Crystal structure of febuxostat-acetic acid (1/1).

The asymmetric unit of the title compound [systematic name: 2-(3-cyano-4-iso-butyl-oxyphen-yl)-4-methyl-thia-zole-5-carb-oxy-lic acid-acetic acid (1/1)], C16H16N2O3S·CH3COOH, contains a febuxostat mol-ecule and an acetic acid mol-ecule. In the febuxostat mol-ecule, the thia-zole ring is nearly coplanar with the benzene ring [dihedral angle = 3.24 (2)°]. In the crystal, the febuxostat and acetic acid mol-ecules are linked by O-H⋯O, O-H⋯N hydrogen bonds and weak C-H⋯O hydrogen bonds, forming supra-molecular chains propagating along the b-axis direction. π-π stacking is observed between nearly parallel thia-zole and benzene rings of adjacent mol-ecules; the centroid-to-centroid distances are 3.8064 (17) and 3.9296 (17) Å.

Related literature

For general apllications of febuxostat in medicine, see: Pascual et al. (2009 ▸); Kataoka et al. (2015 ▸); Gray & Walters-Smith (2011 ▸). For the synthesis, polymorphism, stability and bioavailabitily of febuxostat, see: Hiramatsu et al. (2000 ▸); Maddileti et al. (2013 ▸). For the crystal structures of febuxostat pyridine solvate and febuxostat methanol solvate, see: Zhu et al. (2009 ▸); Jiang et al. (2011 ▸).

Experimental

Crystal data

C16H16N2O3S·C2H4O2

M = 376.42

Triclinic,

a = 7.684 (2) Å

b = 10.580 (3) Å

c = 12.059 (3) Å

α = 84.897 (5)°

β = 84.674 (4)°

γ = 71.081 (5)°

V = 921.6 (4) Å3

Z = 2

Mo Kα radiation

μ = 0.21 mm−1

T = 296 K

0.51 × 0.30 × 0.24 mm

Data collection

Rigaku R-AXIS RAPID/ZJUG diffractometer

Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▸) T min = 0.890, T max = 0.952

7415 measured reflections

3397 independent reflections

2749 reflections with I > 2σ(I)

R int = 0.026

Refinement

R[F 2 > 2σ(F 2)] = 0.040

wR(F 2) = 0.123

S = 1.00

3397 reflections

241 parameters

H-atom parameters constrained

Δρmax = 0.25 e Å−3

Δρmin = −0.26 e Å−3

Data collection: PROCESS-AUTO (Rigaku, 2006 ▸); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 ▸); 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, 2012 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989015005708/xu5836sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015005708/xu5836Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989015005708/xu5836Isup3.cml

Click here for additional data file.

. DOI: 10.1107/S2056989015005708/xu5836fig1.tif

Mol­ecular structure of the title compound (I) showing atom-labelling scheme.

Click here for additional data file.

. DOI: 10.1107/S2056989015005708/xu5836fig2.tif

Part of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.

CCDC reference: 1055245

Additional supporting information: crystallographic information; 3D view; checkCIF report

C16H16N2O3S·C2H4O2	Z = 2
Mr = 376.42	F(000) = 396
Triclinic, P1	Dx = 1.356 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.684 (2) Å	Cell parameters from 2789 reflections
b = 10.580 (3) Å	θ = 3.2–27.4°
c = 12.059 (3) Å	µ = 0.21 mm−1
α = 84.897 (5)°	T = 296 K
β = 84.674 (4)°	Chunk, colorless
γ = 71.081 (5)°	0.51 × 0.30 × 0.24 mm
V = 921.6 (4) Å3

Rigaku R-AXIS RAPID/ZJUG diffractometer	3397 independent reflections
Radiation source: rolling anode	2749 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
Detector resolution: 10.00 pixels mm-1	θmax = 25.5°, θmin = 3.2°
ω scans	h = −8→9
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −12→12
Tmin = 0.890, Tmax = 0.952	l = −14→14
7415 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.123	H-atom parameters constrained
S = 1.00	w = 1/[σ2(Fo2) + (0.0641P)2 + 0.4268P] where P = (Fo2 + 2Fc2)/3
3397 reflections	(Δ/σ)max < 0.001
241 parameters	Δρmax = 0.25 e Å−3
0 restraints	Δρmin = −0.26 e Å−3

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.

	x	y	z	Uiso*/Ueq
S1	0.72628 (8)	0.73569 (5)	0.50085 (4)	0.03662 (17)
O1	0.5945 (3)	1.02293 (15)	0.26948 (14)	0.0507 (4)
H1	0.5889	1.1016	0.2705	0.076*
O2	0.7074 (3)	1.00765 (16)	0.43526 (15)	0.0584 (5)
O3	0.8936 (2)	0.12754 (14)	0.74240 (13)	0.0435 (4)
O4	0.5922 (3)	0.46989 (15)	0.17802 (14)	0.0538 (5)
H4	0.6221	0.4821	0.2387	0.081*
O5	0.5837 (3)	0.28003 (15)	0.26573 (13)	0.0511 (4)
N1	0.6762 (2)	0.60007 (15)	0.34796 (13)	0.0305 (4)
N2	0.9313 (4)	0.3647 (3)	0.90533 (19)	0.0707 (7)
C3	0.6693 (3)	0.81547 (19)	0.37300 (17)	0.0324 (5)
C2	0.6483 (3)	0.72860 (18)	0.30167 (17)	0.0304 (4)
C1	0.7188 (3)	0.59016 (18)	0.45268 (16)	0.0291 (4)
C4	0.6599 (3)	0.9576 (2)	0.36255 (18)	0.0364 (5)
C5	0.6022 (3)	0.7595 (2)	0.18262 (18)	0.0416 (5)
H5A	0.4835	0.7508	0.1747	0.062*
H5B	0.6938	0.6981	0.1365	0.062*
H5C	0.5997	0.8493	0.1601	0.062*
C6	0.7591 (3)	0.46731 (19)	0.52647 (16)	0.0299 (4)
C11	0.7480 (3)	0.3481 (2)	0.49263 (17)	0.0333 (5)
H11	0.7106	0.3464	0.4218	0.040*
C10	0.7910 (3)	0.2323 (2)	0.56132 (18)	0.0361 (5)
H10	0.7836	0.1537	0.5363	0.043*
C9	0.8457 (3)	0.2333 (2)	0.66802 (17)	0.0332 (5)
C8	0.8528 (3)	0.3538 (2)	0.70422 (17)	0.0332 (5)
C7	0.8122 (3)	0.4681 (2)	0.63359 (17)	0.0337 (5)
H7	0.8205	0.5468	0.6580	0.040*
C13	0.8752 (3)	0.0017 (2)	0.71520 (19)	0.0412 (5)
H13A	0.9542	−0.0312	0.6495	0.049*
H13B	0.7487	0.0139	0.7003	0.049*
C14	0.9314 (3)	−0.0965 (2)	0.8147 (2)	0.0450 (6)
H14	1.0592	−0.1062	0.8277	0.054*
C15	0.8132 (4)	−0.0512 (3)	0.9196 (2)	0.0650 (8)
H15A	0.8197	0.0342	0.9362	0.098*
H15B	0.8569	−0.1154	0.9804	0.098*
H15C	0.6878	−0.0434	0.9091	0.098*
C16	0.9239 (4)	−0.2326 (2)	0.7854 (3)	0.0605 (7)
H16A	0.8005	−0.2242	0.7692	0.091*
H16B	0.9601	−0.2966	0.8474	0.091*
H16C	1.0064	−0.2622	0.7212	0.091*
C12	0.8996 (3)	0.3588 (2)	0.81619 (19)	0.0440 (5)
C17	0.5719 (3)	0.3514 (2)	0.18152 (18)	0.0371 (5)
C18	0.5320 (5)	0.3165 (3)	0.0724 (2)	0.0676 (8)
H18A	0.5375	0.2243	0.0769	0.101*
H18B	0.6217	0.3305	0.0159	0.101*
H18C	0.4111	0.3722	0.0538	0.101*

	U11	U22	U33	U12	U13	U23
S1	0.0516 (3)	0.0284 (3)	0.0330 (3)	−0.0157 (2)	−0.0089 (2)	−0.0002 (2)
O1	0.0769 (12)	0.0284 (8)	0.0533 (10)	−0.0232 (8)	−0.0232 (9)	0.0079 (7)
O2	0.0934 (14)	0.0360 (9)	0.0574 (11)	−0.0312 (9)	−0.0266 (10)	−0.0004 (8)
O3	0.0615 (10)	0.0317 (8)	0.0401 (9)	−0.0190 (7)	−0.0145 (7)	0.0104 (6)
O4	0.0965 (14)	0.0329 (8)	0.0406 (9)	−0.0315 (9)	−0.0159 (9)	0.0059 (7)
O5	0.0845 (13)	0.0324 (8)	0.0425 (9)	−0.0267 (8)	−0.0148 (8)	0.0068 (7)
N1	0.0390 (9)	0.0238 (8)	0.0294 (9)	−0.0111 (7)	−0.0063 (7)	0.0025 (6)
N2	0.0975 (19)	0.0752 (16)	0.0407 (13)	−0.0255 (15)	−0.0214 (12)	−0.0011 (11)
C3	0.0372 (11)	0.0281 (10)	0.0332 (11)	−0.0122 (8)	−0.0059 (9)	0.0028 (8)
C2	0.0341 (10)	0.0246 (9)	0.0332 (11)	−0.0110 (8)	−0.0032 (8)	0.0018 (8)
C1	0.0295 (10)	0.0254 (9)	0.0320 (10)	−0.0089 (8)	−0.0008 (8)	−0.0012 (8)
C4	0.0422 (12)	0.0291 (10)	0.0406 (12)	−0.0153 (9)	−0.0052 (9)	0.0013 (9)
C5	0.0627 (14)	0.0295 (10)	0.0352 (12)	−0.0177 (10)	−0.0129 (10)	0.0063 (9)
C6	0.0314 (10)	0.0274 (10)	0.0302 (10)	−0.0090 (8)	−0.0017 (8)	0.0008 (8)
C11	0.0388 (11)	0.0327 (10)	0.0304 (10)	−0.0141 (9)	−0.0061 (9)	0.0023 (8)
C10	0.0462 (12)	0.0292 (10)	0.0364 (11)	−0.0161 (9)	−0.0074 (9)	0.0009 (9)
C9	0.0367 (11)	0.0303 (10)	0.0337 (11)	−0.0136 (9)	−0.0042 (9)	0.0057 (8)
C8	0.0375 (11)	0.0329 (10)	0.0286 (10)	−0.0104 (9)	−0.0039 (8)	0.0009 (8)
C7	0.0404 (11)	0.0279 (10)	0.0338 (11)	−0.0120 (9)	−0.0031 (9)	−0.0017 (8)
C13	0.0506 (13)	0.0313 (11)	0.0437 (13)	−0.0173 (10)	−0.0039 (10)	0.0049 (9)
C14	0.0450 (12)	0.0355 (11)	0.0528 (14)	−0.0126 (10)	−0.0094 (11)	0.0110 (10)
C15	0.088 (2)	0.0519 (15)	0.0481 (15)	−0.0164 (15)	−0.0039 (14)	0.0141 (12)
C16	0.0697 (17)	0.0333 (12)	0.0743 (19)	−0.0146 (12)	−0.0043 (15)	0.0111 (12)
C12	0.0577 (14)	0.0389 (12)	0.0357 (13)	−0.0157 (11)	−0.0094 (10)	0.0032 (9)
C17	0.0473 (12)	0.0272 (10)	0.0388 (12)	−0.0148 (9)	−0.0030 (9)	−0.0010 (9)
C18	0.119 (3)	0.0564 (16)	0.0429 (15)	−0.0473 (17)	−0.0126 (15)	−0.0017 (12)

S1—C3	1.713 (2)	C11—H11	0.9300
S1—C1	1.713 (2)	C10—C9	1.392 (3)
O1—C4	1.316 (3)	C10—H10	0.9300
O1—H1	0.8200	C9—C8	1.403 (3)
O2—C4	1.204 (3)	C8—C7	1.381 (3)
O3—C9	1.344 (2)	C8—C12	1.439 (3)
O3—C13	1.452 (3)	C7—H7	0.9300
O4—C17	1.309 (3)	C13—C14	1.512 (3)
O4—H4	0.8200	C13—H13A	0.9700
O5—C17	1.203 (3)	C13—H13B	0.9700
N1—C1	1.321 (3)	C14—C15	1.506 (4)
N1—C2	1.380 (2)	C14—C16	1.533 (3)
N2—C12	1.135 (3)	C14—H14	0.9800
C3—C2	1.369 (3)	C15—H15A	0.9600
C3—C4	1.477 (3)	C15—H15B	0.9600
C2—C5	1.493 (3)	C15—H15C	0.9600
C1—C6	1.470 (3)	C16—H16A	0.9600
C5—H5A	0.9600	C16—H16B	0.9600
C5—H5B	0.9600	C16—H16C	0.9600
C5—H5C	0.9600	C17—C18	1.482 (3)
C6—C11	1.389 (3)	C18—H18A	0.9600
C6—C7	1.392 (3)	C18—H18B	0.9600
C11—C10	1.380 (3)	C18—H18C	0.9600
C3—S1—C1	89.55 (10)	C8—C7—C6	120.94 (19)
C4—O1—H1	109.5	C8—C7—H7	119.5
C9—O3—C13	118.74 (17)	C6—C7—H7	119.5
C17—O4—H4	109.5	O3—C13—C14	107.20 (18)
C1—N1—C2	110.89 (16)	O3—C13—H13A	110.3
C2—C3—C4	134.5 (2)	C14—C13—H13A	110.3
C2—C3—S1	110.65 (15)	O3—C13—H13B	110.3
C4—C3—S1	114.82 (15)	C14—C13—H13B	110.3
C3—C2—N1	114.23 (18)	H13A—C13—H13B	108.5
C3—C2—C5	126.75 (18)	C15—C14—C13	112.9 (2)
N1—C2—C5	119.01 (17)	C15—C14—C16	110.9 (2)
N1—C1—C6	125.29 (17)	C13—C14—C16	108.2 (2)
N1—C1—S1	114.68 (14)	C15—C14—H14	108.2
C6—C1—S1	120.03 (15)	C13—C14—H14	108.2
O2—C4—O1	123.93 (19)	C16—C14—H14	108.2
O2—C4—C3	121.4 (2)	C14—C15—H15A	109.5
O1—C4—C3	114.69 (18)	C14—C15—H15B	109.5
C2—C5—H5A	109.5	H15A—C15—H15B	109.5
C2—C5—H5B	109.5	C14—C15—H15C	109.5
H5A—C5—H5B	109.5	H15A—C15—H15C	109.5
C2—C5—H5C	109.5	H15B—C15—H15C	109.5
H5A—C5—H5C	109.5	C14—C16—H16A	109.5
H5B—C5—H5C	109.5	C14—C16—H16B	109.5
C11—C6—C7	118.10 (18)	H16A—C16—H16B	109.5
C11—C6—C1	122.16 (18)	C14—C16—H16C	109.5
C7—C6—C1	119.74 (18)	H16A—C16—H16C	109.5
C10—C11—C6	121.79 (19)	H16B—C16—H16C	109.5
C10—C11—H11	119.1	N2—C12—C8	178.0 (3)
C6—C11—H11	119.1	O5—C17—O4	122.5 (2)
C11—C10—C9	119.94 (19)	O5—C17—C18	124.4 (2)
C11—C10—H10	120.0	O4—C17—C18	113.11 (19)
C9—C10—H10	120.0	C17—C18—H18A	109.5
O3—C9—C10	125.95 (18)	C17—C18—H18B	109.5
O3—C9—C8	115.24 (18)	H18A—C18—H18B	109.5
C10—C9—C8	118.81 (18)	C17—C18—H18C	109.5
C7—C8—C9	120.38 (19)	H18A—C18—H18C	109.5
C7—C8—C12	119.81 (19)	H18B—C18—H18C	109.5
C9—C8—C12	119.80 (18)
C1—S1—C3—C2	−0.09 (16)	S1—C1—C6—C7	−3.2 (3)
C1—S1—C3—C4	−178.19 (16)	C7—C6—C11—C10	−1.1 (3)
C4—C3—C2—N1	177.9 (2)	C1—C6—C11—C10	178.15 (18)
S1—C3—C2—N1	0.3 (2)	C6—C11—C10—C9	0.6 (3)
C4—C3—C2—C5	−1.3 (4)	C13—O3—C9—C10	−5.0 (3)
S1—C3—C2—C5	−178.87 (18)	C13—O3—C9—C8	174.90 (18)
C1—N1—C2—C3	−0.4 (2)	C11—C10—C9—O3	−179.0 (2)
C1—N1—C2—C5	178.84 (18)	C11—C10—C9—C8	1.1 (3)
C2—N1—C1—C6	−179.40 (18)	O3—C9—C8—C7	177.91 (18)
C2—N1—C1—S1	0.3 (2)	C10—C9—C8—C7	−2.2 (3)
C3—S1—C1—N1	−0.13 (16)	O3—C9—C8—C12	−3.1 (3)
C3—S1—C1—C6	179.60 (16)	C10—C9—C8—C12	176.8 (2)
C2—C3—C4—O2	−170.3 (2)	C9—C8—C7—C6	1.6 (3)
S1—C3—C4—O2	7.2 (3)	C12—C8—C7—C6	−177.3 (2)
C2—C3—C4—O1	10.4 (4)	C11—C6—C7—C8	0.0 (3)
S1—C3—C4—O1	−172.07 (16)	C1—C6—C7—C8	−179.29 (18)
N1—C1—C6—C11	−2.8 (3)	C9—O3—C13—C14	−177.85 (18)
S1—C1—C6—C11	177.53 (15)	O3—C13—C14—C15	60.1 (3)
N1—C1—C6—C7	176.48 (19)	O3—C13—C14—C16	−176.75 (19)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O5i	0.82	1.87	2.691 (2)	177
O4—H4···N1	0.82	2.05	2.800 (3)	152
C10—H10···O2ii	0.93	2.30	3.192 (3)	162
C11—H11···O5	0.93	2.45	3.344 (3)	161

Table 1

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
O1H1O5i	0.82	1.87	2.691(2)	177
O4H4N1	0.82	2.05	2.800(3)	152
C10H10O2ii	0.93	2.30	3.192(3)	162
C11H11O5	0.93	2.45	3.344(3)	161

Symmetry codes: (i) ; (ii) .