Synthesis and NMR configurational analysis of 1,3-imidazolidin-4-ones derived from (-)-(S)-phenylethylamine.

The preparation and NMR study in the solution state of (-)-(S)-1-acetyl-3-(phenylethyl)-1,3-imidazolidin-4-one, (-)-(2R,1'S)- and (+)-(2S,1'S)-1-acetyl-2-tert-butyl-3-(phenylethyl)-1,3-imidazolidin-4-one, and (-)-(2S,1'S)- and (+)-(2R,1'S)-1-carboethoxy-2-tert-butyl-3-(phenylethyl)-1,3-imidazolidin-4-one are described. The orientations of acetyl, carboethoxy, and phenethyl groups attached to nitrogen atoms N-1 and N-2 were deduced from the proton and (13)C chemical shifts. The typical orientation of phenethyl group, which has the hydrogen H-6 syn and close to the oxygen of carbonyl C-4, was observed in (-)-(S)-1-acetyl-3-(phenylethyl)-1,3-imidazolidin-4-one but not in the other four compounds; nevertheless, interpretation of chemical shifts based on the ring current effects correlated with the true configuration of the new stereogenic center at C-2. Four of these imidazolidinones were analyzed by X-ray diffraction to corroborate the configuration determined by NMR. The structures determined by X-ray diffraction revealed the existence of intramolecular hydrogen bonds capable to control the conformation of the phenethyl and acyl groups in the solution state. Copyright 2003 Wiley-Liss, Inc.