N-(4-Isocyanophenyl)succinamic acid

In the crystal structure of the title compound, C11H10N2O3, inversion-related molecules are connected by pairs of O—H⋯O hydrogen bonds. With the exception of the atoms in the carboxylic acid group, the non-H atoms are roughly coplanar with a maximum deviation from the mean plane of 0.270 (1) Å for the C atom to which the carboxylic group is attached. The C atom of the carboxylic group lies 1.730 (2) Å from the mean plane.

In the crystal structure of the title compound, C 11 H 10 N 2 O 3 , inversion-related molecules are connected by pairs of O-HÁ Á ÁO hydrogen bonds. With the exception of the atoms in the carboxylic acid group, the non-H atoms are roughly coplanar with a maximum deviation from the mean plane of 0.270 (1) Å for the C atom to which the carboxylic group is attached. The C atom of the carboxylic group lies 1.730 (2) Å from the mean plane.
Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX publication routines (Farrugia, 1999). Glycosylasparaginase is a key lysosomal enzyme in the catabolism of N-linked glycoproteins. The natural substrate for the enzyme is N 4 -(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine. In a study of the enzyme-catalyzed reaction in which the structure of the amino acid part of the natural substrate was altered (and the sugar was unchanged), it was found that the binding sites on the enzyme for the sugar and the α-carboxyl group were sufficient for the enzyme to act on the substrate, with the α-amino group acting as an "anchor" in the binding site for the substrate (Risley et al., 2001). In a follow-up study, a series of N 4 -(4′-substituted phenyl)-L-asparagines were synthesized in which the structure of the amino acid part of the natural substrate was unchanged, but the sugar was substituted with para-substituted anilines. All of these β-anilides of asparagine were substrates for the enzyme (Du & Risley, 2003).
In order to better understand the role of the α-amino group in the binding to the enzyme, results from the two studies were used to design a series of N 4 -(4′-substituted phenyl)succinamic acids in which the structure of the amino acid part of the natural substrate was changed to succinamic acid (the α-amino group was replaced with a hydrogen) and the sugar part was substituted with para-substituted anilines. One of the substrate analogues synthesized was the title compound, with the atypical electron-withdrawing isocyano group that should make 4-isocyanoaniline a very good leaving group in the hydrolysis of the amide bond during the enzyme-catalyzed reaction. Initial studies of these analogues with the enzyme, however, indicated that they were neither substrates nor inhibitors. These initial studies would indicate that, for anilide substrates, the α-amino group is required for binding of the substrate to the active site of the enzyme, in contrast to the sugar substrates for which the α-amino group was not required.
The pair of molecules related by the inversion center at (1/2,1/2,0) are joined by two symmetry-equivalent O-H···O hydrogen bonds, as shown in Figure 2 and described in Table 1. The non-hydrogen atoms of the molecule are nearly planar, with the exception of those in the carboxylic acid group. A mean plane was fit to all of the non-hydrogen atoms except those of the carboxylic group; the maximum deviation of the fitted atoms is 0.270 (1) Å, for C10. The carbon of the carboxylic group, C11, lies 1.730 (2) Å from the mean plane.

Refinement
The hydrogen atoms on N2 (HN2) and O3 (HO3) were refined isotropically. The remaining H atoms were included in calculated positions and treated as riding atoms. Aromatic C-H bond lengths were 0.93 Å and methylene C-H bond lengths were 0.97 Å, with U iso (H) = 1.2 U eq (C) in both cases.

Figure 1
View of the title compound. Displacement ellipsoids are drawn at the 50% probability level.   Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s 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 > 2σ(F 2 ) is used only for calculating R-factors(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.