Synthesis of 5-Substituted Tetrazoles: Reaction of Azide Salts with Organonitriles Catalyzed by Trialkylammonium Salts in Non-polar Media

An efficient synthesis of 5-substituted tetrazole derivatives via the addition of azide ions to an organonitrile is presented. This new protocol minimizes the potential generation of hydrazoic acid by employing a catalytic amount of an activating proton source (trialkylammonium chloride) in combination with a phase transfer agent (tetraalkylammonium salt). Both aromatic and aliphatic nitriles are successfully reacted to produce the corresponding 5-substituted-1H-tetrazole products. The superiority of choline chloride as a phase transfer agent, the recyclability of both the catalytic proton source and the phase transfer agent, and the proposed mechanistic role of each of the reaction components are also presented.