Crystal structure of 1,3-dihydroxy-2-(hydroxymethyl)propan-2-aminium 2-(4-isobutylphenyl)propanoate: a simple organic salt of racemic ibuprofen

The title compound is an organic salt of ibuprofen with trometamol, in which the carboxylic acid group of ibuprofen has transferred its proton to the amine N atom of trometamol. In the crystal, the ions are linked by a series of O—H⋯O and N—H⋯O hydrogen bonds, forming sheets parallel to (100).


Chemical context
Salt formation is an effective approach for modifying the properties of active pharmaceutical ingredients (APIs) (Childs et al., 2007). Tris(hydroxymethyl)amino methane, commonly called trometamol, has been successfully exploited for improving the properties of APIs such as ketoprofen (Zippel & Wagenitz, 2006). In this study, trometamol was employed to crystallize with ibuprofen, giving rise to a new crystalline form, whose crystal structure is reported on herein.

Structural commentary
The molecular structure of the title molecular salt is shown in Fig. 1. From difference Fourier maps, it was shown that the carboxylic group of ibuprofen has transferred its proton to the amino N atom of trometamol. This is supported by the C-O bond distances of the carboxylate group of the ibuprofen anion, which are 1.252 (2) and 1.251 (2) Å for C1-O1 and C1-O2, respectively. The carboxylate anion interacts with one hydroxyl group of the trometamol cation through a strong hydrogen bond [O5Á Á ÁO2 = 2.730 (2) Å ; Table 1]. There also exist hydrogen-bonding interactions between the carboxylate anion and aminium H atoms of the cation [N1Á Á ÁO1 = 2.763 (2) Å ; Table 1].

Supramolecular features
In the crystal, the trometamol cations are linked via N-HÁ Á ÁO hydrogen bonds, forming chains along [010];

Figure 1
The molecular structure of the title molecular salt, with atom labeling. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen bonds are shown as dashed lines (see Table 1 for details).
The minor components of the disordered atoms (viz. C2 and C3) have been omitted for clarity in all three figures.

Figure 3
Part of the crystal structure of the title salt, viewed along the b axis, showing the sheets parallel to (100) formed by hydrogen bonding (dashed lines; see Table 1 for details).
The title compound is the first crystal structure of a simple organic salt of racemic ibuprofen.

Synthesis and crystallization
Ibuprofen (206 mg, 1 mmol) and trometamol (121 mg, 1 mmol) were dissolved in methanol (15 mL). The resulting solution was kept in air and after several days colorless platelike crystals were obtained.

1,3-Dihydroxy-2-(hydroxymethyl)propan-2-aminium 2-(4-isobutylphenyl)propanoate
Crystal data 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (