Sustainable access to novel pyridone scaffolds: Efficient one-pot, three-component synthesis in PEG-400

This study presents a straightforward and efficient method for synthesizing a novel series of 1-benzyl-3-((1-benzyl-4-(benzylamino)-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)(aryl)methyl)-4-hydroxy-6-methylpyridin-2(1H)-one derivatives through a one-pot, three-component reaction. The process employs 1-benzyl-4-hydroxy-6-methylpyridin-2(1H)-one, diverse aromatic aldehydes, and 1-benzyl-4-(benzylamino)-6-methylpyridin-2(1H)-one in polyethylene glycol (PEG-400) as an environmentally benign solvent. The methodology prioritizes efficiency, scalability, and reduced environmental impact, offering a practical route to functionalized pyridinones.

We report a catalyst-free protocol for the efficient synthesis of biologically relevant heterocycles, notably functionalized pyridinones. This method features high atom economy, broad functional group tolerance, and minimal purification steps, embodying the sustainable chemistry principles. All products were characterized by multi-spectroscopic analyses (¹H/¹³C NMR, IR, MS) and elemental analysis. Furthermore, single-crystal X-ray diffraction provided unambiguous structural confirmation for a representative derivative.