Direct enantioseparation of 1-(2-hydroxyphenyl) ethylamines via diastereomeric salt formation: chiral recognition mechanism based on the crystal structure

作者：Kodama Koichi^*; Hayashi Naoki; Fujita Mikidai; Hirose Takuji

来源：RSC Advances, 2014, 4(49): 25609-25615.

DOI：10.1039/c4ra00414k

In this study, the direct enantioseparation of unprotected 1-(2-hydroxyphenyl) ethylamines (1a and 1b) via diastereomeric salt formation is reported. After the one-pot synthesis of racemic 1, the screening of seven acidic chiral resolving agents showed that the extraction of (S)-naproxen (6) with dibenzoyl-L-tartaric acid (5) afforded the corresponding 1 : 1 diastereomeric salts that were suitable for the resolution of 1a and 1b. The optimization of the solvents resulted in high efficiencies for the resolution of 1a$ 6 in aqueous alcohols, which was consistent with the fact that the incorporated water molecules in the less-soluble diastereomeric salt reinforced its hydrogen-bonding network. For the efficient enantioseparation of rac-1b with 5, the intramolecular CH...O hydrogen bond played an important role in the chiral recognition.

• 出版日期2014