5-Methylisoxazole-4-carboxylic acid

In the title compound, C5H5NO3, the molecule lies on a crystallographic mirror plane with one half-molecule in the asymmetric unit. An intramolecular C—H⋯O interaction is present. In the crystal, strong intermolecular O—H⋯N hydrogen bonds result in the formation of a linear chain structure along [100], and there are also weak C—H⋯O hydrogen bonds between the chains which help to stabilize the crystal packing.


Related literature
The title compound is an intermediate (Kotchekov et al., 1985) for the synthesis of Leflunomide (Ree, 1998), an important antirheumatoid arthritis drug. For a related structure, see: Lee et al. (2002).

Comment
The title compound, (I), is a good organic intermediate (Kotchekov et al., 1985) for the synthesis of Leflunomide (Ree, 1998), an important antirheumatoid arthritis drug. Here we report its crystal structure.
In the molecule of (I), (Fig. 1), the bond lengths and angles are within normal ranges. There is a mirror plane through all atoms except for two H atoms of the methyl group which are related by the mirror image -one above and one below the symmetry plane while the third methyly H atom lies in the mirror plane. An intramolecular C-H···O hydrogen bond helps to establish the molecular conformation. The molecule is similar to 3-Methylisoxazole-4-carboxylic acid methyl ester (Lee et al. (2002)).
Strong intermolecular hydrogen bonds are found between the H atom of carboxylic group and the N atom of the isoxazole ring (Table 1), which link the molecules into a one-dimensional supramolecular structure along the a axis. There are also weak C-H···O hydrogen bonds between adjacent two linear structures in the same symmetry plane (Fig. 2), which makes the linear structure two molecules wide.
(II) was then refluxed together with acetic acid (300 ml), water (300 ml), and concentrated HCl (300 ml) for 10 h, and crude sample of the title compound (260-270 g) was obtained. Pure compound (I) suitable for X-ray diffraction was collected by recrystallization from ethanol.  Fig. 1. The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids at the 30% probability level.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness 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 threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) 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.