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

摘要

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).