chapter 16 ethers, epoxides, and sulfides. 16.5 preparation of ethers
TRANSCRIPT
Chapter 16Chapter 16Ethers, Epoxides, and SulfidesEthers, Epoxides, and Sulfides
16.516.5
Preparation of EthersPreparation of Ethers
Acid-Catalyzed Condensation of AlcoholsAcid-Catalyzed Condensation of Alcohols
2CH2CH33CHCH22CHCH22CHCH22OHOH
HH22SOSO44, 130°C, 130°C
CHCH33CHCH22CHCH22CHCH22OOCHCH22CHCH22CHCH22CHCH33
(60%)(60%)
HH++
(CH(CH33))22C=CHC=CH22 + CH + CH33OHOH (CH(CH33))33COCHCOCH33
terttert-Butyl methyl ether-Butyl methyl ether
terttert-Butyl methyl ether (MTBE) was produced on a-Butyl methyl ether (MTBE) was produced on a
scale exceeding 15 billion pounds per year in the U.S.scale exceeding 15 billion pounds per year in the U.S.
during the 1990s. It is an effective octane rating booster induring the 1990s. It is an effective octane rating booster in
gasoline, but contaminates ground water if allowed togasoline, but contaminates ground water if allowed to
leak from storage tanks. Further use of MTBE is unlikely.leak from storage tanks. Further use of MTBE is unlikely.
Addition of Alcohols to AlkenesAddition of Alcohols to Alkenes
Think SThink SNN2!2!
PrimaryPrimary alkyl halide + alkoxide nucleophile. alkyl halide + alkoxide nucleophile.
16.616.6
The Williamson Ether SynthesisThe Williamson Ether Synthesis
(71%)(71%)
CHCH33CHCH22CHCH22CHCH22OONa +Na + CHCH33CHCH22II
CHCH33CHCH22CHCH22CHCH22OOCHCH22CHCH33 ++ NaI NaI
ExampleExample
Williamson Ether Synthesis Has LimitationsWilliamson Ether Synthesis Has Limitations
1) Alkyl halide must be primary (RCH1) Alkyl halide must be primary (RCH22X).X).2) Alkoxides can be derived from primary, secondary or 2) Alkoxides can be derived from primary, secondary or tertiary alcohols.tertiary alcohols.
OH
O
O Na
BrSN2
SecondaryAlkoxide
PrimaryAlkyl halide
OH
O
O Na
BrSN2
SecondaryAlkoxide
PrimaryAlkyl halide
++ CHCH33CHCHCHCH33
OONaNa
CHCH22ClCl
(84%)(84%)CHCH22OOCHCHCHCH33
CHCH33
Williamson Ether Synthesis Has LimitationsWilliamson Ether Synthesis Has Limitations
1) Alkyl halide must be primary (RCH1) Alkyl halide must be primary (RCH22X).X).2) Alkoxides can be derived from primary, secondary or 2) Alkoxides can be derived from primary, secondary or tertiary alcohols.tertiary alcohols.
The reaction The reaction works particularly works particularly well with benzyl well with benzyl and allyl halides, and allyl halides, which are which are excellent excellent alkylating agents.alkylating agents.
CHCH33CHCHCHCH33
OOHH
NaNa
CHCH22OHOH
HClHCl
CHCH22OOCHCHCHCH33
CHCH33
CHCH22ClCl ++ CHCH33CHCHCHCH33
OONaNa
(84%)(84%)
Origin of ReactantsOrigin of Reactants
What Happens if the Alkyl Halide Is Not Primary?What Happens if the Alkyl Halide Is Not Primary?
CHCH22OONaNa ++ CHCH33CHCHCHCH33
BrBr
CHCH22OOHH ++ HH22CC CHCHCHCH33
Elimination by the E2 mechanism becomesElimination by the E2 mechanism becomes
the major reaction pathway.the major reaction pathway.
16.716.7
Reactions of Ethers:Reactions of Ethers:
A Review and a PreviewA Review and a Preview
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 Ethers
16.816.8Acid-Catalyzed Cleavage of EthersAcid-Catalyzed Cleavage of Ethers
CHCH33CHCHCHCH22CHCH33
OOCHCH33
CHCH33BrBrHHBrBr
++
(81%)(81%)
CHCH33CHCHCHCH22CHCH33
BrBrheatheat
ExampleExample
CHCH33
CHCH33CHCHCHCH22CHCH33
OO ••••••••
HH BrBr ••••••••
••••
CHCH33CHCHCHCH22CHCH33
OOCHCH33 HH++
••••
BrBr––
•••••••• ••••
••••
MechanismMechanism
CHCH33CHCHCHCH22CHCH33
BrBr
HHBrBr
••••
••••••••
CHCH33BrBr
CHCH33CHCHCHCH22CHCH33
OOHH
••••••••
HHII
150°C150°CIICHCH22CHCH22CHCH22CHCH22II
(65%)(65%)
OO
Cleavage of Cyclic EthersCleavage of Cyclic Ethers
OO••••
••••
HHII
HH
OO••••
++
•••• II ••••••••
••••
––
IICHCH22CHCH22CHCH22CHCH22II
HHII
HH
OO•••• II••••
••••••••
••••
MechanismMechanism
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(6.19).(6.19).
Conversion of alkenes to vicinalConversion of alkenes to vicinalhalohydrins (6.18), followed by treatmenthalohydrins (6.18), followed by treatmentwith base (16.10).with base (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
••••••••
••••
•••• ••••••••––
via:via:
Epoxidation via Vicinal HalohydrinsEpoxidation via Vicinal Halohydrins
BrBr22
HH22OO
OOHH
NaOHNaOH
OO
HHHHHH33CC
CHCH33
HH
HH
CHCH33
HH33CC
BrBr
HHHH33CCCHCH33HH
AntiAnti
additionadditionInversionInversion
Corresponds to overall syn addition ofCorresponds to overall syn addition ofoxygen to the double bond.oxygen to the double bond.
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 15.4 with a Grignard reagent (discussed in 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
HH22CC CHCH22
OO
RR MgMgXX
CHCH22 CHCH22 OOMgMgXX
RR
HH33OO++
RRCHCH22CHCH22OOHH
HH22CC CHCH22
OO
++
1. diethyl ether1. diethyl ether2. H2. H33OO++
(71%)(71%)
Example Example
CHCH22MgMgClCl
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 and other good Anionic and other good nucleophiles in non-nucleophiles in non-acidic conditions attack acidic conditions attack here.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••••
•••• ••••––
••
••CHCH33CHCH22 OO
••••
••••CHCH22CHCH22 OO
••••HH OO CHCH22CHCH33
••••••
••••
••
––
MechanismMechanism
––••
••CHCH33CHCH22 OO
••••
•••• ••••CHCH22CHCH22 OO••••
OO CHCH22CHCH33••••
••
••
HH
ExampleExample
OO
HH22CC CHCH22
KSCHKSCH22CHCH22CHCH22CHCH33
ethanol-water, 0°Cethanol-water, 0°C
(99%)(99%)
CHCH22CHCH22OOHHCHCH33CHCH22CHCH22CHCH22SS
StereochemistryStereochemistry
Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophile.attacked by nucleophile.
Suggests SSuggests SNN2-like transition state.2-like transition state.
NaOCHNaOCH22CHCH33
CHCH33CHCH22OHOHOO
HHHH
HHOOHH
HH
OCHOCH22CHCH33
(67%)(67%)
NHNH33
HH22OO
(70%)(70%)
RR
SS
RR
RR
StereochemistryStereochemistry
HH33CC CHCH33
HH33CC CHCH33
OOHH
HHHH
HH OOHHHH22NN
Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophile.attacked by nucleophile.
Suggests SSuggests SNN2-like transition state.2-like transition state.
NHNH33
HH22OO
(70%)(70%)
--
RR
SS
RR
RR
StereochemistryStereochemistry
HH33CC CHCH33
HH33CC CHCH33
OOHH
HHHH
HH OOHHHH22NN
HH33NN OO
HH33CCHH
HH33CCHH
NaNaOCHOCH33
CHCH33OHOHCHCH33CCHH CCHCCH33
CHCH33
OOHH
CHCH33OO
(53%)(53%)
CCCC
HH
HH33CC CHCH33
CHCH33OO
Consistent with SConsistent with SNN2-like transition state.2-like transition state.
Good Nucleophiles Attack Less-Crowded CarbonGood Nucleophiles Attack Less-Crowded Carbon
Good Nucleophiles Attack Less-Crowded CarbonGood Nucleophiles Attack Less-Crowded Carbon
1. diethyl ether1. diethyl ether2. H2. H33OO++
MgMgBrBr
++
OO
HH22CC CHCHCHCH33
CHCH22CHCHCHCH33
OOHH
(60%)(60%)
Hydride anion attacksHydride anion attacksless-crowdedless-crowded
carbon.carbon.
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
(90%)(90%)OOHH
HH33CC CH(CHCH(CH22))77CHCH33
16.1316.13Acid-Catalyzed Ring-OpeningAcid-Catalyzed Ring-Opening
Reactions of EpoxidesReactions of Epoxides
ExampleExample
OO
HH22CC CHCH22CHCH33CHCH22OOCHCH22CHCH22OOHH
(87-92%)(87-92%)
CHCH33CHCH22OCHOCH22CHCH22OCHOCH22CHCH33 formed only on formed only on
heating and/or longer reaction times.heating and/or longer reaction times.
CHCH33CHCH22OHOH
HH22SOSO44, 25°C, 25°C
ExampleExample
OO
HH22CC CHCH22 HHBrBr
10°C10°CBrBrCHCH22CHCH22OOHH
(87-92%)(87-92%)
BrCHBrCH22CHCH22Br formed only on heating and/or Br formed only on heating and/or
longer reaction times with excess HBr.longer reaction times with excess HBr.
MechanismMechanism
BrBr••••
••••••••
––••••
••••
••
••OO••••
BrBr
CHCH22CHCH22 HH
••••••••
••••OO
HH22CC CHCH22
••••HHBrBr
••••••••
••••
••••OO
HH22CC CHCH22++
HH
Acid-Catalyzed Hydrolysis of Ethylene OxideAcid-Catalyzed Hydrolysis of Ethylene Oxide
••••OO
HH22CC CHCH22
••••
OO••••
HH
HH
HH++
••••OO
HH22CC CHCH22++
HHOO••••
HH
HH
••••
Step 1Step 1Step 1Step 1
••••OO
HH22CC CHCH22++
HH
OO
••••••••
HH
HH
Step 2Step 2Step 2Step 2
••••++
••
••OO
OO
CHCH22CHCH22
HH
HH
HH
••
••
Acid-Catalyzed Hydrolysis of Ethylene OxideAcid-Catalyzed Hydrolysis of Ethylene Oxide
Step 3Step 3Step 3Step 3
••••++
••
••OO
OO
CHCH22CHCH22
HH
HH
HH
OO••••
••••
HH
HH
••
••
OO ••••
HH
HH++
HH
••••
••
••OO
OO
CHCH22CHCH22
HH
HH
••••
••
••
Acid-Catalyzed Hydrolysis of Ethylene OxideAcid-Catalyzed Hydrolysis of Ethylene Oxide
Acid-Catalyzed Ring Opening of EpoxidesAcid-Catalyzed Ring Opening of Epoxides
Nucleophile attacks more substituted carbon Nucleophile attacks more substituted carbon of protonated epoxide.of protonated epoxide.
Inversion of configuration at site of nucleophilic Inversion of configuration at site of nucleophilic attack.attack.
Characteristics:Characteristics:
CHCH33OHOH
CCCC
HH
HH33CC CHCH33
CHCH33OO
Consistent with carbocation character of Consistent with carbocation character of transition state.transition state.
Nucleophile Attacks More-Substituted CarbonNucleophile Attacks More-Substituted Carbon
HH22SOSO44
CHCH33CHCH CCCHCH33
CHCH33OOHH
OCHOCH33
(76%)(76%)
StereochemistryStereochemistry
Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophile.attacked by nucleophile.
(73%)(73%)
HH
HH
OO HHBrBr
HHOOHH
BrBrHH
(57%)(57%)
RR
SS
RR
RR
StereochemistryStereochemistry
HH33CC CHCH33
HH33CC CHCH33
OOHH
HHHH
HH OOHHCHCH33OO
CHCH33OHOH
HH22SOSO44
Inversion of configuration at carbon being Inversion of configuration at carbon being attacked by nucleophile.attacked by nucleophile.
RR
SS
RR
RR
StereochemistryStereochemistry
HH33CC CHCH33
HH33CC CHCH33
OOHH
HHHH
HH OHOHCHCH33OOCHCH33OHOH
HH22SOSO44
++ ++CHCH33OO OO
HH33CCHH
HH33CCHH
HH++
HH
anti-Hydroxylation of Alkenesanti-Hydroxylation of Alkenes
HH
HH
CHCH33COCOOOHH
OO
HH
HH
OO
HH22O,O,
HClOHClO44
(80%)(80%)
HHOOHH
OHOHHH
16.1516.15
Preparation of SulfidesPreparation of Sulfides
Prepared by nucleophilic substitution (SPrepared by nucleophilic substitution (SNN2).2).
Preparation of RSR'Preparation of RSR'
++ R'R' XXSSRR––
••••••••
••••
••••RR SS R'R'
••••
CHCH33CHCHCHCH CHCH22
ClCl
NaSCHNaSCH33
methanolmethanolCHCH33CHCHCHCH CHCH22
SCHSCH33
Section 16.18Section 16.18
Spectroscopic AnalysisSpectroscopic Analysis
ofof
Ethers, Epoxides, and SulfidesEthers, Epoxides, and Sulfides
C—O stretching of ethers: between 1070 and C—O stretching of ethers: between 1070 and 1150 cm1150 cm-1-1 (strong) (strong)
Infrared SpectroscopyInfrared Spectroscopy
Infrared Spectrum of Dipropyl Ether Infrared Spectrum of Dipropyl Ether Infrared Spectrum of Dipropyl Ether Infrared Spectrum of Dipropyl Ether
H—C—H—C—OO proton is deshielded by proton is deshielded by OO; range is; range is 3.2-4.0 ppm. 3.2-4.0 ppm.
11H NMR of EthersH NMR of Ethers
CHCH33CCHH22CCHH22OOCCHH22CCHH22CHCH33
0.8 ppm0.8 ppm 0.8 ppm0.8 ppm 1.4 ppm1.4 ppm
3.2 ppm3.2 ppm
Epoxide ring Epoxide ring protons slightly more shielded: protons slightly more shielded: ~2.5 ppm. ~2.5 ppm.
01.02.03.04.05.06.07.08.09.010.0
Chemical shift (Chemical shift (, ppm), ppm)
CHCH33CCHH22CCHH22OCOCHH22CCHH22CHCH33
Dipropyl EtherDipropyl Ether
H—C—H—C—SS proton is less deshielded than H—C— proton is less deshielded than H—C—OO..
11H NMR of SulfidesH NMR of Sulfides
Oxidation of sulfides to sulfoxide deshields anOxidation of sulfides to sulfoxide deshields anadjacent C—H proton by 0.3-0.5 ppm. Anadjacent C—H proton by 0.3-0.5 ppm. Anadditional 0.3-0.5 ppm downfield shift occursadditional 0.3-0.5 ppm downfield shift occurson oxidation of the sulfoxide to the sulfone. on oxidation of the sulfoxide to the sulfone.
2.5 ppm2.5 ppm
CHCH3 3 CCHH22 CHCH2 2 SSCHCH2 2 CCHH22 CHCH33
1313C NMR of Ethers and EpoxidesC NMR of Ethers and Epoxides
Carbons of C—O—C Carbons of C—O—C appear in the rangeappear in the range 57-87 ppm. 57-87 ppm.
6868
2626
OO
But the ring carbonsBut the ring carbonsof epoxides areof epoxides aresomewhat moresomewhat moreshielded.shielded.
CC CC
OO
HH
HH HH
CHCH22(CH(CH22))22CHCH33
4747 5252