Amine Exchange in Formamidines: An Experimental and Theoretical Study

Abstract

N-H-containing formamidines combine a reasonably strong association to carboxylic acids to form complexes of well-defined geometries with a simultaneous proton-induced electrophilicity enhancement that allows for the exchange of their amine portion. The N=C(H)-NH fragment, therefore, undergoes "imine-like" exchange with N-containing nucleophiles. Because of the prototropic equilibrium, the N=C(H)-NH fragment may behave as a "bisimine" centred on the same carbon, in which both N-containing fragments can be exchanged. Considering the proton-induced sensitisation of both C-N units and the well-defined formamidine-carboxylic acid complex geometry, it should be possible to use carboxylic acids as templates for the synthesis of defined architectures by dynamic amine exchange within formamidines. This study highlights three exchange regimes based on the nature of the incoming amine (aliphatic amines, aromatic amines and alkoxyamines), as well as exchange rules based on the amine leaving groups. Following this analysis, a proof of concept for carboxylic acid templated macrocycle formation through dynamic exchange is provided.

Wavelength‐Controlled Dynamic Metathesis: A Light‐Driven Exchange Reaction between Disulfide and Diselenide Bonds

“…Thus DCBs are of significance at both the molecular and the materials level. The dynamic properties of DCBs are triggered by changes in various conditions, such as temperature, pH value, redox conditions, and light …”

Recent advances in dynamic covalent chemistry

“…The reactivity of several types of amines towards formamidines was tested to explore which of them would exchange both ends of the group without changing the geometry, and do so preferably without breaking free of the carboxylate template (Scheme 17). 29 Various alkyl amines and aryl amines were tested (109-114). Arylamines (e.g.…”

Anion-assisted amidinium exchange and metathesis

“…Our observation is corroborated by computational studies by Petitjean and coworkers who showed that a carboxylate ion served as a proton shuttle in the mechanism proposed for the exchange of N,N 0 -diarylsubstituted formamidinium ions. 19 One of the key features of compounds with dynamic covalent bonds is their ability to undergo metathesis reactions. 34,[36][37][38][39] This type of DCR has been widely used in numerous fields including the synthesis of polymers as well as advanced molecular architectures and the exploration of complex chemical systems.…”

“…18 A remarkable example of an amine-based DCR was reported in 2011 by Petitjean and coworkers who recognized the dynamic covalent nature of amidines. 19 In this first report, the authors focused on the exchange of aryl amines with N,N 0 -diarylformamidines and demonstrated that this DCR could be used for the carboxylate-templated assembly of macrocycles. 19 It occurred to us that amidines and their amidinium salts are widely used in coordination chemistry, 20 biomedical science, 21,22 advanced materials, 23,24 and supramolecular chemistry, 25,26 and therefore deserve a wider exploration from the perspective of DCvC.…”