Application of mixtures of tartaric acid derivatives in resolution via supercritical fluid extraction

Abstract

Racemic N-methylamphetamine (rac-MA) was resolved with 2R,3R-tartaric acid (TA) and its derivatives (O,O'-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA) and O,O'-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA)), individually and using them in different combinations. After partial diastereomeric salt formation, the free enantiomers were extracted by supercritical fluid extraction using carbon dioxide as solvent. DBTA and DPTTA are efficient resolving agents for rac-MA, the best chiral separation being obtained at a molar ratio of 0.25 resolving agent to racemic compound for both resolving agents (ee(E) = 82.5% and ee(E) = 57.9%, respectively). Compared with the two other acids, TA is practically unsuitable for enantiomer separation (ee(E) < 5%). Applying a mixture of one individually active and one ineffective acid in half the equivalent molar ratio, when the acids are in 1:1 ratio in the mixture, the resolution efficiency values obtained exceeded those obtained by using the components individually. Decreasing the molar ratio of resolving agent mixture to 0.25, at which the individual resolving agents give the best chiral separation, the obtained resolution efficiency values did not differ significantly from those expected. The outcome of the resolution process depended only on the amount of the individually active resolving agents in the mixture.

Crystallization and Resolution of cis‐Permethric Acid with Carbon Dioxide Antisolvent

“…Supercritical carbon dioxide (scCO 2 ) is an established industrial solvent with many environmentally desirable properties, i.e., nonflammable, nonexplosive, nontoxic in trace amounts, readily available, etc. Supercritical fluid extraction (SFE) with CO 2 has been successfully used in resolutions of various compounds 2–4. The racemic compound and a chiral resolving agent are dissolved in a conventional solvent.…”

Resolution of racemic trans-1,2-cyclohexanediol with tartaric acid

“…Tartaric acid and its derivatives are widely used as chiral agents in resolutions through diastereomeric complex or salt formation. [29][30][31][32][33][34] These compounds provide the advantages of wide availability and low cost as chiral agents. The resolution of racemic trans-1,2-cyclohexanediol 1 was first attempted with three compounds: O,O 0 -(À)-dibenzoyl-(2R,3R)-tartaric acid monohydrate 2, O,O 0 -(À)-di-p-toluyl-(2R,3R)-tartaric acid 3 and tartaric acid 4.…”