Synthesis of 1,5-Disubstituted Tetrazoles in Aqueous Micelles at Room Temperature

Abstract

The ongoing study is a Ugi-azide four-component reaction for the synthesis of 1,5-disubstituted tetrazole(1,5-DST), which involves an aldehyde, different amines, isocyanides, and as azide’s source the Trimethylsilylazide (TMSN3), in water as solvent using as catalyst the tetradecyltrimethylammonium bromide (TTAB) with a load of (10% mole), which provides a hydrophobic micellar reaction site. This approach is a step toward a green chemistry reaction of 1,5 disubstituted tetrazole. A serie of 1, 5- disubstituted tetrazole was synthesized by engaging a large substrate scope, leading to yields between 43% and 56%, which are compared afterwards with those obtained with methanol as solvent. The results were confirmed by HRMS, IR, and 1D NMR experiments.

Green Synthesis of Aromatic Nitrogen-Containing Heterocycles by Catalytic and Non-Traditional Activation Methods

“…Using water in organic reactions often causes difficulties in terms of solubility. To overcome this challenge, Abdessalam and his coworkers presented a micelle-based Ugi-azide four-component synthesis of 1,5-disubstituted tetrazoles ( Scheme 7 d) [ 94 ]. As starting material, the authors used aldehyde, various amines, isocyanides and trimethylazides in the presence of tetradecyltrimethylammonium bromide (TTAB) with a load of 10 mol% in an aqueous medium.…”

Tetrazole: A privileged scaffold for the discovery of anticancer agents

“…The 1, 5-disubstituted tetrazole was recently synthesized via a four-component Ugi-azide process (Abdessalam et al, 2021). To begin, acetone was combined with aniline to yield imine and water, which was then combined with TMSN 3 to yield hydrazoic acid.…”