Green chemistry approach to the synthesis of 3-substituted-quinazolin-4(3H)-ones and 2-methyl-3-substituted-quinazolin-4(3H)-ones and biological evaluation

• Published in: Green chemistry letters and reviews Vol. 13; no. 2; pp. 93 - 101
• Main Authors: Komar, Mario, Molnar, Maja, Jukić, Marijana, Glavaš-Obrovac, Ljubica, Opačak-Bernardi, Teuta
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 02.04.2020; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 2-methyl-3-substituted-quinazolinones; Amines; Anthranilic acid; Anticancer properties; Antitumor agents; Chemical synthesis; Choline; Deep eutectic solvents; Eutectics; Green chemistry; microwave; Microwaves; NMR; Nuclear magnetic resonance; Quinazolinones; Solvents; Substitutes; Urea; Ureas
• ISSN: 1751-8253; 1751-7192
• DOI: 10.1080/17518253.2020.1741694

A synthesis of two series of 3-substituted quinazolinones was performed utilizing a green chemistry approach, deep eutectic solvents and microwaves, namely. 2-Methyl-3-substituted-quinazolin-4(3H)-one derivatives were synthesized in a two-step reaction, using choline chloride:urea deep eutectic solvent (DES). 3-Substituted-quinazolin-4(3H)-ones were synthesized in one-pot one-step reaction of anthranilic acid, amines and orthoester in a microwave reactor. For the synthesis of 2-methyl-3-substituted-quinazolin-4(3H)-ones, first conventional synthesis of benzoxazinone, as an intermediate, was performed. Further, benzoxazinone in reaction with corresponding amines, in choline choline:urea deep eutectic solvent, furnished desired compounds. These procedures are based on green principles with the aim of developing synthetic routes for the potential antitumor agents. All compounds were characterized by LC/MS, 1 H NMR and 13 C NMR spectral techniques. Compound 1 bearing trifluoromethoxyphenyl group showed promising activity against HuT-78 cell line with IC 50 of 51.4 ± 5.1 µM.