Influence of benzylamine on the resolution of ibuprofen with (+)‐(R)‐phenylethylamine via supercritical fluid extraction

Abstract

The resolution of racemic ibuprofen was studied by partial diastereomer salt formation. The resolution was performed via two methods: resolution with (+)-(R)-phenylethylamine as chiral agent and resolution with a mixture of (+)-(R)-phenylethylamine and benzylamine. The diastereomers and unreacted enantiomers were separated by supercritical fluid extraction with carbon dioxide at 15 MPa and 33 degrees C. The influence of the achiral benzylamine on the resolution efficiency was studied by varying the concentrations of the structurally related amines in their mixtures, keeping the sum molar ratio of the amines to racemic ibuprofen constant at 0.55 +/- 0.02. The presence of benzylamine positively influenced the resolution efficiency at certain concentrations. The crystal structure of the salts of (+)-(R)-phenylethylamine with (-)-(R)-ibuprofen and (+)-(S)-ibuprofen, respectively, as well as the cocrystal of the benzylamine-ibuprofen salt with neutral ibuprofen molecules are presented. These structures were determined by single crystal X-ray diffraction, proving the significantly different stoichiometry of the related amines with the chiral acid, in accordance with mass balance calculations.

Polymorphic supramolecular organic fluorophore composed of 2-naphthalenecarboxylic acid and benzylamine

“…7 The phenomenon that both the neutral and anionic forms of an organic carboxylic acid exist at the same time in a crystal is rare. 8 However, this complex is a racemic crystal; that is, the space group is P2 1 /c. Although the stoichiometry of this complex is different from those of I and II, this crystal also has a 2 1 -helical columnar hydrogen-and ionic-bonded network (indicated by the dotted lines in Fig.…”

Separation of Chiral Compounds: Enantiomeric and Diastereomeric Mixtures

“…The unreacted enantiomer mixture of IBU was removed by scCO 2 extraction from the received diastereomeric salt. The addition of the achiral benzylamine resulted in higher efficiency of resolution (F SCS ) values compared to the experiments without additive (Scheme 25) [80].…”

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

“…A search of the Cambridge Structural Database (Version 5.36, May 2015; Groom & Allen, 2014) revealed only one hit for organic salts of racemic ibuprofen, viz. benzylammonium 2-(4isobutylphenyl)propionate 2-(4-isobutylphenyl)propionic acid (refcode VUCHUX;Molná r et al, 2009). In fact, it is a salt cocrystal based on ibuprofen and the organic salt (Sun, 2013 Part of the crystal structure of the title salt, viewed along the c axis, showing the hydrogen bonds (dashed lines) forming chains along [001]; see Table 1 for details.…”