REACTIONS OF BINARY AND THREE-COMPONENT SYNTHESIS OF 3-PYRIDYL SUBSTITUTED AMINOCHROMENCARBONITRILES AND THEIR IODOMETHYLATES

The unrelenting attention of researchers to 2-aminochromene(pyran)-3-carbonitriles is primarily due to their wide range of biological activity, other practically useful properties and numerous possibilities for their transformation, which is important for pharmacological research. Based on the modern concept of “hybrid drugs”, we have synthesized hybrid systems including pyridine and chromene fragments - mono- and di-3-pyridyl-substituted aminochromene carbonitriles and their water-soluble iodomethylates (thermal, ultrasonic activation, sequence of reagent introduction). Synthetic approaches are based on the use of binary and ternary condensation reactions of available carbonyl compounds under varying conditions. For dipyridyl-substituted systems, three-component reactions turned out to be the most effective (cyclohexanone, 3-pyridinecarbaldehyde, malononitrile and 2,6-dipyridin-3-ylmethylidenecyclohexanone, malononitrile and methyl iodide), which made it possible to reduce the reaction time, eliminate the stages of preliminary preparation of starting substances (chalcone, chromene) while maintaining good product yields. When chalcone interacts with various terminal substituents (phenyl, 3-pyridyl), due to the non-equivalence of the active centers of the substrate, regioisomeric aminochromene carbonitriles are formed, differing in the position of the phenyl and hetaryl substituents at the C-4 and C-8 atoms of the chromene ring, and separated using column chromatography. When iodomethylating a mixture of regioisomers, the corresponding iodomethylates were obtained - products of selective quaternization with the participation of the nitrogen atom of the pyridine ring. The structure of the newly synthesized substances and the ratio of regioisomers were determined by spectral methods (IR, 1H, 13C NMR, HSQC, HMBC). When studying the antibacterial activity of all obtained compounds, dipyridyl-substituted aminochromene carbonitrile turned out to be the leader in relation to Staphylococcus aureus. The data obtained create prospects for further research on four-component variants of the synthesis of compounds of this type. For citation: Nikulin A.V., Vasilkova N.O., Krivenko A.P. Reactions of binary and three-component synthesis of 3-pyridyl substituted aminochromencarbonitriles and their iodomethylates. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2025. V. 68. N 3. P. 20-26. DOI: 10.6060/ivkkt.20256803.7093.