RECIPROCAL RESOLUTION OF 1-(4-METHYLPHENYL)ETHYLAMINE AND 2-HYDROXY-4-PHENYLBUTYRIC ACID, AND HABIT MODIFICATION OF A LESS-SOLUBLE DIASTEREOMERIC SALT WITH A CHIRAL ADDITIVE

A reciprocal resolution was successfully carried out by a diastereomer ic method between 1-(4-methylphenyl)ethylamine (1) and 2-hydroxy-4-phe nylbutyric acid (2); enantiomerically pure 1 was obtained from water s olvent involving hydrochloric acid (0.5 mol) by using enantiomerically pure 2 as a resolving agent, while enantiomerically pure 2 was obtain ed from water solvent involving sodium hydroxide (0.5 mol) by using en antiomerically pure 1. Upon the optical resolution of (RS)-1 with enan tiomerically pure 2, the crystal morphology of the less-soluble salt ( L-salt), (R)-1.(R)-2, was changed by addition of chiral secondary amin es derived from enantiomerically pure amine 1. Effective additives for the habit modification were (R,R)- and (S,S)-bis[1-(4-methylphenyl)et hyl]amine (3). The habit modification experiments showed that molecula r recognition by the cavity created on the surface of the diastereomer ic salt was structure-specific but not stereospecific. The X-ray cryst allography of the L-salt revealed that molecular recognition between r esolving agent 2 and amine 1 or chiral additive 3 was due to the cavit y structure constructed with the resolving agent.