Nano indium oxide: an efficient catalyst for the synthesis of 1,2-disubstituted benzimidazoles in aqueous media Sougata Santra, Adinath Majee ⇑ , Alakananda Hajra ⇑ Department of Chemistry, Visva-Bharati (A Central University), Santiniketan 731 235, India article info Article history: Received 2 October 2011 Revised 2 February 2012 Accepted 6 February 2012 Available online 13 February 2012 Keywords: Nano indium oxide Benzimidazole 1,2-Phenylenediamines Aldehydes Aqueous media abstract Synthesis of 1,2-disubstituted benzimidazoles has been developed by the condensation of diamine with aldehydes using nano In 2 O 3 as an efficient catalyst under mild reaction conditions in aqueous media. The procedure is applicable to aryl, aliphatic, heteroaryl aldehydes. In 2 O 3 nanoparticles are recyclable with- out the loss of significant catalytic activity. Ó 2012 Elsevier Ltd. All rights reserved. Benzimidazole and its derivatives are very important com- pounds due to their pharmacological 1 and biological activities. 2 Many commercial medicines such as Liarozole, 3 Omeprazole, 4 Thiabendazole 5 , and Domperidone 6 contain benzimidazole and its analogue dihydrobenzimidazole. A few methods are available for the synthesis of 1,2-disubstituted benzimidazoles like N-alkylation of o-nitroanilides followed by reductive cyclization, 7 N-alkylation of 2-substituted benzimidazole in the presence of a strong base, 8 cyclocondensation of N-substituted o-aminoanilides, 9 and the condensation of N-substituted phenylenediamines with the sodium salt of a-hydroxybenzylsulfonic acid. 10 Another proto- col is the direct condensation of 1,2-phenylenediamines with aryl aldehydes using a variety of catalysts such as acetic acid, 11 SDS micelles, 12 cobalt(II) chloride, 13 trimethylsilyl chloride, 14 Amber- lite IR-120 15 and organocatalyst like L-proline. 16 But very few methods are less selective in terms of N-1 substitution, as a result 2-substituted benzimidazole along with 1,2-disubstituted benz- imidazole is formed. All these methodologies are applicable to aryl aldehydes only. To the best of our knowledge there is only one example for acyclic aldehyde reported by Radatz et al. 17 Metal nanoparticles have attracted considerable interest in synthetic or- ganic chemistry due to their high catalytic activity, reusability and benign character in the context of green chemistry. 18 However, nano In 2 O 3 catalyzed reactions are rare in organic synthesis. 18i,19a In continuation of our research work using nano In 2 O 3 and indium 19 in organic synthesis here we are pleased to report that a mixture of aldehyde, phenylenediamine in the presence of nano In 2 O 3 (5 mol %) in an EtOH/H 2 O (2:1) mixture at 60 °C furnished 1,2-disubstituted benzimidazoles in good yields (Scheme 1). The experimental procedure 20 is very simple, a mixture of aldehyde (2 mmol), phenylenediamine (1 mmol) was stirred in the presence of nano In 2 O 3 (5 mol %) in an EtOH/H 2 O (2:1) mixture at 60 °C for a certain period as required for the completion (TLC). To optimize the reaction conditions we have used nano In 2 O 3 for the direct condensation between phenylenediamine (1 mmol) and benzaldehyde (2 mmol) under different concentrations and using different solvents as summarized in Table 1. Nano In 2 O 3 (5 mol %) was better suited to afford 1,2-disubstituted benzimidaz- oles in an ethanol/water (2:1) mixture at 60 °C. Ethanol/water (2:1) mixture appeared to be the best choice among the common solvents such as MeOH, CH 3 CN, THF, toluene, dioxane. Lower conversions were obtained when indium oxide powder and other metal catalysts such as NiO (nano), CuO (nano), and ZnO (nano) were used. Negligible amount of the product was formed in the absence of catalyst. 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2012.02.021 ⇑ Corresponding authors. Tel./fax: +91 3463 261526. E-mail addresses: adinath.majee@visva-bharati.ac.in (A. Majee), alakananda. hajra@visva-bharati.ac.in (A. Hajra). NH 2 NH 2 N N R R + 1 mmol 2 mmol Nano In 2 O 3 (5 mol%) EtOH/H 2 O (2:1) 60 °C RCHO N H N R R = aromatic, aliphatic + 84 - 92% 0% Scheme 1. Synthesis of 1,2-disubstituted benzimidazoles. Tetrahedron Letters 53 (2012) 1974–1977 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet