Synthesis of Nano Magnetite Fe 3 O 4 Based Vanadic Acid : A Highly Efficient and Recyclable Novel Nano-catalyst for the Synthesis of 4 , 4 ’-( arylmethylene )-bis ( 3-methyl-1-phenyl-1 H-pyrazol-5-ols )

Nano magnetic Fe3O4 based vanadic acid [MNPs@VO(OH)2] (average diameter 20–26 nm) has been synthesized by grafting VOCl3 on the Fe3O4 surface nanoparticles as a retrievable supporter to produce novel heterogeneous reusable solid acid with dual ability (Bronsted and Lewis acid) followed by stirring in the air. The resultant material was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and energy-dispersive X-ray spectroscopy (EDX). Significantly, the as-prepared [MNPs@VO(OH)2] exhibits a high catalytic activity in the synthesis of 4,4’(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols). Additionally, the newly synthesized heterogeneous solid acid catalyst can be reused for several times without apparent loss of its catalytic activity.

However, some of these methods suffer from at least one of the following disadvantages: using the expensive catalyst at reflux condition, long reaction time, low yield, non-recovered catalyst, tedious work-up procedure and the using of large amount of catalyst.Thus, there is still a need to develop a new and convenient method for the synthesis of 4,4′-(arylmethylene)bis(1Hpyrazol-5-ols).
Therefore, finding an efficient and capable protocol for the preparation of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) is N very important.Thus, design of novel nano magnetically separable catalytic systems have attracted attention in recent times as an interesting alternative to improve the efficient separation of heterogeneous (nano) catalysts from solutions over reaction completion by applying a simple magnet, providing improved recyclability in the designed systems. [16]n addition, surface modification impacts the activity and selectivity of magnetite nano-catalysts. [17]cid catalyzed reactions have been also widely used in the modern chemical industry.It has been showed that catalytic systems that contain both Lewis and Bronsted acidity are more beneficial than Lewis or Bronsted acidic catalysts alone. [18]mong the various transition metals as a Lewis acid, vanadium exists on the surface of the earth more plentifully and vanadium based oxidants are effectively used for various organic reactions. [19]anadium and vanadium peroxides generate a number of biological and biochemical responses and have a potential as insulin-mimetic agents in the treatment of human diabetes.Moreover, vanadium is an essential prosthetic group of some haloperoxidase enzymes. [20]herefore, immobilization of the functionalized acid via covalent attachment to the supporting materials can combine the acid characteristics with the advantages of magnetic nanoparticles to design the acidic catalyst that facilitate catalyst recovery, recycling and reducing effluent contamination.

Chemicals and Apparatus
The materials were purchased from Merck and Fluka and were used without any additional purification.All reactions were monitored by thin layer chromatography (TLC) on gel F254 plates.The synthesized catalyst was characterized by FT-IR, XRD, SEM, TEM, and elemental analysis.
XRD patterns of all catalysts were performed on a APD 2000, Ital structure with Cu Kα radiation (k = 0.1542 nm) operating at 50 kV and 20 mA in a 2 h range of 10-70° with step size 0.01° and time step 1.0 s to assess the crystallinity of the catalyst.
The weight loss between 200 and 600 °C was determined.Semi-quantitative EDX (Röntec, Quantax/QX2) analysis was used for the characterization of element concentration and vanadium distribution within prepared catalysts.The SEM analyses were done with a TESCAN/MIRA with a maximum acceleration voltage of the primary electrons between 10 and 15 kV.Transmission electron microscope, TEM measurements were carried out on a Philips CM10 analyzer.

Typical Procedure for Synthesis of Nano Magnetic Fe3O4 Based Vanadic Acid
MNPs Fe3O4 particles (I) were prepared according to a previous report by Qu et al. [21] MNPs Fe3O4 (1g) suspended in n-Hexane (15 ml) with sonication for 5 minutes.Then, vanadiumoxytrichloride (1 g) was dissolved in n-hexane (10 mL).The mixture was added drop wise to MNPs Fe3O4 suspension (15-20 min) and shaked for 30 minutes.The result material were separated by an external magnet, washed three times with ethanol, dried under vacuum, and shaked in the air for 48 h to promote the hydrolysis of V-Cl bonds to yield the final catalyst.

General Procedure for Synthesis of Bis(pyrazolyl)methanes
To a solution of an aldehyde (1 mmol), 3-methyl-l-phenyl-5-pyrazolone (2 mmol), and 4-5 drop ethanol was added MNPs@VO(OH)2 (20 mg).The resulting mixture was magnetically stirred at 40 °C.The progress of the reaction was monitored by TLC.After the completion of the reaction, the catalyst was separated from the product by an external magnet and washed with ethanol (20 mL) and reused for subsequent runs.The mixture was concentrated to give the crude product.Finally, the products were purified by column chromatography on silica gel (nhexane/EtOAc) or by recrystallization from ethanol.

RESULTS AND DISCUSSION
In continuation of our previously reported methodologies for designing, synthesis and applications of tasked specific heterogeneous catalysts such as silica based sulfuric, [22] phosphoric, [23] vanadic acid, [24] and magnetic nano particles [25] herein, we wish to report the synthesis and application of novel nano magnetite vanadic acid [MNPs@VO(OH)2] was synthesized by the reaction of Fe3O4 particles with VOCl3 followed by stirred in the air (Scheme 1) and its structure was identified by IR, SEM, XRD and EDX.
In order to confirm the modification of the magnetite surface, the FT-IR spectrum of the prepared materials were obtained and have been shown in Figure 1.
Figure 1.shows the FT-IR spectra of the MNPs (a) and MNPs@VO(OH)2 (b).The Fe−O stretching vibra on near 592 cm −1 and the O-H stretching vibration at 3429 cm −1 were observed for the Fe3O4 (Figure 1a).The introduction of VO(OH)2 to the surface of MNPs is confirmed by the bands at 786.In Figure 2b, we can observe that the XRD pattern of the [MNPs@VO(OH)2] is similar to the pattern of Fe3O4 nanoparticles because the structure of [MNPs@VO(OH)2] can be remained after the surface modification with VO(OH)2 and new peaks attributable to these groups could not be detected in the XRD.However, the crystallinity of the samples clearly decreases after the coating process and the catalyst was going to amorphous structure.These results provide further evidence that functionalization on the nano magnetite take place. [26]he EDX elemental analysis is shown in Figure 3. From the spectrum, it can be seen that iron, oxygen and vanadium elements present in the [MNPs@VO(OH)2] samples which is in good agreement with the proposed catalyst structure (Figure 3).
TEM and SEM images of the synthesized catalyst   were recorded and showed in Figure 4.The average diameter of the catalyst is around 25 nm with an approximate spherical shape.The activity of the catalyst was subsequently investigated upon characterization in the synthesis of bis(pyrazolyl)methanes (Scheme 2).
To optimize the reaction conditions, the solvent-free condensation of 3-methyl-1-phenyl-5-pyrazolone (1) (2 mmol) with benzaldehyde (1 mmol), as model reaction using different amounts of catalyst at range of 25-60°C was examined (Table 1).The best results were obtained using 0.02 g of [MNPs@ VO(OH)2] at 40°C.After optimization of the reaction conditions, to explore the efficiency and the scope of the presented protocol, 3-methyl-1-phenyl-5pyrazolone was treated with structurally diverse aromatic aldehydes under the optimized reaction conditions in the presence of [MNPs@VO(OH)2] as catalyst.The corresponding results are depicted in Table 2.
We believe that the [MNPs@VO(OH)2] activates the aldehyde group for nucleophilic attack by 3-methyl-1phenyl-1H-pyrazol-5-ol (IV) 2 to form (V) which undergoes Michael addition with second molecule of 3-methyl-1phenyl-1H-pyrazol-5-ol to form the product (VI) (Scheme 3). [30]he major advantages of the present protocol over existing methods can be seen by comparing our results with the most popular recently reported procedures, as shown in Table 3.The reaction of benzaldehyde with 3-methyl-5-pyrazolones for the preparation 4,4'-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) (entry 1, Table 3) was chosen as a model reaction and the comparison is in terms of reaction time, reaction conditions and percentage yields.Shorter reaction time and milder reaction condition was obtained using SVA instead of Bronsted acid catalyst.

CONCLUSION
In conclusion, we have described the development of a mild efficient and simple method for the one-pot threecomponent condensation reaction of aromatic aldehydes with 1-phenyl-3-methylpyrazol-5-one in ethanol for the synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives, catalyzed by [MNPs@VO(OH)2] as a new and heterogeneous organic catalyst at 40°C.The catalyst is characterized by FT-IR, XRD, TEM, SEM and EDX.The procedure has several advantages such as high reaction rates, ease of preparation and handling of the catalyst, simple experimental procedure and use of a reusable catalyst.

Table 3 .
Comparison of the efficiencies of a number of different reported catalysts with SVA in the condensation of benzaldehyde with 2 equivalents of 3-methyl-l-phenyl-5-pyrazolone