2011 Chinese Journal of Catalysis Vol. 32 No. 7 Article ID: 0253-9837(2011)07-1180-05 DOI: 10.1016/S1872-2067(10)60252-5 Article: 1180–1184 Silica Sulfuric Acid: An Efficient Heterogeneous Catalyst for the One-Pot Synthesis of 1,4-Dihydropyridines under Mild and Solvent-Free Conditions Bandita DATTA, M. Afzal PASHA * Department of Studies in Chemistry, Central College Campus, Bangalore University, Bengaluru 560001, India Abstract: A series of 1,4-dihydropyridines have been prepared by a one-pot condensation of aldehydes, ethyl acetoacetate, and ammonium acetate in the presence of a heterogeneous catalyst silica sulfuric acid at room temperature under solvent-free condition. This new protocol has the advantage of short reaction time and excellent yields, and is an environmentally benign route to the synthesis of 1,4-dihydropyridines. Key words: aldehyde; ethyl acetoacetate; ammonium acetate; silica sulfuric acid; 1,4-dihydropyridine CLC number: O643 Document code: A Received 28 April 2011. Accepted 31 May 2011. *Corresponding author. Tel: +91-80-22961337; Fax: +91-80-22961331; E-mail: m_af_pasha@ymail.com English edition available online at Elsevier ScienceDirect (http://www.sciencedirect.com/science/journal/18722067). In synthetic organic chemistry a one-pot synthesis has become a blue print to improve the efficiency of a reaction wherein a reactant is subjected to successive chemical reac- tions in one vessel [1]. The advantage of this strategy in- volves: i) use of commercially available starting materials; ii) avoiding a lengthy separation of the intermediates; iii) saving time and resources; iv) achieving increase in the chemical yield, and one such one-pot synthesis is of 1,4-dihydropyridines. 1,4-Dihydropyridine (DHP) scaffold has been shown to possess remarkable pharmacological activities [2]. 1,4-Dihydropyridines (DHPs) such as nifedifine, nitrendip- ine, and nimodipine, have been proved to be an important class of calcium-channel modulators [3,4] and have been introduced as potential drugs for the treatment of congestive heart failure [5]. DHPs act as potent vasodilators, anti- hypertensives, bronchodilators, antiatherosclerotics, hepa- toprotective, antitumor, antimutagenic, geroprotective, and antidiabetic agents [6]. They are also useful as cognition enhancers, neuroprotectants, and platelet antiaggregatory agents [7−9]. DHP esters serve as biomimetic reducing agents such as NADPH and NADH models also [10,11]. In 1881, Arthur Rudolf Hantzsch was the first to report the synthesis of DHPs by a one-pot reaction of an aldehyde, a β-ketoester, and aqueous ammonium hydroxide in ethanol [12]. Since then a series of procedures have been developed for the synthesis of DHPs. The reported procedures involve the use of reagents and catalysts such as Montmorillonite K10 [13], TBAB [14], HClO 4 ·SiO 2 [15], I 2 [16], silica gel/NaHSO 4 [17], AlCl 3 ·6H 2 O [18], 2,4,6-trichloro[1,3,5]- triazines (TCT, cyanuric chloride) [19], ionic liq- uid/3,4,5-trifluorobenzeneboronic acid [20], sulfonic acid [21], and fermenting bakers’ yeast [22] under various condi- tions such as ultrasound [23], microwave irradiation [24], and high temperature in refluxing solvent [25]. Moreover, procedures involving use of β-enaminones [26] as substrates have also been reported for the synthesis of DHPs. Recently, CeCl 3 ·7H 2 O [27], PW/SiO 2 [28], and PPh 3 [29] have been employed for this condensation reaction. In the 19th century considering economic and environ- mental aspects, heterogeneous catalysts have gained a lot of importance [30−32], and silica sulfuric acid has been widely used as a stable and an efficient heterogeneous catalyst. Silica sulfuric acid produces little waste with excellent ac- tivity and selectivity. Silica sulfuric acid can be prepared facilely by treating chlorosulfonic acid with silica gel [33,34] and is a better reagent when compared to a solely homogeneous acid such as chlorosulfonic acid or sulfuric acid (Scheme 1). Herein, we report an efficient and convenient procedure for the synthesis of DHPs from ethyl acetoacetate, aldehyde, and ammonium acetate using silica sulfuric acid as catalyst (Scheme 2). Once the reaction goes to completion, the cata- lyst can be filtered, washed with warm ethanol, and reused without decrease in activity for four runs. 1 Experimental All reagents were commercial available and used without further purification. The products were characterized by 1 H