FULL PAPER * E-mail: karami@mail.yu.ac.ir; Tel.: ＋98-7412223048; Fax: ＋98-7412242167 Received August 6, 2011; accepted October 23, 2011. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.20100206 or from the author. Chin. J. Chem. 2012, 30, 959—964 © 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 959 DOI: 10.1002/cjoc.201100206 A Rapid Access to Novel and Known Benzimidazole Deriva- tives Using Silica Chloride as a Reusable Catalyst Karami, Bahador* ,a Ghashghaee, Vahideh b Khodabakhshi, Saeed a a Department of Chemistry, Yasouj University, Yasouj, Zip Code: 75918-74831, P.O.Box 353, Iran b Department of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran A new application of silica chloride as an easily available and reusable solid acid catalyst for the synthesis of benzimidazole and its derivatives through the condensation of o-phenylenediamines and orthoesters under thermal and solvent-free conditions is described. This novel and eco-friendly method is very cheap and has many advan- tages including excellent yields, short reaction time, and simple work-up procedure. Keywords silica chloride, orthoesters, o-phenylenediamine, benzimidazole Introduction Among the wide variety of nitrogen heterocycles that have been explored for developing pharmaceuti- cally important compounds, benzimidazoles showed a relatively high biological activities such as anti-HIV, [1,2] anti-herpes (HSV-1), [3] anti-influenza, [4] antifungal agent, [5] and raf kinase inhibitor. [6] The most prominent benzimidazole compound in nature is N-ribosyldime- thylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B 12 . [7] The discovery of novel syn- thetic methodologies to facilitate the preparation of compound libraries is a pivotal focal point of research activity in the field of modern organic synthesis. Until now, several methods for the synthesis of benzimidazole and its derivatives have been reported. In fact, the most commonly method is the condensation of an ary- lenediamine with a carbonyl equivalent. [8,9] Also, esters, lactones and anhydrides could produce benzimidazoles through the cyclization of amide. However, some of the reported methods suffer from drawbacks such as the use of toxic and expensive catalyst or solvent, long reaction times, low yield of the products, and difficult work-up procedures. Solid supports have found wide applications in organic reactions and they have advantages such as facilitating the work-up of the reaction, and high selec- tivity accompanied with high yields of the products. It should be noted that the silica gel is used extensively as a support in organic chemistry. [10,11] In this work, as can be seen in Scheme 1, we prepared silica chloride 1 from the reaction of readily available materials such as sili- cagel and thionyl chloride. [12] Scheme 1 Synthesis of silica chloride SOCl 2 O O O Si OH O O O Si Cl + Reflux 48 h + HCl + SO 2 1 SiO 2 SiO 2 Considering the wide use of catalyst in chemistry, we tried to report a new application of silica chloride (SiO 2 -Cl) on synthesizing the substituted benzimida- zoles. Recently, silica chloride was used for several or- ganic transformations such as one-pot synthesis of 13- aryl-indeno[1,2-b]naphtha[1,2-e]pyran-12(13H)-ones (Wu and co-workers), [13] deprotection of trimethylsilyl ethers to corresponding alcohols (Bamoniri and co-workers), [14] synthesis of 4-aryl substituted 3,4-dihy- dropyrimidinones (Kaushik and co-workers), [15] multi-component synthesis of amidoalkyl-2-naphthols under sonic conditions (Pasha and co-workers), [16] and oxidation of urazoles (Zolfigol and co-workers). [17] The main aims of this research are to obtain a novel class of benzimidazoles and benzimidazole oximes, and also introduction of a new application of silica chloride as solid acid catalyst in organic synthesis. Results and Discussion In connection with our studies on synthesis of or- ganic compounds, [18] we have now found that silica chloride can be used as an efficient, safe and very cheap catalyst for the condensation of o-phenylenediamines 2 and orthoesters 3 under thermal and solvent-free condi-