Crystal structure of 2,3-dimethylmaleic anhydride: continuous chains of electrostatic attraction

In the structure of 2,3-dimethylmaleic anhydride, intermolecular interactions are dominated by perpendicular and antiparallel δ+C⋯δ−O carbonyl⋯carbonyl interactions that give rise to a layered structure, and weak inter-sheet C—H⋯O interactions between these layers. Carbonyl–carbonyl interactions are persistent across 13 previously reported crystal structures containing a 2,3-disubstituted maleic anhydride moiety.


Chemical context
Maleic anhydride and its symmetrically 2,3-disubstituted derivatives are standard reagents found in nearly all chemical stockrooms due to their importance as metal-organic framework post-synthetic modifiers (Wang & Cohen, 2009), biomolecule denaturation catalysts (Puigserver & Desnuelle, 1975), synthesis reagents (Moad et al., 2003), and temperature and pH-reversible co-polymer grafts (Gao et al., 2009). Although they are seemingly ubiquitous, comparisons of interactions in the solid state of maleic anhydride (Lutz, 2001) and its disubstituted derivatives have not been discussed. Determination of the structure of the title compound, 2,3dimethylmaleic anhydride by single-crystal X-ray diffraction was completed and is reported herein. Computational modeling was also used to determine the intermolecular interactions present in the title compound as well as in other 2,3-disubstituted derivatives.

Structural commentary
The title compound 2,3-dimethylmaleic anhydride (Fig. 1) is a 5-membered cyclic anhydride with a double bond between carbon atoms C2 and C3. The double bond locks the molecule in a planar conformation and stabilizes the acid anhydride against hydration. The lengths of the C-C single bonds between C1 and C2, and C3 and C4 are 1.4841 (11) and 1.4848 (11) Å , respectively, and that of the C C bond between C2 and C3 is 1.3420 (12) Å , suggesting that the alkene region of the molecule is not delocalized with the ISSN 2056-9890 carbonyl groups and that the molecule is non-aromatic. The dipole moment of a molecule in the gas phase was calculated as 4.8999 D from DFT B3LYP with a 6-311G(d,p) basis set using GUUSSIAN03 (Frisch et al., 2004). All bond lengths and angles are consistent with the molecular structure of unsubstituted maleic anhydride (Lutz, 2001).

Supramolecular features
In the title compound, close intermolecular carbonyl-carbonyl contacts with d( + CÁ Á Á À O) ranging from 2.9054 (11) to 3.0509 (11) Å in length are present, which is well below the sum of the carbon and oxygen van der Waals radii of 3.22 Å (Bondi, 1964), suggesting a strong attractive interaction between these two atoms. Close carbonyl-carbonyl interactions, in which d( + CÁ Á Á À O) is < 3.6 Å , persist in 15% of carbonyl-substituted small molecule crystal structures surveyed from the Cambridge Structural Database (CSD) by colleagues in 1998 (Allen et al., 1998). Three carbonyl-carbonyl approach geometries, characterized by specific ranges in angles between the van der Waals radiusoverlapped ketonic carbon and oxygen nuclei, were found to describe 71.2% (945 structures) of the observed interactions in the 1,328 crystal structures identified as having close carbonylcarbonyl contacts: the anti-parallel, perpendicular, and sheared parallel motifs (Fig. 2). Orthogonality of the interacting ketonic nuclei was found to be correlated with multiplicity using ab initio calculations to quantify interaction strength (Allen et al., 1998). Doubly CÁ Á ÁO connected antiparallel carbonyl-carbonyl interactions (Fig. 2a) approached strengths of À22.3 kJ mol À1 , which is competitive with weakto-medium-strength classical hydrogen bonds, while singly CÁ Á ÁO connected perpendicular (Fig. 2b) and sheared parallel interactions (Fig. 2c) were found to have interaction strengths reaching À7.6 kJ mol À1 , which is on a par with strong aromatic stacking interactions (Allen et al., 1998). In addition to the interaction multiplicity, the anti-parallel geometry is strengthened byinteractions, lengthening the mean separation distance between carbonyl-carbonyl contacts relative to those observed in singly connected geometries.
A survey of thirteen previously determined 2,3-disubstituted maleic anhydride crystal structures demonstrates the persistence of the unsubstituted maleic anhydride's carbonylcarbonyl contacts against steric and electrostatic perturbation (CSD, accessed June 2015; Groom & Allen, 2014). These 2,3disubstituted maleic anhydride crystal structures and 2,3-dimethylmaleic anhydride were characterized in the context of the parameters described by Allen et al. (Table 1 to 3). Computational modeling of electrostatic potential and optimized geometric configurations in homomolecular maleic anhydride complexes suggest that non-covalent carbonylcarbonyl interactions further polarize the interacting nuclei, reinforcing the electrostatic attraction, while also polarizing the neighboring anhydride carbonyl, and propagating the Displacement ellipsoid representation of one molecule of 2,3-dimethylmaleic anhydride, with non-H atoms drawn at the 50% probability level.
The perpendicular interactions and pairwise anti-parallel interactions connect neighboring molecules to form several interaction motifs (Fig. 3). Each 2,3-dimethylmaleic anhydride molecule participates in four perpendicular interactions, of which each two are symmetry equivalent: as an electrondensity acceptor (through the carbonyl C atom) in two of the four interactions and in the other two as an electron-density donor (through the carbonyl O atom). The perpendicular carbonyl-carbonyl interactions associated with both the 2.9054 (11) and 3.0509 (11) Å + CÁ Á Á À O distances give rise to pleated chains of 2,3-dimethylmaleic anhydride molecules that extend parallel to the b-axis. There are two parallel chains that arise from the two perpendicular interactions with the 2.9054 (11) and 3.0509 (11) Å + CÁ Á Á À O separations (C1 O2Á Á ÁC4 iii and C4 O3Á Á ÁC2 i ; Fig. 3a). The interactions join parallel chains and combined they create layers perpendicular to the c-axis direction. Molecules within these layers are further connected through the pairwise anti-parallel carbonyl interactions and -stacking, as well as C-HÁ Á ÁO interactions between methyl atom H6A and atom O1 (Table 4) Table 1 Anti-parallel interactions (D, Å , ) in di-substituted maleic anhydrides and the intermolecular carbonyl C-O distances in their crystal structures. Molecule CSD refcode  Table 2 Perpendicular interactions (D, Å , ) in di-substituted maleic anhydrides and the intermolecular carbonyl C-O distances in their crystal structures.   Table 4 Hydrogen-bond geometry (Å , ). between parallel layers of 2,3-dimethylmaleic anhydride molecules, the most pronounced one being between methyl atom H6B and atom O3 (Fig. 3b).

Computational modeling
To better understand the intermolecular interactions that allow the close contact between the carbonyl C atom and the carbonyl O atom, the anti-parallel carbonyl-carbonyl interaction between two molecules of 2,3-dimethylmaleic anhydride was modeled computationally. The perpendicular carbonyl interaction is not a geometric minimum in the gas phase and thus was not modeled due to the unknown contributions from additional solid-state interactions. Geometry optimizations were performed for one molecule of 2,3-dimethylmaleic anhydride and a dimer of 2,3-dimethylmaleic anhydride using DFT B3LYP with the 6-31G(d) basis set using GAUSSIAN03 (Frisch et al., 2004). Geometry optimization of the two-molecule complex revealed a strong interaction between the carbonyl O atom and carbonyl C atom with a short d( + CÁ Á Á À O) of 3.178 Å , which is consistent with the value from the crystal structure [3.220 (11) Å ] and is below the sum of the van der Waals radii for O and C (3.22 Å ). The Mulliken atomic charges of the carbonyl O atom (À0.4496) and carbonyl C atom (+0.5116) suggest that this interaction is likely electrostatic in nature (Fig. 4a). Comparison of the computed Mulliken atomic charges of the two-molecule complex with that of a single molecule indicates that both the carbonyl C atom (+0.6142) and carbonyl O atom (À0.4677) atoms participating in the anti-parallel interaction (Fig. 4b) are further polarized relative to the free molecule (Fig. 4a). More interestingly, in the two-molecule complex, even the carbonyl C atom not directly involved in the electrostatic attraction is further polarized, with a calculated Mulliken atomic charge of +0.5883 versus +0.5116 in the single-molecule model. These data suggest that the carbon-oxygen electrostatic interaction on one end of the anhydride draws electron density from the carbonyl C atom on the other and enables 2,3-dimethylmaleic anhydride to better interact with a neighboring carbonyl O atom. Motifs that arise from non-covalent interactions in 2,3-dimethylmaleic anhydride: (a) perpendicular CÁ Á ÁO interactions (red and blue for C1 O2Á Á ÁC4 iii and C4 O3Á Á ÁC2 i interactions respectively) and anti-parallel carbonyl interactions (black, representing C1 O2Á Á ÁC4 iv and C4 O3Á Á ÁC2 v , respectively), (b) weak C-HÁ Á ÁO interactions (green) between sheets (weak C-HÁ Á ÁO interactions within sheets have been omitted for clarity). Symmetry codes: (iii) Àx + 1 2 , y À 1 2 , z; (iv) x + 1 2 , y, Àz + 3 2 ; (v) x À 1 2 , y, Àz + 3 2 . For other codes, see Table 4.
Induced polarization reinforces the overall strength of the carbonyl-carbonyl network within the crystal structure both between molecules, forming chains through perpendicular interactions, and between anti-parallel chains, forming sheets. Based on these calculations, it can be predicted that with increased polarization of the carbonyl carbon and oxygen nuclei, the strength of the intermolecular interaction between carbonyls would increase and the shortest contact between the interacting nuclei would decrease. Additional inductive effects of dimerization include an increase in the average Mulliken atomic charge of the methyl H atoms (+0.1859) relative to that of the free molecule (+0.1499), which would have the effect of slightly strengthening the weak C-HÁ Á ÁO attractions that connect layers of molecules associated through the carbonylcarbonyl interactions.

Database survey
The Mulliken atomic charges for thirteen 2,3-disubstituted maleic anhydrides found in the CSD were calculated and their crystal structures analyzed for d( + CÁ Á Á À O) and geometries (Tables 1, 2 and 3). The expected trend is most apparent amongst the set of sheared-parallel carbonyl-carbonyl interactions in which the participating nuclei are isolated from additional non-covalent interactions, unlike those found in anti-parallel and perpendicular motifs. This trend supports the prediction that d( + CÁ Á Á À O) decreases with increased carbonyl polarization. The expected trend in anti-parallel d( + CÁ Á Á À O) is disrupted by YUYMIO, a 2,3-diphenylmaleic anhydride, whose packing is also guided by edge-face aromatic interactions [d(C-HÁ Á Ácentroid] of 3.187 Å ). Because of the packing frustration presented by these two competing interactions in 2,3-diphenylmaleic anhydride, its disruption of the d( + CÁ Á Á À O) trend may be disregarded. These data suggest that C2 and C3 functionalization can affect the carbonylcarbonyl interaction distance for a particular interaction geometry (anti-parallel, perpendicular, and sheared-parallel) through polarization of the carbonyl group. The persistence of the major interactions in maleic acid anhydrides indicates that electrostatic distribution and intermolecular interaction-induced polarization of the anhydride's carbonyls contribute strongly to the molecular packing and are competitive with other common supramolecular moieties, such as hydrogenbonding and aromatic stacking.

Synthesis and crystallization
Crystals were grown by dissolving 2 g of 2,3-dimethylmaleic anhydride in 100 mL of deionized H 2 O at 373 K. Once dissolved, the solution was slowly cooled to 277 K, crystallizing colorless plates. Optimized structures of the single molecule model (a) and the 2,3-dimethylmaleic anhydride dimer with a separation distance of 3.187 Å and (b), with indicated Mulliken atomic charges.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. H atoms were positioned geometrically and constrained to ride on their parent atoms, with carbon-hydrogen bond distances of 0.95 Å for C-H, and 0.98 Å for CH 3 moieties, respectively. Methyl H atoms were allowed to rotate but not to tip to best fit the experimental electron density. U iso (H) values were set to a multiple of U eq (C) with 1.5 for CH 3 and 1.2 for C-H. Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015) and SHELXLE (Hübschle et al., 2011); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).