Nitrogen-15 nuclear magnetic resonance spectroscopy. A simple procedure for determination of the rates of nitrogen-hydrogen proton exchange of cis- and trans-1-aza-2-cyclononanone

Several investigations have been made to determine the rates of N-H proton exchange in cis and trans isomers of peptide bonds. N-Methylacetamide and medium-ring have been traditional models for the cis and trans , 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 for both the cis- and trans-amide bonds. We present the results of a ^(15)N NMR study of base-catalyzed N-H -exchange reactions of 1 at the natural-abundance level of the isotope in dimethyl sulfoxide and in 80% aqueous ethanol.