The crystal structures of four dimethoxybenzaldehyde isomers

The crystal structures of four dimethoxybenzaldehyde (C9H10O3) isomers are reported and compared to the previously reported crystal structures of 3,4-dimethoxybenzaldehyde and 2,6-dimethoxybenzaldehyde. All dimethoxybenzaldehyde molecules in the crystal structure are nearly planar.


Chemical context
Dimethoxybenzaldehydes (DMBz) are often used as starting materials in condensation reactions forming Schiff base compounds. Schiff base compounds are versatile ligands in numerous metal-organic complexes that are used as a catalyst. Examples include C-O coupling reactions (Maity et al., 2015), the Suzuiki-Miyaura reaction (Das & Linert, 2016), nitroaldol reactions (Handa et al., 2008) and a wide variety of other reactions (Gupta & Sutar, 2008).

Structural commentary
All four reported isomers crystallize in the monoclinic space group P2 1 /c, which is also the case for the previously reported 2,6-DMBz (Lemercier et al., 2014). On the other hand, 3,4-DMBz was reported to crystallize in space group Pna2 1 (de Ronde et al., 2016). 3,5-DMBz has two molecules in the asymmetric unit, while the other crystal structures have one molecule in the asymmetric unit. The DMBz molecules in the crystal structures are almost planar (Table 1). The biggest deviation is found in the 2,3-DMBz in which one of the methoxy groups deviates by 1.2 Å from the aromatic plane.

Supramolecular features
In the crystal structure of 2,3-DMBz, one of the methoxy groups lies in the plane of the aromatic ring (see Fig. 5). The second methoxy group points towards the aldehyde group of a neighboring 2,3-DMBz molecule. In the crystal structure of 2,4-DMBz, shown in Fig. 6,stacking interactions between the aromatic rings are present along the b-axis direction [centroid-centroid separation = 3.9638 (2) Å ]. Similarly, in the crystal structure of 2,5-DMBz, aromaticstacking interactions are present along the a-axis direction [centroidcentroid separation = 3.8780 (3) Å ], as shown in Fig. 7. The crystal structures of 2,6-DMBz (Lemercier et al., 2014), 3,4-DMBz (de Ronde et al., 2016 and 3,5-DMBz do not exhibit aromaticstacking interactions. As mentioned Table 1 Deviation from the aromatic plane (in Å ). Methoxy 1 and 2 are defined in the same order as the atomic labels, as shown in Fig. 4.

Figure 1
The molecular structure of 2,3-DMBz, showing displacement ellipsoids drawn at the 50% probability level.

Figure 2
The molecular structure of 2,4-DMBz, showing displacement ellipsoids drawn at the 50% probability level.

Figure 3
The molecular structure of 2,5-DMBz, showing displacement ellipsoids drawn at the 50% probability level.

Figure 4
The molecular structure of 3,5-DMBz, showing displacement ellipsoids drawn at the 50% probability level. above, only 3,5-DMBz has two molecules in the asymmetric unit, whereas the other crystal structures have one molecule in the asymmetric unit.

Polymorphism
Polymorph screening using differential scanning calorimetry did not reveal any phase transitions for any DMBz between 133 K and the melting point of the compound (Table 2). On the other hand, a metastable polymorphic form was discovered after rapidly cooling from the melt for both 3,4-DMBz for which the crystal structure was reported previously (de Ronde et al. 2016) and 3,5-DMBz. In the course of hours, these polymorphic forms transformed into the stable forms. Powder X-ray diffraction measurements confirmed the existence of these metastable forms (3,4-DMBz: Figs. 8, 3, 5-DMBz: Fig. 9).

Database survey
A search in the Cambridge Structural Database (Version 5.39, update February 2018, Groom et al., 2016 for dimethoxybenzaldehydes derivatives yielded the crystal structure of 93 compounds, which can be subdivided into fourteen 2,3-DMBz derivatives (including two solvates), fifteen 2,4-DMBz derivatives (including four solvates), ten 2,5-DMBz derivatives (including two solvates), nine 2,6-DMBz derivatives (including one solvate), forty two 3,4-DMBz derivatives (including nine solvates) and three 3,5-DMBz derivatives. Crystal structure of 2,3-DMBz showing the orientation of the methoxy groups. One of the methoxy groups lies in the plane of the aromatic ring. The second methoxy group points towards the aldehyde group of a neighbouring 2,3-DMBz molecule.

Figure 6
A view along the b axis of the crystal structure of 2,4-DMBz, in whichstacking interactions between the aromatic rings are present.

Figure 7
A view along the a axis of the crystal structure of 2,5-DMBz, in whichstacking interactions between the aromatic rings are present.

Table 2
Melting point (in K) of DMBz as determined using the onset temperature of differential scanning calorimetry.

Figure 8
Powder X-ray diffraction measurements of form I (black) and II (blue) of 3,4-DMBz. The powder pattern (red) was calculated from the crystal structure by de Ronde et al. (2016).

Figure 9
Powder X-ray diffraction measurements of form I (black) and II (blue) of 3,5-DMBz. The powder pattern (red) was calculated from the crystal structure.  6. Synthesis and crystallization 6.1. 2,3-dimethoxybenzaldehyde 30 mg of 2,3-dimethoxybenzaldehyde (97%, Fluorochem) was dissolved in 4 mL of isopropyl ether. Slow evaporation of a 1:1 mixture of this solution and heptane yielded colorless block-shaped crystals suitable for single crystal X-ray diffraction.

3,5-dimethoxybenzaldehyde
It was noted that 3,5-dimethoxybenzaldehyde (98%, Aldrich) oils out from solution, therefore the same method was used as had previously been employed for 3,4-dimethoxybenzaldehyde (de Ronde et al., 2016). In short, a few crystals of the commercial powder were added to a saturated solution in water. Subsequently, the temperature was cycled between 298 and 303 K. This resulted in the growth of single crystals suitable for single-crystal X-ray diffraction in several weeks.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. H atoms were positioned geometrically and refined as riding with C-H = 0.95-0.96 and U iso (H) = 1.2-1.5U eq (C). The crystal of 3,5-DMBz studied was refined as a two-component twin.
where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.60 e Å −3 Δρ min = −0.24 e Å −3 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq O01 0.70027 (15)  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.48 e Å −3 Δρ min = −0.25 e Å −3 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. Refined as a two-component twin.