Synthesis and characterization of alumina supported molybdosilicic acid (SiMo12/Al2O3): Efficient solid acid catalyst for the synthesis of pyranopyrazole derivatives

Abstract A series of highly reusable heterogeneous catalysts (10-40 wt.% SiMo12/Al2O3), consisting of molybdosilicic acid (SiMo12) impregnated on alumina (Al2O3) support was synthesized by the wetness impregnation method. The physicochemical properties of synthesized catalyst were studied using FT-IR, XRD, SEM, EDX, TEM, BET and TG-DTA analysis techniques. The study proves that the synthesized SiMo12 catalyst efficiently incorporated on the surface of Al2O3. The catalytic activity of prepared catalyst was investigated for the synthesis of pyranopyrazole(6-amino-4-phenyl-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5carbonitrile) via cyclocondensation reaction of aldehydes, malononitrile, hydrazine hydrate and ethyl-acetoacetate under solvent-free conditions. Among different catalysts, 30% SiMo12 supported on to Al2O3 showed the highest catalytic activity. High yield, shorter reaction time, operational simplicity, solvent-free conditions and reusability of the catalyst are the distinct features of this protocol. Graphical Abstract An economic, sustainable, and straightforward environmentally friendly synthesis of pyranopyrazole derivatives in presence of catalytic amount of SiMo12/Al2O3 under solvent-free condition. Excellent yields, and environmentally sustainability are the main advantages of the present method.


Introduction
[4] They are better alternatives to traditional acid catalysts due to their strong Bronsted acidity and high proton mobility and relatively better stability. [5,6]The catalytic activities of the Keggin type POM's can be accelerated by changing their central heteroatom, framework polyatoms which is represented by the general formula XM 12 O 40 , x-8 where X is the central atom (Si, P, B, Zr etc.), M = metal ion (Mo 6+ , W 6+ , V 5+ ) x = oxidation state. [7]Generally metal atom can be replaced by other metal ions e.g.V 5+ , Ni 2+ , Zn 2+ , Co 2+ etc. [8][9][10][11][12] Heteropoly acids are highly soluble in polar solvents and thermally stable in the solid state. [13]These properties render them potentially promising acids, redox and bi-functional catalysts in homogeneous as well as in heterogeneous systems. [14]However, the major disadvantages of HPAs, as catalyst lies in their low surface area(1-10 m 2 /g), low thermal stability, separation problem from reaction mixture and their recovery and reusability in reaction mixture. [2,15]For the effective access the catalyst needs to be supported on a suitable support material. [2,16,17]The properties of the support material have some direct inference on the presentation of HPA catalyst. [18]While Titanium and Zirconium based oxides are the excellent supports for HPA but these supports have very high costs associated with the origin, which affects the economical sources of bulk production chemicals. [19]On the other hand, Al 2 O 3 is the lower cost supports and leached at a higher rate when compared to the same HPA supported on ZrO 2 and SiO 2 . [20]Al 2 O 3 having higher porosity and surface area. [21]Al 2 O 3 is widely produced, easily accessible, and economically feasible. [22]ulticomponent reaction's [MCRs] plays a vital role in the rapid synthesis of complex molecules from simple starting materials. [23]Target compound can be synthesized by using MCR's with greater efficiency and atom economy by generating structural complexity in a single step. [24,25]The first MCR was described in 1850 by Strecker. [26,27]yranopyrazole is a heterocyclic organic compound in which the skeleton is a pyran ring substituted by pyrazole in the ortho position.They have been applied as fungicidal, [28] bactericidal, [29] vasodilatory, [30] and also act as anticancer. [31]They also used as a pharmaceutical ingredients and biodegradable agrochemicals. [32]Moreover, pyrano [2,3-c]pyrazoles can be act as potential insecticidal and molluscicidal agent. [33]onsiderable analysis have been expended to analyze new direct and simple approaches toward the construction of the pyranopyrazole skeleton.Different catalyst were used for the synthesis of pyranopyrazole like, beta cyclodextrin, [34] L-proline, [35] Fe 3 O 4 NPs, [36] tetra(n-butyl)ammonium bromide, [37] CeCl 3 , [38] Nh 4 H 2 Po 4 /Al 2 O 3 . [39]These catalyst are quite useful but most of them have limitations such as long reaction time, high cost, use of toxic organic solvents and of harsh reaction condition's. [40]Hence, it is important to introduce efficient catalysts for the synthesis of pyranopyrazoles.
In continuation of our interest for the synthesis of Keggin type heteropoly acids and their catalytic applications in organic transformations. [2,12]Herein, we wish to report a alumina supported molybdosilicic acid (SiMo 12 /Al 2 O 3 ) as an efficient, nontoxic environmentally friendly and reusable solid catalyst for the synthesis of pyranopyrazoles via cyclocondensation reaction of aldehyde(1), malononitrile(2), hydrazine hydrate(3) and ethyl-acetoacetate (4) at 60 °C under solvent-free conditions.The Keggin type H 4 SiMo 12 O 40. 14H 2 O catalyst was prepared and supported on Al 2 O 3 using wet impregnation method and its physicochemical properties were studied using the FT-IR, XRD, BET, SEM-TEM, EDS and TG-DTA analysis techniques.Al ions can occupy two sub lattices, tetrahedral sites and octahedral sites.The band close to 491 cm −1 is attributed to a stretching vibration of the AlO 6 atomic group, while the 714 cm −1 structure is a result of the AlO 4 atomic group stretching which is the reason why the Al-O bands are shorter. [41]After being supported on Al 2 O 3 , some of the characteristic bands of the SiMo 12 were observed at 997 (Si-O a in central tetrahedral), 845 (terminal M-O d ) and 556 cm −1 (M-O c -M).While increasing loading percentage of SiMo 12 on Al 2 O 3 , some characteristic bands of SiMo 12 were merged with Al 2 O 3 and some bands are shifted to higher frequencies.This result shows that SiMo 12 had been successfully supported on the Al 2 O 3 support via the formation of strong chemical interaction between the two components.

BET analysis
BET method was used to determine specific area, pore diameter and pore volume of the catalyst.The specific surface area of the SiMo 12 , Al 2 O 3 support and 30% SiMo 12 / Al 2 O 3 catalyst were 3.328, 200.882 and 113.479 m 2 g −1 , respectively (Table 1).The pore diameter of the SiMo 12 , Al 2 O 3 support, and SiMo 12 /Al 2 O 3 catalyst were 5.526,4.116and 3.307 A ο respectively.Also, pore volume of SiMo 12 , Al 2 O 3 and 30% SiMo 12 /Al 2 O 3 catalyst were 9.194, 4.134 and 1.876 cc/g −1 respectively were calculated using the BJH method. [20,22]he N 2 adsorption/desorption isotherm are the type of 4 in nature according to the IUPAC classification.The porosities of these catalyst were investigated by N 2 adsorption and desorption measurement.The bulk SiMo 12 exhibit a well expressed H4 hysteresis loop (Figure 2a), also parent Al 2 O 3 support and 30% SiMo 12 /Al 2 O 3 catalyst exhibit H3 hysteresis loop (Figure 2b,c) in the range of 0.4 − 1.0 P/P 0 at high relative pressure, which is typical for mesoporous materials.It is interesting to mention here that surface area and total pore volume of 30% SiMo 12 /Al 2 O 3 catalyst diminish with respect to the Al 2 O 3 support.The decrease in surface area and pore volume may be attributed to the blockage of pores by SiMo 12 .

SEM and TEM analysis
SEM and TEM analysis was used to investigate the surface morphology and texture of samples (Figure 4a-d).The SEM images of Al 2 O 3 support (Figure 4a), bulk SiMo 12 (Figure 4b) and 30% SiMo 12 /Al 2 O 3 are shown in fig ( Figure 4c).The Al 2 O 3 support structure (Figure 4a) is rough and it contains pores that shows high specific surface area in which SiMo 12 could be perfectly bound and notify irregular particles with a non-uniform morphology of spherical cluster. [22]As seen in Figure 4b, the irregularly shaped particles with rough, flaky edges were observed for bulk SiMo 12 sample.These images clearly shows that the surface morphology of supported catalyst is not approximately similar to that of pure Al

EDX analysis and mapping images
The chemical framework of the bulk SiMo 12 and 30% SiMo 12 /Al 2 O 3 was confirmed using EDS (Elemental-Dispersive X-ray spectroscopy) analysis (Figure 5a).6a).The elemental mapping of Figure 6b represents the composition of the elements Mo, Si, Al, and O in the desired 30% SiMo 12 /Al 2 O 3 catalyst.

TG-DT analysis
The thermal stability of SiMo 12 and 30% SiMo 12 /Al 2 O 3 were examined by TG-DT analysis.The TG and DTA curves of these SiMo 12 were obtained in a hydrated form.The TG curve exhibit a total weight loss of 12.89% below 380 °C indicating that 14 water molecules calculated were lost.Three types of water molecule can be distinguished in these hydrated solid as shown in Figure 7a.The first mass loss of 6.40% appears endothermic peak at 95 °C for 7 molecules of hydrated water.The second mass loss of 4.38% appears endothermic peak at 150 °C for 5.09 protonated water molecules and the third exothermic peak appeared at 380 °C due to mass loss of 2.11% of structural water molecules.The exothermic peak appeared at 380 °C were ascribed to the decomposition of the kegging unit of SiMo 12 to individual oxides, it indicating that this heteropoly acid will remain stable up to 380 °C. [44]Due to lower
To fulfill the better reaction conditions for the pyranopyrazole derivatives the effect of SiMo 12 /Al 2 O 3 loading, the amount of SiMo 12 /Al 2 O 3 the results in different temperature and comparison of different catalyst were observed in Tables.
The effect of catalyst concentration on the rate of model reaction was investigated by using various amounts of SiMo 12 /Al 2 O 3 catalysts and results are summarized in Table 2.
It can be seen from Table 2, bulk SiMo 12 showed a moderate yield of product but after increased reaction time (Table 2, entry 1).It was observed that, yield of product enhanced by increasing the loading of catalyst from 10% to 30% w/w (Table 2, entries 2,3,4) over a short reaction time.Further increase in the loading of catalyst above 30% w/w on Al 2 O 3 support showed no any effect on the reaction time and product yield (Table 2, entry 5).An increase in activity of the 30% SiMo 12 /Al 2 O 3 catalyst was due to increase in its surface area and the active sites as compared to the bulk SiMo 12 catalyst.Hence, 30% SiMo 12 /Al 2 O 3 catalyst was observed to be sufficient and maximum amount to push the reaction in forward direction.
Then we carried out the model reaction using different amounts (25, 50,70,100 and 125 mg) of 30%SiMo 12 /Al 2 O 3 catalyst for optimizing the amount of catalyst in the synthesis of pyranopyrazole derivatives at 80 °C and obtained results are summarized in Table 3.In the absence of catalyst, product 4a was presents in trace amount (Table 3. entry 1) after 4 hrs.After increasing the catalyst amount up to 100 mg a remarkable variation was observed in terms of yield of products and reaction time (Table 3, entries 2-4).There is no notable improvement in the yield of product and time of reaction upon increasing the amount of 30% SiMo 12 /Al 2 O 3 catalyst above 100 mg (Table 3. Entry 9).This might be due to excess of catalyst does not improve the rate of chemical reaction.Hence, we used 100 mg of 30%SiMo 12 /Al 2 O 3 catalyst for optimizing the other parameters of the model reaction.Next, to study the effect of temperature on model reaction, we performed the reaction at different temperatures (60 °C to 80 °C) Consequently, the best results were obtained at 80 °C temperature in the presence of 100 mg of 30% SiMo 12 /Al 2 O 3 (Table 3. entry 5).It was also observed that, there is no considerable change in terms of yield of product and time of reaction after increasing the reaction temperature above 80 °C (Table 3. entry 10).Using different catalyst, reaction required reaction time is longer and also amount of catalyst is higher as compared to 30% SiMo 12 /Al 2 O 3 in solvent free conditions in maximum reaction systems.Hence, 30% SiMo 12 /Al 2 O 3 inspired the reactions superior and most effectively than other catalysts and become investigated as one of the excellent valuables for choosing an economically acceptable and friendly catalyst.
Considering the above optimized reaction conditions, we carried out a series of reactions of ethyl acetoacetate, hydrazine hydrate and malononitrile with various aromatic aldehydes Scheme 2. Plausible reaction mechanism for the synthesis of pyranopyrazole derivatives.in presence of 30% SiMo 12 /Al 2 O 3 catalyst and obtained results are summarized in Table 4. Several aromatic aldehydes carrying either electron-releasing or electron-withdrawing groups reacted successfully and desired products were obtained in good to excellent yields (Table 4).

Recycling of catalyst
Recycling of the catalyst is one of the principal characteristics in the current method.It was noticed, 30% SiMo 12 /Al 2 O 3 catalyst could be reused many times therefore the identical model reaction performed once more studied under the condition of optimization.After completion of the reaction, reaction mixture was diluted with hot ethanol and then filtered for separation of catalyst, the solid catalyst washed using ethanol more times, then dried and calcined at 250 °Cfor 5 h and utilized for resultant reaction.The results of recyclability study (Figure 8) shows that the catalyst could be reused at least six successive cycles with only a slight reduction in its catalytic activity.

Plausible reaction mechanism
A plausible mechanism for the synthesis of pyranopyrazole is given in Scheme 2. As illustrated in the first step, 30% SiMo 12 /Al 2 O 3 catalyst act as a Lewis acid which activates both the aromatic aldehydes and ethyl acetoacetate.In next step, the lone pairs of nitrogen in hydrazine hydrate attacked to the carbonyl group of the activated ethyl acetoacetate.Furthermore, through intramolecular nucleophilic bonding of another amine group of hydrazine to the next carbonyl group of ethyl acetoacetate, 5 methyl-2,4-dihydropyrazole-3-one was formed.Further, by the addition of malononitrile with the activated arylaldehyde, a cyano-olefin compound was formed.At the last step, Michael addition-cyclization reaction of 5 methyl-2,4-dihydropyrazol-3-one with cyano-olefin compound was carried out, to afford the desired corresponding pyranopyrazole. [52,53]

Materials and general characterization
Sodium metasilicate (Na 2 SiO 3 .9H 2 O), sodium molybdate (Na 2 MoO 4 .2H 2 O), and Al 2 O 3 (Alumina) were purchased from MOLYCHEM in India and used without further purification.Other chemicals and solvents required for the organic synthesis were purchased from Sigma Aldrich, Alfa Aesar and Merck.The Fourier-transform infrared (FT-IR) spectrum was recorded on a Bruker ALPHA (ECO-ATR) spectrophotometer.XRD diffraction patterns were obtained on Bruker AXS company, D8 ADVANCE diffractometer (Germany).SEM (Scanning electron microscopy) images were obtained by using a FEI Nova Nano SEM 450 combined with a Bruker x Flash 6130 instrument.Energy dispersive X-ray spectroscopy (EDX) was performed with a scanning electron electrode at 15 kV.TEM (Transmission electron microscopy) images were obtained using a (HR-TEM: Jeol/JEM 2100) working on voltage of 200 kV.Nitrogen adsorption-desorption isotherm was measured on a NOVA station A instrument at 77 K. Brunauer-Emmett-Teller (BET) method was used to calculate the surface area.Pore size distribution derived from adsorption branches of the isotherms using the distribution Barrett-Joyner-Halenda (BJH) method.The thermogravimetric (TG) and differential thermal analysis (DTA) measurements were obtained using a SHIMADZU, DTG-60 H simultaneous DTA-TG apparatus.The progress of reaction was monitored by thin layer chromatography (TLC) using Merck's silica plates and imagining consummate by iodine/ultraviolet light.Melting points of all the integrated analogous were resolute in open capillary tube. 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance 400 spectrometer in CDCl 3 and DMSO.Chemical shifts are indicated in δ parts per million relatives to tetramethyl silane (TMS) as the internal standard.

Preparation of H 4 SiMo 12 O 40 H 2 O 14 catalyst
Keggin type of HPA having general formula H 4 SiMo 12 O 40 , was prepared using the procedure reported by Huixiong. [13,54]Desired amount of sodium metasilicate (Na 2 SiO 3 .9H 2 O) and sodium molybdate (Na 2 MoO 4 .2H 2 O) were dissolved in distilled water separately.The obtained solution was mixed well and stirred at 90 °C.Then, maintain pH 1.5 to 2.0 by adding sulfuric acid solution dropwise.The resulting mixture was heated at 90 °C.for 6 hours.Finally, the cooled solution was extracted with diethyl ether.O catalyst were prepared according to the procedure reported in literature with small modifications. [12]n a typical synthesis of 10% SiMo 12 /Al 2 O 3 , 1.0 g of SiMo 12 was dissolved in dry methanol solution and added dropwise into the flask containing 9 g of Al 2 O 3 and stirred for 3 hr at room temperature.The resulting mixture was heated to 80 °C until complete evaporation of the liquid.The solid residue was then calcined in an oven at 200 K for 5 hr.A series SiMo 12 O 40 /Al 2 O 3 (10,20,30,40 wt.%) were prepared using the same method.

General procedure for the synthesis of pyranopyrazoles
In a typical experiment, a mixture of aromatic aldehydes (1.0 mmol), ethyl-acetoacetate (1.0 mmol), hydrazine hydrate (1.0 mmol), malononitrile (1.0 mmol) were added and stirred at 80 °C by using SiMo 12 /Al 2 O 3 (0.2 g) catalyst under solvent-free condition.After the completion of reaction (Monitored by TLC) the reaction mixture was diluted using hot ethanol (10.0 mL) and filtered for catalyst separation.The product was obtained by solvent evaporation under reduced pressure and recrystallized from ethanol.The recovered catalyst was washed with ethanol and dried overnight at room temperature for further reuse.The physical data (melting point, IR, 1 H and 13 C NMR) of some representative compounds were found to be identical with those reported in the various literature.

Conclusion
In conclusion, we have successfully synthesized a series of alumina supported molybdosilicic acid (SiMo 12 /Al 2 O 3 ) catalysts by wetness impregnation method.The characterization of catalyst was performed by FT-IR, XRD, SEM, TEM, EDX, BET and TG-DTA analysis techniques.FT-IR analysis results confirms Keggin structure of molybdosilicic acid and incorporation of molybdosilicic acid on alumina support.The results of XRD, BET, and SEM-TEM characterization showed that SiMo 12 was finely dispersed on the Al 2 O 3 support.The TG-DTA results indicates that, thermal stability of SiMo 12 increased after supporting it on Al 2 O 3 support.Elemental composition of synthesized catalyst was identified using EDS analysis.The catalytic activity of SiMo 12 /Al 2 O 3 was probed through one-pot synthesis of pyranopyrazoles via cyclocondensation reaction of aldehydes, malononitrile, hydrazine hydrate and ethyl-acetoacetate under solvent-free conditions.The 30% SiMo 12 /Al 2 O 3 showed higher catalytic activity in short reaction time than the bulk SiMo 12 catalyst, as well as the 10% and 40% SiMo 12 /Al 2 O 3 .The effects of various reaction parameters such as catalyst loading, amount of catalyst, influence of temperature on the rate of reaction were investigated.This catalyst recovered easily from reaction mixture and reused at least six times without significant loss of its catalytic activity.Therefore, the newly synthesized 30% SiMo 12 /Al 2 O 3 could be used as a promising heterogeneous catalyst for a wide range of multifunctional applications.
Functionalization of the bulk SiMo 12 /Al 2 O 3 and supported SiMo 12 /Al 2 O 3 was successfully confirmed by Fourier transform infrared spectroscopy (FT-IR).The data obtained from FT-IR is displayed in Figure 1.Bulk SiMo 12 , catalyst spectrum shows four characteristic bands in the range of 1000-480 cm −1 .For bulk SiMo 12 , stretching frequency exhibiting at 965 (Si-O a in central tetrahedral), 895 (terminal M = O d ), 741 (M-O b -M), and 484 cm-1 (M-O c -M) are accorded with asymmetric vibrations in Keggin unit.In Al 2 O 3,
12 /Al 2 O 3 (Figure 3c-f) catalyst shows characteristic properties of both Al 2 O 3 and SiMo 12 i.e., an amorphous like Al 2 O 3 and the crystalline phase of SiMo 12 .In Figure 3 it can be clearly observed that, the peaks of bulk SiMo 12 shows crystalline phases at 12 ο ,17 ο ,26 ο ,28 ο and 35 ο which confirms its Keggin structure.Likewise, whole conclusion vigorously contributes that, SiMo 12 was excellently dispersed on the Al 2 O 3 support in the SiMo 12 / Al 2 O 3 catalyst.The similar diffraction patterns were observed by increasing the percentage of SiMo 12 catalyst from 20,30 and 40% on Al 2 O 3 support.
2 O 3 .There is change in surface morphology of the catalyst reveal that SiMo 12 species are well dispersed inside the hexagonal pores.SiMo 12 and Al 2 O 3 were successfully merged were found in 30% SiMo 12 /Al 2 O 3 .The TEM images of 30% SiMo 12 /Al 2 O 3 (Figure 4d) shows that hexagonal pores mostly covered by dark colored fine particles.This indicates uniform dispersion of SiMo 12 inside the hexagonal pores of Al 2 O 3 support.

Table 1 .
textural properties of various samples.
Sr. noSample Surface area (m 2 g -1 ) Pore size (a ο ) Pore volume (cc/g -1 ) The EDS results confirms that Si, Mo and O are present in the SiMo 12 catalyst.Whereas, EDS results of 30% SiMo 12 /Al 2 O 3 proves presence of Si, Mo, Al and O in catalyst.Additionally, EDS mapping images persistent a uniform distribution of Mo, Si and O in the prepared catalyst SiMo 12 (Figure

Table 2 .
effect of h 4 Simo 12 o 40 loadings on al 2 o 3 support for the synthesis of pyranopyrazole.
bProgress of the reaction monitored by tLc.c isolated yields.

Table 3 .
optimization of amount of catalyst and reaction temperature for the synthesis of pyranopyrazole.
b progress of reaction monitored by tLc.c isolated yields.

Table 4 .
Synthesis of pyranopyrazole using benzaldehyde, ethyl acetoacetate, hydrazine hydrate and malononitrile with different catalysts a .

Preparation of SiMo 12 O 40 /Al 2 O 3 . The
The powder of H 4 SiMo 12 O 40 .14H 2 O was obtained by evaporating etherate solution was dried in vacuum.Al 2 O 3 supported H 4 SiMo 12 O 40 .14H 2