Scalable, Chromatography-Free Synthesis of 2-(3-Bromophenyl)-2H-1,2,3-triazole through N-N Bond Forming Cyclization

2-(3-Bromophenyl)-2H-1,2,3-triazole is a low molecular-weight building block that is not readily accessible in pure form by standard synthetic approaches due to competing formation of the triazol-1-yl regioisomer. After investigation of a wide range of synthetic routes, a process based on construction of the triazole heterocycle by cyclization of an activated dihydrazone was developed. A suitable isolation method had to be identified before embarking on a demonstration run on >100 g scale without the need for chromatography. The new process delivered the desired building block in 48 % overall yield over four telescoped steps with excellent purity (99 % a/a).

Automated summary

A new synthetic process has been developed to prepare the difficult-to-obtain 2-(3-bromophenyl)-2H-1,2,3-triazole with an overall yield of 48% and excellent purity.