Download Crown Ethers

Chapter 16
Ethers, Epoxides, and Sulfides
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Ethers
• Formula is R—O—Rwhere R and R
are alkyl or aryl.
• Symmetrical or unsymmetrical
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Chapter 14
2
Nomenclature of Ethers, Epoxides, and
Sulfides
Substitutive IUPAC Names of Ethers
name as alkoxy derivatives of alkanes
CH3OCH2 CH3
methoxyethane
CH3CH2OCH2CH2CH2Cl
3-chloro-1-ethoxypropane
CH3CH2OCH2 CH3
ethoxyethane
Functional Class IUPAC Names of Ethers
Name the groups attached to oxygen in
alphabetical order as separate words; "ether" is
last word.
CH3OCH2 CH3
ethyl methyl ether
CH3CH2OCH2CH2CH2Cl
3-chloropropyl ethyl ether
CH3CH2OCH2 CH3
diethyl ether
Structure and Bonding
in
Ethers and Epoxides
bent geometry at oxygen analogous
to water and alcohols
Structure and Polarity
•
•
•
•
Oxygen is sp3 hybridized.
Bent molecular geometry.
Tetrahedral C—O—C angle is 110°.
Polar C—O bonds.
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Chapter 14
7
Bond angles at oxygen are sensitive
to steric effects
O
O
H
H
105°
108.5°
O
O
CH3
CH3
112°
H
CH3
(CH3)3C
C(CH3)3
132°
An oxygen atom affects geometry in much the
same way as a CH2 group
Most stable conformation of diethyl ether
resembles that of pentane.
An oxygen atom affects geometry in much the
same way as a CH2 group
Most stable conformation of tetrahydropyran
resembles that of cyclohexane.
Physical Properties of Ethers
Table 16.1 Ethers resemble alkanes more than alcohols
with respect to boiling point
boiling point
36°C
35°C
O
OH
117°C
Intermolecular hydrogen
bonding possible in
alcohols; not possible
in alkanes or ethers.
Table 16.1 Ethers resemble alcohols more than alkanes
with respect to solubility in water
solubility in water (g/100 mL)
very small
7.5
O
OH
9
Hydrogen bonding to
water possible for ethers
and alcohols; not
possible for alkanes.
Hydrogen Bond Acceptor
• Ethers cannot hydrogen bond with other ether
molecules, so they have a lower boiling point than
alcohols.
• Ether molecules can hydrogen bond with water and
alcohol molecules.
• They are hydrogen bond acceptors.
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Chapter 14
14
Ethers as Solvents
• Ethers are widely used as solvents
because
 they can dissolve nonpolar and polar
substances.
 they are unreactive toward strong bases.
Ethers are relatively unreactive.
Their low level of reactivity is one reason why
ethers are often used as solvents in chemical
reactions.
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Chapter 14
15
Ether Complexes
• Grignard reagents: Complexation
of an ether with a Grignard reagent
stabilizes the reagent and helps
keep it in solution.
• Electrophiles: The ether’s
nonbonding electrons stabilize the
borane (BH3).
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Chapter 14
H
_
+
O B H
H
BH3 THF
16
Crown Ethers
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Crown Ethers
structure
cyclic polyethers derived from repeating
—OCH2CH2— units
properties
form stable complexes with metal ions
applications
synthetic reactions involving anions
Crown Ether Complexes
• Crown ethers can complex metal cations in the
center of the ring.
• The size of the ether ring will determine which cation
it can solvate better.
• Complexation by crown ethers often allows polar
inorganic salts to dissolve in nonpolar organic
solvents.
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Chapter 14
19
18-Crown-6
O
O
O
K+
O
O
O
forms stable Lewis acid/Lewis base complex
with K+
Ion-Complexing and Solubility
K+F–
not soluble in benzene
Ion-Complexing and Solubility
O
O
O
K+F–
O
O
benzene
O
add 18-crown-6
Ion-Complexing and Solubility
O
O
O
O
F–
O
O
K+
O
O
benzene
O
O
18-crown-6 complex of K+ dissolves
in benzene
O
O
Ion-Complexing and Solubility
O
O
O
O
O
O
K+
O
O
benzene
O
F– carried into benzene
to preserve electroneutrality
O
O
O
+ F–
Application to organic synthesis
Complexation of K+ by 18-crown-6 solubilizes
potassium salts in benzene.
Anion of salt is in a relatively unsolvated state
in benzene (sometimes referred to as a
"naked anion").
Unsolvated anion is very reactive.
Only catalytic quantities of 18-crown-6 are
needed.
Example
KF
CH3(CH2)6CH2Br
18-crown-6
benzene
CH3(CH2)6CH2F
(92%)
Preparation of Ethers
Acid-Catalyzed Condensation of Alcohols*
2 CH3CH2CH2CH2OH
H2SO4, 130°C
CH3CH2CH2CH2OCH2CH2CH2CH3
(60%)
Method is good for primary alcohols. Diethyl ether is made on
industrial scale using this method. Ethylene will form at higher
temperatures. Secondary and tertiary alcohols give alkenes as
main product.
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 booster in
gasoline, but contaminates ground water if allowed to
leak from storage tanks. Further use of MTBE is unlikely.
The Williamson Ether Synthesis
Williamson Ether Synthesis
• This method involves an SN2 attack of the
alkoxide on an unhindered primary halide or
tosylate.
• The alkoxide is commonly made by adding
Na, K, or NaH to the alcohol
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Chapter 14
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Example
CH3CH2CH2CH2ONa + CH3CH2I
CH3CH2CH2CH2OCH2CH3 + NaI
(71%)
Another Example
Alkyl halide must be
primary or methyl
Alkoxide ion can be derived
from methyl, primary, secondary,
or tertiary alcohol.
CH2Cl
+
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.
Reactions of Ethers:
Acid-Catalyzed Cleavage of Ethers
Ethers can be cleaved by heating with
concentrated HBr and HI.
Reactivity: HI > HBr
Example
CH3CHCH2CH3 HBr
OCH3
heat
CH3CHCH2CH3
Br
(81%)
+ CH3Br
Mechanism of Ether Cleavage
• Step 1: Protonation of the oxygen.
• Step 2: The halide will attack the carbon and
displace the alcohol (SN2).
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Chapter 14
39
Mechanism of Ether Cleavage
Step 3: The alcohol reacts further with the acid
to produce another mole of alkyl halide.
• This does not occur with aromatic alcohols
(phenols).
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Chapter 14
40
Cleavage of Cyclic Ethers
O
HI
150°C
ICH2CH2CH2CH2I
(65%)
Mechanism
••
ICH2CH2CH2CH2I
O
••
HI
•• –
•• I •
•
••
HI
••
O+
H
••
•• I
••
••
•• O
H
Autoxidation of Ethers
• In the presence of atmospheric oxygen,
ethers slowly oxidize to hydroperoxides
and dialkyl peroxides.
• Both are highly explosive.
• Precautions:
 Do not distill to dryness.
 Store in full bottles with tight caps.
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Chapter 14
43
Autoxidation of Ethers
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Chapter 14
44
Preparation of Epoxides:
A Review and a Preview
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Chapter 14
45
Preparation of Epoxides
Epoxides are prepared by two major methods.
Both begin with alkenes.
Reaction of alkenes with peroxy acids
(Section 6.19)
Conversion of alkenes to vicinal
halohydrins, followed by treatment
with base (Section 16.10, this chapter)
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Chapter 14
46
Synthesis of Epoxides
• Peroxyacids are used to convert alkenes to epoxides.
• Most commonly used peroxyacid is metachloroperoxybenzoic acid (MCPBA).
• The reaction is carried out in an aprotic acid to
prevent the opening of the epoxide.
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Chapter 14
47
Halohydrin Cyclization
• If an alkoxide and a halogen are located in
the same molecule, the alkoxide may
displace a halide ion and form a ring.
• Treatment of a halohydrin with a base leads
to an epoxide through this internal SN2 attack.
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Chapter 14
48
Another look
H
H
OH
NaOH
O
H2 O
H
H
Br
•• –
•• O ••
via:
(81%)
H
H
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•• Br ••
•• Chapter 14
49
Epoxidation via Vicinal Halohydrins
Br
Br2
NaOH
H2O
O
OH
anti
addition
inversion
Corresponds to overall syn addition of
oxygen to the double bond.
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Chapter 14
50
Reactions of Epoxides:
A Review and a Preview
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
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%)
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 nucleophiles
attack here:
R
CH2
C
H
O
Anionic Nucleophile Attacks 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 attacks
less-crowded
carbon.
H3C
1. LiAlH4, diethyl ether
2. H2O
CH(CH2)7CH3
OH
(90%)
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.
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%)
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
H
S
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
HClO4
H
(80%)
OH
+ enantiomer