Development and Demonstration of a Safer Protocol for the Synthesis of 5‑Aryltetrazoles from Aryl Nitriles

The search for a faster, safer protocol for the direct synthesis of 5-aryltetrazoles from aryl nitriles in the presence of sodium azide and an amine hydrochloride salt led to the discovery of a buffered system comprised of BnNH2, BnNH2·HCl, and NaN3. After optimization of reaction conditions and a thorough investigation of reaction safety, the procedure was demonstrated for the synthesis of several hundred grams of 4-chloro-2-(2H-tetrazol-5-yl)­phenol. The generality of the developed reaction conditions was established by a small-scale reactivity screen using 16 additional aryl and heteroaryl nitrile substrates.