Download Chapter 16 Ethers, Epoxides, and Sulfides

Chapter 16
Ethers, Epoxides, and Sulfides
16.5
Preparation of Ethers
Acid-Catalyzed Condensation of Alcohols
2CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
Addition of Alcohols to Alkenes
(CH3)2C=CH2 + CH3OH
H+
(CH3)3COCH3
tert-Butyl methyl ether
tert-Butyl methyl ether (MTBE) was produced on a
scale exceeding 15 billion pounds per year in the U.S.
during the 1990s. It is an effective octane rating booster in
gasoline, but contaminates ground water if allowed to
leak from storage tanks. Further use of MTBE is unlikely.
16.6
The Williamson Ether Synthesis
Think SN2!
Primary alkyl halide + alkoxide nucleophile.
Example
CH3CH2CH2CH2ONa + CH3CH2I
CH3CH2CH2CH2OCH2CH3 + NaI
(71%)
Williamson Ether Synthesis Has Limitations
1) Alkyl halide must be primary (RCH2X).
2) Alkoxides can be derived from primary, secondary or
tertiary alcohols.
O Na
OH
Secondary
Alkoxide
SN2
Br
O
Primary
Alkyl halide
Williamson Ether Synthesis Has Limitations
1) Alkyl halide must be primary (RCH2X).
2) Alkoxides can be derived from primary, secondary or
tertiary alcohols.
CH2Cl
The reaction
works particularly
well with benzyl
and allyl halides,
which are
excellent
alkylating agents.
+
CH3CHCH3
ONa
CH2OCHCH3
CH3
(84%)
Origin of Reactants
CH3CHCH3
CH2OH
OH
HCl
CH2Cl
Na
+
CH3CHCH3
ONa
CH2OCHCH3
CH3
(84%)
What Happens if the Alkyl Halide Is Not Primary?
CH2ONa + CH3CHCH3
Br
CH2OH
+
H2C
CHCH3
Elimination by the E2 mechanism becomes
the major reaction pathway.
16.7
Reactions of Ethers:
A Review and a Preview
Summary of Reactions of Ethers
No reactions of ethers encountered to this
point.
Ethers are relatively unreactive.
Their low level of reactivity is one reason why
ethers are often used as solvents in chemical
reactions.
Ethers oxidize in air to form explosive
hydroperoxides and peroxides.
16.8
Acid-Catalyzed Cleavage of Ethers
Example
CH3CHCH2CH3
OCH3
HBr
heat
CH3CHCH2CH3
Br
(81%)
+ CH3Br
Mechanism
CH3CHCH2CH3
CH3CHCH2CH3
O ••
Br
CH3 ••
H
••
Br ••
HBr
••
CH3CHCH2CH3
CH3CHCH2CH3
•• –
•• Br ••
••
O
CH3 ••
+
H
•• O
••
••
•• Br
••
H
CH3
Cleavage of Cyclic Ethers
O
HI
150°C
ICH2CH2CH2CH2I
(65%)
Mechanism
••
ICH2CH2CH2CH2I
O
••
HI
•• –
•• I •
•
••
HI
••
O+
H
••
•• I
••
••
•• O
H
16.9
Preparation of Epoxides:
A Review and a Preview
Preparation of Epoxides
Epoxides are prepared by two major methods.
Both begin with alkenes.
Reaction of alkenes with peroxy acids
(6.19).
Conversion of alkenes to vicinal
halohydrins (6.18), followed by treatment
with base (16.10).
16.10
Conversion of Vicinal Halohydrins
to Epoxides
Example
H
H
OH
NaOH
O
H2 O
H
H
Br
•• –
•• O ••
via:
H
H
•• Br ••
••
(81%)
Epoxidation via Vicinal Halohydrins
H3C
H
Br
H
Br2
H2O
CH3
H3C
H
H
CH3
NaOH
H3C
H
O
OH
Anti
addition
H
CH3
Inversion
Corresponds to overall syn addition of
oxygen to the double bond.
16.11
Reactions of Epoxides:
A Review and a Preview
Reactions of Epoxides
All reactions involve nucleophilic attack
at carbon and lead to opening of the ring.
An example is the reaction of ethylene oxide
with a Grignard reagent (discussed in 15.4
as a method for the synthesis of alcohols).
Reaction of Grignard Reagents
with Epoxides
R
MgX
CH2
H2C
O
R
CH2
CH2
OMgX
H3O+
RCH2CH2OH
Example
CH2MgCl
CH2
+ H2C
O
1. diethyl ether
2. H3O+
CH2CH2CH2OH
(71%)
In General...
Reactions of epoxides involve attack by a
nucleophile and proceed with ring-opening.
For ethylene oxide:
Nu—H
+ H2C
CH2
O
Nu—CH2CH2O—H
In General...
For epoxides where the two carbons of the
ring are differently substituted:
Nucleophiles attack here
when the reaction is
catalyzed by acids.
Anionic and other good
nucleophiles in nonacidic conditions attack
here.
R
CH2
C
H
O
16.12
Nucleophilic Ring-Opening
Reactions of Epoxides
Example
CH2
H2C
O
NaOCH2CH3
CH3CH2OH
CH3CH2O
CH2CH2OH
(50%)
CH3CH2
Mechanism
•• –
O ••
••
CH2
H2C
O ••
••
••
CH3CH2
CH3CH2
••
O
••
••
O
••
CH2CH2
CH2CH2
•• O
•• –
O ••
••
H
••
O
••
CH2CH3
H
– ••
•• O
••
CH2CH3
Example
CH2
H2C
O
KSCH2CH2CH2CH3
ethanol-water, 0°C
CH3CH2CH2CH2S
CH2CH2OH
(99%)
Stereochemistry
H
H
NaOCH2CH3
O
CH3CH2OH
OCH2CH3
H
H
OH
(67%)
Inversion of configuration at carbon being
attacked by nucleophile.
Suggests SN2-like transition state.
Stereochemistry
H3C
H
R
H3C H
CH3
R
O
R
NH3
H2O
H2 N
H
H
S
OH
CH3
(70%)
Inversion of configuration at carbon being
attacked by nucleophile.
Suggests SN2-like transition state.
Stereochemistry
H3C
H
R
CH3
R
R
NH3
H2O
O
H3C H
H2 N
H
H
S
OH
CH3
(70%)
H3C
H
O
H3N
H3C
H
-
Good Nucleophiles Attack Less-Crowded Carbon
H3C
CH3
C
C
H
O
NaOCH3
CH3OH
CH3O
CH3
CH3CH
CCH3
OH
CH3
(53%)
Consistent with SN2-like transition state.
Good Nucleophiles Attack Less-Crowded Carbon
MgBr
+
CHCH3
H2C
O
1. diethyl ether
2. H3O+
CH2CHCH3
OH
(60%)
Lithium Aluminum Hydride Reduces Epoxides
CH(CH2)7CH3
H2C
O
Hydride anion attacks
less-crowded
carbon.
H3C
1. LiAlH4, diethyl ether
2. H2O
CH(CH2)7CH3
OH
(90%)
16.13
Acid-Catalyzed Ring-Opening
Reactions of Epoxides
Example
CH2
H2C
O
CH3CH2OH
CH3CH2OCH2CH2OH
H2SO4, 25°C
(87-92%)
CH3CH2OCH2CH2OCH2CH3 formed only on
heating and/or longer reaction times.
Example
CH2
H2C
O
HBr
10°C
BrCH2CH2OH
(87-92%)
BrCH2CH2Br formed only on heating and/or
longer reaction times with excess HBr.
Mechanism
CH2
H2C
H2C
O ••
••
••
•• Br
••
•• –
•• Br •
•
••
H
CH2
+
O ••
H
••
• Br •
•
•
CH2CH2
••
O
••
H
Acid-Catalyzed Hydrolysis of Ethylene Oxide
Step 1
CH2
H2C
O ••
H
••
•• O
+
H
H
H2C
H
•• O ••
H
CH2
+
O ••
H
Acid-Catalyzed Hydrolysis of Ethylene Oxide
H
Step 2
O ••
H
••
H2C
H
+
O ••
H
+ •
H O•
CH2CH2
CH2
••
O
••
H
Acid-Catalyzed Hydrolysis of Ethylene Oxide
H
+
H O ••
Step 3
H
H
H
H
O ••
••
•O•
• •
H
CH2CH2
+ •
H O•
CH2CH2
••
O
••
H
••
O
••
H
Acid-Catalyzed Ring Opening of Epoxides
Characteristics:
Nucleophile attacks more substituted carbon
of protonated epoxide.
Inversion of configuration at site of nucleophilic
attack.
Nucleophile Attacks More-Substituted Carbon
H3C
CH3
C
C
H
O
CH3OH
H2SO4
CH3
OCH3
CH3CH
OH
CCH3
CH3
(76%)
Consistent with carbocation character of
transition state.
Stereochemistry
H
H
OH
O
HBr
H
H
Br
(73%)
Inversion of configuration at carbon being
attacked by nucleophile.
Stereochemistry
H3C
H
R
H3C H
CH3
R
O
CH3OH
H2SO4
R
CH3O
H
S
H
OH
CH3
(57%)
Inversion of configuration at carbon being
attacked by nucleophile.
Stereochemistry
H3C
H
R
CH3
R
R
CH3OH
O
CH3O
H2SO4
H3C H
H
H
S
CH3
+
CH3O
H
H3C
H
+
H3C
H
+
O H
OH
anti-Hydroxylation of Alkenes
H
O
H
CH3COOH
O
H
H
H2O,
H
OH
H
(80%)
OH
HClO4
16.15
Preparation of Sulfides
Preparation of RSR'
Prepared by nucleophilic substitution (SN2).
–
S ••
••
R
••
CH3CHCH
+
CH2
R'
X
NaSCH3
R
••
S
••
R'
CH3CHCH
methanol
Cl
SCH3
CH2
Section 16.18
Spectroscopic Analysis
of
Ethers, Epoxides, and Sulfides
Infrared Spectroscopy
C—O stretching of ethers: between 1070 and
1150 cm-1 (strong)
Infrared Spectrum of Dipropyl Ether
1H
NMR of Ethers
H—C—O proton is deshielded by O; range is
 3.2-4.0 ppm.
 0.8 ppm
 1.4 ppm
 0.8 ppm
CH3CH2CH2OCH2CH2CH3
 3.2 ppm
Epoxide ring protons slightly more shielded:  ~2.5 ppm.
Dipropyl Ether
CH3CH2CH2OCH2CH2CH3
10.0
9.0
8.0
7.0
6.0
5.0
4.0
Chemical shift (, ppm)
3.0
2.0
1.0
0
1H
NMR of Sulfides
H—C—S proton is less deshielded than H—C—O.
CH3 CH2 CH2 SCH2 CH2 CH3
 2.5 ppm
Oxidation of sulfides to sulfoxide deshields an
adjacent C—H proton by 0.3-0.5 ppm. An
additional 0.3-0.5 ppm downfield shift occurs
on oxidation of the sulfoxide to the sulfone.
13C
NMR of Ethers and Epoxides
Carbons of C—O—C
appear in the range
 57-87 ppm.
 26
O
 68
But the ring carbons
of epoxides are
somewhat more
shielded.
CH2(CH2)2CH3
H
 47 C
H
C  52
O
H