Synthesis of chromone-3-carboxylic acid derivatives; 6-chlorochromone-3-carboxylic acid and 7-chloro-6-fluorochromone-3-carboxylic acid

Abstract

The N-1 substitution of the quinolones has been proposed tobe one of the structural requirements for antibacterial activity.This research is to study the bioisosterism of quinolonecompounds with N-1 position modification because the N-1unsubstituted analogs were known to lose activity. Thebioisosterism of quinolones, chromone-3-carboxylic acidderivatives were designed and synthesized as potentialantibacterial agents. Chromone-3-carboxylic acid derivatives havebeen prepared via 6 steps : 1) Phenyl acetate intermediates wereobtained by the reaction of phenol derivatives with aceticanhydride in alkali condition. 2) 2-Hydroxyacetophenonederivatives were achieved by heating phenyl acetate derivativeswith aluminium chloride. 3) Chromone-3-carboxaldehyde derivativeswere obtained by the reaction of 2-hydroxyacetophenonederivatives with phosphorous oxychloride and dimethylformamide.4) Chromone-3-carboaldoxime derivatives were obtained by thereaction of chromone-3-carboxaldehyde derivatives withhydroxylamine hydrochloride. 5) Chromone-3-carboaldoximederivatives were dehydrated with acetic anhydride to affordchromone-3-carbonitrile derivatives. 6) Chromone-3-carboxylic acidderivatives were accomplished by heating chromone-3-carbo-nitrilederivatives with 55% sulfuric acid. 6-Chlorochromone-3-carboxylicacid found to be active against S. aureus while7-chloro-6-fluorochromone-3-carboxylic acid was active against E.coli.