Chinese Chemical Letters  2014, Vol.25 Issue (01):111-114   PDF    
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Frahad Shirini, Masoumeh Abedini, Reyhaneh Pourhasan-Kisomi.N-Sulfonic acid poly(4-vinylpyridinium) chloride as a highly efficient and reusable catalyst for the Biginelli reaction[J]. Chin. Chem. Lett., 2014,25(01): 111-114   
N-Sulfonic acid poly(4-vinylpyridinium) chloride as a highly efficient and reusable catalyst for the Biginelli reaction
Frahad Shirini , Masoumeh Abedini, Reyhaneh Pourhasan-Kisomi    
* Corresponding authors at:Department of Chemistry, College of Science, University of Guilan, Rasht 41335, Islamic Republic of Iran
Received:2013-6-20, Revised:2013-7-19, online:2013-10-20.
E-mail addresses:shirini@guilan.ac.ir
Abstract: A mild, simple and efficient procedure for the preparation of 3,4-dihydropyrimidin-2(1H)-ones and -thiones is described using N-sulfonic acid poly(4-vinylpyridinium) chloride (NSPVPC) as a heterogeneous and efficient catalyst under solvent-free conditions. Simplemethodologies, easy work-up procedure, easy preparation of the catalyst, excellent yields and very short reaction times are among the other advantages of this work. Further, the catalyst can be reused and recovered for several times without significant decrease in its activity.
Key words: N-sulfonic acid poly(4-vinylpyridinium)     chloride (NSPVPC)     Biginelli reaction     Solvent-free conditions     Reusable catalyst     3,4-Dihydropyrimidin-2(1H)-ones    
1. Introduction

Dihydropyrimidinones (DHPMs) and their derivatives are important classes of compounds in the field of pharmaceuticals and exhibit significant biological properties such as antiviral, antihypertensive and antibacterial as well as anti-HIV and antitumor activities [1]. Some of them are also successfully used as calcium channel blockers and α-1a-antagonists [2, 3, 4, 5, 6].

Because of their importance and wide range of applications, different types of methods are reported for the preparation of DHPMs which of them the Biginelli reaction is the most important ones.

This reaction is based on a one-pot condensation reaction of β-dicarbonyl compounds with aldehydes and urea or thiourea in the presence of an acid catalyst [7]. The method although is useful but suffer from the use of HCl.

In continuation of this study different types of catalysts are reported for the promotion of the Biginelli reaction which of them silica-bonded S-sulfonic acid (SBSSA), sulfonated carbon materials (SCM), bentonite/PS-SO3H, MCM-41-R-SO3H [8, 9, 10, 11], zeolites [12], HClO4-SiO2 [13], Yb(OTf)2, Cu(OTf)2, Zn(OTf)2, and Bi(OTf)2 [14] and different types of ionic liquids [15, 16, 17], melamine trisulfonic acid (MTSA), ZrOCl2⋅8H2O, silica triflate, Fe(HSO4)3, trichloro isocyanuric acid (TCCA) [18, 19, 20, 21, 22] are examples.

Although, these methods are an improvement many of them suffer from disadvantages such as harsh reaction conditions, use of harmful organic solvents, long reaction times, tedious work-up procedure, expensive and moisture sensitive reagents, strongly acidic conditions, unsatisfactory yields, non-recoverability of the catalyst and environmental pollution.

Therefore, introduction of an inexpensive and efficient reagent for this reaction under milder and greener conditions is still in demand.

2. Experimental

Chemicals were purchased from Fluka, Merck and Aldrich Chemical Companies. All yields refer to the isolated products. The purity determination of the substrate and reaction monitoring were accompanied by thin-layer chromatography (TLC) on a silicagel polygram SILG/UV 254 plates. Products were separated and purified by different chromatographic techniques and were identified by the comparison of their IR, NMR and refractive index with those reported for the authentic samples. All yields refer to the isolated products.

The IR spectra were run on a Perkin-Elmer bio-spectrometer. The 1H NMR (300 MHz) was run on a Bruker Avance DPX-300 FTNMR spectrometer (δ in ppm). Melting points were recorded on a Büchi B-545 apparatus in open capillary tubes.

2.1. General procedure for the synthesis of DHPMs under solvent-free conditions

A mixture of the aldehyde (1 mmol), 1,3-dicarbonyl compound (1 mmol), urea (or thiourea) (1.2 mmol) and NSPVPC (20 mg) was heated in an oil-bath (100 ℃) under solvent-free conditions. After completion of the reaction (monitored by TLC) the reaction mixture was cooled to room temperature, EtOH (5 mL) was added and filtered to separate the catalyst. Then the crude product was recrystallized from EtOH to give the pure product. Spectroscopic data for the selected products are as follows:

Ethyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5- carboxylate: IR (KBr, cm-1): υ 3245, 3118, 2978, 1725, 1701, 1649; 1H NMR (300 MHz, DMSO-d6): δ 1.06 (t, 3H, J = 6.84 Hz), 2.24 (s, 3H), 3.94 (q, 2H, J = 6.75 Hz), 5.13 (d, 1H, J = 3.06 Hz), 7.21-7.37 (m, 5H), 7.37 (brs, 1H), 9.19 (brs, 1H).

4-(4-Methoxyphenyl)-6-phenyl-pyrimidin-2(1H)-one: IR (KBr, cm-1): y 3436, 3247, 3113, 2929, 1724, 1705, 1649; 1H NMR (300 MHz, DMSOd6): δ 1.10 (t, 3H, J = 7.08 Hz), 2.17 (s, 3H), 3.71 (s, 3H), 3.96 (q, 2H, J = 7.14 Hz), 5.07 (d, 1H, J = 2.97 Hz), 6.85 (d, 2H, J = 8.49 Hz), 7.12 (d, 2H, J = 8.55 Hz), 7.67 (brs, 1H), 9.15 (brs, 1H).

3. Results and discussion

Very recently we have reported the preparation of N-sulfonic acid poly(4-vinylpyridinum) chloride (NSPVPC) and its application in different types of organic reactions [23, 24, 25].

Herein, and in continuation of these studies we wish to report the applicability of this reagent in the promotion of the synthesis of DHPMs under solvent-free conditions.

To optimize the reaction conditions the reaction of 4- nitrobenzaldehyde, ethyl acetoacetate and urea was studied in different conditions in the presence of different amounts of NSPVPC (Table 1). The obtained results showed that the reaction using 20 mg of the catalyst at 100 ℃ proceeded with highest yield in shorter reaction times (Table 1, entry 2).

Table 1
Effects of temperature and the amount of catalyst on the Biginelli reaction under solvent-free conditions.
It is important to note that using lower amounts of the catalyst or temperature lead to the product in longer times while using higher amounts of NSPVPC or proceeding the reaction at higher temperature resulted in the formation of by-products.

To assess the efficiency of NSPVPC in the preparation of 3,4- dihydropyrimidin-2(1H)-ones derivatives, other aromatic aldehydes were also reacted under the optimal reaction conditions to furnish the corresponding products in good to high yields in very short reaction times (Scheme 1). It is clear from Table 2.

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Scheme 1.NSPVPC catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-ones and -thiones.

Table 2
Preparation of 3,4-dihydropyrimidin-2(1H)-ones and -thiones using NSPVPC as the catalyst under solvent-free conditions.a
Acetyl acetone and thiourea can also be used with similar success to provide the corresponding products (Table 2, entries 11- 19). It seems that the electronic nature of the functional group and their position (Table 1, entries 2-4 and 6-8) on the ring of the aldehyde exerted a slightly influence on the reaction time. However, the reaction proceeded smoothly with thiourea (Table 2, entries 16-19).

In continue, we decided to study the catalytic activity of the recycled catalyst for the synthesis of DHPMs. After the separation of the product, the catalyst was washed with EtOAc and acetone and derived at 50 ℃. As shown in Fig. 1, NSPVPC can be recycled at least five times without significant decrease in its activity. It should be note that the IR spectra of the recovered catalyst was the same as the catalyst used for the first run and also pH analysis of the recovered catalyst showed nearly the same loading of H+ as the freshly prepared catalyst. These observations suggest that the nature of the catalyst remains intact after each run and leaching of the acid species is not occurred during the course of the reaction.

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Fig. 1.Recyclability of the catalyst.
Table 3 compares our results with the results reported using some of the other catalysts in the synthesis of DHPMs.

Table 3
Comparison of the results of the reaction of ethyl acetoacetate, urea with 4-OMePhCHO using NSPVPC with those obtained by reported catalysts.
The results indicated that in most cases, the reaction time is too long using larger amounts of the other catalysts (Table 3, entries 1- 4,6). In addition, to compare the applicability and efficiency of NSPVPC with the other catalysts, we have tabulated the TON (turnover number) and TOF (turnover frequency) of these catalysts in this reaction. As it is clear NSPVPC is superior in terms of TOF to the compared catalysts.

A plausible mechanism for the Biginelli reaction in the presence of NSPVPC is shown in Scheme 2.

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Scheme 2.Proposed mechanism of the reaction.
4. Conclusion

In summary, we have introduced NSPVPC as a highly efficient catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones and -thiones via the one-pot multi-component condensation reactions. This method in accompanied will several advantages such as: ease of preparation and handling of the catalyst, simplicity and easy work-up, high reaction rates and excellent yields. Also, the recovered catalyst can be reused several times without significant decrease in its activity.

Acknowledgments

The authors are thankful to the University of Guilan Research Council for the partial support of this work.

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