Ethers and Epoxides

Ethers
Ethers are compounds of the general formula R –O-R , Ar-O-R or Ar-O Ar.
nomenclature of ethers
To name ethers we usually name the two groups that are attached to oxygen, and follow these names
by the word ether:

If one group has no simple name, the compound may be named as an alkoxy derivative:

The simplest aryl alkyl ether has the special name of anisole

Physical properties of ethers

1- Since the C-O C bond angle is not 180, the dipole moments of the two C-O bonds do not
cancel each other; consequently, ethers possess a small net dipole moment

2- the boiling points of ethers same as those of alkanes having comparable molecular weights and
much lower than those of isomeric alcohols
3- The hydrogen bonding that holds alcohol molecules strongly together is not possible for ethers,
since they contain hydrogen bonded only to carbon
4-ethers show a solubility in water comparable to that of the alcohols, both ethyl ether and w-
butyl alcohol, for example,being soluble to the extent of about 8 g per 100g of water. the water
solubility of th lower alcohols to hydrogen bonding between water molecules and alcohol
molecules; presumably the water solubility of ether arises in the same way

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IndustriaKsources of ethers. Dehydration of alcohols
A number of symmetrical ethers containing the lower alkyl groups are prepared on a large scale,
chiefly for use as solvents. The most important of these is ethyl ether, the familiar anesthetic and the
solvent we use in extractions and in the preparation of Grignard reagents; others include isopropyl
ether and tf-butyl ether.
These ethers are prepared by reactions of the corresponding alcohols with sulfuric acid. Since a
molecule of water is lost for every pair of alcohol molecules, the reaction is a kind of dehydration.

Dehydration to ethers rather than to alkenes is controlled by the choice of reaction conditions. For
example, ethylene is prepared by heating ethyl alcohol with concentrated sulfuric acid to 180; ethyl
ether is prepared by heating a mixture of ethyl alcohol and concentrated sulfuric acid to 140, alcohol
being continuously added to keep it in excess. Dehydration is generally limited to the preparation of
symmetrical ethers, because, as we might expect, a combination of two alcohols usually yields a
mixture of three ethers. Ether formation by dehydration is an example of nucleophilic substitution^
with the protonated alcohol as substrate and a second molecule of alcohol as nucleophile.

Preparation of ethers
1. Williamson synthesis.
alkyl halide (or substituted alkyl halide) is allowed to react with a sodium alkoxide or a sodium
phenoxide:

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Note1 The Williamson synthesis involves nucleophilic substitution of alkoxide ion or phenoxide ion
for halide ion; it is strictly analogous to the preparation of alcohols by treatment of alkyl halides with
aqueous hydroxide
Note2Sodium alkoxides are made by direct action of sodium metal on dry alcohols:

Sodium phenoxides because of the appreciable acidity ofphenols are made by the action of aqueous
sodium hydroxide on phenols:

If we wish to make an unsymmetrical dialkyl ether, we have a choice of two combinations of

reagents; one of these is nearly always better than the other
In the preparation of ethyl ten-butyl ether, for example,the following combinations are conceivable:

note3 since the aryl halide is quite unreactive toward alkoxides.

2. Alkoxymercuration-demercuration.
Alkenes react with mercuric trifluoroacetate in the presence of an alcohol to give alkoxymercurial
compounds which on reduction yield ethers.
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Reactions of ethers
1- Cleavage by acids
The ether linkage is quite stable toward bases, oxidizing agents,it cleavage by acids :

Cleavage involves nucleophilic attack by halide ion on the protonated ether, with displacement of the
weakly basic alcohol molecule:

Such a reaction occurs much more readily than displacement of the strongly basic alkoxide ion from
the neutral ether

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Reaction can proceed by either an SN 1 or SN2 mechanism, depending upon conditions and the
structure of the ether.

a primary alkyl group tends to undergo SN2 displacement, whereas a tertiary alkyl group tends to
undergo SNl displacement.

2- Electrophilic substitution in aromatic ethers

The alkoxy group,OR,was listed as ortho,para-direclmg toward electrophilic aromatic substitution
and moderately activating It is a much stronger activator than R, but much weaker than OH. The
carbonium ions resulting from ortho and para attack were considered to be stabilized by contribution
from structures I and II.

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 EPOXIDES
Epoxides are compounds containing the three-membered ring:

They are ethers, but the three-membered ring gives them unusual properties.
Note Epoxides are ethers, but the three-membered ring gives them unusual properties. By far the
most important epoxide is the simplest one,ethylene oxide. It is prepared on an industrial scale by
catalytic oxidation of ethylene by air.

PREPARATION OF EPOXIDES
From halohydrins.
In the laboratory, the Williamson synthesis of ethers is important because of its versatility: it can be
used to make unsymmetrical ethers as well as symmetrical ethers, and aryl alkyl ethers as well as
dialkyl ethers. In the Williamson synthesis an alkyl halide (or substituted alkyl halide) is
1. allowed to react with a sodium alkoxide or a sodium phenoxide:

2. Peroxidation of carbon-carbon double bonds.

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The conversion of halohydrins into epoxides by the action of base is simply an adaptation of the
Williamson synthesis a cyclic compound is obtained because both alcohol and halide happen to be
part of the same molecule.
In the presence of hydroxide ion a small proportion of the alcohol exists as alkoxide; this alkoxide
displaces halide ion from another portion of the same molecule to yield the cyclic ether.

the carbon-carbon double bond may be oxidized directly to the epoxide group by peroxybenzoic
acid :

When allowed to stand in ether or chloroform solution, the peroxy acid and the unsaturated
compoundwhich need not be a simple alkene react to yield benzoic acid and the epoxide. For
example:

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Reactions of epoxides
1. Acid-catalyzed cleavage.
Like other ethers, aji epoxide is converted by acid into the protonated epoxide, which can then
undergo attack by any. of a number of-nucleophilic reagents. An important feature of the reactions of
epoxides is the formation of compounds that contain two functional groups. Thus, reaction with
water yields a glycol ; reaction with an alcohol yields a compound that is both ether and alcohol.

2. Base-catalyzed cleavage.
Unlike ordinary ethers, epoxides can be cleaved under alkaline conditions.Here it is the epoxide itself,
not the protonated epoxide, that undergoes nucleophilicattack. The lower reactivity of the non-
protonated epoxide is compensated for by the more basic, more strongly nucleophilic reagent:
alkoxide, phenoxide, ammonia, etc.

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 3. Reaction with Grignard reagents
Reaction of Grignard reagents with ethylene oxide is an important method of preparing primary
alcohols since the product contains two carbons more than the alkyl or aryl group of the Grignard
reagent

Orientation of cleavage of epoxides

There are two carbon atoms in an epoxide ring and, in principle, either one can suffer nuclcophilic
attack. In a symmetrical epoxide like ethylene oxide, the two carbons are equivalent, and attack
occurs randomly at both. But in an unsymmetrical epoxide, the carbons are not equivalent, and the
product we obtain depends upon which one is preferentially attacked.

Q/ what is the orientation of cleavage of epoxides, and how does one account for it?
The preferred point of attack, it turns out, depends chiefly on whether the reaction is acid-catalyzed
or base-catalyzed. Consider, for example, two reactions of isobutylene oxide:

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How, then, are we toaccount for the difference in orientation in particular, for SN2 attack at the
more hindered position in acid-catalyzed cleavage?
Tn an SN2 reaction, carbon loses electrons to the leaving group and gains electrons from the
nucleophile, and as a result does not become appreciably positive or negative in the transition state;
electronic factors are unimportant, and steric factors control reactivity. But in acid-catalyzed
cleavage of an epoxide, the carbon-oxygen bond, already weak because of the angle strain of the
three-membered ring, is further weakened by protonation:
the leaving group is a very good one, a weakly basic alcohol hydroxyl. The nucleophile, on the other
hand, is a poor one (water, alcohol, phenol),Although there are both bond-breaking and bond-making
in the transition state, bond-breaking has proceeded further than bond-making; the leaving group has
taken electrons away to a much greater extent than the nucleophile has brought them up, and the
carbon has acquired a considerable positive charge. Crowding, on the other hand, is relatively
unimportant, because both leaving group and nucleophile arc far away. Stability of the transition
state is determined chiefly by electronic factors, not steric factors. We speak of such a reaction as
having considerable SN 1 character. Attack occurs not at the less hindered carbon, but at the carbon
that can best accommodate the positive charge.

In base-catalyzed cleavage, the leaving group is a poorer one a strongly basic alkoxide oxygen-- and
the nucleophile is a good one (hydroxide, alkoxide, phenoxide). Bond-breaking and bond-making are
more nearly balanced, and reactivity is controlled in the more usual way, by steric factors. Attack
occurs at the less hindered carbon.

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