2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo­[4,3-c][1,2]benzothia­zin-2-yl)acetic acid

Sana Aslam; Hamid Latif Siddiqui; Matloob Ahmad; Muhammad Zia-ur-Rehman; Masood Parvez

doi:10.1107/S1600536812023677

. 2012 May 31;68(Pt 6):o1970–o1971. doi: 10.1107/S1600536812023677

2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo[4,3-c][1,2]benzothiazin-2-yl)acetic acid

Sana Aslam ^a, Hamid Latif Siddiqui ^a,^*, Matloob Ahmad ^b, Muhammad Zia-ur-Rehman ^c, Masood Parvez ^d

PMCID: PMC3379518 PMID: 22719716

Abstract

In the title molecule, C₁₃H₁₃N₃O₄S, the heterocyclic thiazine ring adopts a half-chair conformation in which the S and an adjacent C atom are displaced by 0.919 (3) and 0.300 (4) Å, respectively, on the same side of the mean plane formed by the remaining ring atoms. The mean planes of the benzene and pyrazole rings are inclined at a dihedral angle of 18.32 (12)° with respect to each other. The acetate group is oriented at 80.75 (8)° with respect to the pyrazole ring. The crystal structure is stabilized by O—H⋯N and C—H⋯O hydrogen bonds, resulting in fused eight- and seven-membered rings with R ₂ ²(8) and R ₂ ²(7) graph-set motifs, respectively.

Related literature

For the biological activity of benzothiazine derivatives, see: Turck et al. (1996 ▶); Silverstein et al. (2000 ▶); Lombardino et al. (1973 ▶); Zinnes et al. (1973 ▶); Ahmad et al. (2010 ▶). For related structures, see: Siddiqui et al. (2008 ▶, 2009 ▶). For graph-set notation, see: Bernstein et al. (1995 ▶). graphic file with name e-68-o1970-scheme1.jpg

Experimental

Crystal data

C₁₃H₁₃N₃O₄S
M _r = 307.32
Monoclinic,
a = 10.495 (4) Å
b = 8.415 (2) Å
c = 15.136 (6) Å
β = 91.034 (19)°
V = 1336.5 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 173 K
0.14 × 0.12 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SORTAV; Blessing, 1997 ▶) T _min = 0.964, T _max = 0.974
5770 measured reflections
3048 independent reflections
2196 reflections with I > σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.110
S = 1.03
3048 reflections
193 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.35 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶); data reduction: SCALEPACK (Otwinowski & Minor, 1997 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812023677/pk2415sup1.cif

e-68-o1970-sup1.cif^{(18.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812023677/pk2415Isup2.hkl

e-68-o1970-Isup2.hkl^{(146.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812023677/pk2415Isup3.cml

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—H4O⋯N2ⁱ	0.84	1.90	2.724 (2)	165
C9—H9A⋯O2ⁱⁱ	0.98	2.59	3.297 (3)	129
C5—H5⋯O4ⁱⁱⁱ	0.95	2.59	3.476 (3)	155
C12—H12B⋯O3ⁱⁱⁱ	0.99	2.35	3.303 (3)	160

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

Acknowledgments

The authors are grateful to the Higher Education Commission, Pakistan, and the Institute of Chemistry, University of the Punjab, Lahore, Pakistan, for financial support.

supplementary crystallographic information

Comment

Meloxicam and Celecoxib are well known for their selective inhibition of the cox-2 enzyme that is responsible for inflammation (Turck et al., 1996; Silverstein et al., 2000). Though a number of benzothiazine based compounds have shown anti-inflammatory and analgesic character, yet there is a huge scope for selective cox-2 inhibitors in this family of heterocyclic compounds (Lombardino et al., 1973; Zinnes et al., 1973). In continuing the pursuit of potential drugs in this category, we have fused benzothiazine and pyrazole heterocycles that are core nuclei of meoxicam and celecoxib, respectively (Ahmad et al., 2010), we have synthesized and determined the crystal structure of the title compound which is presented in this paper.

The bond distances and angles in the title compound (Fig. 1) agree very well with the corresponding bond distances and angles reported in closely related compounds (Siddiqui et al., 2008; 2009). The heterocyclic thiazine ring adopts a twist chair conformation with atoms S1 and C1 displaced by 0.919 (3) and 0.300 (4) Å, respectively, on the same side of the mean plane formed by the remaining ring atoms (r.m.s. deviation 0.012 for N1/C6–C8 atoms). The mean-plane of the benzene ring C1–C6 makes a dihedral angle 18.32 (12)° with the mean-plane of the pyrazolyl ring (N2/N3/C7/C8/C10). The mean-plane of the acetate group (O3/O4/C12/C13) lies at 80.75 (8)° with respect to the pyrazolyl ring. The crystal structure is stabilized by intermolecular hydrogen bonding interactions (Fig. 2 and Table 1). The hydrogen bonds O4—H4O···N2 and C12—H12B···O3 result in eight membered rings with a R₂²(8) motif while C5—H5···O4 hydrogen bonding results in a seven membered ring with a R₂²(7) motif (Bernstein et al., 1995); both rings are fused together and result in chains of molecules along the b-axis in a zigzag fashion. Moreover, C9—H9A···O2 interactions link the title molecules into chains along the b-axis further consolidating the crystal packing.

Experimental

3,4-Dimethyl-2,4-dihydropyrazolo[4,3-c][1,2]benzothiazine 5,5-dioxide (5.0 g, 0.020 mole) and bromoacetic acid (3.31 g, 0.024 mole) were dissolved in anhydrous dimethyl formamide (15 ml) and anhydrous potassium carbonate (6.62 g, 0.048 mole) was added to it in small portions. The resulting reaction mixture was stirred for 2.5 h under a nitrogen atmosphere. The contents of the flask were poured over ice cold 10% HCl. Transparent crystals were grown from an aqueous solution, and were used for X-ray crystallographic studies.