Deep Eutectic Solvent Choline Chloride/p‑toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition

• Published in: Journal of organic chemistry 2021-01, Vol.86 (1), p.223-234
• Main Authors: Gutiérrez-Hernández, Abelardo, Richaud, Arlette, Chacón-García, Luis, Cortés-García, Carlos J, Méndez, Francisco, Contreras-Celedón, Claudia Araceli
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c02039

Deep eutectic solvents (DESs) have been considered “the organic reaction medium of the century” because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample. This article shows a systematic study of the impact of DES choline chloride/p-toluenesulfonic acid and DES choline chloride/p-toluenesulfonic acid–water in the aza-Michael addition of arylamines to maleimide to obtain aminopyrrolidine-2,5-dione derivatives. The derivatives are obtained under very mild reaction conditions with good yield. The global reaction is exothermic, spontaneous, permitted by enthalpy, and prohibited for entropy. The calculated potential energy surface shows a reaction mechanism of six steps controlled by enthalpy (except the last step that is controlled by entropy). The water incorporated in the supramolecular DES complex stabilizes the transition states and favors the enthalpy-driven binding. A set of H/D exchange NMR experiments validates the transition state existing in the fourth stage of the mechanism.