Solution Chemistry of N,N’‐Disubstituted Amidines: Identification of Isomers and Evidence for Linear Dimer Formation

Abstract

Amidines have found widespread use, but their solution chemistry remains poorly understood. In this work, X-ray crystallographic and detailed 1D and 2D NMR spectroscopic studies have been performed to elucidate the preferred isomers and their interconversion mechanisms. Amidines are shown to exist as a mixture of E-syn and Z-anti isomers in solution and to form dimeric H-bonded aggregates that are also observed in the solid state. Rapid proton exchange/tautomerization reactions occur within the dimers, allowing fast interconversion of E-syn and Z-anti isomers even at very low temperatures. Three different exchange processes were identified in solution, and on this basis the unusual concentration and temperature dependence of the NMR spectra of these amidines could be explained. This work thus resolves some of the puzzles of the complex solution chemistry of this prominent class of compounds.

Experiments and DFT Computations Combine to Decipher Fe-Catalyzed Amidine Synthesis through Nitrene Transfer and Nitrile Insertion

“…The amidine Ph-CH(Me)-NH-C(Me)=NTs can indeed exist as two isomers with the tosyl and methyl groups located on the same side (E isomer) of the imine double bond or the opposite one (Z isomer). 44 It must be noted that the values of the chemical shifts and the coupling constants of these doublets are close to those of the amine Ph-CH(Me)- 15 NHTs (Figure 6a) in agreement with a similar structure. To summarize, these 15 N-NMR experiments indicate that the nitrogen bound to ethylbenzene benzylic carbon originates from acetonitrile as suggested by the DFT study.…”

“…It is very similar to that of N-(1-phenylethyl)-N'tosylacetimidamide reported by Bagchi et al 26 and shows the E-syn configuration of the amidine function between the substrate and the tosyl group. 44 However, it does not provide any clue on the origins of the two N atoms. As a matter of fact, the possibility that the substrate-bound nitrogen N2 comes from the tosyliminoiodinane cannot be ruled out owing to the fact that tosyl migration has been observed in similar reactions in certain instances.…”

Rhodium(I) Complexes of N‐Aryl‐Substituted Mono‐ and Bis(amidinates) Derived from Their Alkali Metal Salts

“…A plausible explanation is aggregation in solution. In 2016, Meyer et al described the formation of linear dimers of symmetric N , N′ ‐disubstituted amidines in solution. They were able to identify dimeric aggregates of the ( E/Z, syn/anti ) isomers of bulky amidines, derived through rotation and tautomerization.…”

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide)

“…In the case of amidines, the formation of mixtures of E and Z isomers of 1-6 was detected using thin-layer chromatography, but all attempts to separate them by column chromatography on silica were failed. This can be explained by fast isomerization of pure isomers in solution with the formation of equilibrium mixtures of E and Z isomers, which is typical for organic amidines [82]. In all mixtures of isomers we observed an excess of Z isomers over E isomers with the E:Z ratio varying from 1:1.2 to 1:2.3 depending on the amine used (the measurements were performed by comparing the integrated intensities of signals of the same groups for different isomers in the 1 H NMR spectra).…”

“…Although the formation of mixtures of the E and Z isomers for organic amidines is well known [82], the presence of E-and Z-isomers in solutions of boronated amidines prepared by addition of primary amines to nitrilium derivatives of polyhedral boron hydrides was reported only for the nido-decaborane [72] and nido-carborane [77,79] based amidines. This could be an indication that for the other boronated amidines only one isomer is present in solution, or that the interconversion between the E-and Z-isomers is fast on the NMR time scale.…”