1:1 Co-crystal of 3-ethyl-4-methyl-3-pyrrolin-2-one and 3-ethyl-4-methyl-3-pyrroline-2,5-dione

Crystallization from a 20-year-old commercial source of 3-ethyl-4-methyl-3pyrrolin-2-one afforded 1:1 co-crystals of this compound (C7H11NO) with its oxidized derivative, 3-ethyl-4-methyl-3-pyrroline-2,5-dione (C7H9NO2). The compound crystallizes in the space group P1, with two molecules of each species in the asymmetric unit. These four molecules form a hydrogen-bonded tetramer with a dimer of 3-ethyl-4-methyl-3-pyrrolin-2-one as the core flanked by one molecule of the dione on each side.


Structure description
3-Ethyl-4-methyl-3-pyrrolin-2-one, C 7 H 11 NO (1) is an ,-unsaturated lactam derivative. It has medical applications and is used as a starting material to synthesize glimepiride, the only sulfonyl urea approved by the US Food and Drug Administration (FDA) for use with insulin to treat type 2 diabetes. (Tanwar et al., 2017). We attempted to crystallize 3ethyl-4-methyl-3-pyrrolin-2-one from a 20-year-old commercial source (Aldrich), but upon solving the structure, it was determined that the compound crystallized as a 1:1 cocrystal with its oxidized derivative, 3-ethyl-4-methyl-3-pyrrolin-2,5-dione, C 7 H 9 NO 2 (2), which is also known as 2-ethyl-3-methylmaleimide. The source of this maleimide is unclear, though it is reported to form through certain aerobic photoxidation pathways, for example from chlorophyls (Xian et al., 2006;Kozono et al., 2002), and therefore aerobic oxidation cannot be ruled out.
The asymmetric unit of the triclinic co-crystal consists of two molecules of each compound (Fig. 1). These four molecules are held together by four N-HÁ Á ÁO hydrogen bonds, Table 1. At the center of the tetramer is a dimer of 3-ethyl-4-methyl-3-pyrrolin-2one molecules held together by two N-HÁ Á ÁO hydrogen bonds with NÁ Á ÁO distances of 2.8487 (15) and 2.9222 (15) Å . The oxygen atom of each pyrrolinone unit also accepts a data reports second hydrogen bond from the N-H unit of a maleimide molecule; these DÁ Á ÁA distances are similar to those in the core, being 2.8202 (15) Å and 2.8677 (15) Å . The oxygen atoms of the maleimide molecules do not engage in hydrogen bonding -the shortest intermolecular distances to the maleimide carbonyls are long (> 2.70 Å ) C-HÁ Á ÁO contacts.
The C O bonds of all four molecules in the asymmetric unit are consistent with the degree of resonance delocalization of the molecule. The C O bonds of pyrrolinone 1 are longer [1.2495 (15)

Synthesis and crystallization
Commercial 3-ethyl-4-methyl-3-pyrrolin-2-one (Aldrich) was purchased in 1997 and stored under air at room temperature. A sample was crystallized in 2019 by slow evaporation of a dichloromethane solution at room temperature over several days. Nearly colorless blocks were obtained and data were collected on these crystals at 100 K.

Figure 1
The asymmetric unit of the crystal contains two molecules of each component of the co-crystal, linked together by four hydrogen bonds. Displacement ellipsoids are drawn at the 50% probability level.

Data collection
Bruker APEXII CCD diffractometer φ and ω scans Absorption correction: multi-scan (SADABS; Bruker, 2014) T min = 0.638, T max = 0.746 22087 measured reflections 7807 independent reflections 5738 reflections with I > 2σ(I) R int = 0.042 θ max = 29.6°, θ min = 1.7°h 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.