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

Abstract

In CDCl 3 solution, enantiopure ( S)-1-benzyl-6-methylpiperazine-2,5-dione ( S)- 1a formed diastereomeric C O⋯ 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 CDCl 3 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 CDCl 3. 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.