About this Journal Submit a Manuscript Table of Contents
Journal of Catalysts
Volume 2013 (2013), Article ID 392162, 8 pages
http://dx.doi.org/10.1155/2013/392162
Research Article

Microwave-Assisted Synthesis of Spirofused Heterocycles Using Decatungstodivanadogermanic Heteropoly Acid as a Novel and Reusable Heterogeneous Catalyst under Solvent-Free Conditions

Laboratory of Heterocycles, School of Studies in Chemistry and Biochemistry, Vikram University, Ujjain 456010, Madhya Pradesh, India

Received 8 October 2012; Accepted 7 January 2013

Academic Editor: Mohammed M. Bettahar

Copyright © 2013 Srinivasa Rao Jetti et al. 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

Decatungstodivanadogermanic acid (H6GeW10V2O40·22H2O) was synthesized and used as a novel, green heterogeneous catalyst for the synthesis of spirofused heterocycles from one-pot three-component cyclocondensation reaction of a cyclic ketone, aldehyde, and urea in high yields under solvent-free condition in microwave irradiation at 80°C. This catalyst is efficient not only for cyclic ketones, but also for cyclic β-diketones, β-diester, and β-diamide derivatives such as cyclohexanone, dimedone, and Meldrum's acid, or barbituric acid derivatives.

1. Introduction

Dihydropyrimidinones and their derivatives have attracted great attention recently in synthetic organic chemistry due to their pharmacological and therapeutic properties such as antibacterial and antihypertensive activity as well as behaving as calcium channel blockers, α-1a-antagonists [1], and neuropeptide Y (NPY) antagonists [2]. The biological activity of some alkaloids isolated recently has been attributed to a dihydropyrimidinone moiety [3]. The first procedure to these compounds reported by Biginelli [4] more than a century ago makes use of the three-component, one-pot condensation of a β-ketoester, an aldehyde, and a urea under strongly acidic conditions [4]. However this method suffers from low yields in the case of substituted aromatic and aliphatic aldehydes [5]. Owing to the versatile biological activity of dihydropyrimidinones, development of an alternative synthetic methodology is of paramount importance.

Recently, many reviews [8, 9] and papers for preparing these compounds have been reported including classical conditions, with microwave and ultrasound irradiation and by using some other different catalysts such as phosphorus pentoxide-methanesulfonic acid [10], potassium terbutoxide (t-BuOK) [11], ammonium dihydrogen phosphate [12], silica-gel [13], mesoporous molecular sieve MCM-41 [14], cyanuric chloride [15], nano-BF3·SiO2 [16], silica gel-supported polyphosphoric Acid [17], zirconium(IV) chloride [18], indium(III) bromide [19], ytterbium(III)-resin [20], 1-n-butyl-3-methylimidazolium tetrafluoroborate (BMImBF4) or hexafluorophosphorate (BMImPF6) [21], ceric ammonium nitrate (CAN) [22], Mn(OAc)3·2H2O [23], lanthanide triflate [24], indium(III) chloride [25], lanthanum chloride [26], H2SO4 [27], montmorillonite KSF [28], polyphosphate ester (PPE) [29], BF3-OEt2/CuCl/HOAc [30], and conc. HCl [31, 32].

However, in spite of their potential utility, many of these methods involve expensive reagents, strongly acidic conditions, long reaction times, high temperatures, and stoichiometric amounts of catalysts and give unsatisfactory yields. Therefore, the discovery of a new catalyst for the preparation of pyrimidinones under neutral and mild conditions is of prime importance. Heterogeneous acid catalysis by heteropoly acids (HPAs) has attracted much interest because of its potential of great economic rewards and green benefits [3335]. Unlike metal oxides and zeolites, HPAs possess very strong Bronsted acidity, and their acid sites are more uniform and easier to control than those in other solid acid catalysts. These catalysts make them suitable solid heterogeneous catalysts for organic transformations.

Microwave reaction under solvent-free conditions and/or in the presence of a catalyst, resulting in shorter reaction time and higher product yields than those obtained by using conventional heating, offer low cost together with simplicity in processing and handling [36]. In connection with our previous works on synthesis of pyrimidinones derivatives [3739] and Meldrum’s acid and barbituric acid derivatives [40], we wish to report the results obtained from a study of the reaction of aldehydes, urea, cyclohexanone, and Meldrum’s acid or barbituric acid derivatives as a CH-acid, instead of open-chain cyclic β-dicarbonyl compounds, in microwave irradiation under solvent-free conditions. The procedure not only gives products in good yields but also avoids problems connected with solvent use (cost, handling, safety, and pollution), and the reaction times.

2. Experimental

2.1. Materials and Methods

All reactions were carried out in an LG domestic unmodified microwave oven model MS-1947C/01. Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470 spectrometer. 1H and 13C NMR spectra were recorded on a BRUKER DRX-500 AVANCE spectrometer at 500.13 and 125.77 MHz, respectively. NMR spectra were obtained on solutions in DMSO- . The chemicals used in this work were purchased from Fluka (Buchs, Switzerland) Chemical Company. Decatungstodivanadogermanic acid (H6GeW10V2O40·22H2O) was prepared according to a reported procedure [41].

2.2. Synthesis of Catalyst

0.8 g of GeO2 was dissolved in a hot solution of 10% NaOH, and a solution of 22.8 g of Na2WO4·2H2O in 100 mL of hot water was added to get mixture A. The pH of A was adjusted to 6 with HCl (1 : 1) and heated for 1 h. Then a solution of 7.5 g of Na2CO3 dissolved in 25 mL of hot water was added. The mixture was concentrated to 100 mL by heating. 2.4 g of NaVO3·2H2O and 2.5 g of Na2WO4·2H2O were dissolved in 30 mL of hot water, respectively, and the two solutions were mixed to get mixture B. The pH of mixture B was adjusted to 2.5 with H2SO4 (1 : 1). Then A was added dropwise, and the pH was kept at 2.5 while dropping. After stirring for 3 h at 60°C, the solution was cooled to room temperature. The cooled solution was extracted with ether in sulfuric acid medium, and the extractant was dissolved with a small amount of water. After the ether was evaporated, the remaining mixture was placed in the desiccators until orange crystals were separated out. The final yield was about 70%. Anal. Calcd. for H6GeW10V2O40·22H2O: Ge, 2.38; W, 60.18; V, 3.33; H2O, 12.96. Found: Ge, 2.38; W, 60.06; V, 3.29; H2O, 12.97% (TG analysis). FT-IR (KBr, cm−1): 3450 υ (O–H); 1620 δ (O–H); 964 (M–Od); 885 (M–Ob–M); 818 (Ge–Oa); 780 (M–Oc–M); 464 δ (O–Ge–O), (M=W and V; Oa, inner oxygen; Ob, corner-shared oxygen; Oc, edge-shared oxygen; Od, terminal oxygen) [41]. UV-Vis spectrum (CH3CN  nm); (Od → M, CT); 262 ( → M, CT).

The number of hydrogen in the HPA and the states of ionization can be determined by potentiometric titration. The potentiometric titration curve (Figure 1) shows that the six protons of H6GeW10V2O40·22H2O are equivalent and they are ionized in one step.

392162.fig.001
Figure 1: Potentiometric titration curve of H6GeW10V2O40·22H2O.

X-ray powder diffraction is widely used to study the structural features of HPA and explain their properties [42]. The data of X-ray powder diffraction are listed in Table 1.

tab1
Table 1: Data of X-ray powder diffraction of H6GeW10V2O40·22H2O.

The result of X-ray powder diffraction of H6GeW10V2O40·22H2O displays that the diffraction peaks are primarily distributed in four ranges of 2 which are 7–10°, 16–22°, 25–30°, and 33–38°. The positions and intensities of the main peaks are similar to those expected for the Keggin structure. Combined with IR and UV spectra, it is sure that H6GeW10V2O40·22H2O possesses Keggin structure.

HPA consists of protons, HPA anions, and hydration water. Figure 2 is the thermogram of H6GeW10V2O40·22H2O. The TG curve shows that the total percent of weight loss is 12.96%, which indicates that each HPA molecule has 22 molecules of water, and there are three steps of weight loss. The first is the loss of 16 molecules of hydration water, the second is the loss of 6 molecules of protonized water and the third is the loss of 3 molecules of structural water. Thus, the accurate molecular formula of the product is (H5O2)3H3GeW10V2O40·16H2O.

392162.fig.002
Figure 2: Thermogram of H6GeW10V2O40·22H2O.

In general, we took the temperature of the exothermic peak of DTA curves as a sign of their thermostability [43]. In the DTA curve, there was an exothermic peak at 481.6°C.

2.3. General Procedure for the Reaction of Benzaldehyde Meldrum’s Acid and Urea

An intimate mixture of benzaldehyde (0.30 g, 2 mmol), Meldrum’s acid (0.144 g, 1 mmol), urea (0.06 g, 1 mmol), and decatungstodivanadogermanic acid (0.03 g 3 mmol) was subjected to microwave irradiation for appropriate time in 600 W microwave oven for 6-7 min (successive irradiation of 30–40 sec with cooling intervals of time as the temperature being 80°C) as indicated by TLC. After cooling, H6GeW10V2O40·22H2O was separated by simple filtration due to its heterogeneous nature, and the reaction mixture was poured onto crushed ice (40 g) and stirred for 5–10 min. The precipitate was filtered under suction, washed with cold water (40 mL) and ethyl acetate (5 mL) to afford the pure product 1a.

2.4. General Procedure for the Reaction of Cyclohexanone, Aldehydes, and Urea

The mixture of cyclohexanone (1.0 mmol), aldehyde (2.0 mmol), urea (3.0 mmol), and Decatungstodivanadogermanic acid (3 mmol) was subjected to microwave irradiation for appropriate time in 600 W microwave oven for 6-7 min (successive irradiation of 30–40 sec with cooling intervals of time as the temperature being 80°C) as indicated by TLC. After cooling, H6GeW10V2O40·22H2O was separated by simple filtration due to its heterogeneous nature and the reaction mixture was poured onto crushed ice (40 g) and stirred for 5–10 min. The precipitate was filtered under suction, washed with cold water (40 mL) and ethyl acetate (5 mL) to afford the pure product 2a.

2.5. Spectral Data of Compounds

3,3-Dimethyl-(7S, 11R)-diphenyl-2,4-dioxa-8,10-diazaspiro[5.5]undecane-1,5,9-trione (1a). White powder. Mp 223–225°C dec. IR (KBr) ( , cm−1): 3195 and 3060 (NH), 1771, 1731 and 1685 (C=O). NMR (DMSO, Me4Si): 0.49 (6H, s, CMe2), 5.29 (2H, s, 2CH), 7.20–7.37 (10H, m, Ar), 7.28 (2H, s, 2NH). NMR (DMSO, Me4Si): 27.67 (CMe2), 57.99 (Cspiro), 61.48 (2CH), 105.51 (CMe2), 127.72, 128.71, 129.26, and 135.54 (Ar), 155.22, 159.69, 165.55 (3C=O). MS (m/z, %) 380 (M+, 11), 322 (7), 294 (13), 234 (12), 175 (17), 106 (100), 77 (44), 43 (56).

3,3-Dimethyl-(7S,11R)-bis(4-methylphenyl)-2,4-dioxa-8,10diazaspiro[5.5]undecane-1,5,9-trione (1b). White powder. Mp 199-200°C dec. IR (KBr) ( , cm−1): 3200 and 3060 (NH), 1765, 1730 and 1686 (C=O). NMR (DMSO, Me4Si): 0.51 (6H, s, CMe2), 2.25 (6H, s, 2CH3), 5.22 (2H, s, 2CH), 7.07–7.2 (8H, m, Ar), 7.17 (2H, s, 2NH). NMR (DMSO, Me4Si): 20.62 (2CH3), 27.73 (CMe2), 57.99 (Cspiro), 61.21 (2CH), 105.44 (CMe2), 127.56, 129.12, 132.52 and 138.66 (Ar), 155.31, 159.77, 165.64 (3C=O). MS (m/z, %) 408 (M+, 14), 350 (7), 322 (11), 189 (27), 173 (36), 120 (100), 91 (69), 75 (14), 43 (59).

3,3-Dimethyl-(7S,11R)-bis(4-chlorophenyl)-2,4-dioxa-8,10diazaspiro[5.5]undecane-1,5,9-trione (1c). White powder. Mp 204–206°C dec. IR (KBr) ( , cm−1): 3205 and 3065 (NH), 1770, 1731 and 1687 (C=O). NMR (DMSO, Me4Si): 0.60 (6H, s, CMe2), 5.32 (2H, s, 2CH), 7.21–7.47 (8H, m, Ar), 7.46 (2H, s, 2NH). NMR (DMSO, Me4Si): 27.81 (CMe2), 57.75 (Cspiro), 60.73 (2CH), 105.69 (CMe2), 128.76, 129.62, 133.92 and 134.33 (Ar), 155.15, 159.63 and 165.32 (3C=O). MS (m/z, %) 449 (M+, 16), 390 (7), 209 (22), 173 (36), 166 (57), 140 (98), 75 (14), 43 (100).

3,3-Dimethyl-(7S,11r)-bis(4-fluorophenyl)-2,4-dioxa-8,10-diazaspiro[5.5]undecane-1,5,9-trione (1d). White powder. Mp 216–218°C dec. IR (KBr) ( , cm−1): 3205 and 3065 (NH), 1770, 1725 and 1680 (C=O). NMR (DMSO, Me4Si): 0.59 (6H, s, CMe2), 5.32 (2H, s, 2CH), 7.24–7.26 (8H, m, Ar), 7.47 (2H, s, 2NH). NMR (DMSO, Me4Si): 27.80 (CMe2), 58.03 (Cspiro), 60.69 (2CH), 105.62 (CMe2), 115.65, 129.92, 131.64 and 155.27 (Ar), 159.79, 163.45 and 165.48 (3C=O). MS (m/z, %) 417 (M+ +1, 136), 358 (12), 316 (9), 193 (26), 149 (68), 124 (90), 75 (34), 43 (100).

(7S,11R)-Diphenyl-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1e). White powder. Mp 240–242°C dec. IR (KBr) ( , cm−1): 3240 and 3065 (NH), 1729 and 1695 (C=O). NMR (DMSO, Me4Si): 5.21 (2H, s, 2CH), 7.17–7.31(10 H, m, Ar), 7.31 (2H, s, 2NH), 11.01 and 11.39 (2H, 2s, NH). NMR (DMSO, Me4Si): 57.49 (Cspiro), 61.59 (2CH), 127.81, 128.91, 129.36 and 136.12 (Ar), 149.11, 156.05, 165.88 and 170.31 (4C=O). MS (m/z,%) 364 (M+, 5), 304 (10), 215 (95), 104 (100), 77 (96), 51 (98).

(7S,11R)-bis(4-Methylphenyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1f). White powder. Mp 246–248°C dec. IR (KBr) ( , cm−1): 3235 and 2975 (NH), 1724 and 1692 (C=O). NMR (DMSO, Me4Si): 2.23 (6H, s, 2CH3), 5.14 (2H, s, 2CH), 7.03–7.11 (8H, m, Ar), 7.01 (2H, s, 2NH), 10.97 and 11.33 (2H, 2s, NH). NMR (DMSO, Me4Si): 20.66 (2CH3), 57.02 (Cspiro), 60.91 (2CH), 127.21, 128.98, 132.66 and 138.11 (Ar), 148.75, 155.66, 165.51 and 169.94 (C=O). MS (m/z, %) 364 (M+ −CO, 7), 338 (25), 277 (31), 215 (100), 105 (87), 91 (23), 77 (39), 51 (45).

(7S,11R)-bis(4-Chlorophenyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1g). Cream powder. Mp 291–293°C dec. IR (KBr) ( , cm−1): 3146 and 3065 (NH), 1735 and 1708 (C=O). NMR (DMSO, Me4Si): 5.21 (2H, s, 2CH), 7.15–7.41(8H, m, Ar), 7.20 (2H, s, 2NH), 11.14 and 11.51 (2H, 2s, NH). NMR (DMSO, Me4Si): 56.82 (Cspiro), 60.33 (2CH), 128.48, 129.23, 133.47 and 134.50 (Ar), 148.58, 155.42, 165.18 and 169.47 (C=O). MS (m/z, %) 432 (M+ −1, 10), 400 (35), 372 (26), 249 (78), 215 (56), 138 (100), 75 (39), 51 (69).

(7S,11R)-bis(4-Fluorophenyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1h). White powder. Mp 213–215°C dec. IR (KBr) ( , cm−1): 3195 and 3070 (NH), 1757, 1694 (C=O). NMR (DMSO, Me4Si): 5.21 (2H, s, 2CH), 7.11–7.22 (8H, bs, Ar), 7.29 (2H, s, 2NH), 11.15 and 11.49 (2H, 2s, NH). NMR (DMSO, Me4Si): 57.05 (Cspiro), 60.28 (2CH), 115.27, 129.43, 131.73 and 150.19 (Ar), 155.47, 161.20, 165.35 and 169.62 (C=O). MS (m/z, %) 400 (M+, 10), 350 (25), 233 (100), 190 (56), 122 (98), 95 (73), 75 (69), 51 (69).

2,4-Dimethyl-(7S,11R)-diphenyl-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1i). White powder. Mp 232–234°C dec. IR (KBr) ( , cm−1): 3180 and 3060 (NH), 1739 and 1685 (C=O). NMR (DMSO, Me4Si): 2.68 and 2.85 (6H, s, 2NMe), 5.28 (2H, s, 2CH), 7.08–7.28 (10 H, m, Ar), 7.18 (2H, s, 2NH). NMR (DMSO, Me4Si): 27.87 and 28.71 (2NMe), 58.83 (Cspiro), 62.04 (2CH), 127.43, 128.84, 129.49, and 135.93 (Ar), 149.44, 155.87, 163.67 and 168.27 (4C=O). MS (m/z, %) 392 (M+, 17), 260 (13), 243 (31), 186 (18), 106 (100), 77 (39), 51 (33).

2,4-Dimethyl-(7S,11R)-bis(4-methylphenyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1j). White powder. Mp 228–230°C dec. IR (KBr) ( , cm−1): 3195 and 3055 (NH), 1738 and 1686 (C=O). NMR (DMSO, Me4Si): 2.21 (6H, s, 2C ), 2.71 and 2.85 (6H, s, 2NMe), 5.22 (2H, s, 2CH), 6.97–7.09 (8H, m, Ar), 7.08 (2H, s, 2NH). NMR (DMSO, Me4Si): 20.64 (2C ), 27.42 and 28.72 (2NMe), 58.28 (Cspiro), 61.36 (2CH), 126.84, 128.86, 132.51, and 138.21 (Ar), 149.40, 155.35, 163.28 and 167.83 (4C=O). MS (m/z, %) 420 (M+, 10), 360 (6), 274 (28), 257 (31), 186 (13), 120 (100), 106 (11), 91 (23), 77 (9).

2,4-Dimethyl-(7S,11R)-bis(4-chlorophenyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1k). White powder. Mp 271–273°C dec. IR (KBr) ( , cm−1): 3195 and 3060 (NH), 1744 and 1659 (C=O). NMR (DMSO, Me4Si): 2.74 and 2.87 (6H, s, 2NMe), 5.30 (2H, s, 2CH), 7.10–7.38 (8H, m, Ar), 7.25 (2H, s, 2NH). NMR (DMSO, Me4Si): 27.53 and 28.34 (2NMe), 56.67 (Cspiro), 60.82 (2CH), 128.39, 128.97, 129.36, and 133.46 (Ar), 155.14, 156.72, 159.30 and 162.98 (4C=O). MS (m/z, %) 460 (M+, 14), 400 (16), 321 (14), 294 (23), 277 (89), 220 (31), 140 (100), 75 (34).

2,4-Dimethyl-(7S,11R)-bis(4-fluorophenyl)-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,9-tetraone (1l). White powder. Mp 244–246°C dec. IR (KBr) ( , cm−1): 3190 and 3065 (NH), 1740, 1656 (C=O). NMR (DMSO, Me4Si): 2.75 and 2.87 (6H, s, 2NMe), 5.30 (2H, s, 2CH), 7.13–7.15 (8H, m, Ar), 7.26 (2H, s, 2NH). NMR (DMSO, Me4Si): 27.47 and 28.27 (2NMe), 58.28 (Cspiro), 60.76 (2CH), 115.21, 129.20, 131.60, and 148.93 (Ar), 155.24, 161.16, 163.12 and 167.53 (4C=O). MS (m/z, %) 428 (M+, 10), 385 (6), 305 (17), 278 (33), 261 (69), 204 (31), 124 (100), 95 (35), 75 (34).

4,8-Diphenyloctahydro-1H-pyrimido[5,4-i]quinazoline-2,10(3H,11H)-dione (2a). Mp 327–329°C; NMR (DMSO- ): δ 7.40–7.19 (m, 10 H), 7.08 (s, 1H), 6.97 (s, 1H), 6.62 (s, 1H), 6.39 (s, 1H), 4.50 (d, 1H), 4.82 (d, 1H), 2.02 (m, 2H), 1.38 (m, 2H), 1.24 (m, 2H), 0.82 (t, 2H); -NMR (DMSO- ) δ: 155.9, 140.5, 128.1, 128.6, 126.0, 63.7, 50.2, 49.1, 17.8; ESI-MS 377 (M+H); C22H24N4O2; (376.45); Calcd. C, 70.19; H, 6.43; N, 14.88; O, 8.50. Found. C, 70.03; H, 6.21; N, 14.45; O, 8.23.

4,8-bis(2-Chlorophenyl)octahydro-1H-pyrimido[5,4-i]quinazoline-2,10(3H,11H)-dione (2d). Mp 321–323°C; NMR (DMSO- ): δ 7.42 (s, 1H), 7.35–7.10 (m, 9H), 6.75 (s, 1H), 5.32 (s, 1H), 5.32 (s, 1H), 3.91 (m, 3H), 3.69 (m, 3H), 2.30 (m, 2H), 2.01 (m, 1H), 1.84 (m, 1H), 1.32 (m, 1H), 1.19 (m, 1H), 0.89 (m, 1H); -NMR (DMSO- ) δ: 155.9, 140.5, 133.4, 129.5, 128.6, 127.4, 63.7, 48.6, 45.1, 23.6, 17.8; ESI-MS 445 (M+H); C22H22Cl2N4O2 (445.34); Calcd. C, 59.33; H, 4.98; Cl, 15.92; N, 12.58; O, 7.19. Found. C, 59.12; H, 4.56; Cl, 15.74; N, 12.28; O, 7.02.

3. Results and Discussion

The reaction of cyclic β-ketoesters [44] and β-diamides, Meldrum’s acid, or barbituric acid derivatives with 1 equivalent of urea and 2 equivalents of aldehydes gives a family of σ symmetric spiroheterobicyclic compounds in good yields in the presence of H6GeW10V2O40·22H2O as a catalyst under solvent-free conditions at 80°C (Scheme 1 and Table 2).

tab2
Table 2: H6GeW10V2O40·22H2O catalyzed synthesis of spiroheterobicyclic rings 1(a-l).
392162.sch.001
Scheme 1

To explore the scope and limitations of this reaction further, we have extended it to various para-substituted benzaldehydes in the presence of Meldrum’s acid and barbituric acid (Scheme 1). We have found that the reaction proceeds very efficiently with benzaldehyde and electron withdrawing para-substituted benzaldehydes, but it proceeded only up to Knoevenagel adducts, when electron releasing para-substituted benzaldehydes were used (X = OMe, NMe2).

This investigation has been extended to cyclic ketones like cyclohexanone (Scheme 2). The products formed 2(a–d) are listed in Table 3.

tab3
Table 3: H6GeW10V2O40·22H2O catalyzed reaction of cyclohexanone, aldehyde, and urea.
392162.sch.002
Scheme 2

It was shown that no desirable product could be detected when a mixture react in the absence of H6GeW10V2O40·22H2O, which indicated that the catalyst should be necessary. Then the model reaction to synthesize 1a by the reaction of Meldrum’s acid, benzaldehyde, and urea was investigated with different amounts of H6GeW10V2O40·22H2O (0–5 mol%). Yields of the reaction in different conditions were shown in Table 4.

tab4
Table 4: Yields of the reaction in different conditions.

We found that most of the Lewis acids could promote the reaction, but the yields were not so high. In comparison with other catalysts, the use of 3 mol% of H6GeW10V2O40·22H2O could make the yield 80% under the microwave power of 600 W and the irradiation time of 7 min. It could be seen that 3 mol% of H6GeW10V2O40·22H2O gave the best result of this reaction, although other factors could not yet be optimized.

Based on the above optimized results, that is, 3 mol% amount of H6GeW10V2O40·22H2O as a catalyst, we further examined the effects of the microwave power and the irradiation time on the same model reaction to afford 1a, as shown in Scheme 1. The results are listed in Table 5. It could be found that with the increase of the microwave power from 250 W to 900 W, the yield of 1a showed a linear increase from 47% to 80% when the irradiation time was 4 min. However, with the microwave power of 900 W, when we increased the microwave irradiation time, the yield of 1a increased first, but a slight decrease was observed for more than 7 min. So the optimized microwave power and the irradiation time were 900 W and 7 min, respectively.

tab5
Table 5: Effect of the microwave power and the irradiation time on the formation of 1a.

In order to show the merit of the present work in terms of time, yield, and reaction conditions in comparison to the earlier reported works, the results of the present study were compared with those of the earlier studies in Table 6. As it can be seen from Table 6, the present method is simpler, more efficient for the synthesis of dihydropyrimidinone derivatives.

tab6
Table 6: Comparison of the results of the present work with those of the earlier works.

In order to confirm the reusability of H6GeW10V2O40·22H2O catalyst, after the completion of the reaction it was separated from the reaction mixture and washed with ethyl acetate. The recovered catalyst was found to be reusable for four cycles without significant loss in activity (Table 7). At the same time the concentrations of Wand V in the filtrate were determined to be less than 1% by ICP-AES. On the other hand, the IR and UV-Vis spectra of the recovered catalyst were identical with fresh catalyst. All these findings confirm that the leaching of the catalyst did not take place under the reaction conditions.

tab7
Table 7: Reusability of the catalyst for the synthesis of 3,3-dimethyl-(7S, 11R)-diphenyl-2,4-dioxa-8,10-diazaspiro[5.5]undecane-1,5,9-trionea.

4. Conclusion

In conclusion we have investigated the application of a V-containing HPA as a green and recyclable heterogeneous catalyst for the synthesis spirofused heterocycles from one-pot three-component cyclocondensation reaction of a cyclic ketone, aldehyde, and urea in high yields under solvent-free condition in microwave irradiation. It is an efficient, mild, and green method for the synthesis of spirofused heterocycles. It is noteworthy that the catalyst can be used for subsequent cycles without appreciable loss of activity. In contrast to many other acids, the storage of this nonhygroscopic and noncorrosive solid heteropoly acid does not require special precautions; for example, it can be stored on a bench top for months without losing its catalytic activity.

Acknowledgment

The financial support from Madhya Pradesh Council of Science & Technology (MPCST) is highly appreciated.

References

  1. C. O. Kappe, W. M. F. Fabian, and M. A. Semones, “Conformational analysis of 4-aryl-dihydropyrimidine calcium channel modulators. A comparison of ab initio, semiempirical and X-ray crystallographic studies,” Tetrahedron, vol. 53, no. 8, pp. 2803–2816, 1997. View at Publisher · View at Google Scholar · View at Scopus
  2. G. C. Rovnyak, S. D. Kimball, B. Beyer et al., “Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators,” Journal of Medicinal Chemistry, vol. 38, no. 1, pp. 119–129, 1995. View at Scopus
  3. B. B. Snider and Z. Shi, “Biomimetic syntheses of (±)-crambines A, B, C1, and C2. Revision of the structures of crambines B and C1,” Journal of Organic Chemistry, vol. 58, no. 15, pp. 3828–3839, 1993. View at Scopus
  4. C. O. Kappe, “100 years of the Biginelli dihydropyrimidine synthesis,” Tetrahedron, vol. 49, no. 32, pp. 6937–6963, 1993. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Barluenga, M. Tomás, A. Ballesteros, and L. A. López, “1,4-Cycloaddition of 1,3-diazabutadienes with enamines: an efficient route to the pyrimidine ring,” Tetrahedron Letters, vol. 30, no. 34, pp. 4573–4576, 1989. View at Scopus
  6. S. R. Jetti, D. Verma, and S. Jain, “NBS/AIBN promoted one-pot multi component regioselective synthesis of spiro heterobicyclic rings via Biginelli-like condensation reaction,” Journal of Chemical and Pharmaceutical Research, vol. 4, no. 5, pp. 2373–2379, 2012.
  7. S. R. Jetti, D. Verma, and S. Jain, “An efficient one-pot green protocol for the synthesis of 5-unsubstituted 3, 4-dihydropyrimidin-2(1H)-ones using recyclable amberlyst 15 DRY as a heterogeneous catalyst via three-component Biginelli-like reaction,” ISRN Organic Chemistry, vol. 2012, Article ID 480989, 8 pages, 2012. View at Publisher · View at Google Scholar
  8. S. Panda, K. Siva, K. Pankaj, and Leena, “Biginelli reaction: a green perspective,” Current Organic Chemistry, vol. 16, no. 4, pp. 507–520, 2012. View at Publisher · View at Google Scholar
  9. Suresh and S. J. Sandhu, “Past, present and future of the Biginelli reaction: a critical perspective,” Arkivoc, vol. 1, pp. 66–133, 2012.
  10. A. Borse, P. Mahesh, P. Nilesh, and S. Rohan, “A green, expeditious, one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones using a mixture of phosphorus pentoxide-methanesulfonic acid at ambient temperature,” ISRN Organic Chemistry, vol. 2012, Article ID 415645, 6 pages, 2012. View at Publisher · View at Google Scholar
  11. D. Abdelmadjid, C. Louisa, B. Raouf, and C. Bertrand, “A one-pot multi-component synthesis of dihydropyrimidinone/thione and dihydropyridine derivatives via Biginelli and Hantzsch condensations using t-BuOK as a catalyst under solvent-free conditions,” The Open Organic Chemistry Journal, vol. 6, pp. 12–20, 2012. View at Publisher · View at Google Scholar
  12. T. Reza, M. Behrooz, and G. Malihe, “Ammonium dihydrogen phosphate catalyst for one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones,” Chinese Journal of Catalysis, vol. 33, no. 4–6, pp. 659–665, 2012. View at Publisher · View at Google Scholar
  13. S. Agarwal, U. Aware, A. Patil et al., “Silica-gel catalyzed facile synthesis of 3, 4-dihydropyrimidinones,” Bulletin of Korean Chemical Society, vol. 33, no. 2, pp. 377–378, 2012. View at Publisher · View at Google Scholar
  14. R. Hekmatshoar, M. Heidari, M. M. Heravi, and B. Baghernejad, “Mesoporous molecular sieve MCM-41 catalyzed one-pot synthesis of 3,4-dihydro-2(1H)-pyrimidinones and -thiones under solvent-free conditions,” Bulletin of the Chemical Society of Ethiopia, vol. 25, no. 2, pp. 309–313, 2011. View at Scopus
  15. J. A. Kumar, C. Shanmugam, and P. H. Babu, “One pot synthesis of dihydropyrimidinones catalyzed by Cyanuric chloride: an improved procedure for the Biginelli reaction,” Der Pharma Chemica, vol. 3, no. 4, pp. 292–297, 2011.
  16. B. F. Mirjalili, A. Bamoniri, and A. Akbari, “One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones (thiones) promoted by nano-BF3.SiO2,” Journal of the Iranian Chemical Society, vol. 8, no. 1, pp. S135–S140, 2011. View at Scopus
  17. M. Zeinali-Dastmalbaf, A. Davoodnia, M. M. Heravi, N. Tavakoli-Hoseini, A. Khojastehnezhad, and H. A. Zamani, “Silica gel-supported polyphosphoric acid (PPA-SiO2) catalyzed one-pot multi-component synthesis of 3, 4-dihydropyrimidin-2(1H)-ones and -thiones: an efficient method for the Biginelli reaction,” Bulletin of the Korean Chemical Society, vol. 32, no. 2, pp. 656–658, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. C. V. Reddy, M. Mahesh, P. V. K. Raju, T. R. Babu, and V. V. N. Reddy, “Zirconium(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Tetrahedron Letters, vol. 43, no. 14, pp. 2657–2659, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. N. Y. Fu, Y. F. Yuan, Z. Cao, S. W. Wang, J. T. Wang, and C. Peppe, “Indium(III) bromide-catalyzed preparation of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction,” Tetrahedron, vol. 58, no. 24, pp. 4801–4807, 2002. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Dondoni and A. Massi, “Parallel synthesis of dihydropyrimidinones using Yb(III)-resin and polymer-supported scavengers under solvent-free conditions. A green chemistry approach to the Biginelli reaction,” Tetrahedron Letters, vol. 42, no. 45, pp. 7975–7978, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Peng and Y. Deng, “Ionic liquids catalyzed Biginelli reaction under solvent-free conditions,” Tetrahedron Letters, vol. 42, no. 34, pp. 5917–5919, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. J. S. Yadav, B. V. S. Reddy, K. B. Reddy, K. S. Raj, and A. R. Prasad, “Ultrasound-accelerated synthesis of 3,4-dihydropyrimidin-2(1H)-ones with ceric ammonium nitrate,” Journal of the Chemical Society, no. 16, pp. 1939–1941, 2001. View at Scopus
  23. K. A. Kumar, M. Kasthuraiah, C. S. Reddy, and C. D. Reddy, “Mn(OAc)3·2H2O-mediated three-component, one-pot, condensation reaction: an efficient synthesis of 4-aryl-substituted 3,4-dihydropyrimidin-2-ones,” Tetrahedron Letters, vol. 42, no. 44, pp. 7873–7875, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Ma, C. Qian, L. Wang, and M. Yang, “Lanthanide triflate catalyzed biginelli reaction. One-pot synthesis of dihydropyrimidinones under solvent-free conditions,” Journal of Organic Chemistry, vol. 65, no. 12, pp. 3864–3868, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. B. C. Ranu, A. Hajra, and U. Jana, “Indium(III) chloride-catalyzed one-pot synthesis of dihydropyrimidinones by a three-component coupling of 1,3-dicarbonyl compounds, aldehydes, and urea: an improved procedure for the Biginelli reaction,” Journal of Organic Chemistry, vol. 65, no. 19, pp. 6270–6272, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. J. Lu, Y. Bai, Z. Wang, B. Yang, and H. Ma, “One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a catalyst,” Tetrahedron Letters, vol. 41, no. 47, pp. 9075–9078, 2000. View at Scopus
  27. J. C. Bussolari and P. A. McDonnell, “A new substrate for the Biginelli cyclocondensation: direct preparation of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones from a β-keto carboxylic acid,” Journal of Organic Chemistry, vol. 65, no. 20, pp. 6777–6779, 2000. View at Publisher · View at Google Scholar · View at Scopus
  28. F. Bigi, S. Carloni, B. Frullanti, R. Maggi, and G. Sartori, “A revision of the biginelli reaction under solid acid catalysis. Solvent-free synthesis of dihydropyrimidines over montmorillonite KSF,” Tetrahedron Letters, vol. 40, no. 17, pp. 3465–3468, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. C. O. Kappe, D. Kumar, and R. S. Varma, “Microwave-assisted high-speed parallel synthesis of 4-aryl-3,4- dihydropyrimidin-2(1H)-ones using a solventless biginelli condensation protocol,” Synthesis, no. 10, pp. 1799–1803, 1999. View at Scopus
  30. E. H. Hu, D. R. Sidler, and U. H. Dolling, “Unprecedented catalytic three component one-pot condensation reaction: an efficient synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydropyrimidin- 2(1H)-ones,” Journal of Organic Chemistry, vol. 63, no. 10, pp. 3454–3457, 1998. View at Publisher · View at Google Scholar · View at Scopus
  31. K. S. Atwal, G. C. Rovnyak, B. C. O'Reilly, and J. Schwartz, “Substituted 1,4-dihydropyrimidines. 3. Synthesis of selectively functionalized 2-hetero-1,4-dihydropyrimidines,” Journal of Organic Chemistry, vol. 54, no. 25, pp. 5898–5907, 1989. View at Scopus
  32. V. I. Saloutin, Y. V. Burgart, O. G. Kuzueva, C. O. Kappe, and O. N. Chupakhin, “Biginelli condensations of fluorinated 3-oxo esters and 1,3-diketones,” Journal of Fluorine Chemistry, vol. 103, no. 1, pp. 17–23, 2000. View at Scopus
  33. I. V. Kozhevnikov, “Catalysis by heteropoly acids and multicomponent polyoxometalates in liquid-phase reactions,” Chemical Reviews, vol. 98, no. 1, pp. 171–198, 1998. View at Scopus
  34. I. V. Kozhevnikov, “Sustainable heterogeneous acid catalysis by heteropoly acids,” Journal of Molecular Catalysis A, vol. 262, no. 1-2, pp. 86–92, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. F. Saeid and P. Somayeh, “Decatungstodivanadogermanic heteropoly acid (H6GeW10V2O40. 22H2O): a novel, green and reusable catalyst for efficient acetylation of alcohols and phenols under solvent-free conditions,” European Journal of Chemistry, vol. 1, no. 4, pp. 335–340, 2010. View at Publisher · View at Google Scholar
  36. Y. Zhu, Y. Pan, and S. Huang, “Trimethylsilyl chloride: a facile and efficient reagent for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Synthetic Communications, vol. 34, no. 17, pp. 3167–3174, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. S. R. Jetti, D. Verma, and S. Jain, “Carbon-based solid acid as an efficient and reusable catalyst for the synthesis of 4, 6-diarylpyrimidin-2(1H)-ones under solvent-free conditions,” Der Chemica Sinica, vol. 3, no. 3, pp. 636–640, 2012.
  38. J. S. Rao, G. N. Babu, P. Pradeep, B. Anjna, T. Kadre, and J. Shubha, “Amberlyst 15 DRY resin: a green and recyclable catalyst for facile and efficient one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones,” Der Pharma Chemica, vol. 4, no. 1, pp. 417–427, 2012.
  39. T. Kadre, S. R. Jetti, A. Bhatewara, P. Paliwal, and S. Jain, “Green protocol for the synthesis of 3, 4-Dihydropyrimidin-2(1H)-ones/thiones using TBAB as a catalyst and solvent free condition under microwave irradiation,” Archives of Applied Science Research, vol. 4, no. 2, pp. 988–993, 2012.
  40. P. Pradeep, J. S. Rao, and J. Shubha, “DABCO promoted multi-component one-pot synthesis of xanthene derivatives,” Research Journal of Chemical Sciences, vol. 2, no. 8, pp. 21–25, 2012.
  41. Q. Wu, Q. Chen, X. Cai, J. Wang, and J. Zhang, “Preparation and conductivity of solid high-proton conductor silica gel containing 80wt.% decatungstodivanadogermanic acid,” Materials Letters, vol. 61, no. 3, pp. 663–665, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. Q. Y. Wu, S. K. Wang, D. N. Li, and X. F. Xie, “Preparation and characterization of decatungstomolybdoniobogermanic heteropoly acid H5[GeW10MoNbO40] · 20H2O,” Inorganic Chemistry Communications, vol. 5, no. 5, pp. 308–311, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. U. B. Mioe, M. R. Todorovic, S. M. Uskokovic-Markovic et al., “Structure and proton conductivity in a magnesium salt of 12-tungstophosphoric acid,” Solid State Ionics, vol. 162-163, no. EX-1-EX-8, pp. 217–223, 2003. View at Publisher · View at Google Scholar
  44. G. Byk, H. E. Gottlieb, J. Herscovici, and F. Mirkin, “New regioselective multicomponent reaction: one pot synthesis of spiro heterobicyclic aliphatic rings,” Journal of Combinatorial Chemistry, vol. 2, no. 6, pp. 732–735, 2000. View at Scopus