Page 140 - Chemical and process design handbook

Speight_Part II_B 11/7/01 3:11 PM Page 2.81

BENZODIAZEPINES

Benzodiazepines are a series of compounds that have a benzene ring fused
to a seven-membered ring containing two nitrogen atoms. The two most
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successful members of the group are diazepam (Valium ) and chlor-
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diazepoxide (Librium ); Flurazepam (Dalmane ) is a hypnotic.
The production of diazepam (Fig. 1) starts from p-chloroaniline pre-
pared from benzene by nitration, reduction of the nitro group to an amine,
and chlorination of the o,p-directing aniline) followed by reaction with
benzoyl chloride (from toluene by oxidation to benzoic acid, followed by
acid chloride formation) in a Friedel-Crafts acylation. Acylation occurs at
the o-position, and formation of the oxime derivative is followed by
methylation and then acylation of the amino group with chloroacetyl chlo-
ride. Heating with base eliminates hydrogen chloride to form the ring and
reduction of the amine oxide with hydrogen gives diazepam.
Diazepam is used for the control of anxiety and tension, the relief of
muscle spasms, and the management of acute agitation during alcohol
withdrawal, but it may be habit forming.

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