Reciprocal resolutions between 1-phenylethylamine and carboxyesters of isopropylidene glycerol: improvement of the method by replacing mono-phthalatewith 3-carboxy-2-naphthoate

A novel resolving agent, isopropylidene glycerol 3-carboxy-2-naphthoate 2, was designed on the basis of the consideration that replacement of phenyl g roup with a naphthyl group would improve the resolving ability of isopropyl idene glycerol hydrogen phthalate 1 while also conferring more suitable phy sicochemical properties for such a specific use. Indeed, 1-phenylethylamine 4 was resolved by 2 more efficiently than by I (respective resolution effi ciencies, (S) 0.88 and 0.81), while 1 and 2 were resolved by 4 with S rangi ng between 0.54 and 0.59. Furthermore, 2 is a solid, whereas 1 is a viscous oil, and its recovery at the end of the resolution procedure is easier tha n that of 1. In order to understand the chiral discrimination mechanism of the two reciprocal resolutions, the binary melting point phase diagrams of the four diastereomeric systems (S)-2.(S)-4/(S)-2.(R)-4, (S)-2.(S)-4/(R)-2. (S)-4, (S)-1.(S)-4/(S)-1.(R)-4 and (S)-1.(S)-4/(R)-1.(S)-4 were determined. The first two systems form ideal conglomerates, characterised by identical diagrams, in which the eutectic corresponds to a 0.10 molar ratio of (S)-2 -(S)-4. The same behaviour was shown by the other two systems, whose eutect ics, however, correspond to a 0.18 molar ratio of (S)-1.(S)-4. On the basis of the present results, which indicate an excellent resolution ability of 2 for 4, the application of this new acid to the resolution of other 1-aryl alkylamines seems to have very good prospects, worthy of investigation. (C) 2001 Elsevier Science Ltd. All rights reserved.