Catalyst-free synthesis of triazoloquinoline derivatives via HOSA-mediated nitrile intermediates: Mechanistic insight, substrate scope, and in vitro biological evaluation

A novel, catalyst-free method was developed for the synthesis of pharmaceutically significant triazoloquinoline derivatives from substituted 2-chloroquinoline-3-carbaldehydes, using hydroxy(tosyloxy) iodobenzene (HOSA) as a mild oxidative dehydrating agent in acetonitrile at 60°C, in the presence of sodium acetate. The protocol yields nitrile intermediates (68%-85%) and is compatible with a wide range of functional groups, supporting the synthesis of diverse drug candidates. Infrared spectroscopy confirmed oxime formation followed by dehydration to nitrile. Subsequent intramolecular cyclization generated [1,2,4] triazolo[4,3-a] quinoline-4-carbonitrile (C₁₁H₆N₄, melting point (MP) 160–163°C) in good purity and yield. The compound exhibited in vitro antimicrobial and cytotoxic activity, highlighting its potential for pharmaceutical applications. The method avoids toxic cyanide sources, operates under mild conditions, and is scalable, making triazoloquinoline derivatives promising medicinal candidates.