Methyl 4-eth­oxy-2-methyl-2H-1,2-benzothia­zine-3-carboxyl­ate 1,1-dioxide

Muhammad Zia-ur-Rehman; Jamil Anwar Choudary; Mark R J Elsegood; Noshin Akbar; Hamid Latif Siddiqui

doi:10.1107/S1600536808021363

. 2008 Jul 16;64(Pt 8):o1508. doi: 10.1107/S1600536808021363

Methyl 4-ethoxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide

Muhammad Zia-ur-Rehman ^a, Jamil Anwar Choudary ^b, Mark R J Elsegood ^c, Noshin Akbar ^d,^*, Hamid Latif Siddiqui ^b

PMCID: PMC2962229 PMID: 21203217

Abstract

In the crystal structure of the title compound, C₁₃H₁₅NO₅S, the molecules exhibit weak S=O⋯H—C and C=O⋯H—C intermolecular interactions and arrange themselves into centrosymmetric dimers by means of π–π interactions (ring centroids are separated by 3.619 Å, while the closest C⋯C contacts are 3.514 Å). 1,2-Benzothiazines of this kind have a range of biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis.

Related literature

For related literature on benzothiazines, see: Ahmad et al. (2008 ▶); Bihovsky et al. (2004 ▶); Fabiola et al. (1998 ▶); Golič et al. (1987 ▶); Kojić-Prodić & Rużić-Toroš (1982 ▶); Lombardino et al. (1971 ▶); Reck et al. (1988 ▶); Zia-ur-Rehman et al. (2005 ▶, 2006 ▶, 2007 ▶).

Experimental

Crystal data

C₁₃H₁₅NO₅S
M _r = 297.32
Triclinic,
a = 7.9810 (4) Å
b = 8.1215 (4) Å
c = 10.8173 (6) Å
α = 89.4783 (7)°
β = 79.5124 (8)°
γ = 79.3434 (7)°
V = 677.33 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 150 (2) K
0.57 × 0.17 × 0.10 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.867, T _max = 0.975
8153 measured reflections
4069 independent reflections
3678 reflections with I > 2σ(I)
R _int = 0.014

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.096
S = 1.07
4069 reflections
184 parameters
H-atom parameters constrained
Δρ_max = 0.47 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and local programs.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808021363/bt2743sup1.cif

e-64-o1508-sup1.cif^{(18.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808021363/bt2743Isup2.hkl

e-64-o1508-Isup2.hkl^{(199.4KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯O2ⁱ	0.95	2.51	3.2726 (13)	137
C13—H13A⋯O5ⁱ	0.98	2.58	3.3715 (15)	138

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Symmetry code: (i) Inline graphic .

Acknowledgments

We are grateful to PCSIR Laboratories Complex, Lahore, for the provision of necessary chemicals.

supplementary crystallographic information

Comment

1,2-Benzothiazine 1,1-dioxides are heterocyclic compounds with numerous types of biological activity reported. For example, some are found useful as medicaments in the treatment of inflammation and rheumatoid arthritis (Lombardino et al., 1971). Other 1,2-benzothiazine 1,1-dioxides exhibit hyperlipidemic, anti-bacterial and Calpain I inhibition activities while they have also been found useful as endothelin receptor antagonists (Bihovsky et al., 2004). In continuation to our ongoing work on the synthesis of benzothiazine 1,1-dioxides (Zia-ur-Rehman et al., 2005, 2006, 2007; Ahmad et al., 2008), we herein report the synthesis and crystal structure of the title compound, (I).

In (I), the thiazine ring exhibits a distorted half-chair conformation with S1/C1/C6/C7 relatively planar (within +/- 0.0336 (6) Å) and N1 showing significant deviation from this plane due to its pyramidal geometry with the methyl group pointing approximately perpendicular to the plane. Compared with related molecules having no substitution at O3 [1.352 (9) Å; Golič et al., 1987; 1.339 (15) Å; Kojić-Prodić & Rużić-Toroš, 1982; 1.350 (9) Å; Reck et al., 1988; 1.336 (2) Å; Fabiola et al., 1998], C9—O4 in (I) is found to be shorter due to the absence of hydrogen bonding at O4. Each molecule of (I) is linked to its neighbours through inter-molecular C-H···S and C-H···O interactions giving rise to chains of molecules parallel to b (Fig. 2). Additionally, the molecules in are linked into centro-symmetric dimers by means of π-π interactions. The ring centroids are separated by 3.619 Å, while the closest C···C contacts are between C2 and C4'', separated by 3.514 Å (symmetry operator -x, -y, 1 - z).

Experimental

A mixture of methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (1.33 g; 5.0 mmoles), ethyl iodide (3.90 g; 25.0 mmoles), anhydrous potassium carbonate (10.0 g) and acetonitrile (100 ml) was stirred and refluxed for a period of 7 h. After removal of acetonitrile and excess methyl iodide under vacuum, chloroform (30 ml) was added and the resultant mixture was filtered. The filtrate was washed with water to remove potassium carbonate, dried with anhydrous sodium sulfate and filtered. Slow evaporation of the solvent afforded the crystalline product. Yield:1.26 g; 77.8%; m.p.147°C.