Preparation of 1, 4-Benzothiazine-2, 3-dicarboximides via Intramolecular Cyclization of N-Substituted 2-[(2-Acylaminophenyl)thio]maleimides and Investigation of Their Antibacterial Activity

Abstract

N-Substituted 2-[(2-acylaminophenyl)thio]maleimides were treated with a weak base such as triethylamine to give 4-acyl-2, 3-dihydro-1, 4-benzothiazine-2, 3-dicarboximides in a fairly good yield via Michael type intramolecular cyclization. The chlorination of the dicarboximides, followed by dehydrochlorination, produced 4-acyl-1, 4-benzothiazine-2, 3-dicarboximides.2-[(2-Acetamidophenyl)thio]-N-methylmaleimides was treated with dilute hydrochloric acid to give 2, 3-dihydro-1, 4-benzothiazine-2, 3-dicarboximide. Antibacterial activity of those compounds was examined. All 2-[(2-acylaminophenyl)thio]maleimides exhibited good antibacterial activity against Gram-positive bacteria such as Bacillus subtilis and Staphylococcus aureus. All compounds tested were inactive against Gram-negative bacteria except for 2-[(2-acetamidophenyl)thio]-N-methylmaleimide and N-methyl-substituted 4 H-1, 4-benz othiazine2, 3-dicarboximide which were marginally active.