Crystal structure, Hirshfeld surface analysis and DFT study of (2Z)-2-(2,4-dichlorobenzylidene)-4-[2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]-3,4-dihydro-2H-1,4-benzothiazin-3-one

In the title compound, the heterocyclic portion of the dihydrobenzothiazine unit adopts a flattened-boat conformation, while the oxazolidine ring adopts an envelope conformation. The 2-carbon link to the oxazole ring is perpendicular to the best plane through the dihydrobenzothiazine unit. In the crystal, the molecules form stacks extending along the normal to (104) through π-stacking interactions between the two carbonyl groups and inversion-related oxazole rings. Aromatic rings from neighbouring stacks intercalate to form an overall layer structure.

The title compound, C 20 H 16 Cl 2 N 2 O 3 S, is built up from a dihydrobenzothiazine moiety linked by -CH-and -C 2 H 4 -units to 2,4-dichlorophenyl and 2-oxo-1,3oxazolidine substituents, where the oxazole ring and the heterocyclic portion of the dihydrobenzothiazine unit adopt envelope and flattened-boat conformations, respectively. The 2-carbon link to the oxazole ring is nearly perpendicular to the mean plane of the dihydrobenzothiazine unit. In the crystal, the molecules form stacks extending along the normal to (104) with the aromatic rings from neighbouring stacks intercalating to form an overall layer structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from HÁ Á ÁH (28.4%), HÁ Á ÁCl/ClÁ Á ÁH (19.3%), HÁ Á ÁO/OÁ Á ÁH (17.0%), HÁ Á ÁC/CÁ Á ÁH (14.5%) and CÁ Á ÁC (8.2%) interactions. Weak hydrogen-bonding and van der Waals interactions are the dominant interactions in the crystal packing. 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. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Chemical context
Compounds containing a 1,4-benzothiazine backbone have been studied extensively both in academic and industrial laboratories. These molecules exhibit a wide range of biological applications indicating that the 1,4-benzothiazine moiety is a template potentially useful in medicinal chemistry research and therapeutic applications such as antipyretic (Warren & Knaus, 1987), anti-microbial (Armenise et al., 2012;Rathore & Kumar, 2006;Sabatini et al., 2008) , anti-viral (Malagu et al., 1998), herbicide (Takemoto et al., 1994), anticancer (Gupta & Kumar, 1986) and anti-oxidant (Zia-ur-Rehman et al., 2009) areas. They have also been reported as precursors for the syntheses of new compounds (Vidal et al., 2006) possessing anti-diabetic (Tawada et al., 1990) and anticorrosion activities (Ellouz et al., 2016a,b). 1,4-Benzothiazinecontaining compounds are important because of their potential applications in the treatment of diabetes complications, by inhibiting aldose reductase (Aotsuka et al., 1994). They are ISSN 2056-9890 also used as analgesics (Wammack et al., 2002) and and antagonists of Ca 2+ (Fujimura et al., 1996). As a continuation of our previous work on the syntheses and the biological properties of new 1,4-benzothiazine derivatives (Sebbar et al., 2016a,b;Ellouz et al., 2015aEllouz et al., ,b, 2017a, we report herein on the synthesis and the molecular and crystal structures of the title compound, (I), along with the Hirshfeld surface analysis and the density functional theory (DFT) calculations.

Figure 1
The molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. overall layer structure with the layers approximately parallel to (101) (Fig. 3).

Hirshfeld surface analysis
In order to visualize the intermolecular interactions in the crystal of 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. 5), 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, respectively (Venkatesan et al., 2016). The brightred 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), as shown in Fig. 6. The blue regions indicate positive electrostatic potential (hydrogen-bond donors), while the red regions indicate negative electrostatic potential (hydrogen-bond acceptors). The shape-index of the HS is a tool to visualize thestacking by the presence of adjacent red and blue triangles; if there are no adjacent red and/or blue triangles, then there are no ringring interactions. A partial packing diagram viewed along the b-axis direction with thestacking interactions shown by dashed lines.

Figure 4
A partial packing diagram viewed along the c-axis direction with thestacking interactions shown by dashed lines.

Figure 5
View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range À0.1152 to 1.5656 a.u.

Figure 6
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. Hydrogen-bond donors and acceptors are shown as blue and red regions around the atoms, corresponding to positive and negative potentials, respectively.

DFT calculations
The optimized structure of the title compound, (I), in the gas phase was generated theoretically via density functional theory (DFT) using standard B3LYP functional and 6-311 G(d,p) basis-set calculations (Becke, 1993) as implemented in GAUSSIAN 09 (Frisch et al., 2009). The theoretical and experimental results were in good agreement. 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. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 10. The HOMO and LUMO are localized in the plane extending from the whole (2Z)-2-[(2,4-dichlorophenyl)methylidene]-4-[2-(2-oxo-1,3oxazolidin-3-yl)ethyl]3,4-dihydro-2H-1,4-benzothiazin-3-one ring. The energy band gap [ÁE = E LUMO À E HOMO ] of the molecule is about 3.42 eV, and the frontier molecular orbital energies, E HOMO and E LUMO are À5.44 and À2.02 eV, respectively.  . In the majority of these, the heterocyclic ring is quite non-planar with the dihedral angle between the plane defined by the benzene ring plus the nitrogen and sulfur atoms and that defined by nitrogen and sulfur and the other two carbon atoms separating them ranging from ca 29 in CH 2 C CH (Sebbar et al., 2014a), to 36 in IId (Sebbar et al., 2015), which includes the value of ca 30 for 2H-1,4-benzothiazin-3(4H)-one (WAKLUQ 01; Merola, 2013). The other three (IIa, IIc and R 1 = 4-ClC 6 H 4 and R 2 = CH 2 Ph2;  have the benzothiazine unit nearly planar with a corresponding dihedral angle of ca 3-4 . In the case of IIa, the displacement ellipsoid for the sulfur atom shows a considerable elongation perpendicular to the mean plane of the heterocyclic ring, suggesting disorder, and a greater degree of non-planarity, but for the other two, there is no obvious source for the near planarity.

Figure 10
The energy-band gap of the title compound.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms were located in a difference-Fourier map, and freely refined.

(2Z)-2-(2,4-Dichlorobenzylidene)-4-[2-(2-oxo-1,3-oxazolidin-3-yl)ethyl]-3,4-dihydro-2H-1,4-benzothiazin-3-one
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.37 e Å −3 Δρ min = −0.38 e Å −3 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. 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.