Mosher Amides: Determining the Absolute Stereochemistry of Optically-Active Amines

摘要

The use of chiral reagents for the derivatization of optically-active amines and alcohols for the purpose of determining their enantiomeric purity or absolute configuration is a tool used by many chemists. Among the techniques used, Mosher's amide and Mosher's ester analyses are among the most reliable and one of the most often used. Despite this, these techniques are rarely introduced in the undergraduate organic laboratory. In this experiment teams of students are given optically-pure amines of known structure but unknown stereochemistry. One half of the team derivatizes a sample of the amine with optically-pure (R)-Mosher's acid chloride and the other half of the team derivatizes a sample of the amine with optically-pure (S)-Mosher's acid chloride. The resulting amide diastereomers can be analyzed by 1H NMR spectroscopy and, using Mosher's model, distinguished from one another. Through careful analysis the students can determine the absolute configuration of their starting amine. Sample reactions are presented as well as spectral data for 18 Mosher amides that have been used in this experiment.