Structural Analysis of d -Phenylglycinamide Salts Uncovers Potential Pitfalls in Chiral Resolution via Diastereomeric Salt Formation

d-Phenyglycinamide (d-PGA) was shown to form diastereomeric salts with a series of dicarboxylic acids (malic, methylsuccinic, camphoric) and the drug naproxen. Structural analysis of the 21 newly discovered forms was performed in order to investigate the potential of d-PGA as a base agent for chiral resolution via diastereomeric salt formation. Malic and methylsuccinic dicarboxylic acids formed salts with 1:1 and 2:1 stoichiometries, whereas camphoric acid and naproxen yielded only 1:1 salts. In the d-PGA/naproxen system, variable-temperature in situ synchrotron X-ray diffraction gave access to two additional nonambient 1:1 salts. d-PGA subjected to liquid-assisted grinding with the racemic forms of the tested compounds to study chiral resolution in the solid state yielded in most of the cases complicated mixtures of diastereomeric salts or salts with the racemates (when both enantiomers and d-PGA crystallize in one structure), thereby suggesting that the use of d-PGA for chiral resolution may be challenging.