Coupling of N‐Tosylhydrazones with Tetrazoles: A Regioselective Synthesis of 2,5‐Disubstituted‐2H‐Tetrazoles

Abstract

Herein we describe the CÀ N coupling reaction of N-tosylhydrazones with tetrazoles using thermic activation in the presence of different bases. The reactions proved to be highly regioselective to result in the corresponding 2,5-disubstituted-2H-tetrazoles as main products and 1,5-disubstituted-1H-tetrazoles as minor products. Owing to its mild conditions, the method enabled the use of a wide range of substrates.

Preparation of 2,5‐Disubstituted Tetrazoles using a Copper‐Catalysed Regioselective Direct Coupling of Tetrazoles with Free NH Groups and Boronic Acid Derivatives

“…[1][2][3][4][5] Notably, they have the highest number of nitrogen atoms among the stable N-heterocycles and have been widely considered as a suitable precursor to various important scaffolds. [6][7][8][9][10] Recent studies have shown that there has been renewed interest in the preparation of tetrazoles as a substantial number of active pharmaceutical ingredients (API) contain the tetrazole ring. [11][12][13][14] For instance,numerous pharmacological applications of tetrazoles are anti-inflammatory, antihypertensive, anticancer, antiallergic, antibiotic, diuretics and receptor modulatory agents.…”

“…Amongst the various nitrogen‐containing heterocycles, scaffolds based on tetrazole offer a plethora of applications in the domain of medicinal chemistry, coordination chemistry, material sciences, high energy materials, biochemistry, pharmacology, and agriculture (as herbicides and fungicides) [1–5] . Notably, they have the highest number of nitrogen atoms among the stable N‐ heterocycle s and have been widely considered as a suitable precursor to various important scaffolds [6–10] . Recent studies have shown that there has been renewed interest in the preparation of tetrazoles as a substantial number of active pharmaceutical ingredients (API) contain the tetrazole ring [11–14] .…”