Transfer of structural units through imine exchanges, in solution or without solvent: successive transiminations, stimuli (pH)-modulated covalent switches, and mathematical models

Transfer of structural units through covalent constitutional (non mechanical) switches based on (bis-)imine/amine exchanges (transiminations), can reversibly be modulated by external stimuli, namely by pH changes through alternate additions of acid and base. This is illustrated in this work, in solution, by means of mono- and dialdehydes derived from pyridine. For example, in the case of a dialdehyde Ald, its reaction with an aromatic amine Am1, produces a first bis-imine Im1. Reaction of bis-imine Im1 with an aliphatic amine Am2 produces the aliphatic bis-imine Im2. Addition of acid regenerates the first bis-imine Im1. Subsequent addition of base produces again the second bis-imine Im2. The aromatic amines Am1 used in this work are aniline-based ones, while the aliphatic ones Am2 are primary alkylamines. Trifluoroacetic acid (TFA) and triethylamine (TEA) are used as pH-triggers (external stimuli) in solution. No metal ions are needed to perform the exchanges. In several cases, an excess of aromatic amine Am1, and further, correlatively, an excess of amine Am2 were used to increase the yields. It is also shown that it is possible to invert the steps and to start with aliphatic amine Am2, to continue with aromatic amine Am1 and acid, then, after appropriate adjustments, with base. (Bis-, tris-)imine/(di)aldehyde exchanges in solution were investigated as well. In addition, in a green chemistry approach, under solvent-free conditions, were performed formation of imines, (bis-)imine/amine exchanges and (bis-)imine/(di)aldehyde exchanges, as well as multistep sequences of successive transiminations. In the solvent-free imine/aldehyde-type sequence of successive exchanges, a monoimine is converted into a tris-imine, the tris-imine, into a bis-imine, which finally generates a new monoimine. In the solvent-free imine/amine-type sequence of transiminations, three monoimines derived from the same aldehyde, are successively generated. The experimental work is complemented with an equilibrium-constants-based, mathematical treatment of exchanges between amines and dialdehyde-based bis-imines at equilibrium, in solution: calculation of the composition at equilibrium, modeling of the pH-adaptive behavior of small dynamic libraries of imines, as well as water-dependent distribution curves. Under particular conditions, a simplified mathematical approach to exchanges (transiminations) can be used, where equilibriums involving di- or monoaldehydes do not appear directly.