Chinese Journal of Applied Chemistry ›› 2016, Vol. 33 ›› Issue (11): 1279-1283.DOI: 10.11944/j.issn.1000-0518.2016.11.160035

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Metal-Free Synthesis of 3,3-Difluoro-2-Oxindoles

MAI Wenpeng(),YANG Liu,LYU Mingxiu,WANG Yanwei,CAO Yi,LU Kui()   

  1. School of Materials and Chemical Engineering,He'nan Institute of Engineering,Zhengzhou 450006,China
  • Received:2016-01-21 Accepted:2016-04-07 Online:2016-11-01 Published:2016-11-01
  • Contact: MAI Wenpeng,LU Kui
  • Supported by:
    Supported by the National Natural Science Foundation of China(No.2172046, No.21302042)

Abstract:

A novel method for the synthesis of 3,3-difluoro-2-oxindoles was developed. 2-Bromo-2,2-difluoro-N-phenylacetamide was prepared from neat simple aromatic amines with ethyl bromodifluoroacetate. Reflux of the product in CH3CN with CH3I for 24 h gave 2-bromo-2,2-difluoro-N-methyl-N-phenylacetamide in 75%~90% yields. In the presence of 3.0 chemometric number sodium formaldehyde sulfoxylate, this key intermediate undergoes intramolecular radical cyclization in aqueous solution(N,N-dimethylformamide/H2O) and affords the final product 3,3-difluoro-1-methylindolin-2-ones in 53%~72% yields. This method can be performed in aqueous solution from commercially available and affordable starting materials without any metal catalysts. It shows potential in industrial production of 3,3-difluoro-2-oxindoles.

Key words: acetanilide, sodium formaldehyde sulfoxylate, difluoro-methylindolin-one, metal-free