This work explores the self-disproportionation of enantiomers (SDE) via achiral, gravity-driven column chromatography as typically used in laboratory settings for the purpose of enantiomeric enrichment using N-(1-phenylethyl)acetamide (PEA) as a case study. The major finding of this work is the very large magnitude of the SDE for PEA across a variety of conditions and broad range of starting ee values, thereby facilitating a simple, reliable, and predictable means of obtaining enantiomerically pure samples. For example, starting with a sample of PEA of ee as low as 28%, a single column run yielded an enantiomerically pure sample (〉99.9% ee) from the first fractions and a significantly enantiomerically depleted sample (〈17% ee) from the final fractions. An assessment of SDE via achiral, gravity-driven column chromatography was also rendered with regard to the differing objectives that workers might target - a large magnitude of the SDE, obtaining an optimum sample of desired ee, or preparative-scale separation of the excess enantiomer. Overall, it can be considered that the SDE phenomenon via achiral, gravity-driven column chromatography - readily applicable in the usual laboratory settings - is a simple and convenient method for enantiomeric enrichment with a high degree of proficiency. Advantages of SDE via achiral, gravity-driven column chromatography over conventional fractional recrystallization for the enantiomeric enrichment of amides/amines, and applicable also to many other classes of compounds as well, are discussed.
Type of Publication:
Journal article published