Methyl 2-(3-chloro-2-methylanilino)pyridine-3-carboxylate

The title compound arose from an unexpected alcoholysis of a prodrug by the methanol solvent.

The title compound, C 14 H 13 ClN 2 O 2 , was obtained during an attempt to grow single crystals of 4-acetylphenyl 2-[(3-chloro-2-methylphenyl)amino]nicotinate in methanol, and was probably generated by alcoholysis. Two intramolecular hydrogen bonds are formed, one between the N-H group and the carbonyl O atom of the ester and the other between the ortho sp 2 CH group of the benzene ring and the pyridine N atom. Aromaticstacking [shortest centroidcentroid separation = 3.598 (2) Å ] is observed in the extended structure.

Structure description
The title compound (I) was first synthesized when preparing esters of anthranilic acid as possible analgesic and anti-inflammatory agents (Velingkar et al., 2011). In our study, it was obtained during an effort to obtain single crystals of a codrug, 4-acetylphenyl 2-[(3chloro-2-methylphenyl)amino]nicotinate, by slow evaporation in methanol. Colorless needles were harvested and structure determination by single-crystal X-ray diffraction revealed it to be the title compound: alcoholysis by methanol obviously led to the generation of I. The asymmetric unit of I consists of one molecule with a near planar conformation as evidenced by the dihedral angle of 5.31 (1) between the C1-C6 benzene and N2/C8-C12 pyridine rings (Fig. 1). Two intramolecular hydrogen bonds are observed (Table 1), one between the N-H group and the carbonyl oxygen atom of the ester group with a donor-acceptor distance of 2.687 (3) Å , and the other between the ortho sp 2 C-H grouping of the aniline ring and the pyridine N atom [2.895 (4) Å ]: both of these close S(6) rings. The cohesion of the crystal structure is ensured by aromaticstacking between the benzene and pyridine rings [shortest centroid-centroid separation = 3.598 (2) Å ] and hydrophobic interactions (Fig. 2).

data reports
Synthesis and crystallization 4-Acetylphenyl 2-[(3-chloro-2-methylphenyl)amino]nicotinate, synthesized by a condensation reaction between clonixin and paracetamol (Gupta & Moorthy, 2007), was dissolved in HPLC grade methanol to make a saturated solution. The solution underwent slow evaporation at room temperatures and colorless needle-shaped crystals of the title compound ( Fig. 3) were harvested after about a week. Alcoholysis by methanol likely resulted in the formation of the title compound ( Fig. 4).

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.

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. H atoms were located in difference Fourier maps and subsequently placed in idealized positions with C-H = 0.95-0.96 and N-H = 0.86 Å: U iso (H) values were constrained to 1.2U eq (C,N) or 1.5U eq (methyl C).