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ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 11 11.15 Synthesis of Ethers
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.15 Synthesis of Ethers
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.15A Ethers by Intermolecular Dehydration of Alcohols
+R O H ROHH+
R O R + H2O
CH3CH2OH
H2SO4
140°C
H2SO4180°C
CH2 CH2
CH3CH2OCH2CH3
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Mechanism Mechanism OH2
SN2 H2OCH3CH2OHH+
CH3CH2HOCH2CH3
CH3CH2OCH2CH3H+
CH3CH2OCH2CH3
H
ROH + R'OHH2SO4
ROR'ROR
R'OR'H2O+
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.15B The Williamson Synthesis of Ethers
ROR'ArOR'+RONa
ArONa LR' + NaL
L = Br, I, OSO2R'' , OSO2OR''
OK
+ CH3CH2Br
OCH2CH3
(CH3)3CONa + CH3I (CH3)3COCH3
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.15C tert-Butyl Ethers by Alkylation of Alcohols. Protecting Groups
RCH2OH CH2 CCH3CH3
+H2SO4 RCH2O C
CH3
CH3
CH3 tert-Butylprotectinggroup
HOCH2CH2CH2Br CHNaC+ NaOCH2CH2CH2Br
CHHC+
CHCHOCH2CH2CH2no
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
HOCH2CH2CH2Br CH2 CCH3CH3
+H2SO4 BrCH2CH2CH2O C
CH3
CH3
CH3
CHNaCCH2CH2CH2O C
CH3
CH3
CH3CHC
H2OH+
CH2CH2CH2OHCHC CCH3
CH3CH3
OH+
4-Pentyn-1-ol
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.15D Silyl Ether Protecting Groups
ROH SiCH3
C(CH3)3
CH3Cl+
imidazoleDMF
RO SiCH3
C(CH3)3
CH3
tert-Butylchlorodimethylsilane(TBDMSCl) (RO TBDMS)
HN Nimidazole
RO SiCH3
C(CH3)3
CH3
THFROH Si
CH3
C(CH3)3
CH3F+
Bu4N F
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.16 Reactions of Ethers
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
The oxygen of ether linkage makes ether basic. Ether can react with proton donors to form oxonium salts.
R O R R O RH
HBr
An oxonium salt
R O RR
OR
BF3+
RO
RMgR
R
RO
R
BF3
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Heating dialkyl ethers with very strong acids (HI, HBr, and H2SO4) cause tem to undergo reactions in which the carbon-oxygen bond breaks.
CH3CH2BrCH3CH2OCH2CH3 + HBr
+ H2O
CH3CH2OH+
HBr
CH3CH2Br
CH3 O CH3 + HI CH3OH + CH3I
CH3I
(CH3)3C O CH3 + HI (CH3)3CI + CH3OH
OCH3 OH+ HI + CH3I
HI
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Mechanism Mechanism
CH3CH2OH
CH3CH2OCH2CH3
H+
CH2CH3
Br
CH3CH3OH + CH3CH2Br
CH3CH3OHH+
CH3CH2 OH2 BrCH3CH2Br
+ H2O
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.17 Epoxides
环氧化合物
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Epoxides are cyclic ethers with three-membered rings.
C CO
An epoxide
H2C CH2
O
IUPAC name: oxirane
H2C CH2 + O2Ag
H2C CH2
OPreparation Preparation
RCH CHR + C O OHO
R' RCH CHRO
C OHO
R'+
C CO
CH3
H HCH3
C CO
CH3
H CH3H
C CO
HCH3 H
CH3
CH2 CO
CH3H
C CH2
O
HCH3
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.18 Reactions Epoxides
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
O
HOCH2CH2OHH2O/ H+
ROH/H+ROCH2CH2OH
HX XCH2CH2OHHCN NCCH2CH2OHBH3 (CH3CH2O)3BNH3 H2NCH2CH2OHRMgX
RCH2CH2OHLiAlH4 HCH2CH2OH
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Acid-Catalyzed Ring Opening of an Epoxide
CH3 CH CH2
OCH3 CH CH2
O
CH3 CH CH2
OH
Nu
H+H
Nu
CH3 CH CH2
OH
CH3 CH CH2
Oδ+ δ+
More stable Nu Nu
H
Less stable
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Base-Catalyzed Ring Opening of an Epoxide
CH3 CH CH2
OCH3 CH CH2OCH3
OHCH3O
CH3 CH CH2
OCH3 CH CH2OCH3
OCH3O
CH3OHCH3 CH CH2OCH3
OH
CH3 CH CH2
O
CH3 CH CH2
O
OCH3 OCH3
1° Carbon is less hindered.
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.18A Polyether Formation
CH2 CH2
OCH3O + CH2 CH2 OCH3O
CH2 CH2
O
CH2 CH2 OCH3O CH2 CH2 O
etc.CH3OH
CH2 CH2 OCH3O CH2 CH2 OH
Poly(ethylene glycol)
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.19 Anti Hydroxylation of Alkenes Via Epoxides
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
O
H
H
H2OOH
OH
H
H
H
H
OH
OH
+
C CO
CH3
H HCH3
H2O
CH3OHHHHO
CH3
CH3HHOOHH
CH3
C CO
CH3
H CH3H
C CO
HCH3 H
CH3
H2O H2O
CH3OHHOHH
CH3
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.20 Crown Ethers: Nucleophilic Substitution Reactions in Relatively
Nonpolar Aprotic Solvents by Phase-Transfer Catalysis
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.20A Crown Ethers (冠醚)
OO
O
OOO
18-Crown-618-冠-6
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
OO
O
OOO
K+O
OO
OOO
K+
Host-guest relationship
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
OO
O
OOO
+ KMnO4 +
OO
O
OOO
K+
MnO4紫色苯
"Purper benzene"
CH3
KMnO4
CO2H
100%Dicyclohexano-18-crown-6
Benzene
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Phase-Transfer Catalysis
CH3(CH2)4CH2Br + KCN(s)
CH2Cl + KCN CH3CN25� , 72 h
CH2CN
20%
CH2Cl + KCN CH3CN25� , 0.4 h
CH2CN
100%
18-C-6
CH3CN18-C-6
CH3(CH2)4CH2CN
90%
Br(CH2)4Br + 2 KCN(s)CH3CN18-C-6
NC(CH2)4CN100%
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
Phase-Transfer Catalysis
OO
O
OOO
K+
CN
RX +O
OO
OOO
K+
CN
RCN +O
OO
OOO
K+
Cl
OO
O
OOO
K+
Cl+K CNKX +
Aqueous phase
Interphase
Organic phase
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.20B Transport Antibiotics and Crown Ethers
O O OCH3
O CH3
HOO
OOOCH3
OCH3
HH H H
H H H
CH3
CH3
O
O
H3C
H3C
Nonactin
ORGANIC CHEMISTRY
Department of Chemistry, Xiamen University
Chapter 11
11.21 Summary of Reactions of Alkenes, Alcohols, and Ethers
