CuBr2-catalysed intramolecular oxidative CN bond formation for synthesis of indoline-2,3-diones and anticancer drug semaxanib under continuous-flow conditions

A new and efficient CuBr2-catalysed continuous-flow method for the synthesis of indoline-2,3-diones is presented. This is an intramolecular oxidative CN bond formation reaction which proceeds via a bromo intermediate, followed by benzylic CH oxidation in presence of molecular oxygen as an oxidant. T...

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Bibliographic Details
Main Authors: Charu Arya, Moumita Khanra, K. Naveen Kumar, Sharada Prasanna Swain
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Applied Catalysis O: Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950648425000379
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Summary:A new and efficient CuBr2-catalysed continuous-flow method for the synthesis of indoline-2,3-diones is presented. This is an intramolecular oxidative CN bond formation reaction which proceeds via a bromo intermediate, followed by benzylic CH oxidation in presence of molecular oxygen as an oxidant. The reaction in a flow reactor needed lower catalyst loading, and reaction time was reduced from 15 h to 40 min. Running the reaction is fairly easy from an operational standpoint. Under the ideal reaction conditions, it works well for both 1° and 2° amines, and provides corresponding indoline-2,3-diones in 60–81 % yields. A new reaction mechanism is proposed and the formation of proposed intermediates is confirmed by high resolution mass data. The reaction was successfully applied for the synthesis of the anticancer drug semaxanib and antiviral drug metisazone.
ISSN:2950-6484