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

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 R 2 2(8) loops.

In the title compound, C 12 H 11 NO 4 , 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-HÁ Á ÁO hydrogen bonds generate R 2 2 (8) loops.
Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; 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. 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 synperiplanar 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).

Experimental
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
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; U iso (H) = 1.2U eq (carrier atom) for all H atoms.

Figure 1
Perspective diagram of the molecule with 50% probability displacement ellipsoids.

Special details
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 F 2 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 F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The observed criterion of F 2 > σ(F 2 ) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.