Synthesis and characterization of three 14C-labelled derivatives of 4-chloro-3-sulfamoylbenzoic acid

✍ Scribed by C. E. Blackburn; M. L. Hoefle; S. F. Chang; G. W. Gwynn; R. E. Ober

• Publisher: John Wiley and Sons
• Year: 1966
• Tongue: French
• Weight: 223 KB
• Volume: 2
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2590020409

✦ Synopsis

This paper describes the synthesis and characterization of three '"C labelled compounds prepared for use in drug metabolism studies of certain 4-chloro-3sulfamoylbenzoic acid derivatives possessing diuretic and antihypertensive activity. ( l ' 2, The compounds prepared were : 4-chloro-N-methyl-3-(methylsulfamoyl) -ben~amide(carbonyl-'~C) ; 4-chloro-3-sulfamoylbenzoic acid 2,2dimethylhydrazide(carbony1-'"C) ; 4-chloro-3-sulfamoylbenzoic acid 2,2-dimethylhydrazide(methy1-'"C). These compounds will hereinafter be referred to by the code numbers of CI-456 (carbonyl-'"C), (3-546 (carbonyl-'"C) and C1-546 (methyl-'"C), respectively. CI-456 (~arbonyl-'~C) and CI-546 (~arbonyl-'~C) were synthesized from p-chlorobenzoic acid (carbonyl-'"C). The carbonyl-'"C label was introduced by reacting p-chlorophenylmagnesium bromide with carbon dioxide-'"C. The procedure, scale, and reaction conditions used followed closely those described in Murray and Williams ( 3 ) for the synthesis of benzoic acid (carbonyl-'"C) from bromobenzene. In our experience, the highest yields of carbonyl labelled p-chlorobenzoic acid were obtained using a 50% excess of the Grignard reagent (yields based on Ba '"CO, ranged from 53% to 79%). SYNTHESIS OF Several synthetic routes to CI-456 have been described. (") The reaction sequence used in the synthesis of (21-456 (carbonyl-'"C) is indicated below : Chlorosulfonation was accomplished by adding 1.65g (10.5 mmoles,7.15mc '"C) p-chlorobenzoic acid (carbonyl-'"C) to 30 ml chlorosulfonic acid and