Nickel Nanoparticles as a Sustainable Catalyst for the Synthesis of 2H ‐Pyran Derivatives under Microwave Irradiation, and their Anti‐Inflammatory Activity

Abstract This study includes an environmentally and effectively green method for the synthesis of novel 2 H ‐pyran derivatives 4 a–h via a one‐pot reaction of different aromatic aldehydes 1 a–h with ethyl cyanoacetate ( 2 ) and 2‐acetylphenyl‐4‐tolylsulfonate ( 3 ) in the presence of nickel oxide nanoparticles (NiO NPs) as a green catalyst in an aqueous mixed solution (EtOH: H 2 O, 1 : 3 ratio) using microwave irradiation. The structure of all prouducts were confirmed by spectral data and elemental analysis. All compounds were investigated for anti‐inflammatory activity compared with celecoxib as a reference drug. The obtained results indicate that 2‐[4‐(4‐tosyl oxy phenyl)‐3‐cyano‐2‐oxo‐2 H ‐pyran‐6‐yl]phenyl 4‐tolylsulfonate ( 4 b ) is the most anti‐inflammatory effective, which showed after 5 h., significantly inhibited inflammation compared with the carrageenan alone group (P < 0.0001)., and when compared to the treated group with celecoxib, inflammation was inhibited 42.38 % for compound 4 b compared to celecoxib 48.39 % simultaneously. Moreover, its histopathological examination was studied and showed a significant attenuation of inflammation and edema. The results indicated that pyran derivatives could serve as promising lead compounds for further optimization as anti‐inflammatory agents. The present protocol offers several advantages, such as inexpensive, easy work, pure products, shorter reaction times, excellent yields, environmental friendliness, and easy reuse of the catalyst several times.