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Cu-Catalyzed Coupling Reactions of Sulfonamides with (Hetero)Aryl Chlorides/Bromides.

Qiaoli LiLanting XuDawei Ma
Published in: Angewandte Chemie (International ed. in English) (2022)
Direct N-arylation of sulfonamides is a very attractive approach for preparing pharmaceutically important N-(hetero)aryl sulfonamides because it avoids the potential genotoxic problem resulting from the previous condensation method. Most known catalytic methods suffer from limited reaction scope and inconveniency on metal catalyst and ligand availability. Here we described that the combination of copper and oxalamides (or 4-hydroxypicolinamides) offers a powerful catalytic system for N-arylation of sulfonamides. A wide range of primary and secondary sulfonamides were able to couple with a series of (hetero)aryl bromides in the presence of 2-5 mol % copper salts and oxalamides at 100 °C. Coupling of primary sulfonamides with (hetero)aryl chlorides worked well under the catalysis of Cu<sub>2</sub> O and a 4-hydroxypicolinamide. The catalytic method enabled direct sulfonamidation of four chloro-containing marketed drugs and preparation of two sulfonamide drugs from the corresponding aryl halides.
Keyphrases
  • solid phase extraction
  • room temperature
  • ionic liquid
  • molecularly imprinted
  • metal organic framework
  • risk assessment
  • drug induced
  • highly efficient
  • tandem mass spectrometry
  • electron transfer
  • liquid chromatography