Methyl 2-methyl-4-(oxiran-2-ylmeth­oxy)-2H-1,2-benzothia­zine-3-carboxyl­ate 1,1-dioxide

Matloob Ahmad; Hamid Latif Siddiqui; Muhammad Zia-ur-Rehman; Mark R J Elsegood; George W Weaver

doi:10.1107/S1600536810000668

. 2010 Jan 9;66(Pt 2):o333. doi: 10.1107/S1600536810000668

Methyl 2-methyl-4-(oxiran-2-ylmethoxy)-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide

Matloob Ahmad ^a,^b, Hamid Latif Siddiqui ^a, Muhammad Zia-ur-Rehman ^b,^*, Mark R J Elsegood ^c, George W Weaver ^c

PMCID: PMC2979684 PMID: 21579762

Abstract

In the title compound, C₁₄H₁₅NO₆S, the thiazine ring adopts a distorted half-chair conformation. The structure displays several cooperative weak intermolecular C—H⋯O hydrogen-bonding interactions, giving rise to a two-dimensional sheet packing motif. The CH₂ group in the methoxy linker to the oxirane ring, and the CH group in that ring, exhibit twofold positional disorder. The three-membered oxirane ring is twisted approximately perpendicular with respect to thiazine ring (dihedral angle = 60/86° for the major/minor disorder components). 1,2-Benzothiazines of this kind have a wide range of biological activities and are mainly used as medicines in the treatment of inflammation and rheumatoid arthritis.

Related literature

For the synthesis of related molecules, see: Zia-ur-Rehman et al. (2006 ▶, 2007 ▶, 2009 ▶). For the biological activity of 1,2-benzothiazine 1,1-dioxides, see: Bihovsky et al. (2004 ▶); Fabiola et al. (1998 ▶); Kojić-Prodić & Rużić-Toroš (1982 ▶). For similar molecules, see: Ahmad et al. (2008 ▶); Arshad et al. (2009 ▶). For reference bond-length data, see: Weast et al. (1984 ▶).

Experimental

Crystal data

C₁₄H₁₅NO₆S
M _r = 325.33
Monoclinic,
a = 7.2007 (3) Å
b = 12.8435 (6) Å
c = 15.7820 (7) Å
β = 96.5250 (7)°
V = 1450.10 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 300 K
0.44 × 0.37 × 0.24 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ▶) T _min = 0.897, T _max = 0.942
11439 measured reflections
4516 independent reflections
3651 reflections with I > 2σ(I)
R _int = 0.016

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.155
S = 1.08
4516 reflections
220 parameters
H-atom parameters constrained
Δρ_max = 0.70 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL and local programs.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810000668/bt5151sup1.cif

e-66-0o333-sup1.cif^{(21.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810000668/bt5151Isup2.hkl

e-66-0o333-Isup2.hkl^{(221.3KB, 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
C7—H7⋯O6ⁱ	0.93	2.49	3.377 (3)	158
C15—H15⋯O3ⁱⁱ	0.98	2.50	3.317 (4)	140

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors are grateful to Loughborough University for the analysis of the title compound.

supplementary crystallographic information

Comment

Due to the verstaile applications of 1,2-benzothiazine 1,1-dioxides, much attention has been given to their synthesis. Some derivatives act as potent calpain I inhibitors (Bihovsky et al., 2004) while others possess anti-bacterial, anti-fungal and anti-oxidant properties (Zia-ur-Rehman et al., 2006, 2009). In continuation of our work on the synthesis (Zia-ur-Rehman et al., 2006), biological activity (Zia-ur-Rehman et al., 2009) and crystal structures (Zia-ur-Rehman et al., 2007; Ahmad et al., 2008; Arshad et al., 2009) of various 1,2-benzothiazine-1,1-dioxides, we herein report the crystal structure of the title compound (I) (scheme and Fig. 1). Like the previously reported 1,2-benzothiazine1,1-dioxides (Zia-ur-Rehman et al., 2007; Ahmad et al., 2008; Arshad et al., 2009), the thiazine ring involving two double bonds, exhibits a distorted half-chair conformation; with atoms S1/C10/C5/C4 coplanar within ±0.022 Å and N2 and C3 lying 0.961 and 0.525 Å respectively out of this plane. The geometry at N2 is pyramidal. The C10—S1 [1.7484 (17) Å] bond is shorter than a normal C—S single bond (1.81–2.55 Å) (Weast et al., 1984) due to partial double bond character and this value is in agreement with similar, partially delocalized, bonds (Kojić-Prodić & Rużić-Toroš, 1982; Fabiola et al., 1998]. The

positions the partially disordered oxirane group approximately perpendicular to the planar portion of the thiazine ring; dihedral angles between C4/C5/C10/S1 and the two diordered oxirane positions: 103 (major) and 108° (minor). There are two significant, intermolecular C—H···O interactions (Fig 2 & Table 1). Each molecule makes a total of four such interactions, two as donor and two as acceptor, resulting in a two-dimensional thick sheet structure, where the depth of the sheet is due to the elevation of the methoxy-oxirane group with respect to the thiazine ring system.

Experimental

A mixture of methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (1.33 g, 5.0 mmol), 1-chloro-2,3-epoxypropane (2.313 g, 25.0 mmol), 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 1-chloro-2,3-epoxypropane 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.