N-acyl derivatives of chiral amines as novel, readily prepared phases for the separation of optical isomers by gas chromatography

Abstract The results reported demonstrate that it suffices for a chiral stationary phase to contain an amide group and an asymmetric carbon atom, attached to the nitrogen atom [RCONHCH(CH 3 )R′], in order to show selectivity in its interaction with the enantiomers of amides such as N-trifluoroacetylamines, N-trifluoroacetylamino acid esters and α-methyl- and α-phenylcarboxylic acid amides. The best efficiency is obtained when R′ is aromatic, particularly α-naphthyl, as in N-lauroyl- S -α-(1-naphthyl)ethylamine. The highest resolution factors were found for aromatic solutes, such as N-trifluoroacetyl-α-phenylethylamine and α-phenylbutyric acid amides, which could be resolved readily on packed columns. The enantiomers of α-branched carboxylic acids were separated for the first time by gas chromatography. Based on the packing arrangement in the crystalline form of the N-acetyl homologue of N-lauroyl- S -α-(1-naphthyl)ethylamine, a mechanism for the resolution is proposed. It is assumed that the mode of association found in the solid state is at least partially retained in the melt through a network of hydrogen bonds. The mechanism proposed is developed with particular reference to the aromatic solute-solvent systems. It is suggested that the solute is intercalated (“sandwiched”) between two solvent molecules. Arguments, based on X-ray data, are given to explain the selectivity observed.