Two general methods for the selective incorporation of an (15)N-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 (15)N-labeled nitrous acid, and the second approach was based on fusion of the azine ring to [2-(15)N]-5-aminotetrazole. The synthesized compounds were studied by (1)H, (13)C, and (15)N 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 (15)N-label led to the appearance of (13)C-(15)N J coupling constants (J(CN)), which can be measured easily using either 1D (13)C spectra with selective (15)N decoupling or with amplitude modulated 1D (13)C spin-echo experiments with selective inversion of the (15)N 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 (15)N chemical shifts was found to be the most efficient way to study the azido-tetrazole equilibrium.

Selective methods for the incorporation of stable isotopes 15 N and 2 H into the structure of antiviral medicine "triazavirine" 1 were developed. The synthesized isotopically modified "tri azavirine" 1 2 H 3 , 15 N 3 contained the labeled atoms in both the azole and the azine rings. 13 C and 15 N NMR spectra of the isotope containing sample 1 2 H 3 , 15 N 3 were thoroughly analyzed.

ABSTRACT:The selectively 15 N labeled azido-1,2,4-triazine 2*A and azidopyrimidine 4*A were synthesized by treating hydrazinoazines with 15 N-labeled nitrous acid. The synthesized compounds were studied by 1 H, 13 C, and 15 N 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 15 N label led to the appearance of long-range 1 H− 15 N coupling constants (J HN ), which can be measured easily by using amplitude-modulated 1D 1 H spin−echo experiments with selective inversion of the 15 N 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 15 N-labeled compounds provides a simple and efficient method for direct NMR studies of the azide−tetrazole equilibrium in solution.

This review provides a generalization of effective examples of 15N labeling followed by an analysis of JCN and JHN couplings in solution as a tool to study the structural aspects and pathways of chemical transformations in nitrogen heterocycles.

A new method was developed for the investigation of an azido tetrazole equilibrium based on using a complex analysis of 13 С-15 N and 1 H-15 N spin spin coupling constants. The use of this approach became possible due to the selective inclusion of 15 N isotopes into the structures of 2 azidopyrimidines and their cyclic analogs tetrazolo[1,5 a]pyrimidines.