Green Synthesis of Novel Pyridines via One-Pot Multicomponent Reaction and Their Anti-Inflammatory Evaluation.

A functional and environmentally green procedure for the design of novel pyridine 5a-h and 7a-d derivatives through two pathways is presented. The first pathway is via a one-pot, four-component reaction of p-formylphenyl-4-toluenesulfonate (1), ethyl cyanoacetate (2), acetophenone derivatives 3a-h or acetyl derivatives 6a-d, and ammonium acetate (4) under microwave irradiation in ethanol. The advantages of this method are an excellent yield (82%-94%), pure products, a short reaction time (2-7 min), and low-cost processing. The second pathway was obtained by the traditional method with treatment of the same mixture under refluxing in ethanol, which afforded the same products, 5a-h and 7a-d, in less yield (71%-88%) and over a longer reaction time (6-9 h). The constructions of the novel compounds were articulated via spectral and elemental analysis. Overall, the compounds have been designed, synthesized, and studied for their in vitro anti-inflammatory activity using diclofenac as a reference drug (5 mg/kg). The most potent four compounds, 5a, 5f, 5g, and 5h, showed promising anti-inflammatory activity.