Organic Chemistry

Section 11.9 Substitution and Elimination Reactions in Synthesis 425

PROBLEM 19

Indicate whether the alkyl halides listed will give mostly substitution products, mostly

elimination products, or about equal amounts of substitution and elimination products

when they react with the following:

a. methanol under conditions

b. sodium methoxide under conditions

1. 1-bromobutane 3. 2-bromobutane


2. 1-bromo-2-methylpropane 4. 2-bromo-2-methylpropane

PROBLEM 20

1-Bromo-2,2-dimethylpropane has difficulty undergoing either or reactions.

a. Explain why. b. Can it undergo E2 and E1 reactions?

11.9 Substitution and Elimination

Reactions in Synthesis

When substitution or elimination reactions are used in synthesis, care must be taken to

choose reactants and reaction conditions that will maximize the yield of the desired

product. In Section 10.4, you saw that nucleophilic substitution reactions of alkyl

halides can lead to a wide variety of organic compounds. For example, ethers are syn-

thesized by the reaction of an alkyl halide with an alkoxide ion. This reaction, discov-

ered by Alexander Williamson in 1850, is still considered one of the best ways to

synthesize an ether.

The alkoxide ion for the Williamson ether synthesisis prepared by using

sodium metal or sodium hydride (NaH) to remove a proton from an alcohol.

The Williamson ether synthesis is a nucleophilic substitution reaction. It is an

reaction because it requires a high concentration of a good nucleophile. If you

want to synthesize an ether such as butyl propyl ether, you have a choice of starting

materials: You can use either a propyl halide and butoxide ion or a butyl halide and

propoxide ion.

If, however, you want to synthesize tert-butyl ethyl ether, the starting materials must

be an ethyl halide and tert-butoxide ion. If you tried to use a tert-butyl halide and

ethoxide ion as reactants, you would obtain the elimination product and little or no

ether because the reaction of a tertiary alkyl halide under conditions forms

primarily the elimination product. So, in carrying out a Williamson ether synthesis, the

SN 2 >E2

propyl bromide butoxide ion butyl propyl ether

CH 3 CH 2 CH 2 Br + CH 3 CH 2 CH 2 CH 2 O− CH 3 CH 2 CH 2 OCH 2 CH 2 CH 2 CH 3 + Br−

butyl bromide propoxide ion butyl propyl ether

CH 3 CH 2 CH 2 CH 2 Br + CH 3 CH 2 CH 2 O− CH 3 CH 2 CH 2 OCH 2 CH 2 CH 2 CH 3 + Br−

SN 2

ROH + Na RO− + Na+ + 21 H 2

ROH + NaH RO− + Na+ + H 2

(RO-)

Williamson ether synthesis

alkyl halide alkoxide ion ether

RBr+ RO− ROR + Br−

SN 2 SN 1

SN 2 >E2

SN 1 >E1

Alexander William Williamson

(1824–1904)was born in London to

Scottish parents. As a child, he lost

an arm and the use of an eye. He was

midway through his medical

education when he changed his mind

and decided to study chemistry. He

received a Ph.D. from the University

of Geissen in 1846. In 1849, he

became a professor of chemistry at

University College, London.

Tutorial:

E2 Promoting factors

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