Synthesis of [2-aryl-6-oxo-6H-chromeno[6,7-d]oxazol-8-yl]-acetic acid ethyl esters

Abstract

A number of coumarino[6,7-d]oxazoles (nitrogen analogs of psoralens) have been synthesized from (7-hydroxy-2-oxo-2H-chromen-4-yl) acetic acid ethyl ester 1. The synthetic route began with the nitration of 1 with nitric acid in acetic acid to give (6-nitro-7-hydroxy-2-oxo-2H-chromen-4-yl) acetic acid ethyl ester 2; (3,6-dinitro-7-hydroxy-2-oxo-2H-chromen-4-yl) acetic acid ethyl ester 3 and (3,6,8-trinitro-7-hydroxy-2-oxo-2H-chromen-4-yl) acetic acid ethyl ester 4. The reduction of 2 was accomplished with tin(II) chloride, tin, and concentrated hydrochloric acid in ethanol giving (6-amino-7-hydroxy-2-oxo-2H-chromen-4-yl) acetic acid ethyl ester 5. After the condensation of aminocoumarin 5 with aromatic aldehyde in glacial acetic acid medium, followed the dehydrocyclization to coumarino[6,7-d]oxazoles 7a-k. The intermediate Schiff's bases 6a-k have been obtained from 5 with aromatic aldehyde in ethanol. Antibacterial and antifungal activities of the compounds have been evaluated.