Toward the Computational Design of Diastereomeric Resolving Agents: An Experimental and Computational Study of 1-Phenylethylammonium-2-phenylacetate Derivatives

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• 作者：Panagiotis G. Karamertzanis ; Parathy R. Anandamanoharan ; Phillipe Fernandes ; Peter W. Cains ; Martin Vickers ; Derek A. Tocher ; Alastair J. Florence ; Sarah L. Price
• 刊名：Journal of Physical Chemistry B
• 出版年：2007
• 出版时间：May 17, 2007
• 年：2007
• 卷：111
• 期：19
• 页码：5326 - 5336
• 全文大小：129K
• 年卷期：v.111,no.19(May 17, 2007)
• ISSN：1520-5207

文摘

The crystal structures, including two new polymorphs, of three diastereomerically related salt pairs formedby (R)-1-phenylethylammonium (1) with (S&R)-2-phenylpropanoate (2), (S&R)-2-phenylbutyrate (3), and(S&R)-mandelate (4) ions were characterized by low-temperature single crystal or powder X-ray diffraction.Thermal, solubility, and solution calorimetry measurements were used to determine the relative stabilities ofthe salt pairs and polymorphs. These were qualitatively predicted by lattice energy calculations combiningrealistic models for the dominant intermolecular electrostatic interactions and ab initio calculations for theions' conformational energies due to the distortion of their geometries by the crystal packing forces. Crystalstructure prediction studies were also performed for the highly polymorphic diastereomeric salt pair (R)-1-phenylethylammonium-(S&R)-2-phenylbutyrate (1-3) in an attempt to predict the separation efficiency withoutrelying on experimental information. This joint experimental and computational investigation provides astringent test for the reliability of lattice modeling approaches to explain the origins of chiral resolution viadiastereomer formation (Pasteurian resolution). The further developments required for the computationalscreening of single-enantiomer resolving agents to achieve optimal chiral separation are discussed.