Controlling the Conformation of Arylamides: Computational Studies of Intramolecular Hydrogen Bonds between Amides and Ethers or Thioethers

Graphical Abstract

Conformational control by intramolecular hydrogen bonds: DFT calculations show that introducing an ortho-methylthio group into acetanilide ensures that the amide NH group points toward the S atom. This lowest energy conformation is stabilized by NH⋅⋅⋅S and CH⋅⋅⋅O hydrogen bonds (picture, left), which, relative to the conformation with CCNC≈180°, feature lengthened NH and shortened CH bond lengths, respectively (right).

Abstract

The role of an ortho-alkylthioether group in controlling the conformation around the ringN bonds of meta-connected arylamide oligomers is studied. Density functional theory (DFT) geometries of model compounds, including acetanilide, an ether acetanilide, and a thioether acetanilide, and their corresponding diamides, show that for either monoamide or diamide the alkyl side chain of the thioether should be perpendicular to the aryl plane, whereas for the ether monoamide, the alkyl side chain is in the aryl plane. DFT ringN torsional potentials and constrained geometries of the model compounds demonstrate that carbonylS repulsion leads to a high torsional barrier and that intramolecular NH⋅⋅⋅S and CH⋅⋅⋅O hydrogen bonds and ring–amide conjugation lead to NH having a preferred orientation in the benzene plane pointing towards S. The NH bond lengthens and the ortho-ring CH bond shortens in a regular pattern in the approach to the preferred orientation. Calculated IR frequencies for the NH stretch show a clear red shift between model compounds without and with the thioether side chain.