Synthesis Characterization and Antibacterial, Antifungal Activity of N-(Benzyl Carbamoyl or Carbamothioyl)-2-hydroxy Substituted Benzamide and 2-Benzyl Amino-Substituted Benzoxazines

Abstract

New N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13, 20, and 21 were synthesized using sodium bicarbonate and benzyl amine with 2-thioxo-substituted-1,3-benzoxazines 6, 10a, b, 11c, and 12a–n. The 2-thioxo-substituted-1,3-oxazines 6, 10a-b, 11d 12a–n, and 26 were converted to the corresponding 2-methylthio-substituted-1,3-oxazines 14a–l and 24 which were then converted to 2-benzyl amino-substituted-benzoxazines 15a–i by refluxing with benzylamine. Products 15a, b, e, f, and g were also synthesized by boiling the corresponding N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13a, b, f, l, and m in acetic acid. 2-Oxo-substituted-1,3-benzoxazines 22 and 25 were prepared by treating the corresponding 2-methylthio-substituted-1,3-oxazines 14 and 24 with dilute HCl. The N-(benzyl carbamoyl)-2-hydroxy substituted benzamide 23 was synthesized from the reaction of 2-oxo-substituted-1,3-benzoxazine 22 with benzylamine. The new products were characterized using IR, 1H, and 13C NMR in addition to microanalysis. Selected compounds were tested in vitro for antibacterial and antifungi activity and the most active compounds were found to be the 4-(substituted-benzylamino)-2-hydroxy benzoic acids 9a and d (M. chlorophenolicum, MIC 50 and 25 µgm L−1, resp.), N1, N3-bis (benzyl carbamothioyl)-4,6-dihydroxy-substituted phthalamides 20a and 20c (B. subtilis MIC 12.5, 50 µgm L−1, resp.) and 21 (M. chlorophenolicum, MIC 50 µgm L−1).