ETHERS & EPOXIDES

EPOXIDES

• These are cyclic ethers with three membered rings

• In IUPAC nomenclature, epoxides are called oxiranes

H2C CH2
C C
O
O
IUPAC: Oxiranes
An epoxide
Common: Ethylene oxide

ORGANIC CHEMISTRY I 2
• They are prepared by the reaction of an alkene with an
organic peroxy acid (peracid)
O O O
epoxidation
RHC CHR + R' C O OH RH2C CH2R + R' C OH
An alkene A peroxy acid An epoxide
(or oxirane)

• In the reaction the peroxy acid transfers oxygen to the alkene

• The peroxy acid most often used is magnesium

monoperoxyphthalate (MMPP)

ORGANIC CHEMISTRY I 3
 O R' O R'
C C C
O C
+ O +
C C O
H O
H
Alkene Peroxy acid Epoxide Carboxylic acid

The peroxy acid transfers an oxygen atom to the alkene in the

cyclic, single-step mechanism

The result is the syn addition of oxygen to the alkene, with the
formation of an epoxide and a caroboxylic acid

ORGANIC CHEMISTRY I 4
• Cyclohexene, reacts with MMPP in ethanol to give 1,2-
epoxycyclohexane
H

MMPP O
CH3CH2OH
H
1,2-Epoxycyclohexane
Cyclohexene
cyclohexene oxide

O
C
O OH
MMPP =
O Mg2+
C
O 2
MMPP: Magnesium monoperoxyphthalate hexahydrate

ORGANIC CHEMISTRY I 5
REACTIONS OF EPOXIDES

• The highly strained three-membered ring in molecules of

epoxides makes them more reactive toward nucleophilic
substitution than other ethers

• Acid catalysis assists epoxide ring opening by providing a

better leaving group (an alcohol) at the carbon atom
undergoing nucleophilic attack

• This catalysis is especially important if the nucleophile is

weak such as water or an alcohol

ORGANIC CHEMISTRY I 6
 C C + H O H C C + O H
O H O H
Epoxide H
Protonated epoxide

The acid reacts with the epoxide to produce a protonated epoxide

H H
O H O H O
C C + O H C C H O H
H C C +
O
H O O H
weak nucleophile
H
H H
Protonated epoxide Protonated glycol
Glycol
The a protonated epoxide reacts with the weak nucleophile (water) to form a
protonated glycol, which then transfers a proton to a molecule of water to form
the glycol and hydronium ion
ORGANIC CHEMISTRY I 7
• Epoxides can also undergo base catalyzed ring opening, such
reaction do not occur with other ethers

• This can happen provided that the attacking nucleophile is

also a strong base such as an alkoxide ion or hydroxide ion

R O + C C RO C C O H OR RO C C OH + RO
O
Strong
nucleophile Epoxide An alkoxide ion

A strong nucleophile such as an alkoxide ion or hydroxide ion is able to open the
strained epoxide ring in a direct SN2 reaction

ORGANIC CHEMISTRY I 8
• If the epoxide is unsymmetrical, in base-catalyzed ring
opening, attack by the alkoxide ion occurs primarily at the less
substituted carbon atom

• Primary substrates react more rapidly in SN2 reactions

because they are less sterically hindered

• In the acid-catalyzed ring opening of unsymmetrical epoxide

the nucleophile attacks primarily the more substituted carbon
atom because the it bears a greater positive charge
(resembles tertiary carbocation)

ORGANIC CHEMISTRY I 9
 ETHERS

• Ethers differ from alcohols in that the oxygen atom of an ether

is bonded to two carbon atoms
• The hydrocarbon may be alkyl, alkenyl, vinyl, alkynyl, or aryl
Examples:

H3CH2C O CH2CH3 H2C HC O CH CH2

Diethyl ether Divinyl ether

H2C HCH2C O CH3 OCH3

Allyl methyl ether Methyl phenyl ether

(Methoxybenzene)
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NOMENCLATURE OF ETHERS

• Simple ethers are normally given common names (as

shown in the previous slide)

• IUPAC names should be used for complicated ethers,

however, and for compounds with more than one linkage

• In this case, ethers are named as alkoxyalkanes,

alkoxyalkenes, and alkoxyarenes

• RO-group is an alkoxy group

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 H
H3C OCH2CH3 H3C C CH2CH2CH3

OCH3
1-Ethoxy-4-methylbenzene 2-Methoxypentane

O
CH3OCH2CH2OCH3

2-Methoxypropane
(Isopropyl methyl ether) 1,2-Dimethoxyethane

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• Cyclic ethers can be named in several ways:
– Replacement nomenclature, in which we relate the cyclic ether to the
corresponding hydrocarbon ring system and use the prefix oxa to
indicate that an oxygen atom replaces a CH2

• Another system, a cyclic three-membered ether is named

oxirane and a four-membered ether is called oxetane

• Several simple cyclic ethers also have common names

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 O O

Oxycyclopropane or oxirane Oxacyclobutane

(ethylene oxide) or oxetane

O
O
Oxacyclopentane 1,4-Dioxacyclohexane
(tetrahydrofuran THF) (1,4-dioxane)

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PHYSICAL PROPERTIES OF ETHERS

• Ethers have boiling points that are roughly comparable with

those of hydrocarbons of the same molecular weight
Example: the boiling point of diethyl ether (MW = 74) is 34.6˚C, that of
pentane (MW=72) is 36˚C
– Alcohols have much higher boiling points than comparable ethers or
hydrocarbons, butyl alcohol (MW=74) is 117.7˚C
– This is because the molecules of alcohols associate with each other
through hydrogen bonding whereas those of ethers and
hydrocarbons can not
R
d- d+ d-
O H O

H R
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• Ethers are able to form hydrogen bonds with compounds
such as water

• Have solubilities in water that are similar to those of

alcohols of the same molecular weight

16
SYNTHESIS OF ETHERS

• Primary alcohols can be dehydrated to form ethers

H+
R OH + HO R R O R
(-H2O)

H2SO4
H2C CH2
180ÝC
Ethene
CH3CH2OH

H2SO4
CH3CH2OCH2CH3
14OÝC Diethyl ether
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 MECHANISM H

H3CH2C O H + H OSO3H H3CH2C O H + OSO3H

This is an acid-base reaction in which the alcohol accepts a

proton from sulfuric acid
H H
H

H3CH2C O H + H3CH2C O H H3CH2C O CH2CH3 + O H

Another molecule of the alcohol acts as a nucleophile and

attacks the protonated alcohol in an SN2 reaction

H H H

H3CH2C O CH2CH3 + O H H3CH2C O CH2CH3 + H O H

Another acid-base reaction converts the protonated ether to an ether

by transferring a proton to a water molecule (or another molecule of
the alcohol)
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 THE WILLIAMSON SYNTHESIS OF ETHERS

• An important route to unsymmetrical ethers is a nucleophilic

substitution reaction known as the the Williamson synthesis

• The reaction consists of an SN2 reaction of a sodium alkoxide

with an alkyl halide, alkyl sulfonate or alkyl sulfate (good
leaving groups)

• The alkoxide is prepared by allowing the alcohol to react with

NaH

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Mechanism

R O Na R' L R O R'
Sodium Alkyl halide, Ether
(or potassium) alkyl sulfonate
alkoxide or dialkyl sulfate

The alkoxide ion reacts with the substrate in an SN2 reaction,

with the resulting formation of an ether

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 tert-BUTYL ETHERS BY ALKYLATION OF
ALCOHOLS: PROTECTING GROUPS

• Primary alcohols can be converted to tert-butyl ether by

dissolving them in strong acids such as sulfuric acid and then
adding isobutylene to the mixture

• This method is often used to protect the hydroxyl group of a

primary alcohol while another reaction is carried out on some
other parts of the molecule

• The protecting group can be removed easily by treating the

ether with dilute aqueous acid

21
 CH3
H2SO4 tert-Butyl
RCH2OH + H2C CCH3 RH2CO C CH3 protecting
group
CH3 CH3

22
REACTIONS OF ETHERS

• Dialkyl ethers react with very few reagents other than

acids, the only reactive site are:
– C-H bonds of the alkyl groups
– The -O- group of the ether linkage

• Ethers resist attack by nucleophiles and by bases

• Lack of reactivity, coupled with the ability of ethers to

solvate cations (by donating an electron pair from their
oxygen atom) makes them useful solvents in many
reactions
23
• Ether are like alkanes, in that they undergo halogenation
reactions

• The oxygen of the ether linkage makes ethers basic, react

with proton donors to form oxonium salts

H3CH2C O CH2CH3 + HBr H3CH2C O CH2CH3 -Br

H
An oxonium salt

24
• Heating dialkyl ethers with very strong acids (HI, HBr and
H2SO4) causes them to undergo reaction in which the C-O
bond breaks

H3CH2C O CH2CH3 + 2HBr 2CH3CH2Br + H2O

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 CROWN ETHERS
• These are cyclic polymers of ethylene glycol such as 18-crown-6
O

O O

O O
O

• Crown ethers are named as x-crown-y

– where x is the total number of atoms in the ring and y is the number of
oxygen atoms

• They are used as phase transfer catalysts and are able to transfer
ionic compounds into an organic phase

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 O O

O O O O
K
K

O O O O

O O

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