(S)‐(−)‐N‐(Pentafluorobenzylcarbamoyl)prolyl chloride: a chiral derivatisation reagent designed for gas chromatography/negative ion chemical ionisation mass spectrometry of amino compounds

Abstract

The synthesis of a novel chiral derivatisation reagent, (S)-(-)-N-(pentafluorobenzylcarbamoyl)prolyl chloride is described which is preferably useful for negative-ion chemical ionisation mass spectrometry. Preparation of the reagent followed a general strategy used to prepare enantioselective reagents based on the N-substitution of L-proline. Pentafluorobenzyl chloroformate smoothly reacted with L-proline to give the desired derivatisation reagent after conversion into the acyl chloride. The product was sufficiently pure to be used in the following steps without any additional purification. The reagent was tested against selected chiral and non-chiral analytical targets. Chromatographic enantioseparation was at least equal to the commonly used (S)-(-)-N-(heptafluorobutyryl)prolyl derivatives. The derivatives exhibit excellent mass spectral properties under negative ion chemical ionisation, i.e. reduced fragmentation and thus high ion current for the targeted m/z during analysis. With electron ionisation, the fragmentation that occurs is mainly directed by the introduced group. Enantioseparation with gas chromatography/negative-ion chemical ionisation mass spectrometry of the derivatives was demonstrated for the enantiomers of amphetamine, α-aminocaprylic acid methyl ester and threo-methylphenidate. The new derivatisation reagent shows highly improved mass spectral properties for negative-ion chemical ionisation mass spectrometry and is thus suitable for sensitive chiral detection of amino compounds. The reagent extends the applicability of dissociative resonance electron capture using pentafluorobenzyl derivatives to chiral analysis.