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

HERRERA-CANO, NATIVIDAD; URANGA, JORGE; NARDI, M; PROCOPIO A.; WUNDERLIN D.A.; SANTIAGO, A.N.

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY

BEILSTEIN-INSTITUT

Año: 2016 vol. 12 p. 2410 - 2419

1860-5397

An improved andgreener protocol for the synthesis of benzimidazole derivatives, starting from o-phenylenediamine, with differentaldehydes is reported. Di-condensation products were selectively obtained whenEr(OTf)3 was used as catalyst in presence of electron-rich aldehydes.Conversely, the formation ofmono-condensation products was the preferred path in absence of this catalyst. Oneadditional advantage of using Er(OTf)3as catalyst was the formation of a single product, avoiding extensive isolationand purification of products, which is frequently found with these reactions inabsence of this catalyst. Theoreticalcalculations helped to understand the different reactivity found for thesereactions. Thus, we found that the charge density on the oxygen of the carbonylgroup was a significant factor to facilitate the reaction pathway. Moreover, electron-richaldehydes facilitated the coordination of aldehydes to the catalyst, which favouredthe addition of the amine group to the carbonyl group, helping with theformation of di-condensation products. Reactions with aliphatic or aromatic aldehydeswere possible, without using organic solvents and by a one-pot procedure withshort reaction time (2-5 min), affording excellent yields (75-99 %) and asingle product. So far, this convenient and eco-friendly methodology offers numerous benefits withrespect to different protocols reported for similar compounds.