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
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,
Recently, many reviews [
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 [
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 [
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-
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
The number of hydrogen in the HPA and the states of ionization can be determined by potentiometric titration. The potentiometric titration curve (Figure
Potentiometric titration curve of H6GeW10V2O40·22H2O.
X-ray powder diffraction is widely used to study the structural features of HPA and explain their properties [
Data of X-ray powder diffraction of H6GeW10V2O40·22H2O.
2 |
9.27 | 10.34 | 16.76 | 18.75 | 19.10 | 20.76 | 25.52 |
d/nm | 0.954 | 0.855 | 0.529 | 0.473 | 0.465 | 0.428 | 0.349 |
I | 95.8 | 100.0 | 14.6 | 25.0 | 47.9 | 41.7 | 45.8 |
2 |
27.09 | 28.00 | 29.57 | 34.70 | 35.40 | 36.72 | 37.79 |
d/nm | 0.329 | 0.319 | 0.302 | 0.529 | 0.254 | 0.245 | 0.238 |
I | 70.8 | 60.4 | 27.1 | 33.3 | 22.9 | 35.4 | 27.1 |
The result of X-ray powder diffraction of H6GeW10V2O40·22H2O displays that the diffraction peaks are primarily distributed in four ranges of 2
HPA consists of protons, HPA anions, and hydration water. Figure
Thermogram of H6GeW10V2O40·22H2O.
In general, we took the temperature of the exothermic peak of DTA curves as a sign of their thermostability [
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
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
The reaction of cyclic
H6GeW10V2O40·22H2O catalyzed synthesis of spiroheterobicyclic rings
Entry | X–Z–X | G | Product | Yield (%) | M.P. (°C) |
---|---|---|---|---|---|
1 | O–C(Me)2–O | H |
|
80 | 223–225 |
2 | O–C(Me)2–O | Me |
|
68 | 199-200 |
3 | O–C(Me)2–O | Cl |
|
66 | 204–206 |
4 | O–C(Me)2–O | F |
|
67 | 216–218 |
5 | HN–CO–NH | H |
|
87 | 240–242 |
6 | HN–CO–NH | Me |
|
84 | 246–248 |
7 | HN–CO–NH | Cl |
|
82 | 291–293 |
8 | HN–CO–NH | F |
|
77 | 213–215 |
9 | MeN–CO–NMe | H |
|
83 | 232–234 |
10 | MeN–CO–NMe | Me |
|
85 | 228–230 |
11 | MeN–CO–NMe | Cl |
|
77 | 271–273 |
12 | MeN–CO–NMe | F |
|
75 | 244–246 |
To explore the scope and limitations of this reaction further, we have extended it to various
This investigation has been extended to cyclic ketones like cyclohexanone (Scheme
H6GeW10V2O40·22H2O catalyzed reaction of cyclohexanone, aldehyde, and urea.
Entry | R | Productsa | Yieldb (%) | M.P (°C) |
---|---|---|---|---|
1 | C6H5 |
|
87 | 327–329 |
2 | 4-(NO2)C6H4 |
|
79 | 341–343 |
3 | 4-(CH3)C6H4 |
|
83 | 348–351 |
4 | 2-(Cl)–C6H4 |
|
82 | 321–323 |
aReaction conditions: cyclohexanone (1.0 mmol), aldehyde (2.0 mmol), urea (3.0 mmol), and decatungstodivanadogermanic acid (3 mmol) irradiated at 80°C under solvent-free condition.
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
Yields of the reaction in different conditions.
Amount of catalyst |
Reaction time |
Yields (%) |
---|---|---|
0 | 7/80 | 46 |
1 | 7/80 | 52 |
2 | 7/80 | 63 |
3 | 7/80 | 80 |
4 | 7/80 | 75 |
5 | 7/80 | 73 |
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
Effect of the microwave power and the irradiation time on the formation of
Entry | Time (min) | Power (W) | Yields (%) |
---|---|---|---|
1 | 4 | 250 | 47 |
2 | 4 | 300 | 52 |
3 | 4 | 400 | 55 |
4 | 4 | 500 | 58 |
5 | 4 | 600 | 63 |
6 | 4 | 700 | 69 |
7 | 4 | 750 | 71 |
8 | 4 | 800 | 74 |
9 | 4 | 900 | 80 |
10 | 2 | 900 | 36 |
11 | 3 | 900 | 62 |
12 | 5 | 900 | 88 |
13 | 7 | 900 | 97 |
14 | 8 | 900 | 94 |
15 | 9 | 900 | 92 |
Reaction conditions: 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) in microwave irradiation at 80°C under solvent-free condition.
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
Comparison of the results of the present work with those of the earlier works.
Catalyst | Conditions | Yield (%) | Time | Reference |
---|---|---|---|---|
NBS/AIBN | Solvent-free/80°C | 72–74 | 4 h | [ |
AlCl3 | Ethanol/Reflux | 82–84 | 5 h | [ |
H6GeW10V2O40·22H2O | MWI/Solvent free | 87–90 | 6-7 min | This work |
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
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.
Cycle | 0 | 1st | 2nd | 3rd | 4th |
---|---|---|---|---|---|
Time (min) | 7 | 7 | 8 | 9 | 9 |
Yield (%)b | 80 | 78 | 76 | 73 | 71 |
aReaction conditions: 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) in microwave irradiation at 80°C under solvent-free condition.
bIsolated yields.
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.
The financial support from Madhya Pradesh Council of Science & Technology (MPCST) is highly appreciated.