Tetrazole derivatives synthesis via green one-pot oxidation of benzyl alcohol using Cu(ii) immobilized on nanodiamond@folic acid catalyst

Abstract

Tetrazoles are highly significant in pharmaceuticals, drug delivery, and anticancer treatments. In this work, the development of a highly effective nanocatalyst, which was synthesized by functionalizing nanodiamonds (NDs) substrate with folic acid (FA) and stabilizing Cu(II) on the nanocomposite. The ND@FA-Cu(II) nanocatalyst has demonstrated superior thermal stability, non-toxicity, little catalyst consumption, and reusability (up to five cycles), rendering it both cost-effective and environmentally sustainable. The catalytic efficacy of ND@FA-Cu(II) was assessed in the production of 1H-tetrazole derivatives employing two methodologies. A one-pot synthesis using malononitrile, sodium azide, and benzyl alcohol (oxidized in acetonitrile) effectively yielded 5-substituted 1H-tetrazoles. The second strategy involved the synthesis of 1H-tetrazoles from benzaldehyde, malononitrile, and sodium azide in ethanol under mild conditions via Knoevenagel condensation and 1,3-dipolar cycloaddition. This one-pot multicomponent reaction (MCR) minimizes by-products, enhances yields, and reduces reaction durations and solvent usage, providing a sustainable technique for tetrazole synthesis with 97% yield.