Quantum chemical study of the impact of protective association on the chemoselective synthesis of carboxybetaine from 2-(dimethylamino)ethanol and acrylic acid

Abstract Targeted carboxybetaine synthesis is an important process that one can apply to prepare polymeric materials with various unique properties or low molecular weight products, such as deep eutectic solvents based on acrylic acid formulated for the specific tasks. Analyzing the mechanism of carboxybetaine formation, it was found that with an excess of amine, the H-bond formed between amine nitrogen and the acidic proton of the acrylic acid was strong enough to protect the intermediate obtained after carbanion protonation from the interaction with acrylate anion, thus facilitating the formation of quaternary ammonium salts as the final product at the beginning of the reaction instead of the desired carboxybetaine. Similarly, a threefold excess of acrylic acid should also lead to the preferential formation of the quaternary salt due to the protection of the half-product from the interaction with acrylate anion via cyclic dimer formation with two strong H-bonds. From the other side, calculations revealed that a twofold excess of acrylic acid should provide formation of carboxybetaine as the dominant product. The discussed energy profiles were supplemented with extensive natural bond order analysis in the course of which delocalization energies were calculated and used to discuss the strength of intermolecular donor–acceptor interactions within the considered molecular systems.