Nitrogen pyramidal amides and related compounds

Abstract

A planar amide bond is a fundamental linkage in the structures of peptides and proteins. The rigid planarity of the amide linkage, due to a conjugation between carbonyl and amine groups, may be requisite for encoded protein folding and many other biological processes. Non-planar amides in the ground state will decode the significance of the planarity and rigidity of the amide linkage. We show here that simple amides of 7-azabicyclo[2.2.1]heptane, free from steric bias, including parent N-benzoyl 7-azabicyclo[2.2.1]heptane, are nitrogen-pyramidal amides in the crystalline state. We can suggest that pyramidalized amide nitrogen is a general feature and intrinsic to the 7-azabicyclo[2.2.1]heptane motif. Low rotational barriers of the amide C-N bond in a series of N-benzoyl amides of 7-azabicyclo[2.2.1]heptane, compared to monocyclic amides, may imply that ground-state nitrogen pyramidalization of the former amides also exist in solution. The 7-azabicyclo[2.2.1]heptane motif also favors nitrogen pyramidalization of sulfonamides and N-nitrosoamines, which can lead to pharmacophores after appropriate modification.