Supramolecular cyclodextrin catalysis for green click synthesis of tetrazoles

Abstract

Tetrazole-containing molecules have attracted considerable interest owing to their chemical stability and wide-ranging biological applications. In this study, cyclodextrins (CDs) were investigated as phase-transfer catalysts for the green synthesis of 5-substituted tetrazoles from benzaldoximes and sodium azide in aqueous medium. The reaction conditions, including the concentration of α-, β-, and γ-CDs (2–6 mmol%) and the stirring time (30–60 min), were optimized using a central composite design to maximize product yield. Under optimized conditions, various aldoximes were efficiently converted into the corresponding 5-substituted tetrazoles. The formation of the benzaldoxime–β-CD inclusion complex was confirmed by 1 H NMR, FTIR, SEM, EDX, and PXRD, while the tetrazole products were characterized by NMR. Statistical analyses, including analysis of variance and desirability tests, demonstrated that β-CD catalyzed the reaction with high efficiency, affording excellent yields and facilitating straightforward purification.