Absolute Configuration and Polymorphism of 2-Phenylbutyramide and α-Methyl-α-phenylsuccinimide

Abstract

Crystal structures of racemic and homochiral forms of 2-phenylbutyramide (1) and 3-methyl-3-phenylpyrrolidine-2,5-dione (2) were investigated in detail by a single crystal X-ray diffraction study. Absolute configurations of the homochiral forms of 1 and 2, obtained by chromatographic separation of racemates, were determined. It was revealed that racemate and homochiral forms of 1 are very similar in terms of supramolecular organization (H-bonded ribbons) in crystal, infrared (IR) spectral characteristics, and melting points. The presence of two different molecular conformations in homochiral forms of 1 allowed mimicking of crystal packing of the H-bonded ribbons in racemate 1. Two polymorph modifications (monoclinic and orthorhombic) comprising very similar H-bonded zigzag-like chains were found for the homochiral forms of compound 2 that were significantly different in terms of crystal structure, IR spectra, and melting points from the racemic form of 2. Unlike compound 1, homochiral forms of compound 2 have a higher density than the corresponding racemate which contradicts the Wallach rule and indicates that, in this case, homochiral forms are more stable than racemate forms.

Crystal structure of (E)-1-(4-methoxyphenyl)ethanoneO-dehydroabietyloxime

“…A similar conformation of the five-membered ring was also observed in other N-substituted succinimide derivatives (Argay & Seres, 1973;Kwiatkowski & Karolak-Wojciechowska, 1992). It should be noted that the five-membered ring in the N-unsubstituted succinimide derivatives adopts almost planar conformation (Argay & Kálmán, 1973;Argay & Carstensen-Oeser, 1973;Khrustalev et al, 2014). The phenyl substituent is practically perpendicular to the five-membered ring; the dihedral angle between the planar part of the five-membered ring and the phenyl plane is 87.01 (5) °.…”

“…Moreover, we have found and described the different polymorphic modifications of this compound (Khrustalev et al, 2014). In this paper we report crystal structure of 1,3-dimethyl-3-phenylpyrrolidine-2,5-dione (methsuximide, trade-mark is Celontin).…”

“…Very recently we have studied the solid-state properties and crystal structures of racemic and homochiral forms of α-methyl-α-phenylsuccinimide (Khrustalev et al, 2014;Chen et al, 2014). Moreover, we have found and described the different polymorphic modifications of this compound (Khrustalev et al, 2014).…”

Racemic and enantiopure forms of 3‐ethyl‐3‐phenylpyrrolidin‐2‐one adopt very different crystal structures

“…In our previous work, 12 we successfully used chiral HPLC in the reversed-phase mode to separate enantiomers of 2-phenylbutyramide and 3-methyl-3-phenylpyrrolidine-2,5-dione on a gram scale. In our previous work, 12 we successfully used chiral HPLC in the reversed-phase mode to separate enantiomers of 2-phenylbutyramide and 3-methyl-3-phenylpyrrolidine-2,5-dione on a gram scale.…”

“…27 The melting points of the EPP enantiomers are about 25°C higher than the melting point of rac-EPP (Table 5) implying lower aqueous solubility. 12 However, in the case of 4-phenyl-1,3-oxazolidine-2-thione, 29 the 46°C higher melting point of its racemic form corresponds to a crystal density increase of only 0.05 g/cm 3 . For comparison, crystals of enantiopure forms of 3methyl-3-phenylpyrrolidine-2,5-dione have about 33°C higher melting points and 0.09 g/cm 3 higher densities compared to the racemates crystals.…”