Mechanistic Studies on Lewis Acid Catalyzed Biginelli Reactions in Ionic Liquids: Evidence for the Reactive Intermediates and the Role of the Reagents

Abstract

This paper describes the use of common Lewis acids supported in imidazolium-based ionic liquids as the catalysts to promote the Biginelli reaction. The ionic liquid effect and the reaction mechanism are discussed on the basis of nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS), and theoretical calculations. Indeed, the results showed that the ionic medium plays a fundamental role in the synthesis of biologically active dihydropyrimidinones due to the stabilization of the charged intermediates proposed in the mechanism. When conducted in an ionic liquid as solvent, the reaction mechanism is more complex than in other Lewis acid catalyzed Biginelli reactions.

Charge-tagged ligands: useful tools for immobilising complexes and detecting reaction species during catalysis

“…This reaction catalysed by a Lewis acid in an IL was evaluated by Neto and co-workers using ESI-MS. 112 This multi-component reaction was used to obtain the biologically active 3,4-dihydropyrimidin-2(1H)-one (DHPMs). As indicated by ESI-MS experiments, the ionic medium plays a fundamental role in this synthesis, owing to the stabilisation of the charged intermediates.…”

Styrene polymerization efficiently catalyzed by iron-containing imidazolium-based ionic liquids: Reaction mechanism and enhanced ionic liquid effect

“…For instance, we have shown that BMI.InCl 4 is capable of promoting the tetrahydropyranylation of alcohols [12], in situ generation and stabilization of iminium ions [13] and to copromote the formation and stabilization of charged-intermediates during transesterification reactions [14]. We have also recently investigated iron-based ILs as catalysts for oxidation [15], reduction [16] and multicomponent reactions [17][18][19]. In this sense, we have therefore envisaged that the iron-containing ILs could also work as efficient catalysts for the styrene polymerization.…”

The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction

“…45,49,[55][56][57][58] Soon after its discovery, various mechanisms involving protonated intermediates were proposed, as shown in Figure 1. The first mechanism, the so-3 called iminium route, 55 considers the condensation of the aldehyde and urea to form a C-N bond to give the iminium and followed by a nucleophilic addition of the β-keto ester.…”