A pseudopolymorph of valdecoxib

Valdecoxib, C₁₆H₁₄N₂O₃S, is a non-steroidal anti-inflammatory drug containing a planar isoxazole heterocycle which is substituted at the C atoms with two aromatic rings and a methyl group. In addition to one mol­ecule of valdecoxib, there is half a mol­ecule of ethyl methyl ketone in the asymmetric unit of the title compound [systematic name: 4-(5-methyl-3-phenyl­isoxazol-4-yl)­benzene­sulfon­amide ethyl methyl ketone hemisolvate], viz. C₁₆H₁₄N₂O₃S·0.5C₄H₈O. The crystal packing is stabilized by N—H...O hydrogen bonds. Apart from the orientation of the sulfon­amide group, the conformation of the title compound agrees well with that of the recently published orthorhombic polymorph which does not contain any solvent.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](C-C) = 0.003 Å
• Disorder in solvent or counterion
• R factor = 0.044
• wR factor = 0.131
• Data-to-parameter ratio = 14.6

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT305_ALERT_2_A Isolated Hydrogen Atom (Outside Bond Range ??)         H2LA

Author Response: There is a molecule disordered about a centre of inversion.

PLAT305_ALERT_2_A Isolated Hydrogen Atom (Outside Bond Range ??)         H2LB

Author Response: There is a molecule disordered about a centre of inversion.

PLAT305_ALERT_2_A Isolated Hydrogen Atom (Outside Bond Range ??)         H2LC

Author Response: There is a molecule disordered about a centre of inversion.

PLAT410_ALERT_2_A Short Intra H...H Contact  H2LA   ..  H2LB    ..       1.57 Ang.
PLAT410_ALERT_2_A Short Intra H...H Contact  H2LA   ..  H2LC    ..       1.57 Ang.
PLAT410_ALERT_2_A Short Intra H...H Contact  H2LB   ..  H2LC    ..       1.57 Ang.
PLAT773_ALERT_2_A Suspect C-C Bond in CIF:      C1L    -C2L     ..       1.73 Ang.

Author Response: There is a molecule disordered about a centre of inversion.

PLAT773_ALERT_2_A Suspect C-C Bond in CIF:      C2L    -C1L     ..       1.73 Ang.

Author Response: There is a molecule disordered about a centre of inversion.

PLAT780_ALERT_1_A Coordinates do not Form a Properly Connected Set          ?

Alert level B
PLAT367_ALERT_2_B Long?  C(sp?)-C(sp?) Bond  C1L    -   C2L_d  ...       1.73 Ang.

Alert level C
PLAT041_ALERT_1_C Calc. and Rep. SumFormula Strings    Differ ....          ?
PLAT042_ALERT_1_C Calc. and Rep. MoietyFormula Strings Differ ....          ?
PLAT045_ALERT_1_C Calculated and Reported Z Differ by ............       0.50 Ratio
PLAT165_ALERT_3_C Nr. of Status R Flagged Non-Hydrogen Atoms .....          2
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       3.15 Ratio
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C23
PLAT302_ALERT_4_C Anion/Solvent Disorder .........................      17.00 Perc.
PLAT313_ALERT_2_C Oxygen with three covalent bonds (rare) ........        O1L
PLAT366_ALERT_2_C Short? C(sp?)-C(sp?) Bond  C1L    -   C1L_c  ...       1.31 Ang.
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          5
PLAT751_ALERT_4_C Bond    Calc     1.30508, Rep    1.305(4) ......  Senseless su
              C1L  -C1L     1.555   3.565
PLAT751_ALERT_4_C Bond    Calc     1.72763, Rep    1.727(6) ......  Senseless su
              C1L  -C2L     1.555   4.565
PLAT751_ALERT_4_C Bond    Calc     1.72763, Rep    1.727(6) ......  Senseless su
              C2L  -C1L     1.555   4.566

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

   4 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
  13 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
   5 ALERT type 4 Improvement, methodology, query or suggestion

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Computing details

Data collection: X-AREA (Stoe & Cie, 2001); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 1991); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 1990).

4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide ethyl methyl ketone hemisolvate

Crystal data

C16H14N2O3S·0.5C4H8O	F(000) = 736
Mr = 350.40	Dx = 1.327 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 24673 reflections
a = 13.0201 (14) Å	θ = 3.5–25.7°
b = 7.7930 (5) Å	µ = 0.21 mm^−1
c = 17.3305 (19) Å	T = 173 K
β = 94.373 (9)°	Plate, colourless
V = 1753.3 (3) Å^3	0.40 × 0.37 × 0.14 mm
Z = 4

Data collection

STOE IPDS-II two-circle diffractometer	3345 independent reflections
Radiation source: fine-focus sealed tube	2768 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.057
ω scans	θmax = 25.8°, θmin = 3.5°
Absorption correction: multi-scan (MULABS; Spek, 1990; Blessing, 1995)	h = −15→15
Tmin = 0.912, Tmax = 0.962	k = −9→9
24057 measured reflections	l = −21→21

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.131	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0755P)^2 + 0.4033P] where P = (Fo^2 + 2Fc^2)/3
3345 reflections	(Δ/σ)max = 0.001
229 parameters	Δρmax = 0.60 e Å^−3
0 restraints	Δρmin = −0.56 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	Occ. (<1)
S1	0.06511 (3)	0.75708 (5)	0.22545 (2)	0.02823 (16)
N1	−0.04516 (12)	0.7592 (2)	0.26081 (11)	0.0339 (4)
H1A	−0.0598 (17)	0.667 (3)	0.2835 (13)	0.037 (6)*
H1B	−0.053 (2)	0.843 (4)	0.2872 (15)	0.052 (7)*
O11	0.07021 (10)	0.60084 (16)	0.18285 (7)	0.0356 (3)
O12	0.07531 (10)	0.91506 (16)	0.18463 (7)	0.0336 (3)
C1	0.40159 (14)	0.7225 (2)	0.48139 (10)	0.0300 (4)
C2	0.50930 (14)	0.7445 (2)	0.47417 (11)	0.0328 (4)
N3	0.56210 (14)	0.7312 (2)	0.54123 (10)	0.0434 (4)
O4	0.48920 (12)	0.7000 (2)	0.59505 (8)	0.0451 (4)
C5	0.39420 (15)	0.6941 (3)	0.55751 (11)	0.0374 (4)
C51	0.30683 (19)	0.6607 (3)	0.60542 (12)	0.0512 (5)
H51A	0.2428	0.7019	0.5781	0.077*
H51B	0.3184	0.7211	0.6549	0.077*
H51C	0.3015	0.5372	0.6149	0.077*
C11	0.31684 (13)	0.7340 (2)	0.42022 (10)	0.0292 (4)
C12	0.30512 (14)	0.8795 (2)	0.37443 (11)	0.0339 (4)
H12	0.3504	0.9741	0.3840	0.041*
C13	0.22815 (13)	0.8884 (2)	0.31496 (10)	0.0317 (4)
H13	0.2208	0.9878	0.2833	0.038*
C14	0.16212 (13)	0.7510 (2)	0.30212 (10)	0.0278 (4)
C15	0.17113 (14)	0.6062 (2)	0.34832 (11)	0.0349 (4)
H15	0.1243	0.5134	0.3398	0.042*
C16	0.24890 (14)	0.5982 (2)	0.40694 (11)	0.0339 (4)
H16	0.2560	0.4987	0.4385	0.041*
C21	0.56250 (15)	0.7697 (2)	0.40305 (13)	0.0381 (4)
C22	0.65232 (17)	0.8662 (3)	0.40405 (18)	0.0588 (7)
H22	0.6798	0.9193	0.4505	0.071*
C23	0.7015 (2)	0.8839 (4)	0.3357 (3)	0.0876 (12)
H23	0.7623	0.9513	0.3358	0.105*
C24	0.6641 (3)	0.8065 (4)	0.2689 (2)	0.0806 (11)
H24	0.6989	0.8197	0.2230	0.097*
C25	0.5761 (2)	0.7094 (4)	0.26801 (15)	0.0633 (7)
H25	0.5504	0.6547	0.2215	0.076*
C26	0.52496 (14)	0.6907 (3)	0.33418 (10)	0.0439 (5)
H26	0.4639	0.6238	0.3330	0.053*
O1L	0.11783 (14)	0.9379 (3)	0.49816 (10)	0.1092 (18)	0.50
C1L	0.04893 (14)	0.4843 (3)	−0.00214 (10)	0.253 (6)
H1LA	0.0904	0.9672	0.5397	0.303*	0.50
H1LB	0.0731	0.9823	0.4496	0.303*	0.50
C2L	0.0467 (5)	0.2365 (7)	0.5065 (3)	0.138 (2)
H2LA	0.1155	1.2793	0.5044	0.207*
H2LB	0.0034	1.2840	0.4645	0.207*
H2LC	0.0207	1.2689	0.5547	0.207*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0256 (3)	0.0257 (3)	0.0325 (3)	0.00253 (15)	−0.00352 (17)	0.00003 (15)
N1	0.0251 (8)	0.0273 (9)	0.0489 (10)	0.0009 (6)	−0.0009 (7)	0.0009 (7)
O11	0.0388 (7)	0.0303 (7)	0.0366 (7)	0.0036 (5)	−0.0046 (5)	−0.0032 (5)
O12	0.0339 (7)	0.0300 (7)	0.0363 (7)	0.0028 (5)	−0.0016 (5)	0.0044 (5)
C1	0.0272 (9)	0.0306 (9)	0.0317 (8)	−0.0018 (7)	−0.0010 (7)	−0.0009 (7)
C2	0.0267 (9)	0.0330 (10)	0.0377 (9)	−0.0020 (7)	−0.0040 (7)	0.0005 (7)
N3	0.0365 (9)	0.0482 (10)	0.0437 (9)	−0.0049 (7)	−0.0093 (7)	0.0009 (7)
O4	0.0463 (8)	0.0535 (9)	0.0335 (7)	−0.0018 (7)	−0.0096 (6)	0.0018 (6)
C5	0.0367 (10)	0.0405 (10)	0.0344 (9)	0.0005 (8)	−0.0016 (7)	0.0001 (8)
C51	0.0541 (13)	0.0597 (14)	0.0411 (11)	0.0054 (11)	0.0132 (9)	0.0077 (10)
C11	0.0232 (8)	0.0343 (9)	0.0301 (8)	0.0002 (7)	0.0013 (7)	−0.0009 (7)
C12	0.0287 (9)	0.0325 (9)	0.0398 (9)	−0.0062 (7)	−0.0016 (7)	0.0020 (7)
C13	0.0288 (9)	0.0297 (9)	0.0361 (9)	−0.0016 (7)	−0.0008 (7)	0.0041 (7)
C14	0.0221 (8)	0.0295 (9)	0.0313 (8)	0.0019 (6)	−0.0005 (6)	−0.0010 (6)
C15	0.0302 (9)	0.0299 (9)	0.0432 (10)	−0.0055 (7)	−0.0061 (8)	0.0036 (7)
C16	0.0314 (9)	0.0315 (9)	0.0375 (9)	−0.0029 (7)	−0.0053 (7)	0.0065 (7)
C21	0.0275 (9)	0.0358 (10)	0.0513 (11)	0.0046 (7)	0.0056 (8)	0.0097 (8)
C22	0.0351 (11)	0.0439 (12)	0.0995 (19)	−0.0040 (9)	0.0189 (12)	−0.0026 (12)
C23	0.0591 (17)	0.0496 (15)	0.163 (4)	0.0019 (13)	0.066 (2)	0.0164 (19)
C24	0.081 (2)	0.0673 (18)	0.101 (2)	0.0298 (17)	0.059 (2)	0.0371 (18)
C25	0.0616 (16)	0.0811 (17)	0.0497 (13)	0.0335 (14)	0.0197 (11)	0.0238 (12)
C26	0.0349 (10)	0.0580 (13)	0.0389 (10)	0.0104 (9)	0.0033 (8)	0.0099 (9)
O1L	0.080 (3)	0.128 (4)	0.125 (4)	0.030 (3)	0.038 (3)	−0.007 (4)
C1L	0.139 (5)	0.565 (18)	0.054 (2)	−0.186 (9)	0.003 (3)	−0.036 (5)
C2L	0.141 (5)	0.159 (5)	0.110 (4)	0.033 (4)	−0.026 (3)	0.014 (3)

Geometric parameters (Å, º)

S1—O11	1.4280 (13)	C14—C15	1.383 (2)
S1—O12	1.4311 (13)	C15—C16	1.380 (2)
S1—N1	1.6036 (18)	C15—H15	0.9500
S1—C14	1.7628 (18)	C16—H16	0.9500
N1—H1A	0.85 (3)	C21—C22	1.389 (3)
N1—H1B	0.81 (3)	C21—C26	1.398 (3)
C1—C5	1.348 (3)	C22—C23	1.395 (5)
C1—C2	1.428 (3)	C22—H22	0.9500
C1—C11	1.473 (2)	C23—C24	1.363 (6)
C2—N3	1.309 (3)	C23—H23	0.9500
C2—C21	1.472 (3)	C24—C25	1.372 (5)
N3—O4	1.402 (2)	C24—H24	0.9500
O4—C5	1.354 (2)	C25—C26	1.377 (3)
C5—C51	1.482 (3)	C25—H25	0.9500
C51—H51A	0.9800	C26—H26	0.9500
C51—H51B	0.9800	O1L—C1L^i	1.083 (2)
C51—H51C	0.9800	O1L—H1LA	0.8593
C11—C16	1.387 (3)	O1L—H1LB	1.0461
C11—C12	1.386 (3)	C1L—O1L^ii	1.083 (2)
C12—C13	1.383 (3)	C1L—C1L^iii	1.305 (4)
C12—H12	0.9500	C1L—C2L^iv	1.727 (6)
C13—C14	1.380 (2)	C2L—C1L^v	1.727 (6)
C13—H13	0.9500
O11—S1—O12	117.92 (8)	C12—C13—H13	120.4
O11—S1—N1	106.54 (9)	C13—C14—C15	121.00 (16)
O12—S1—N1	107.43 (8)	C13—C14—S1	120.14 (13)
O11—S1—C14	107.93 (8)	C15—C14—S1	118.85 (13)
O12—S1—C14	107.92 (8)	C16—C15—C14	119.20 (17)
N1—S1—C14	108.85 (9)	C16—C15—H15	120.4
S1—N1—H1A	114.0 (15)	C14—C15—H15	120.4
S1—N1—H1B	111.9 (19)	C15—C16—C11	120.71 (17)
H1A—N1—H1B	113 (2)	C15—C16—H16	119.6
C5—C1—C2	104.43 (16)	C11—C16—H16	119.6
C5—C1—C11	127.49 (17)	C22—C21—C26	119.2 (2)
C2—C1—C11	128.05 (16)	C22—C21—C2	120.7 (2)
N3—C2—C1	111.46 (17)	C26—C21—C2	119.98 (17)
N3—C2—C21	120.34 (18)	C21—C22—C23	118.9 (3)
C1—C2—C21	128.12 (17)	C21—C22—H22	120.6
C2—N3—O4	105.55 (16)	C23—C22—H22	120.6
C5—O4—N3	109.05 (14)	C24—C23—C22	121.4 (3)
C1—C5—O4	109.51 (17)	C24—C23—H23	119.3
C1—C5—C51	133.80 (19)	C22—C23—H23	119.3
O4—C5—C51	116.69 (17)	C23—C24—C25	119.8 (3)
C5—C51—H51A	109.5	C23—C24—H24	120.1
C5—C51—H51B	109.5	C25—C24—H24	120.1
H51A—C51—H51B	109.5	C24—C25—C26	120.4 (3)
C5—C51—H51C	109.5	C24—C25—H25	119.8
H51A—C51—H51C	109.5	C26—C25—H25	119.8
H51B—C51—H51C	109.5	C25—C26—C21	120.3 (2)
C16—C11—C12	119.22 (16)	C25—C26—H26	119.8
C16—C11—C1	120.39 (16)	C21—C26—H26	119.8
C12—C11—C1	120.38 (16)	C1L^i—O1L—H1LA	57.2
C13—C12—C11	120.61 (17)	C1L^i—O1L—H1LB	53.1
C13—C12—H12	119.7	H1LA—O1L—H1LB	110.2
C11—C12—H12	119.7	O1L^ii—C1L—C1L^iii	134.9 (4)
C14—C13—C12	119.24 (16)	O1L^ii—C1L—C2L^iv	125.3 (3)
C14—C13—H13	120.4	C1L^iii—C1L—C2L^iv	99.2 (3)
C5—C1—C2—N3	−0.4 (2)	O12—S1—C14—C13	2.30 (17)
C11—C1—C2—N3	177.69 (18)	N1—S1—C14—C13	−114.00 (15)
C5—C1—C2—C21	176.34 (18)	O11—S1—C14—C15	−48.70 (16)
C11—C1—C2—C21	−5.6 (3)	O12—S1—C14—C15	−177.15 (14)
C1—C2—N3—O4	−0.1 (2)	N1—S1—C14—C15	66.55 (16)
C21—C2—N3—O4	−177.13 (16)	C13—C14—C15—C16	−1.5 (3)
C2—N3—O4—C5	0.6 (2)	S1—C14—C15—C16	177.99 (15)
C2—C1—C5—O4	0.8 (2)	C14—C15—C16—C11	0.7 (3)
C11—C1—C5—O4	−177.35 (17)	C12—C11—C16—C15	0.8 (3)
C2—C1—C5—C51	−179.8 (2)	C1—C11—C16—C15	−178.15 (17)
C11—C1—C5—C51	2.1 (4)	N3—C2—C21—C22	−34.5 (3)
N3—O4—C5—C1	−0.9 (2)	C1—C2—C21—C22	149.0 (2)
N3—O4—C5—C51	179.58 (18)	N3—C2—C21—C26	143.0 (2)
C5—C1—C11—C16	−58.0 (3)	C1—C2—C21—C26	−33.5 (3)
C2—C1—C11—C16	124.4 (2)	C26—C21—C22—C23	1.1 (3)
C5—C1—C11—C12	123.1 (2)	C2—C21—C22—C23	178.6 (2)
C2—C1—C11—C12	−54.5 (3)	C21—C22—C23—C24	−1.1 (4)
C16—C11—C12—C13	−1.5 (3)	C22—C23—C24—C25	0.3 (5)
C1—C11—C12—C13	177.46 (17)	C23—C24—C25—C26	0.5 (4)
C11—C12—C13—C14	0.7 (3)	C24—C25—C26—C21	−0.4 (4)
C12—C13—C14—C15	0.8 (3)	C22—C21—C26—C25	−0.4 (3)
C12—C13—C14—S1	−178.65 (14)	C2—C21—C26—C25	−177.97 (19)
O11—S1—C14—C13	130.75 (15)

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

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O12^vi	0.85 (3)	2.05 (3)	2.881 (2)	165 (2)
N1—H1B···O11^vii	0.81 (3)	2.09 (3)	2.863 (2)	160 (3)

Symmetry codes: (vi) −x, y−1/2, −z+1/2; (vii) −x, y+1/2, −z+1/2.