Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy. A Simple Procedure for Determination of the Rates of N-H Proton Exchange of cis- and trans-1-Aza-2-cyclononanone

Abstract

Several investigations have been made to determine the relative rates of N-H proton exchange in cis and trans isomers of peptide bonds. N-Methylacetamide and medium-ring lactams have been traditional models for the cis and trans isomers, respectively. Klotz and Feidelseit have reported that base-catalyzed N-H proton exchange of 1-aza-2-cyclopentanone is much faster than that of N-methylacetamide. However, Chen and Swenson4 subsequently found that amide protons of 1-aza-2-cycloheptanone exchange more slowly than those of N-methylacetamide in deuterium oxide solution. The nine-membered ring lactam, 1-aza-2-cyclononanone (l), is well established, to exist in several solvents as a nearly 1:l mixture of the cis and trans isomers and, as such, is well suited as a model for both the cis- and trans-amide bonds. We present here the results of a ^(15)N NMR study of base-catalyzed N-H proton-exchange reactions of 1 at the natural-abundance level of the isotope in dimethyl sulfoxide and in 80% aqueous ethanol.