Crystal structure, Hirshfeld surface analysis and interaction energy, DFT and antibacterial activity studies of (Z)-4-hexyl-2-(4-methylbenzylidene)-2H-benzo[b][1,4]thiazin-3(4H)-one

The benzothiazine moiety is folded along the N⋯S axis and a puckering analysis of the conformation of the heterocyclic ring was performed. The hexyl chain is mainly in an extended conformation. In the crystal, inversion dimers are formed by weak C—HMthn⋯OBnzthz hydrogen bonds and are linked into chains extending along the a-axis direction by weak C—HBnz⋯OBnzthz (Bnz = benzene, Bnzthz = benzothiazine and Mthn = methine) hydrogen bonds.

In a continuation of our research devoted to the development of substituted 1,4-benzothiazine derivatives (Ellouz et al., 2015(Ellouz et al., , 2019Sebbar et al., 2015Sebbar et al., , 2017a, we have ISSN 2056-9890 synthesized the title compound, I, by reaction of hexyl chloride with 2-(4-methylbenzylidene)-3,4-dihydro-2H-1,4benzothiazin-3 -one and potassium carbonate in the presence of tetra-n-butylammonium bromide (as catalyst). We report herein the synthesis, the molecular and crystal structures along with the Hirshfeld surface analysis and interaction energy calculation [using CE-B3LYP/6-31G(d,p) energy model] and the density functional theory (DFT) computational calculation carried out at the B3LYP/6-311 G(d,p) level for comparing with the experimentally determined molecular structure in the solid state of the title compound. Moreover, the antibacterial activity of I is evaluated against gram-positive and gram-negative bacteria (viz., Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus fasciens).

Figure 3
A partial packing diagram down the a-axis direction giving an end view of three adjacent chains.

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 Crystal Explorer 17.5 (Turner et al., 2017). In the HS plotted over d norm (Fig. 4), 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 appearing near O1 and hydrogen atoms H4 and H15 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. 5. The blue regions indicate the positive electrostatic potential (hydrogen-bond donors), while the red regions indicate the 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 nointeractions. Fig. 6 clearly suggests that there are nointeractions in (I).
The overall two-dimensional fingerprint plot, Fig. 7a, and those delineated into HÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH, HÁ Á ÁS/SÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH and HÁ Á ÁN/NÁ Á ÁH contacts (McKinnon et al., 2007) are illustrated in Fig. 7 b--f, respectively, together with their relative contributions to the Hirshfeld surface. The most important interaction is HÁ Á ÁH, contributing 59.2% to the overall crystal packing, which is reflected in Fig. 7b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.14 Å . In the absence of C-HÁ Á Á interactions, the pair of characteristic wings in the fingerprint plot delineated into HÁ Á ÁC/CÁ Á ÁH contacts (Fig. 7c, 27.9% contribution to the HS) has the tips at d e + d i = 2.77 Å . The pair of spikes in the fingerprint plot delineated into HÁ Á ÁS/SÁ Á ÁH (Fig. 7d  View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range À0.2415 to 1.4195 a.u.

Figure 5
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.

Figure 6
Hirshfeld surface of the title compound plotted over shape-index.

Figure 7
The full two-dimensional fingerprint plots for the title compound The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing. The large number of HÁ Á ÁH and HÁ Á ÁC/CÁ Á ÁH interactions suggest that van der Waals interactions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015).

DFT calculations
The optimized structure of the title compound 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 are in good agreement ( Table 2). 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 DFT calculations provide some 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, electronegativity (), hardness (), potential (), electrophilicity (!) and softness () are recorded in Table 3. The significance of and is for the evaluation of both the reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 9 Table 2 Comparison of the selected (X-ray and DFT) geometric data (Å , ).
In the majority of these, the thiazine ring is significantly folded about the SÁ Á ÁN axis with dihedral angles between the two S/C/C/N planes ranging from ca 35 [IIf (Sebbar et al., 2016b) and IId ] to ca 27 [IIc  and IIc (Sebbar et al., 2014)].

Antibacterial activity
To compare and analyse the antibacterial behaviour of the title compound and commercial antibiotics such as Chloramphenicol (Chlor), we have tested I against Escherichia coli The energy band gap of the title compound.

Figure 10
Antibacterial activity of the title compound (I) and commercial antibiotic Chloramphenicol (Chlor) against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus fasciens. 5 mg ml À1 for Streptococcus fasciens, which corresponds to the best MIC activity as compared to the commercial antibiotic. In addition, the maximum effect of I was recorded against Pseudomonas aeruginosa (diameter of inhibition 12.1 mm). Chlor presents an antibacterial activity diameter of inhibition of between 19 mm and 27 mm and no zone inhibition was observed with dimethylsulfoxide (DMSO) [(1%): 1 mL of DMSO added to 99 mL ofulltra-pure water] [The test samples were first dissolved in DMSO (1%), which did not affect the microbial growth.] On one hand, the chemical structure of I can explain this biological effect. The mechanism of action of I is not attributable to one specific mechanism, but there are several targets in the cell: degradation of the cell wall, damage to membrane proteins, damage to cytoplasmic membrane, leakage of cell contents and coagulation of cytoplasm. On the other hand, it should be noted that the functionalized derivatives by ester groups and benzene rings have the highest antibacterial coefficient (92% of pathogenic bacteria are sensitive). This study is expected to take anti-inflammatory, antifungal, anti-parasitic and anti-cancer activities, because the literature gives a lot of interesting results on these topics. Some other types of bacteria may possibly be tested by employing the same method so as eventually to generalize the suggested investigation method (Alderman & Smith, 2001).

Refinement
The experimental details including the crystal data, data collection and refinement are summarized in Table 5. The Cbound H atoms were positioned geometrically, with C-H = 0.95 Å (for aromatic and methine H atoms), 0.99 Å (for methylene H atoms) and 0.98 Å (for methyl H atoms), and constrained to ride on their parent atoms, with U iso (H) = k Â U eq (C), where k = 1.5 (for methyl H atoms) and k = 1.2 for other H atoms.    program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure:

(Z)-4-Hexyl-2-(4-methylbenzylidene)-2H-benzo[b][1,4]thiazin-3(4H)-one
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.002 Δρ max = 0.54 e Å −3 Δρ min = −0.22 e Å −3 Special details Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = -30.00 and 210.00°. The scan time was 20 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. Hatoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.99 Å). All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms.