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Journal of Chemistry
Volume 2013, Article ID 235818, 5 pages
http://dx.doi.org/10.1155/2013/235818
Research Article

Bi-SO3H Functionalized Ionic Liquid Based on DABCO: New and Efficient Catalyst for Facile Synthesis of Dihydropyrimidinones

Department of Chemistry, Semnan University, Semnan 35131-19111, Iran

Received 25 May 2013; Revised 11 July 2013; Accepted 13 July 2013

Academic Editor: Angelo de Fatima

Copyright © 2013 Firouzeh Nemati and Sara G. Alizadeh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A simple and efficient method for the one-pot Biginelli condensation reaction of aldehydes, β-dicarbonyl compounds, and urea or thiourea employing [DABCO](SO3H)2Cl2 as a novel ionic liquid catalyst is described.

1. Introduction

Over the past decade, ionic liquids have attracted extensive interest in organic synthesis, which has been recognized by a number of articles covering various aspects of ionic liquids as the catalyst or as dual catalyst-solvent in synthetic organic chemistry [1, 2]. With increasing environmental concerns, the design of simple, easily separable, nontoxic, and low-cost acidic ionic liquids has become an important research field [35]. In this context, ionic liquids as homogenous acid catalyst have attracted a great deal of attention due to their outstanding properties such as simple preparation, undetectable vapor pressure, nonflammability and high thermal stability. Introduction of functional groups, especially the SO3H-functional group, obviously enhanced their acidity and water solubility. These functionalized ILs are designed for a special use and are referred to as “task-specific ILs.”

Multicomponent reactions (MCRs), defined as one-pot reactions in which at least three different substrates join through covalent bonds, have steadily gained importance in synthetic organic chemistry. MCRs allow the creation of several bonds in a single operation and offer remarkable advantages like simple procedure, high bond forming efficiency, time and energy saving, extraction and purification processes, and hence minimize waste generation [610]. MCRs are useful for the expedient creation of chemical libraries of drug-like compounds with high levels of molecular complexity and diversity, thereby facilitating identification/optimization in drug discovery programmes [1116]. Therefore, researchers have made great efforts to develop new MCRs with green procedure, especially in the areas of drug discovery, organic synthesis, and material science [17, 18].

In this paper, a novel bi-SO3H functionalized ionic liquid based on DABCO was designed as a simple and powerful acid catalyst and applied for synthesis of dihydropyrimidinones in mild reaction condition.

2. Materials and Methods

2.1. Procedure for the Preparation of Ionic Liquid

A round-bottomed flask (100 mL) was charged with a solution of 1,4-diazabicyclo[2.2.2]octane, DABCO (0.56 g, 5 mmol) in dry CH2Cl2 (50 mL), and then chlorosulfonic acid (1.21 g, 10.4 mmol) was added dropwise over a period of 10 min at room temperature. After the addition was completed, the reaction mixture was left for 1 hour. In this period of time, a white solid was produced. Afterward, the CH2Cl2 was decanted. The residue was triturated with dry diethylether and dried under vacuum to give [DABCO](SO3H)2Cl2 as a very viscous colorless oil at 98% yield.

Spectral data of [DABCO](SO3H)2Cl2: 1HNMR (300 MHz, DMSO-d6): δ (ppm) 3.5 (s, 6H), 7.32 (s, 1H); 13CNMR (75 MHz, DMSO-d6): δ (ppm) 43.2; MS: m/z = 346 (M+ + 1), 345 (M+). IR (KBr, cm−1) : 3500-2800 (broad), 1319 (N-SO2), 1179 (N-SO2). Calcd. For C6H14N2S2O6Cl2: C, 20.86; H, 4.05; N, 8.11. Found: C, 20.63; H, 4.31; N, 7.89.

2.2. General Procedure for the Synthesis of Dihydropyrimidinones Derivatives

Aldehydes (1 mmol), ethyl acetoacetate (1 mmol), and urea or thiourea (1.5 mmol) were dissolved in 4 mL of ethanol containing [DABCO](SO3H)2Cl2 (0.07 mmol, 0.024 g). The mixture was heated under reflux. After completion of the reaction, as monitored by TLC, water (10 mL) was added to the reaction mixture. The solid product was filtered, dried, and recrystallized from ETOH to give the pure product.

3. Results and Discussion

In continuation with our interest in developing efficient and environmental benign synthetic methodologies [1921], we have prepared a new type of brnsted acidic ionic liquid catalyst based on DABCO, and found that it is highly active for the synthesis of dihydropyrimidinones.

To prepare the brnsted acidic ionic liquid, [DABCO](SO3H)2Cl2, chlorosulfonic acid (2 equiv.) was added dropwise to a solution of DABCO (1 equiv.) in dry CH2Cl2 at room temperature (Scheme 1).

235818.sch.001
Scheme 1: Synthesis of brnsted acidic ionic liquid.

For identification of structure of ionic liquid, we have studied the 1H NMR spectra of [DABCO](SO3H)2Cl2. The presence of sulfonate groups causes a significant downfield shift of the hydrogens of ionic liquid (3.5δ) compared with DABCO (2.7δ). Acidic hydrogens of SO3H groups were observed in 7.32 ppm that confirmed the sulfur atoms in the catalyst were connected to nitrogen atoms of DABCO [5]. Furthermore, according to the literature reports, in the reaction of triethylamine, 1-methyl imidazole, or imidazole with chlorosulfonic acid, the nitrogen atoms of amines act as a nucleophile (not base) and attack the sulfur atom of ClSO3H [22].

Thermogravimetric analysis (TGA) was used to study the thermal stability of the acid catalyst (Figure 1). The catalyst is stable up to 250°C and it is safe to carry out the reaction at 80–140°C, which is sufficient for organic reaction.

235818.fig.001
Figure 1: The TGA curve of [DABCO](SO3H)2Cl2.

To investigate the efficiency and applicability of the new catalyst, its role as brnsted acidic ionic liquid was evaluated for synthesis of dihydropyrimidinones (DHPMs) derivatives in EtOH under mild heating (Scheme 2).

235818.sch.002
Scheme 2: Application of [DABCO](SO3H)2Cl2(IL) in the Biginelli reaction.

For optimization of the reaction condition, ethyl acetoacetate (1 mmol), benzaldehyde (1 mmol), and urea (1.5 mmol) were heated under refluxing EtOH in the presence of [DABCO](SO3H)2Cl2 (0.07 mmol) to afford ethyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate in 98% yield (Table 1, Entry 1). To check the real effect of the catalyst, the reaction was performed without [DABCO](SO3H)2Cl2. The yield of catalyst-free reaction was lower than 12%. Further, we carried out the above reaction with ClSO3H as catalyst (0.14 mmol, 0.07 g) in the same reaction condition; it leads to several very close spots on TLC, and the desired product could not be isolated.

tab1
Table 1: [DABCO](SO3H)2Cl2-catalyzed synthesis of dihydropyrimidinones derivatives in EtOH.

The promising results obtained with [DABCO](SO3H)2Cl2 prompted us to further investigate the effect of solvents on Biginelli reactions. So, the model reaction was performed in various solvents, such as EtOH, MeOH, acetonitrile, THF, and CH2Cl2 under reflux, and it was found that EtOH provided the best solvents because of yield, reaction rate, cost, and environmental acceptability. Further experiments revealed the optimum amount of catalyst to be 0.07 mmol.

Structural varieties of arylaldehydes have been successfully utilized for this transformation, and in most cases, good yields were obtained (Table 1).

The reaction in refluxing ethanol alone gave poor yields. It is also a well-established fact that brnsted ionic liquids produced H+. Based on these two facts, a possible mechanism is depicted in Scheme 3 [23].

235818.sch.003
Scheme 3: A plausible mechanism.

Table 2 compares the efficiency of the present method for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones with other reported catalysts in the literature. As can be seen, [DABCO](SO3H)2Cl2 acts as a highly effective catalyst in terms of time, temperature, and yield of the reaction.

tab2
Table 2: Comparison of the results obtained for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones catalyzed by [DABCO](SO3H)2Cl2 with other recently reported catalysts.

4. Conclusion

In summary, a novel and highly efficient methodology for the synthesis of DHPMs in the presence of catalytic amounts of novel ionic liquid, [DABCO](SO3H)2Cl2, under reflux conditions is reported. This protocol describes a nonmetal catalyst, safe and easy work-up procedure for the synthesis of these products. In addition, simplicity and ease of preparation of the catalyst are promising points for the presented methodology.

Acknowledgments

The authors thank the Department of Chemistry and Office of Gifted Student at Semnan University for their financial support.

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