Gas-liquid Chromatographic Separation of Amine Enantiomers as N-Trifluoroacetyl-L-prolylamide Derivatives

Separation of asymmetric amines by derivatization to the corresponding amides with N-trifluoroacetyl-L-prolyl chloride was carried out by gas-liquid chromatography, and the structure-separation relationship was studied. For a series of ring-substituted 1-phenyl or naphthylalkylamines, diastereoisomeric amides were better resolved on a relatively polar column than on a nonpolar column with the L(+) forms eluted before the L(?) forms and the separation was poorer as the alkyl group attached to the asymmetric carbon atom was varied from isopropyl to methyl to n-propyl to isobutyl. On the contrary, for another series of ring-substituted 1,2-diphenylethylamines, the isomeric amides were better resolved on a nonpolar column than on a polar column, the L(+) forms being eluted with longer retention than the L(?) forms, and the separation was better when the alkyl group substituted for a hydrogen of the phenyl group at α-position was bulkier. Furthermore, the optical purity of asymmetric amines was determined by measuring gas chromatographic peak areas of diastereoisometic amide components.