Organic Chemistry

456 CHAPTER 12 Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing Compounds

The more substituted carbon is more likely to be attacked because, after the epoxide

is protonated, it is so reactive that one of the bonds begins to break before the

nucleophile has a chance to attack. As the bond starts to break, a partial positive

charge develops on the carbon that is losing its share of the oxygen’s electrons. The

protonated epoxide breaks preferentially in the direction that puts the partial positive

charge on the more substituted carbon, because a more substituted carbocation is more

stable. (Recall that tertiary carbocations are more stable than secondary carbocations,

which are more stable than primary carbocations.)

The best way to describe the reaction is to say that it occurs by a pathway that is

partially and partially It is not a pure reaction because a carbocation

intermediate is not fully formed; it is not a pure reaction because the leaving

group begins to depart before the compound is attacked by the nucleophile.

In Section 12.6, we saw that an ether does not undergo a nucleophilic substitution

reaction unless the very basic leaving group is converted by protonation into a

less basic ROH group. Because of the strain in the three-membered ring, epoxides are

reactive enough to open without first being protonated. When a nucleophile attacks an

unprotonated epoxide, the reaction is a pure reaction. That is, the bond

does not begin to break until the carbon is attacked by the nucleophile. In this case, the

nucleophile is more likely to attack the less substitutedcarbon because the less sub-

stituted carbon is more accessible to attack. (It is less sterically hindered.) Thus, the

site of nucleophilic attack on an unsymmetrical epoxide under neutral or basic condi-

tions (when the epoxide is notprotonated) is different from the site of nucleophilic

attack under acidic conditions (when the epoxide isprotonated).

After the nucleophile has attacked the epoxide, the alkoxide ion can pick up a proton

from the solvent or from an acid added after the reaction is over.

site of nucleophilic attack

under acidic conditions

site of nucleophilic attack

under basic conditions

CH 3 CH CH 2

O

SN 2 C¬O

• OR

SN 2

SN 1 SN2. SN 1

C¬O

C¬O

3-D Molecule:

Propylene oxide

H+ CH 3 OH

CH 3 CH ++

O

CH 2 CH 3 CHCH 2 OH H+

OCH 3

CH 3 CH CH 2

+

O

H

CH 3 CHCH 2 OCH 3

OH

2-methoxy-1-propanol

major product

1-methoxy-2-propanol

minor product

+

+

δ+

δ+

δ+

δ+

major product

minor product

CH 3 CH CH 2

OH+

CH 3 CHCH 2 OH

OCH 3

H

CH 3 CHCH 2 OH

OCH 3

CH 3 CH CH 2

O

H

CH 3 CHCH 2 OCH 3

H

OH

CH 3 CHCH 2 OCH 3

OH

CH 3 CH CH 2

O

H

CH 3 OH

CH 3 OH

developing secondary carbocation

developing primary carbocation

+ H+

+ H+

− CH 3 OH

or

H+

+ CH 3 CHCH 2 OCH 3

O−

CH 3 CH CH 2

O

CH 3 CHCH 2 OCH 3

OH

CH 3 O + CH 3 O−

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