Time-Optimized and Green Synthesis of New Tetrazole-Benzothiazole Hybrids Incorporating Azo-Maleimide Linkages: A Sustainable Approach

Abstract

A high-efficiency synthetic approach toward a new generation of multi-functional tetrazole-benzothiazole hybrids containing azo-maleimide linkages is identified in this study. One of the significant contributions of this work is that the reaction time has been greatly reduced; the critical [3+2] cycloaddition is completed in fewer than 6-10 hours, which is much faster than conventional methods. Based on the principles of green chemistry, absolute ethanol was chosen as a sustainable and environmentally friendly solvent. Although glacial acetic acid was necessary to the complete closure of the final ring, its use was primarily limited to reducing the environmental footprint. Chemical forms of the hybrids were confirmed using spectroscopic methods, including Fourier-transform infrared spectroscopy (FT-IR), Proton nuclear magnetic resonance (¹H-NMR), and Carbon-13 nuclear magnetic resonance (¹³C-NMR), which provide conclusive evidence of successful hybridization. The Gram-positive (S. aureus, S. epidermidis) and Gram-negative (E. coli, K. pneumoniae) screening on biological grounds showed that these hybrids have a strong antibacterial effect. The findings make the developed scaffolds promising, environmentally friendly, and well-suited for use in modern medicinal chemistry.