APPLICATION OF GREEN CHEMISTRY IN THE SYNTHESIS OF 2-(2- FLUOROBIPHENYL-4-YL) PROPANOIC ACID DERIVATIVES

Abstract

Present study complies with different principles of green chemistry utilizing efficient instrumental techniques i.e; microwaves, ultrasonic waves and replacement of hazardous solvents with greener ones. The overall progress of chemical reactions achieved through application of green chemistry, was compared with the traditional methods. In the first part of this research work, synthesis of N’-benzylidene-2-(2-fluorobiphenyl)propanehydrazides was carried out for which, 2-(2-fluorobiphenyl-4-yl)propanoic acid was esterified to methyl 2-(2- fluorobiphenyl-4-yl)propanoate under the influence of microwaves followed by its hydrazinolysis. 2-(2-Fluorobiphenyl-4-yl)propanehydrazide thus obtained, was then reacted in an ultrasonic bath with different benzaldehydes to get a series of N’-benzylidene-2-(2- fluorobiphenyl)propanehydrazides. In the second series, 2-(2-fluorobiphenyl-4-yl)propane hydrazide was converted to 4-amino-5- [1-(2-fluoro-biphenyl-4-yl)-ethyl]-4H-[1,2,4]triazole-3-thiole followed by its reaction with different benzaldehydes under conventional and green technologies to get a series of 4- (benzylidene-amino)-5-[1-(2-fluorobiphenyl-4-yl]-4H-[1,2,4]triazole-3-thiole compounds. In another series, different substituted chalcones were prepared by clasian condensation method which were then reacted with 2-(2-fluorobiphenyl-4-yl) propane hydrazide in a mixture of water and ethanol to get a series of 2-(2-fluorobiphenyl-4-yl)-propionic acid(1,3- diphenyl-allylidene)-hydrazide. These reactions were conducted utilizing green technologies and were compared with using conventional methods. Comparison of both the conventional and microwaves/ultrasound assisted reactions indicates a significant reduction in reaction times and improvement in reaction yields. Besides, chemical characterization and X-ray crystallography of selected compounds, all the synthesized compounds were evaluated for their anti-oxidant potential [Total anti-oxidant activity, ferric reducing anti-oxidant power (FRAP) and total phenolic contents], and analgesic activities using (tail flick, hot plate and writhing methods) and most of them were found to possess potential as lead compounds for drug discovery.