A Quantitative Scale for the Extent of Conjugation of the Amide Bond. Amidity Percentage as a Chemical Driving Force

The amide bond may be considered as one of the most important chemical building blocks, playing an important role not only in living organisms but in organic chemistry as well. The exact description and precise quantification of the amide bond strength is difficult, requiring a particular type of theoretical investigation. The present paper suggests a novel, yet simple, method toward quantifying amide bond strength on a linear scale, defined as the "amidity scale". This is achieved using the computed enthalpy of hydrogenation (DeltaHH2) of the compound examined. In the present conceptual work, the DeltaHH2 value for dimethylacetamide is used to define perfect amidic character (amidity=+100%), while azaadamantane-2-on represents complete absence of amidic character (amidity=0%). The component DeltaHH2 values were computed at differing levels of theory, providing a computational and quasi-"method-independent" measure of amidity. A total of 29 well-known amides were examined to demonstrate the "scoring" accuracy of this methodology. For the compounds examined, a correlation has been made between the computed amidity percentage and their common COSNAR resonance energy values, proton affinities, and reactivity in a nucleophilic addition reaction. Selected chemical reactions were also studied. It has been shown that the change of the amidity value, during acyl transfer reactions, represents a thermodynamic driving force for the reaction.