Selective Synthesis of Benzimidazoles from o-Phenylenediamine and Aldehydes Promoted by Supported Gold Nanoparticles.

Marina A Tzani,Ioannis N Lykakis,Catherine Gabriel

doi:10.3390/nano10122405

Marina A Tzani, Ioannis N Lykakis + Show 1 more

Open Access

https://doi.org/10.3390/nano10122405

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Abstract

We investigated the catalytic efficacy of supported gold nanoparticles (AuNPs) towards the selective reaction between o-phenylenediamine and aldehydes that yields 2-substituted benzimidazoles. Among several supported gold nanoparticle platforms, the Au/TiO2 provides a series of 2-aryl and 2-alkyl substituted benzimidazoles at ambient conditions, in the absence of additives and in high yields, using the mixture CHCl3:MeOH in ratio 3:1 as the reaction solvent. Among the AuNPs catalysts used herein, the Au/TiO2 containing small-size nanoparticles is found to be the most active towards the present catalytic methodology. The Au/TiO2 can be recovered and reused at least five times without a significant loss of its catalytic efficacy. The present catalytic synthetic protocol applies to a broad substrate scope and represents an efficient method for the formation of a C–N bond under mild reaction conditions. Notably, this catalytic methodology provides the regio-isomer of the anthelmintic drug, Thiabendazole, in a lab-scale showing its applicability in the efficient synthesis of such N-heterocyclic molecules at industrial levels.

Highlights

Benzimidazole or 1H-1,3-benzodiazole-based heterocycles are structurally similar to naturally occurring nucleotides, i.e., adenine base of the DNA, as well as a component of vitamin B12, and have extensively been used in drug synthesis and medicinal chemistry (Figure 1) and display a wide range of biological and clinical applications [1,2,3,4,5,6]
The first route involves the coupling between o-phenylenediamine with carboxylic acids or their derivatives [22,23,24]
Synthesis of 2-Aryl and 2-Alkyl Benzimidazoles Catalyzed by Gold Nanoparticles

Summary

Introduction

Benzimidazole or 1H-1,3-benzodiazole-based heterocycles are structurally similar to naturally occurring nucleotides, i.e., adenine base of the DNA, as well as a component of vitamin B12, and have extensively been used in drug synthesis and medicinal chemistry (Figure 1) and display a wide range of biological and clinical applications [1,2,3,4,5,6]. The second route involves condensation reactions between o-phenylenediamine and aldehydes or alcohols via a dehydrogenated coupling, followed by oxidative cyclodehydrogenation [24,25], but in many of these methods, a stoichiometric amount of oxidizing agents is a prerequisite (Scheme 1) [26,27,28,29] Other methods such as thermal- or acid-promoted synthesis as well as microwave, sonicator, or ultrasound methods are known [24].

Materials

Catalytic Reaction

Recycling Reaction

Evaluation of the Catalytic Conditions