Remarkable similarity of molecular packing in crystals of racemic and enantiopure 2-phenylpropionamide: Z' = 4 structures, molecular disorder, and the formation of a partial solid solution.

Abstract

Substituted acetamides (many of which are chiral) are known to be pharmacologically active. 2-Phenylpropionamide (2PPA) is one of the simplest chiral α-substituted acetamides and thus is of interest as a model compound in the growth and design of pharmaceutical crystals. In this study, the crystal structures of racemic and enantiopure forms of 2PPA were determined for the first time using single crystal X-ray diffraction at 100 K. The relationship between the signs of optical rotation and the absolute configurations is (+)-(S)-2PPA and (-)-(R)-2PPA. Four symmetrically independent molecules with different conformations are observed in crystals of both racemic and enantiopure forms. Remarkably, all forms adopt very similar supramolecular structures, H-bonded corrugated layers, that can be described using a graph set. The outer surfaces of these layers are built of nonpolar phenyl groups, and their inner structures are composed of H-bonded amide groups. The presence of these layers determines the thin plate shape of 2PPA crystals. Spectroscopically, the racemic and enantiopure forms substantially differ only in the low-frequency Raman region. X-ray diffraction data suggest that the racemic form of 2PPA is a partial solid solution made possible by statistical occupancy of molecular positions by (R)- and (S)-enantiomers.