Reciprocal resolutions between 1-phenylethylamine and carboxyesters of isopropylidene glycerol: improvement of the method by replacing mono-phthalate with 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 group with a naphthyl group would improve the resolving ability of isopropylidene glycerol hydrogen phthalate 1 while also conferring more suitable physicochemical properties for such a specific use. Indeed, 1-phenylethylamine 4 was resolved by 2 more efficiently than by 1 (respective resolution efficiencies, (S) 0.88 and 0.81), while 1 and 2 were resolved by 4 with S ranging 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 than 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 eutectics, 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-arylalkylamines seems to have very good prospects, worthy of investigation.