Regioselective Copper-Catalyzed Amination of Chlorobenzoic Acids:  Synthesis and Solid-State Structures ofN-Aryl Anthranilic Acid Derivatives

  • 10.1021/jo0518809
  • The Journal of Organic Chemistry
  • p 142-149, Volume 71, Issue 1,
  • journal-article
A chemo- and regioselective copper-catalyzed cross-coupling reaction for effective amination of 2-chlorobenzoic acids with aniline derivatives has been developed. The method eliminates the need for acid protection and produces a wide range of N-aryl anthranilic acid derivatives in up to 99% yield. The amination was found to proceed with both electron-rich and electron-deficient aryl chlorides and anilines and also utilizes sterically hindered anilines such as 2,6-dimethylaniline and 2-tert-butylaniline. The conformational isomerism of appropriately substituted N-aryl anthranilic acids has been investigated in the solid state. Crystallographic analysis of seven anthranilic acid derivatives showed formation of two distinct supramolecular architectures exhibiting trans−anti and unprecedented trans−syn dimeric structures.


Synthesis of N-(4-carboxyphenyl) anthranilic acid

N-(4-carboxyphenyl) anthranilic acid (compound 31)

A mixture of 2-chlorobenzoic acid (1 mmol), 4-aminobenzoic acid (1 mmol), K2CO3 (2 mmol), Cu powder (0.009 mmol), and Cu2O (0.009 mmol) in 0.3 mL of 2-ethoxyethanol was refluxed at 130°C under inert atmosphere for 24 h. The...