Efficient synthesis of quinazolinones through base promoted dehydrocyclization using copper (II) catalyst

Abstract

Two keto-pyrazole based ligands (2a, 2b) having N^{^}N^{^}O chelating Schiff base and its Cu(II) complexes, (Z)-5-methyl-2-phenyl-4-((quinolin-8-ylimino)(p-tolyl)methyl)-pyrazol Cu(II) chloride (3a) and (Z)-5-methyl-2-phenyl-4-((pyridin-2-ylmethyl)imino)(p-tolyl)methyl)-2pyrazol Cu(II) chloride (3b) are reported here. Single-crystal X-ray diffraction analysis confirms a four-coordinate square planar environment around Cu(II) centre. The complexes act as catalysts, facilitating the dehydrogenation of primary alcohols with amino benzamide to form quinazolin-4(3H)-one cores. The optimized catalytic system demonstrates broad substrate tolerance and high functional group compatibility, delivering products in excellent yields (up to 96%). Mechanistic investigations, including mercury poisoning tests and HRMS analysis, validates a non-radical, two-electron hydride transfer pathway for alcohol dehydrogenation. This sustainable method utilizes readily available earth-abundant phosphine-free copper catalysts, providing a practical and environmentally benign route to biologically significant N-heterocycles.