Efficient (bromodimethyl)sulfonium bromide mediated synthesis of benzimidazoles I Biswanath Das, * Harish Holla and Yallamalla Srinivas Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India Received 18 September 2006; revised 20 October 2006; accepted 2 November 2006 Available online 21 November 2006 Abstract—Benzimidazoles have been efficiently synthesized in high yields by treatment of 1,2-phenylenediamine with aldehydes using (bromodimethyl)sulfonium bromide at room temperature. Ó 2006 Elsevier Ltd. All rights reserved. 1. Introduction The benzimidazole moiety is found in various bioactive compounds having antiviral, antiulcer, antihypertension and anticancer properties. 1 General methods for the synthesis of benzimidazoles involve treatment of 1,2- phenylenediamines with carboxylic acids or various derivatives under strongly acidic conditions or with aldehydes followed by oxidation. 2,3 2. Results and discussion In continuation of our work 4 on the development of useful synthetic methodologies, we have observed that benzimidazoles can be synthesized efficiently by treat- ment of 1,2-phenylenediamine with aldehydes using (bromodimethyl)sulfonium bromide at room tempera- ture (Scheme 1). Several aldehydes (aromatic, heteroaromatic and ali- phatic) underwent the above conversion to form a series of benzimidazoles (Table 1). Aromatic aldehydes con- taining both electron-donating and electron-withdrawing groups worked well. Aliphatic a,b-unsaturated aldehydes (Table 1, entry 3m) also afforded the desired products in high yields. The method is suitable for the preparation of benzimidazoles from an acid sensitive aldehyde such as furfuraldehyde (entry 3n) and the sterically hindered aldehyde 2-naphthaldehyde (entry 3o). The reaction conditions are mild and the experimental procedure is simple. The products were formed in high yields (72– 91%). The structures of the products were determined from their spectral ( 1 H NMR, IR and MS) data. (Bromodimethyl)sulfonium bromide is an inexpensive reagent. It has been used mainly as a catalyst but its scope has not been fully explored. 5 Here it has been applied for oxidative dehydrogenation of the cyclic NH 2 NH 2 + O H N H N R R Me 2 SBrBr MeCN r.t., 4-8 h + - 1 2 3 72-91% Scheme 1. 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.11.018 Keywords: Aldehyde; Diamine; (Bromodimethyl)sulfonium bromide; Benzimidazole. q Part 119 in the series, ‘Studies on novel synthetic methodologies’. IICT Communication No. 061021. * Corresponding author. Tel./fax: +91 40 27160512; e-mail: biswanathdas@yahoo.com Tetrahedron Letters 48 (2007) 61–64