Etoricoxibium picrate

Jerry P Jasinski; Ray J Butcher; M S Siddegowda; H S Yathirajan; A R Ramesha

doi:10.1107/S1600536810050993

. 2010 Dec 11;67(Pt 1):o107–o108. doi: 10.1107/S1600536810050993

Etoricoxibium picrate

Jerry P Jasinski ^a,^*, Ray J Butcher ^b, M S Siddegowda ^c, H S Yathirajan ^c, A R Ramesha ^d

PMCID: PMC3050426 PMID: 21522619

Abstract

In the cation of the title salt (systematic name: 5-{5-chloro-3-[4-(methylsulfonyl)phenyl]-2-pyridyl}-2-methylpyridinium 2,4,6-trinitrophenolate), C₁₈H₁₆ClN₂O₂S⁺·C₆H₂N₃O₇ ⁻, the mean planes of the two pyridine rings in the bipyridine unit are twisted by 33.9 (2)° with respect to each other. The dihedral angles between the mean planes of the sulfonylbenzene ring and the chloropyridine and methylpyridine rings are 51.2 (0) and 49.3 (9)°, respectively. The picrate anion interacts with the protonated N atom through a bifurcated N—H⋯(O,O) hydrogen bond, forming an R ₁ ²(6) ring motif with the N atom from the methylpyridine group of an adjacent cation. N—H⋯O hydrogen bonds, weak C—H⋯O and π–π stacking interactions [centroid–centroid distances = 3.8192 (9)and 3.6749 (9)] occur in the crystal packing, creating a two-dimensional network structure along [110].

Related literature

For the selective COX-2 inhibitor etoricoxib, see: Patrignani et al. (2003 ▶). For background to coxibs, traditional non-steroidal anti-inflammatory drugs, see: Rimon et al. (2010 ▶); Shriner et al. (1980) ▶; Patrignani et al. (2003 ▶). For related structures, see: Malathy Sony et al. (2005 ▶); Vasu Dev et al. (1999 ▶); Yathirajan et al. (2005 ▶). For standard bond lengths, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₈H₁₆ClN₂O₂S⁺·C₆H₂N₃O₇ ⁻
M _r = 587.94
Monoclinic,
a = 9.0250 (1) Å
b = 12.7496 (1) Å
c = 21.8011 (3) Å
β = 98.114 (1)°
V = 2483.43 (5) Å³
Z = 4
Cu Kα radiation
μ = 2.74 mm⁻¹
T = 123 K
0.48 × 0.42 × 0.24 mm

Data collection

Oxford Diffraction Xcalibur Ruby Gemini diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007 ▶) T _min = 0.607, T _max = 1.000
9467 measured reflections
4932 independent reflections
4454 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.104
S = 1.03
4932 reflections
363 parameters
H-atom parameters constrained
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.38 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Oxford Diffraction, 2007 ▶); 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.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810050993/zl2336sup1.cif

e-67-0o107-sup1.cif^{(25.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810050993/zl2336Isup2.hkl

e-67-0o107-Isup2.hkl^{(241.6KB, 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
N2A—H2AB⋯O1B	0.88	1.79	2.6588 (18)	172
N2A—H2AB⋯O7B	0.88	2.46	2.8898 (19)	111
C2A—H2AA⋯O1Aⁱ	0.95	2.56	3.455 (2)	156
C9A—H9AA⋯O1B	0.98	2.60	3.357 (2)	134
C13A—H13A⋯O2Aⁱⁱ	0.95	2.35	3.294 (2)	173
C18A—H18C⋯O2Bⁱⁱⁱ	0.98	2.38	3.249 (2)	147
C5A—H5AA⋯O6B^iv	0.95	2.45	3.329 (2)	153
C7A—H7AA⋯O4B^v	0.95	2.52	3.326 (2)	143

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

Acknowledgments

HSY thanks the University of Mysore for sanctioning his sabbatical leave and MSS thanks the University of Mysore for access to their research facilities. RJB acknowledges the NSF MRI program (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.

supplementary crystallographic information

Comment

Coxibs are the traditional non-steroidal anti-inflammatory drugs that counter the positive effects of aspirin in preventing blood clots. The research, published in the Proceedings of the National Academy of Sciences (Rimon et al., 2010)), indicates that people who are taking aspirin and coxibs together are in fact inhibiting the aspirin's effectiveness in preventing heart attacks and strokes. Some of the important class of coxib drugs are valdecoxib, celecoxib, rofecoxib, lumiracoxib, etoricoxib etc. Etoricoxib (brand name Arcoxia worldwide; also Algix and Tauxib in Italy) is a novel selective COX-2 inhibitor (Patrignani et al., 2003). Like any other COX-2 selective inhibitor, etoricoxib selectively inhibits isoform 2 of the enzyme cyclo-oxigenase (COX-2). The crystal structure of valdecoxib, a non-steroidal anti-inflammatory drug (Malathy Sony et al., 2005), a pseudopolymorph of valdecoxib (Yathirajan et al., 2005) and celecoxib, a COX-II inhibitor (Vasu Dev et al., 1999) have been reported. In the view of the importance of etoricoxib, this paper presents the crystal structure of the title compound, etoricoxib picrate.

In the crystal structure of the title compound, C₁₈H₁₆ClN₂O₂S⁺. C₆H₂N₃O₇^-, there is one cation-anion pair in the asymmetric unit (Fig. 1). In the cation, the mean planes of the two pyridine rings in the bipyridine moiety are twisted by 33.9 (2)° against each other. The dihedral angle between the mean planes of the sulfonylbenzene ring and the chloropyridine and methylpyridine rings are 51.2 (0)° and 49.3 (9)°, respectively. The picrate anion interacts with the protonated N atom through a bifurcated N—H···O hydrogen bond forming a R₁²(6) ring motif with the N atom from the methylpyridine group of an adjacent cation.

The dihedral angles between the mean planes of the anion benzene ring and three chloropyridine, methylpyridine and sulfonylbenzene rings of the cation are 53.9 (1)°, 49.3 (9)° and 3.8 (8)°, respectively. The mean planes of the two o-NO₂ and single p-NO₂ groups in the picrate anion are twisted by 3.0 (5)°, 30.4 (7)° and 6.5 (9)° with respect to the mean plane of the 6-membered benzene ring. Bond distances and angles are in normal ranges (Allen et al., 1987). N—H···O hydrogen bonds, weak C—H···O (Table 1) and π–π stacking interactions (Table 2) dominate the crystal packing creating an infinite 2-D network structure along the 110 (Fig. 2).

Experimental

Etoricoxib (3.59 g, 0.01 mmol) and picric acid (2.29 g, 0.01 mmol) in the ratio 1:1 were mixed together in a hot methanol solution. The mixture was warmed to 330 K for few minutes. The resultant precipitate was dried and recrystallized using DMSO. Crystals of the title compound were obtained by the slow evaporation of DMSO solution at room temperature after a few days. (m.p.: 463 – 465 K).