- About this Journal ·
- Abstracting and Indexing ·
- Aims and Scope ·
- Article Processing Charges ·
- Articles in Press ·
- Author Guidelines ·
- Bibliographic Information ·
- Citations to this Journal ·
- Contact Information ·
- Editorial Board ·
- Editorial Workflow ·
- Free eTOC Alerts ·
- Publication Ethics ·
- Reviewers Acknowledgment ·
- Submit a Manuscript ·
- Subscription Information ·
- Table of Contents
Journal of Catalysts
Volume 2013 (2013), Article ID 657409, 4 pages
Catalytic Synthesis of Pyrazolo[3,4-d]pyrimidin-6-ol and Pyrazolo[3,4-d]pyrimidine-6-thiol Derivatives Using Nanoparticles of NaX Zeolite as Green Catalyst
1Department of Chemistry, Islamic Azad University, Mashhad, Iran
2Agricultural Researches and Services Center, Mashhad, Iran
Received 12 August 2012; Revised 9 February 2013; Accepted 20 February 2013
Academic Editor: Piyasan Praserthdam
Copyright © 2013 Ali Gharib 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.
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 . Synthesis of such biologically important compounds assumes great importance. Pyrazolopyrimidine derivatives are purine analogues, and as such they have useful properties as antimetabolites in purine biochemical reaction . Moreover, these compounds also display marked antitumor and antileukemic activities . Pyrazolopyrimidine derivatives have received a great deal of attention due to their pharmacological activity , such as allopurino , which is still the drug of choice for the treatment of hyperuricemia and gouty arthritis . 1-Phenyl-3-methyl-4-arylmethylene-5-pyrazolones are very useful intermediates in the synthesis of substituted pyrazolones, generally, which were prepared by the condensation of 3-methyl-1-phenyl-5-pyrazolone with aromatic aldehydes . The incorporation of another heterocyclic moiety in pyrans either in the form of a substituent or as a fused component changes its properties and converts it into an altogether new and important heterocyclic derivative. Pyrazoles have attracted particular interest over the last few decades due to the use of such ring system as the core nucleus in various drugs. They are well known for their popular pharmacological activities. Considering the importance of pyrazolone derivatives, it was thought worthwhile to synthesize new compounds incorporating both these moieties. All the compounds synthesized in the present study were screened for their antibacterial activity against some bacteria (both gram-negative and gram-positive) namely, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and C. albicans by filter paper disc technique. Zeolite X is a highly versatile molecular sieve from the faujasite family of zeolites whose 7.4?Å, three-dimensional pore structure and solid acidity make it useful as a catalyst, adsorbent, membrane, and others [8–10]. This type of zeolite is used for heavy metal adsorption , aromatics from aromatic/alkane mixtures , and para-xylene  separation, as well as natural gas desulfurization . The powerful catalytic properties of X zeolite due to its use in the reaction between MeOH and PhNH2 , hydrocarbons cracking , chlorination of toluene , and the ammonia synthesis . In this paper, nanozeolite NaX was synthesized via hydrothermal methods with agitation and temperature controlling. We did not use the addition of organic templates, directing agent, seeding crystals, and other additives in this synthesis.
2.1. Chemicals and Apparatus
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 d units (ppm). Mass spectra were measured on FAB/MS INCOS XL Finnigan MAT. Microanalyses were performed on a LECO-CHNS-932 elemental analyzer.
2.2. Nanozeolite NaX Synthesis
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.
2.3. Nanozeolite Characterization
The X-ray powder diffraction (XRD) patterns were recorded at 25°C on a Philips instrument (X’pert diffractometer using CuKa radiation) with a scanning speed of 0.03° () min-1. The crystallinity of sample was determined from the peak areas of 6° , 16° , and 27° , and the average crystal dimension was calculated using Scherrer’s equation [12, 13]. Also, the particle size distribution was measured by the Mastersizer 2000 (Malvern instrument). The SEM (Hitachi, model S-4160) was used to particle size distribution of nanozeolite crystals, and the Si/Al ratio, elemental compositions of nanoparticles was determined by XRF (Philips instrument).
2.4. Synthesis of Pyrazolone-Pyrimidine Derivatives
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).
2.5. Selected Spectra Data
Compound (4a). IR (KBr, cm-1): 3505, 3422, 3005, 1634, 1573. 1H-NMR (400?MHz, CDCl3, d/ppm): 8.53 (s, 1H),4.88 (s, 1H), 3.74 (m, 8H), 2.28 (m, 8H), 2.45 (s, 3H),7.48 (m, 9H). 13C-NMR (400?MHz, CDCl3, d/ppm): 163.1, 155.7, 143.7, 136.5, 129.6, 128.7, 128.2, 126.1, 120.7, 116.6, 26.8. HRMS (EI) Calcd. for C18H17N4O [M]+, 305.1003, Found 305.1006; Anal Calcd for C18H17N4O: C 70.82, H 5.60, N 18.36. Found: C 70.88, H 5.52, N 18.39%.
Compound (5a). IR (KBr, cm-1): 2552, 3427, 3005, 1636, 1575, 662. 1H-NMR (400?MHz, CDCl3, d/ppm): 8.54 (s, 1H), 1.26 (m, 1H), 3.73 (m, 8H), 2.27 (m, 8H), 2.36 (s, 3H), 7.54 (m, 9H). 13C-NMR (400?MHz, CDCl3, d/ppm): 163.2, 155.7, 143.7, 136.5, 129.6, 128.9, 128.2, 126.1, 116.5, 62.6, 52.2, 43.9, 26.6. HRMS (EI) Calcd. for C18H17N4S [M]+, 321.1001, Found 321.1008; Anal Calcd for C18H17N4S: C 67.25, H 5.37, N 17.45. Found: C 67.29, H 5.41, N 17.54%.
3. Results and Discussion
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 1).
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 1 and 2.
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 [12–16] indicating that the synthesized crystal is pure FAU zeolite and shows that nanozeolite NaX sample has more than 95% crystalline (Figure 1).
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 1 showed that strong broad peaks of pure silica are centered range on ˜22-23° (), which are in keeping with the strong broad peak of a characteristic of amorphous SiO2 . The result showed that pure silica is in an amorphous state.
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 2 results indicated a narrow distribution of particle size, with an average crystal size of 112?nm. The average crystal dimension of ?nm was calculated by Scherrer’s equation from the diffraction peaks at values of 6° , 16° , and 27° . The average particle size (Å) was calculated by (1).
Scherrer’s equation is where is the shape factor, is the X-ray wavelength, typically 1.54 Å, is the line broadening at half the maximum intensity (FWHM) in radians, and is the Bragg angle. The result of DLS is more important than XRD methods because the DLS calculates the particle distribution, but the Scherrer’s equation measures an average particle size. The SEM image recorded for the as-synthesized nanozeolite sample is shown in Figure 2. The Field-Emission Scanning Electron Microscope (FESEM) image recorded for the as-synthesized nanozeolite sample is shown in Figure 2 which clearly indicates that the particle size of nano-NaX is ultrafine and within a range of 40–150?nm which is consistent with the results calculated from the XRD pattern and dynamic light scattering (Figure 3).
The particle size distributions of nanozeolite crystal from dynamic light scattering (DLS) are shown in Figure 3; results indicated a narrow distribution of particle size, with an average crystal size of 112?nm.
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.
- B. G. Hildick and G. Shaw, “Purines, pyrimidines, and imidazoles. Part XXXVII. Some new syntheses of pyrazolo[3,4-d]pyrimidines, including allopurinol,” Journal of the Chemical Society C, pp. 1610–1613, 1971.
- E. W. Satherland, G. A. Robinson, and R. W. Butcher, “Some aspects of the biological role of adenosine 3′,5′-monophosphate (Cyclic AMP),” Circulation, vol. 37, pp. 279–306, 1968.
- R. A. Earl, R. J. Pugmire, G. R. Revankar, and L. B. Townsend, “A chemical and carbon-13 nuclear magnetic resonance reinvestigation of the N-methyl isomers obtained by direct methylation of 5-amino-3,4-dicyanopyrazole and the synthesis of certain pyrazolo [3,4-d]pyrimidines,” Journal of Organic Chemistry, vol. 40, no. 12, pp. 1822–1828, 1975.
- D. Villemin and B. Labiad, “Clay catalysis: dry condensation of 3-Methyl-1- Phenyl-5-Pyrazolone with aldehydes under microwave irradiation,” Synthetic Communications, vol. 20, pp. 3213–3220, 1990.
- T. Welton, “Room-temperature ionic liquids. Solvents for synthesis and catalysis,” Chemical Reviews, vol. 99, no. 8, pp. 2071–2084, 1999.
- P. Traxler, G. Bold, J. Frie, M. Lang, N. Lydon, and H. Mett, “Steroidal affinity labels of the estrogen receptor. 3. Estradiol 11α-n-Alkyl derivatives bearing a terminal electrophilic group: antiestrogenic and cytotoxic properties,” Journal of Medicinal Chemistry, vol. 40, pp. 2217–2225, 1997.
- G. Desimoni, L. Astolfi, M. Cambieri, A. Gamba, and G. Tacconi, “Heterodiene syntheses-XII. The conformational analysis of cis and trans 2-alkoxy-4-phenyl-2,3-dihydropyran[2,3-c] pyrazoles: steric interactions and the anomeric effect,” Tetrahedron, vol. 29, no. 17, pp. 2627–2634, 1973.
- S. Sanga, Z. Liu, P. Tiana, Z. Liua, L. Qua, and Y. Zhang, “Synthesis of small crystals zeolite NaY,” Materials Letters, vol. 60, pp. 1131–1131, 2006.
- B. H. Wang, Y. Y. Xia, S. Y. Zhuang, Y. H. Zhang, and T. T. Yan, The Imaging Science Journal, vol. 25, pp. 131–135, 1998.
- S. Mintova and V. Valtchev, “Synthesis of nanosized fau-type zeolite,” Studies in Surface Science and Catalysis, vol. 125, pp. 141–148, 1999.
- Y. S. Ok, J. E. Yang, Y. S. Zhang, S. J. Kim, and D. Y. Chung, “Heavy metal adsorption by a formulated zeolite-Portland cement mixture,” Journal of Hazardous Materials, vol. 147, no. 1-2, pp. 91–96, 2007.
- M. Fathizadeh and M. Nikazar, “Adsorption of aromatic from alkane/aromatic mixtures by NaY zeolite,” Journal of Chemical Engineering of Japan, vol. 42, no. 4, pp. 241–247, 2009.
- C. R. Jacob, S. P. Varkey, and P. Ratnasamy, “Oxidation of para-xylene over zeolite-encapsulated copper and manganese complexes,” Applied Catalysis A, vol. 182, no. 1, pp. 91–96, 1999.
- M. W. Ackley, S. U. Rege, and H. Saxena, “Application of natural zeolites in the purification and separation of gases,” Microporous and Mesoporous Materials, vol. 61, pp. 25–42, 2003.
- L. J. Garces, V. D. Makwana, B. Hincapie, A. Sacco, and S. L. Suib, “Selective N,N-methylation of aniline over cocrystallized zeolites RHO and zeolite X (FAU) and over Linde type L (Sr,K-LTL),” Journal of Catalysis, vol. 217, no. 1, pp. 107–116, 2003.
- F. N. Guerzoni and J. Abbot, “Catalytic cracking of a binary mixture on zeolite catalysts,” Applied Catalysis A, vol. 103, no. 2, pp. 243–258, 1993.
- M. C. Hausladen and C. R. F. Lund, “Zeolite-catalyzed chlorination of toluene by sulfuryl chloride: activity, selectivity and deactivation of NaX and NaY zeolites,” Applied Catalysis A, vol. 190, no. 1-2, pp. 269–281, 2000.
- C. T. Fishel, R. J. Davis, and J. M. Garces, “Ammonia synthesis catalyzed by ruthenium supported on basic zeolites,” Journal of Catalysis, vol. 163, no. 1, pp. 148–157, 1996.
- B. W. Jo, C. H. Kim, G. H. Tae, and J. B. Park, “Characteristics of cement mortar with nano-SiO2 particles,” Construction and Building Materials, vol. 21, no. 6, pp. 1351–1355, 2007.