Design, synthesis and structure of 2,4-Dicarbo substituted Quinazoline 3-Oxides

Abstract

2-Amino-5-bromoacetophenone was prepared by treating 2-aminoacetophenone with pyridinium tribromide in dichloromethane. The 2-amino-5-iodoacetophenone was synthesized by the reaction of 2-aminoacetophenone with N-iodosuccinimide in acetic acid. Acetylation and benzoylation of the 2-aminoacetophenone and its 5-halogeno derivatives with 1.2 equiv. of acetic anhydride and aryl chloride derivatives in pyridine under reflux afforded the N-(2- acetylphenyl)amides and N-(2-acetyl-4-halo-phenyl)amide derivatives, respectively. Nucleophilic substitution reaction of the latter with hydroxylamine hydrochloride in pyridine under reflux afforded the corresponding N-[2-(1-hydroxyiminoethyl)phenyl]amide and N-(4- halo-2-(1-(hydroxyimino)ethyl)phenyl)amide derivatives. The N-[2-(1- hydroxyiminoethyl)phenyl]amide and N-(4-halo-2-(1-(hydroxyimino)ethyl)phenyl)amide derivatives were, in turn, subjected to intramolecular cyclization with triflouroacetic acid under reflux to afford the 2,4-dicarbo substituted quinazoline 3-oxides. The 6-iodo substituted quinazoline 3-oxides were subjected to palladium catalysed Suzuki-Miyaura cross-coupling reaction with 4-fluorophenylboronic acid to afford 2,4,6-tricarbo substituted quinazoline 3- oxides. The prepared compounds were characterized using a combination of NMR (1H and 13C), IR and mass spectrometric techniques. The geometry of the 2,4-dicarbo substituted quinazoline 3-oxides were confirmed through X-ray diffraction analysis of compound 92b.