SYNTHESIS AND EVALUATION OF SOME NEWLY TRIAZOLYLINDOLE DERIVATIVES FOR ANTIFUNGAL ACTIVITY

Abstract

A series of novel 2 - ((2 - (phenyl/4 - chl orophenyl) - 1 - ((4 - ((Z) - 1 - (substitutedphenyl)ethylideneamino) - 5 - mercapto - 4H - 1,2,4 - triazol - 3 - yl)methyl) - 1H - indol - 3 - yl)methyleneamino)benzoic acid (9 - 16) were synthesized by treating 2 - ((1 - ((4 - amino - 5 - mercapto - 4H - 1,2,4 - triazol - 3 - yl)methyl) - 2 - (phenyl/4 - chloroph enyl) - 1H - indol - 3 - yl)methyleneamino)benzoic acid (7 - 8) with various substituted acetophenone. The structure of the compounds was characterized by IR and 1 General procedure for preparation of 2 - ((2 - phenyl/4 - chlorophenyl - 1H - indol - 3 - yl)methyleneamino)benzoic acid (1 - 2) A mixture of 2 - phenyl/4 - chlorophenyl - 1H - indole - 3 - carbaldehydes (0.1 mol) and anthranilic acid (0.1 mol) in absolute ethanol (90 ml) cont aining few drops of glacial acetic acid was refluxed for 28 h and excess of solvent was distilled off. The solids thus obtained were filtered, dried and re crystallized from ethyl acetate to yield compounds 1 - 2 2 - ((1 - (2 - ethoxy - 2 - oxoethyl) - 2 - (phenyl/4 - chlo rophenyl) - 1H - indol - 3 - yl)methyleneamino)benzoic acid (3 - 4) A mixture of compounds 1 - 2 (0.1 mol), ethyl chloroacetate (0.1 mol), anhydrous acetone (90 ml) and NaOH (16 g) was heated under reflux of 22 h. The reaction mixtures were cooled, wash with excess of water, filtered and dried, again washed with ethanol and re c r ystallized from appropriate solvent to yield compounds 3 - 4. 2 - ((1 - (2 - hydrazinyl - 2 - oxoethyl) - 2 - phenyl - 1H - indol - 3 - yl)methyleneamino)benzoic acid (5 - 6) A mixture of compounds 3 - 4 (0.1 mol) and hy drazine hydrate (0.2 mol) in absolute ethanol (80 ml) was refluxed for 18 h then cooled and poured on crushed ice and separated. The solids were filtered, washed with cold water, dried and re c r ystallized from appropriate solvent to yield compounds 5 - 6. 2 - ((1 - ((4 - amino - 5 - mercapto - 4H - 1,2,4 - triazol - 3 - yl)methyl) - 2 - (phenyl/4 - chlorophenyl) - 1H - indol - 3 - yl)methylene amino)benzoic acid (7 - 8) To the ice cold mixture of compounds 5 - 6 (0.1 mol) and KOH (0.4 mol) in dry ethanol (90 ml), carbon disulphide (0.1 mol) was a dded with magnetic stirring. The reaction mixtures were stirred further at room temperature for 24 h. The separated solids were filtered washed with dry ether and dried. These were further magnetically stirred with hydrazine hydrate (0.15 mol) on boiling w ater bath for 4 h till the evolution of H 2 S ceased. The reaction mixtures were poured into ice - cold water then filtered, washed with water, dried and re crystallized from acetic acid to yield compounds 7 - 8.