CH 18: Ethers and Epoxides Renee Y. Becker Valencia Community College CHM 2211 1
Dec 24, 2015
Ethers and Their Relatives
• An ether has two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, R–O–R
• Diethyl ether is used industrially as a solvent
• Tetrahydrofuran (THF) is a solvent that is a cyclic ether
• Epoxides contain a C-O-C unit which make-up a three membered ring
• Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for oxygen) analogs of alcohols and ethers
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Naming Ethers
• Ethers are named two ways:
– As alkoxy derivatives of alkanes
– Derived by listing the two alkyl groups in the general structure of ROR’ in alphabetical order as separate words and adding the word ether
• When both alkyl groups are the same, the prefix di- precedes the name of the alkyl group
• (Ethers can be described as symmetrical or unsymmetrical)
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Naming Ethers
CH3CH2 O CH2CH3
Diethyl etherEthoxyethane
CH3CH2 O CH3
Ethyl methyl etherMethoxyethane
CH3CH2 O CH2CH2CH2Cl
3-Chloropropyl ethyl ether1-Chloro-3-ethoxypropane
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Naming Ethers
• Epoxides (oxiranes)– “epoxy” always preceeds the name of the alkane
O
1,2-Epoxycyclohexane
O
2-Methyl-2,3-epoxybutane
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Example 1: Name
7
1
2
3
4
5
6
7
8
O
O
O
Br
O
BrCl
Br OCH3
OCH3
O
O
1
2
3
4
5
6
7
8
O
O
O
Br
O
BrCl
Br OCH3
OCH3
O
O
Example 2: Draw
1. Isopropyl methyl ether
2. 4-t-butoxy-1-cyclohexene
3. Phenyl propyl ether
4. O- nitro anisole
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Structure, Properties, and Sources of Ethers
• R–O–R ~ tetrahedral bond angle (112° in dimethyl ether)
• Oxygen is sp3-hybridized
• Oxygen atom gives ethers a slight dipole moment (diethyl ether 1.2 D)
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Structure, Properties, and Sources of Ethers (comparative boiling points)
CH3CH2OCH2CH3Diethyl ether
bp =35oCsolubility in water: 7.5 g/100mL
CH3CH2CH2CH2CH3Pentanebp =36oC
solubility in water: insoluble
CH3CH2CH2CH2OH1-Butanolbp =117oC
solubility in water: 9 g/100mL
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Preparation of Ethers
• Acid catalyzed synthesis of ethers:
H2SO4
Dibutyl ether
130oCOH2
butanolO
+ H2O
Limited to symmetrical ethers. WHY?
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Mechanism 1: Acid catalyzed synthesis of ethers
12
2130 C
H---Cl
H3O+
Cl-
H3O+ Cl-OH O
OH O+
H
H OH
O+
H
OHH
O
HCl
+
+
+
+2130 C
H---Cl
H3O+
Cl-
H3O+ Cl-OH O
OH O+
H
H OH
O+
H
OHH
O
HCl
+
+
+
+
Preparation of Ethers
• Williamson ether synthesis
•Metal alkoxides react with primary alkyl halides by an SN2 pathway to yield ethers.
•Secondary and tertiary substrates react following an E2 mechanism
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Mechanism 2: Williamson Ether Synthesis
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NaH
THFCH3CH2----I
THF
H2
Na+ H-
NaI
H2
CH3CH2----I
NaI
THF
Na+
Na+
OH O– O
O–O
H
O
+
+
+
+
+
+
N a H
T H F
C H
3CH2----ITHF
H2
Na+ H-
NaI
H2
CH3CH2----I
NaI
THF
Na+
Na+
OH O– O
O–O
H
O
+
+
+
+
+
+
Example 4
How would you prepare the following compounds using a Williamson synthesis?
• Methyl propyl ether
• Anisole (methyl phenyl ether)
16
Alkoxymercuration of Alkenes
• React alkene with an alcohol and mercuric acetate or trifluoroacetate
• Demercuration with NaBH4 yields an ether
• Overall Markovnikov addition of alcohol to alkene
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Reactions of Ethers: Acidic Cleavage
• Ethers are generally unreactive
• Strong acid will cleave an ether at elevated temperature
• HI, HBr produce an alkyl halide from less hindered component by SN2 (tertiary ethers undergo SN1)
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Mechanism 3: Acidic Cleavage
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Note that the halide attacks the protonated ether at the less highly substituted site.
Reactions of Ethers: Claisen Rearrangement
• Specific to allyl aryl ethers, ArOCH2CH=CH2
• Heating to 200–250°C leads to an o-allylphenol• Result is alkylation of the phenol in an ortho position
25
Mechanism 4: Claisen Rearrangement
• Concerted pericyclic 6-electron, 6-membered ring transition state
• Mechanism consistent with 14C labeling
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Cyclic Ethers: Epoxides
• Cyclic ethers behave like acyclic ethers, except if ring is 3-membered
• Dioxane and tetrahydrofuran are used as solvents
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Epoxides (Oxiranes)
• Three membered ring ether is called an oxirane (root “ir” from “tri” for 3-membered; prefix “ox” for oxygen; “ane” for saturated)
• Also called epoxides
• Ethylene oxide (oxirane; 1,2-epoxyethane) is industrially important as an intermediate
• Prepared by reaction of ethylene with oxygen at 300 °C and silver oxide catalyst
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Mechanism 5: Preparation of Epoxides Using a Peroxyacid
32
(E)-1,2-diphenylethene
peroxyacetic acid
trans-1,2-diphenyloxirane acetic acid
CH3
OH
OO
O
HO
CH3
H
HC6H5
H5C6
O
H
H C6H5
H5C6
+ +
( E ) - 1 , 2 - d i p h e n y l e t h e n e
p e r o x y a c e t i c a c i d
t r a n s - 1 , 2 - d i p h e n y l o x i r a n ea c e t i c a c i d
CH3
OH
OO
O
HO
CH3
H
HC6H5
H5C6
O
H
H C6H5
H5C6
+ +
Epoxides from Halohydrins
• Addition of HO-X to an alkene gives a halohydrin• Treatment of a halohydrin with base gives an epoxide• Intramolecular Williamson ether synthesis
33
Ring-Opening Reactions of Epoxides
• Water adds to epoxides with dilute acid at room temperature
• Product is a 1,2-diol (on adjacent C’s: vicinal)
• Mechanism: acid protonates oxygen and water adds to opposite side (anti-addition)
35
Ethylene Glycol
• 1,2-ethanediol from acid catalyzed hydration of ethylene
• Widely used as automobile antifreeze (lowers freezing point of water solutions)
37
Halohydrins from Epoxides
• Anhydrous HF, HBr, HCl, or HI combines with an epoxide
• Gives trans product
38
Base-Catalyzed Epoxide Opening
• Strain of the three-membered ring is relieved on ring-opening
• Hydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols– Complete the reaction
CH2
O
OH-
H2O, 100oC
Methylenecyclohexane oxide 41
Mechanism 7: Base-Catalyzed Epoxide Opening
42
-OH
100 C
-OHCH2
O O–
CH2OH
OHH OH
CH2OH+
-OH
100 C
-OHCH2
O O–
CH2OH
OHH OH
CH2OH+
Addition of Grignards to Ethylene Oxide
• Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain
• Acyclic and other larger ring ethers do not react
44
Thiols
• Thiols (RSH), are sulfur analogs of alcohols– Named with the suffix -thiol
– SH group is called “mercapto group”
45
Example 9: Draw
1. Cyclopentanethiol
2. 3-methyl-4-heptanethiol
3. 4-ethyl-4-isopropyl-2-methyl-3-hexanethiol
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Sulfides
• Sulfides (RSR), are sulfur analogs of ethers– Named by rules used for ethers, with sulfide in
place of ether for simple compounds and alkylthio in place of alkoxy
48
Example 10: Name or Draw
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1
2
3
4
ethyl phenyl sulfide
sec-butyl isopropyl sulfide
S
S1
2
3
4
e t h y l p h e n y l s u l f i d e
s e c - b u t y l i s o p r o p y l s u l f i d e
S
S
Thiols: Formation and Reaction
• From alkyl halides by displacement with a sulfur nucleophile such as SH – The alkylthiol product can undergo further
reaction with the alkyl halide to give a symmetrical sulfide, giving a poorer yield of the thiol
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