Synthesis of 2-(Di/tri/tetraazolyl)-2 H-azirine-2-carboxylates by Halogen Substitution: Evidence for an SN2'-SN2' Cascade Mechanism

Anastasiya V Agafonova; Nikolai V Rostovskii; Ilia A Smetanin; Galina L Starova; Alexander F Khlebnikov; Mikhail S Novikov

doi:10.1021/acs.joc.8b02295

Synthesis of 2-(Di/tri/tetraazolyl)-2 H-azirine-2-carboxylates by Halogen Substitution: Evidence for an S_N2'-S_N2' Cascade Mechanism

J Org Chem. 2018 Nov 2;83(21):13473-13480. doi: 10.1021/acs.joc.8b02295. Epub 2018 Oct 18.

Authors

Anastasiya V Agafonova¹, Nikolai V Rostovskii¹, Ilia A Smetanin¹, Galina L Starova¹, Alexander F Khlebnikov¹, Mikhail S Novikov¹

Affiliation

¹ St. Petersburg State University , Institute of Chemistry , 7/9 Universitetskaya nab. , St. Petersburg 199034 , Russia.

PMID: 30335384
DOI: 10.1021/acs.joc.8b02295

Abstract

An effective and operationally simple method for the preparation of methyl 2-(di/tri/tetraazol-1-yl)-2 H-azirine-2-carboxylates from accessible methyl 2-halo-2 H-azirine-2-carboxylates and NH-azoles has been developed. The azoles having enhanced NH acidity, react with 2-halo-2 H-azirines in the presence of Et₃N in a deprotonated form, while the azoles having highly nucleophilic sp² nitrogen react in neutral form. According to the DFT calculations, the substitution of the halogen by the azole proceeds via an S_N2'-S_N2' cascade, with the initial conjugate substitution of the halogen being the rate-determining step. The formation of 2,3-dipyrazolylaziridines in the reaction of pyrazole provides experimental evidence for the cascade mechanism of the reaction.