Crystal structure and DFT study of benzyl 1-benzyl-2-oxo-1,2-dihydroquinoline-4-carboxylate

In the title quinoline derivative, the two benzyl rings are inclined to the quinoline ring mean plane by 74.09 (8) and 89.43 (7)°.


Chemical context
Heterocyclic compounds have paved the way for exceptional achievements in the fight against many life-threatening diseases (Alcaide et al., 2010). It is therefore no surprise that the development of new methodologies to synthesize biologically active heterocyclic compounds persists as a very important goal in organic chemistry (Jones et al., 2011). Quinolones and their derivatives have contributed substantially to the evolution of antimicrobial agents. The development of antibiotic quinolone began in 1962 with the discovery of nalidixic acid, which was used to treat urinary tract infections (Lesher et al., 1962). Quinolone derivatives are a classical division of organic chemistry; many of these molecules have shown remarkable biological properties, including exceptional antibacterial activity (Beena & Rawat, 2013;Chai et al., 2011;Hoshino et al., 2008) and are used as anti-fungal (Musiol et al., 2010), anti-tumoral (Bergh et al., 1997) and anti-cancer drugs (Elderfield & LeVon, 1960). Recently, complexes based on quinoline-4-carboxylic acid have been reported (Bu et al., 2005;Xiong et al., 2000). The present study is a continuation of the synthesis of heterocyclic derivatives performed by our team (Chkirate et al., 2019a,b). It is part of an ongoing structural study of heterocyclic compounds and their utilization as molecular (Faizi et al., 2016) and fluorescence sensors (Mukherjee et al., 2018); Kumar et al., 2017Kumar et al., , 2018. We report herein the synthesis and the molecular and crystal structures of the title compound, benzyl 1-benzyl-2-oxo-1,2-dihydroquinoline-4-carboxylate, along with the density functional theory (DFT) calculations.

Structural commentary
The molecular structure of the title compound is illustrated in Fig. 1. It is composed of two substituted aromatic rings attached to a planar quinolone ring (N1/C9-C17; r.m.s. deviation = 0.017 Å ). The attached benzyl rings (C2-C7 and C19-C24) are inclined to the quinolone ring system by 74.09 (8) and 89.43 (7) , respectively, and to each other by 63.97 (10) . The carboxylate group is twisted from the quinoline ring system by 32.2 (2) . The carboxylate group is involved in a short intramolecular C-HÁ Á ÁO contact forming an S(6) ring motif ( Fig. 1 and Table 1).

Supramolecular features
In the crystal, molecules are linked by bifurcated C-H,HÁ Á ÁO hydrogen bonds, forming layers lying parallel to the ac plane (Table 1 and Fig. 2). The layers are linked by C-HÁÁÁ interactions, so forming a supramolecular three-dimensional structure (Table 1 and Fig. 3).

Frontier molecular orbital analysis
The highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) are named as frontier molecular orbitals (FMOs). The FMOs play an important role in the optical and electric properties, as well as in quantum chemistry and UV-Vis spectra. The frontier orbital gap helps characterize the chemical reactivity and the kinetic stability of the molecule. A molecule with a small frontier orbital gap is generally associated with a high A view of the molecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 40% probability level. The intramolecular C-HÁ Á ÁO contact (see Table 1) is shown as a dashed line. Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
A view of along the b axis of the crystal packing of the title compound. Hydrogen bonds (see Table 1) are shown as dashed lines. For clarity, only H atoms H6 and H22 have been included.

Figure 3
A view of along the c axis of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines and the C-HÁ Á Á interactions as blue arrows (see Table 1). For clarity, only H atoms H6, H22 and H13 have been included (as grey balls). chemical reactivity, low kinetic stability and is also termed a soft molecule. DFT quantum-chemical calculations for the title compound were performed at the B3LYP/6-311 G(d,p) level (Becke, 1993) as implemented in GAUSSIAN09 (Frisch et al., 2009). DFT structure optimization was performed starting from the X-ray geometry and the values compared with experimental values of bond lengths and bond angles matching with theoretical values. The basis set 6-311G(d,p) is well suited in its approach to the experimental data. The DFT study shows that the HOMO and LUMO are localized in the plane extending from the whole tetra-substituted benzene ring. The electron distribution of the HOMO-1, HOMO, LUMO and the LUMO+1 energy levels are shown in Fig. 4. The HOMO molecular orbital exhibits both and character, whereas HOMO-1 is dominated by -orbital density. The LUMO is mainly composed of -density while LUMO+1 has both and electronic density. The HOMO-LUMO gap is found to be 0.15223 a.u. and the frontier molecular orbital energies, E HOMO and E LUMO are À0.22932 and À0.07709 a.u., respectively.

Database survey
A search of the Cambridge Structural Database (CSD, version 5.40, update May 2019; Groom et al., 2016) for the 1-benzylquinolin-2(1H)-one skeleton gave ten hits. The dihedral angle between the benzyl and quinoline rings varies from ca 71.0 to 89.6 , compared to 89.43 (7) in the title compound. Only two of these compounds have a carboxylate group in position 4 on the quinoline ring, viz. ethyl 1-benzyl-3-hydroxy-2-oxo-1,2dihydroquinoline-4-carboxylate (CSD refcode ZINHEL; Paterna et al., 2013) and benzyl 1-benzyl-2-oxo-3-vinyl-1,2dihydroquinoline-4-carboxylate (FAVZEK; Malini et al., 2017). The latter compound most closely resembles the title compound, with a vinyl substituent in position 3 of the quinoline ring. A view of the structural overlap of FAVZEK and the title compound is given in Fig. 5. The conformation of the two compounds differs essentially in the orientation of the carboxylate group with respect to the quinoline ring: 85.6 (3) in FAVZEK compared to 32.2 (2) in the title compound. This is the result of steric hindrance resulting from the presence of the vinyl substituent in position 3 on the quinoline ring in FAVZEK. In the title compound, the benzyl rings (C19-C24 and C2-C7) are inclined to the quinoline ring by 89.43 (7) and 74.09 (8) , respectively, while in FAVZEK the corresponding dihedral angles are 88.55 (11) and 76.44 (13) . The two benzyl rings are inclined to each other by 63.97 (10) in the title compound compared to 73.38 (16) in FAVZEK.

Synthesis and crystallization
A mixture of 2-oxo-1,2-dihydroquinoline-4-carboxylic acid (1 g, 5.29 mmol), K 2 CO 3 (1.46 g, 10.58 mmol), benzyl chloride (1.21 ml, 10.58 mmol) and tetra n-butylammonium bromide as catalyst in DMF (50 ml) was stirred at room temperature for 48 h. The solution was filtered by suction and the solvent was removed under reduced pressure. The residue was chromatographed on a silica-gel column using hexane and ethyl acetate (v/v, 95/5) as eluents to afford the title compound. Colourless prismatic crystals of the title compound were obtained by slow evaporation of a solution in ethanol (yield 53%).

Figure 4
Electron distribution of the HOMO-1, HOMO, LUMO and the LUMO+1 energy levels for the title compound.
in calculated positions and included in the refinement in the riding-model approximation: C-H = 0.93-0.97 Å with U iso (H) = 1.2U eq (C).  (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2018/3 (Sheldrick, 2015b), WinGX (Farrugia, 2012) and PLATON (Spek, 2009). 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.