Kinetic Selectivity and Thermodynamic Features of Competitive Imine Formation in Dynamic Covalent Chemistry

Abstract

The kinetic and thermodynamic selectivities of imine formation have been investigated for several dynamic covalent libraries of aldehydes and amines. Two systems were examined, involving the reaction of different types of primary amino groups (aliphatic amines, alkoxy-amines, hydrazides and hydrazines) with two types of aldehydes, sulfobenzaldehyde and pyridoxal phosphate in aqueous solution at different pD (5.0, 8.5, 11.4) on one hand, 2-pyridinecarboxaldehyde and salicylaldehyde in organic solvents on the other hand. The reactions were performed separately for given amine/aldehyde pairs as well as in competitive conditions between an aldehyde and a mixture of amines. In the latter case, the time evolution of the dynamic covalent libraries generated was followed, taking into consideration the operation of both kinetic and thermodynamic selectivities. The results showed that, in aqueous solution, the imine of the aliphatic amine was not stable, but oxime and hydrazone formed well in a pH dependent way. On the other hand, in organic solvents, the kinetic product was the imine derived from an aliphatic amine and the thermodynamic products were oxime and hydrazone. The insights gained from these experiments provide a basis for the implementation of imine formation in selective derivatization of mono-amines in mixtures as well as of polyfunctional compounds presenting different types of amino groups. They may in principle be extended to other dynamic covalent chemistry systems.

Rewiring Chemical Networks Based on Dynamic Dithioacetal and Disulfide Bonds

“…Differences in reactivity between isolated and networked reversible reactions have been previously described by the group of Lehn for imine formation and exchange, showing that competition between different amino compounds may lead to out‐of‐equilibrium states in which a slow formation step leads towards the equilibrium with a nonlinear kinetics. In other example, some simultaneous communicating reactions have been shown to have a very slow velocity, impeding the exact determination as to whether the equilibrium point has been reached or not …”

Dynamic Covalent Self‐Assembly Based on Oxime Condensation

“…Thepartially negatively-charged carbon atom is therefore less electrophilic,p rotecting the C=Nb ond from nucleophilic attack by water molecules or other nucleophiles. Oxime, [21] namely -C= N À O-, is reported [22] to be more robust than hydrazone both thermodynamically and kinetically.T here are af ew reasons that can explain the enhanced stability of oxime compared to its hydrazone counterparts.F irst, the NH 2 unit in either the alkoxyamino (-OÀNH 2 )o rh ydrazide (-NHÀNH 2 )p recursor could undergo protonation in water, which could be considered as ac ompetitive process of nucleophilic addition. Thed ynamic nature of hydra-zone,however, jeopardizes the inherent stabilities of the selfassembled products.F or example,w eo bserved that the catenanes [18,19] containing hydrazone undergo decomposition via hydrazone exchange during counteranion exchange or solvent removal, even in the condition of low temperature and/or in the absence of acid catalyst.…”

“…Avariety of macrocycles, [15,16] cages, [17] catenanes [18,19] as well as knots [20] were obtained in water based on hydrazone condensation in pure water. Oxime, [21] namely -C= N À O-, is reported [22] to be more robust than hydrazone both thermodynamically and kinetically.T here are af ew reasons that can explain the enhanced stability of oxime compared to its hydrazone counterparts.F irst, the NH 2 unit in either the alkoxyamino (-OÀNH 2 )o rh ydrazide (-NHÀNH 2 )p recursor could undergo protonation in water, which could be considered as ac ompetitive process of nucleophilic addition. Oxime, [21] namely -C= N À O-, is reported [22] to be more robust than hydrazone both thermodynamically and kinetically.T here are af ew reasons that can explain the enhanced stability of oxime compared to its hydrazone counterparts.F irst, the NH 2 unit in either the alkoxyamino (-OÀNH 2 )o rh ydrazide (-NHÀNH 2 )p recursor could undergo protonation in water, which could be considered as ac ompetitive process of nucleophilic addition.…”

“…Thed ynamic nature of hydra-zone,however, jeopardizes the inherent stabilities of the selfassembled products.F or example,w eo bserved that the catenanes [18,19] containing hydrazone undergo decomposition via hydrazone exchange during counteranion exchange or solvent removal, even in the condition of low temperature and/or in the absence of acid catalyst. Oxime, [21] namely -C= N À O-, is reported [22] to be more robust than hydrazone both thermodynamically and kinetically.T here are af ew reasons that can explain the enhanced stability of oxime compared to its hydrazone counterparts.F irst, the NH 2 unit in either the alkoxyamino (-OÀNH 2 )o rh ydrazide (-NHÀNH 2 )p recursor could undergo protonation in water, which could be considered as ac ompetitive process of nucleophilic addition. Protonation of NH 2 ,t os ome extent, suppresses the latter process leading to C = Nb ond formation.…”

Molecular Networks in Dynamic Multilevel Systems

“…Therefore, the two exchange pools can mutuallya ffect each other as ac onsequenceo ft heir competence for the buildingb lock type they both have in common. Some pairs of reversible reactions that communicatew ith each other are:t he exchange of disulfides and thioesters, [6] dithioacetals, [23] and thio-Michaela dducts; [24] the exchange of imines and hydrazones, oximes, [25] and nitrones; [26] andt he exchange of nitroaldol adducts and hemithioacetals. [27] Simultaneous one-pot setting…”