Structural, Hirshfeld surface and three-dimensional interaction-energy studies of 1,3,5-triethyl 2-amino-3,5-dicyano-4,6-bis(4-fluorophenyl)cyclohex-1-ene-1,3,5-tricarboxylate

The various intermolecular interactions, such as N—H⋯O, C—H⋯N and C—H⋯O, were investigated using Hirshfeld surface analysis and the three-dimensional interaction energies were calculated.


Chemical context
Organic compounds containing hetero atoms such as fluorine, nitrogen, sulfur and oxygen exhibit significant biological activities such as antioxidant (Fu et al., 2010), insecticidal (Carbonnelle et al., 2005), antibacterial, antifungal (Sener et al., 2000), anti-inflammatory (Khanum et al., 2004), anticonvulsant, analgesic and antitumor (Kushwaha et al., 2011). These compounds find a wide range of applications in the fields of agriculture and biochemistry as well as in the pharmaceuticals industry. Hence, hetero organic compounds have attracted the attention of chemists with the aim of designing and synthesizing new organic compounds. The title compound was synthesized, its structure was studied by X-ray diffraction techniques and a computational analysis was performed to understand the intermolecular interactions.

Supramolecular features
In the crystal, the molecules are held together by an intermolecular interactions of the types N1-H2NÁ Á ÁO1, C14-H14BÁ Á ÁN3, and C24-H24BÁ Á ÁO3 (Table 1) Packing of the molecules along the b axis, showing the R 2 2 (10) ring motif.

Figure 1
View of the title molecule with displacement ellipsoids drawn at 40% probability level. Table 1 Hydrogen-bond geometry (Å , ).

Hirshfeld surfaces and 2D fingerprint calculations
The Hirshfeld surface (HS) mapped over d norm was generated using CrystalExplorer17.5 (Spackman et al., 2009) with a colour scale of À0.3124 a.u. for red to +1.7877 a.u. for blue. The area and volume of the d norm surface are 681.46 Å 2 and 527.71 Å 3 , respectively. The front and rear views of the Hirshfeld surface mapped over d norm are depicted in Fig. 4. The bright-red circular spots on d norm indicates the presence of intermolecular N1-H2NÁ Á ÁO1, C14-H14BÁ Á ÁN3 and C24-H24BÁ Á ÁO3 interactions. The percentage contribution from different intermolecular interactions towards the formation of a three dimensional Hirshfeld surface (HS) was computed using two-dimensional fingerprint calculations (Fig. 5). The results showed that the HÁ Á ÁH (40.1%) contacts make the major contribution to the crystal packing, while the CÁ Á ÁH (11.2%), NÁ Á ÁH (14.7%), HÁ Á ÁF (16.3%), HÁ Á ÁO (14.5%) contacts also make a significant contribution to the total area of the HS surface.

Three-dimensional-framework analysis of interaction energies
CrystalExplorer 17.5 software calculates interaction energies between crystal molecular pairs. Energy calculations were carried out using the B3LYP/6-31G(d,p) basis set within a default radius of 3.8 Å (Turner et al., 2015(Turner et al., , 2017Gavezzotti,  Hirshfeld surface mapped over d norm (front and back views are shown).

Figure 5
Two-dimensional fingerprint plots showing the pecentage contributions of various interatomic contacts.
2002; Grimme, 2006). The interaction of different molecules with the reference molecule (black ball-and-stick model at the centre) in the cluster of energy frameworks is depicted in Fig. 6. Fig. 7 depicts the energy frameworks, visualizing the strength of the interactions, with the Coulombic, dispersion and total energies shown in red, green and blue, respectively. The radii of the cylinders connecting the centroids of the molecules indicate the relative strengths of the interaction energies. A table of interaction energies in component form is given in the table in Fig. 6. The highest total interaction energy (E tot = À67.4 kJ mol À1 ) is associated with a pair of yellow molecules with the short centroid distance R = 9.29 Å with rotational symmetry Àx, y + 1 2 , Àz + 1 2 , while the lowest total interaction energy (E tot = À17.6 kJ mol À1 ) was observed for a pair of green molecules interacting at the longer centroid distance R = 12.86 Å ; this is in accordance with the classical laws of electrostatics. In each of the energy terms, the dispersion component is dominant over the others.

Synthesis and crystallization
Piperidine (6 mmol) was added to ethyl cyanoacetate (30 mmol) and the mixture was stirred for 10 min. Then 4-fluorobenzaldehyde (20 mmol) was added dropwise and during the addition, the temperature of the reaction mass rose to 333 K (it should not be cooled), and the mass was stirred for 30 min. The temperature slowly came down to 293-298 K over 30 min. The progress of the reaction was monitored by TLC and found to be complete. Methylene chloride (30 ml) and water (20 ml) were added and the mixture was stirred for 10 min. The organic layer was separated and washed with sat. aq. NaCl solution and dried over anhydrous Na 2 SO 4 , then concentrated under reduced pressure to get the crude product. This was purified by silica gel column chromatography using nheptane/ethyl acetate as eluent. The mixture was quenched in cold water and the organic layer was extracted with ethyl acetate, washed with 5% sodium bicarbonate solution, and dried over anhydrous sodium sulfate. Slow evaporation of the solvent lead to crystals of the title compound, which were recrystallized from ethanol solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2 Visualization of the interaction energy values between the reference molecule and the constituents of a cluster within the default radius of 3.8 Å . The table gives information on the number of molecules (N) interacting with the reference nolecule in a cluster, the rotational symmetry (Symop) and the corresponding molecular centroid-centroid distances (R, in Å ) and the interaction energies in component form.

Figure 7
Three-dimensional energy frameworks of Coulombic, dispersion and total energy terms.   program(s) used to solve structure: SHELXT2018/2 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: SHELXL2018/3 (Sheldrick, 2015b); software used to prepare material for publication: PLATON (Spek, 2020). 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 Occ. (