Base promoted coupling of α-ketoacids and 2-substituted aromatic amines: Green synthesis of diverse benzoxazoles, benzothiazoles, quinoxalinones and benzoxazinones and its practical application

Abstract

Synthesis of 2-aryl substituted benzoxazoles, benzothiazoles, and quinoxalinones via decarboxylative coupling of α-keto acids with 2-aminophenol, 2-aminothiophenol, and OPD (o-phenylenediamine), using K₂CO₃ as a base in water at room temperature, and as well as solvent-free grinding and the synthesis of benzoxazinones from the reaction of α-keto acids with 2-aminophenol at 60 °C have been reported. Both the protocols afforded a wide range of desired products with excellent functional group tolerance in yields of 87–99%. The major advantages of these approaches are catalyst-free protocol, short reaction times, straightforward workup, and chromatography-free processing of the products. Additionally, to test the translational demand of this methodology, the synthesis of 2-(3,5-dichlorophenyl)-6-methylbenzo[d]oxazole was carried out which is a key structure of tafamidis, a commercially available drug.