Microwave-Assisted, Sustainable, and Click-Chemistry Synthetic Approaches to 2-(4-(((Benzo[4,5]oxazolo[2,3-c]triazol-3-yl)thio)-methyl)-1H-1,2,3-triazol-1-yl)-N-(substituted)acetamides and Their Antimicrobial Activity

Abstract Objective: An efficient, sustainable, and click-chemistry-driven protocol is described for the synthesis of novel 2-(4-(((benzo[4,5]oxazolo[2,3-c]triazol-3-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(substituted)acetamides under microwave irradiation. Methods: The target scaffolds were assembled via a one-pot copper-catalyzed azide–alkyne cycloaddition (CuAAC) between 3-(prop-2-yn-1-ylthio)benzo[4,5]oxazolo[2,3-c]triazole and various 2-azido-N-phenylacetamides. The transformations were mediated by a CuSO4/sodium ascorbate catalytic system in a ternary DMF : t-BuOH : H2O solvent mixture, evaluated under both conventional thermal heating and microwave irradiation profiles. Results and Discussion: A comparative analysis demonstrated that the microwave-assisted methodology significantly enhanced reaction kinetics and efficiency, affording the desired products in superior yields (80–94%) within 6–12 min, whereas conventional heating required 1.0–2.5 h to achieve moderate yields of 64–80%. Biological screening indicated that the synthesized cycloadducts possess moderate in vitro activity against the tested microbial strains. Conclusions: A rapid, sustainable, click-chemistry protocol was developed for the synthesis of novel benzooxazolo-triazole acetamides via one-pot CuAAC. Microwave irradiation offered clear advantages over conventional heating, accelerating reaction kinetics and improving yields. In vitro screening showed weak to moderate antibacterial activity for compounds III–VIII and distinct antifungal activity for II, III, and VI.