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Influence of benzylamine on the resolution of ibuprofen with (+)‐( R )‐phenylethylamine via supercritical fluid extraction
Author(s) -
Molnár Péter,
Bombicz Petra,
Varga Csaba,
Bereczki Laura,
Székely Edit,
Pokol György,
Fogassy Elemér,
Simándi Béla
Publication year - 2009
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20655
Subject(s) - chemistry , benzylamine , diastereomer , enantiomer , resolution (logic) , ibuprofen , chromatography , extraction (chemistry) , chirality (physics) , cocrystal , organic chemistry , molecule , hydrogen bond , medicine , chiral symmetry breaking , physics , quantum mechanics , artificial intelligence , computer science , nambu–jona lasinio model , pharmacology , quark
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°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. Chirality, 2008. © 2009 Wiley‐Liss, Inc.