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Clonazepam is a benzodiazepine-class medication whose synthesis was reported in 1962 by Leo H. Sternbach and co-workers at Hoffmann–LaRoche (Nutley, NJ).1 The report was the tenth in a series on quinazolines and 1,4-benzodiazepines. Sternbach was a pioneer in the development of the psychotherapeutic benzodiazepines, the best known of which is former Molecule of the Week diazepam2 (Valium).
Clonazepam was originally developed as an anticonvulsant; but it is more frequently used to treat anxiety, seizures (including those associated with epilepsy), panic disorder, and some psychoses. Although the drug is considered to be nonhazardous, the US Drug Enforcement Administration classifies it as a Schedule IV controlled substance because abusing it can lead to psychological dependence.
Sternbach’s clonazepam synthesis ended with nitration of the previously unsubstituted benzene ring. The current manufacturing method, according to R. S. Vardanyan and V. J. Hruby in Synthesis of Essential Drugs, is similar to Sternbach’s synthesis: five steps starting from 2-chloro-2′-nitrobenzophenone and ending with the same nitration step.
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