Correlation between the reactivity and spectroscopic properties ofN‐substituted secondary thioamides. New intramolecular N···H+···N binding approach and proton complexes based on thioamide ligation

Abstract

AbstractOn the basis of a comparison of chemical shifts and wavenumbers of several secondary thioamides and amides having monocationic substituents attached to thiocarbamoyl or carbamoyl groups by a polymethylene chain, new intramolecular unconventional N···H+···N hydrogen bonding effects were discovered. It is argued that the CH2—N rotation is hindered and two+H···NHCH3non‐equivalent protons occur in a proton spectrum of hydrochloride1a(at 10.68 and 2.77 ppm, respectively) instead of two+NH2CH3protons. Presumably, the above steric factors inhibit the acidic hydrolysis of1a(stabilized by strong intramolecular N···H+···N hydrogen bonds) to an amide and prevent intramolecular cyclization of2a(stabilized by strong intramolecular neutral–neutral N···HN hydrogen bonds) to a cyclic amidine. Postulation of additional dihydrogen bond formation is helpful in understanding the spectroscopic differences of4and5. The above new bonding is also compared with intramolecular N···H—N+hydrogen bonds in primary amine salts7and8. In contrast to3, a cooperative hydrogen bonded system is observed in9and10. The weak hydrogen bonds in7–10facilitate the hydrolysis and cyclization reactions of secondary thioamides. The spectroscopic data for secondary (thio)amides are especially useful for characterizing the electronic situation at the (thio)carbamoyl nitrogen atoms and they are perfectly correlated with the reactivity. Examples of chelation of protons by thioamides (11and12), which contain strongly electron‐donating pyrimidine groups, are presented to show the contribution of dihydrogen bonding in the protonation reaction similar to1and4. Copyright © 2003 John Wiley & Sons, Ltd.