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

Abstract

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 4 telescoped steps with excellent purity (99% a/a).

Stereochemical and Computational NMR Survey of 1,2,3-Triazoles: in Search of the Original Tauto-Conformers

“…The structural peculiarities of 1,2,3-triazole enable it to mimic different functional groups that justify its broad application as a bioisostere for the synthesis of new active molecules. ,− The unique properties of the 1,2,3-triazole cycle as an intriguing ring system in drug discovery, and novel medicinal chemistry strategies used for the design and development of 1,2,3-triazole analogues as inhibitors of various biological targets were summarized in a review . 1,2,3-Triazole derivatives are readily available through the “click chemistry” to create collections of compounds against various diseases, and the use of 1,2,3-triazoles in medicinal chemistry has recently received increasing attention due to the development of new methodologies allowing their regioselective synthesis. − The synthetic feasibility and versatility of triazole chemistry make it certainly an ideal building block for generating libraries of compounds for more comprehensive studies of structure–activity relationships.…”