The technical preparation of dimidium bromide: A new phenanthridine synthesis

Abstract

Abstract In the course of process development for the trypanocidal drug dimidium bromide, a study has been made of the Morgan‐Walls phosphoryl chloride cyclintion of 4:4′‐dinitro‐z‐bewmidodi‐phenyl to the corresponding pheananthridine. The reaction involves the readily isolated intermediate iminochloride which undergoes facile cyclization only in presence of certain inorganic halide catalysts. The analogy to the Friedel‐Crafts reaction is discussed. A novel synthesis of the same phenanthridine by direct interaction of 4 :4′‐dinitro‐2‐aminodiphenyl and benzotrichloride is reported. This reaction entails the intermediate formation successively of an amidine and the iminochloride, and also requires catalysis by metal halides. It has been developed to a much simplified process giving excellent over‐all yields. A new type of derivative of dimidium is also described. This is 2: 7‐diamino‐9‐butoxy‐9‐phenyl‐10‐methyl‐9:10‐dihydrophenanthridine (‘butoxide’); it is valuable in the preparation of dimidium salts.