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.

Graphical Abstract

Keywords:

• α-Keto acid
• benzothiazoles
• benzoxazinones
• benzoxazoles
• green synthesis
• quinoxalinones

Acknowledgments

R.B.R.D.Y. is grateful to DST-SERB, New Delhi, for the Early Career Research Award [Grant No. ECR/2016/001041] and S. M. is thankful to DST-SERB for the fellowship. We also thank the SASTRA Deemed University for providing lab space.

Additional information

Funding

The authors gratefully acknowledge the DST-FIST NMR facility [Grant No. SR/FST/CS-I/2018/62] at the Department of Chemistry, SASTRA Deemed University. This work was supported by Science and Engineering Research Board.