A Chiral Bisthiourea as a Chiral Solvating Agent for Carboxylic Acids in the Presence of DMAP

A simple chiral bisthiourea has been used as a highly effective and practical chemical solvating agent (CSA) for diverse alpha-carboxylic acids in the presence of DMAP. Excellent enantiodiscrimination based on well-resolved alpha-H NMR signals of the enantiomers of carboxylic acids can be obtained without interference from the chiral bisthiourea and DMAP. To check the practicality of the chiral bisthiourea/DMAP for enantiomeric determination, the ee values of mandelic acid (MA) samples over a wide ee range were determined by integration of the alpha-H signal of MA in H-1 NMR. A discrimination mechanism is proposed, that the formation of two diasteromeric ternary complexes between the chiral bisthiourea and two in situ formed enantiomeric carboxylate-DMAPH(+) ion pairs discriminates the enantiomers of carboxylic acids. Computational modeling studies show that the chemical shift value of alpha-H of (S)-MA is greater than that of (R)-MA in ternary complexes, which is consistent with experimental observation. 1D and 2D NOESY spectra demonstrate the intermolecular noncovalent interactions between the protons on the aromatic rings of chiral bisthiourea and alpha-H of the enantiomers of racemic alpha-methoxy phenylacetic acids in the complexes