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

J Org Chem. 2018 Mar 16;83(6):3159-3163. doi: 10.1021/acs.joc.8b00019. Epub 2018 Mar 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.