Synthesis of 4-(pyrazol-1-yl)pyrimidines from 4-hydrazinopyrimidines and investigation of their structure and some chemical properties

Abstract

By reacting 2-benzyl-4-hydrazinopyrimidines with ethoxymethylidene derivatives of β-dicarbonyl compounds, the corresponding substituted 4-(1H-pyrazol-1-yl)pyrimidines were synthesized. In a number of examples, intermediates - products of condensation of the reagents in ethanol, were isolated, indicating that the initial attack on the nitrogen atom of the hydrazine fragment involves the ethoxymethylidene group. It was noted that subsequent cyclization of the intermediates in acetic acid leads to 4-(1H-pyrazol-1-yl)pyrimidines. Alkylation of the synthesized non-fused bicyclic systems was carried out and it was proved that the nitrogen atom N-1 of the pyrimidine ring undergoes alkylation. A complex of 2-benzyl-4-(5′-methyl-4′-ethoxycarbonylpyrazol-1′-yl)-6-methylpyrimidine with copper (II) chloride was synthesized. X-ray diffraction analysis proved that, in contrast to the metal complexes of similar pyrazolylpyrimidines, in this case, a single-dentate complex with a linear structure of the composition ligand:metal, 2/1, is formed, and the nitrogen atom N-1 of the pyrimidine ring participates in the formation of a bond with the metal atom, as well as during alkylation. It was found that H/D exchange occurs in pyrazolylpyrimidine molecules in a solution of CD3ONa in CD3OD. Using the methods of 1H NMR spectroscopy and high-resolution mass spectrometry, it was proved that the hydrogen atoms of the alkyl groups of the studied systems undergo isotope exchange. The kinetics of H/D exchange was studied using some examples. It has been shown that the presence of an allyl group in the pyrimidine ring significantly affects the direction and rate of the H/D exchange. The structure of all synthesized substances was confirmed by NMR methods (1H, 13C, NOESY), high-resolution mass spectrometry and in some examples X-ray diffraction analysis was also performed.