Novel synthesis and anti-microbial activity study of innovative mannich bases containing 2-phenoxy-1,3, 2-dioxa phospholanes and indole systems

Abstract

In the present study, synthesis, characterization, antimicrobial activity on some novel pyrazolone derivatives has been taken up. The primary amines were diazotized with sodium nitrite and HCl mixture at 0-5°C which were further coupled with ethyl acetoacetic ester to afford phenyl diazonium acetoacetic esters (II). Condensation of 4-substituted aryl hydrazono acetoacetic ester, 4-hydrazinylbenzenamine in the presence of catalytic amount of DMF under microwave irradiation afforded (4Z)-4-(2-substituted aryl hydrazono)-1-(4-aminophenyl)-3-methyl-1H-pyrazol-5(4H)-one (III). Subjecting (III) to anhydrous K 2 CO 3 in DMF for 8 hours afforded 2-{4-[(4Z)-4-(2-substituted aryl hydrazono)-4, 5-dihydro-3-methyl-5-oxopyrazol-1-yl] phenyl amino} acetate( IV) which was further reacted with hydrazine hydrate to afford 2-{4-[(4Z)-4-(2-substituted aryl hydrazono)-4, 5-dihydro-3-methyl-5-oxopyrazol-1-yl] phenylamino} acetohydrazide (V). Reaction of (V) and Isatin (VI b) in DMF afforded (4Z)-2-(4-((15Z)-4-(2-phenylhydrazono)-4,5-dihydro-3-methyl-5 oxopyrazol-1-yl)phenylamino)-N'-(2-oxoindolin-3-ylidene)acetohydrazide (VII). Compound (VII) was subsequently subjected to Mannich reaction with cyclic secondary amines (piperidine/morpholine/N-methyl piperidine) in the presence of formaldehyde in DMF to afford (4Z)-2-(4-((15Z)-4-(2-substituted aryl hydrazono)-4,5-dihydro-3-methyl-5-oxopyrazol-1-yl)phenylamino)-N'-(2-oxo-1-((piperidin-1-yl)methyl)indolin-3-ylidene)acetohydrazide (VIII) which was characterized by I.R, 1HNMR and Mass data. The anti-bacterial activity of synthesized compounds was studied by the disc diffusion method against pathogenic bacteria and fungi.