Chiral Recognition of Hydantoin Derivatives Enabled by Tetraaza Macrocyclic Chiral Solvating Agents Using 1H NMR Spectroscopy

Enantiomers of a series of hydantoin derivatives were prepared from d- and l-amino acids with p -tolyl isocyanate and 3,5-bis(trifluoromethyl)phenyl isocyanate as guests for chiral recognition by 1 H NMR spectroscopy. Meanwhile, several tetraaza macrocyclic compounds were synthesized as chiral solvating agents from d-phenylalanine and (1 S ,2 S )-(+)-1,2-diaminocyclohexane. An uncommon enantiomeric discrimination has been successfully established for hydantoin derivatives, representatives of five-membered N,N-heterocycles, in the presence of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1c by means of 1 H NMR spectroscopy. Several unprecedented nonequivalent chemical shifts (up to 1.309 ppm) were observed in the split 1 H NMR spectra. To evaluate practical applications in the determination of enantiomeric excess (ee), the ee values of samples with different optical purities (up to 95% ee) were accurately calculated by the integration of relevant proton peaks. To better understand the chiral discriminating behavior, Job plots of (±)-G 1 with TAMCSA 1a were investigated. Furthermore, in order to further explore any underlying intermolecular hydrogen bonding interactions, theoretical calculations of the enantiomers of ( S )-G 1 and ( R )-G 1 with TAMCSA 1a were performed by means of the hybrid density functional theory (B3LYP/6-31G*) of the Gaussian 16 program.