Ecofriendly synthesis of pyrano[2,3‐d]pyrimidine derivatives and related heterocycles with anti‐inflammatory activities

A versatile, efficient, clean, and facile method was used for the synthesis of pyrano[2,3‐d]pyrimidine derivatives by the one‐pot three‐component condensation reaction of thiobarbituric acid and malononitrile with p‐chlorobenzaldehyde, using Fe3O4 or ZnO or Mn3O4 as nanostructure catalysts. The catalyst could be easily recovered using an external magnet and reused for six cycles with almost a consistent activity. A series of polyheterocyclic compounds containing five and/or six rings fused with each other was designed. The anti‐inflammatory activities for some of the newly synthesized compounds were evaluated. All the synthesized compounds were characterized on the basis of their elemental analyses and spectral data. A one‐pot multicomponent cyclocondensation protocol was developed for 7‐amino‐5‐(4‐chlorophenyl)‐4‐oxo‐2‐thioxo‐2,3,4,5‐tetrahydro‐1H‐pyrano[2,3‐d]pyrimidine‐6‐carbonitrile (1) in the presence of a catalytic amount of (Fe3O4 or Mn3O4 or ZnO) nanoparticles as a catalyst, using refluxing conditions in ethanol. The investigation of the anti‐inflammatory activity of some compounds showed a remarkable in vitro anti‐inflammatory activity as they inhibit COX‐2, LOX, and TNF‐α.