SYNTHESIS AND MODIFICATION OF NICOTINIC ACID AZIDE

Nicotinic acid derivatives have a wide range of biological activity and are widely used in medical practice as first-line drugs for the treatment of tuberculosis [1], pulmonary arterial hypertension [2], vitamin B₆-dependent epilepsy [3], inhibitors of blood clotting factor IXa [4, 5], human immunodeficiency virus inhibitor [6,7], etc. It should be noted that the pyridine cycle is part of many vital organic compounds, which determines it’s one of the dominant roles among heterocycles. Therefore, the development of convenient preparative methods for the synthesis of new nicotinic acid derivatives is an urgent task, since these compounds are of practical and theoretical interest. The purpose of this work is the targeted synthesis of nicotinic acid azide and its further modification in order to obtain new pharmacologically active compounds.

In this work, the synthesis of nicotinic acid azide was carried out by the interaction of sodium nitrite with nicotinic hydrazide with a yield of 99%. The interaction of nicotinic acid azide with alcohols (isopropyl and butyl alcohols) and a secondary amine (cytisine alkaloid) has been studied. It has been shown that when heated in a dry benzene medium, nicotinic acid azide undergoes a Curcius rearrangement to form isocyanate, which reacts in situ with alcohols and the alkaloid cytisine to form the corresponding urethanes and urea. In order to synthesize 1,2,3-triazole derivatives, the interaction of nicotinic acid azide with terminal acetylene - prop-2-inyl ether of 3-tert-butyl-5-ethyl-2-hydroxybenzoic acid was carried out in a DMFA and heated (70-80 °C) in the presence of copper sulfate CuSO₄×5H₂O and sodium ascorbate (NaAsc). It was found that as a result of the reaction, not the expected 1,2,3-triazole compound is formed, but 3-aminopyridine and the initial acetylene compound. It is shown that when heated, the azide decomposes to form an intermediate particle, nitrene, and the subsequent migration of the pyridyl radical to the nitrogen atom (Curtius rearrangement) leads to isocyanate. As a result of hydration of isocyanate and subsequent decarboxylation of the resulting carbamic acid, 3-aminopyridine is obtained. Conclusion. The synthesis of nicotinoylazide was carried out by the interaction of sodium nitrite with nicotinic acid hydrazide. The interaction of nicotinic acid azide with terminal acetylen - prop-2-vinyl ester of 3-tert-butyl-5-ethyl-2-hydroxybenzoic acid did not lead to the formation of the expected 1,2,3-triazole compound. It was found that the initial azide undergoes Curcius rearrangement upon heating in situ with the formation of corresponding urethanes and urea. The structure of the synthesized compounds was confirmed by NMR ¹H and ¹³C spectroscopy, as well as data from the two-dimensional spectra COZY (¹H-¹H) and HMQC (¹H-¹³C).