N-(2,4-Difluoro-phen-yl)-5-methyl-1,2-oxazole-4-carboxamide hemihydrate.

In the title compound, C(11)H(8)F(2)N(2)O(2)·0.5H(2)O, the dihedral angle between the benzene and isoxazole rings is 8.08 (3)°. In the crystal, the components are linked by O-H⋯N and N-H⋯O hydrogen bonds, in which the water mol-ecule acts as both a donor and an acceptor, into a tape with an R(4) (4)(16) graph-set motif along the a axis. The water mol-ecule is located on a twofold rotation axis. The methyl H atoms were treated as disordered groups over two sites with a refined site-occupancy ratio of 0.48 (6):0.52 (6).

Related literature

For applications of leflunomide [systematic name: 5-methyl-N-[4-(trifluoro­meth­yl) phen­yl]-isoxazole-4-carboxamide] in the treatment of rheumatoid arthritis, see: Shaw et al. (2011 ▶); Schattenkirchner (2000 ▶); For leflunomide analogs, see: Huang et al. (2003 ▶). For graph-set motifs, see: Bernstein, et al. (1995 ▶).

Experimental

Crystal data

C11H8F2N2O2·0.5H2O

M = 247.20

Monoclinic,

a = 15.182 (3) Å

b = 13.803 (3) Å

c = 12.159 (2) Å

β = 120.06 (3)°

V = 2205.3 (8) Å3

Z = 8

Mo Kα radiation

μ = 0.13 mm−1

T = 293 K

0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

Absorption correction: multi-scan (North et al., 1968 ▶) T min = 0.962, T max = 0.987

2076 measured reflections

1997 independent reflections

1486 reflections with I > 2σ(I)

R int = 0.050

3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.050

wR(F 2) = 0.130

S = 1.04

1997 reflections

168 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.28 e Å−3

Δρmin = −0.18 e Å−3

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, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812029431/nk2167sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812029431/nk2167Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812029431/nk2167Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C11H8F2N2O2·0.5H2O	F(000) = 1016
Mr = 247.20	Dx = 1.489 Mg m−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 25 reflections
a = 15.182 (3) Å	θ = 9–13°
b = 13.803 (3) Å	µ = 0.13 mm−1
c = 12.159 (2) Å	T = 293 K
β = 120.06 (3)°	Block, white
V = 2205.3 (8) Å3	0.30 × 0.20 × 0.10 mm
Z = 8

Enraf–Nonius CAD-4 diffractometer	1486 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.050
Graphite monochromator	θmax = 25.2°, θmin = 2.1°
ω/2θ scans	h = 0→18
Absorption correction: multi-scan (North et al., 1968)	k = 0→16
Tmin = 0.962, Tmax = 0.987	l = −14→12
2076 measured reflections	3 standard reflections every 200 reflections
1997 independent reflections	intensity decay: 1%

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.050	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.130	w = 1/[σ2(Fo2) + (0.060P)2 + 1.6P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max < 0.001
1997 reflections	Δρmax = 0.28 e Å−3
168 parameters	Δρmin = −0.18 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0247 (19)

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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	Occ. (<1)
O1W	0.5000	0.52321 (17)	0.2500	0.0620 (7)
H1W	0.505 (2)	0.564 (2)	0.193 (3)	0.093*
N1	0.65863 (15)	0.36286 (13)	0.32726 (18)	0.0484 (5)
H1A	0.6314 (18)	0.4180 (19)	0.332 (2)	0.058*
O1	0.66094 (13)	0.20060 (11)	0.36060 (16)	0.0611 (5)
F1	0.88573 (17)	0.40738 (15)	0.0910 (2)	0.1141 (8)
C1	0.75004 (19)	0.28877 (17)	0.2259 (2)	0.0584 (6)
H1B	0.7336	0.2263	0.2381	0.070*
F2	0.71615 (12)	0.53616 (10)	0.28913 (16)	0.0739 (5)
O2	0.49066 (13)	0.27282 (12)	0.53567 (16)	0.0615 (5)
N2	0.51344 (18)	0.37236 (15)	0.5487 (2)	0.0658 (6)
C2	0.8072 (2)	0.3024 (2)	0.1673 (3)	0.0720 (8)
H2B	0.8293	0.2495	0.1403	0.086*
C3	0.8304 (2)	0.3937 (2)	0.1496 (3)	0.0720 (8)
C4	0.80009 (19)	0.47406 (19)	0.1878 (2)	0.0649 (7)
H4A	0.8162	0.5362	0.1742	0.078*
C5	0.74512 (18)	0.45851 (16)	0.2468 (2)	0.0530 (6)
C6	0.71701 (16)	0.36750 (15)	0.2668 (2)	0.0461 (5)
C7	0.63608 (16)	0.28191 (15)	0.37245 (19)	0.0454 (5)
C8	0.57905 (16)	0.30012 (15)	0.43950 (19)	0.0450 (5)
C9	0.56469 (19)	0.38588 (17)	0.4907 (2)	0.0556 (6)
H9A	0.5893	0.4460	0.4838	0.067*
C10	0.53140 (17)	0.23129 (16)	0.4714 (2)	0.0492 (6)
C11	0.5167 (2)	0.12579 (18)	0.4509 (3)	0.0674 (7)
H11A	0.4739	0.1028	0.4827	0.101*	0.48 (6)
H11B	0.5815	0.0938	0.4950	0.101*	0.48 (6)
H11C	0.4850	0.1121	0.3617	0.101*	0.48 (6)
H11D	0.5423	0.1049	0.3970	0.101*	0.52 (6)
H11E	0.4454	0.1109	0.4112	0.101*	0.52 (6)
H11F	0.5526	0.0929	0.5311	0.101*	0.52 (6)

	U11	U22	U33	U12	U13	U23
O1W	0.0925 (18)	0.0490 (13)	0.0742 (16)	0.000	0.0640 (15)	0.000
N1	0.0634 (12)	0.0366 (9)	0.0596 (11)	0.0022 (8)	0.0415 (10)	0.0026 (8)
O1	0.0854 (12)	0.0377 (9)	0.0823 (12)	0.0037 (8)	0.0584 (10)	0.0019 (8)
F1	0.1517 (18)	0.1052 (14)	0.1635 (19)	0.0058 (12)	0.1374 (17)	0.0148 (13)
C1	0.0760 (16)	0.0463 (12)	0.0695 (15)	−0.0001 (11)	0.0489 (14)	0.0005 (11)
F2	0.0977 (11)	0.0427 (8)	0.1108 (12)	−0.0031 (7)	0.0743 (10)	−0.0029 (7)
O2	0.0787 (11)	0.0558 (10)	0.0700 (11)	−0.0022 (8)	0.0522 (9)	0.0004 (8)
N2	0.0953 (16)	0.0509 (12)	0.0720 (14)	−0.0040 (11)	0.0574 (14)	−0.0064 (10)
C2	0.092 (2)	0.0656 (17)	0.0854 (18)	0.0076 (14)	0.0646 (17)	0.0003 (14)
C3	0.0829 (19)	0.0760 (18)	0.0865 (19)	−0.0005 (15)	0.0644 (17)	0.0076 (15)
C4	0.0736 (17)	0.0581 (15)	0.0808 (18)	−0.0062 (13)	0.0518 (15)	0.0070 (13)
C5	0.0591 (13)	0.0448 (12)	0.0642 (14)	0.0004 (10)	0.0376 (12)	0.0015 (10)
C6	0.0505 (12)	0.0457 (12)	0.0474 (12)	0.0001 (10)	0.0283 (11)	0.0022 (9)
C7	0.0525 (13)	0.0397 (11)	0.0467 (12)	−0.0004 (9)	0.0268 (10)	−0.0004 (9)
C8	0.0548 (13)	0.0427 (12)	0.0415 (11)	−0.0009 (9)	0.0270 (10)	0.0009 (9)
C9	0.0759 (16)	0.0490 (13)	0.0541 (13)	−0.0033 (11)	0.0418 (13)	−0.0016 (10)
C10	0.0572 (13)	0.0459 (13)	0.0509 (12)	0.0001 (10)	0.0318 (11)	0.0007 (10)
C11	0.0874 (19)	0.0469 (14)	0.0852 (19)	−0.0087 (12)	0.0561 (16)	0.0020 (12)

O1W—H1W	0.92 (3)	C3—C4	1.368 (4)
N1—C7	1.362 (3)	C4—C5	1.363 (3)
N1—C6	1.409 (3)	C4—H4A	0.9300
N1—H1A	0.88 (3)	C5—C6	1.387 (3)
O1—C7	1.215 (2)	C7—C8	1.478 (3)
F1—C3	1.360 (3)	C8—C10	1.363 (3)
C1—C2	1.384 (3)	C8—C9	1.404 (3)
C1—C6	1.389 (3)	C9—H9A	0.9300
C1—H1B	0.9300	C10—C11	1.475 (3)
F2—C5	1.354 (3)	C11—H11A	0.9600
O2—C10	1.344 (3)	C11—H11B	0.9600
O2—N2	1.406 (3)	C11—H11C	0.9600
N2—C9	1.299 (3)	C11—H11D	0.9600
C2—C3	1.355 (4)	C11—H11E	0.9600
C2—H2B	0.9300	C11—H11F	0.9600
C7—N1—C6	126.79 (19)	C4—C5—C6	123.9 (2)
C7—N1—H1A	117.3 (16)	C5—C6—C1	116.6 (2)
C6—N1—H1A	115.8 (16)	C5—C6—N1	117.51 (19)
C2—C1—C6	120.6 (2)	C1—C6—N1	125.85 (19)
C2—C1—H1B	119.7	O1—C7—N1	123.6 (2)
C6—C1—H1B	119.7	O1—C7—C8	121.66 (19)
C10—O2—N2	108.88 (17)	N1—C7—C8	114.70 (18)
C9—N2—O2	105.04 (18)	C10—C8—C9	103.82 (19)
C3—C2—C1	119.3 (2)	C10—C8—C7	125.4 (2)
C3—C2—H2B	120.4	C9—C8—C7	130.7 (2)
C1—C2—H2B	120.4	N2—C9—C8	112.8 (2)
C2—C3—F1	119.4 (3)	N2—C9—H9A	123.6
C2—C3—C4	122.8 (2)	C8—C9—H9A	123.6
F1—C3—C4	117.8 (2)	O2—C10—C8	109.43 (19)
C5—C4—C3	116.7 (2)	O2—C10—C11	116.39 (19)
C5—C4—H4A	121.6	C8—C10—C11	134.2 (2)
C3—C4—H4A	121.6	H11D—C11—H11E	109.5
F2—C5—C4	118.5 (2)	H11D—C11—H11F	109.5
F2—C5—C6	117.62 (19)	H11E—C11—H11F	109.5
C10—O2—N2—C9	1.0 (3)	C6—N1—C7—O1	−3.4 (4)
C6—C1—C2—C3	−0.2 (4)	C6—N1—C7—C8	176.0 (2)
C1—C2—C3—F1	−179.4 (3)	O1—C7—C8—C10	−13.8 (3)
C1—C2—C3—C4	0.3 (5)	N1—C7—C8—C10	166.8 (2)
C2—C3—C4—C5	0.6 (4)	O1—C7—C8—C9	162.3 (2)
F1—C3—C4—C5	−179.7 (3)	N1—C7—C8—C9	−17.1 (3)
C3—C4—C5—F2	178.2 (2)	O2—N2—C9—C8	−0.6 (3)
C3—C4—C5—C6	−1.6 (4)	C10—C8—C9—N2	0.0 (3)
F2—C5—C6—C1	−178.2 (2)	C7—C8—C9—N2	−176.8 (2)
C4—C5—C6—C1	1.6 (4)	N2—O2—C10—C8	−1.0 (3)
F2—C5—C6—N1	1.3 (3)	N2—O2—C10—C11	178.9 (2)
C4—C5—C6—N1	−178.9 (2)	C9—C8—C10—O2	0.6 (2)
C2—C1—C6—C5	−0.7 (4)	C7—C8—C10—O2	177.6 (2)
C2—C1—C6—N1	179.9 (2)	C9—C8—C10—C11	−179.2 (3)
C7—N1—C6—C5	−169.5 (2)	C7—C8—C10—C11	−2.2 (4)
C7—N1—C6—C1	9.9 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1W	0.88 (3)	2.26 (3)	3.052 (3)	150 (2)
O1W—H1W···N2i	0.92 (3)	2.03 (3)	2.934 (2)	167 (3)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1W	0.88 (3)	2.26 (3)	3.052 (3)	150 (2)
O1W—H1W⋯N2i	0.92 (3)	2.03 (3)	2.934 (2)	167 (3)

Symmetry code: (i) .