Valdecoxib, a non-steroidal anti-inflammatory drug

Valdecoxib [systematic name: 4-(5-methyl-3-phenyl­isoxazol-4-yl)benzene­sulfonamide], C₁₆H₁₄N₂O₃S, a diaryl-substituted isoxazole, is a non-steroidal anti-inflammatory drug (NSAID) that is used for the treatment of rheumatoid arthritis, osteoarthritis and dysmenorrhea pain. The planar isoxazole ring is oriented at angles of 22.2 (1) and 54.3 (1)° with respect to the phenyl and benzene­sulfonamide groups, respectively. N—H...O and C—H...O hydrogen bonds and N—H...π, C—H...π and π–π interactions stabilize the crystal packing.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.055
• wR factor = 0.179
• Data-to-parameter ratio = 20.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT199_ALERT_1_C Check the Reported cell_measurement_temperature         293
PLAT200_ALERT_1_C Check the Reported cell_ambient_temperature ....        293
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          5
PLAT420_ALERT_2_C D-H Without Acceptor       N15    -   H15B   ...          ?
PLAT480_ALERT_4_C Long H...A H-Bond Reported H7     ..  N2      ..       2.82 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H8     ..  O1      ..       2.82 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H11    ..  O13     ..       2.65 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H17    ..  O14     ..       2.61 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H18    ..  O14     ..       2.84 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H18    ..  O13     ..       2.61 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H19    ..  CG2     ..       3.10 Ang.
PLAT731_ALERT_1_C Bond    Calc     0.90(3), Rep   0.900(10) ......       3.00 su-Rat
              N15  -H15A    1.555   1.555
PLAT731_ALERT_1_C Bond    Calc     0.90(3), Rep   0.900(10) ......       3.00 su-Rat
              N15  -H15B    1.555   1.555
PLAT735_ALERT_1_C D-H     Calc     0.90(3), Rep   0.900(10) ......       3.00 su-Rat
              N15  -H15A    1.555   1.555
PLAT735_ALERT_1_C D-H     Calc     0.90(3), Rep   0.900(10) ......       3.00 su-Rat
              N15  -H15B    1.555   1.555

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
  15 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   6 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   7 ALERT type 4 Improvement, methodology, query or suggestion

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Computing details

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1990) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

4-(5-Methyl-3-phenylisoxazol-4-yl)benzenesulfonamide

Crystal data

C16H14N2O3S	F(000) = 1312
Mr = 314.35	Dx = 1.412 Mg m^−3
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 12.872 (2) Å	θ = 8–15°
b = 9.282 (3) Å	µ = 0.23 mm^−1
c = 24.761 (7) Å	T = 293 K
V = 2958.4 (14) Å^3	Rectangular block, colourless
Z = 8	0.35 × 0.30 × 0.20 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.000
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 1.6°
Graphite monochromator	h = 0→18
Non–profiled ω/2θ scans	k = 0→13
4295 measured reflections	l = −34→0
4295 independent reflections	3 standard reflections every 120 min
2167 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.179	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0714P)^2 + 1.6196P] where P = (Fo^2 + 2Fc^2)/3
4295 reflections	(Δ/σ)max = 0.002
208 parameters	Δρmax = 0.32 e Å^−3
2 restraints	Δρmin = −0.35 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	1.15965 (17)	0.3866 (3)	0.51380 (9)	0.0494 (6)
N2	1.1623 (2)	0.5202 (3)	0.48722 (11)	0.0483 (7)
C3	1.1025 (2)	0.5060 (3)	0.44440 (12)	0.0380 (7)
C4	1.0586 (2)	0.3633 (3)	0.44195 (12)	0.0376 (7)
C5	1.0969 (2)	0.2970 (4)	0.48605 (12)	0.0420 (7)
C6	0.9901 (2)	0.2968 (3)	0.40085 (12)	0.0379 (7)
C7	0.8985 (3)	0.2296 (4)	0.41593 (13)	0.0482 (8)
H7	0.8791	0.2293	0.4521	0.058*
C8	0.8354 (3)	0.1628 (4)	0.37838 (14)	0.0478 (8)
H8	0.7739	0.1187	0.3891	0.057*
C9	0.8649 (2)	0.1624 (3)	0.32468 (12)	0.0354 (6)
C10	0.9558 (2)	0.2295 (3)	0.30860 (12)	0.0417 (7)
H10	0.9749	0.2299	0.2724	0.050*
C11	1.0179 (2)	0.2959 (3)	0.34657 (12)	0.0405 (7)
H11	1.0791	0.3406	0.3357	0.049*
S12	0.78698 (6)	0.07136 (8)	0.27683 (3)	0.0396 (2)
O13	0.8479 (2)	−0.0422 (2)	0.25403 (10)	0.0543 (6)
O14	0.69142 (18)	0.0354 (3)	0.30245 (11)	0.0643 (8)
N15	0.7617 (3)	0.1799 (3)	0.22818 (13)	0.0525 (8)
C16	1.0897 (2)	0.6331 (3)	0.40898 (13)	0.0406 (7)
C17	1.0030 (3)	0.6489 (4)	0.37623 (13)	0.0451 (8)
H17	0.9531	0.5765	0.3749	0.054*
C18	0.9908 (3)	0.7723 (4)	0.34559 (15)	0.0567 (9)
H18	0.9328	0.7823	0.3235	0.068*
C19	1.0638 (3)	0.8802 (4)	0.34752 (16)	0.0618 (10)
H19	1.0550	0.9633	0.3270	0.074*
C20	1.1497 (3)	0.8650 (4)	0.37979 (17)	0.0625 (10)
H20	1.1993	0.9378	0.3810	0.075*
C21	1.1630 (3)	0.7427 (4)	0.41026 (15)	0.0530 (9)
H21	1.2216	0.7333	0.4320	0.064*
C22	1.0883 (3)	0.1486 (4)	0.50805 (15)	0.0576 (9)
H22A	1.0355	0.1461	0.5354	0.086*
H22B	1.1537	0.1204	0.5235	0.086*
H22C	1.0702	0.0833	0.4795	0.086*
H15A	0.724 (3)	0.256 (3)	0.2393 (16)	0.077 (14)*
H15B	0.8188 (17)	0.189 (4)	0.2075 (13)	0.069 (13)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0506 (13)	0.0556 (14)	0.0419 (12)	0.0000 (12)	−0.0073 (11)	0.0018 (11)
N2	0.0451 (15)	0.0507 (16)	0.0492 (17)	−0.0031 (14)	−0.0059 (13)	−0.0052 (14)
C3	0.0305 (14)	0.0431 (17)	0.0404 (16)	0.0018 (14)	−0.0009 (13)	−0.0063 (14)
C4	0.0340 (14)	0.0397 (16)	0.0391 (16)	−0.0001 (13)	0.0021 (13)	−0.0034 (14)
C5	0.0395 (16)	0.0492 (19)	0.0374 (17)	−0.0001 (15)	0.0066 (14)	−0.0023 (14)
C6	0.0378 (16)	0.0369 (16)	0.0390 (17)	−0.0001 (14)	0.0022 (13)	−0.0039 (13)
C7	0.0489 (18)	0.059 (2)	0.0361 (17)	−0.0121 (17)	0.0102 (14)	−0.0093 (16)
C8	0.0410 (17)	0.053 (2)	0.0490 (19)	−0.0121 (16)	0.0113 (15)	−0.0060 (16)
C9	0.0369 (15)	0.0297 (14)	0.0395 (16)	0.0010 (13)	0.0017 (13)	−0.0073 (12)
C10	0.0460 (17)	0.0424 (17)	0.0367 (16)	−0.0061 (15)	0.0063 (14)	−0.0033 (13)
C11	0.0391 (16)	0.0430 (17)	0.0395 (17)	−0.0079 (14)	0.0091 (14)	−0.0012 (14)
S12	0.0427 (4)	0.0331 (3)	0.0432 (4)	−0.0016 (3)	0.0008 (4)	−0.0073 (4)
O13	0.0666 (16)	0.0377 (12)	0.0586 (14)	0.0090 (12)	−0.0053 (13)	−0.0149 (11)
O14	0.0515 (15)	0.0792 (18)	0.0623 (16)	−0.0238 (14)	0.0103 (12)	−0.0156 (14)
N15	0.065 (2)	0.0439 (16)	0.0488 (17)	0.0063 (15)	−0.0108 (17)	0.0006 (15)
C16	0.0383 (16)	0.0407 (16)	0.0428 (17)	0.0010 (14)	−0.0021 (14)	−0.0083 (14)
C17	0.0432 (17)	0.0440 (18)	0.0480 (19)	0.0015 (16)	−0.0047 (15)	−0.0050 (16)
C18	0.056 (2)	0.051 (2)	0.062 (2)	0.0091 (19)	−0.0146 (18)	0.0006 (18)
C19	0.076 (3)	0.0422 (19)	0.067 (2)	0.009 (2)	−0.001 (2)	0.0044 (18)
C20	0.066 (2)	0.042 (2)	0.079 (3)	−0.009 (2)	−0.007 (2)	−0.001 (2)
C21	0.0455 (19)	0.050 (2)	0.063 (2)	−0.0053 (18)	−0.0113 (17)	−0.0014 (18)
C22	0.063 (2)	0.055 (2)	0.055 (2)	0.0032 (19)	0.0104 (18)	0.0054 (18)

Geometric parameters (Å, º)

O1—C5	1.348 (4)	S12—O14	1.424 (2)
O1—N2	1.404 (4)	S12—O13	1.430 (2)
N2—C3	1.317 (4)	S12—N15	1.603 (3)
C3—C4	1.441 (4)	N15—H15A	0.90 (1)
C3—C16	1.479 (5)	N15—H15B	0.90 (1)
C4—C5	1.347 (4)	C16—C21	1.387 (5)
C4—C6	1.482 (4)	C16—C17	1.388 (4)
C5—C22	1.486 (5)	C17—C18	1.383 (5)
C6—C11	1.391 (4)	C17—H17	0.93
C6—C7	1.385 (4)	C18—C19	1.375 (5)
C7—C8	1.382 (4)	C18—H18	0.93
C7—H7	0.93	C19—C20	1.372 (5)
C8—C9	1.383 (4)	C19—H19	0.93
C8—H8	0.93	C20—C21	1.373 (5)
C9—C10	1.384 (4)	C20—H20	0.93
C9—S12	1.768 (3)	C21—H21	0.93
C10—C11	1.379 (4)	C22—H22A	0.96
C10—H10	0.93	C22—H22B	0.96
C11—H11	0.93	C22—H22C	0.96
C5—O1—N2	108.7 (2)	O13—S12—N15	106.10 (17)
C3—N2—O1	106.0 (3)	O14—S12—C9	107.69 (15)
N2—C3—C4	110.8 (3)	O13—S12—C9	107.80 (15)
N2—C3—C16	117.5 (3)	N15—S12—C9	108.55 (15)
C4—C3—C16	131.6 (3)	S12—N15—H15A	112 (3)
C5—C4—C3	104.0 (3)	S12—N15—H15B	109 (2)
C5—C4—C6	125.8 (3)	H15A—N15—H15B	123 (4)
C3—C4—C6	130.2 (3)	C21—C16—C17	118.9 (3)
C4—C5—O1	110.5 (3)	C21—C16—C3	119.7 (3)
C4—C5—C22	133.9 (3)	C17—C16—C3	121.3 (3)
O1—C5—C22	115.5 (3)	C18—C17—C16	120.0 (3)
C11—C6—C7	118.5 (3)	C18—C17—H17	120.0
C11—C6—C4	120.9 (3)	C16—C17—H17	120.0
C7—C6—C4	120.6 (3)	C17—C18—C19	120.5 (3)
C8—C7—C6	121.4 (3)	C17—C18—H18	119.8
C8—C7—H7	119.3	C19—C18—H18	119.8
C6—C7—H7	119.3	C20—C19—C18	119.8 (4)
C9—C8—C7	119.1 (3)	C20—C19—H19	120.1
C9—C8—H8	120.4	C18—C19—H19	120.1
C7—C8—H8	120.4	C19—C20—C21	120.4 (4)
C8—C9—C10	120.5 (3)	C19—C20—H20	119.8
C8—C9—S12	119.3 (2)	C21—C20—H20	119.8
C10—C9—S12	120.1 (2)	C16—C21—C20	120.6 (3)
C11—C10—C9	119.7 (3)	C16—C21—H21	119.7
C11—C10—H10	120.2	C20—C21—H21	119.7
C9—C10—H10	120.2	C5—C22—H22A	109.5
C6—C11—C10	120.8 (3)	C5—C22—H22B	109.5
C6—C11—H11	119.6	H22A—C22—H22B	109.5
C10—C11—H11	119.6	C5—C22—H22C	109.5
O14—S12—O13	118.51 (17)	H22A—C22—H22C	109.5
O14—S12—N15	107.87 (18)	H22B—C22—H22C	109.5
C5—O1—N2—C3	−0.7 (3)	S12—C9—C10—C11	−177.7 (2)
O1—N2—C3—C4	0.4 (3)	C7—C6—C11—C10	0.0 (5)
O1—N2—C3—C16	179.1 (2)	C4—C6—C11—C10	177.7 (3)
N2—C3—C4—C5	0.1 (3)	C9—C10—C11—C6	−0.3 (5)
C16—C3—C4—C5	−178.4 (3)	C8—C9—S12—O14	11.5 (3)
N2—C3—C4—C6	−178.0 (3)	C10—C9—S12—O14	−170.1 (3)
C16—C3—C4—C6	3.6 (5)	C8—C9—S12—O13	−117.4 (3)
C3—C4—C5—O1	−0.5 (3)	C10—C9—S12—O13	61.0 (3)
C6—C4—C5—O1	177.7 (3)	C8—C9—S12—N15	128.1 (3)
C3—C4—C5—C22	−177.2 (3)	C10—C9—S12—N15	−53.5 (3)
C6—C4—C5—C22	1.0 (6)	N2—C3—C16—C21	21.1 (4)
N2—O1—C5—C4	0.8 (3)	C4—C3—C16—C21	−160.5 (3)
N2—O1—C5—C22	178.1 (3)	N2—C3—C16—C17	−155.6 (3)
C5—C4—C6—C11	−123.7 (4)	C4—C3—C16—C17	22.8 (5)
C3—C4—C6—C11	54.0 (5)	C21—C16—C17—C18	0.0 (5)
C5—C4—C6—C7	54.0 (5)	C3—C16—C17—C18	176.8 (3)
C3—C4—C6—C7	−128.3 (4)	C16—C17—C18—C19	−0.4 (5)
C11—C6—C7—C8	−0.1 (5)	C17—C18—C19—C20	0.4 (6)
C4—C6—C7—C8	−177.8 (3)	C18—C19—C20—C21	−0.2 (6)
C6—C7—C8—C9	0.5 (5)	C17—C16—C21—C20	0.2 (5)
C7—C8—C9—C10	−0.8 (5)	C3—C16—C21—C20	−176.6 (3)
C7—C8—C9—S12	177.6 (3)	C19—C20—C21—C16	−0.1 (6)
C8—C9—C10—C11	0.7 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N15—H15A···O13^i	0.90 (1)	2.12 (3)	3.010 (4)	168 (2)
N15—H15B···Cg3^ii	0.90 (1)	2.59 (3)	3.429 (4)	156 (2)
C7—H7···N2^iii	0.93	2.82	3.429 (5)	124
C8—H8···O1^iv	0.93	2.82	3.529 (4)	134
C11—H11···O13^v	0.93	2.65	3.383 (4)	136
C17—H17···O14^i	0.93	2.61	3.273 (4)	128
C18—H18···O14^i	0.93	2.84	3.387 (5)	119
C18—H18···O13^vi	0.93	2.61	3.389 (5)	142
C19—H19···Cg2^vi	0.93	3.10	3.708 (4)	125
C21—H21···Cg1^vii	0.93	2.88	3.631 (4)	138
C22—H22A···Cg3^iii	0.96	2.74	3.637 (4)	157

Symmetry codes: (i) −x+3/2, y+1/2, z; (ii) −x+2, y−1/2, −z+1/2; (iii) −x+2, −y+1, −z+1; (iv) x−1/2, −y+1/2, −z+1; (v) −x+2, y+1/2, −z+1/2; (vi) x, y+1, z; (vii) −x+5/2, y+1/2, z.