Barriers to Rotation in ortho-Substituted Tertiary Aromatic Amides: Effect of Chloro-Substitution on Resonance and Distortion

Planarity of the amide bond represents
one of the most widely recognized
properties of amides. Herein, we report a combined structural and
computational study on the effect of ortho-substitution on resonance
and barriers to rotation in tertiary aromatic amides. We demonstrate
that ortho-chloro substitution in a class of benzamides that are important
from the reactivity and medicinal chemistry perspective results in
increased barriers to rotation around both the N–C­(O) and C–C­(O)
axes. The effect of steric hindrance on structures, resonance energies,
barriers to rotation, and proton affinities is discussed. The present
study strongly supports the use of ortho-substitution in common benzamides
to strengthen amidic resonance.