An efficient and environmental benign method is reported for the synthesis of some pyrazolopyrimidine derivatives using 3-methyl-1-phenyl-5-pyrazolone with carbonyl compounds in the presence of nanozeolite Nax catalysts, solvent-free and at reflux conditions. It is noteworthy to mention that this method of the synthesis requires less time, less temperature, and better yield.
Pyrazolopyrimidine derivatives have received a great deal of attention due to their pharmacological activities. Pyrazolopyrimidine derivatives have demonstrated promising antimicrobial activity against gram-positive bacteria [
All melting points are uncorrected. IR spectra were recorded in KBr discs using a Shimadzu IR-740 spectrophotometer. 1H- and 13C-NMR spectra were recorded on a Bruker DPX 400 MHz super-conducting NMR spectrometer with CDCl3 as a solvent and TMS as an internal standard; chemical shifts are reported in
The chemical reagents such as fumed silica (7 nm, Sigma-Alderich), NaOH (Merck, Darmstadt, Germany), and NaAlO2 (Sigma-Aldrich) were used for zeolite synthesis. The nanometer-sized faujasite-X zeolite was synthesized by hydrothermal crystallization in a temperature-controlled shaker. Aluminosilicate gel was prepared by mixing freshly prepared aluminate and silicate solutions together in the molar ratio 5.5 Na2O : 1.0 Al2O3 : 4.0 SiO2 : 190 H2O. Typically, an aluminosilicate gel containing 5.34 g of NaOH, 2.42 g of NaAlO2, 3.43 g of SiO2, and 50.0 g of H2O was adopted. First, a 250 mL plastic bottle containing freshly prepared sodium aluminate solution and SM-30 and fumed silica, the silicate sources were directly mixed with freshly prepared aluminate solution at room temperature and then immediately moved to a shaker at the desired temperature for hydrothermal crystallization. Hydrothermal crystallization was conducted at 60°C for 4 days in a shaker with a rotation rate of 250 rpm. The powdered products were recovered with centrifugation, washed with DI water until pH < 8, and then dried at room temperature for 24 h for further characterization.
The X-ray powder diffraction (XRD) patterns were recorded at 25°C on a Philips instrument (X’pert diffractometer using CuK
Urea/thiourea (0.01 mol), 3-methyl-1-phenyl-5-pyrazolone (0.01 mol) and various substituted aldehydes (0.01 mol) were added nano zeolite NaX (0.02 mol). The reaction mixture was refluxed for appropriate time; the reaction was monitored by thin liquid chromatography. Upon completion of the reaction the clear solution thus obtained was treated with crushed ice to give the solid product which was filtered and dried. The crude product was purified by recrystallization from ethanol (absolute ethanol).
The preparation of the pyrazolone-pyrimidine derivatives involved the reaction of the respective urea/thiourea, 3-methyl-1-phenyl-5-pyrazolone with aromatic aldehydes by using nanoparticles of NaX zeolite catalyst under solvent-free and at reflux conditions (Scheme
Synthesis of pyrazolone-pyrimidine derivatives by using nanoparticles of NaX Zeolite catalysts.
All the tested aromatic aldehydes bearing various substituents such as chloro, nitro, methoxyl, and other substituents could successfully react with 3-methyl-1-phenyl-5-pyrazolone within 60–90 minutes with high yields. The results were summarized in Tables
Synthesis of several pyrazolone-pyrimidine derivatives using urea and nanoparticles of NaX zeolite catalyst.
Entry | Product | Time (h) | aYield (%) | MP (°C) |
---|---|---|---|---|
1 |
|
1 | 90 | 185 |
2 |
|
1.5 | 95.5 | 171 |
3 |
|
1.5 | 93.5 | 156 |
4 |
|
1.5 | 91 | 166 |
5 |
|
2.5 | 84 | 154 |
6 |
|
2.5 | 80 | 150 |
7 |
|
1 | 92 | 138 |
8 |
|
1 | 94 | 145 |
9 |
|
3 | 77 | 188 |
10 |
|
3 | 81 | 183 |
11 |
|
3.5 | 71 | 124 |
Synthesis of several pyrazolone-pyrimidine derivatives using thiourea and nanoparticles of NaX zeolite catalyst.
Entry | Product | Time (min) | aYield (%) | MP (°C) |
---|---|---|---|---|
1 |
|
1 | 91 | 186 |
2 |
|
1.5 | 96.5 | 180 |
3 |
|
1.5 | 93 | 176 |
4 |
|
1.5 | 91.5 | 184 |
5 |
|
2.5 | 84 | 181 |
6 |
|
2.5 | 80 | 185 |
7 |
|
1 | 92.5 | 182 |
8 |
|
1 | 95 | 285 |
9 |
|
3 | 76 | 216 |
10 |
|
3 | 81.5 | 224 |
11 |
|
3.5 | 72 | 151 |
Interestingly, we have not obtained the side products which were usually accompanied with the target compounds when the reaction was carried out in solvent-free. The formation of the pyrazolopyrimidine system was unequivocally established after analysis of NMR data of the products. The chemical shifts and multiplicity of the protons were in consonance with the expected values, for example, the proton at position 3 of all the compounds was found between 8.50 and 9.07 ppm as a sharp singlet. The XRD pattern matches very well with the simulated XRD powder pattern for FAU zeolite [
XRD pattern of as-synthesized sample crystallized.
The crystalline phase of aluminosilicate could be produced NaX hydrate zeolite phase after left it in the suitable temperature and time. From the experimental results, it can be explained that the silica content in fly ash is not enough to form NaX hydrate zeolite phase after incubated at 60°C for 4 × 24 h. Figure
The nanozeolite NaX is very hydrophilic with entrance pores of approximately 7.4 Å. The particle size distributions of nanozeolite crystal from dynamic light scattering (DLS) are shown in Figure
The FESEM image of nanozeolite NaX.
Distribution of particle size of nanozeolite NaX.
The particle size distributions of nanozeolite crystal from dynamic light scattering (DLS) are shown in Figure
Also, the Si/Al ratio of the nanoozeolite NaX was calculated 1.25 through XRF analysis. The unit cell mass of NaY zeolite was calculated using the composition provided by XRF test: Na106[(Al106Si86O384].
We have demonstrated that the reaction between 3-methyl-1-phenyl-5-pyrazolone with aldehydes and urea/thiourea could be effectively performed in the presence of nanozeolite NaX catalyst at reflux and solvent-free conditions. The present method has many obvious advantages over classical procedures, including being environmentally more benign, simple, the ease of product isolation, higher yield, shorter reaction times, and the potential for recycling ionic liquid and catalyst. The recyclability and reusability of the catalyst have been tested. The new catalyst was inexpensive, easy to prepare, and stable. It maintained its original activity during a period of more than a year that constituted this study.