The Mosher Method of Determining Enantiomeric Ratios

Mosher’s established technique of measuring the enantiomeric ratio of a chiral compound has been adapted to be suitable for an undergraduate organic chemistry experiment. In this technique a chiral alcohol or amine reacts with the Mosher acyl chloride, α-methoxy-α-(trifluoromethyl) phenylacetyl chloride (MTPA-Cl), to yield the corresponding diastereomeric ester or amide. The ester or amide products are analyzed by 1H and/or 19F NMR spectroscopy, and signals for diastereotopic groups on the products are integrated to determine the ratio of the diastereomeric products and consequently the ratio of enantiomeric substrates. This experiment has the benefits of helping students (1) apply advanced topics in stereochemistry, such as stereoheterotopic ligands and kinetic resolution; (2) learn a quantitative application of NMR spectroscopy, including 19F NMR; and (3) be introduced to microscale techniques. Furthermore, even though this is a microscale NMR technique, it can be conducted on a low-field (60- or 90-MHz) NMR spectrometer with satisfactory results.