Cu(II)-catalyzed Friedel-Crafts reaction of 2-thiopyrimidine derivatives with aldehydes utilizing water as cocatalyst in the presence of surfactant: elucidation the role of water on reaction mechanism and tautomerism

Abstract

Here, we reported a Cu(II)-catalyst with a water-tolerant active site for Friedel-Craft reaction of 4-amino-6-hydroxy-2-mercatopyrimidine with various aldehydes in aqueous medium using a surfactant. A portion of the hydrated homogeneous copper(II)-complex still acts as an effective Lewis acid in this reaction, which aligns with the theoretical study (DFT) and various control experiments. The study revealed that the involvement of a water-assisted hydrogen atom transfer (HAT) was found, indicating the importance of water surrounding. The influence of explicit water solvation models (20 and 60 molecules shells) on the structures and energies of selected intermediates and transition states was studied. Furthermore, the gram-scale synthesis, recyclability of the reaction medium and various green chemistry parameters demonstrated the sustainability of our process. Additionally, the structure and relative energies of the various tautomers of product bis-(2-thiopyrimidine) compounds were investigated at the DFT and SCS-MP2 levels. The water-assisted tautomerization mechanism is described, showing that keto-form is prevalent in neutral solutions. The doubly protonated and quadruply deprotonated forms exist in acidic and basic media, which is confirmed by the TDDFT theoretically predicted UV-vis spectra and DFT calculated 1H-NMR shifts that are supported by the respective experimental spectra.