How Strong is Hydrogen Bonding to Amide Nitrogen?

The protonation of the carboxamide nitrogen atom is an essential part of in vivo and in vitro processes (cis‐trans isomerization, amides hydrolysis etc). This phenomenon is well studied in geometrically strongly distorted amides, although there is little data concerning the protonation of undistorted amides. In the latter case, the participation of amide nitrogen in hydrogen bonding (which can be regarded as the incipient state of a proton transfer process) is less well‐studied. Thus, it would be a worthy goal to investigate the enthalpy of this interaction. We prepared and investigated a set of peri‐substituted naphthalenes containing the protonated dimethylamino group next to the amide nitrogen atom (“amide proton sponges”), which could serve as models for the study of an intramolecular hydrogen bond with the amide nitrogen atom. X‐Ray analysis, NMR spectra, basicity values as well as quantum chemical calculations revealed the existence of a hydrogen bond with the amide nitrogen, that should be attributed to the borderline between moderate and weak intramolecular hydrogen bonds (2–7 kcal ⋅ mol−1). The hydrogen bond (HB) in the series of “amide proton sponges” is investigated by X‐ray spectroscopy, NMR, and computational analysis. Overall this HB should be classified as weak to moderate (2–7 kcal ⋅ mol−1). The factors fortifying or subduing the HB formation with amide nitrogen are discussed.