Exploration and Mechanistic Study of Ni(II)‐Catalyzed Biginelli Reaction for Regio‐ and Chemo‐Selective Synthesis of Diverse 4 <i>H</i> ‐Pyrimido[2,1‐ <i>b</i> ]benzothiazoles

Abstract Pyrimido[2,1‐ b ]benzothiazoles can be easily synthesized from multicomponent reactions MCRs, which can effectively synthesize diverse heterocyclic analogues with pharmaceutical potential. Their one‐pot process efficiently creates functionalized molecules and libraries for discovering therapeutic leads. In this study, we disclosed a simple and efficient nickel chloride hexahydrate‐catalyzed method to synthesize a series of pyrimido[2,1‐ b ]benzothiazoles through Biginelli's reaction. It was found to promote the formation of pyrimido[2,1‐ b ]benzothiazoles via nickel metal‐coordinated stabilization of the polar intermediates' carbonyl functionality. We observed that Ni(II) catalyzed the reaction very efficiently and afforded a variety of pyrimido[2,1‐ b ]benzothiazoles with good to excellent yield in a shorter reaction time. This Lewis acid catalyst has been shown for regio‐ and chemo‐selective synthesis of pyrimido[2,1‐ b ]benzothiazoles. The optimized reaction was further explored to afford the easy and gram‐scale synthesis of pyrimido[2,1‐ b ]benzothiazoles.