Chiral solvating properties of (S)-1-benzyl-6-methylpiperazine-2,5-dione

In CDCl3 solution, enantiopure (S)-1-benzyl-6-methylpiperazine-2,5-dione (S)-1a formed diastereomeric CO⋯H–N hydrogen-bonded associates with racemic (RS,Z)-1-benzyl-3-[(dimethylamino)methylidene]piperazine-2,5-diones 2a and 2b, (RS)-tert-butyl pyroglutamate (RS)-2c and (RS)-N-benzoylalanine methyl ester (RS)-2d. This resulted in splitting (doubling) of the characteristic signals in the 1H NMR and 13C spectra of racemic compounds 2a–d in the presence of 1 equiv of (S)-1a. The formation of hydrogen-bonded dimers in CDCl3 solution was studied by 1H NMR, 13C NMR and 2D NMR and confirmed by the intermolecular NOE observed between the hydrogen-bonded amide protons from each of the monomeric units, (S)-1a and 2a–c. On the other hand, a slightly different binding mode was proposed for association of (S)-1a with alaninamide (RS)-2d. Enantiomer compositions of known (weighed) mixtures of both enantiomers of tert-butyl pyroglutamate 2c were re-determined by 1H NMR in the presence of (S)-1a in CDCl3. The experimental values were in good agreement with the theoretical values, thus indicating the potential applicability of (S)-1a and related diketopiperazines as chiral solvating agents in NMR spectroscopy.

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(S)-1-Benzyl-6-methylpiperazine-2,5-dioneC12H14N2O2Ee = 100%[α]D20=+37.5 (c 2.90, CHCl3)Source of chirality: (S)-alanine methyl esterAbsolute configuration: (S)