Effect of a substituent on an aromatic group in diastereomeric resolution

The diastereomeric resolution of p-substituted 1-arylethylamines by enantiopure (S)-3',4'-methylenedioxymandelic acid ((S)-2) was carried out in order to know how an electron-donating or -withdrawing group on the aromatic group of the racemic amines would affect the efficiency of resolution. As a result, it was found that 1-arylethylamines having an electron-withdrawing substituent could be efficiently resolved by (S)-2, while the amines having an electron-donating group could not. The crystal structures of the less- and more-soluble salts, and the molecular orbital calculations of the ammonium cations indicated that the p-substituted electron-withdrawing group enhanced the positive charge on the meta-hydrogen of the aromatic group of the ammonium cations, which is favorable for the formation of a CH ...pi interaction in crystal. (C) 2000 Elsevier Science Ltd. All rights reserved.