Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

Abstract

An improved and greener protocol for the synthesis of benzimidazole derivatives, starting from o-phenylenediamine, with different aldehydes is reported. Double-condensation products were selectively obtained when Er(OTf)3 was used as the catalyst in the presence of electron-rich aldehydes. Conversely, the formation of mono-condensation products was the preferred path in absence of this catalyst. One of the major advantages of these reactions was the formation of a single product, avoiding extensive isolation and purification of products, which is frequently associated with these reactions.Theoretical calculations helped to understand the different reactivity established for these reactions. Thus, we found that the charge density on the oxygen of the carbonyl group has a significant impact on the reaction pathway. For instance, electron-rich aldehydes better coordinate to the catalyst, which favours the addition of the amine group to the carbonyl group, therefore facilitating the formation of double-condensation products.Reactions with aliphatic or aromatic aldehydes were possible, without using organic solvents and in a one-pot procedure with short reaction time (2–5 min), affording single products in excellent yields (75–99%). This convenient and eco-friendly methodology offers numerous benefits with respect to other protocols reported for similar compounds.

Green Synthesis of Privileged Benzimidazole Scaffolds using Active Deep Eutectic Solvent

“…The reactions performed with 2 molar amount of aldehydes containing electron withdrawing groups such as p-chloro or p-nitro benzaldehyde (Table 4, entries 7-8) afforded the corresponding 2-monosubstituted benzimidazoles (7a and 8a) in good yields without observing the formation of disubstituted derivative. This result is in accordance with the data reported in the literature [21].…”

“…Spectral data were in accordance with the literature [21]. Spectral data were in accordance with the literature [21].…”

Erbium Salts as Non-Toxic Catalysts Compatible with Alternative Reaction Media

“…Er(OTf) 3 efficiently catalyzed the selective formation of benzimidazole derivatives, avoiding tedious work-up and procedures for product separation [39]. Two-substituted benzimidazoles were selectively obtained in high yields, with short reaction times, through the reaction of phenylenediamine with various aldehydes at a low temperature (1-2 • C), or at 80 • C in the case of electron-deficient aldehydes.…”

Montmorillonite K10-Catalyzed Solvent-Free Conversion of Furfural into Cyclopentenones

“…Taking into account the stability and catalytic activity of MK10, and considering our knowledge in developing eco-friendly reactions for the synthesis of pharmaceutical compounds [70][71][72][73][74][75][76][77][78], we decided to test the MK10 as catalyst in the cyclization of the furfural for the synthesis of bifunctionalized cyclopentenones. The catalytic process showed high conversion and selectivity under MW irradiation.…”