Design‐Expert a Powerful Tool for Optimizing Organic Synthesis: A Green and Facile Multicomponent Synthesis of New 2‐Pyridone‐pyrimidine Derivatives by p‐Toluene Sulfonic Acid in Water

Abstract An efficient synthesis of a novel series of 2‐pyridone‐pyrimidine derivatives via multicomponent reaction of different 4‐hydroxy‐6‐methylpyridine‐2‐ones, aromatic aldehydes, and barbituric acid or 6‐aminouracil in the presence of p‐toluene sulfonic acid in water has been reported. At first, the modified conditions to afford the best yield of a sample product were obtained (100 °C, one hour, and 100 mole % of p‐TSA) and then used for the others. The significant point of this report is to use Design‐Expert software for optimizing conditions. This reaction addition to having all the advantages of a green approach for synthesizing potentially bioactive compounds, such as eco‐compatibility, high yield of products, simple operation, and so, due to the using the methodic and pre‐calculated statistical optimization process, has high precision and accuracy. This approach can show a new path in optimizing the synthetic procedures of organic compounds.