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E cient
Synthesis
of 3-
Hydroxy-
1,4-
benzodiazepines
Oxazepam
and
Lorazepam
by New
Acetoxylation
Reaction
of 3-
Position
of 1,4-
Benzodiazepine
Ring
Ivica Cepanec, Mladen Litvić and Ivan Pogorelić

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 Cite this: Org.

Process Res. Dev.
2006, 10, 6, 1192-
1198
Publication
Date: October 28,
2006 
https://doi.org/10.1021/op068009u
Copyright © 2006
American Chemical
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SUBJECTS: Organic acids, Iodine, Potassium, Organic compounds Anions

Abstract

Simple,
efficient, and
scalable
syntheses of
3-hydroxy-
1,4-
benzodiazepines,
oxazepam (1),
and
lorazepam (2)
were
developed.
The
syntheses are
based on the
new
acetoxylation
reaction of
 
the 3-position
of the 1,4-
benzodiazepine
ring. The
reaction
involves
iodine (20−50
mol %)-
catalyzed
acetoxylation
in the
presence of
potassium
acetate (2
equiv) and
potassium
peroxydisulfate
(1−2 equiv) as
a
stoichiometric
oxidant
affording the
corresponding
3-acetoxy-1,4-
benzodiazepines
in good-to-
high yields.
The latter
were
converted by
selective
saponification
to 3-hydroxy-
1,4-
benzodiazepines
of very high
purity
(>99.8%) in
an overall
yield of 83%
(oxazepam)
and 64%
(lorazepam).
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