Organic Chemistry

Section 12.7 Reactions of Epoxides 455

Free energy

Progress of the reaction

∆G‡

∆G‡

25 kcal/mol

ethylene oxide

diethyl ether

(105 kJ/mol)

>Figure 12.2

The reaction coordinate diagrams

for nucleophilic attack of hydroxide

ion on ethylene oxide and on

diethyl ether. The greater reactivity

of the epoxide is a result of the

strain (ring strain and torsional

strain) in the three-membered ring,

which increases its free energy.

Although an epoxide and an ether have the same leaving group, epoxides are much

more reactive than ethers in nucleophilic substitution reactions because the strain in

the three-membered ring is relieved when the ring opens (Figure 12.2). Epoxides,

therefore, readily undergo ring-opening reactions with a wide variety of nucleophiles.

Epoxides, like other ethers, react with hydrogen halides. In the first step of the re-

action, the nucleophilic oxygen is protonated by the acid. The protonated epoxide is

then attacked by the halide ion. Because epoxides are so much more reactive than

ethers, the reaction takes place readily at room temperature. (Recall that the reaction

of an ether with a hydrogen halide requires heat.)

Protonated epoxides are so reactive that they can be opened by poor nucleophiles, such

as and alcohols. ( is any acid in the reaction mixture; is any base.)

If different substituents are attached to the two carbons of the protonated epoxide

(and the nucleophile is something other than ), the product obtained from

nucleophilic attack on the 2-position of the oxirane ring will be different from that

obtained from nucleophilic attack on the 3-position. The major product is the one

resulting from nucleophilic attack on the more substitutedcarbon.

H 2 O

H 2 O HB+ B≠

H 2 CCH 2 + HBr CH 2 + Br HOCH 2 CH 2 Br

+

H 2 C

H

−

OO

protonation of the

epoxide oxygen atom back-side attack

by the nucleophile

H 2 CCH 2 CH (^2) H 2 O CH 2 CH 2 OH
+OH
H
HOCH 2 CH 2 OH

• H 2 C
  O
  H
  B
  H B+
  B
  1,2-ethanediol
  ethylene glycol
  CH 3 OH
  CH 3 CH CHCH 3 CH 3 CHCHCH 3
  +OCH
  3
  OH
  H
  CH 3 CH CHCH 3 CH 3 CHCHCH 3 HB+


• 
  


• 
  


• HB+
  O
  H
  OCH 3
  OH
  3-methoxy-2-butanol
  O
  H B+
  O
  BRUI12-437_480r3 27-03-2003 11:51 AM Page 455