Crystal structure of 1,3-dimethyl-3-phenylpyrrolidine-2,5-dione: a clinically used anticonvulsant

In the title compound, C12H13NO2, the five-membered ring has an envelope conformation; the disubstituted C atom lies out of the mean plane through the four other ring atoms (r.m.s. deviation = 0.0038 Å) by 0.1877 (18) Å. The plane of the phenyl substituent is practically perpendicular to that of the planar part of the five-membered ring, with a dihedral angle of 87.01 (5)°. In the crystal, molecules are linked by weak C—H⋯O hydrogen bonds, forming inversion dimers. The dimers are linked by further C—H⋯O hydrogen bonds, as well as carbonyl–carbonyl attractive interactions [O⋯C = 3.2879 (19) Å], forming a three-dimensional framework structure.

Very recently we have studied the solid-state properties and crystal structures of racemic and homochiral forms of αmethyl-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). In this paper we report crystal structure The molecule of the title compound, C 12 H 13 NO 2 , contains the five-membered ring in a flattened envelope conformation; the C3 carbon atom is out of the mean plane passed through the other atoms of the ring (r.m.s. deviation is 0.0038) by 0.1877 (18) Å ( Fig. 1). 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) °.
In the crystal, the molecules are linked by weak intermolecular C-H···O hydrogen bonds (Table 1) attractive interactions (Allen et al., 1998) into a three-dimensional framework (Fig. 2).
It is important to point out that atom O2 does not form any intermolecular C-H···O hydrogen bonds due to the abovementioned carbonyl-carbonyl interactions. Interestingly, molecular docking indicates that methsuximide seems to be incapable of forming hydrogen bonds with its protein target(s), which may explain why methsuximide, unlike 3methyl-3-phenylpyrrolidine-2,5-dione, does not inhibit the nicotinic acetylcholine receptor (Chen et al., 2014).

Figure 1
Molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
A view along the b axis of the crystal packing of the title compound. The C-H···O hydrogen bonds (see Table 1 for details) and attractive C═ O···C═O interactions are shown as dashed lines. Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.