Crystal conformations and molecular packing of (S)-2-methoxy-2-(9-phenanthryl)propanoic acid and a diastereomeric amide prepared from (R)-2-methoxy-2-(1-naphthyl)propanoic acid

Abstract

This paper reports the first evidence of the contribution of T-shaped aromatic CH⋯π interactions to the crystallization of 2-aryl-2-methoxypropanoic acid and amide. The crystal structures of (S)-2-methoxy-2-(9-phenanthryl)propanoic acid [(S)-M9PP acid, (S)-3] and a diastereomeric amide 6, prepared from (R)-2-methoxy-2-(1-naphthyl)propanoic acid [(R)-MαNP acid, (R)-1] and (S)-1-(1-naphthyl)ethylamine [(S)-4], were determined by X-ray crystallography. Like those of M9PP and MαNP esters, the carbonyl and methoxy groups of (S)-3 exhibited syn conformation. The crystal structure of (S)-3 was stabilized by consecutive intermolecular OH⋯O hydrogen bonds between the carboxy groups. In addition, the 9-phenanthryl groups formed a herringbone structure via aromatic CH⋯ π interactions. The anti conformation of the carbonyl and methoxy groups was observed in the crystal of amide 6, indicating an NH⋯O hydrogen bond. The two 1-naphthyl groups were parallel to one another and located on the same side of the MαNP plane, forming a herringbone structure with adjacent molecules. NMR analyses suggest that, in solution, intramolecular aromatic CH⋯π interactions induce the 1-naphthyl groups to form a slant-parallel conformation. Namely, both the length and interactions between the substituents are important for crystallization. Normal-phase HPLC separation of diastereomeric amides is also discussed.