Organic Chemistry

O 2 cytochrome P 450

a diol epoxide

O

O

H 2 O

epoxide hydrolase

HO

HO

HO

HO

Section 12.8 Arene Oxides 461

BENZO[a]PYRENE AND CANCER

Benzo[a]pyrene is one of the most carcinogenic of

the aromatic hydrocarbons. This hydrocarbon is

formed whenever an organic compound undergoes incomplete

combustion. For example, benzo[a]pyrene is found in cigarette

smoke, automobile exhaust, and charcoal-broiled meat. Several

The 4,5-oxide is harmful because it forms a carbocation that

cannot be stabilized by electron delocalization without destroy-

ing the aromaticity of an adjacent benzene ring. Thus, the car-

bocation is relatively unstable, so the epoxide will tend not to

open until it is attacked by a nucleophile. The 7,8-oxide is

harmful because it reacts with water to form a diol, which then

forms a diol epoxide. The diol epoxide does not readily under-

go rearrangement (the harmless pathway), because it opens to a

carbocation that is destabilized by the electron-withdrawing

OH groups. Therefore, the diol epoxide can exist long enough

to be attacked by nucleophiles (the carcinogenic pathway).

benzo[a]pyrene 4,5-benzo[a]pyrene oxide 7,8-benzo[a]pyrene oxide

O O

cytochrome P 450

O 2

+

12 1

11

10

9

8

765

4

3

2

arene oxides can be formed from benzo[a]pyrene. The two most

harmful are the 4,5-oxide and the 7,8-oxide. It has been suggest-

ed that people who develop lung cancer as a result of smoking

may have a higher than normal concentration of cytochrome

P 450 in their lung tissue.

CHIMNEY SWEEPS AND CANCER

In 1775, a British physician named Percival Potts

was the first to recognize that environmental fac-

tors can cause cancer, when he became aware that chimney

sweeps had a higher incidence of scrotum cancer than the male

population as a whole. He theorized that something in the chim-

ney soot was causing cancer. We now know that it was

benzo[a]pyrene. Titch Cox, the chimney

sweep responsible for

cleaning the 800 chimneys

at Buckingham Palace.

the electron-withdrawing nitro group increases the arene oxide’s susceptibility to

nucleophilic attack, the cancer-causing pathway.

O

OCH 3 OCH 3

OH

H 2 O +

O

N+

H 2 O

+

−OO

N+

−OO

OH

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