2012 Chinese Journal of Catalysis Vol. 33 No. 9 Article ID: 0253-9837(2012)09-1542-04 DOI: 10.1016/S1872-2067(11)60432-4 Article: 1542–1545 A Simple and Environmentally Benign Protocol for Biginelli Reactions Catalyzed by Silica-Bonded S-Sulfonic Acid Mahmood TAJBAKHSH 1,* , Yousef RANJBAR 2 , Abdolhosein MASUODI 2 , Samad KHAKSAR 3 1 Chemistry Department, University of Mazandaran, PO Box 453, Babolsar, Iran 2 Chemistry Department, Payame Noor University, PO Box 4697, Tehran, Iran 3 Chemistry Department, Islamic Azad University, Ayatollah Amoli Branch, PO Box 678, Amol, Iran Abstract: A protocol for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones and -thiones was developed by means of a three-component condensation of an aldehyde, a β-dicarbonyl compound, and urea or thiourea in acetic acid catalyzed by silica-bonded S-sulfonic acid. Com- pared to the classical Biginelli reaction conditions, this new protocol has the advantages of consistently excellent yields and short reaction times. After the reaction, the catalyst could be recovered easily and reused with little change in its activity. Key words: Biginelli reaction; silica-bonded S-sulfonic acid; dihydropyrimidinone CLC number: O643 Document code: A Received 20 February 2012. Accepted 11 July 2012. *Corresponding author. Tel: +98-1125234338; Fax: +98-1125242002; E-mail: tajbaksh@umz.ac.ir This work was supported by the Research Council of Payame Noor University. English edition available online at Elsevier ScienceDirect (http://www.sciencedirect.com/science/journal/18722067). Organic syntheses in which heterogeneous acid catalysts [1] are used in place of homogeneous acid reagents have received much attention owing to their potential for use in the development of green [2] and sustainable chemical proc- esses [3]. Reactions catalyzed by solid acids have the poten- tial to be safe and highly atom efficient, and they typically involve simple workup procedures that do not produce large amounts of salt wastes [4]. In recent decades, dihydro- pyrimidinones and their derivatives have drawn attention because of their antibacterial, antiviral, antitumor, and anti-inflammatory activities [5]. For example, Biginelli compounds (3,4-dihydropyrimidin-2(1H)-ones) act as cal- cium channel blockers, antihypertensive agents, a 1A-antagonists, and neuropeptide Y antagonists [6–9]. Batzelladine B, an alkaloid isolated from a marine sponge, contains a dihydropyrimidine unit and shows anti-HIV ac- tivity [10]. Numerous procedures for preparing dihydro- pyrimidinones have been reported, involving reagents and catalysts such as H 4 PMo 11 VO 40 [11], Dowex-50W [12], H 3 PW 12 O 40 /SiO 2 [13], MgBr 2 [14], polymer-supported 4-aminoformoyldiphenylammonium triflate [15], Na- HSO 4 /SiO 2 [16], FeCl 3 [17], ZrCl 4 [18], Cu(OTf) 2 [19], Bi(OTf) 3 [20], ytterbium triflate [21], NH 2 SO 3 H [22], 12-molybdophosphoric acid [23], natural HEU-type zeolites [24], Sr(OTf) 2 [25], ZrOCl 2 ·8H 2 O [26], silica triflate [27], Fe(HSO 4 ) 3 [28], TCICA [29], PPh 3 [30], melamine trisulfo- nic acid [31], Fe 3 O 4 nanoparticles [32], sulfonated β-cyclodextrine [33], metal hydrogen sulfates [34], ionic liquids [35–37], and sulfonated carbon materials [38]. However, some of these procedures require expensive reagents, strongly acidic conditions, long reaction times, high temperatures, or stoichiometric amounts of catalysts, or they result in environmental pollution or give unsatisfactory yields. Therefore, there is a need for new catalysts that are readily available or easy to prepare, inexpensive, and re- coverable (hence reusable and environmentally friendly). Moreover, the workup procedure should be simple. In this regard, functionalized silica particles and mesoporous silica materials have been synthesized and have found many ap- plications [39–43]. As part of our continuing studies of or- ganic processes mediated by heterogeneous acid catalysts, we now report a highly efficient synthesis of 3,4-dihydro- pyrimidin-2(1H)-ones and -thiones (Scheme 1) by means of a three-component condensation reaction catalyzed by sil- O R 1 H X H 2 N NH 2 H 3 C O O OR 2 R 2 O H 3 C N H NH R 1 X O + + SBSSA 1 2 3 4a-4r Scheme 1. SBSSA-catalyzed synthesis of 3,4-dihydropyrimidin- 2(1H)-ones and -thiones.