Crystal structure, Hirshfeld surface analysis and DFT studies of ethyl 2-{4-[(2-ethoxy-2-oxoethyl)(phenyl)carbamoyl]-2-oxo-1,2-dihydroquinolin-1-yl}acetate

The title compound, C24H24N2O6, consists of ethyl 2-(1,2,3,4-tetrahydro-2-oxoquinolin-1-yl)acetate and 4-[(2-ethoxy-2-oxoethyl)(phenyl]carbomoyl units, where the oxoquinoline unit is almost planar and the acetate substituent is nearly perpendicular to its mean plane. In the crystal, C—HOxqn⋯OEthx and C—HPhyl⋯OCarbx (Oxqn = oxoquinolin, Ethx = ethoxy, Phyl = phenyl and Carbx = carboxylate) weak hydrogen bonds link the molecules into a three-dimensional network structure. A π–π interaction with a centroid-centroid distance of 3.675 (1) Å between the constituent rings of the oxoquinoline unit may further stabilize the structure.


Chemical context
In recent years, research has been focused on existing molecules and their modifications in order to reduce their side effects and to explore their other pharmacological properties. Quinolone derivatives have constituted an important class of heterocyclic compounds which, even when part of a complex molecule, possesses a wide spectrum of biological activities, such as anticancer (Elderfield & Le Von, 1960), antifungal (Musiol et al., 2010), antitubercular (Fan et al., 2018a;Xu et al., 2017), antimalarial (Fan et al., 2018b;Hu et al., 2017), anti-HIV (Sekgota et al., 2017;Luo et al., 2010), anti-HCV (Manfroni et al., 2014;Cheng et al., 2016) and antimicrobial (Musiol et al., 2006). They have been developed for the treatment of many diseases, like malaria (Lutz et al., 1946) and HIV (Ahmed et al., 2010). As a continuation of our research work devoted to the development of N-substituted quinoline derivatives and the assessments of their potential pharmacological activities (Filali Baba et al., 2016aBouzian et al., 2018Bouzian et al., , 2019a, we report herein the synthesis and molecular and crystal structure of the title compound, along with the Hirshfeld surface (HS) analysis and density functional theory (DFT) computational calculations carried out at the B3LYP/6-311G(d,p) level of an N-substituted quinoline derivative by an alkylation reaction of ethyl bromoacetate with 2-oxo-Nphenyl-1,2-dihydroquinoline-4-carboxamide under phasetransfer catalysis conditions using tetra-n-butylammonium bromide (TBAB) as a catalyst and potassium carbonate as a base.

Figure 3
A view of the three-dimensional Hirshfeld surface for the title compound, plotted over d norm in the range À0.2380 to 1.5740 a.u.

Figure 1
The molecular structure of the title compound, showing the atomnumbering scheme and displacement ellipsoids drawn at the 50% probability level. For the sake of clarity, the minor component of disorder is not shown. deviation of 0.017 (3) Å for atom C7. Atoms O1 and C10 deviate only by 0.007 (2) and 0.022 (2) Å from that plane and so are essential coplanar. The acetate substituent is nearly perpendicular to that plane, with a torsion angle of C1-N1-C10-C11 = À104.8 (2) . The mean plane of the phenyl ring, C (C19-C24), is oriented with respect to the oxoquinoline unit at a dihedral angle of 68.17 (6) . The carboxyl groups, O5/O6/ C11 and O3/O4/C16, are twisted out of coplanarity with the best least-squares plane of the oxoquinoline unit and phenyl ring C by dihedral angles of 79.7 (2) and 62.9 (2) , respectively.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the title compound, a Hirshfeld surface (HS) analysis (Hirshfeld, 1977;Spackman & Jayatilaka, 2009) was carried out by using CrystalExplorer17.5 (Turner et al., 2017). In the HS plotted over d norm (Fig. 3), the white surface indicates contacts with distances equal to the sum of the van der Waals radii, and the red and blue colours indicate distances shorter (in close contact) or longer (distinct contact) than the van der Waals radii, respectively (Venkatesan et al., 2016). The bright-red spots appearing near O2 and H atoms H7 and H22 indicate their roles as the respective donors and/or acceptors; they also appear as blue and red regions corresponding to positive and negative potentials on the HS mapped over the electrostatic potential (Spackman et al., 2008;Jayatilaka et al., 2005), as A view of the three-dimensional Hirshfeld surface of the title compound, plotted over the electrostatic potential energy in the range À0.0500 to 0.0500 a.u. using the STO-3G basis set at the Hartree-Fock level of theory. Weak hydrogen-bond donor and acceptor intermolecular interactions are shown as blue and red regions around the atoms corresponding to positive and negative potentials, respectively.

Figure 5
A view of the Hirshfeld surface for the title compound, plotted over the shape-index.

Figure 6
The full two-dimensional fingerprint plots for the title compound  Table 2 Comparison of the selected (X-ray and DFT) geometric data (Å , ).
Bonds/angles X-ray B3LYP/6-311G(d,p)   CÁ Á ÁC contacts (Fig. 6e) have an arrow-shaped distribution of points with the tip at d e = d i = 1.81 Å . Finally, the pair of the scattered points of wings from the fingerprint plot are delineated into OÁ Á ÁC/CÁ Á ÁO (Fig. 6f) contacts, with a 1.1% contribution to the HS, and has a nearly symmetrical distribution of points with the edges at d e + d i = 3.15 Å . The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the HÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH and CÁ Á ÁC interactions in Figs. 7(a)-(d), respectively.
The Hirshfeld surface analysis confirms the importance of weak H-atom contacts in establishing the packing structure. The large number of HÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁC/CÁ Á ÁH interactions suggest that van der Waals interactions and weak hydrogen-bond intermolecular interactions play major roles in the crystal packing (Hathwar et al., 2015).

DFT calculations
The geometry optimized structure of the title compound in the gas phase was generated theoretically via density functional theory (DFT) computational calculations using a standard B3LYP functional and a 6-311G(d,p) basis set (Becke, 1993), as implemented in GAUSSIAN09 (Frisch et al., 2009). The theoretical and experimental results were in good agreement (Table 2). A DFT molecular orbital calculation indicated that the highest-occupied molecular orbital (HOMO), acting as an electron donor, and the lowest-unoccupied molecular orbital (LUMO), acting as an electron acceptor, are very important parameters for quantum chemistry. When the energy gap is small, the molecule is highly polarizable and has high chemical reactivity. Therefore, these DFT calculations provide important information on the reactivity and site selectivity of the molecular framework. E HOMO and E LUMO clarify the inevitable charge exchange collaboration inside the studied material, as well as electronegativity (), hardness (), potential (), electrophilicity (!) and softness (), which are listed in Table 3. The significance of and is to evaluate both reactivity and stability. The electron transition from a HOMO to a LUMO energy level is shown in Fig. 8

Synthesis and crystallization
To a solution of 2-oxo-N-phenyl-1,2-dihydroquinoline-4carboxamide (1.89 mmol) in dimethylformamide (DMF, 10 ml) were added ethyl bromoacetate (4.16 mmol), K 2 CO 3 (5.67 mmol) and tetrabutylammonium bromide (TBAB, 0.23 mmol). The reaction mixture was stirred at room temperature for 6 h. After removal of the salts by filtration, the DMF was evaporated under reduced pressure and the resulting residue was dissolved in dichloromethane. The organic phase was dried with Na 2 SO 4 and then concentrated under reduced pressure. The pure compound was obtained by column chromatography using as eluate hexane/ethyl acetate (3:1 v/v). The isolated solid was recrystallized from hexanediethyl acetate (1:1 v/v) to afford colourless crystals (yield 75%; m.p. 427 K).

Ethyl 2-{4-[(2-ethoxy-2-oxoethyl)(phenyl)carbamoyl]-2-oxo-1,2-\ dihydroquinolin-1-yl}acetate
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.