Methyl 5-chloro-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate: structure and Hirshfeld surface analysis

The molecular and crystal structure as well as the Hirshfeld surface were analysed for this benzothiazine derivative with potential analgesic activity.


Chemical context
Alkyl 4-hydroxy-2,2-dioxo-1H-2 6 ,1-benzothiazine-3-carboxylates are known to be highly active analgesics (Ukrainets et al., 2013). The influence of substituents at the cyclic nitrogen atom on the biological properties of these substances has been studied in detail (Ukrainets et al., 2013(Ukrainets et al., , 2017. Continuing our research in this direction, we have synthesized and studied a new compound of this class with a substituent on the benzene part of the molecule. The biological properties of benzothiazine derivatives are known to depend on their molecular structure (Ukrainets et al., 2019a,b). In addition, such molecules can form polymorphic modifications possessing different biological activity, as was shown in our previous studies (Ukrainets et al., 2016a(Ukrainets et al., , 2018. Therefore, the molecular and crystal structure study as well as a Hirshfeld surface analysis were performed for the title compound, 1. ISSN 2056-9890

Hirshfeld surface analysis
Hirshfeld surface analysis and 2D fingerprint plots are useful tools to investigate the different types of intra-and intermolecular interactions in a crystal (Turner et al., 2017). The Hirshfeld surface of the title compound was obtained using a standard (high) surface resolution, mapped over d norm . The areas coloured red on the d norm surfaces correspond to contacts that are shorter than the van der Waals radii sum of the closest atoms (Fig. 3). In this way, red spots on the Hirshfeld surface indicate atoms participating in hydrogen bonds or other short contacts. Such red spots are observed at the hydrogen atom of the NH group, one of the oxygen atoms The molecular structure of compound 1. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms are shown as spheres of arbitrary radius. Table 1 Hydrogen-bond geometry (Å , ).  (5)  117 Symmetry codes: (i) Àx þ 3 2 ; y þ 1 2 ; Àz þ 1 2 ; (ii) Àx þ 3 2 ; y À 1 2 ; Àz þ 3 2 ; (iii) x À 1 2 ; Ày À 1 2 ; z À 1 2 .

Figure 2
A chain of molecules of 1 bound by N-HÁ Á ÁO hydrogen bonds about the 2 1 -screw axis parallel to the b axis.
of the SO 2 group, and the chlorine atom. Smaller red spots are also present at one of the hydrogen atoms of the methyl group. All of the hydrogen bonds and short contacts of the title compound are evident in the two-dimensional fingerprint plot presented in Fig. 4a. The pair of very sharp spikes indicates the presence of strong hydrogen bonds in the crystal of 1. The main contribution (42.0%) to these spikes is provided by OÁ Á ÁH/HÁ Á ÁO interactions (Fig. 4b). The contributions of CÁ Á ÁH/HÁ Á ÁC (17.3%) and ClÁ Á ÁH/HÁ Á ÁCl (14.2%) (Fig. 4c,d) interactions are similar, but the presence of sharp spikes in the fingerprint plot delineated ClÁ Á ÁH/HÁ Á ÁCl interactions suggests that these contacts are stronger. Surprisingly, the contribution of HÁ Á ÁH interactions (11.1%) (Fig. 4e) is very small, which is unusual for molecular crystals. The title compound may be considered as a structural analogue of methyl 4-hydroxy-2,2-dioxo-1-methyl-1H-2,1benzothiazine-3-carboxylate (Ukrainets et al., 2013), which is substituted by chlorine on the benzene ring of the molecule and dealkylated at the cyclic nitrogen atom.

Figure 5
The synthesis of compound 1.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2   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.