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

Waseeq Ahmad Siddiqui; Muhammad Ali; Muhammad Zia-ur-Rehman; Saima Sharif; Graham John Tizzard

doi:10.1107/S1600536809010058

. 2009 Mar 28;65(Pt 4):o900–o901. doi: 10.1107/S1600536809010058

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

Waseeq Ahmad Siddiqui ^a,^*, Muhammad Ali ^a, Muhammad Zia-ur-Rehman ^b, Saima Sharif ^c, Graham John Tizzard ^d

PMCID: PMC2968962 PMID: 21582605

Abstract

1,2-Benzothiazines similar to the title compound, C₁₈H₁₈N₂O₄S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. The thiazine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intramolecular O—H⋯O hydrogen bond, forming a six-membered ring. In the crystal, molecules arrange themselves into centrosymmetric dimers by means of pairs of weak intermolecular N—H⋯O hydrogen bonds.

Related literature

For the synthesis of related molecules, see: Siddiqui et al. (2007 ▶); Zia-ur-Rehman et al. (2005 ▶). For the biological activity of 1,2-benzothiazine-1,1-dioxides, see: Turck et al. (1996 ▶); Zia-ur-Rehman et al. (2006 ▶, 2009 ▶). For related structures, see: Golič & Leban (1987 ▶). For the pharmacological background to 1,2-benzothiazine-3-carboxamide 1,1-dioxide derivatives, see Gennari et al. (1994 ▶); Bihovsky et al. (2004 ▶).

Experimental

Crystal data

C₁₈H₁₈N₂O₄S
M _r = 358.40
Triclinic,
a = 7.5458 (4) Å
b = 8.0214 (3) Å
c = 14.4832 (7) Å
α = 89.864 (3)°
β = 79.530 (2)°
γ = 73.812 (3)°
V = 826.78 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 120 K
0.27 × 0.13 × 0.03 mm

Data collection

Bruker–Nonius CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.942, T _max = 0.993
13798 measured reflections
3783 independent reflections
2808 reflections with I > 2σ(I)
R _int = 0.055

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.119
S = 1.05
3783 reflections
230 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.45 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/S1600536809010058/bt2906sup1.cif

e-65-0o900-sup1.cif^{(20.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809010058/bt2906Isup2.hkl

e-65-0o900-Isup2.hkl^{(181.7KB, 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
O4—H4⋯O3	0.84	1.80	2.545 (2)	146
N2—H2⋯O1ⁱ	0.88	2.39	3.231 (2)	161

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

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

supplementary crystallographic information

Comment

In order to discover new useful therapeutic agents, many new compounds are continuously being synthesized. Owing to their applications as non-steroidal anti-inflammatory compounds (Turck et al., 1996), considerable attention has been given to 1,2-benzothiazine 1,1-dioxides and their precursor intermediates (Golič & Leban, 1987). Some of the 1,2-benzothiazines are also known as potent calpain I inhibitors (Bihovsky et al., 2004), while benzothiaine-3-yl-quinazolin-4-ones showed marked activity against Bacillus subtilis (Zia-ur-Rehman et al., 2006). 1,2-Benzothiazines are also 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). As part of a research program synthesizing various bioactive benzothiazines (Siddiqui et al., 2007, Zia-ur-Rehman et al., 2005, 2006, 2009), we herein report the crystal structure of the title compound (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.

Experimental

A mixture of methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (2.693 g; 10.0 mmoles), 3,4-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: 79.5%.