Efficient Synthesis of Heterocyclic-Fused Quinoline-2-thiones with TCDI

Abstract Pyrrolo[1,2-a]quinoxaline-4(5H)-thione and quinoline-2-thione, as privileged thiocarbonyl-containing compounds, exhibit broad application prospects in drug molecule development. Their rigid planar structure and ability to bind effectively to biological targets make them attractive motifs in medicinal chemistry. Current approaches to these compounds typically depend on intramolecular cyclization of 2-substituted anilines with thiocarbonyl-transfer reagents. However, the reported methods to access these attractive scaffolds by using existing thiocarbonyl sources usually require high reaction temperature or raise safety concerns, hindering their use on larger scales. To address these limitations, we report a practical and efficient synthesis of diverse heterocycle-fused quinoline-2-thiones using 1,1′-thiocarbonyldiimidazole (TCDI) as a safe, commercially available thiocarbonyl donor. The products are easily isolated by filtration, and the core scaffold demonstrates promising derivatization potential for accessing pharmacologically relevant sulfur-containing heterocycles.