5-Methyl-N-[2-(trifluoro-meth-yl)phen-yl]isoxazole-4-carboxamide.

In the title compound, C(12)H(9)F(3)N(2)O(2), the benzene ring is nearly perpendicular to the isoxazole ring, making a dihedral angle of 82.97 (2)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into a supra-molecular chain running along the c axis.

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 ▶); Wang et al. (2011 ▶).

Experimental

Crystal data

C12H9F3N2O2

M = 270.21

Monoclinic,

a = 15.839 (3) Å

b = 8.3260 (17) Å

c = 9.4250 (19) Å

β = 101.29 (3)°

V = 1218.9 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.13 mm−1

T = 293 K

0.20 × 0.10 × 0.10 mm

Data collection

Enref–Nonius CAD-4 diffractometer

Absorption correction: ψ scan (North et al., 1968 ▶) T min = 0.974, T max = 0.987

2193 measured reflections

2193 independent reflections

1125 reflections with I > 2σ(I)

3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.062

wR(F 2) = 0.164

S = 1.00

2193 reflections

172 parameters

H-atom parameters constrained

Δρmax = 0.19 e Å−3

Δρmin = −0.19 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: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812016467/xu5516sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812016467/xu5516Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812016467/xu5516Isup3.cml

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

C12H9F3N2O2	F(000) = 552
Mr = 270.21	Dx = 1.472 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 15.839 (3) Å	θ = 9–13°
b = 8.3260 (17) Å	µ = 0.13 mm−1
c = 9.4250 (19) Å	T = 293 K
β = 101.29 (3)°	Block, colorless
V = 1218.9 (4) Å3	0.20 × 0.10 × 0.10 mm
Z = 4

Enref–Nonius CAD-4 diffractometer	1125 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Graphite monochromator	θmax = 25.2°, θmin = 1.3°
ω/2θ scans	h = −18→18
Absorption correction: ψ scan (North et al., 1968)	k = 0→9
Tmin = 0.974, Tmax = 0.987	l = 0→11
2193 measured reflections	3 standard reflections every 200 reflections
2193 independent reflections	intensity decay: 1%

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)] = 0.062	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.164	H-atom parameters constrained
S = 1.00	w = 1/[σ2(Fo2) + (0.068P)2] where P = (Fo2 + 2Fc2)/3
2193 reflections	(Δ/σ)max < 0.001
172 parameters	Δρmax = 0.19 e Å−3
0 restraints	Δρmin = −0.19 e Å−3

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
N1	0.73554 (18)	0.2300 (3)	0.9712 (3)	0.0540 (8)
H1A	0.7386	0.2533	1.0610	0.065*
O1	0.67807 (16)	0.2925 (3)	0.7394 (2)	0.0647 (8)
F1	0.9108 (2)	0.3541 (4)	1.0116 (3)	0.1322 (13)
C1	0.9018 (3)	−0.0106 (6)	0.8447 (4)	0.0732 (12)
H1B	0.9526	0.0039	0.8108	0.088*
O2	0.55089 (19)	0.6534 (3)	0.9342 (3)	0.0782 (9)
N2	0.6083 (3)	0.6480 (4)	1.0694 (4)	0.0790 (11)
F2	0.97802 (18)	0.2773 (4)	0.8551 (4)	0.1233 (11)
C2	0.8701 (3)	−0.1615 (6)	0.8525 (5)	0.0844 (14)
H2B	0.8989	−0.2489	0.8232	0.101*
F3	0.85728 (19)	0.3827 (3)	0.7915 (3)	0.1128 (10)
C3	0.7957 (3)	−0.1853 (5)	0.9035 (5)	0.0805 (13)
H3A	0.7746	−0.2886	0.9103	0.097*
C4	0.7526 (3)	−0.0551 (5)	0.9447 (4)	0.0650 (11)
H4A	0.7023	−0.0707	0.9797	0.078*
C5	0.7837 (2)	0.0983 (4)	0.9344 (3)	0.0512 (9)
C6	0.8601 (2)	0.1205 (5)	0.8858 (4)	0.0574 (10)
C7	0.9005 (3)	0.2832 (5)	0.8849 (5)	0.0680 (11)
C8	0.6852 (2)	0.3198 (4)	0.8696 (4)	0.0486 (9)
C9	0.6396 (2)	0.4541 (4)	0.9236 (4)	0.0488 (9)
C10	0.5722 (3)	0.5371 (5)	0.8487 (4)	0.0589 (10)
C11	0.6589 (3)	0.5281 (5)	1.0597 (4)	0.0641 (11)
H11A	0.7029	0.4948	1.1343	0.077*
C12	0.5197 (3)	0.5268 (5)	0.7026 (4)	0.0761 (12)
H12A	0.4770	0.6101	0.6897	0.114*
H12B	0.4919	0.4240	0.6897	0.114*
H12C	0.5559	0.5397	0.6327	0.114*

	U11	U22	U33	U12	U13	U23
N1	0.066 (2)	0.0617 (19)	0.0402 (15)	0.0153 (17)	0.0235 (14)	0.0065 (15)
O1	0.0783 (18)	0.0810 (19)	0.0400 (13)	0.0171 (15)	0.0239 (12)	−0.0014 (13)
F1	0.172 (3)	0.127 (3)	0.112 (2)	−0.071 (2)	0.062 (2)	−0.0454 (19)
C1	0.064 (3)	0.081 (3)	0.083 (3)	0.013 (2)	0.035 (2)	0.003 (2)
O2	0.093 (2)	0.0569 (17)	0.094 (2)	0.0188 (16)	0.0402 (19)	0.0020 (16)
N2	0.111 (3)	0.063 (2)	0.069 (2)	0.010 (2)	0.035 (2)	−0.0060 (19)
F2	0.0791 (18)	0.124 (2)	0.182 (3)	−0.0192 (18)	0.0619 (19)	0.010 (2)
C2	0.091 (3)	0.071 (3)	0.100 (4)	0.022 (3)	0.040 (3)	0.003 (3)
F3	0.108 (2)	0.087 (2)	0.135 (3)	−0.0171 (17)	0.0032 (18)	0.0453 (18)
C3	0.097 (3)	0.049 (3)	0.102 (3)	0.003 (2)	0.034 (3)	0.014 (2)
C4	0.065 (3)	0.068 (3)	0.070 (3)	−0.001 (2)	0.033 (2)	0.015 (2)
C5	0.059 (2)	0.054 (2)	0.045 (2)	0.0066 (19)	0.0234 (18)	0.0067 (16)
C6	0.058 (2)	0.069 (3)	0.050 (2)	0.006 (2)	0.0218 (18)	0.0051 (19)
C7	0.065 (3)	0.075 (3)	0.071 (3)	0.000 (2)	0.033 (2)	0.004 (2)
C8	0.050 (2)	0.049 (2)	0.052 (2)	0.0024 (18)	0.0254 (17)	0.0047 (17)
C9	0.061 (2)	0.044 (2)	0.0470 (19)	−0.0004 (18)	0.0261 (17)	0.0010 (17)
C10	0.064 (3)	0.049 (2)	0.070 (2)	−0.004 (2)	0.030 (2)	0.004 (2)
C11	0.091 (3)	0.056 (2)	0.051 (2)	0.003 (2)	0.026 (2)	0.0006 (19)
C12	0.076 (3)	0.072 (3)	0.081 (3)	−0.001 (2)	0.017 (2)	0.015 (2)

N1—C8	1.346 (4)	C3—C4	1.377 (5)
N1—C5	1.417 (4)	C3—H3A	0.9300
N1—H1A	0.8600	C4—C5	1.379 (5)
O1—C8	1.231 (4)	C4—H4A	0.9300
F1—C7	1.314 (4)	C5—C6	1.387 (4)
C1—C2	1.361 (6)	C6—C7	1.499 (5)
C1—C6	1.370 (5)	C8—C9	1.475 (4)
C1—H1B	0.9300	C9—C10	1.350 (5)
O2—C10	1.345 (4)	C9—C11	1.401 (5)
O2—N2	1.415 (4)	C10—C12	1.465 (5)
N2—C11	1.295 (5)	C11—H11A	0.9300
F2—C7	1.312 (4)	C12—H12A	0.9600
C2—C3	1.370 (6)	C12—H12B	0.9600
C2—H2B	0.9300	C12—H12C	0.9600
F3—C7	1.302 (5)
C8—N1—C5	121.8 (3)	F3—C7—F1	106.5 (4)
C8—N1—H1A	119.1	F2—C7—F1	104.9 (4)
C5—N1—H1A	119.1	F3—C7—C6	114.2 (4)
C2—C1—C6	121.1 (4)	F2—C7—C6	112.7 (4)
C2—C1—H1B	119.5	F1—C7—C6	112.2 (3)
C6—C1—H1B	119.5	O1—C8—N1	122.2 (3)
C10—O2—N2	108.9 (3)	O1—C8—C9	121.8 (3)
C11—N2—O2	105.0 (3)	N1—C8—C9	115.9 (3)
C1—C2—C3	120.3 (4)	C10—C9—C11	105.2 (3)
C1—C2—H2B	119.9	C10—C9—C8	126.8 (3)
C3—C2—H2B	119.9	C11—C9—C8	128.0 (4)
C2—C3—C4	119.5 (4)	O2—C10—C9	108.7 (3)
C2—C3—H3A	120.3	O2—C10—C12	116.3 (4)
C4—C3—H3A	120.3	C9—C10—C12	135.0 (4)
C3—C4—C5	120.4 (3)	N2—C11—C9	112.2 (4)
C3—C4—H4A	119.8	N2—C11—H11A	123.9
C5—C4—H4A	119.8	C9—C11—H11A	123.9
C4—C5—C6	119.5 (3)	C10—C12—H12A	109.5
C4—C5—N1	118.9 (3)	C10—C12—H12B	109.5
C6—C5—N1	121.6 (3)	H12A—C12—H12B	109.5
C1—C6—C5	119.2 (4)	C10—C12—H12C	109.5
C1—C6—C7	119.2 (3)	H12A—C12—H12C	109.5
C5—C6—C7	121.6 (3)	H12B—C12—H12C	109.5
F3—C7—F2	105.6 (3)
C10—O2—N2—C11	−1.6 (4)	C1—C6—C7—F1	−123.8 (4)
C6—C1—C2—C3	−0.7 (7)	C5—C6—C7—F1	52.7 (5)
C1—C2—C3—C4	1.0 (7)	C5—N1—C8—O1	0.1 (5)
C2—C3—C4—C5	0.2 (6)	C5—N1—C8—C9	−179.3 (3)
C3—C4—C5—C6	−1.7 (6)	O1—C8—C9—C10	16.6 (5)
C3—C4—C5—N1	177.1 (4)	N1—C8—C9—C10	−163.9 (3)
C8—N1—C5—C4	−100.9 (4)	O1—C8—C9—C11	−160.1 (3)
C8—N1—C5—C6	77.9 (4)	N1—C8—C9—C11	19.4 (5)
C2—C1—C6—C5	−0.8 (6)	N2—O2—C10—C9	1.4 (4)
C2—C1—C6—C7	175.8 (4)	N2—O2—C10—C12	−179.2 (3)
C4—C5—C6—C1	2.0 (5)	C11—C9—C10—O2	−0.7 (4)
N1—C5—C6—C1	−176.7 (3)	C8—C9—C10—O2	−177.9 (3)
C4—C5—C6—C7	−174.5 (4)	C11—C9—C10—C12	−180.0 (4)
N1—C5—C6—C7	6.7 (5)	C8—C9—C10—C12	2.8 (6)
C1—C6—C7—F3	114.9 (4)	O2—N2—C11—C9	1.2 (4)
C5—C6—C7—F3	−68.6 (5)	C10—C9—C11—N2	−0.4 (4)
C1—C6—C7—F2	−5.7 (6)	C8—C9—C11—N2	176.9 (3)
C5—C6—C7—F2	170.9 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1i	0.86	2.13	2.855 (3)	142

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1i	0.86	2.13	2.855 (3)	142

Symmetry code: (i) .