An Evaluation of Amide Group Planarity in 7-Azabicyclo[2.2.1]heptane Amides. Low Amide Bond Rotation Barrier in Solution

Here we show that amides of bicyclic 7-azabicyclo[2.2.1]heptane are intrinsically nitrogen-pyramidal. Single-crystal X-ray diffraction structures of some relevant bicyclic amides, including the prototype
N-benzoyl-7-azabicyclo[2.2.1]heptane, exhibited nitrogen-pyramidalization in the solid state. We evaluated
the rotational barriers about the amide bonds of various N-benzoyl-7-azabicyclo[2.2.1]heptanes in solution.
The observed reduction of the rotational barriers of the bicyclic amides, as compared with those of the
monocyclic pyrrolidine amides, is consistent with a nitrogen-pyramidal structure of 7-azabicyclo[2.2.1]heptane
amides in solution. A good correlation was found between the magnitudes of the rotational barrier of
N-benzoyl-7-azabicyclo[2.2.1]heptanes bearing para-substituents on the benzoyl group and the Hammett's
σp+ constants, and this is consistent with the similarity of the solution structures. Calculations with the
density functional theory reproduced the nitrogen-pyramidal structures of these bicyclic amides as energy
minima. The calculated magnitudes of electron delocalization from the nitrogen nonbonding nN orbital to
the carbonyl π* orbital of the amide group evaluated by application of the bond model theory correlated
well with the rotational barriers of a variety of amides, including amides of 7-azabicyclo[2.2.1]heptane. The
nonplanarity of the amide nitrogen of 7-azabicyclo[2.2.1]heptanes would be derived from nitrogen-pyramidalization due to the CNC angle strain and twisting of the amide bond due to the allylic strain.