Solvent-free Friedel-Crafts Reaction for Regioselective Synthesis of Ethyl (9-Anthryl)glyoxylate and Chiral Resolution of (±)-(9-Anthryl)hydroxyacetic Acid

A green chemistry-based highly regioselective synthesis of ethyl (9-anthryl)glyoxylate was achieved by solvent-free Friedel-Crafts reaction at r. t. Several derivatives of ethyl (9-anthryl)glyoxylate were also synthesized. Ethyl (9-anthryl)hydroxyacetate was obtained almost quantitatively by reduction of ethyl (9-anthryl)glyoxylate with NaBH4, and (9-anthryl)methoxyacetic acid was prepared by methylation of ethyl (9-anthryl)hydroxyacetate with CH3I in the presence of Ag2O and hydrolysis of ethyl (9-anthryl)methoxyacetate. The hydrolysis of ethyl (9-anthryl)hydroxyacetate gave racemic (9-anthryl)hydroxyacetic acid, and the racemate was successfully resolved by crystallization of the diastereomeric salts resulting from the reaction of (±)-(9-anthryl)hydroxyacetic acid with (–)-ephedrine. As a byproduct, crystals containing racemic (±)-(9-anthryl)hydroxyacetate and protonated (–)-ephedrine were isolated and their structures determined by X-ray diffraction.