organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

5-Methyl-N-(1,3-thia­zol-2-yl)isoxazole-4-carboxamide

aState Key Laboratory of Materials-Oriented Chemical Engineering, School of Pharmaceutical Sciences, Nanjing University of Technology, Xinmofan Road No.5 Nanjing, Nanjing 210009, People's Republic of China
*Correspondence e-mail: dcwang@njut.edu.cn

(Received 22 April 2013; accepted 3 May 2013; online 11 May 2013)

In the title compound, C8H7N3O2S, the dihedral angle between the thia­zol and isoxazole rings is 34.08 (13)°. In the crystal, the mol­ecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers, and C—H⋯O inter­actions, resulting in chains along the b-axis direction.

Related literature

For background to isoxazole-containing drugs, see: Shaw et al. (2011[Shaw, J. J., Chen, B., Wooley, P., Palfey, B., Lee, A. R., Huang, W. H. & Zeng, D. (2011). Am. J. Biomed. Sci. 3, 218-227.]); Schattenkirchner (2000[Schattenkirchner, M. (2000). Immunopharmacology, 47, 291-298.]); Huang et al. (2003[Huang, W. H., Yang, C. L., Lee, A. R. & Chiu, H. F. (2003). Chem. Pharm. Bull. 51, 313-314.]). For the crystal structure of a related compound, see: Wang et al. (2011[Wang, D.-C., Huang, L.-C., Liu, H.-Q., Peng, Y.-R. & Song, J.-S. (2011). Acta Cryst. E67, o3207.]).

[Scheme 1]

Experimental

Crystal data
  • C8H7N3O2S

  • Mr = 209.23

  • Monoclinic, P 21 /c

  • a = 8.8460 (18) Å

  • b = 10.742 (2) Å

  • c = 10.024 (2) Å

  • β = 107.27 (3)°

  • V = 909.6 (3) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.33 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[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.907, Tmax = 0.968

  • 3462 measured reflections

  • 1676 independent reflections

  • 1298 reflections with I > 2σ(I)

  • Rint = 0.060

  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement
  • R[F2 > 2σ(F2)] = 0.051

  • wR(F2) = 0.152

  • S = 1.00

  • 1676 reflections

  • 128 parameters

  • H-atom parameters constrained

  • Δρmax = 0.38 e Å−3

  • Δρmin = −0.34 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2A⋯N1i 0.86 2.14 2.970 (3) 162
C6—H6A⋯O1ii 0.93 2.36 3.287 (4) 171
Symmetry codes: (i) -x+1, -y, -z+1; (ii) [-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}].

Data collection: CAD-4 EXPRESS (Enraf–Nonius,1994)[Enraf-Nonius (1994). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]; cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information


Comment top

Leflunomide is one of the most effective isoxazole-containing disease-modifying drugs for treating rheumatoid arthritis (Shaw et al., 2011; Schattenkirchner, 2000). Many leflunomide analogs have been synthesized which exhibit potent immunomodulating effect (Huang et al., 2003). In our previous work, some anolog has been sucessfully sythesized (Wang et al., 2011). A new leflunomide analog, N-5-methyl-N-(thiazol-2-yl)isoxazole-4-carboxamide, was synthesized in our laboratory as a novel and potent immunomodulating drug. In this paper we report its crystal structure.

The bond distances and angles in the title compound (Fig. 1) agree very well with the corresponding bond distances and angles reported in a closely related compound (Wang et al., 2011). The dihedral angle between the C1/C2/N1/C3/S thiazol ring and the C5/C6/N3/O2/C7 isoxazole ring is 34.08 (13) °. In the crystal, the molecules are linked by N—H···N hydrogen bonds forming diamers about inversion centers and C—H···O hydrogen bonding interactions resulting in chains lying along the b-axis (Tab. 1 & Fig. 2).

Related literature top

For background to isoxazole-containing drugs, see: Shaw et al. (2011); Schattenkirchner (2000); Huang et al. (2003). For the crystal structure of a related compound, see: Wang et al. (2011).

Experimental top

A solution of 5-methylisoxazole-4-carboxylic acid chloride (7.3 g, 0.05 mol) in acetonitrile (20 ml) was added dropwise, while stirring, to thiazol-2-amine (12.9 g, 0.10 mol) dissolved in acetonitrile (150 ml), at room temperature. After stirring for 40 more minutes, the precipitated 5-methyl-N-(thiazol-2-yl)isoxazole-4-carboxamide was filtered off and washed with 100 ml portions of acetonitrile, and the combined filtrates were concentrated under reduced pressure yielded the title compouind as yellow crytalline product(Yield: 8.2 g; 60%). Crystals suitable for X-ray diffraction were obtained by slow evaporation of toluene solution.

Refinement top

All H atoms were placed geometrically at the distances of 0.93–0.96 Å for C—H and 0.86 Å for N—H and included in the refinement in riding motion approximation with Uiso(H) = 1.2 or 1.5Ueq of the carrier atom.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius,1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius,1994); 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: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 35% probability level. H atoms are presented as small spheres of arbitrary radius.
[Figure 2] Fig. 2. A view of the N—H···N and C—H···O hydrogen bonds (dotted lines) in the crystal structure of the title compound. H atoms non-participating in hydrogen-bonding were omitted for clarity.
5-Methyl-N-(1,3-thiazol-2-yl)isoxazole-4-carboxamide top
Crystal data top
C8H7N3O2SF(000) = 432
Mr = 209.23Dx = 1.528 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 8.8460 (18) Åθ = 10–13°
b = 10.742 (2) ŵ = 0.33 mm1
c = 10.024 (2) ÅT = 293 K
β = 107.27 (3)°Block, yellow
V = 909.6 (3) Å30.30 × 0.20 × 0.10 mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer
1298 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.060
Graphite monochromatorθmax = 25.4°, θmin = 2.4°
ω/2θ scansh = 010
Absorption correction: ψ scan
(North et al., 1968)
k = 1212
Tmin = 0.907, Tmax = 0.968l = 1211
3462 measured reflections3 standard reflections every 200 reflections
1676 independent reflections intensity decay: 1%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.051H-atom parameters constrained
wR(F2) = 0.152 w = 1/[σ2(Fo2) + (0.1P)2 + 0.180P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
1676 reflectionsΔρmax = 0.38 e Å3
128 parametersΔρmin = 0.34 e Å3
0 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.021 (5)
Crystal data top
C8H7N3O2SV = 909.6 (3) Å3
Mr = 209.23Z = 4
Monoclinic, P21/cMo Kα radiation
a = 8.8460 (18) ŵ = 0.33 mm1
b = 10.742 (2) ÅT = 293 K
c = 10.024 (2) Å0.30 × 0.20 × 0.10 mm
β = 107.27 (3)°
Data collection top
Enraf–Nonius CAD-4
diffractometer
1298 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)
Rint = 0.060
Tmin = 0.907, Tmax = 0.9683 standard reflections every 200 reflections
3462 measured reflections intensity decay: 1%
1676 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0510 restraints
wR(F2) = 0.152H-atom parameters constrained
S = 1.00Δρmax = 0.38 e Å3
1676 reflectionsΔρmin = 0.34 e Å3
128 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S0.27245 (9)0.30807 (7)0.46506 (9)0.0578 (3)
O10.5024 (2)0.36916 (17)0.3546 (2)0.0517 (6)
N10.3255 (3)0.0745 (2)0.5154 (2)0.0463 (6)
C10.1512 (4)0.2266 (3)0.5378 (4)0.0629 (9)
H1A0.06540.26050.56070.075*
O20.8730 (2)0.2660 (2)0.1941 (2)0.0532 (6)
N20.5011 (2)0.16438 (19)0.4088 (2)0.0390 (5)
H2A0.54750.09380.41060.047*
C20.1958 (3)0.1078 (3)0.5573 (3)0.0558 (8)
H2B0.14260.05070.59690.067*
N30.8148 (3)0.1439 (3)0.1552 (3)0.0569 (7)
C30.3761 (3)0.1719 (2)0.4640 (3)0.0371 (6)
C40.5547 (3)0.2644 (2)0.3512 (3)0.0358 (5)
C50.6762 (3)0.2373 (2)0.2825 (2)0.0349 (5)
C60.6993 (3)0.1306 (3)0.2088 (3)0.0459 (6)
H6A0.63840.05870.19980.055*
C70.7873 (3)0.3192 (2)0.2679 (3)0.0395 (6)
C80.8309 (4)0.4479 (3)0.3178 (3)0.0546 (7)
H8A0.91690.47610.28550.082*
H8B0.86260.44930.41800.082*
H8C0.74130.50180.28210.082*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S0.0540 (5)0.0548 (5)0.0796 (6)0.0179 (3)0.0427 (4)0.0136 (4)
O10.0510 (12)0.0391 (10)0.0740 (14)0.0077 (8)0.0325 (10)0.0069 (9)
N10.0408 (12)0.0511 (13)0.0544 (13)0.0009 (10)0.0255 (10)0.0066 (11)
C10.0458 (17)0.081 (2)0.076 (2)0.0194 (16)0.0384 (16)0.0196 (18)
O20.0447 (11)0.0687 (13)0.0561 (12)0.0065 (9)0.0302 (9)0.0037 (10)
N20.0395 (11)0.0359 (10)0.0499 (12)0.0032 (9)0.0260 (10)0.0014 (9)
C20.0403 (15)0.076 (2)0.0595 (17)0.0020 (14)0.0282 (13)0.0169 (15)
N30.0598 (15)0.0630 (15)0.0570 (15)0.0005 (13)0.0312 (12)0.0131 (12)
C30.0320 (12)0.0434 (14)0.0378 (13)0.0024 (10)0.0133 (10)0.0014 (10)
C40.0314 (12)0.0372 (12)0.0410 (13)0.0014 (10)0.0144 (10)0.0008 (10)
C50.0329 (12)0.0382 (13)0.0356 (12)0.0004 (10)0.0132 (10)0.0014 (10)
C60.0498 (15)0.0436 (14)0.0482 (15)0.0031 (12)0.0207 (12)0.0060 (12)
C70.0358 (13)0.0501 (15)0.0351 (13)0.0006 (11)0.0143 (11)0.0039 (10)
C80.0531 (17)0.0512 (16)0.0616 (18)0.0123 (13)0.0203 (14)0.0034 (14)
Geometric parameters (Å, º) top
S—C11.707 (3)N2—H2A0.8600
S—C31.729 (2)C2—H2B0.9300
O1—C41.222 (3)N3—C61.296 (4)
N1—C31.303 (3)C4—C51.468 (3)
N1—C21.381 (3)C5—C71.358 (4)
C1—C21.332 (5)C5—C61.411 (4)
C1—H1A0.9300C6—H6A0.9300
O2—C71.334 (3)C7—C81.483 (4)
O2—N31.420 (3)C8—H8A0.9600
N2—C41.369 (3)C8—H8B0.9600
N2—C31.377 (3)C8—H8C0.9600
C1—S—C388.31 (14)O1—C4—C5122.1 (2)
C3—N1—C2109.1 (2)N2—C4—C5115.9 (2)
C2—C1—S111.0 (2)C7—C5—C6104.4 (2)
C2—C1—H1A124.5C7—C5—C4125.2 (2)
S—C1—H1A124.5C6—C5—C4130.3 (2)
C7—O2—N3109.2 (2)N3—C6—C5112.4 (3)
C4—N2—C3122.9 (2)N3—C6—H6A123.8
C4—N2—H2A118.5C5—C6—H6A123.8
C3—N2—H2A118.5O2—C7—C5109.3 (2)
C1—C2—N1116.1 (3)O2—C7—C8117.0 (2)
C1—C2—H2B122.0C5—C7—C8133.7 (3)
N1—C2—H2B122.0C7—C8—H8A109.5
C6—N3—O2104.7 (2)C7—C8—H8B109.5
N1—C3—N2121.6 (2)H8A—C8—H8B109.5
N1—C3—S115.55 (19)C7—C8—H8C109.5
N2—C3—S122.86 (19)H8A—C8—H8C109.5
O1—C4—N2122.0 (2)H8B—C8—H8C109.5
C3—S—C1—C20.8 (3)N2—C4—C5—C7152.8 (2)
S—C1—C2—N10.6 (4)O1—C4—C5—C6145.8 (3)
C3—N1—C2—C10.1 (4)N2—C4—C5—C632.8 (4)
C7—O2—N3—C60.6 (3)O2—N3—C6—C50.1 (3)
C2—N1—C3—N2177.4 (2)C7—C5—C6—N30.8 (3)
C2—N1—C3—S0.7 (3)C4—C5—C6—N3176.1 (3)
C4—N2—C3—N1178.5 (2)N3—O2—C7—C51.2 (3)
C4—N2—C3—S0.6 (3)N3—O2—C7—C8179.9 (2)
C1—S—C3—N10.9 (2)C6—C5—C7—O21.2 (3)
C1—S—C3—N2177.2 (2)C4—C5—C7—O2176.7 (2)
C3—N2—C4—O15.7 (4)C6—C5—C7—C8179.8 (3)
C3—N2—C4—C5173.0 (2)C4—C5—C7—C84.6 (5)
O1—C4—C5—C728.5 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···N1i0.862.142.970 (3)162
C6—H6A···O1ii0.932.363.287 (4)171
Symmetry codes: (i) x+1, y, z+1; (ii) x+1, y1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC8H7N3O2S
Mr209.23
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)8.8460 (18), 10.742 (2), 10.024 (2)
β (°) 107.27 (3)
V3)909.6 (3)
Z4
Radiation typeMo Kα
µ (mm1)0.33
Crystal size (mm)0.30 × 0.20 × 0.10
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.907, 0.968
No. of measured, independent and
observed [I > 2σ(I)] reflections
3462, 1676, 1298
Rint0.060
(sin θ/λ)max1)0.604
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.051, 0.152, 1.00
No. of reflections1676
No. of parameters128
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.38, 0.34

Computer programs: CAD-4 EXPRESS (Enraf–Nonius,1994), XCAD4 (Harms & Wocadlo,1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···N1i0.862.142.970 (3)162
C6—H6A···O1ii0.932.363.287 (4)171
Symmetry codes: (i) x+1, y, z+1; (ii) x+1, y1/2, z+1/2.
 

References

First citationEnraf–Nonius (1994). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.
First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.
First citationHuang, W. H., Yang, C. L., Lee, A. R. & Chiu, H. F. (2003). Chem. Pharm. Bull. 51, 313–314.  CrossRef PubMed CAS
First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science
First citationSchattenkirchner, M. (2000). Immunopharmacology, 47, 291–298.  Web of Science CrossRef PubMed CAS
First citationShaw, J. J., Chen, B., Wooley, P., Palfey, B., Lee, A. R., Huang, W. H. & Zeng, D. (2011). Am. J. Biomed. Sci. 3, 218–227.  CrossRef CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals
First citationWang, D.-C., Huang, L.-C., Liu, H.-Q., Peng, Y.-R. & Song, J.-S. (2011). Acta Cryst. E67, o3207.  Web of Science CSD CrossRef IUCr Journals

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds