyzed Condensation of Alcohols*Acid-Catalyzed Condensation of Alcohols*
2CH2CH33CHCH22CHCH22CHCH22OHOH
HH22SOSO44, 130°C, 130°C
CHCH33CHCH22CHCH22CHCH22OCHOCH22CHCH22CHCH22CHCH33
(60%)(60%)
*Discussed earlier in Section 15.7*Discussed earlier in Section 15.7
Dr. Wolf's CHM 201 & 202 16-30
HH++
(CH(CH33))22C=CHC=CH22 + CH + CH33OHOH (CH(CH33))33COCHCOCH33
terttert-Butyl methyl ether-Butyl methyl ether
Addition of Alcohols to AlkenesAddition of Alcohols to AlkenesAddition of Alcohols to AlkenesAddition of Alcohols to Alkenes
Dr. Wolf's CHM 201 & 202 16-31
Think SThink SNN2!2!
primaryprimary alkyl halide + alkoxide nucleophile alkyl halide + alkoxide nucleophile
The Williamson Ether SynthesisThe Williamson Ether Synthesis
Dr. Wolf's CHM 201 & 202 16-32
(71%)(71%)
CHCH33CHCH22CHCH22CHCH22OONa + Na + CHCH33CHCH22II
CHCH33CHCH22CHCH22CHCH22OOCHCH22CHCH3 3 + NaI+ NaI
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 16-33
++ CHCH33CHCHCHCH33
ONaONa
(84%)(84%)
Another ExampleAnother ExampleAnother ExampleAnother Example
CHCH22ClCl
CHCH22OCHCHOCHCH33
CHCH33
Dr. Wolf's CHM 201 & 202 16-34
++ CHCH33CHCHCHCH33
ONaONa
(84%)(84%)
Another ExampleAnother ExampleAnother ExampleAnother Example
CHCH22ClCl
CHCH22OCHCHOCHCH33
CHCH33
Alkyl halide must Alkyl halide must
be primarybe primary
Alkoxide ion can be derived Alkoxide ion can be derived
from primary, secondary, or from primary, secondary, or
tertiary alcoholtertiary alcohol
Dr. Wolf's CHM 201 & 202 16-35
CHCH22OCHCHOCHCH33
CHCH33
CHCH22ClCl ++ CHCH33CHCHCHCH33
ONaONa
(84%)(84%)
CHCH33CHCHCHCH33
OHOH
NaNa
CHCH22OHOH
HClHCl
Origin of ReactantsOrigin of ReactantsOrigin of ReactantsOrigin of Reactants
Dr. Wolf's CHM 201 & 202 16-36
CHCH22ONaONa ++ CHCH33CHCHCHCH33
BrBr
What happens if the alkyl halide is not primary?What happens if the alkyl halide is not primary?What happens if the alkyl halide is not primary?What happens if the alkyl halide is not primary?
Dr. Wolf's CHM 201 & 202 16-37
CHCH22ONaONa ++ CHCH33CHCHCHCH33
BrBr
CHCH22OHOH ++ HH22CC CHCHCHCH33
Elimination by the E2 mechanism becomesElimination by the E2 mechanism becomesthe major reaction pathway.the major reaction pathway.
What happens if the alkyl halide is not primary?What happens if the alkyl halide is not primary?What happens if the alkyl halide is not primary?What happens if the alkyl halide is not primary?
Dr. Wolf's CHM 201 & 202 16-38
Reactions of Ethers:Reactions of Ethers:
A Review and a PreviewA Review and a Preview
Dr. Wolf's CHM 201 & 202 16-39
No reactions of ethers encountered to this No reactions of ethers encountered to this point.point.
Ethers are relatively unreactive.Ethers are relatively unreactive.
Their low level of reactivity is one reason why Their low level of reactivity is one reason why ethers are often used as solvents in chemical ethers are often used as solvents in chemical reactions.reactions.
Ethers oxidize in air to form explosive Ethers oxidize in air to form explosive hydroperoxides and peroxides.hydroperoxides and peroxides.
Summary of reactions of ethersSummary of reactions of ethersSummary of reactions of ethersSummary of reactions of ethers
Dr. Wolf's CHM 201 & 202 16-40
Acid-Catalyzed Cleavage of Ethers
Dr. Wolf's CHM 201 & 202 16-41
CHCH33CHCHCHCH22CHCH33
OCHOCH33
CHCH33BrBrHHBrBr
++
(81%)(81%)
CHCH33CHCHCHCH22CHCH33
BrBrheatheat
ExampleExampleExampleExample
Dr. Wolf's CHM 201 & 202 16-42
CHCH33
CHCH33CHCHCHCH22CHCH33
OO ••••••••
CHCH33CHCHCHCH22CHCH33
OOCHCH33 HH
++
••••
HH BrBr ••••••••
••••
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 16-43••••
CHCH33
••••••••
CHCH33BrBr
CHCH33CHCHCHCH22CHCH33
OO ••••••••
CHCH33CHCHCHCH22CHCH33
OOHH
••••••••
CHCH33CHCHCHCH22CHCH33
OOCHCH33 HH
++
••••BrBr––
•••••••• ••••
••••
HH BrBr ••••••••
••••
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 16-44••••
CHCH33CHCHCHCH22CHCH33
BrBrCHCH33
••••••••
CHCH33BrBr
HHBrBr
CHCH33CHCHCHCH22CHCH33
OO ••••••••
CHCH33CHCHCHCH22CHCH33
OOHH
••••••••
CHCH33CHCHCHCH22CHCH33
OOCHCH33 HH
++
••••BrBr––
•••••••• ••••
••••
HH BrBr ••••••••
••••
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 16-45
HIHI
150°C150°CICHICH22CHCH22CHCH22CHCH22II
(65%)(65%)
OO
Cleavage of Cyclic EthersCleavage of Cyclic EthersCleavage of Cyclic EthersCleavage of Cyclic Ethers
Dr. Wolf's CHM 201 & 202 16-46
HIHI
ICHICH22CHCH22CHCH22CHCH22II
OO••••
••••
HH
OO••••
++
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 16-47
HIHI
ICHICH22CHCH22CHCH22CHCH22II
OO
HH
OO••••
••••
HH
OO••••
++
•••• II ••••••••
••••
–– •••• II••••
••••••••
••••
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 16-48
HIHI
ICHICH22CHCH22CHCH22CHCH22II
OO
HH
OO••••
••••
HH
OO••••
++
•••• II ••••••••
••••
–– •••• II••••
••••
HIHI
••••••••
MechanismMechanismMechanismMechanism
Dr. Wolf's CHM 201 & 202 16-49
Preparation of Epoxides:Preparation of Epoxides:
A Review and a PreviewA Review and a Preview
Dr. Wolf's CHM 201 & 202 16-50
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 6.19)(Section 6.19)
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 EpoxidesPreparation of EpoxidesPreparation of Epoxides
Dr. Wolf's CHM 201 & 202 16-51
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
Reactions 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
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
Acid-Catalyzed Ring-OpeningReactions 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%)
CC
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
HH22SOSO44C
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
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
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
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
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
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
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