Ammonia → Nordiazepam

Participants

Reaction Steps

A mixture of paraformaldehyde (147.2 g.) and methanol (550 ml.) was stirred and heated to reflux with a steady stream of ammonia bubbling in. The crystal slurry of hexamethylenetetramine which formed was cooled to room temperature and 2-chloroacetamido-5-chlorobenzophenone (308.2 g., 1.0 mol) was added in one portion. With ammonia bubbling in, the reaction mixture was heated at reflux for 10 hours. The flow of ammonia was interrupted and the reaction mixture was cooled to room temperature, filtered, washed with methanol (2 × 125 ml.) and hot water (4 × 500 ml) and dried. There was obtained 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (220.4 g., 81.4%) melting at 212.5° to 215° C.

Provenance & Evidence