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

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3-(4-Meth­­oxy­phen­yl)-5-methylisoxazole-4-carb­­oxy­lic acid

aDepartment of Studies in Physics, Manasagangotri, University of Mysore, Mysore 570 006, India, bDepartment of Chemistry, Yuvaraja's College, University of Mysore, Mysore 570 005, India, and cSER-CAT, APS, Argonne National Laboratory, Argonne, IL 60439, USA
*Correspondence e-mail: mahendra@physics.uni-mysore.ac.in

(Received 6 February 2013; accepted 9 February 2013; online 16 February 2013)

In the title compound, C12H11NO4, the dihedral angle between the benzene and isoxazole rings is 42.52 (8)°. The carb­oxy­lic acid group is close to being coplanar with the isoxazole ring [dihedral angle = 5.3 (2)°]. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R22(8) loops.

Related literature

For the biological and pharmaceutical properties of isoxazoles, see: Changtam et al. (2010[Changtam, C., Hongmanee, P. & Suksamrarn, A. (2010). Eur. J. Med. Chem. 45, 4446-4457.]); Eddington et al. (2002[Eddington, N. D., Cox, D. S., Roberts, R. R., Butcher, R. J., Edafiogho, I. O., Stables, J. P., Cooke, N., Goodwin, A. M., Smith, C. A. & Scott, K. R. (2002). Eur. J. Med. Chem. 37, 635-648.]); Kozikowski et al. (2008[Kozikowski, A. P., Tapadar, S., Luchini, D. N., Kim, K. H. & Billadeau, D. D. (2008). J. Med. Chem. 51, 4370-4373.]); Lee et al. (2009[Lee, Y., Park, S. M. & Kim, B. H. (2009). Bioorg. Med. Chem. Lett. 19, 1126-1128.]); Panda et al. (2009[Panda, S. S., Chowdary, P. V. R. & Jayashree, B. S. (2009). Indian J. Pharm. Sci. 71, 684-687.]); Shin et al. (2005[Shin, K. D., Lee, M. Y., Shin, D. S., Lee, S., Son, K. H., Koh, S., Paik, Y. K., Kwon, B. M. & Han, D. C. (2005). J. Biol. Chem. 280, 41439-41448.]). For the agrochemical importance of isoxazoles, see: Pinho e Melo (2005[Pinho e Melo, T. M. V. D. (2005). Curr. Org. Chem. 9, 925-958.]7). For a related structure, see: Wolf et al. (1995[Wolf, R., Wong, M. W., Kennard, C. H. L. & Wentrup, C. (1995). J. Am. Chem. Soc. 117, 6789-6790.]).

[Scheme 1]

Experimental

Crystal data
  • C12H11NO4

  • Mr = 233.22

  • Monoclinic, P 21 /c

  • a = 6.4147 (2) Å

  • b = 14.6321 (6) Å

  • c = 11.9911 (5) Å

  • β = 97.220 (2)°

  • V = 1116.57 (7) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.11 mm−1

  • T = 296 K

  • 0.20 × 0.15 × 0.10 mm

Data collection
  • Bruker APEXII CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.979, Tmax = 0.989

  • 11200 measured reflections

  • 2811 independent reflections

  • 2083 reflections with I > 2σ(I)

  • Rint = 0.031

Refinement
  • R[F2 > 2σ(F2)] = 0.045

  • wR(F2) = 0.125

  • S = 1.04

  • 2811 reflections

  • 156 parameters

  • H-atom parameters constrained

  • Δρmax = 0.23 e Å−3

  • Δρmin = −0.22 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O17—H17⋯O16i 0.82 1.79 2.6034 (16) 173
Symmetry code: (i) -x+1, -y+1, -z.

Data collection: APEX2 (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; 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: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

Isoxazoles are five-membered heterocyclic ring structure with one oxygen atom and one nitrogen atom at adjacent positions. Isoxazoles have been widely used as a key building block for biological and pharmaceutical agents such as antiviral (Lee et al., 2009), anti-mycobacterial (Changtam et al., 2010), anti-tumor agents (Kozikowski et al., 2008), anticonvulsant (Eddington et al., 2002), antibacterial (Panda et al., 2009) and anti-HIV activities (Shin et al., 2005). In addition, derivatives of isoxazoles have been also studied as potential agrochemical properties including herbicidal and soil fungicidal activities; thus they have been used as pesticides and insecticides (Pinho e Melo, 2005). With this extensive backround of isoxazole derivatives, we have synthesized the title compound to study its crystal structure. Its potential antitumor activity against the aurora kinase enzyme will be described later.

In the molecular structure of the title compound (Fig. 1), the dihedral angle between the phenyl ring (C3/C4/C5/C6/C7/C8) and isoxazole ring (C9/N10/O11/C12/C14) is 42.52 (8)°. The isoxazole moiety is in syn-periplanar conformation with respect to the phenyl ring, as indicated by the torsion angle value of 0.60 (16)°. The carboxylic acid group of the isoxazole ring is nearly in the same plane (torsion angle = -5.3 (2)°) The bond lengths and angles agree with the observed values and are comparable to a related structure (Wolf et al., 1995). The packing diagram of the molecules viewed down the b axis exhibits inversion dimers (Fig. 2).

Related literature top

For the biological and pharmaceutical properties of isoxazoles, see: Changtam et al. (2010); Eddington et al. (2002); Kozikowski et al. (2008); Lee et al. (2009); Panda et al. (2009); Shin et al. (2005). For the agrochemical importance of isoxazoles, see: Pinho e Melo (20057). For a related structure, see: Wolf et al. (1995).

Experimental top

A mixture of 4-methoxybenzaldehyde oxime (1 g, 0.0066 mmol), ethyl acetoacetate (1.7219 g, 0.0132 mmol), and chloramine-T trihydrate (1.8591 g, 0.0066 mmol) was warmed on a water bath for 3 h. After the reaction, it was cooled to room temperature. The sodium chloride formed in the reaction mixture was filtered off and washed with ethanol. The combined filtrate and washings were evaporated in vacuum. The residual part was extracted into ether (25 ml), washed successively with water (25 ml), 10% sodium hydroxide (25 ml) and saturated brine solution (10 ml). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent yielded the white solid. The isoxazole ester thus formed was refluxed with 10% NaOH for 4 hr. After the reaction, the reaction mass was acidified with dil. HCl to get title compound.

Refinement top

H atoms were placed at idealized positions and allowed to ride on their parent atoms with C–H distances in the range of 0.93 to 0.96 Å; Uiso(H) = 1.2Ueq(carrier atom) for all H atoms.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Perspective diagram of the molecule with 50% probability displacement ellipsoids.
[Figure 2] Fig. 2. Packing diagram of the molecule viewed down the [010].
3-(4-Methoxyphenyl)-5-methylisoxazole-4-carboxylic acid top
Crystal data top
C12H11NO4F(000) = 488
Mr = 233.22Dx = 1.387 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2811 reflections
a = 6.4147 (2) Åθ = 2.2–28.5°
b = 14.6321 (6) ŵ = 0.11 mm1
c = 11.9911 (5) ÅT = 296 K
β = 97.220 (2)°Block, yellow
V = 1116.57 (7) Å30.20 × 0.15 × 0.10 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
2083 reflections with I > 2σ(I)
ω and ϕ scansRint = 0.031
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
θmax = 28.5°, θmin = 2.2°
Tmin = 0.979, Tmax = 0.989h = 88
11200 measured reflectionsk = 1919
2811 independent reflectionsl = 1615
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.125H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0516P)2 + 0.2571P]
where P = (Fo2 + 2Fc2)/3
2811 reflections(Δ/σ)max < 0.001
156 parametersΔρmax = 0.23 e Å3
0 restraintsΔρmin = 0.22 e Å3
Crystal data top
C12H11NO4V = 1116.57 (7) Å3
Mr = 233.22Z = 4
Monoclinic, P21/cMo Kα radiation
a = 6.4147 (2) ŵ = 0.11 mm1
b = 14.6321 (6) ÅT = 296 K
c = 11.9911 (5) Å0.20 × 0.15 × 0.10 mm
β = 97.220 (2)°
Data collection top
Bruker APEXII CCD
diffractometer
2811 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
2083 reflections with I > 2σ(I)
Tmin = 0.979, Tmax = 0.989Rint = 0.031
11200 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0450 restraints
wR(F2) = 0.125H-atom parameters constrained
S = 1.04Δρmax = 0.23 e Å3
2811 reflectionsΔρmin = 0.22 e Å3
156 parameters
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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
O20.2009 (2)0.37793 (11)0.57223 (11)0.0848 (6)
O110.25133 (16)0.31776 (8)0.04335 (11)0.0656 (4)
O160.35249 (16)0.46156 (8)0.09298 (9)0.0573 (3)
O170.30828 (17)0.44090 (8)0.09213 (9)0.0639 (4)
N100.2230 (2)0.31499 (10)0.07570 (13)0.0649 (5)
C10.4132 (4)0.37406 (19)0.62109 (19)0.0930 (9)
C30.1563 (3)0.37111 (12)0.45858 (15)0.0627 (6)
C40.2992 (3)0.34453 (12)0.38735 (15)0.0632 (6)
C50.2364 (2)0.33990 (11)0.27343 (15)0.0595 (5)
C60.0325 (2)0.36064 (9)0.22778 (14)0.0530 (5)
C70.1095 (3)0.38676 (11)0.30087 (16)0.0610 (6)
C80.0479 (3)0.39210 (13)0.41410 (17)0.0673 (6)
C90.0393 (2)0.35217 (9)0.10713 (14)0.0522 (5)
C120.0825 (2)0.35580 (9)0.07996 (14)0.0534 (5)
C130.0912 (3)0.36697 (12)0.20259 (15)0.0668 (6)
C140.0574 (2)0.37919 (9)0.01037 (13)0.0482 (4)
C150.2528 (2)0.42983 (9)0.00688 (12)0.0456 (4)
H1A0.472400.316200.604000.1390*
H1B0.420500.380800.701100.1390*
H1C0.490700.422500.591300.1390*
H40.436500.329900.416200.0760*
H50.333200.322400.225900.0710*
H70.247400.400700.272300.0730*
H80.144200.410000.461700.0810*
H13A0.196500.327000.239900.1000*
H13B0.043100.352000.225200.1000*
H13C0.125900.429100.222600.1000*
H170.418700.469700.087200.0960*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O20.0740 (9)0.1114 (11)0.0710 (9)0.0108 (8)0.0169 (7)0.0006 (7)
O110.0456 (6)0.0581 (6)0.0920 (9)0.0111 (5)0.0041 (6)0.0073 (6)
O160.0490 (6)0.0642 (6)0.0598 (6)0.0145 (5)0.0111 (5)0.0062 (5)
O170.0533 (6)0.0795 (8)0.0600 (7)0.0195 (5)0.0115 (5)0.0047 (5)
N100.0499 (7)0.0596 (8)0.0863 (10)0.0112 (6)0.0135 (7)0.0006 (7)
C10.0791 (14)0.1213 (19)0.0774 (13)0.0088 (13)0.0054 (11)0.0043 (12)
C30.0609 (10)0.0593 (9)0.0704 (11)0.0010 (7)0.0178 (8)0.0052 (8)
C40.0501 (9)0.0661 (10)0.0749 (11)0.0067 (7)0.0133 (8)0.0095 (8)
C50.0490 (8)0.0571 (9)0.0759 (11)0.0060 (7)0.0211 (7)0.0057 (7)
C60.0474 (8)0.0423 (7)0.0716 (10)0.0025 (6)0.0164 (7)0.0062 (6)
C70.0448 (8)0.0596 (9)0.0810 (12)0.0012 (6)0.0177 (7)0.0056 (8)
C80.0557 (9)0.0705 (11)0.0805 (12)0.0050 (8)0.0274 (8)0.0019 (9)
C90.0408 (7)0.0392 (7)0.0783 (10)0.0009 (5)0.0138 (7)0.0021 (6)
C120.0421 (7)0.0393 (7)0.0786 (10)0.0005 (5)0.0067 (7)0.0073 (6)
C130.0615 (10)0.0635 (10)0.0727 (11)0.0017 (8)0.0017 (8)0.0166 (8)
C140.0398 (7)0.0375 (6)0.0679 (9)0.0006 (5)0.0086 (6)0.0021 (6)
C150.0388 (7)0.0410 (6)0.0576 (8)0.0012 (5)0.0089 (6)0.0011 (6)
Geometric parameters (Å, º) top
O2—C11.414 (3)C9—C141.438 (2)
O2—C31.361 (2)C12—C141.361 (2)
O11—N101.417 (2)C12—C131.474 (2)
O11—C121.3397 (17)C14—C151.4612 (18)
O16—C151.2347 (18)C1—H1A0.9600
O17—C151.2918 (18)C1—H1B0.9600
O17—H170.8200C1—H1C0.9600
N10—C91.3096 (19)C4—H40.9300
C3—C41.385 (3)C5—H50.9300
C3—C81.385 (3)C7—H70.9300
C4—C51.376 (3)C8—H80.9300
C5—C61.387 (2)C13—H13A0.9600
C6—C91.467 (2)C13—H13B0.9600
C6—C71.395 (2)C13—H13C0.9600
C7—C81.368 (3)
C1—O2—C3118.84 (16)O16—C15—C14121.52 (13)
N10—O11—C12109.60 (12)O17—C15—C14115.23 (13)
C15—O17—H17109.00O16—C15—O17123.22 (13)
O11—N10—C9105.96 (13)O2—C1—H1A109.00
O2—C3—C8116.04 (17)O2—C1—H1B109.00
C4—C3—C8119.47 (17)O2—C1—H1C109.00
O2—C3—C4124.49 (17)H1A—C1—H1B109.00
C3—C4—C5119.48 (17)H1A—C1—H1C110.00
C4—C5—C6121.66 (15)H1B—C1—H1C109.00
C5—C6—C7118.04 (16)C3—C4—H4120.00
C5—C6—C9122.30 (13)C5—C4—H4120.00
C7—C6—C9119.60 (13)C4—C5—H5119.00
C6—C7—C8120.63 (17)C6—C5—H5119.00
C3—C8—C7120.71 (18)C6—C7—H7120.00
N10—C9—C6118.58 (14)C8—C7—H7120.00
N10—C9—C14110.23 (14)C3—C8—H8120.00
C6—C9—C14131.18 (12)C7—C8—H8120.00
O11—C12—C13116.25 (14)C12—C13—H13A109.00
O11—C12—C14108.85 (14)C12—C13—H13B109.00
C13—C12—C14134.83 (14)C12—C13—H13C109.00
C9—C14—C15128.39 (13)H13A—C13—H13B109.00
C12—C14—C15125.95 (14)H13A—C13—H13C109.00
C9—C14—C12105.36 (12)H13B—C13—H13C109.00
C1—O2—C3—C412.0 (3)C7—C6—C9—C14138.29 (16)
C1—O2—C3—C8168.49 (19)C5—C6—C7—C80.4 (2)
C12—O11—N10—C90.60 (16)C9—C6—C7—C8177.77 (15)
N10—O11—C12—C13177.70 (13)C6—C7—C8—C30.4 (3)
N10—O11—C12—C140.41 (15)N10—C9—C14—C120.32 (16)
O11—N10—C9—C140.55 (16)N10—C9—C14—C15174.29 (13)
O11—N10—C9—C6178.83 (11)C6—C9—C14—C12178.95 (14)
O2—C3—C8—C7179.51 (17)C6—C9—C14—C155.0 (2)
C4—C3—C8—C70.1 (3)O11—C12—C14—C90.07 (14)
C8—C3—C4—C50.4 (3)O11—C12—C14—C15174.09 (12)
O2—C3—C4—C5179.90 (17)C13—C12—C14—C9176.64 (16)
C3—C4—C5—C60.4 (3)C13—C12—C14—C152.5 (3)
C4—C5—C6—C9177.26 (14)C9—C14—C15—O165.3 (2)
C4—C5—C6—C70.1 (2)C9—C14—C15—O17176.71 (13)
C5—C6—C9—N10136.35 (15)C12—C14—C15—O16167.52 (14)
C5—C6—C9—C1444.4 (2)C12—C14—C15—O1710.5 (2)
C7—C6—C9—N1040.94 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O17—H17···O16i0.821.792.6034 (16)173
Symmetry code: (i) x+1, y+1, z.

Experimental details

Crystal data
Chemical formulaC12H11NO4
Mr233.22
Crystal system, space groupMonoclinic, P21/c
Temperature (K)296
a, b, c (Å)6.4147 (2), 14.6321 (6), 11.9911 (5)
β (°) 97.220 (2)
V3)1116.57 (7)
Z4
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.20 × 0.15 × 0.10
Data collection
DiffractometerBruker APEXII CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2009)
Tmin, Tmax0.979, 0.989
No. of measured, independent and
observed [I > 2σ(I)] reflections
11200, 2811, 2083
Rint0.031
(sin θ/λ)max1)0.671
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.125, 1.04
No. of reflections2811
No. of parameters156
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.23, 0.22

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O17—H17···O16i0.821.792.6034 (16)173
Symmetry code: (i) x+1, y+1, z.
 

Acknowledgements

C thanks the University of Mysore for the award of an RFSMS fellowship under the head DV5/Physics/389/RFSMS/2009–2010/10.07.2012.

References

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First citationShin, K. D., Lee, M. Y., Shin, D. S., Lee, S., Son, K. H., Koh, S., Paik, Y. K., Kwon, B. M. & Han, D. C. (2005). J. Biol. Chem. 280, 41439–41448.  Web of Science CrossRef PubMed CAS
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals
First citationWolf, R., Wong, M. W., Kennard, C. H. L. & Wentrup, C. (1995). J. Am. Chem. Soc. 117, 6789–6790.  CSD CrossRef CAS Web of Science

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