Synthesis and Characterization of Novel Benzothiazinonic N-Acylhydrazone Derivatives

Abstract

Several recent research studies have demonstrated that N-acylhydrazones are well known as privileged scaffolds frequently used in the discovery of new potential antiparasitic compounds. The investigation of literature revealed that the synthesis of N˗acylhydrazones bearing the 1,4˗benzothiazin˗3-one pharmacophore has not been described. Therefore, it was considered interesting to attempt the synthesis of new N˗acylhydrazone derivatives containing 1,4˗benzothiazine˗3˗one fragment, thus obtaining a series of novel (E)-N′-(substituted benzylidene)-2(3-oxo-2H-benzo[b][1,4]thiazin-4(3H)-yl)acetohydrazides. Thus, the targeted compounds were successfully synthesized via an easy and general procedure. Hence, 2-aminothiophenol was reacted with maleic anhydride to produce the ester 3,4-dihydro-2-methoxycarbonylmethyl-3-oxo-2H-1,4-benzothiazine. The hydrazinolysis of the obtained ester-based benzothiazinon-3-one was also realized to give the corresponding benzothiazinonic acid hydrazide derivative as a precursor for the synthesis of the desired N˗acylhydrazones, by their condensation with various substituted benzaldehydes. In an attempt to explain the duplication of some peaks observed from the ¹H and ¹³C˗NMR spectral analysis performed on the structures of all newly synthesized N˗acylhydrazones in DMSO˗d₆; it was concluded that they exist as a mixture of syn˗E and anti˗E diastereoisomers with different isomeric yield ratio. Generally, the results obtained in this study indicate that these N˗acylhydrazones may be envisaged for supplementary structural investigations, and as potential biologically active compounds in diverse applications.