Rational application of self-disproportionation of enantiomers via sublimation—a novel methodological dimension for enantiomeric purifications

The preliminary results presented in this work show that an enantiomer purification approach based on SDE via sublimation can be extended to non-volatile liquid compounds such as α-(phenyl)ethylamine and its β-fluoro-derivatives by way of their rational modification with a sublimation enabling tag. 3,3,3-Trifluoro-2-(trifluoromethyl)-2-methyl-propanoic acid was found to perfectly serve the role of such a modifying tag. Thus, the corresponding amides derived from the amines and the fluorinated propanoic acid were highly crystalline and reasonably volatile compounds allowing for their sublimation at room temperature under normal pressure. All of these derivatives showed substantial self-disproportionation of enantiomers (SDEs) via sublimation under kinetic conditions (on a Petri dish in the open air). These preliminary results serve as a proof of a new principle that may extend the generality of enantiomer purification via sublimation to various organic compounds with physico-chemical properties of which render them otherwise unsuitable for a sublimation procedure. In particular, the very attractive cost structure of sublimation procedure renders this approach of potentially high practical and economic efficiency.

Graphical abstractThe concept of rational application of self-disproportionation of enantiomers (SDEs), via sublimation, presented here is operationally simple and should be applicable for chiral compounds of virtually any physico-chemical properties. In particular, very attractive cost structure of sublimation procedure renders this approach of potentially high practicality and economical efficiency.Figure optionsDownload full-size imageDownload as PowerPoint slide

2,2-Ditrifluoromethyl-N-(2,2,2-trifluoro-1-phenylehtyl)-propamideC13H10F9NO[α]D23=-68.1 (c 0.73, CHCl3).Source of chirality: (R)-2,2,2-Trifluoro-1-phenylethylamineAbsolute configuration: R

2,2-Ditrifluoromethyl-N-(2,2-difluoro-1-phenylehtyl)-propamideC13H11F8NO[α]D23=-60.9 (c 0.99, CHCl3).Source of chirality: (R)-2,2,2-Trifluoro-1-phenylethylamineAbsolute configuration: R

2,2-Ditrifluoromethyl-N-(1-phenylehtyl)propamideC13H13F6NO[α]D23=+56.1 (c 0.05, CHCl3).Source of chirality: (R)-1-phenylethylamineAbsolute configuration: R