Green Synthesis of Quinazolinone Scaffolds from the Cascade Reaction of o-Aminobenzamides/o-Aminobenzonitrile and Calcium Carbide mediated by K2S

An efficient multicomponent methodology has been developed for the synthesis of quinazolinones and dihydroquinazolinones through the reaction of o-aminobenzamides or o-aminobenzonitriles with CaC 2 mediated by K 2S. The process begins with the formation of thioacetaldehyde, which results from the direct nucleophilic attack of sulfur anions on the acetylene generated from CaC 2. Subsequently, the thioacetaldehyde reacts with o-aminobenzamides to produce an imine intermediate, which then undergoes cyclization to generate the target compound in moderate to excellent yields. Moreover, this methodology has been extended to a one-pot synthesis of dihydroquinazolinone using 2-aminobenzonitrile and CaC 2. In this approach, the nitrile group is hydrolyzed to form an amide, and then reacts with CaC 2 to yield the target product. Notably, this protocol exhibits excellent scalability and has been successfully applied to sythesize pharmaceutical compounds or drug intermediates. By using cost-effective and eco-friendly reagents such as CaC 2 and inorganic sulfides, this strategy provides a valuable and sustainable alternative to existing methods for the synthesis of quinazolinones.