N-(2,6-Dichloro-phen-yl)-5-methyl-1,2-oxazole-4-carboxamide monohydrate.

In the title compound, C(11)H(8)Cl(2)N(2)O(2)·H(2)O, the dihedral angle between the benzene and isoxazole rings is 59.10 (7)°. In the crystal, the components are linked by N-H⋯O and O-H⋯O hydrogen bonds into a three-dimensional network. The crystal structure is further stabilized by π-π stacking inter-actions [centroid-centroid distance = 3.804 (2) Å].

Related literature

The title compound was synthesised as a new and potent immunomodulating leflunomide {systematic name: 5-methyl-N-[4-(trifluoro­meth­yl)phen­yl]-isoxazole-4-carboxamide} ana­log (Huang et al., 2003 ▶). For the application of leflunomide in the treatment of rheumatoid arthritis, see: Shaw et al. (2011 ▶); Schattenkirchner et al. (2000 ▶).

Experimental

Crystal data

C11H8Cl2N2O2·H2O

M = 289.11

Orthorhombic,

a = 12.047 (2) Å

b = 8.2290 (16) Å

c = 13.086 (3) Å

V = 1297.3 (4) Å3

Z = 4

Mo Kα radiation

μ = 0.50 mm−1

T = 293 K

0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

Absorption correction: ψ scan (SADABS; Sheldrick, 1996 ▶) T min = 0.864, T max = 0.952

2333 measured reflections

2333 independent reflections

1906 reflections with I > 2σ(I)

3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.045

wR(F 2) = 0.118

S = 1.00

2333 reflections

164 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.19 e Å−3

Δρmin = −0.18 e Å−3

Absolute structure: Flack (1983 ▶), 1107 Friedel pairs

Flack parameter: 0.04 (9)

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/S1600536811044734/gw2111sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811044734/gw2111Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811044734/gw2111Isup3.cml

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

C11H8Cl2N2O2·H2O	Dx = 1.480 Mg m−3
Mr = 289.11	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21	Cell parameters from 25 reflections
a = 12.047 (2) Å	θ = 9–13°
b = 8.2290 (16) Å	µ = 0.50 mm−1
c = 13.086 (3) Å	T = 293 K
V = 1297.3 (4) Å3	Block, white
Z = 4	0.30 × 0.20 × 0.10 mm
F(000) = 592

Enraf–Nonius CAD-4 diffractometer	1906 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
graphite	θmax = 25.4°, θmin = 3.0°
ω/2θ scans	h = 0→14
Absorption correction: ψ scan (SADABS; Sheldrick, 1996)	k = −9→0
Tmin = 0.864, Tmax = 0.952	l = −15→15
2333 measured reflections	3 standard reflections every 200 reflections
2333 independent reflections	intensity decay: 1%

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.045	w = 1/[σ2(Fo2) + (0.073P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.118	(Δ/σ)max < 0.001
S = 1.00	Δρmax = 0.19 e Å−3
2333 reflections	Δρmin = −0.18 e Å−3
164 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraint	Extinction coefficient: 0.038 (3)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 1107 Friedel pairs
Secondary atom site location: difference Fourier map	Flack parameter: 0.04 (9)

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
Cl1	0.34861 (10)	−0.10973 (15)	0.99733 (8)	0.0766 (4)
N1	0.4813 (2)	0.0638 (3)	0.8429 (2)	0.0426 (6)
H1A	0.5009	0.1294	0.8907	0.051*
O1	0.5393 (2)	−0.1120 (4)	0.7213 (2)	0.0572 (7)
C1	0.2951 (3)	−0.0268 (5)	0.8868 (3)	0.0482 (9)
Cl2	0.40753 (8)	0.20917 (15)	0.64182 (8)	0.0679 (3)
N2	0.8178 (3)	0.0689 (5)	0.9349 (3)	0.0695 (10)
C2	0.1817 (3)	−0.0353 (5)	0.8670 (4)	0.0654 (12)
H2B	0.1340	−0.0829	0.9142	0.078*
O2	0.85611 (19)	−0.0172 (4)	0.8485 (2)	0.0633 (8)
C3	0.1411 (3)	0.0275 (6)	0.7769 (4)	0.0689 (12)
H3A	0.0654	0.0213	0.7631	0.083*
C4	0.2092 (3)	0.0973 (5)	0.7089 (4)	0.0605 (10)
H4A	0.1807	0.1369	0.6478	0.073*
C5	0.3222 (3)	0.1113 (4)	0.7288 (3)	0.0479 (8)
C6	0.3673 (3)	0.0494 (4)	0.8180 (3)	0.0405 (7)
C7	0.5598 (3)	−0.0226 (4)	0.7937 (2)	0.0400 (7)
C8	0.6743 (3)	−0.0017 (4)	0.8333 (3)	0.0447 (8)
C9	0.7686 (3)	−0.0582 (4)	0.7899 (3)	0.0474 (8)
C10	0.7108 (3)	0.0774 (5)	0.9239 (3)	0.0579 (10)
H10A	0.6636	0.1291	0.9698	0.069*
C11	0.7943 (3)	−0.1487 (6)	0.6956 (3)	0.0623 (11)
H11A	0.8728	−0.1679	0.6919	0.094*
H11B	0.7712	−0.0863	0.6374	0.094*
H11C	0.7558	−0.2508	0.6962	0.094*
OW	0.9991 (2)	0.2436 (4)	1.02747 (19)	0.0577 (7)
HWA	0.9856	0.1441	1.0398	0.069*
HWB	0.9882	0.3005	1.0807	0.069*

	U11	U22	U33	U12	U13	U23
Cl1	0.0827 (8)	0.0957 (8)	0.0513 (6)	−0.0078 (6)	0.0037 (5)	0.0203 (6)
N1	0.0319 (13)	0.0569 (17)	0.0391 (14)	0.0007 (12)	−0.0025 (12)	−0.0103 (13)
O1	0.0431 (13)	0.0740 (18)	0.0546 (16)	0.0039 (13)	−0.0028 (12)	−0.0211 (14)
C1	0.045 (2)	0.055 (2)	0.0453 (19)	0.0018 (16)	0.0044 (16)	0.0008 (17)
Cl2	0.0573 (6)	0.0872 (7)	0.0594 (6)	−0.0051 (5)	0.0004 (5)	0.0229 (5)
N2	0.0433 (19)	0.087 (3)	0.078 (3)	−0.0051 (17)	−0.0078 (16)	−0.007 (2)
C2	0.041 (2)	0.069 (3)	0.086 (3)	−0.0103 (18)	0.016 (2)	−0.004 (2)
O2	0.0347 (14)	0.080 (2)	0.0756 (19)	0.0004 (12)	0.0016 (14)	0.0016 (16)
C3	0.035 (2)	0.077 (3)	0.094 (4)	−0.001 (2)	−0.008 (2)	−0.001 (3)
C4	0.039 (2)	0.070 (3)	0.073 (3)	0.0044 (19)	−0.0099 (19)	0.005 (2)
C5	0.0416 (18)	0.051 (2)	0.051 (2)	−0.0009 (16)	−0.0008 (15)	−0.0015 (17)
C6	0.0289 (15)	0.0504 (18)	0.0423 (17)	0.0050 (13)	−0.0009 (13)	−0.0030 (14)
C7	0.0285 (16)	0.0519 (19)	0.0397 (18)	0.0010 (14)	0.0024 (13)	0.0005 (16)
C8	0.0377 (17)	0.0455 (19)	0.051 (2)	0.0009 (14)	0.0019 (16)	0.0037 (17)
C9	0.0363 (19)	0.050 (2)	0.055 (2)	−0.0010 (16)	0.0024 (16)	0.0094 (17)
C10	0.038 (2)	0.077 (3)	0.059 (2)	−0.0035 (18)	−0.0050 (18)	−0.007 (2)
C11	0.053 (2)	0.071 (3)	0.063 (2)	0.0140 (19)	0.010 (2)	0.001 (2)
OW	0.0544 (14)	0.0756 (18)	0.0430 (12)	−0.0051 (13)	0.0021 (12)	−0.0017 (12)

Cl1—C1	1.724 (4)	C3—H3A	0.9300
N1—C7	1.347 (4)	C4—C5	1.391 (5)
N1—C6	1.416 (4)	C4—H4A	0.9300
N1—H1A	0.8600	C5—C6	1.384 (5)
O1—C7	1.224 (4)	C7—C8	1.483 (4)
C1—C2	1.392 (5)	C8—C9	1.352 (5)
C1—C6	1.400 (5)	C8—C10	1.423 (5)
Cl2—C5	1.733 (4)	C9—C11	1.474 (5)
N2—C10	1.299 (5)	C10—H10A	0.9300
N2—O2	1.412 (5)	C11—H11A	0.9600
C2—C3	1.378 (6)	C11—H11B	0.9600
C2—H2B	0.9300	C11—H11C	0.9600
O2—C9	1.347 (4)	OW—HWA	0.8500
C3—C4	1.340 (6)	OW—HWB	0.8499
C7—N1—C6	121.8 (3)	C5—C6—N1	123.0 (3)
C7—N1—H1A	119.1	C1—C6—N1	119.4 (3)
C6—N1—H1A	119.1	O1—C7—N1	123.0 (3)
C2—C1—C6	120.8 (4)	O1—C7—C8	121.9 (3)
C2—C1—Cl1	120.2 (3)	N1—C7—C8	115.2 (3)
C6—C1—Cl1	119.0 (3)	C9—C8—C10	104.4 (3)
C10—N2—O2	105.2 (3)	C9—C8—C7	126.5 (3)
C3—C2—C1	119.3 (4)	C10—C8—C7	129.2 (3)
C3—C2—H2B	120.4	O2—C9—C8	109.4 (3)
C1—C2—H2B	120.4	O2—C9—C11	116.0 (3)
C9—O2—N2	109.0 (3)	C8—C9—C11	134.6 (4)
C4—C3—C2	120.7 (4)	N2—C10—C8	112.0 (4)
C4—C3—H3A	119.6	N2—C10—H10A	124.0
C2—C3—H3A	119.6	C8—C10—H10A	124.0
C3—C4—C5	120.7 (4)	C9—C11—H11A	109.5
C3—C4—H4A	119.6	C9—C11—H11B	109.5
C5—C4—H4A	119.6	H11A—C11—H11B	109.5
C6—C5—C4	120.8 (4)	C9—C11—H11C	109.5
C6—C5—Cl2	119.5 (3)	H11A—C11—H11C	109.5
C4—C5—Cl2	119.7 (3)	H11B—C11—H11C	109.5
C5—C6—C1	117.6 (3)	HWA—OW—HWB	110.3
C6—C1—C2—C3	2.1 (6)	C7—N1—C6—C1	109.6 (4)
Cl1—C1—C2—C3	−178.1 (4)	C6—N1—C7—O1	4.0 (5)
C10—N2—O2—C9	−0.8 (4)	C6—N1—C7—C8	−176.2 (3)
C1—C2—C3—C4	−0.5 (7)	O1—C7—C8—C9	8.6 (6)
C2—C3—C4—C5	−1.5 (7)	N1—C7—C8—C9	−171.2 (3)
C3—C4—C5—C6	1.8 (6)	O1—C7—C8—C10	−170.2 (4)
C3—C4—C5—Cl2	−177.5 (4)	N1—C7—C8—C10	9.9 (6)
C4—C5—C6—C1	−0.2 (5)	N2—O2—C9—C8	0.6 (4)
Cl2—C5—C6—C1	179.1 (3)	N2—O2—C9—C11	179.7 (3)
C4—C5—C6—N1	−178.5 (3)	C10—C8—C9—O2	−0.2 (4)
Cl2—C5—C6—N1	0.8 (5)	C7—C8—C9—O2	−179.2 (3)
C2—C1—C6—C5	−1.8 (5)	C10—C8—C9—C11	−179.0 (4)
Cl1—C1—C6—C5	178.5 (3)	C7—C8—C9—C11	1.9 (7)
C2—C1—C6—N1	176.6 (3)	O2—N2—C10—C8	0.7 (5)
Cl1—C1—C6—N1	−3.1 (5)	C9—C8—C10—N2	−0.3 (5)
C7—N1—C6—C5	−72.1 (4)	C7—C8—C10—N2	178.7 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···OWi	0.86	2.07	2.897 (4)	161.
OW—HWB···O1ii	0.85	2.00	2.839 (3)	168.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯OWi	0.86	2.07	2.897 (4)	161
OW—HWB⋯O1ii	0.85	2.00	2.839 (3)	168

Symmetry codes: (i) ; (ii) .