N Chemical Shifts and -Couplings as Diagnostic Tools for Determination of the Azide-Tetrazole Equilibrium in Tetrazoloazines.

Selectively N-labeled tetrazolo[1,5-][1,2,4]triazines and tetrazolo[1,5-]pyrimidines bearing one, two, or three N labels were synthesized. The synthesized compounds were studied by H, C, and N NMR spectroscopy in DMSO and TFA solutions, where the azide-tetrazole equilibrium can lead to the formation of two tetrazole (, ) isomers and one azide () isomer for each compound. Incorporation of the N-label(s) leads to the appearance of N-N coupling constants (), which can be easily measured via simple 1D N NMR spectra, even at natural abundance between labeled and unlabeled N atoms. The chemical shifts for the N nuclei in the azole moiety are very sensitive to the ring opening and azide formation, thus providing information about the azido-tetrazole equilibrium. At the same time, the couplings between N-labeled atoms in the azole and azine fragments unambiguously determine the fusion type between tetrazole and azine rings in the cyclic isomers and . Thus, combined analysis of N chemical shifts and values in selectively isotope-enriched compounds provides an effective diagnostic tool for direct structural determination of tetrazole isomers and azide form in solution. This method was found to be the most simple and efficient way to study the azido-tetrazole equilibrium.