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Updated: May 28, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
A Synthesis of 4-Quinolone N-Oxides and NMR Evidence of Their Protonation-Assisted Enolisation
Plamen Angelov1,2, Yordanka Sapundzhieva1,2, Francisco Alonso3
1University Centre on Tautomeric Research and Education in Science and Technology (ERA Chair UCTREST), University of Plovdiv Paisii Hilendarski, 24 Tsar Asen Str., 4000 Plovdiv, Bulgaria.
Abstract:
An operationally simple procedure for the synthesis of 2-alkyl-4-quinolone N-oxides, relying on controlled platinum-catalyzed partial hydrogenation of 2-nitrobenzoyl enamines, has been developed. The Pseudomonas aeruginosa metabolite 2-heptyl-4-quinolone-N-oxide (HQNO) and four analogous products have been prepared in good yield and high purity by this method. All products showed ampholytic properties, with a tendency to form isolable organic-soluble hydrochlorides by switching from the N-hydroxy-4-quinolone to 4-hydroxyquinoline-N-oxide tautomeric form upon partitioning between dichloromethane and 1M aqueous HCl. In basic medium, on the other hand, water-soluble salts of the N-hydroxy-4-quinolone tautomers were formed. NMR measurements indicate pH-dependent equilibrium with fast exchange between the 4-quinolone and the protonated 4-quinolinol tautomer.
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