Molecular and crystal structure of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate

The molecular and crystal structures of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate, which possesses analgesic properties, have been determined


Chemical context
Methyl 4-methyl-2,2-dioxo-1H-2 6 ,1-benzothiazine-3-carboxylate (I) displays moderate analgesic properties (Azotla-Cruz et al., 2017) but has been used for the synthesis of highly active analgesic and anti-inflammatory compounds (Ukrainets et al., 2018). Earlier it was shown (Ukrainets et al., 2016a,b) that the biological properties of 2,1-benzothiazine derivatives depend to a considerable degree on their molecular and crystal structures. Thus knowledge of both the molecular and crystal structures of I is very important.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The dihydrothiazine heterocycle adopts a twist-boat conformation with puckering parameters (Zefirov et al., 1990) S = 0.57, Â = 53.3 , É = 25.2 . The S1 and C8 atoms deviate from the mean plane of the remaining ring atoms by 0.7941 (6) and 0.260 (2) Å , respectively. Some steric repulsion between the methyl substituent at the C7 atom and the ester group [the short intramolecular contact C11Á Á ÁO1 is 2.986 (5) Å compared to the van der Waals radii sum of 3.00 Å (Zefirov, 1997)] is compensated for by the formation of the intramolecular C11-H11CÁ Á ÁO1 hydrogen bond (Table 1)

Figure 2
The packing showing columns of molecules along the c-axis direction.

Figure 1
The molecular structure of I with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.  carbonyl group of the ester substituent relative to the endocyclic double bond.

Synthesis and crystallization
Methyl (chlorosulfonyl)acetate (1.90 g, 0.011 mol) was added dropwise with stirring to a solution of ortho-aminoacetophenone (1.35 g, 0.010 mol) and triethylamine (1.54 mL, 0.011 mol) in CH 2 Cl 2 (20 mL) and cooled to 268-273 K. After 10 h, water (50 mL) was added to the reaction mixture, which was then acidified to pH 4 with 1 N HCl and mixed thoroughly. The organic layer was separated off, dried over anhydrous CaCl 2 , and the solvent distilled (at reduced pressure at the end). The resulting anilide was subjected to heterocyclization without purification. A solution of sodium methylate in anhydrous methanol [from metallic sodium (0.69 g, 0.030 mol) and absolute methanol (15 mL)], the mixture was boiled and then kept for 15 h at room temperature. The reaction mixture was diluted with cold water and acidified with 1 N HCl to pH 4. Finally, the solid ester, I, was separated by filtration, washed with water, and dried in air giving colourless block-shaped crystals, yield: 2.25 g (89%); m.p.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All of the H atoms were located in difference-Fourier maps. The N-bound H atoms were refined isotropically. The C-bound H atoms were included in calculated positions and treated as riding: C-H = 0.96 Å with U iso (H) =1.5U eq (C) for the methyl groups and C-H = 0.93 Å with U iso (H) = 1.2U eq (C) for all others.  (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2014/7 (Sheldrick, 2015).

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.