Green and Sustainable Syntheses of Quinoxaline Derivatives via Nicotinamide Catalysis in Water

Abstract The synthesis of medicinally significant quinoxaline derivatives, utilizing quinoxaline as a heterocyclic scaffold, was efficiently achieved with catalytic amounts of nicotinamide, one of the B-vitamins and a cost-effective, nontoxic, and readily available catalyst, in water, yielding excellent results with merely 10 mol% catalyst loading. A systematic examination of the reaction parameters, including solvent and catalyst loading, was conducted to optimize the yield. Various aromatic and aliphatic 1,2-diketones and 1,2-diamines, such as substituted phenylenediamines and heterocyclic diamines, were subjected to nicotinamide-catalyzed condensation, producing 20 quinoxaline derivatives in high yields (85–96%). The reaction products were characterized by 1H and 13C NMR, FT-IR, and mass spectral analyses. This green and sustainable method, utilizing water as a solvent, highlights quinoxaline’s potential as a valuable scaffold in the medicinal chemistry of small-molecule drugs for diverse therapeutic applications.