Long-Range <sup>1</sup>H–<sup>15</sup>N <i>J</i> 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
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Abstract
The
selectively <sup>15</sup>N labeled azido-1,2,4-triazine <b>2</b>*<b>A</b> and azidopyrimidine <b>4</b>*<b>A</b> were synthesized by treating hydrazinoazines with <sup>15</sup>N-labeled
nitrous acid. The synthesized compounds were studied by <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N NMR spectroscopy in
DMSO, TFA, and DMSO/TFA solutions, where the azide–tetrazole
equilibrium could lead to the formation of two tetrazoles (<b>T</b>, <b>T′</b>) and one azide (<b>A</b>) isomer for
each compound. The incorporation of the <sup>15</sup>N label led to
the appearance of long-range <sup>1</sup>H–<sup>15</sup>N coupling
constants (<i>J</i><sub>HN</sub>), which can be measured
easily by using amplitude-modulated 1D <sup>1</sup>H spin–echo
experiments with selective inversion of the <sup>15</sup>N nuclei.
The observed <i>J</i><sub>HN</sub> patterns enable the unambiguous
determination of the mode of fusion between the azole and azine rings
in the two groups of tetrazole isomers (<b>2</b>*<b>T′,
4</b>*<b>T′</b> and <b>2</b>*<b>T, 4</b>*<b>T</b>), even for minor isoforms with a low concentration
in solution. However, the azide isomers (<b>2</b>*<b>A</b> and <b>4</b>*<b>A</b>) are characterized by the absence
of detectable <i>J</i><sub>HN</sub> coupling. The analysis
of the <i>J</i><sub>HN</sub> couplings in <sup>15</sup>N-labeled
compounds provides a simple and efficient method for direct NMR studies
of the azide–tetrazole equilibrium in solution