Thiocyanate-induced N-activation and nucleophilic 1,2-dearomatization of pyridinedicarbonyl dichloride: a synthetic route to a novel 1,2-dihydropyridine-based heterocyclic compound

• Published in: Journal of the Iranian Chemical Society Vol. 20; no. 10; pp. 2657 - 2664
• Main Authors: Mukiza, Janvier, Habarurema, Gratien, Nkuranga, Jean Bosco, Sezirahiga, Jurdas, Akin-Ojo, Omololu, Nkurunziza, Jean Baptiste, Kampire, Edwidge, Gakuba, Emmanuel, Blacque, Olivier
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2023; Springer Nature B.V
• Subjects: Analytical Chemistry; Biochemistry; Chemistry; Chemistry and Materials Science; Chromatography; Communication Papers; Crystallography; Density functional theory; Dichlorides; Heterocyclic compounds; Inorganic Chemistry; Liquid chromatography; Mass spectrometry; NMR; Nuclear magnetic resonance; Organic Chemistry; Physical Chemistry; Pyridines; Reagents; Single crystals; Structural analysis; Thiocyanates; Dearomatization; Pyridinedicarbonyl dichloride; 1,2-Dihydropyridine; Heterocyclic; Thiocyanate
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-023-02863-1

The 1,2-dearomatized pyridine derivatives are among the most beneficial scaffolds for synthetic and medicinal chemistry and have along with others substantially contributed to pharmaceutical research. We report uncatalyzed thiocyanate-induced N -activation and nucleophilic 1,2-dearomatization of pyridinedicarbonyl dichloride with further addition of diphenylamine leading to the novel 1,2-dihydropyridine-based heterocyclic compound; ( ±) 2′-(diphenylamino)-3-thioxo-2,3-dihydro-1H,4′H-spiro[imidazo[1,5-a]pyridine-5,5′-thiazole]-1,4′-dione ( 1 ). The previously reported dearomatizations of pyridine and its derivatives usually demand a specific catalyst. Therefore, uncatalyzed 1,2-dearomatization of pyridinedicarbonyl dichloride observed in this study is unusual. Heterocyclic compound 1 will act as potential mother reagent for the synthetic route to a variety of novel heterocyclic compounds derivative to 1,2-dihydropyridine. The purity of the product was assessed by Ultraperformance Liquid Chromatography (UPLC), and the structural characterization was achieved by 1 H NMR, 13 C NMR, DEPT-135-NMR, IR, Liquid Chromatography Mass Spectrometry (ESI–MS), single crystal X-ray crystallography and density function theory (DFT). Graphical abstract The reaction of pyridine-2,6-dicarbonyl dichloride with potassium thiocyanate (KSCN) and diphenylamine in acetone led to the novel heterocyclic compound typically (±) 2′-(diphenylamino)-3-thioxo-2,3-dihydro-1H,4′H-spiro[imidazo[1,5-a]pyridine-5,5′-thiazole]-1,4′-dione.