Crystal structure, Hirshfeld surface analysis, interaction energy and DFT calculations and energy frameworks of methyl 6-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate

In the title compound, the dihydroquinoline moiety is not quite planar and an intramolecular C—H⋯O hydrogen bond helps to establish the rotational orientation of the carboxyl group. In the crystal, sheets of molecules parallel to (10 ) are generated by C—H⋯O and C—H⋯Cl hydrogen bonds.

In the title compound, C 12 H 10 ClNO 3 , the dihydroquinoline moiety is not planar with a dihedral angle between the two ring planes of 1.61 (6) . An intramolecular C-HÁ Á ÁO hydrogen bond helps to establish the rotational orientation of the carboxyl group. In the crystal, sheets of molecules parallel to (101) are generated by C-HÁ Á ÁO and C-HÁ Á ÁCl hydrogen bonds, and are stacked through slipped -stacking interactions between inversion-related dihydroquinoline units. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from HÁ Á ÁH (34.2%), HÁ Á ÁO/OÁ Á ÁH (19.9%), HÁ Á ÁCl/ClÁ Á ÁH (12.8%), HÁ Á ÁC/CÁ Á ÁH (10.3%) and CÁ Á ÁC (9.7%) interactions. Computational chemistry indicates that in the crystal, the C-HÁ Á ÁCl hydrogen-bond energy is À37.4 kJ mol À1 , while the C-HÁ Á ÁO hydrogen-bond energies are À45.4 and À29.2 kJ mol À1 . An evaluation of the electrostatic, dispersion and total energy frameworks revealed that the stabilization is dominated via the dispersion energy contribution. Density functional theory (DFT) optimized structures at the B3LYP/6-311 G(d,p) level are compared with the experimentally determined molecular structure in the solid state, and the HOMO-LUMO behaviour was elucidated to determine the energy gap.
They are also considered to be important scaffolds for the development of new molecules of pharmaceutical interest (Filali Baba et al., 2020;Bouzian et al., 2018).
In a continuation of our research work devoted to the study of O-and N-alkylation reactions involving quinoline derivatives, we report here the synthesis and crystal structure of methyl 6-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-4carboxylate obtained by the alkylation reaction of 6-chloro-2oxo-1,2-dihydroquinoline-4-carboxylic acid with an excess of methyl iodide as an alkylating reagent in phase transfer catalysis (PTC). The molecular and crystal structure as well as the Hirshfeld surface analysis of the title compound are reported. The results obtained using density functional theory (DFT) calculations, performed at the B3LYP/6-311G(d,p) level, are compared with the experimental results determined from the molecular and crystal structures in the solid state of the title compound, (I).

Structural commentary
The bicyclic molecular core is not planar as there is a dihedral angle of 1.61 (6) between the mean planes of its constituent rings. The dihedral angle between the mean plane of the (C1/ N1/C6-C9) ring and the plane defined by atoms C7, C11, O2 and O3 is 4.08 (8) with the near coplanarity of the carboxyl group and the heterocyclic ring being caused, in part, by the intramolecular C5-H5Á Á ÁO2 hydrogen bond (Table 1, Fig. 1).

Supramolecular features
In the crystal, C2-H2Á Á ÁO2 iii hydrogen bonds (Table 1) form ribbons of molecules extending along [010], which are further linked into sheets parallel to (101) by C12-H12CÁ Á ÁO1 ii and weak C8-H8Á Á ÁCl1 iv (HÁ Á ÁCl is 0.11 Å less than the sum of the van der Waals radii) hydrogen bonds (Table 1,  The title molecule with labelling scheme and displacement ellipsoids drawn at the 50% probability level. The intramolecular C-HÁ Á ÁO hydrogen bond is depicted by a dashed line.

Figure 2
A portion of one layer projected on (101) with C-HÁ Á ÁO and C-HÁ Á ÁCl hydrogen bonds depicted, respectively, by black and green dashed lines.

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of (I), a Hirshfeld surface (HS) analysis (Hirshfeld, 1977) was carried out by using CrystalExplorer17.5 (Turner et al., 2017). In the HS plotted over d norm (Fig. 4a), the white surface indicates contacts with distances equal to the sum of 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 (Venkatesan et al., 2016). Selected contacts are given in Table 2. The bright-red spots 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 electrostatic potential (Spackman et al., 2008;Jayatilaka et al., 2005) shown in Fig. 4b. The blue regions indicate a positive electrostatic potential (hydrogen-bond donors), while the red regions indicate a negative electrostatic potential (hydrogenbond acceptors). The shape-index of the HS is a tool to visualizestacking by the presence of adjacent red and blue triangles: if there are no adjacent red and/or blue triangles, then there are nointeractions. Fig. 4c clearly suggests that there areinteractions in (I). The overall twodimensional fingerprint plot is shown in Fig. 5a  (b) view of the three-dimensional Hirshfeld surface of the title compound plotted over electrostatic potential energy in the range À0.0500 to 0.0500 a.u. using the STO-3 G basis set at the Hartree-Fock level of theory; (c) Hirshfeld surface of the title compound plotted over shape-index. Symmetry codes: (ii) Àx; y þ 1 2 ; Àz þ 1 2 ; (iii) Àx þ 1; y À 1 2 ; Àz þ 3 2 ; (iv) x À 1; y; z À 1.

Figure 5
The full two-dimensional fingerprint plots for the title compound contributions to the Hirshfeld surface. The most important interaction is HÁ Á ÁH, contributing 34.2% to the overall crystal packing, which is reflected in Fig. 5b Fig. 6a-e, respectively.

Energy frameworks
Energy frameworks combine the calculation of intermolecular interaction energies with a graphical representation of their magnitude (Turner et al., 2015). Energies between molecular pairs are represented as cylinders joining the centroids of pairs of molecules with the cylinder radius proportional to the relative strength of the corresponding interaction energy. Energy frameworks were constructed for E ele (red cylinders), E dis (green cylinders) and E tot (blue cylinders) (Fig. 7a-  Symmetry codes: (i) x þ 1; y; z þ 1; (ii) Àx; y þ 1 2 ; Àz þ 1 2 ; (iii) Àx þ 1; y À 1 2 ; Àz þ 3 2 . frameworks indicates that the stabilization is dominated by the dispersion energy contributions in (I).

DFT calculations
The geometrical parameters and energies of (I) in the gas phase were computed via density functional theory (DFT) using the standard B3LYP functional and 6-311G(d,p) basisset calculations (Becke, 1993) as implemented in GAUSSIAN 09 (Frisch et al., 2009), see Table 3. The theoretical bond lengths and angles are in good agreement with those based on the X-ray analysis. However, a few differences exists in case of some dihedral angles (N1-C1-C6-C7; C10-N1-C1-C6; O1-C9-N1-C1; O2-C11-C7-C6; O3-C11-C7-C6; C12-O3-C11-C7), because in the DFT calculations there is only one molecule treated in the gas phase whereas in the solid state several molecules interact by hydrogen-bonding interactions (Fig. 2, Table 1). The torsion angles show that the conformation of the molecule in the gas phase has C 1 symmetry. The infrared spectrum of (I) on basis of the B3LYP/6-311G calculation is shown in the supporting information. All harmonic frequencies are positive, demonstrating the minimal signature of (I). The spectrum mainly constitutes 75 vibration Energy frameworks of (I). modes. The CH 3 torsion appears in the 17-119 cm À1 region, the C C stretching mode is at 1363 cm À1 , the vibrations of the aromatic N-CH 3 appear at 1091 cm À1 , and the O-CH 3 and the C-Cl stretching bands are observed, respectively, at 1033 cm À1 and 1124 cm À1 . The C-H stretch of the CH 3 group appears at 3182 cm À1 , however the aromatic C-H stretches appear in the 3208-3256 cm À1 region. The bending of CH 3 appear between 1528 cm À1 and 1556 cm À1 , Finally, the band positions of the bending of the HCC, HCN and HCO groups are respectively at 1169 cm À1 , 1119 cm À1 and 1204 cm À1 . The HOMO and LUMO energies are predicted with the B3LYP method in combination of basis sets 6-31G(d,p). This molecule contains 65 occupied molecular orbitals and 309 unoccupied virtual molecular orbitals. The frontier molecular orbitals are shown in Fig. 8. The positive phase is shown in red and the negative phase is shown in green. The HOMO-LUMO energy gap of (I) reflects the chemical activity and was calculated by the DFT/B3LYP/6-31G(d,p) method (Table 4). The high value of the energy gap (3.68 eV) implies a high electronic stability and low reactivity. In general, low values mean that it will be easier to remove an electron from the HOMO orbital towards the LUMO orbital.

Molecular electrostatic potential (MESP) analysis
The study of MESP is a useful tool in the investigation of the molecular structure with its relation to physico-chemical properties. The MESP analysis of (I) was performed with the functional B3LYP and the basis set 6-311G (d,P). The different values of the electrostatic potential are represented by different colours (Seminario, 1996;Murray & Sen, 1996) such that red represents the region of the most negative electrostatic potential (electrophilic sites), blue represents the region of the most positive electrostatic potential (the nucleophilic reactivity) and green represents the region of zero potential. The potential increases in the following order: red < orange < yellow < green < blue. Fig. 9 reveals that the negative potential sites are on oxygen and chlorine atoms, as well as the positive potential site is around hydrogen atoms. From these results, we can deduce that the H atoms show the strongest attraction and the oxygen and chlorine atoms show the strongest repulsion in the density curve. The H atom of the methoxy and amine group has a higher positive value than the other H atoms.

Database survey
A search of the Cambridge Crystallographic Database (updated to Dec. 31, 2021;Groom et al., 2016) using the fragment shown in the scheme below yielded 20 hits of which 16 contained an ester group attached to C7 (the remainder contained an alkyl group at this position) and, of these, only two, ROKCIG (Filali Baba et al., 2019) and REYREV (Filali Baba et al., 2018) contain a halogen atom attached to the aromatic ring. The former is more closely related to the title molecule by having an ethyl group attached to nitrogen and also in the ester substituent. In contrast to the title molecule, that in ROKCIG forms inversion dimers through C-HÁ Á ÁO hydrogen bonds (rather than ribbons), which are connected into layers approximately parallel to (104) The energy band gap of (I).

Figure 9
Contour surface of the electrostatic potential of (I).

Synthesis and crystallization
To a solution of 6-chloro-2-oxo-1,2-dihydroquinoline-4-carboxylic acid (1 g, 4.47 mmol) in 10 ml of DMF were added 3.30 ml (9.83 mmol) of methyl iodide, 3.17 g (22.36 mmol) of K 2 CO 3 and 0.17 g (0.5 mmol) of tetra n-butylammonium bromide (TBAB). The reaction mixture was stirred at room temperature in DMF for 6 h. After removal of salts, the solvent was evaporated under reduced pressure and the residue obtained was dissolved in dichloromethane. The organic phase was dried over Na 2 SO 4 and then concentrated in vacuo. A pure compound was obtained after recrystallization from dichloromethane/hexane (v/v 1/3).

Refinement
Crystal, data collection and refinement details are presented in Table 5. Hydrogen atoms were included as riding contributions in idealized positions with isotropic displacement parameters tied to those of the attached atoms. Two reflections obscured by the beamstop were omitted from the final refinement.

Special details
Experimental. The diffraction data were obtained from 12 sets of frames, each of width 0.5° in ω or φ, collected with scan parameters determined by the "strategy" routine in APEX3. The scan time was 15 sec/frame. 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. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.98 Å). All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms. Two reflections obscured by the beamstop were omitted from the final refinement.