Microwave assisted synthesis and structure–activity relationship of 4-hydroxy-N′-[1-phenylethylidene]-2H/2-methyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides as anti-microbial agents

A series of 4-hydroxy-N′-[1-phenylethylidene]-2H/2-methyl, 1,2-benzothiazine-3-carbohydrazide 1,1-dioxides was synthesized from commercially available sodium saccharin. Base catalyzed ring expansion of methyl (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)acetate followed by ultrasound mediated hydrazinolysis and subsequent reaction with 1-phenylethanones under the influence of microwaves yielded the title compounds. Besides, microwave assisted synthesis of 1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol 5,5-dioxide and 4-methyl-1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol 5,5-dioxide is also discussed. Most of the synthesized compounds were found to possess moderate to significant anti-microbial (anti-bacterial and anti-fungal) activities. It is found that compounds with greater lipophilicity (N-methyl analogues) possessed higher anti-bacterial activities. Microwave assisted synthesis of a series of biologically active 4-hydroxy-N′-[1-phenylethylidene]-2H/2-methyl, 1,2-benzothiazine-3-carbohydrazide 1,1-dioxides along with the synthesis of 1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol-5,5-dioxide and 4-methyl-1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol-5,5-dioxide from commercially available sodium saccharin is reported. [Display omitted] ► 4-Hydroxy-N′-[1-phenylethylidene]-2H/2-methyl, 1,2-benzothiazine-3-carbohydrazide 1,1-dioxides. ► 1,4-Dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol 5,5-dioxide. ► 4-Methyl-1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol 5,5-dioxide. ► Anti-fungal and anti-bacterial assay. ► Microwave assisted synthesis.