N-(2,3-Dimethyl­phen­yl)-4-hydr­oxy-2-methyl-2H-1,2-benzothia­zine-3-carboxamide 1,1-dioxide

Waseeq Ahmad Siddiqui; Iftikhar Hussain Bukahari; Muhammad Zia-ur-Rehman; Islam Ullah Khan; Graham John Tizzard

doi:10.1107/S1600536809006837

. 2009 Feb 28;65(Pt 3):o644–o645. doi: 10.1107/S1600536809006837

N-(2,3-Dimethylphenyl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide

Waseeq Ahmad Siddiqui ^a,^*, Iftikhar Hussain Bukahari ^a, Muhammad Zia-ur-Rehman ^b, Islam Ullah Khan ^c, Graham John Tizzard ^d

PMCID: PMC2968491 PMID: 21582293

Abstract

In the crystal structure of the title compound, C₁₈H₁₈N₂O₄S, the thiazine ring adopts a distorted half-chair conformation. 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. The enolic H atom is involved in an intramolecular O—H⋯O hydrogen bond, forming a six-membered ring. The molecules arrange themselves into centrosymmetric dimers by means of intermolecular N—H⋯O hydrogen bonds. A weak intermolcular C—H⋯O interaction is also present.

Related literature

For the synthesis of related molecules, see: Siddiqui, Ahmad, Khan et al. (2007 ▶); Zia-ur-Rehman et al. (2006 ▶); For the biological activity of 1,2-benzothiazine-1,1-dioxides, see: Zia-ur-Rehman et al. (2009 ▶). For related structures, see: Siddiqui et al. (2008 ▶); Siddiqui, Ahmad, Siddiqui et al. (2007 ▶). For the pharmacological background to 1,2-benzothiazine-3-carboxamide 1,1-dioxide derivatives, see Gennari et al. (1994 ▶); Lombardino & Wiseman (1972 ▶).

Experimental

Crystal data

C₁₈H₁₈N₂O₄S
M _r = 358.40
Monoclinic,
a = 10.2461 (3) Å
b = 8.5421 (2) Å
c = 19.8944 (5) Å
β = 104.832 (1)°
V = 1683.20 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 120 K
0.30 × 0.10 × 0.10 mm

Data collection

Bruker–Nonius CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.855, T _max = 0.978
18371 measured reflections
3828 independent reflections
3000 reflections with I > 2σ(I)
R _int = 0.055

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.114
S = 1.06
3828 reflections
234 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.57 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶) and COLLECT; data reduction: DENZO and COLLECT; 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/S1600536809006837/bt2887sup1.cif

e-65-0o644-sup1.cif^{(21KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809006837/bt2887Isup2.hkl

e-65-0o644-Isup2.hkl^{(183.9KB, 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
O1—H1O⋯O2	0.84	1.79	2.5320 (18)	147
N2—H1N⋯O3ⁱ	0.85 (2)	2.26 (2)	2.972 (2)	141 (2)
C3—H3⋯O4ⁱⁱ	0.95	2.49	3.352 (3)	150

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

Acknowledgments

The authors are grateful to the Higher Education Commission of Pakistan for a grant.

supplementary crystallographic information

Comment

1,2-Benzothiazine-3-carboxamide 1,1-dioxide derivatives belonging to oxicams, a class of non-steroidal anti-inflammatory drugs (NSAIDs), are well known as analgesic and anti-inflammatory agents since the introduction of Piroxicam (Lombardino & Wiseman, 1972) in the United States in 1982 where it gained immediate acceptance and remained among the top fifty prescription drugs for several years. Besides having anti-inflammatory activity, these have also been found to be used for the treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis and other inflammatory rheumatic and non- rheumatic processes, including onsets and traumatologic lesions (Gennari et al., 1994).

In continuation of our work on the synthesis (Siddiqui, Ahmad, Khan et al., 2007, Zia-ur-Rehman et al., 2006, biological activity (Zia-ur-Rehman et al, 2009) and crystal structures (Siddiqui, Ahmad, Siddiqui et al., 2007, Siddiqui et al., 2008) of various 1,2-benzothiazine-1,1-dioxides, we herein report the synthesis and crystal structure of the title compound (I) (Scheme and figure 1). The thiazine ring, involving two double bonds, exhibits a distorted half-chair conformation. The enolic hydrogen on O1 is involved in intramolecular hydrogen bonding giving rise to a six-membered hydrogen bond ring (Table 1). The molecules form centrosymmetric dimers through intermolecular N—H···O hydrogen bonds. In addition, the crystal packing is stabilized by weak C—H···O contacts.

Experimental

A mixture of methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (2.693 g; 10.0 mmoles), 2,3-dimethyl aniline (1.818 g; 15.0 mmoles) and xylene (25.0 ml) was refluxed under nitrogen atmosphere in a Soxhlet apparatus having Linde type 4Å molecular sieves. Three fourth of the xylene was then distilled off and the remaining contents were allowed to stand overnight at room temperature. Settled solids were filtered off, washed with diethyl ether and crystallized from ethanol. Yield: 78%.