Synthesis, crystal structure and Hirshfeld surface analysis of diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate

In the title 1,4-dihydropyridine derivative, the 1,4-dihydropyridine ring makes an angle of 82.19 (13)° with the thiophene ring. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds as well as C—H⋯π interactions link the molecules into a three-dimensional network.

In the title compound, C 17 H 21 NO 4 S, the 1,4-dihydropyridine ring has an envelope conformation with the Csp 3 atom at the flap. The thiophene ring is nearly perpendicular to the best plane through the 1,4-dihydropyridine ring, the dihedral angle being 82.19 (13) . In the crystal, chains running along the b-axis direction are formed through N-HÁ Á ÁO interactions between the 1,4-dihydropyridine N atom and one of the O atoms of the ester groups. Neighbouring chains are linked by C-HÁ Á ÁO and C-HÁ Á Á interactions. A Hirshfeld surface analysis shows that the most prominent contributuion to the surface contacts are HÁ Á ÁH contacts (55.1%).

Supramolecular features and Hirshfeld surface analysis
In the crystal, the 1,4-dihydropyridine N6 atom acts as a hydrogen-bond donor to the O14 atom of one of the ester groups, resulting in chain formation along the b-axis direction (Fig. 2, Table 1). Parallel chains are linked by C-HÁ Á ÁO hydrogen bonds between the thiophene H5 atom and the carbonyl O19 atom of the second ester group (Fig. 2, Table 1). In addition, inversion dimers are formed by C-HÁ Á Á interactions ( Fig. 3 Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Partial crystal packing of the title compound, showing the chain formation along the b axis by N-HÁ Á ÁO interactions (blue dashed lines). Parallel chains are linked by C-HÁ Á ÁO interactions (red dashed lines; see Table 1 for symmetry codes).

Figure 3
Partial crystal packing of the title compound, showing the inversion dimer formation through C-HÁ Á Á interactions (grey dashed lines; Cg1 is the centroid of the S1/C2-C5 ring; see Table 1 for symmetry code).

Figure 1
A view of the molecular structure of the title compound, with atom labels and displacement ellipsoids drawn at the 50% probability level. H atoms are shown as small circles of arbitrary radii.
In order to gain further insight into the packing, the Hirshfeld surface and fingerprint plots were calculated using CrystalExplorer (Turner et al., 2017). The Hirshfeld surface (Spackman & Jayatilaka, 2009) mapped over d norm in Fig. 4 shows bright-red spots near the atoms participating in the already discussed intermolecular interactions. In addition a faint-red spot is present near atoms H9 and H23A indicating a short H9Á Á ÁH23A iv contact distance of 2.276 Å [symmetry code: (iv) x, y + 1, z]. The associated two-dimensional fingerprint plots (McKinnon et al., 2007) are shown in Fig. 5 and give additional information about the intermolecular contacts. HÁ Á ÁH Van der Waals contacts dominate (55.1%) and appear in the middle of the scattered points in the fingerprint plot (Fig. 5b). The contribution (16.4%) from the OÁ Á ÁH/HÁ Á ÁO contacts shows a pair of sharp spikes corresponding to the N-HÁ Á ÁO interactions (Fig. 5c). In addition, CÁ Á ÁH/HÁ Á ÁC and SÁ Á ÁH/HÁ Á ÁS contacts contribute 15.7 and 9.6%, respectively, to the Hirshfeld surface. A further small contribution is from NÁ Á ÁH/HÁ Á ÁN contacts (1.5%, Fig. 5f). The percentage contributions of the other contact types are negligible.
Enrichment ratios (Table 2) were calculated according to the method described by Jelsch et al. (2014). A ratio E XY greater than unity for a pair of elements X and Y indicates a high likelihood of forming XÁ Á ÁY contacts in the crystal packing. The favourable OÁ Á ÁH and HÁ Á Á contacts in the crystal packing are reflected in the enrichment ratios E OH of 1.24 and E CH of 1.23 for these contacts. The slight E SH enrichment (1.11) refers to the multiple SÁ Á ÁH contacts between S1 and neighbouring methyl groups (SÁ Á ÁH distances ranging from 3.01 to 3.50 Å ). However, the high enrichment ratio E NH must be interpreted with caution as it results from the quotient of two small numbers (Jelsch et al., 2014).

Database survey
A search of the Cambridge Structural Database (CSD, Version 5.40, update of May 2019; Groom et al., 2016) for diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives with a ring substituent at C4 results in 70 hits for which coordinates are available. Most similar to the title compound is the 4-(2-thienyl) derivative (refcode QIWWEY; Caignan et al., 2000;refcode QIWWEY01;Huang & Cui, 2016). In these compounds the thienyl group is disordered over two sets of sites with an occupancy ratio of 0.51:0.49. An overlay between the title compound and QIWWEY excluding the thiophene ring gives an r.m.s. deviation of 0.318 Å . In QIWWEY, the 1,4-dihydropyridine and thiophene rings make an angle of 83.19 (17) . Fig. 6 shows the four possible orientations of the two C O substituents on the 1,4-dihydropyridine ring. Most popular are the s-trans/s-cis (35%), the s-cis/s-cis (31%) and the s-cis/s-trans conformation (29%). The s-trans/s-trans conformation occurs only for 5% of the deriv- Two views of the Hirshfeld surface mapped over d norm for the title compound in the range À0.4662 to +1.2830 arbitrary units.

Synthesis and crystallization
The reaction scheme for the synthesis of the title compound is given in Fig. 7. Synthesis of diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4dihydropyridine-3,5-dicarboxylate: A mixture of thiophene-3-carbaldehyde (3 mmol), ethyl acetoacetate (6 mmol) and NH 4 OAc (3 mmol) in ethanol (10 mL) was exposed to microwave radiation for 3 min. at a power of 450W. The reaction mixture was cooled down and the solid product was separated by filtration and purified by recrystallization in ethanol to give the compound as yellowish transparent crystals (yield 82%), m.p.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. H atom H6 was found in a difference electron-density map and refined freely. The other H atoms were placed in idealized positions and included as riding contributions with U iso (H) values of 1.2U eq or 1.5U eq of the parent atoms, with C-H distances of 0.93 (aromatic), 0.98 (CH), 0.97 (CH 2 ) and 0.96 Å (CH 3 ). In the final cycles of refinement, four outlying reflections were omitted. Reaction scheme for the synthesis of the title compound.    CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Diethyl 2,6-dimethyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarboxylate
Crystal data 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.