Design, synthesis and structure of 2,4-Dicarbo substituted Quinazoline 3-Oxides
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Authors
Onwu, Eugene Ebubechukwu
Issue Date
2021-07
Type
Dissertation
Language
en
Keywords
2-Amino-5-halogenoacetophenones , Amides , Oximes , 2,4-dicarbo substituted quinazoline 3-oxides , Suzuki-Miyaura cross-coupling reaction , 2,4,6-tricarbo substituted quinazoline 3-oxides , X-ray diffraction analysis
Alternative Title
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.