Conformational analysis of (R,R)- and (R,S)-N,N-bis(1-phenylethyl)-acetamide and -thioacetamide. A study by NMR spectroscopy and by empirical force-field and AM1 calculations

Abstract

The static and dynamic stereochemistry of the diastereoisomeric (R,S)- and (R,R)-N,N-bis(1-phenylethyl)acetamides and their thio analogues has been studied by 1H NMR spectroscopy and by the MM2 and AM1 methods. Assignment of the methyl and methine proton resonances was performed by a 2D-NOESY study, which also gave information about exchange processes. Two different processes were identified, the normal (thio) amide rotation leading to exchange of the E and Z 1-phenylethyl groups and a process with lower energy barrier exchanging two rotamers differing in the orientation of the 1-phenylethyl groups. Rate constants and free energy barriers for these processes were determined by bandshape analysis. The rotamers were identified with the aid of the chemical shifts and by AM1 and empirical force-field calculations and the interconversion trajectories were studied by the same theoretical methods. Barrier differences between the R,S and R,R diastereoisomers were qualitatively reproduced by the AM1 calculations.