A new method is described for the enrichment of enantiomeric mixtures having an enantiomeric ratio other than 1: 1. The method is based on partial salt formation of the enantiomeric mixture with an achiral substance followed by the distillation of the free enantiomer. The distillate has a different enantiomeric composition than the starting mixture. The method was performed on enantiomeric mixtures of a-phenylethylamine using four different dicarboxilic acids. o 1995 wiley-Liss, Inc. KE Y WORDS: enantiomers, enantiomeric enrichment, optical purity, selective separation, a-phenylethylamine Stereoselective syntheses' and optical resolutions2 rarely result in optically pure enantiomers. The product usually contains some amount of the unwanted enantiomer. The separation of the enantiomer in excess from the racemic part can be achieved by fractional cry~tallisation~ or by selective separation methods. The selective separation means salt formation cal rotations were measured for the distillate and for the Liberated base using a Perkin-Elmer 241 polarimeter. The optical rotation of the optical pure (R)-a-phenylethylamine is [ . I D = +28.92" (c: 0.1; ethanol). RESULTS AND DISCUSSIONwith a nonequivalent amount of an achiral agent accompanied by a phase alteration, like selective pre~ipitation,~'~ or selective liberation combined with extraction. 6,7 The selective separation can give a very effective enantiomeric enrichment.In this work we investigated another way to achieve a selective separation, which is based on partial salt formation of the enantiomeric mixture with an achiral substance followed by the distillation of the free enantiomer. The main advantage of distillation over other selective separations is that the use of solvent can be avoided. In our investigation the a-phenylethylamine served as the model compound. Four different achiral dicarboxilic acids, oxalic acid, succinic acid, maleic acid and fumaric acid, were used as salt-forming agents. This method has never been used for any salts of a-phenylethylamine or any other chiral bases to our knowledge.The optical purity of the distillate and the residue are plotted against the optical purity of the starting a-phenylethylamine mixtures on Figures 1 through 4. In each case, 0.75 molar equivalents of salt-forming agent were added.It can be seen from the figures that all four acids give enantiomeric enrichment to some extent. It should be mentioned that none of the acids gives an optical pure or racemic base in either the distillate or in the residue of our experiments.The fumaric acid gives the best separation, namely the curves of the distillate and the residue are further from the diagonal. If the optical purity of the starting a-phenylethylamine mixture is higher than 40%, the optical purity of the distillate will be higher than 80%.In the other three cases (oxalic acid, succinic acid, and MATERIALS AND METHODS maleic acid) the curves of the distillate and the residue intersect each other and the diagonal. *The intersections are important in these s...

We investigated the enantiomeric enrichment of enantiomeric mixtures of alpha-phenylethylamine by achiral dicarboxylic acids. As achiral agents oxalic, malonic, fumaric, and phthalic acids were used. The results of the enantiomeric enrichment via partial salt formation followed by distillation were compared with enantiomer separation via crystallization of the neutral salt. Without the presence of a solid phase, enantiomeric separation is impossible. Our results show that the properties of the solid phase determine the separation. It is also confirmed by our observation that the eutectic points, which are observed on the 3-phase solubility diagrams of the solid neutral salts, can be found at the same initial enantiomeric composition as the point of intersection of distillate and residue of the distillation curves and the point of intersection of precipitated salt and mother liquor of the crystallization curves. Copyright 2000 Wiley-Liss, Inc.

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