Ammonia → Diazepam

Participants

Reaction Steps

A mixture of hexamethylenetetramine (17.5 g., 0.125 mol), methanol (135.5 ml) and 2(2-chloro-N-methylacetamido)-5-chlorobenzophenone (80.5 g., 0.25 mol) was saturated with ammonia. Heat the stirred mixture slowly to reflux with a steady stream of ammonia flowing through the mixture. During the course of the reaction ##STR5## was prepared. The product was not isolated. Hold at reflux for 6 hours. Stop the flow of ammonia and remove the solvent under vacuum. Take up the residue in a mixture of toluene (500 ml.) and hot water (500 ml). Separate the toluene phase and add to it, with stirring, 3N nitric acid (169 ml). The crystals which separate are filtered, wash with toluene (50 mls) and resuspended in a mixture of toluene (250 ml) and water (250 ml). Concentrated ammonia (30 ml) is added to pH 8. The toluene phase is separated, washed with water (250 ml) and then distilled to dryness in vacuo yielding 96.09% of 7-chloro-1-methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, melting point 125° to 127° C.

Provenance & Evidence