Organic Chemistry

Section 12.10 Thiols, Sulfides, and Sulfonium Salts 465

The blistering caused by mustard gas is due to the high local

concentrations of HCl that are produced when water—or any

other nucleophile—reacts with the gas when it comes into

contact with the skin or lungs. Autopsies of soldiers killed by

mustard gas in World War I—estimated to be about 400,000—

showed that they had extremely low white blood cell counts,

indicating that the gas interfered with bone marrow develop-

ment. An international treaty in the 1980s banned its use and

required that all stockpiles of mustard gas be destroyed.

+

ClCH 2 CH 2 SCH 2 CH 2 ClCH 2 CH 2 S

CH 2

CH 2

Cl Cl CH 2 CH 2 SCH 2 CH 2 OH

Cl−

+ H+

H 2 O

H 2 O

+

SCH 2 CH 2 OH

CH 2

CH 2

H+ + HOCH 2 CH 2 SCH 2 CH 2 OH + Cl−

+

mustard gas sulfonium salt

ANTIDOTE TO A WAR GAS

Lewisite is a war gas developed in 1917 by W. Lee

Lewis, an American scientist. The gas rapidly

penetrates clothing and skin and is poisonous because it con-

tains arsenic, which combines with thiol groups on enzymes,

thereby inactivating the enzymes. During World War II, the

Allies were concerned that the Germans would use lewisite, so

British scientists developed an antidote to lewisite that the Al-

lies called “British anti-lewisite”(BAL). BAL contains two

thiol groups that react with lewisite, thereby preventing it from

reacting with the thiol groups of enzymes.

+

CH 2 SH

CH 2 OH

BAL

CHSH

Cl

lewisite

H

C

H

C

H Cl

As

CH C

2 S

CHS

As

Cl

Cl

CH 2 OH

H

C + 2 HCl

if the group undergoing nucleophilic attack is a methyl group or a primary alkyl group.

In Section 10.11, we saw that SAM, a biological methylating agent, is a sulfonium salt.

PROBLEM 26

Using an alkyl halide and a thiol as starting materials, how would you prepare the following

compounds?

a. c.

b. d. SCH 2

CH 3

CH 3 SCCH 3

CH 3

CH 2 CHCHSCH 2 CH 3

CH 3

CH 3 CH 2 SCH 2 CH 3

HO CH 3 SCH 3 CH 3 OH

CH 3

− + + CH 3 SCH 3

+

MUSTARD GAS

Chemical warfare occurred for the first time in

1915, when Germany released chlorine gas

against French and British forces in the battle of Ypres. For the

remainder of World War I, both sides used a variety of chemical

agents. One of the more common war gases was mustard gas, a

reagent that produces blisters over the surface of the body. It is

a very reactive compound because the highly nucleophilic

sulfur easily displaces a chloride ion by an intramolecular

reaction, forming a cyclic sulfonium salt that reacts rapidly

with a nucleophile. The sulfonium salt is particularly reactive

because of the strained three-membered ring.

SN 2

BRUI12-437_480r3 27-03-2003 11:51 AM Page 465