Catalytical Synthesis of Pyrazolines Using Nanoparticles of Preyssler Heteropolyacid Supported on Nano-SiO2, H14[NaP5W30O110]/SiO2: A Green and Reusable Catalyst
Ali Gharib1, 2, *, Nader Noroozi Pesyan3, Leila Vojdani Fard4, Mina Roshani1
1Department of Chemistry, Islamic Azad University, Mashhad, Iran
2Department of Chemistry, Agricultural Researches and Services Center, Mashhad, Iran
3Department of Chemistry, Faculty of Science, Urmia University, Urmia, Iran
4Education Ministry, Education Organization of Razavi Khorasan, Mashhad, Iran
Ali Gharib, Nader Noroozi Pesyan, Leila Vojdani Fard, Mina Roshani. Catalytical Synthesis of Pyrazolines Using Nanoparticles of Preyssler Heteropolyacid Supported on Nano-SiO2, H14[NaP5W30O110]/SiO2: A Green and Reusable Catalyst. Frontiers in Heterocyclic Chemistry. Vol. 1, No. 1, 2015, pp. 6-12. doi: 10.11648/j.ajhc.20150101.12
Abstract: Different Pyrazoline derivatives were synthesized by cyclization of substituted chalcone derivatives in presence of hydrazine hydrate. A series of novel 1,3,5-triaryl pyrazoline derivatives has been synthesized by the reaction of chalcone and phenylhydrazine in the presence of Silica-supported Preyssler Nanoparticles, H14[NaP5W30O110]/SiO2, Preyssler H14[NaP5W30O110] and Keggin heteropolyacids, H3PW12O40, H7[PMo8V4O40], H6[PMo9V3O40], H5[PMo10V2O40], H4[PMo11VO40], H3[PMo12O40] as catalyst under aqueous conditions is described. The best conditions were observed using Preyssler and Silica-supported Preyssler Nanoparticles as catalysts. The catalyst is recyclable and reusable. The structures of compounds obtained were determined by IR and 1H NMR spectra.
Keywords: Pyrazoline, Nanoparticles, Preyssler, Heteropolyacids, Catalyst, Synthesis
Heterocyclic compounds have gained much importance in medicinal chemistry due to its presence in large number of pharmacologically active moieties. Among the five membered heterocyclic containing two hetero atoms in its ring structure, pyrazole is one of the most important one as large variety of biological activities have been reported for various pyrazole derivatives. Pyrazolines are well known, and important nitrogen-containing five-membered heterocyclic compounds and the pyrazoline ring protons were bonded with carbon atoms on a spatially different environment . Pyrazolines are widely used and studied privileged pharmacophores in medicinal chemistry due to their synthetic and biological importance. Some studies have confirmed that pyrazoline derivatives possess antimicrobial activity and they have found to possess anti-fungal, anti-depressant, anti-convulsant, anti-inflammatory, anti-bacterial, anti-cancer, antioxidant, anti-pyretic, anti-neoplastic activities, anti-viral, anti-amoebic, acaricidal agro chemical fungicides or insecticides, anti-cholinergic, antidiabetic, anti-HIV, antimalarial, anaxiolytic, antiparasitic, anti-allergic, anti-microbial, anti-tuberculosis, tyrosinase inhibitor, hypoglycemic, hypotensive, immuno suppressive, anti-tumor [2-7]. Conventional method of synthesis of pyrazolines involves the base-catalyzed condensation of aromatic ketones to give α, β- unsaturated ketones (also called as chalcones), which undergo subsequent cyclization with hydrazine and hydrazine derivatives yielding 2- pyrazoline and 2-pyrazoline derivatives. In this method, hydrazones are formed as intermediates that can subsequently cyclized to 2-pyrazolines in presence of a suitable catalyst such as NaOH  or acetic acid . The α,β-unsaturated ketones can play the role of versatile precursors in the synthesis of the corresponding pyrazolines [10-15]. Numerous methods have been reported for the preparation of pyrazoline compounds. Fischer and Knoevenagel in the nineteenth century studied the reaction of α,β-unsaturated aldehydes and ketones with phenyl hydrazine in acetic acid by refluxing, which became one of the most popular methods for the preparation of 2-pyrazolines . In 1998, Powers et al.  have reported the reaction of chalcones with phenyl hydrazine hydrochloride in the presence of sodium hydroxide and absolute ethanol at 70 °C, where the longer reaction time is the disadvantage of the reaction. K2CO3-mediated microwave irradiation has been shown to be an efficient method for the synthesis of pyrazolines . Recently, the application of nanoparticles (NPs) as catalysts has attracted worldwide attention because of their high catalytic activity and improved selectivity . Heteropolyacids as solid acid catalysts are green with respect to corrosiveness, safety, quantity of waste and separability and it is well known that the use of heteropolyacid catalysts for organic synthesis reactions can give a lot of benefits. One of the unique features that make solid heteropoly acids economically and environmentally attractive is their stability and bronsted acidity. The catalytic function of heteropolyacids (HPAs) and related polyoxometalate compounds has attracted much attention, particularly in the last two decades . These compounds exhibit high activity in acid-base type catalytic reactions, hence they are used in many catalytic areas as homogeneous and heterogeneous catalysts. The application of Preyssler catalysts is highly limited and only a few examples of catalytic activity have been reported . The important advantages of this heteropolyacid are: strong Brønsted acidity with 14 acidic protons, high thermal stability,
2.1. Chemicals and Apparatus
Melting points were determined by Thieles tube method (Table 1) and were uncorrected. 1H-NMR spectra were recorded on a Bruker AM 300 MHz and 13C NMR (Brucker Gemini 100 MHz) spectrometer using CDCl3 as a solvent and tetramethylsilane as an internal standard. The chemical shifts are expressed in δ (ppm). FT-IR spectrometer of Perkin Elmer was used for study. Thin layer chromatography (TLC) was done with pre-coated silica gel plates (GF254 Merck) using benzene:ethyl acetate (9.5:0.5, v/v) as the mobile phase.
2.2. Catalyst Synthesis Procedure
2.2.1. Synthesis of SiO2 Nanoparticles
The materials used in this work include tetraethyl orthosilicate (TEOS) (Merck, 98%) as the SiO2 precursor. Besides the main precursor, nitric acid (65%) and double distilled water were used for peptization and solvent, respectively. The sol-gel precursor solution was obtained by mixing tetraethyl orthosilicate (TEOS) and ethanol with specific molar ratios of ethanol to TEOS. The mixture was stirred using magnetic stirring.
2.2.2. Preyssler Heteropolyacid Catalyst Preparation
Preyssler catalyst, H14[NaP5W30O110] was prepared by passage of a solution of the potassium salt (30 mL) in water (30 mL) through a column (50 cm × 1 cm) of Dowex 50w×8 in the H+ form. The eluent was evaporated to dryness under vacuum [25,26].
2.2.3. Synthesis Procedure of Nanoparticles of Preyssler Heteropolyacid Supported on Nano-SiO2, H14[NaP5W30O110]/SiO2 Catalyst
To a solution of the surfactant, sodium bis(2-ethylhexyl) sulphosuccinate, in cyclohexane (0.2 mol L–1), a solution of Preyssler acid in a specified amount of water was added. The molar ratio of water to surfactant was selected to be 3, 5 and 7. Tetraethoxysilane (TEOS) was then added to the micro-emulsion phase. After mixing for various times (8, 12, 18, 25 and 30 h) at room temperature, dispersed Preyssler acid/SiO2 nanostructures were centrifuged and the particles were rinsed with acetone (4 times) and dried in a vacuum oven. The optimum ratio of water to surfactant was 3:1 and the optimum time was 30 h.
2.2.4. Preparation of Various Heteropolyacids Caralysts
The catalysts of H4[PMo11VO40], H5[PMo10V2O40], H6[PMo9V3O40], H7[PMo8V4O40] and Wells-Dawson, H6[P2W18O62] were prepared in according to the literature [27-35]. H6[P2W18O62], H7[PMo8V4O40], H6[PMo9V3O40], H5[PMo10V2O40], H4[PMo11VO40] and H3[PMo12O40] were prepared according to the literatures [35,36]. The integrity of the synthesized heteropolyacids has been proven by comparing of spectral data with those reported in literatur [25,29,37,38].
2.3. Synthesis of Substituted Pyrazoline Derivatives
2.3.1. Procedure for the Synthesis of Substituted Chalcone Derivative
A solution of sodium hydroxide (40%) in water and rectified spirit was placed in a flask provided with a mechanical stirrer. The flask was immersed in a bath of crushed ice. Substituted acetophenone (0.008 mol) was poured with constant stirring, Substituted benzaldehydes (0.008 mol) was added to the solution. The temperature of the mixture was kept at room temperature (25 oC) and stirred vigorously until the mixture was thick enough to retard the stirring (5 h). The stirrer was removed and the reaction mixture was kept at 5 oC overnight. The product was filtered with suction on a buchner funnel, washed with cold water until the washings were neutral to litmus and then with ice cold ethanol. The crude product was recrystallized from ethanol.
2.3.2. Procedure for the Synthesis of Substituted Pyrazoline Derivatives
In a mixture of substituted chalcone (0.02 mol) in nanoparticles of Preyssler heteropolyacid supported on Nano-SiO2, H14[NaP5W30O110]/SiO2 as catalyst (0.05 mmol), glacial acetic acid (1 mL), ethanol (60 mL), hydrazine hydrate (0.04 mol) was added drop wise in a round bottom flask. The reaction mixture was heated under reflux for appropriate time on a water bath and then the reaction was continued for a certain period of time as required for completion (monitored by TLC). The reaction mixture was then filtered to separate the catalyst and this solvent followed with addition of ice cold water at room temperature. The mixture was kept overnight at 5 oC. The precipitates were filtered, washed with distilled water and dried. The product was recrystallized with ethanol to get final product.
2.4. Selected Spectral Data
IR (KBr, cm−1): ν 1120, 1506, 1591. 1H NMR (300 MHz, CDCl3): δH 3.13 (dd, J = 7.1, 17.0 Hz, 1H), 3.89 (dd, J = 12.2, 17.1 Hz, 1H), 5.30 (dd, J = 7.3, 12.4 Hz, 1H) 6.83-7.65 (m, 14H). 13C NMR (100 MHz, CDCl3): δC 42.36, 61.30, 113.51, 117.25, 126.80, 126.92, 128.63, 129.16, 129.39, 130.56, 132.15, 132.18, 136.04, 139.60, 143.70, 147.38. Anal. calcd. for C21H17N2Cl: C 84.85, H 5.72, N 9.43; found C 84.81, H 5.77, N 9.47.
IR (KBr, cm−1): ν 1120, 1263, 1511, 1595. 1H NMR (300 MHz, CDCl3): δH 3.11 (dd, J = 7.1, 17.1 Hz, 1H), 3.80 (s, 3H, OCH3), 3.85 (dd, J = 12.1, 16.9 Hz, 1H), 5.26 (dd, J = 7.2, 12 Hz, 1H) 6.75-7.83 (m, 14H). 13C NMR (100 MHz, CDCl3): δC 44.04, 55.63, 64.15, 113.70, 114.45, 119.56, 126.40, 127.90, 128.48, 128.87, 129.18, 130.57, 133.20, 135.02, 145.34, 147.19. Anal. calcd. for C22H20N2O: C 84.62, H 6.41, N 8.97; found C 84.56, H 6.40, N 8.93.
IR (KBr, cm−1): ν 1125, 1501, 1597. 1H NMR (300 MHz, CDCl3): δH 3.05 (dd, J = 7.1, 17.0 Hz, 1H), 3.33 (dd, J =12.1, 16.9 Hz, 1H), 5.67 (dd, J = 6.9, 12.7 Hz, 1H) 6.80-7.73 (m, 14H). 13C NMR (100 MHz, CDCl3): δC 42.36, 60.45, 113.33, 119.50, 124.22, 127.95, 128.07, 129.05, 129.15, 129.34, 130.58, 132.41, 133.18, 139.66, 145.25, 147.14. Anal. calcd. for C21H17N2Br: C 85.85, H 5.72, N 9.43; found C 85.78, H 5.69, N 9.43.
IR (KBr, cm−1): ν 1115, 1501, 1587. 1H NMR (300 MHz, CDCl3): δH 3.01 (dd, J = 6.6, 17.6 Hz, 1H), 3.96 (dd, J =12.5, 17.5 Hz, 1H), 5.57 (dd, J = 6.6, 12.2 Hz, 1H), 6.69-7.70 (m, 13H); 13C NMR (100 MHz, CDCl3): δC 41.54, 60.94, 113.51, 119.50, 124.30, 125.69, 127.42, 127.72, 128.61, 128.50, 128.59, 129.29, 129.55, 132.10, 133.92, 137.73, 144.40, 147.55. Anal. Calcd. for C21H16Cl2N2: C, 68.67; H, 4.39; N, 7.62. Found: C, 68.73; H, 4.39; N, 7.71%.
IR (KBr, cm−1): ν 1122, 1498, 1593. 1H NMR (300 MHz, CDCl3): δH 3.05 (dd, J = 4.8, 17.6 Hz, 1H), 3.95 (dd, J =11.2, 17.7 Hz, 1H), 5.62 (dd, J = 4.7, 11.0 Hz, 1H), 6.76-7.70 (m, 14H); 13C NMR (100 MHz, CDCl3): δC 41.71, 61.46, 113.33, 119.27, 125.90, 127.52, 127.98, 128.34, 128.55, 128.88, 129.38. 129.86, 131.40, 132.24, 139.56, 144.65, 147.48. Anal. Calcd. for C21H17ClN2: C, 75.78; H, 5.15; N, 8.41. Found: C, 75.83; H, 5.23; N, 8.38%.
IR (KBr, cm−1): ν 1123, 1504, 1590. 1H NMR (300 MHz, CDCl3): δH 3.05 (dd, J = 6.8, 17.0 Hz, 1H), 3.41 (dd, J = 12.2, 17.2 Hz, 1H), 5.65 (dd, J = 6.9, 12.4 Hz, 1H) 6.85-7.72 (m, 14H) ppm. 13C NMR (100 MHz, CDCl3): δC 42.37, 61.54, 113.58, 119.60, 124.44, 127.79, 128.07, 128.92, 129.18, 129.48, 130.67, 132.53, 133.04, 135.04, 139.67, 144.84, 147.53. Anal. calcd. for C21H17N2Cl: C 85.85, H 5.72, N 9.43; found C 85.79, H 5.70, N 9.41.
IR (KBr, cm−1): ν 1121, 1493, 1595. 1H NMR (300 MHz, CDCl3): δH 3.01 (dd, J = 7.4, 17.6 Hz, 1H), 3.75 (dd, J = 11.6, 17.6 Hz, 1H), 5.64 (dd, J = 7.4, 11.6 Hz, 1H), 6.71-7.60 (m, 14H); 13C NMR (100 MHz, CDCl3): δC 43.45, 63.85, 113.42, 119.41, 125.73, 127.37, 128.52, 128.76, 128.92, 129.30, 129.93, 132.54, 133.37, 141.10, 144.68, 146.73. Anal. Calcd. for C21H17ClN2: C, 75.78; H, 5.15; N, 8.41. Found: C, 75.69; H; 5.10; N, 8.49%.
IR (KBr, cm−1): ν 1115, 1496, 1590. 1H NMR (300 MHz, CDCl3): δH 2.35 (s, 3H, CH3), 3.14 (dd, J = 7.1, 17.0 Hz, 1H), 3.852 (dd, J = 12.1, 17.0 Hz, 1H), 5.24 (dd, J = 6.9, 12 Hz, 1H) 6.77-7.70 (m, 14H). 13C NMR (100 MHz, CDCl3): δC 21.67, 44.06, 64.70, 113.63, 119.46, 126.21, 128.41, 128.84, 129.31, 129.50, 130.15, 133.04, 137.66, 141.52, 145.41, 147.19. Anal. calcd. for C22H20N2: C 84.62, H 6.41, N 8.97; found C 84.61, H 6.43, N 9.00.
3. Result and Discussion
The propenones (1a-h) were then reacted with hydrazines in the presence of silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2 catalyst to give pyrazolines drivatives (Table 1, 5a-h) and Scheme 1.
This reaction probably takes place via an appropriate α,β-unsaturated hydrazone intermediate followed by the attack of NH on the carbon-carbon double bond of the propenone moiety to give a pyrazoline ring.
|Entry||Product||Time (h)||aYield (%)||Mp (oC)|
|3||89 (89, 88, 88,87.5)b||142-144||143-145|
aIsolated yields. bCatalyst was reused over three runs.
3.1. Catalyst Rcovery
In our experiments, the reusability of the catalyst were examined by repetitive use of the catalyst. The wet catalyst was recycled and no appreciable change in activity was noticed after three cycles (Table 1, entries 1, 2, 5-8).
3.2. Effects of the Solvent
Different organic solvents were examined for the reaction and we found that ethanol was the solvent of choice (Table 2). CH3OH, CHCl3 and THF proved to be almost as good as ethanol, with CH2Cl2 giving a slightly better yield than CCl4. When the reactions were conducted in ethanol, the expected products were obtained in good yields and with better reaction times compared to organic solvents (Tables 1 and 2).
|Entry||Solvent||Time (h)||aYield (%)|
3.3. Effects of the Catalyst Type
Initially, we compared the catalytic performance of Preyssler and four Keggin-type heteropolyacids (H14[NaP5W30O110], H7[PMo8V4O40], H6[PMo9V3O40], H5[PMo10V2O40], H4[PMo11VO40], H6[P2W18O62] and H3[PMo12O40]) catalyst, in the synthesis of 5-(4-Methylphenyl)-1,3-diphenyl-2-pyrazoline (Table 1, entry 8, product 5h). The results are shown in Table 3. The yield of product decreases in the following order:
silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2>H14[NaP5W30O110]>H7[PMo8V4O40]>H6[P2W18O62]>H6[PMo9V3O40]>H5[PMo10V2O40]>
ZnCl2>H2SO4>SiO2 nanoparticles> no Catalyst
As could be seen, silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2 catalyst is more effective than the other catalysts, and in the presence of this catalyst the highest yields of products are obtained. The results (Table 3) show that silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2 catalyst is better with respect to yield and to reaction. In all cases, the silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2 catalyst shows higher activity compared with other catalysts (Table 3, Entries 2-4). This catalyst is an efficient solid acid catalyst for the synthesis of synthesis of 5-(4-Methylphenyl)-1,3-diphenyl-2-pyrazoline (Table 1, Entry 8, product 5h).
|Entry||Catalyst||Time (h)||aYield (%)|
|1||Preyssler nanoparticles, H14[NaP5W30O110]/SiO2||3.5||99|
a Isolated yield.
A plausible mechanism for the reaction of chalcone with phenylhydrazine in the presence of silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2 catalyst is also presented by Scheme 2.
Herein is reported a relatively simple and useful method for the synthesis of pyrazolines in good yield using silica-supported Preyssler nanoparticles, H14[NaP5W30O110]/SiO2 catalyst in ethanol as solvent. This catalyst is a safe and recoverable heterogeneous system for promoting the synthesis of 1,3,5-triaryl pyrazoline. The advantages of this catalytic system is mild reaction conditions, short reaction times, high product yields, easy preparation of the catalysts, non-toxicity of the catalysts, stable, simple and clean work-up of the desired products. In addition, the catalyst can be recycled after washing ethanol followed by drying. and the catalysts can be reused several times but they will be less active. Therefore, the method is eco-friendly.