SiO2–H3BO3 promoted solvent-free, green and sustainable synthesis of bioactive 1-substituted-1H-tetrazole analogues

Abstract

In the present study, a focused library of multi functionalized 1-substituted-1H-tetrazole analogues 4(a–o) were synthesized, which were typically accessed via a facile, solvent-free and green synthetic protocol. The reaction involves expeditious reusable catalyst (SiO₂–H₃BO₃) promoted condensation between a variety of heterocyclic/aromatic amines, sodium azide and triethyl ortho-formate, eliminating the use of an environmentally toxic solvent. This new eco-friendly and sustainable protocol resulted in a remarkable enhancement in the synthetic efficiency (90–97%, yield) with high purity. This silica–boric acid catalyst is air and water stable and easy to prepare from cheap silica and boric acid. The present methodology is a green protocol offering several advantages such as an excellent yield of products, a simple operational procedure, minimizing production of chemical wastes, mild reaction conditions, a shorter reaction profile, easy preparation of the catalyst and its recyclability up to five cycles without any appreciable loss in catalytic activity. The optimization conditions achieved in the present study revealed that 2.5 mol% of the SiO₂–H₃BO₃ catalyst under solvent-free conditions at 90 °C are the best suited conditions for the synthesis of tetrazole derivatives in excellent yields. The present protocol is applicable to a broader substrate scope (electron-rich and electron-deficient). Compounds possessing a nicotinic acid nucleus (4e, 4f, 4g) displayed strongest inhibition against AChE with IC₅₀ values of 0.43 μM, 0.21 μM and 0.26 μM, respectively. The results revealed that the electronic effect of substituents inflicts a prominent effect on AChE activity.