Synthesis of N-(5-(Methylsulfanyl)-4H-1,2,4-triazol-3-yl)pyridin-2-amine Derivatives and Their 1,2,4-Triazine Precursors

• Published in: Russian journal of organic chemistry 2024-04, Vol.60 (4), p.684-689
• Main Authors: Shtaitz, Ya. K., Ladin, E. D., Sharutin, V. V., Kopchuk, D. S., Rybakova, A. V., Sharafieva, E. R., Krinochkin, A. P., Zyryanov, G. V., Pospelova, T. A., Matern, A. I.
• Format: Article
• Language: English
• Subjects: Chemistry; Chemistry and Materials Science; Crystal structure; Crystallization; Crystallography; Cyano groups; Electron impact; Mass spectrometry; NMR; Nuclear magnetic resonance; Organic Chemistry; Protons; Pyridines; Substitution reactions; Triclinic crystals; X ray analysis
• ISSN: 1070-4280; 1608-3393
• DOI: 10.1134/S1070428024040171

The reaction of 5-cyano-1,2,4-triazines with 5-(methylsulfanyl)-4 H -1,2,4-triazol-3-amine under solvent-free conditions gave product of nucleophilic substitution of the cyano group of 1,2,4-triazine by the 1,2,4-triazol-3-amine residue. The product structure was determined by 1 H NMR and mass spectrometry (electron impact). Its 1 H NMR spectrum showed a characteristic three-proton singlet at δ 2.61 ppm, which was assigned to methylsulfanyl group. The subsequent reaction of the obtained product with norborna­diene under pressure resulted in the transformation of the 1,2,4-triazine ring into pyridine, while the methyl­sulfanyl group remained intact. This was confirmed by X-ray analysis of the resulting functionalized pyridine. According to the X-ray diffraction data, it crystallized as two crystallographically independent molecules in non-centrosymmetric space group P -1 belonging to the triclinic crystal system. The crystal structure is formed via numerous intermolecular N···H contacts between the two crystallographically independent triazolylpyridin-2-amine molecules. The 1 H NMR spectrum displayed two doublets at δ 7.37 and 7.61 ppm due to protons of the newly formed pyridine ring. Thus, the behavior of 5-(methylsulfanyl)-4 H -1,2,4-triazol-3-amine differs from the behavior of its analogue containing a thiol group at C 5 . As we showed previously, in the reaction of the latter with 5-cyano-1,2,4-triazine, substitution of the cyano group was accompanied by desulfurization of the triazole-5-thiol.