ETD

• DES
• DFT
• Diels Alder
• Green Chemistry
• NBO
• NEB-TS
• ONIOM
• QTAIM
• XTB

This thesis explores Diels–Alder reactions in deep eutectic solvents (DESs) through computational methods within the framework of green chemistry. The study aims to clarify the reaction mechanisms and the factors governing regio- and stereoselectivity, focusing on the effects of substituents and solvent. The reaction of 5-hydroxymethylfurfural (HMF), a renewable compound from lignocellulosic biomass, provides sustainable access to valuable intermediates for bioactive and pharmaceutical molecules. Local reactivity descriptors (Fukui functions, softness, nucleophilicity and electrophilicity indices) were used to identify the most reactive sites, while NBO and QTAIM analyses explained the electronic origin of selectivity and specific solute–solvent interactions. Using an ONIOM multilayer approach, a choline chloride/propylene glycol DES was modeled. Results show that the endo product is kinetically favored, with secondary interactions lowering the activation energy and the solvent selectively stabilizing endo conformations.