Long-Range 1H-15N J Couplings Providing a Method for Direct Studies of the Structure and Azide-Tetrazole Equilibrium in a Series of Azido-1,2,4-triazines and Azidopyrimidines

The selectively N-15 labeled azido-1,2,4-triazine 2*A and azidopyrimidine 4*A were synthesized by treating hydrazinoazines with N-15-labeled nitrous acid. The synthesized compounds were studied by H-1, C-13, and N-15 NMR spectroscopy in DMSO, TFA, and DMSO/TFA solutions, where the azide-tetrazole equilibrium could lead to the formation of two tetrazoles (T, T') and one azide (A) isomer for each compound. The incorporation of the N-15 label led to the appearance of long-range H-1-N-15 coupling constants (J(HN)), which can be measured easily by using amplitude-modulated 1D H-1 spin echo experiments with selective inversion of the N-15 nuclei. The observed J(HN) patterns enable the unambiguous determination of the mode of fusion between the azole and azine rings in the two groups of tetrazole isomers (2*T', 4*T' and 2*T, 4*T), even for minor isoforms with a low concentration in solution. However, the azide isomers (2*A and 4*A) are characterized by the absence of detectable J(HN) coupling. The analysis of the J(HN) couplings in N-15-labeled compounds provides a simple and efficient method for direct NMR studies of the azide tetrazole equilibrium in solution.