Selective 15N-Labeling and Analysis of 13C−15N J Couplings as an Effective Tool for Studying the Structure and Azide−Tetrazole Equilibrium in a Series of Tetrazolo[1,5-b][1,2,4]triazines and Tetrazolo[1,5-a]pyrimidines

Abstract

Two general methods for the selective incorporation of an ¹⁵N-label in the azole ring of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines were developed. The first approach included treatment of azinylhydrazides with ¹⁵N-labeled nitrous acid, and the second approach was based on fusion of the azine ring to [2-¹⁵N]-5-aminotetrazole. The synthesized compounds were studied by ¹H, ¹³C, and ¹⁵N NMR spectroscopy in both DMSO and TFA solution, in which the azide−tetrazole equilibrium is shifted to tetrazole and azide forms, respectively. Incorporation of the ¹⁵N-label led to the appearance of ¹³C−¹⁵N J coupling constants (J_CN), which can be measured easily using either 1D ¹³C spectra with selective ¹⁵N decoupling or with amplitude modulated 1D ¹³C spin−echo experiments with selective inversion of the ¹⁵N nuclei. The observed J_CN patterns permit unambiguous determination of the type of fusion between the azole and azine rings in tetrazolo[1,5-b][1,2,4]triazine derivatives. Joint analysis of J_CN patterns and ¹⁵N chemical shifts was found to be the most efficient way to study the azido-tetrazole equilibrium.