Letters in Organic Chemistry, 2012, 9, 155-159 155 1875-6255/12 $58.00+.00 © 2012 Bentham Science Publishers Efficient Synthesis of 3-Aminoimidazo[1,2-a] Pyridines Using Silica- Supported Perchloric Acid (HClO 4 -SiO 2 ) as a Novel Heterogenous Catalyst Azizollah Habibi* ,1 , Zahra Tarameshloo 1 , Shahnaz Rostamizadeh 2 and Ali M. Amani 2 1 Faculty of Chemistry, Tarbiat Moallem University, No. 43, Mofateh Avenue, Tehran, Iran 2 Department of Chemistry, Faculty of Sciences, K.N. Toosi University of Technology, Tehran, Iran Received September 09, 2011: Revised January 16, 2012: Accepted January 17, 2012 Abstract: One pot three-component reaction of 2-amino pyridines, aldehydes and isocyanides in the presence of silica- supported perchloric acid (HClO 4 -SiO 2 ), produces 3-aminoimidazo[1,2-a] pyridines in excellent yields. The reaction time is short and work up of reaction is very easy. New compounds were identified by IR, 1 H NMR, 13 C NMR and Mass spectrum. Keywords: 3-Aminoimidazo[1,2-a] pyridine, isocyanide, multi-component reaction, silica-supported perchloric acid (HClO 4 - SiO 2 ). INTRODUCTION Heterocyclic compounds are particularly interested in all branches of chemistry especially in medicinal chemistry. These classes of compounds are widely distributed in nature and are essential to life. Extensive researches have been done to discover new heterocyclic compounds and develop novel methods. The imidazo[1,2-a]annulanes bearing pyridine, pyrazine and pyrimidine core constitute are an important heterocycles which they show broadly biologically activities such as anticytomegalo-zoster and antivaricella-zoster virus [1], antifungal, antibacterial [2, 3], anti-inflammatory [4], antiviral, antiulcer [5] and calcium channel blocker activities [6]. Among new studies in 2007, Gudmundsson described synthetic approach of novel imidazo[1,2-a] pyridines and their anti-HSV activity [7, 8]. In recent years, considerable efforts have been devoted to introduce new routes for the synthesis of imidazo[1,2- a]pyridines and other analogs. An earlier method for the synthesis of imidazo[1,2-a]pyridine is coupling of - halocarbonyl compound with 2-amino pyridine. Although, this reaction has been used for imidazo[1,2-a]annulated pyrazines and pyrimidines, but has restricted for generation of a diverse library of this heterocycles. Another one-pot method is coupling of 2-amino annulated heterocycle, sodium cyanide and formaldehyde which have limitation for desired diversification in the molecules. These protocols because of their restrictions could not be introduced as a good general method. RESULTS AND DISCUSSION In recent years, significant isocyanide-based multi- component reactions (ISMCRs) have been reported [9-11]. Multi-component reactions are important tools for the rapid *Address correspondence to this author at the Faculty of Chemistry, Tarbiat Moallem University, No. 43, Mofateh Avenue, Tehran, Iran; Tel/Fax: +98- 21-88848949; E-mail: habibi@tmu.ac.ir and efficient synthesis of a wide variety of organic molecules. In the usual organic chemistry, only a few MCRs are known and each reaction produces compounds with similar skeleton and only different substituent, whereas in the chemistry of the isocyanides, a much greater variation of MCRs is known and more different educts and products can participate than the conventional reactions. Three-component reaction of 2-amino pyridine, aldehyde and isocyanide was performed in different situations and their results were published in the literature. Some of these needs long time [for instance, reaction in the presence of protic acid (AcOH, HClO 4 )] [12] whereas reactions which were performed in the presence of Lewis acid (Sc(OTf) 3 ) [13] had complicated work up procedure. Other synthetic routes for three condensation reaction in the condition of solid acid (montmorillonite clay K10 [14], (Sc (OTf) 3 ) [13], solid support {using isonitrile resin [3], resin bound aldehydes [15] or immobilized acid [16]}; catalyst-free, in water [17]; synthesis in ionic liquid medium [18], application of TMSCN as a non-classical isonitrile equivalent [19], were recently reported. Table 1, shows differences in situation and condition, time of reaction, simplicity of work up and finally yields of reactions that recently reported. In spite of these interesting and suitable methods [13-24], there is a need to develop a facile route that can be easily used as a general and efficient synthetic approach. On the basis of information of Table 1, our procedure is a fast, simple and has easily worked up procedure that we can suggest as a general and efficient method for the synthesis of imidazo[1,2-a]pyridines derivatives. Here, we wish to report a three component condensation of aldehyde 1, 2-aminopyridine 2 and isocyanide 3 in the presence of silica-supported perchloric acid as catalyst (Scheme 1). This reaction was carried out at 70-90 ºC in a short time and excellent yield (Table 2). New products (4d, 4f, 4g, 4h, 4i, 4j, 4l, 4n, 4o) were identified by IR, 1 H NMR, 13 C NMR and Mass spectrum. The melting point and spectral data of