Cascade aza-Michael Addition-Cyclizations; Toward Renewable and Multifunctional Carboxylic Acids for Melt-Polycondensation

Abstract

Although the aza-Michael addition reaction on various unsaturated (di-)carboxylic acids and esters of, for example, itaconic acid, is well-known, the consecutive cyclization reaction has not received much attention in literature. The products of this aza-Michael cascade reaction, being mono- or di-carboxylic acid or ester functionalized N-alkyl-pyrrolidone structures, prove interesting for melt-polycondensation reactions as they exhibit excellent stability at elevated temperatures. In other words, this reaction is a toolbox for the generation of renewable monomers and, in turn, polymers with tunable physiological properties. Therefore, this work provides an overview of the state-of-the-art of the cascade aza-Michael addition-cyclization reactions on biobased unsaturated acids and esters, and their use in polymerization reactions. Furthermore, we extend this overview with the cascade aza-Michael addition-cyclization reaction of trans-trimethyl aconitate with di-amines to form a tetra-functional N-alkyl-bis-(pyrrolidone dimethylcarboxylate), which exhibits excellent thermal stability and could effectively be used as monomer in polycondensation reactions. Importantly, the aza-Michael addition reaction between primary amines and trans-trimethyl aconitate can be considered a click-reaction; it proceeds quantitatively within minutes under ambient conditions and follows the principles of green chemistry.

Direct Conjugation of Streptavidin to Encoded Hydrogel Microparticles for Multiplex Biomolecule Detection with Rapid Probe-Set Modification

“…In our case, α,β-unsaturated compounds are unreacted double bonds, and nitrogen donors are primary amine groups of streptavidin. Although the aza-Michael addition reaction is not the part of the classically defined click reactions, their concepts are similar to that of click reactions including (1) proceeds in mild and aqueous conditions, (2) insensitivity to oxygen or water, and (3) applicability to biomolecules without producing hazardous substances, and thus has been considered to fit click criteria [32][33][34][35]. In addition, the reaction is one of the most widely used reactions for the addition of amines to acrylates, especially in protein modification [36,37].…”

Highlight on the Mechanism of Linear Polyamidoamine Degradation in Water

“…Among the factors that influence the reactivity of aliphatic amines, nucleophilicity and steric hindrance are of fundamental importance. These elements may conflict: Dibutylamine, notwithstanding its higher nucleophilicity, reacts slower than aliphatic prim-amines [ 38 ]. Prim-amines can undergo double aza-Michael addition [ 39 ].…”

Aconitic Acid Recovery from Renewable Feedstock and Review of Chemical and Biological Applications

“…There are multiple studies incorporating forms of aconitic acid, especially trimethyl- trans -aconitate, in “green chemistry” reactions. For instance, trimethyl trans -aconitate can be used in an aza-Michael reaction with primary amines as a “green” click reaction to produce “tetra-functional N-alkyl- bis-(pyrrolidone dimethylcarboxylate)” as a monomer for polymer reactions [ 23 ]. Furthermore, aconitic acid, along with other polycarboxylates such as itaconic, fumaric, and malic acids, can be used to produce green surfactants by addition reactions [ 25 ].…”