Efficiency of NaHSO4 modified periodic mesoporous organosilica magnetic nanoparticles as a new magnetically separable nanocatalyst in the synthesis of [1,2,4]triazolo quinazolinone/pyrimidine derivatives

Article abstract of DOI:10.1016/j.molstruc.2018.05.112

Immobilized NaHSO₄ on core/shell phenylene bridged Periodic mesoporous organosilica magnetic nanoparticles (γ-Fe₂O₃@Ph-PMO-NaHSO₄) as a new acidic magnetically separable nanocatalyst was successfully prepared in three steps: (i) preparation of γ-Fe₂O₃ nanoparticles by a precipitation method, (ii) synthesis of an organic-inorganic periodic mesoporous organosilica structure with phenyl groups on the surface of γ-Fe₂O₃ magnetic nanoparticles (MNPs) and (iii) finally adsorption of NaHSO₄ on periodic mesoporous organosilica (PMO) network. The results of N₂ adsorption-desorption isotherms, XRD and TEM showed formation of the Periodic mesoporous organosilica magnetic nanocomposite with the uniform size up to 15 nm. The efficiency of the new catalyst was evaluated in promoting the synthesis of [1,2,4]triazolo quinazolinone/pyrimidine derivatives as important biologically active compounds. Eco-friendly protocol, high yields, short reaction times, reusability of the catalyst and easy and quick isolation of the products are the main advantages of this procedure.

Full text of DOI:10.1016/j.molstruc.2018.05.112

Accepted Manuscript
Efficiency of NaHSO modified periodic mesoporous organosilica magnetic
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nanoparticles as a new magnetically separable nanocatalyst in the synthesis of
[1,2,4]triazolo quinazolinone/pyrimidine derivatives
Mahdieh Haghighat, Farhad Shirini, Mostafa Golshekan
PII:
S0022-2860(18)30699-9
10.1016/j.molstruc.2018.05.112
MOLSTR 25285
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 24 February 2018
Revised Date: 29 May 2018
Accepted Date: 31 May 2018
Please cite this article as: M. Haghighat, F. Shirini, M. Golshekan, Efficiency of NaHSO modified
4
periodic mesoporous organosilica magnetic nanoparticles as a new magnetically separable nanocatalyst
in the synthesis of [1,2,4]triazolo quinazolinone/pyrimidine derivatives, Journal of Molecular Structure
(2018), doi: 10.1016/j.molstruc.2018.05.112.
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Graphical Abstract
Efficiency of NaHSO4 modified periodic mesoporous organosilica
magnetic nanoparticles as a new magnetically separable nanocatalyst in
the synthesis of [1,2,4]triazolo quinazolinone/pyrimidine derivatives.
Mahdieh Haghighat a, Farhad Shirini a,*, Mostafa Golshekan b
a Department of Chemistry, College of Sciences, University of Guilan, Rasht, 41335-19141, Iran
b Institute of Medical Advanced Technologies, Guilan University of Medical Science, Rasht,41346-45971, Iran
γ-Fe2O3@Ph-PMO-NaHSO4 as a new magnetically separable solid acid nanocatalyst is prepared and applied for the synthesis of
[1,2,4]triazolo quinazolinone/pyrimidine derivatives.

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Efficiency of NaHSO4 modified periodic mesoporous organosilica
magnetic nanoparticles as a new magnetically separable
nanocatalyst in the synthesis of [1,2,4]triazolo
quinazolinone/pyrimidine derivatives
Mahdieh Haghighata, Farhad Shirinia*, Mostafa Golshekanb
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a Department of Chemistry, College of Science, University of Guilan, Rasht, 41335-19141, Iran, Tel/Fax: +981313233262; e-mail:
shirini@guilan.ac.ir (and also fshirini@gmail.com).
b Institute of Medical Advanced Technologies, Guilan University of Medical Science, Rasht,41346-45971, Iran
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Abstract— Immobilized NaHSO4 on core/shell phenylene bridged Periodic mesoporous organosilica magnetic nanoparticles (γ-
Fe2O3@Ph-PMO-NaHSO4) as a new acidic magnetically separable nanocatalyst was successfully prepared in three steps: (i) preparation of
γ-Fe2O3 nanoparticles by a precipitation method, (ii) synthesis of an organic-inorganic periodic mesoporous organosilica structure with
phenyl groups on the surface of γ-Fe2O3 magnetic nanoparticles (MNPs) and (iii) finally adsorption of NaHSO4 on periodic mesoporous
organosilica (PMO) network. The results of N2 adsorption-desorption isotherms, XRD and TEM showed formation of the Periodic
mesoporous organosilica magnetic nanocomposite with the uniform size up to 15 nm. The efficiency of the new catalyst was evaluated in
promoting the synthesis of [1,2,4]triazolo quinazolinone/pyrimidine derivatives as important biologically active compounds. Eco-friendly
protocol, high yields, short reaction times, reusability of the catalyst and easy and quick isolation of the products are the main advantages
of this procedure.
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Keywords: PMO, nanocatalyst; [1,2,4]triazolo quinazolinone, γ-Fe2O3@Ph-PMO-NaHSO4.
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1. Introduction
Multi-component reactions are one of the most attractive and favourite areas from chemists point of view and play a major role
in organic chemistry and pharmaceutical industry because of their significant advantages including feasibility of one-pot synthesis
which avoids the extra cost of sequential separation and purification process of the synthetic intermediates, high yields compared
with multi-step reactions, better selectivity, short reaction times and experimental cost. Generally, multi-component reactions
(MCRs) define as chemical processes which in them more than two substrates condense to provide a product and they are notably
perfect and eco-friendly reaction system in the synthesis of condensed heterocycle molecules [1-3].
Synthesis of quinazolinones derivatives as nitrogen-containing heterocycles has drawn a huge consideration because of their
biological activities, various applications in pharmaceutical industries and their important role in research and industry [4-12].
Antifungal Epoxiconazole, fluconazole, and albaconazole are examples of some biologically active compounds because of the
presence of this group of materials in their structure (see part III in the Supplimentary material) [13-14]. Hence, there is a growing
demand for the efficient synthetic ways to make the substituted triazolo quinazolinones. In this way the most common strategy is
the reaction of 3-amino-1,2,4-triazole as amine source with various aldehydes and dimedone under different conditions which have
been reported in the literature such as MW radiation [15-16], refluxing in DMF [17-18] or in the presence of a variety of promotors
including H6P2W18O62 [19], NH2SO3H [20], 1-n-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4) [21], p-toluenesulfonic
acid [22], acetic acid [23], nano-SiO2 [24], and sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H) [25]. Despite
undeniable advantages of these methods, many of them suffer from some drawbacks such as the use of expensive and hazardous
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catalysts [19, 24] or solvents [ 17, 18, 15], harsh conditions [17,18], long reaction times [18] and low yields [17,18]. Now at this
time, it is important to develop a more efficient method for the synthesis of triazolo quinazolinones using new catalysts which
follows green chemistry principles. It can be achieved by the preparation of nanocatalysts which possesses both properties of
homogeneous and heterogeneous systems including high activity and selectivity and easy separation and recovery.
In recent years, porous materials have played a very important role in science and industry so that billion dollars are spent
annually in the use of these materials in various fields. Some of these important fields are ionic exchange, separation, catalysis,
preparation of batteries, fuel cells, sensors and many others. Among these materials, mesoporous silica has attracted considerable
attention in the field of adsorption and catalysis because of its uniform pore size, large pore volume and high surface area [26].
Periodic mesoporous organosilica materials as a member of this family, are a class of hybrid materials which organic groups are
distributed in uniformly inside the framework, causing properties including mechanical and hydrothermal stability, diffusion of
guest molecule and lack of pore blocking and they are more hydrophobic and stable in water than pure organized silicas (MCM-41
or SBA-15). This feature expands the range of applications in, for example, optical gas sensing, catalysis, chromatography,
separation and nanotechnology [27-28]. For the preparation of this kind of materials, a common method included the hydrolysis and
condensation of a bridged organosilane precursor of the type (R`O)3 Si-R-Si(OR`)3 ( R` is methyl or ethyl and R is an organic
group) in the presence of a structure directing agent can be used. Based on this, one-pot synthesis was used as a method for the
preparation of periodic mesoporous organosilica magnetic nanocomposite which is possible by the co-condensation of magnetic
nanoparticles and tetraethyl orthosilicate (TEOS) with a bridged organosilane precursor of the type (R`O)3 Si-R-Si(OR`)3 in the
presence of a surfactant.
So, the synthesis of nanocatalysts with simultaneous use of magnetic nanoparticles and mesoporous silica materials like periodic
mesoporous organosilica with the mentioned properties provide the opportunity to chemists to develop catalysts with high surface
area and easy separation which can cover some drawbacks of restricted use of inorganic acid or conventional Lewis acids in organic
syntheses which is related to their handling, disposal, recovery and reuse them from the reaction mixture.
In continuation of our ongoing research program on the development of nanocatalysts in organic transformations [29-31] and in
order to develop simple, efficient, and mild strategies using reusable solid catalysts, in this study a new magnetically separable solid
acid nanocatalyst which possesses both features of homogeneous and heterogeneous systems is prepared and applied to the
synthesis of [1,2,4]triazolo quinazolinone/pyrimidine. This strategy involves γ-Fe2O3 nanoparticles as the magnetic core coated by
Ph-PMO as a thin layer on which NaHSO4 is adsorbed.
2. Experimental
2.1. Materials
All chemicals including FeCl3.6H2O (cat. No: 103943), FeCl2.4H2O (cat. No: 103861), tetraethylorthosilicate (TEOS) (cat. No:
800658), 1,4-bis(triethoxysilyl)benzene ( cat. No: 598038), sodium bisulfate monohydrate, Pluronic P-123 (Mn:5800 g.mol-1 , cat
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no: 435465), NaOH, benzaldehyde derivatives, 1,3-cyclohexanedione, dimedone, ethyl acetoacetate and 3-amino-1,2,4-triazole,
were purchased with high purity from Sigma-Aldrich and Merck Chemical Company. The purity of the substrates was assessed by
TLC on silica-gel polygram SILG / UV 254 plates.
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2.2. Characterization techniques
The crystallinity of the prepared nanocatalyst was determined with an X-PERT High Score X-ray diffraction (PANalitical) and
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measured with Cu Kα radiations in the range of 0.6–80◦ (2θ). To characterize the composition of the synthesized nanoparticles, a
Perkin-Elmer spectrum BX series in the range of 400–4000 cm−1 were employed. The determination of particles size and
morphology were performed via a Philips transmission electron microscopy (TEM, CM10 HT 100 kV). For measuring melting
points, a Büchi B-545 apparatus in open capillary tubes were used. N2 adsorption-desorption was measured by a BELSORP-mini II
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instrument at 77 K. Before using the samples, they were degassed for 2 h at 120 C. The specific surface area of each material was
calculated using the Brunauer–Emmett Tellet (BET) method. The EDX characterization of the catalyst was conducted on a field
emission scanning electron microscope making by TE-SCAN Company and equipped with energy dispersive X-ray spectrometer
operating at 15 kV.
2.3. Preparation of the catalyst
2.3.1 Preparation of γ-Fe2O3-MNPs
γ-Fe2O3-MNPs were chemically synthesized with a little modification in the methodology already described in the literature [32].
For the synthesis of γ-Fe2O3-MNPs, ferric chloride hexahydrate FeCl3·6H2O (11.0 g, 40.7 mmol) and ferrous chloride tetrahydrate
FeCl2·4H2O (4.0 g, 20.1 mmol) were dissolved in deionized water (250 mL) under nitrogen atmosphere with mechanical stirrer at
85 °C in order to prepare the stock solution of ferrous and ferric chloride. Then the prepared solution was slowly added to 250 mL
of a 2 mol L−1 ammonia solution heated at 80 ◦C under argon gas protection and stirred vigorously. During the process, the solution
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temperature was kept constant at 80 C and argon gas was purged to prevent the intrusion of oxygen. After completion of the
reaction, the obtained precipitate of γ-Fe2O3-MNPs was separated from the reaction medium by the magnetic field and then was
washed four times with 500 mL double-distilled water. Finally, the obtained γ-Fe2O3-MNPs were suspended in 500 mL of degassed
deionized water.
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2.3.2 Preparation of γ-Fe2O3@Ph-PMO nanocomposite
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For the synthesis of γ-Fe2O3@Ph-PMO, 3.3 g Pluronic p123 (Mn = 5800 g/mol) was dissolved in a mixture of γ-Fe2O3 (2 g) and
concentrated HCl (0.55 mL) in distilled water (120 mL) under argon gas protection at room temperature. Then, 1,4-bis
(triethoxysilyl) benzene (2.3) mL and tetraethoxysilane (1.5 mL) were added simultaneously to the mixture dropwise and stirred for
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2 hours at 40 C. At the end of this process, the magnetic composite was kept at 100 C for 24 h under static conditions. The
resultant solid was filtered, and the template was removed by solvent extraction. For this purpose, the magnetic nanocomposite was
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dispersed in acetone and refluxed at 56 C for 10 h, then washed with distilled water and hot ethanol. This procedure was repeated
twice to be sure of removing of the surfactant.
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2.3.3 Preparation of γ-Fe2O3@ Ph-PMO-NaHSO4 nanocatalyst
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Based on the method of Golshekan et al [33], γ-Fe2O3@Ph-PMO-NaHSO4 was prepared by adding the synthesized mesoporous
γ-Fe2O3@Ph-PMO nanoparticles (1.5 g) to an aqueous solution of NaHSO4·H2O (20 mL, 0.7 g, 5 mmol) and the mixture was
sonicated at 25 °C for 1 min. In continue, the mixture was stirred for 30 min. Finally, water was removed by decanting and the
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powder was dried in an oven at 90 C for 2 h. A brown solid acid formulated as γ-Fe2O3@ph-PMO-NaHSO4 was obtained.
Schematic preparation of γ-Fe2O3@ph-PMO-NaHSO4 is shown in Fig. 1.
2.4. General procedure for the synthesis of triazoloquinazolinone/pyrimidine derivatives
20 mg of γ-Fe2O3@Ph-PMO-NaHSO4 was added to a round-bottom flask containing an aromatic aldehyde (1mmol), 3-amino-
1,2,4-triazole 2 (1.0 mmol), β-diketones (dimedone 3, 1,3-cyclohexadione 4 or ethyl acetoacetate 5) (1.0 mmol) and stirred under
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solvent-free conditions at 100 C in certain times. Meanwhile, the progress of the reaction was indicated by TLC (n-hexane: ethyl
acetate; 7:3). With completing the reaction, 3 ml ethanol was poured and the magnetic nanocomposite was separated in the presence
of a magnetic stirring bar; the reaction mixture became clear. The crude product was recrystallized from ethanol to give the pure
product. The pure products were characterized by conventional spectroscopic methods. Physical and spectral data for the selected
compounds are represented below.
9-(4-Bromophenyl)-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (7c).
White powder; M.p.: 306-308 (oC); IR (KBr, ꢀ, cm-1) 3429 (N-H), 3129 (CH-arom), 2883 (CH-aliph), 1648 (C=O), 1578 (N-H),
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621 (C-Br); H NMR (400 MHz, DMSO-d6): δ (ppm) 1.89-2.01 (2H, m, CH2), 2.22-2.34 (2H, m, CH2), 2.61-2.71 (2H, m, CH2),
6.23 (1H, s, CH), 7.18 (2H, d, J = 8.4 Hz, CH-Ph), 7.49 (2H, d, J = 8.4 Hz, CH-Ph), 7.71 (1H, s, CH-triazole), 11.21 (1H, s, NH);
13C NMR (100 MHz, DMSO-d6): δ (ppm) 21.1, 26.8, 36.7, 44.4, 57.7, 106.6, 121.3, 129.7, 131.6, 141.3, 147.1, 150.6, 153.2, 193.8;
Anal. Calcd for C15H13BrN4O: C, 52.19; H, 3.80; Br, 23.15; N, 16.23; O, 4.63.
9-(2-Nitrophenyl)-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (7d).
White powder; M.p.: 300-304 (oC); IR (KBr, ꢀ, cm-1) 3444 (N-H), 3213 (CH-arom), 2910 (CH-aliph), 1643 (C=O), 1569 (NO2),
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1357 (NO2); H NMR (400 MHz, DMSO-d6): δ (ppm) 1.88-1.99 (2H, m, CH2), 2.17-2.27 (2H, m, CH2), 2.64-2.67 (2H, m, CH2),
6.98 (1H, s, CH), 7.30 (1H, d, J = 1.2 Hz, CH-Ph), 7.49 (1H, dt, J1 = 7.6 Hz, J2 = 0.8 Hz, CH-Ph), 7.61 (1H, dt, J1 = 7.6 Hz, J2 = 1.2
Hz, CH-Ph), 7.73 (1H, s, CH-triazole), 7.86 (1H, dd, J1 = 8 Hz, J2 = 1.2 Hz, CH-Ph), 11.32 (1H, s, NH); 13C NMR (100 MHz,
DMSO-d6): δ (ppm) 21.1, 26.8, 36.4, 53.4, 106.19, 124.4, 129.4, 129.8, 133.8, 135.3, 147.2, 149.0, 150.8, 153.7, 193.9; Anal. Calcd
for C15H13N5O3: C, 57.87; H, 4.21; N, 22.50; O, 15.42.
3. Results and discussion
3.1. Characterization of the catalyst
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3.1.1. FT-IR analysis
Fig. 2 shows the FT-IR spectra of the synthesized γ-Fe2O3@Ph-PMO (before and after removal of the template) and γ-
Fe2O3@Ph-PMO-NaHSO4 MNPs, respectively. Before removal of the template (Fig. 2a), the FT-IR spectra showed high-intensity
peaks for the CH2 stretching modes located at ∼2870 and 2970 cm−1 (symmetric and asymmetric), as well as for the CH2 bending
mode at ∼1473 cm−1 which are related to the surfactant tail. The absence of CH2 peaks in Fig. 2b, confirms the surfactant removal.
The sharp band at 1075 cm-1 from Si-O stretching confirms the formation of siloxane bonds. The band at 3435 cm-1 is from the Si-
OH groups. The bands at ∼570 and 430 cm−1 are related to the Fe-O vibrations. The sulfonic acid bonds can be observed at ∼1200–
1250, 1010–1100 and 650 cm−1, which are attributed to the O=S=O asymmetric and symmetric stretching vibrations and S-O
stretching vibration of SO3H groups, respectively. However, in the FT-IR spectra of the synthesized nanoparticles, such bands could
not be observed because they are probably overlapped by the bands of SiO2.
3.1.2. X-ray diffraction (XRD) analysis
Fig. 3 shows the powder X-ray diffraction (XRD) pattern of the synthesized γ-Fe2O3@Ph-PMO. The peak at 2 theta near 0.9 in
the low-angle XRD pattern (Fig. 3a), corresponding to (100) diffraction, characteristics of the formation of mesoporous material
with hexagonal mesostructure [34]. Fig. 3b shows the wide-angle XRD measurements between 2 and 80 degrees 2theta of γ-
Fe2O3@Ph-PMO. The patterns indicates peaks with 2 theta at 30.06°, 35.67°, 43.47°, 53.83°, 57.36° and 62.96° which is quite
identical to pure maghmetite and matched well with the XRD pattern of the standard γ-Fe2O3 from Joint Committee on Powder
Diffraction Standards (JCPDS No. 39-1346)[35]. The average nanoparticel diameter of γ-Fe2O3@Ph-PMO was calculated about 12
nm from the XRD results by Scherrer equation.
3.1.3 BET analysis
The results of N2 adsorption-desorption isotherms of γ-Fe2O3@Ph-PMO and γ-Fe2O3@Ph-PMO-NaHSO4 were shown in Fig. 4.
From N2 adsorption-desorption analysis of samples, a type IV BET isotherm for both samples was obtained, as shown in Fig. 4,
which is attributed to mesoporous structures [34]. The Brunauer-Emmet-Teller (BET) surface areas and total pore volume of γ-
Fe2O3@Ph-PMO were 357.83 m2.g-1 and 0.5154 cm3.g, respectively. The BET surface area and total pore volume of γ-Fe2O3@Ph-
PMO-NaHSO4 decreased which proves the adsorption of NaHSO4 on the surface and successful synthesis of the nanocatalyst. Table
1 summarizes the structural parameters obtained from N2 adsorption-desorption.
3.1.4 EDX analysis
The energy-dispersive Xray analysis (EDX) analysis (see part IV in the Supplimentary material) of the catalyst showed the
presence of Fe, Si, Na, S, O, and C elements in the expected nanocatalyst.
3.1.5 TEM analysis
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Fig. 5 shows TEM image of the synthesized γ-Fe2O3@Ph-PMO-NaHSO4. The TEM image revealed that all samples were
spherical-like particles. Based on the TEM images, analysis of the γ-Fe2O3@Ph-PMO-NaHSO4 surface morphology demonstrated
that the aggregation of the particles is uniform and the size of them is up to 15 nm.
3.1.6 H+ Content determination
The amount of exchangeable H+ for γ-Fe2O3@Ph-PMO and γ-Fe2O3@Ph-PMO-NaHSO4 was determined by neutralization
titration. For this purpose, 0.02 g γ-Fe2O3@Ph-PMO and γ-Fe2O3@Ph-PMO-NaHSO4 separately, were dispersed in 10 mL of NaCl
solution (0.1 M) and stirred for 30 minutes then the mixture was titrated with NaOH (0.02 M) in the presence of phenolphthalein as
indicator. The amounts of acidic protons were found to be 0.2 and 0.8mmol. g−1 respectively. This result confirms the synthesis of
γ-Fe2O3@Ph-PMO-NaHSO4 nanocatalyst and acting it as a solid acid catalyst.
3.2. Catalytic activity
The above mentioned structural analysis results directed us to accept that γ-Fe2O3@Ph-PMO-NaHSO4 can be used as an acidic
catalyst in organic transformations. In order to stabish this suggestion the promoting ability of this reagent was studied in the
preparation of [1,2,4]triazolo quinazolinone/pyrimidine derivatives. To stablish the best reaction conditions, the reaction of 4-
chlorobenzaldehyde (1.0 mmol), 3-amino-1,2,4-triazole (1.0 mmol), dimedone (1.0 mmol), was selected as a model. The effect of
the amounts of the catalyst, temperature, and solvent for the more efficient conditions by using γ-Fe2O3@Ph-PMO-NaHSO4 was
investigated and the obtained results were arranged in Table 2. Optimization of the model reaction was performed in different polar
(CH3CN, EtOH, H2O) and nonpolar (CH2Cl2) solvents and under solvent-free conditions. As shown in Table 2, solvent-free
conditions is more suitable for the synthesis of 9-(4-chlorophenyl)-6,6-dimethyl-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-
8(4H)-one. To determine the optimum amount of the catalyst, we performed the reaction using different amounts of the catalyst. It
is clarified that 0.02 g γ-Fe2O3@Ph-PMO-NaHSO4 can effectively catalyze the reaction and resulted the product in the highest yield.
Also, we investigated the efficiency of NaHSO4 and γ-Fe2O3@Ph-PMO separately for the model reaction. The compiled outcomes
in Table 2 represented that using these materials as catalysts led not to complete the reaction (Entry 13, Table 2) or obtained low
yield of the products (Entry12, Table 2). But by using γ-Fe2O3@Ph-PMO-NaHSO4, the result became noticeably better. After the
selection of the best conditions, as indicated in Scheme 1, a wide range of aromatic aldehydes were reacted with 3-amino-1,2,4-
triazole 2 (1.0 mmol), β-diketones (dimedone 3, 1,3-cyclohexadione 4 or ethyl acetoacetate 5) (1.0 mmol) in the presence of γ-
Fe2O3@Ph-PMO-NaHSO4 to generate the requested products and the results were summarized in Table 3. Some products were
characterized by IR and NMR spectroscopy data. Melting points are compared with reported values in the literature as shown in
Table 3.
It is important to note that the super paramagnetic property of the synthesized nanocatalyst made the separation and reuse of this
catalyst very easy. Fig. 6 shows the separation of this nanocatalyst from its aqueous dispersion within a few minutes by simple use
of an external magnet.
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To demonstrate the worthiness of the prepared catalyst, the results obtained from the synthesis of 9-(4-chlorophenyl)-6,6-
dimethyl-5,6,7,9-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (6b) (Entry 2, Table 3) using this method is compared with
the selected catalysts in Table 4. This comparison shows the effectiveness of the heterogeneous catalyst γ-Fe2O3@Ph-PMO-
NaHSO4 in increasing of the rate and yield of the reaction. The turnover frequency (TOF) was also calculated and the higher
amount of it displays the better performance of the prepared catalyst in comparison with others as shown in Table 4. On the other
hand, as we have mentioned previously the presented catalyst can be easily separated using an external magnetic field, and the
reaction proceeds under mild conditions.
A suggested mechanism for the studied reactions is shown in Scheme 2. According to this mechanism, the γ-Fe2O3@Ph-PMO-
NaHSO4 catalyst activates the carbonyl group of the aromatic aldehyde which then condenses with enol (b) to produce the
intermediate (c). In continue, the process can be divided into two routes. In route 1, Michael addition reaction of nitrogen number 2
in 3-amino-1, 2, 4-triazolo 2 to intermediate (d) makes intermediate (e). An intra-molecular cyclization in (e) happens and it loses
water to produce the desired enamine product 6. On the other hand, in route 2, intermediate (d) is attacked by NH2 group in 3-
amino-1, 2, 4-triazolo 2 and after losing water the process continues via intermediate (f) to produce the requested product.
3.3. Reusability of the catalyst
The recovery ability of γ-Fe2O3@Ph-PMO-NaHSO4 was measured in the synthesis of 9-(4-chlorophenyl)-6,6-dimethyl-5,6,7,9-
tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (6b), under optimized reaction conditions. After completion of the reaction
and separation of the catalyst from the reaction mixture, the catalyst was washed with ethanol, dried in air, and reused with the least
change in the reaction time and yield even after five cycles of the synthesis of the product (Fig. 7 ). The amount of acidic protons
for both fresh and the recovered catalyst after fifth run was measured by the neutralization titration. According to this, the amount
of acidic protons was changed from 0.8 mmol/g for fresh catalyst to 0.6 mmol/g for the recycled catalyst, whereas this factor was
0.2 mmol/g for γ-Fe2O3@Ph-PMO, showing that although washing with water/ethanol leached out a small amount of NaHSO4, due
to its high solubility, and the products were obtained in the least change in reaction times and yields
210
211
212
213
214
215
216
217
4. Conclusion
In conclusion, γ-Fe2O3@Ph-PMO-NaHSO4 as a new nanocatalyst was successfully synthesized and utilized as an efficient
catalyst for the preparation of [1,2,4]triazolo quinazolinone derivatives under mild conditions and compared with NaHSO4 and γ-
Fe2O3@Ph-PMO as catalysts. It turned out that γ-Fe2O3@Ph-PMO-NaHSO4 functioned better and conveniently. This catalyst is
thermally stable, green, recyclable, easy to prepare. In addition, it can be easily separated from the reaction mixture and recovered
up to five times without any significant influence on its activity or the reaction yield.
Acknowledgments
We are thankful to the Research Council of the University of Guilan for the partial support of this research.
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Fig. 1 Preparation of γ-Fe2O3@Ph-PMO-NaHSO4.
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1.4
1.3
1.2
1.1
1.0
0.9
0.8
(a)
C=C
Fe-O
C-H
OH
Si-O-Si
(b)
(c)
Fe-O
OH
O=S=O , Si-O-Si
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber [cm-1]
308
309
310
Fig. 2 The FT-IR spectra of γ-Fe2O3@Ph-PMO, before removal of the template (a), γ-Fe2O3@Ph-PMO, after removal of the
template (b) and γ-Fe2O3@Ph-PMO-NaHSO4 (c).
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313
Fig. 3 The XRD pattern of γ-Fe2O3@Ph-PMO after removal of the template in low angle (a) and wide angle (b).
13

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Fig. 4 N2 adsorption-desorption of γ-Fe2O3@Ph-PMO (a), and γ-Fe2O3@Ph-PMO-NaHSO4 (b).
14

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Fig. 5 The TEM images of γ-Fe2O3@Ph-PMO-NaHSO4.
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Fig. 6 Photographs of an aqueous suspension of γ-Fe2O3@Ph-PMO-NaHSO4 before (a) and after (b) magnetic capture.
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325
Fig. 7 Reusability of γ-Fe2O3@Ph-PMO-NaHSO4 in the synthesis of 9-(4-chlorophenyl)-6,6-dimethyl-5,6,7,9-tetrahydro-
[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-one (6b).
17

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328
Scheme 1 Synthesis of [1,2,4] triazolo quinazolinone/pyrimidine derivatives catalyzed by γ-Fe2O3@Ph-PMO-NaHSO4 under
solvent-free condition.
18

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329
330
331
Scheme 2 Plausible mechanism for the preparation of [1,2,4]-triazolo-quinazolinone derivatives in the presence of γ-
Fe2O3@Ph-PMO-NaHSO4.
19

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332
333
Table 1. Structural parameters of the synthesized γ-Fe2O3@Ph-PMO, and γ-Fe2O3@Ph-PMO-NaHSO4.
SBET (m2.g-1)
357.83
V(cm3.g)
0.5154
γ-Fe2O3@Ph-PMO
γ-Fe2O3@Ph-PMO-NaHSO4
163.5
0.3093
SBET: specific surface area; V: total pore volume at relative pressure 0.99
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334
335
Table 2. Optimization of the amount of the catalyst, temperature and solvent in the synthesis of [1,2,4]triazolo quinazolinone
derivative of 4-chlorobenzaldehyde.
Time
Entry
Amount of the catalyst (g)
Solvent
Temp. (oC)
Conversion ( Yield %)a
(min)
120
120
120
120
120
120
80
1
2
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.01
0.02
0.03
0.02b
0.02c
CH2Cl2
r.t.
Reflux
r.t.
Trace
Trace
CH2Cl2
3
CH3CN
Trace
4
CH3CN
Reflux
r.t.
Trace
5
H2O
Not completed
Not completed
100(75)
6
H2O
Reflux
Reflux
Reflux
100
7
C2H5OH
8
C2H5OH : H2O (1:1)
90
100(70)
9
---
---
---
---
---
25
100(92)
10
11
12
13
100
10
100(96)
100
20
100(90)
100
120
120
Trace
100
Not completed
336
337
338
a Isolated yields.
b the used catalyst in this procedure was γ-Fe2O3@Ph-PMO
c the used catalyst in this procedure was NaHSO4
21

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Table 3. Preparation of [1,2,4]triazolo quinazolinone/pyrimidine derivatives using γ-Fe2O3@Ph-PMO-NaHSO4 as the catalyst.
M.P. (oC)
Entry
Aldehyde
Product
Time (min)
Yield (%)a
[Ref.]
Found
Reported
1
C6H5CHO
6a
6b
6c
6d
25
93
248-250
250-252
[17]
2
3
4
4-ClC6H4CHO
4-BrC6H4CHO
4-NO2C6H4CHO
10
15
35
96
94
90
294-296
283-285
290-294
303-305
284-288
307-309
[20]
[20]
[17]
5
6
3-NO2C6H4CHO
2-NO2C6H4CHO
6e
6f
30
25
90
91
265-267
288-290
266-269
290-292
[19]
[36]
7
8
4-OHC6H4CHO
4-MeOC6H4CHO
6g
6h
35
40
90
90
>300
>300
[19]
[17]
224-225
222-224
9
3-MeOC6H4CHO
2-MeOC6H4CHO
6i
6j
35
20
93
93
>300
>300
[37]
[36]
10
242-244
240-243
11
12
4-MeC6H4CHO
2-MeC6H4CHO
6k
6l
30
16
90
92
260-264
293-295
264-269
295-299
[20]
[37]
22

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13
2-Naphthaldehyde
6m
30
96
285-287
287-290
[19]
14
15
C6H5CHO
7a
7b
30
25
90
89
296-299
293-295
296-299
294-296
[37]
[37]
4-ClC6H4CHO
16
17
4-BrC6H4CHO
7c
7d
30
40
90
89
>300
>300
306-308
300-304
[37]
[37]
2-NO2C6H4CHO
18
19
20
4-MeOC6H4CHO
3-NO2C6H4CHO
4-MeC6H4CHO
7e
7f
8a
35
35
40
90
89
90
>300
306-308
292-296
246-248
[37]
[37]
[21]
293-297
238-242
4-
21
22
8b
8c
30
24
87
85
257-260
232-236
263-264
220-223
[21]
[21]
NO2OC6H4CHO
4-MeOC6H4CHO
a Isolated yields
23

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1
Table 4. Catalytic activity and reaction conditions comparison of γ-Fe2O3@Ph-PMO-NaHSO4 with other reported catalysts.
Time
(min)
30
TOF (S-
Entry
1
Product
Catalyst
---
Amount
---
Condition
DMF/ Reflux.
Solvent free/ 110 oC
Yield (%)
[Ref.]
[17]
1 a
)
---
65
87
---
---
300
---
[38]
2
3
4
H6P2W18O62.H2O
Sulfamic acid
(0.01 mol)
(0.005 mol)
CH3CN/ Reflux
CH3CN/ 80 oC
H2O: CH3CN/
Reflux
30
35
97
95
0.001
0.09
[19]
[20]
5
Iodine
(0.1 mol)
10
96.1
0.006
[37]
p-Toluenesulfonic
acid
6
7
8
9
(0.15 mol)
(0.087 mol)
0.05 g
CH3CN/ 40-50 oC
Solvent free/ 60 oC
Solvent free / 100
oC
10
30
5
96
85
90
94
0.0062
0.009
6
[22]
[23]
[25]
[24]
Acetic acid
SBA-Pr-SO3H
Nano-SiO2
0.15 mol
CH3CN / r.t.
10
0.017
10
Nafion-H®
0.06 g
PEG-400 / 50 oC
35
94
0.746
[39]
γ-Fe2O3@Ph-PMO-
Solvent free / 100
oC
[This
work]
11
0.02 g
10
96
8
NaHSO4
2
3
a The amounts of catalysts in TOF were calculated in term of gram of catalysts for all mentioned catalysts in the Table.
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Highlights:
•
•
•
Preparation of Immobilized NaHSO4 on core/shell phenylene bridged Periodic
mesoporous organosilica magnetic nanoparticles.
Introduction of a simple method for the preparation of [1,2,4]triazolo
quinazolinone/pyrimidine derivatives.
Easy separation and reusability of the nanocatalyst.