High-performance liquid chromatographic determination of α-aminonitrile enantiomers after derivatization with o-phthalaldehyde and chiral thiols

o-Phthalaldehyde in combination with chiral thiols is described as a chiral reagent for the resolution of the enantiomers of α-H-α-aminonitriles and α-alkyl-α-aminonitriles. Separation of the resulting diastereomers was carried out by reversed-phase chromatography and the derivatives were detected at UV 340 nm. The identity of the diastereomeric derivatives was confirmed by LC–MS. Among the chiral thiols tested, N-acetyl-d-penicillamine and β-mercaptoisobutyric acid gave the best resolution for the α-aminonitriles studied. For quantitative enantiomeric excess determination, β-mercaptoisobutyric acid was chosen as this thiol could be obtained in high enantiomeric purity from a commercial source. The rate of the reaction of various α-aminonitriles with o-phthalaldehyde and β-mercaptoisobutyric acid was studied. The accuracy of the method was investigated by a comparison of theoretical and measured enantiomeric excess.