Synthesis of Benzo[f]coumarin Incorporated Sulfonohydrazones as Potential Anti-proliferative-Agents

Abstract

2-Acetyl-3H-benzo[j]chromen-3-one finds wide applications as significant structural motifs of pharmacological importance. The 2-acetyl-3H-benzo[j]chromen-3-one core appears as a constituent of anti-cancer, anti-bacterial, anti-viral, anti-oxidant, anti fungal, anti-adipogenic, and anti-proliferative drugs. Besides, aromatic sulfonyl hydrazides also hold vast utilization as pharmaceutical agents. In the present work, N-(1-(3-oxo-3H-benzo [j]chromen-2-yl)ethylidene )benzene sulfonohydrazides were synthesized from 2-acetyl-3H-benzo[j]chromen-3-one and aromatic sulfonyl hydrazides by convergent synthesis pathway. The target molecules, N-(1-(3-oxo-3H-benzo[j]chromen-2-yl)ethylidene)benzenesulfonohydrazides (IXa-i), were produced following four-step reaction sequence. In the first step, 2-acetyl-3H benzo[j]chromen-3-one (III) was prepared by condensation of 2 hydroxynaphthaldehyde (I) with ethyl acetoacetate (II) using morpho line as a catalyst. In the next step, sulfonyl chlorides (VIf-i) were synthesized from different benzene derivatives (IVf-i). In the third step, substituted benzenesulfonyl hydrazides (VIlla-i) were synthesized by nucleophilic substitution of aromatic sulfonyl chlorides (VIa-i) using hydrazine hydrate (VII). In the final step, 2-acetyl-3H benzo[j]chromen-3-one (III) was coupled with substituted benzenesulfonyl hydrazides (VIlla-i) employing acetic acid as a catalyst to afford the final products, N-(1-(3-oxo-3H-benzo[j]chromen-2-yl)ethylidene)benzenesulfonohydrazides (IXa-i). The synthesis of target compounds N-(1-(3-oxo-3H-benzo[j]chromen-2 yl)ethylidene)benzenesulfonohydrazides (IXa-i), was confirmed engaging FT-IR, IH and 13C_NMR spectroscopy. The synthesized compounds will be evaluated for anti-proliferative activities.