Regioselective Copper-Catalyzed Amination of Chlorobenzoic Acids:  Synthesis and Solid-State Structures of <i>N</i>-Aryl Anthranilic Acid Derivatives

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 <i>N</i>-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-<i>tert</i>-butylaniline. The conformational isomerism of appropriately substituted <i>N</i>-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<i>−</i>anti and unprecedented trans<i>−</i>syn dimeric structures.