Formation and Out‐of‐Equilibrium, High/Low State Switching of a Nitroaldol Dynamer in Neutral Aqueous Media

Abstract

The nitroaldol reaction is demonstrated as an efficient dynamic covalent reaction in phosphate buffers at neutral pH. Rapid equilibration was recorded with pyridine‐based aldehydes, and dynamic oligomerization could be achieved, leading to nitroaldol dynamers of up to 17 repeating units. The dynamers were applied in a coherent stimuli‐responsive molecular system in which larger dynamers transiently existed out‐of‐equilibrium in a neutral aqueous system rich in formaldehyde, controlled by nitromethane.

Interdependent Dynamic Nitroaldol and Boronic Ester Reactions for Complex Dynamers of Different Topologies

“…Thus, compounds with one, two, or multiple reacting groups were selected, including ditopic species with different geometries. For the nitroaldol products, ditopic bisnitroalkanediol 2, produced from pyridine-2,6-dicarboxaldehyde (A2) and 2-nitroethanol (N2), and polytopic dynamer 3 (poly(A2-N1)), [33] produced from aldehyde A2 and nitromethane (N1), were chosen. These nitroaldol species contain two or multiple 1,3-diol functionalities in a linear arrangement, thereby leading to main chain dynamers.…”

“…[16,[19][20][21][22][23][24][25][26][27][28][29][30][31] Systems based on dynamic covalent bonds can furthermore be applied to chemical oscillation, and lead to complex behavior, switching modes, or out-of-equilibrium regimes. [32][33][34][35][36][37][38][39][40] Moreover, the unique chemistries of reversible chemical bonds enable transfer, inhibition, or emergence of systemic properties, typically based on multiple dynamic processes operating in conjunction. [41][42][43][44] In this regard, dynamic covalent polymers (dynamers) are gaining a lot of attention due to their many features, such as self-assembly/self-organization, adaptive/responsive functions, and emergent properties.…”

“…This challenge has been addressed in the present study where such complex dynamic systems have been established and applied to dynamer formation. In complement to the dynamic nitroaldol (Henry) reaction, for example applied to dynamer formation, [33] reversible boronic ester formation was chosen for the systems. The high chemoselectivity of boronic acids towards diols makes them attractive for a variety of structures, such as macrocycles and cages.…”

Polymerization, Stimuli-induced Depolymerization, and Precipitation-driven Macrocyclization in a Nitroaldol Reaction System

“…45 Hence, employing reversible C-C bonds in molecules can potentially increase the dynamic performance of the whole entity since even the molecular skeleton is dynamic. 3 Due to its efficiency in generating new C-C bonds, the nitroaldol (Henry) reaction has been widely applied in organic synthesis since it was first discovered in 1895. [46][47][48] The reaction is robust, stereogenic, self-contained, and can be carried out under mild conditions.…”

Design of Stimuli‐Responsive Dynamic Covalent Delivery Systems for Volatile Compounds (Part 1): Controlled Hydrolysis of Micellar Amphiphilic Imines in Water

“…[29] For practical implementation, dynamic covalent bonds usually need to combine fast equilibration times together with sufficient thermodynamic stabilities. [30,31] Among the efficient systems described in the literature, one can find examples based on the exchange of disulfides [32] and thioesters; [33,34] on Diels-Alder [35] and nitroaldol [36] reactions; on dynamic native chemical ligation; [37] and on acetal, [38] aminal, [39,40] boronic esters, [41,42] and imine (Schiff base) condensations. [19,43,44] In the present article, we take a closer look at the possibility of increasing imine bond stability in water by taking advantage of surfactant micellization.…”