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

On 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 CH 2 -N rotation is hindered and two + H· · ·NHCH 3 non-equivalent protons occur in a proton spectrum of hydrochloride 1a (at 10.68 and 2.77 ppm, respectively) instead of two + NH 2 CH 3 protons. Presumably, the above steric factors inhibit the acidic hydrolysis of 1a (stabilized by strong intramolecular N· · ·H + · · ·N hydrogen bonds) to an amide and prevent intramolecular cyclization of 2a (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 of 4 and 5. The above new bonding is also compared with intramolecular N· · ·H -N + hydrogen bonds in primary amine salts 7 and 8. In contrast to 3, a cooperative hydrogen bonded system is observed in 9 and 10. The weak hydrogen bonds in 7-10 facilitate 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 (11 and 12), which contain strongly electron-donating pyrimidine groups, are presented to show the contribution of dihydrogen bonding in the protonation reaction similar to 1 and 4.

Stabilization of N‐, N,N‐, N,N′‐methylated and unsubstituted simple amidine salts by multifurcated hydrogen bonds

“…The hydrogen bonds enhance both the stability and the reaction rate. Contrary to this analysis, which presents an extension of my earlier work [17], the ∆δ NH results of some amides can be only a tool to detect interactions [31][32][33]. This is logical since different intermolecular hydrogen bonds could compete with weaker intramolecular interactions {see spectroscopic [34] and crystallographic [35] data for (1-thyminyl)acetamide, ∆δ NH 0.37 ppm}.…”

“…The GHMBC (gradient heteronuclear multiple bond correlation) spectra provide further insight into the cyclic structures. This investigation was facilitated by the previous confirmation of the assignment of the N1 and N3 correlations [17]. The spectra were recorded according to the literature [17,29,30].…”

“…The relative donor and acceptor capabilities (angles, arrangement, distances, spectroscopic features, structure, type) and the additional effects (cooperative, anticooperative, competitive, synergetic) influence the strength of hydrogen bonds [15,16]. The dependence of reactivity and stabilization of the products in the hydrolysis and cyclization reactions on the hydrogen bonding systems appears to be very important (strong hydrogen bonds in substrates or intermediates inhibit the reaction and the weaker types facilitate it) [17].…”

(Z)-N-[2-(Dimethylammonio)ethyl]thioacetamide chloride

“…For details of the synthesis, see Spychała (2000Spychała ( , 2003. For bond-length data, see: Allen (2002).…”

“…Starting from thioacetamide and the appropriate diaminoalkane, the title compound was obtained by the transamination Wallach reaction by refluxing the reaction mixture in ethanol. The reaction was carried out under literature conditions described in the previous papers (Spychała 2000(Spychała , 2003. Solvent: 2-propanol / diethyl ether.…”