Synthesis of 5-Substituted Tetrazoles: Reaction of Azide Salts with Organonitriles Catalyzed by Trialkylammonium Salts in Non-polar Media
S. Chand, Josh Aronson, Carol Gelbaum, Kris Griffith, Jonathan Faris, Azhar B. Moihdeen, Mikhil Patel, Maryellen Malone, Kent W. Richman, Charles A. Eckert, Charles L. Liotta, Paméla Pollet
Abstract
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.