Synthesis and antimicrobial activity of 6-iodo-2-(trifluoromethyl)-4(3H)-quinazolinone derivatives

Abstract

The reaction of 2-(trifluoromethyl)-3,1-benzoxazone with amines was studied. At first, when one mole equivalent of 2-(trifluoromethyl)-3,1-benzoxazone was treated with one mole equivalent of phenylenediamine afforded bis-benzamide derivatives rather than 3-(aminophenyl)quinazolinone derivatives. Many trials to obtain the 3-(aminophenyl)quinazolinones were carried out, and the final result is that it is difficult to obtain the 3-(aminophenyl)quinazolinones in acceptable yield and purity from the reaction of phenylenediamine with 2-(trifluoromethyl)-benzoxazinone. The synthesis of new 6-iodo-3-substituted-2-(trifluoromethyl)quinazolin-4(3H)-one derivatives was studied as follows: when the 6-iodo-2-(trifluoromethyl)-3,1-benzoxazin-4-one was fused with some amines at 140 °C for 10 min, it afforded 5-iodo-N-(methyl and aryl)-2-(trifluoroacetamido)benzamide derivatives. While, when 6-iodo-2-(trifluoromethyl)-3,1-benzoxazinone was condensed with the same amines in acetic acid under reflux conditions, it afforded 6-iodo-3-(methyl and aryl)-2-(trifluoromethyl)quinazolin-4(3H)-one derivatives. Condensation of the 6-iodo-2-(trifluoromethyl)-3,1-benzoxazinone with hydrazine hydrate gave 3-amino-6-iodo-2-(trifluoromethyl)quinazolinone. Condensation of the latter 3-aminoquinazolinone with some aldehydes and isatin afforded the corresponding Schiff's bases. The expected antimicrobial properties of the synthesized compounds were investigated. Most of the compounds showed moderate effects on some bacteria. Most compounds had no effects on fungi. Schiff's base of isatin showed the best results among all the tested compounds. The latter Schiff's base showed potent activity, like ketoconazole toward fungi.

Graphical abstract