An Explanation about the Use of (S)-Citronellal as a Chiral Derivatizing Agent (CDA) in 1H and 13C NMR for Sec-Butylamine, Methylbenzylamine, and Amphetamine: A Theoretical-Experimental Study

Abstract

A chiral derivatizing agent (CDA) with the aldehyde function has been widely used in discriminating chiral amines because of the easy formation of imines under mild conditions. There is a preference for the use of cyclic aldehydes as a CDA since their lower conformational flexibility favors the differentiation of the diastereoisomeric derivatives. In this study, the imines obtained from the reaction between (S)-citronellal and the chiral amines (sec-butylamine, methylbenzylamine, and amphetamine) were analyzed by the nuclear Overhauser effect (NOE). Through NOE, it was possible to observe that the ends of the molecules were close, suggesting a quasi-folded conformation. This conformation was confirmed by theoretical calculations that indicated the London forces and the molecular orbitals as main justifications for this conformation. This conformational locking explains the good separation of 13C NMR signals between the diastereomeric imines obtained and, consequently, a good determination of the enantiomeric excess using the open chain (S)-citronellal as a CDA.

Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents

“…NMR spectroscopy stands out as a relatively advantageous tool not only for structural elucidation, but also for the assessment of chiral purity in terms of enantiomeric excess (ee) of chiral molecules. − Importantly, NMR spectroscopy offers several advantages such as convenience, simplicity, speed, and environmental friendliness. As NMR miniaturization and routinization progress in most synthetic laboratories, chemists increasingly favor chiral recognition depending on a chiral auxiliary such as chiral solvating agents (CSA), chiral derivatizing agents (CDA), chiral metal complexes, and chiral liquid crystals based on dipole interaction to induce enantiospecificity for the determination of ee. − Among the methods, the chiral recognition of an analyte using chiral solvating agents is rapid and robust, involves minimal sample manipulation, and does not require derivatization or isotopically labeling of the sample.…”