Rationalization of Chiral Discrimination upon Crystallization of Diastereomeric Salt and Development of Novel Practical Resolving Reagent

点击翻译按钮获取中文摘要

In order to understand the mechanism of chiral discrimination upon crystallization of diastereomeric salt and to develop novel resolving reagents, the resolution of 1-arylalkylamines by mandelic acid was studied. As a result, it was found that the position of a substituent on the aromatic group of the amines was correlated with the resolution efficiency to a considerable extent. A substituent, which elongated the molecular length of the amine, diminished the resolution efficiency. The crystal structures of less-soluble diastereomeric salts revealed that a characteristic hydrogen-bond layr, consisting of hydrogen-bond columns and having planar boundary surfaces, was commonly formed ; these crystals were considered to be stable from the viewpoint of both hydrogen-bonding and van der Waals interactions. Such a stable layr would be necessary for efficient resolution, and in order to realize such a stable hydrogen-bond layr, the molecular length of a racemate should be similar to or a little shorter than that of the resolving reagent. In contrast, in the cases of the corresponding more-soluble salts and diastereomeric salts, which could not be separated by crystallization, such a stable crystal structure was not realized in all cases. On the basis of these results, (S)-p-methylmandelic acid and (R)-p-methoxymandelic acid were selected as new resolving reagents for 1-arylalkylamines ; these resolving reagents were found to have a higher resolving ability for 1-arylalkylamines than mandelic acid.