Abstract

DESIGN, SYNTHESIS AND BIOLOGICAL ACTIVITIES OF 1,3,4-OXADIAZOLE DERIVATIVES OF THYMOL ISOLATED FROM TRACHYSPERMUM AMMI

Chaluvaraju K. C.*, Amith Kumar B. S., Basavaraj S. Unakalla and Bhagyshree Khot

ABSTRACT

In the current study, a series of four novel substituted 5-{[5-methyl-2-(propan-2- yl)phenoxy] methyl}-2,3-dihydro-1,3,4-oxadiazole-2-thiol (4a-4d) were synthesized by four steps. The first step involves the generation of ether linkage between thymol and ethyl chloroacetate in the presence of anhydrous Potassium carbonate resulting in the formation of Ethyl[5-methyl-2-(propan-2-yl)phenoxy]acetate (2). In the second step, the ester (2) was refluxed with Hydrazine hydrate to give 2-[5-methyl-2-(propan-2- yl) phenoxy] acetohydrazide (3). The third step involves cyclization where the thiol group was introduced into compound (3) to give 5-{[5-methyl-2-(propan-2-yl) phenoxy] methyl}-2,3- dihydro-1,3,4-oxadiazole-2-thiol (4). In the fourth step, 5-{[5-methyl-2-(propan-2- yl)phenoxy] methyl}-2,3-dihydro-1,3,4-oxadiazole-2-thiol was made to react separately with Benzyl chloride, Ethyl-2-bromoisobutyrate, Benzoyl chloride and acetyl chloride to give (4a-4d) respectively in the presence of anhydrous potassium carbonate and solvent dimethylformamide. These synthesized compounds were characterized by melting point, TLC, chemical tests, IR,1H NMR, and Mass spectrometric studies. All the synthesized compounds (4a-4d) were evaluated for antioxidant activity and anti-inflammatory activity by using DPPH assay and anti-inflammatory models such as the carrageenan-induced rat paw edema method and Protein denaturation method respectively.

Keywords: Thymol, 1,3,4-oxadiazole, antioxidant, anti-inflammatory, Diclofenac, Ascorbic acid, etc.