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

Selectively 15 N-labeled tetrazolo[1,5- b ][1,2,4]triazines and tetrazolo[1,5- a ]pyrimidines bearing one, two, or three 15 N labels were synthesized. The synthesized compounds were studied by 1 H, 13 C, and 15 N NMR spectroscopy in DMSO and TFA solutions, where the azide-tetrazole equilibrium can lead to the formation of two tetrazole ( T , T' ) isomers and one azide ( A ) isomer for each compound. Incorporation of the 15 N-label(s) leads to the appearance of 15 N- 15 N coupling constants ( J NN ), which can be easily measured via simple 1D 15 N NMR spectra, even at natural abundance between labeled and unlabeled 15 N atoms. The chemical shifts for the 15 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 1-2 J NN couplings between 15 N-labeled atoms in the azole and azine fragments unambiguously determine the fusion type between tetrazole and azine rings in the cyclic isomers T and T' . Thus, combined analysis of 15 N chemical shifts and J NN 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.