N-(4-Chloro-2-nitro-phen-yl)-5-methyl-isoxazole-4-carboxamide.

In the title compound, C(11)H(8)ClN(3)O(4), the dihedral angle between benzene and isoxazole rings is 9.92 (1) °. The nitro group is almost coplanar with the benzene ring with an O-N-C-C torsion angle of 8.4 (3)°. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond, closing a six-membered ring.

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 ▶). The title compound was synthesized as an immunomodulating leflunomide analog; for another immunomodulating leflunomide analog, see: Huang et al. (2003 ▶).

Experimental

Crystal data

C11H8ClN3O4

M = 281.65

Monoclinic,

a = 5.3870 (11) Å

b = 23.537 (5) Å

c = 9.4600 (19) Å

β = 99.86 (3)°

V = 1181.8 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.34 mm−1

T = 293 K

0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

Absorption correction: ψ scan (North et al., 1968 ▶) T min = 0.905, T max = 0.967

4645 measured reflections

2121 independent reflections

1558 reflections with I > 2σ(I)

R int = 0.044

3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.042

wR(F 2) = 0.143

S = 1.02

2121 reflections

174 parameters

H-atom parameters constrained

Δρmax = 0.18 e Å−3

Δρmin = −0.22 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/S1600536811047994/ld2035sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811047994/ld2035Isup2.hkl

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

C11H8ClN3O4	F(000) = 576
Mr = 281.65	Dx = 1.583 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 5.3870 (11) Å	θ = 9–13°
b = 23.537 (5) Å	µ = 0.34 mm−1
c = 9.4600 (19) Å	T = 293 K
β = 99.86 (3)°	Block, white
V = 1181.8 (4) Å3	0.30 × 0.20 × 0.10 mm
Z = 4

Enraf–Nonius CAD-4 diffractometer	1558 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.044
graphite	θmax = 25.2°, θmin = 1.7°
ω/2θ scans	h = 0→6
Absorption correction: ψ scan (North et al., 1968)	k = −28→28
Tmin = 0.905, Tmax = 0.967	l = −11→11
4645 measured reflections	3 standard reflections every 200 reflections
2121 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)] = 0.042	H-atom parameters constrained
wR(F2) = 0.143	w = 1/[σ2(Fo2) + (0.090P)2] where P = (Fo2 + 2Fc2)/3
S = 1.02	(Δ/σ)max < 0.001
2121 reflections	Δρmax = 0.18 e Å−3
174 parameters	Δρmin = −0.22 e Å−3
0 restraints	Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.010 (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
Cl	1.14810 (15)	0.27507 (3)	0.51209 (9)	0.0712 (3)
N1	0.5249 (4)	0.33771 (10)	0.8313 (2)	0.0534 (6)
C1	0.8613 (5)	0.42551 (11)	0.5906 (3)	0.0476 (6)
H1A	0.8768	0.4628	0.5606	0.057*
O1	0.5463 (5)	0.28905 (9)	0.8742 (3)	0.0868 (8)
O2	0.3751 (4)	0.37087 (9)	0.8716 (2)	0.0611 (5)
C2	0.9988 (5)	0.38350 (11)	0.5390 (3)	0.0507 (6)
H2A	1.1070	0.3927	0.4757	0.061*
N2	0.5564 (4)	0.45566 (9)	0.7398 (2)	0.0469 (5)
H2B	0.4559	0.4440	0.7951	0.056*
N3	0.0876 (5)	0.56302 (12)	0.9317 (3)	0.0656 (7)
O3	0.6784 (4)	0.53680 (8)	0.6379 (2)	0.0586 (5)
C3	0.9774 (5)	0.32777 (11)	0.5806 (3)	0.0475 (6)
O4	0.1878 (4)	0.61421 (9)	0.8857 (2)	0.0658 (6)
C4	0.8225 (5)	0.31427 (11)	0.6765 (3)	0.0501 (6)
H4A	0.8099	0.2768	0.7060	0.060*
C5	0.6850 (5)	0.35645 (10)	0.7294 (2)	0.0434 (6)
C6	0.6978 (4)	0.41348 (10)	0.6875 (2)	0.0406 (5)
C7	0.5541 (5)	0.51330 (10)	0.7158 (2)	0.0433 (6)
C8	0.3842 (4)	0.54381 (11)	0.7965 (2)	0.0444 (6)
C9	0.2056 (5)	0.52340 (12)	0.8774 (3)	0.0555 (7)
H9A	0.1763	0.4850	0.8901	0.067*
C10	0.3644 (5)	0.60153 (11)	0.8058 (3)	0.0522 (7)
C11	0.4990 (7)	0.65000 (12)	0.7545 (4)	0.0731 (9)
H11A	0.4181	0.6848	0.7737	0.110*
H11B	0.4958	0.6464	0.6532	0.110*
H11C	0.6705	0.6503	0.8035	0.110*

	U11	U22	U33	U12	U13	U23
Cl	0.0730 (5)	0.0583 (5)	0.0884 (6)	0.0099 (4)	0.0308 (4)	−0.0103 (4)
N1	0.0613 (14)	0.0467 (13)	0.0561 (12)	−0.0111 (11)	0.0211 (11)	0.0031 (10)
C1	0.0504 (14)	0.0448 (14)	0.0502 (13)	−0.0018 (12)	0.0158 (11)	0.0077 (11)
O1	0.121 (2)	0.0491 (13)	0.1062 (18)	−0.0060 (12)	0.0648 (16)	0.0174 (11)
O2	0.0612 (12)	0.0607 (12)	0.0687 (12)	−0.0006 (10)	0.0320 (10)	0.0094 (9)
C2	0.0515 (15)	0.0515 (16)	0.0530 (14)	−0.0043 (12)	0.0199 (12)	0.0013 (11)
N2	0.0524 (12)	0.0432 (12)	0.0493 (11)	−0.0006 (9)	0.0210 (10)	0.0049 (9)
N3	0.0568 (14)	0.0717 (18)	0.0722 (15)	0.0055 (12)	0.0221 (12)	−0.0037 (12)
O3	0.0713 (13)	0.0431 (11)	0.0691 (11)	−0.0025 (9)	0.0335 (10)	0.0048 (8)
C3	0.0449 (13)	0.0467 (15)	0.0520 (14)	0.0003 (11)	0.0112 (11)	−0.0044 (11)
O4	0.0620 (12)	0.0666 (14)	0.0703 (12)	0.0135 (10)	0.0152 (10)	−0.0107 (10)
C4	0.0541 (15)	0.0379 (14)	0.0587 (15)	−0.0039 (11)	0.0107 (13)	0.0027 (11)
C5	0.0434 (13)	0.0429 (14)	0.0454 (13)	−0.0068 (11)	0.0123 (11)	0.0015 (10)
C6	0.0430 (13)	0.0411 (13)	0.0377 (11)	−0.0023 (10)	0.0069 (10)	0.0009 (9)
C7	0.0459 (13)	0.0408 (13)	0.0431 (13)	−0.0014 (11)	0.0069 (11)	0.0017 (10)
C8	0.0433 (13)	0.0464 (15)	0.0428 (12)	0.0017 (11)	0.0053 (10)	−0.0003 (10)
C9	0.0513 (15)	0.0590 (18)	0.0577 (15)	−0.0006 (13)	0.0140 (13)	−0.0033 (13)
C10	0.0521 (15)	0.0536 (16)	0.0506 (14)	0.0088 (13)	0.0080 (12)	−0.0030 (12)
C11	0.089 (2)	0.0471 (17)	0.086 (2)	0.0019 (16)	0.0222 (18)	−0.0016 (15)

Cl—C3	1.734 (3)	O3—C7	1.210 (3)
N1—O1	1.214 (3)	C3—C4	1.371 (4)
N1—O2	1.230 (3)	O4—C10	1.346 (3)
N1—C5	1.467 (3)	C4—C5	1.382 (3)
C1—C2	1.374 (4)	C4—H4A	0.9300
C1—C6	1.405 (3)	C5—C6	1.405 (3)
C1—H1A	0.9300	C7—C8	1.475 (3)
C2—C3	1.380 (4)	C8—C10	1.367 (4)
C2—H2A	0.9300	C8—C9	1.412 (4)
N2—C7	1.375 (3)	C9—H9A	0.9300
N2—C6	1.393 (3)	C10—C11	1.477 (4)
N2—H2B	0.8600	C11—H11A	0.9600
N3—C9	1.285 (3)	C11—H11B	0.9600
N3—O4	1.419 (3)	C11—H11C	0.9600
O1—N1—O2	121.7 (2)	C6—C5—N1	122.4 (2)
O1—N1—C5	118.0 (2)	N2—C6—C1	122.0 (2)
O2—N1—C5	120.3 (2)	N2—C6—C5	121.6 (2)
C2—C1—C6	121.5 (2)	C1—C6—C5	116.3 (2)
C2—C1—H1A	119.2	O3—C7—N2	124.1 (2)
C6—C1—H1A	119.2	O3—C7—C8	123.3 (2)
C1—C2—C3	120.4 (2)	N2—C7—C8	112.5 (2)
C1—C2—H2A	119.8	C10—C8—C9	103.6 (2)
C3—C2—H2A	119.8	C10—C8—C7	125.4 (2)
C7—N2—C6	129.4 (2)	C9—C8—C7	131.0 (2)
C7—N2—H2B	115.3	N3—C9—C8	113.6 (3)
C6—N2—H2B	115.3	N3—C9—H9A	123.2
C9—N3—O4	104.7 (2)	C8—C9—H9A	123.2
C4—C3—C2	119.9 (2)	O4—C10—C8	109.1 (2)
C4—C3—Cl	120.2 (2)	O4—C10—C11	116.5 (3)
C2—C3—Cl	119.8 (2)	C8—C10—C11	134.3 (3)
C10—O4—N3	109.1 (2)	C10—C11—H11A	109.5
C3—C4—C5	119.8 (2)	C10—C11—H11B	109.5
C3—C4—H4A	120.1	H11A—C11—H11B	109.5
C5—C4—H4A	120.1	C10—C11—H11C	109.5
C4—C5—C6	121.9 (2)	H11A—C11—H11C	109.5
C4—C5—N1	115.7 (2)	H11B—C11—H11C	109.5
C6—C1—C2—C3	0.7 (4)	C4—C5—C6—C1	−1.0 (3)
C1—C2—C3—C4	−1.5 (4)	N1—C5—C6—C1	179.2 (2)
C1—C2—C3—Cl	178.87 (19)	C6—N2—C7—O3	2.0 (4)
C9—N3—O4—C10	−0.4 (3)	C6—N2—C7—C8	−177.5 (2)
C2—C3—C4—C5	1.1 (4)	O3—C7—C8—C10	−7.0 (4)
Cl—C3—C4—C5	−179.31 (19)	N2—C7—C8—C10	172.5 (2)
C3—C4—C5—C6	0.2 (4)	O3—C7—C8—C9	171.5 (2)
C3—C4—C5—N1	180.0 (2)	N2—C7—C8—C9	−8.9 (4)
O1—N1—C5—C4	8.4 (3)	O4—N3—C9—C8	0.4 (3)
O2—N1—C5—C4	−171.8 (2)	C10—C8—C9—N3	−0.2 (3)
O1—N1—C5—C6	−171.8 (2)	C7—C8—C9—N3	−179.0 (2)
O2—N1—C5—C6	7.9 (4)	N3—O4—C10—C8	0.3 (3)
C7—N2—C6—C1	−3.1 (4)	N3—O4—C10—C11	−177.0 (2)
C7—N2—C6—C5	176.7 (2)	C9—C8—C10—O4	−0.1 (3)
C2—C1—C6—N2	−179.6 (2)	C7—C8—C10—O4	178.8 (2)
C2—C1—C6—C5	0.6 (3)	C9—C8—C10—C11	176.5 (3)
C4—C5—C6—N2	179.2 (2)	C7—C8—C10—C11	−4.6 (5)
N1—C5—C6—N2	−0.6 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2B···O2	0.86	1.94	2.629 (3)	136.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2B⋯O2	0.86	1.94	2.629 (3)	136