Synthesis of 5-phenyltetrazole and its N-methyl Derivatives in a Microreactor

E. A. Popova, R. S. Abiev, L. A. Lappalainen, S. D. Svetlov, T. V. Andreeva, R. E. Trifonov and V. A. Ostrovskii

Abstract
Azidation of benzonitrile with dimethylammonium azide yielding 5-phenyltetrazole dimethylammonium salt was performed under microreactor conditions. The kinetics of azidation of benzonitrile in DMF was investigated at the range 80–95 °С. The reaction rate constants were determined: kII·104 (L mol–1 s–1): 0.79, 0.97, 1.19, 1.51, at 80, 85, 90, and 95 °С, respectively. It was found that the reaction rate constants obtained in a microreactor are comparable to ones for a batch-type reactor. The thermodynamic parameters of azidation under the microreactor conditions correspond to the mechanism of the 1,3-dipolar cycloaddition of azides to nitriles. It was established that the excessive pressure in the microreactor notably accelerates the process. The alkylation of 5-phenyltetrazole with methyl iodide in microreactor was performed in dichloromethane-aqueous sodium hydroxide system. The accumulation of regioisomers of N1- and N2-methyl-5‑phenyltetrazole in the microreactor under the conditions of slug flow of the reaction mixture occurs considerably faster than in the batch-type reactor in the conditions of phase-transfer catalysis.

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Keywords
azidation of nitriles, tetrazoles, synthesis, alkylation, rate constants, microreactor