Facile synthesis of 2-benzoxazoles via CuI/2,2'-bipyridine catalyzed intramolecular C-O coupling of 2-haloanilides

Abstract

Development of newer methods for the synthesis of Benzoxazoles has of greater interest due to their wide range of biological activities and pharmaceutical importance. We herein report a facile and general method for the synthesis of 2-substituted Benzoxazoles via copper catalyzed intramolecular C-O cross-coupling of 2-haloanilides. A combination of CuI (5 mol%), 2,2'-bipyridine (10 mol%), Cs₂CO₃ (2 equiv.) in DMF solvent with 4 Å molecular sieves at 140 °C, illustrated the scope for tuning the reactivity of 2-haloanilides toward the selective formation of a series of 2-alkyl benzoxazole derivatives in moderate to good yields. This is the first systematic study using CuI/2,2'-Bipyridine as the catalytic system for the synthesis of 2-substituted Benzoxazoles. The outcome of the reaction was found to be significantly influenced by the aromatic and amide substituents of 2-haloanilides.

Graphical Abstract

Keywords:

• Benzoxazole
• copper
• 2-haloanilides
• 2,2'-bipyridine
• C-O coupling

Acknowledgments

TVS and SPR thank Council of Scientific and Industrial Research (CSIR, India) for Junior Research Fellowships. Authors thank Inter University Instrumentation Centre (IUIC), Mahatma Gandhi University, Kottayam for HRMS and IR analysis. We also thank Institute for Intensive Research in Basic Sciences IIRBS, Mahatma Gandhi University, Kottayam and Sophisticated Test and Instrumentation Centre (STIC), Cochin University of Science and Technology, Cochin for NMR analyses.