Evolution in the synthesis of 1,4-benzothiazines over the last decade (2014 to 2024)

Abstract

1,4-Benzothiazine (1,4-BT) is a heterocyclic compound consisting of a benzene ring fused with a thiazine ring, incorporating both nitrogen and sulfur atoms. The fusion of the benzene and thiazine frameworks enhances its biological properties, making it a valuable scaffold for designing innovative heterocyclic systems. This versatile and significant member of the heteroarene family bridges synthetic organic chemistry with medicinal, pharmaceutical, and industrial applications. This structural motif demonstrates remarkable potential for accommodating a wide range of substrates and functionalizations, giving rise to diverse biological activities such as antipsychotropic, antiviral, antithyroid, antimicrobial, antifungal, antitubercular, antioxidant, and anti-inflammatory properties. Numerous derivatives have been synthesized as target structures in drug development. This review highlights various synthetic approaches to prepare 1,4-BTs. Well-established methods, such as the reactions of 2-aminothiophenol (2-ATP) with alkenes, enaminones, carboxylic acids, esters, furan-2,3-dione, aroylmethylidene malonate and 1,3-dicarbonyl compounds, are summarized. Additionally, the miscellaneous syntheses of 1,4-BTs were also outlined. These methods have utilized various catalysts, including nanocatalysts and metal-based catalysts, under diverse reaction conditions for efficient synthesis. The deep analysis of the synthesis of 1,4-BTs will grasp the scientific community towards their synthetic aspects and further advances in the field.