Pot, atom and step economic (PASE) assembly of salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones into medicinally relevant 5H-chromeno[2,3-b]pyridine scaffold

Mol Divers. 2020 Aug;24(3):617-626. doi: 10.1007/s11030-019-09968-x. Epub 2019 Jun 8.

Abstract

The new multicomponent reaction (MCR) has been found: one-pot selective and efficient formation of the new 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridines in 61-97% yields directly from simple and easily available salicylaldehydes, malononitrile dimer and 4-hydroxypyridine-2(1H)-ones in small amount of pyridine-ethanol catalyst/solvent system. This complex "domino" transformation includes Knoevenagel condensation of salicylaldehyde with malononitrile dimer, Michael addition of 4-hydroxypyridine-2(1H)-one, double Pinner-type reaction cyclization and isomerization with following protonation. This facile multicomponent process opens a new way to 5-(4-hydroxy-2-oxo-1,2-dihydropyridin-3-yl)-substituted 5H-chromeno[2,3-b]pyridine systems, which are promising compounds for the treatment for human inflammatory TNFα-mediated diseases and different biomedical applications.

Keywords: 4-Hydroxy-6-methylpyridine-2(1H)-ones; 5H-Chromeno[2,3-b]pyridines; Catalysis; Malononitrile dimer; Multicomponent reaction; Salicylaldehydes; “On-solvent” process.

MeSH terms

  • Aldehydes / chemistry*
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry*
  • Chemistry Techniques, Synthetic
  • Cyclization
  • Isomerism
  • Nitriles / chemistry*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridones / chemistry*

Substances

  • Aldehydes
  • Anti-Inflammatory Agents
  • Nitriles
  • Pyridines
  • Pyridones
  • salicylaldehyde
  • 4-pyridone
  • Malononitrile dimer