L-Proline functionalized magnetic nanoparticles: A novel magnetically reusable nanocatalyst for one-pot synthesis of 2,4,6-triarylpyridines

In this work, an efficient method for the immobilization of L-proline on magnetic nanoparticles was offered and evaluated as a recoverable magnetic nanocatalyst for synthesis of 2,4,6-triarylpyridines through one-pot three-component reaction of acetophenone, aryl aldehydes and ammonium acetate. This article is the first report of the catalytic application of L-proline functionalized magnetic nanoparticles in organic reactions as a magnetic nanocatalyst. This novel magnetic nanocatalyst proved to be effective and provided the products in high to excellent yield under solvent-free conditions. The structure of obtained nanoparticles was characterized by Fourier transform infrared spectrophotometry (FT-IR), field-emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA) and energy-dispersive X-ray spectroscopy (EDX). TGA result revealed that it is stable up to 200 °C for using as a catalyst in organic reactions. FE-SEM image of the synthesized nanocatalyst showed that it has nearly core-shell spherical shape and uniform size distribution with an average size about 80 nm. Moreover, the catalyst could be easily recovered by facile separation by magnetic forces and recycled for several times without significant loss of its catalytic activity. The benefits of this study are simplicity, nontoxicity, low cost, simple workup, and an environmentally benign nature.

between acetophenones, benzaldehydes, and ammonium acetate in the presence of various catalyst such as nanoparticles 57 , heteropolyacid 58 , HClO 4 -SiO 2 59 , and ionic liquid 60 . However, most of these methods suffer from drawbacks such as long reaction time, harsh reaction conditions, the use of volatile organic solvents, low yields, high catalyst loading, thermal conditions and expensive or difficult procedures of catalyst preparation. Therefore, design and development of mild and efficient methods with more environmentally-friendly catalysts is in of prime importance.

Results and Discussion
In this work, we have synthesized a novel nanomagnetic organocatalyst Fe 3 O 4 \SiO 2 \propyltriethoxysi-lane\L-proline (LPSF) and applied for the synthesis of 2,4,6-triarylpyridines. As can be seen in Fig. 2, LPSF nanocatalyst was prepared after several steps. At first, L-proline N-hydroxysuccinimide ester was prepared from L-proline and N-hydroxy succinimide (NHS) in the presence of N,N'-dicyclohexylcarbodiimide (DCC). After that, the synthesized Fe 3 O 4 \SiO 2 was treated by (3-aminopropyl)triethoxysilane (APTES) to synthesize Fe 3 O 4 \SiO 2 \ 3-aminopropyltriethoxysilane. Finally, the synthesize Fe 3 O 4 \SiO 2 \3-aminopropyltriethoxysilane was treated by NHS-L-proline to synthesize the aimed LPSF magnetic nanocatalyst. Then, the characterizations of the prepared nanocomposite were investigated by several analyses methods which will be discussed further.

Characterization of the prepared Fe 3 O 4 \SiO 2 \propyltriethoxysilane\L-proline (LPSF). FT-IR
spectra. As can be seen in Fig. 3, the FT-IR spectrum of the LPSF magnetic nanocatalyst can verify the preparation of the expected product. The bending vibration band at 585 cm −1 is indicated Fe-O vibration. In addition, the sharp bands appearing at 1084 and 1120 cm −1 are attributed to Si-O-Si asymmetric stretching vibration confirmatory to the SiO 2 formation. The asymmetric and symmetric aromatic C-H stretching vibrations are appeared at 2920 and 2852 cm −1 . Furthermore, the asymmetric stretching vibrations of O-H and N-H groups observed at 3401 cm −1 . Furthermore, we have characterized the recycled LPSF magnetic nanocatalyst. As shown in Fig. S1, there was no considerable deformation or leaching after seven times reusing.
FE-SEM images. Field-emission scanning electron microscopy (FE-SEM) images are used to investigate the surface structure of the nanocomposite. As it is seen in Fig. 4a, FE-SEM images show that the LPSF nanocatalyst has nearly spherical shape and uniform size distribution with an average size of 80 ± 40 nm.   Thermal analysis. As can be seen in Fig. 5, the thermal behaviour of the prepared nanocomposite was evaluated by thermogravimetric analysis (TGA) over the temperature range of 20-800 °C at air atmosphere. The first weight loss between 0-100 °C was due to evaporation of adsorbed water in the sample. After that, the weight loss from 200 to 600 is related to the destruction of the organic compounds.    conditions, we evaluated the reaction of acetophenone, 4-chloro-benzaldehyde and ammonium acetate in the presence of different catalytic amounts of LPSF magnetic nanocatalyst at 60 °C under solvent-free conditions, as a model reaction to yield 4b. It was observed that 0.01 g of catalyst was enough to catalyze the reaction to produce high yields of products (Table S1 in Supplementary Information file). To study of the solvent effect and comparing the efficiency of ethanol, the model reaction was performed in several solvents with different polarities in the presence of LPSF magnetic nanocatalyst. As can be seen in Table S1 (Entries 6-9), the efficiency and the yield of the model reaction under solvent-free conditions were higher than those obtained in other solvents. In addition, a comparison was done between the present work and others earlier reports for the synthesis of 4b. The results summarized in Table S2 in Supplementary Information file clearly demonstrate the superiority of the present work in saving energy, high yields of the products and the reusability of the nanocatalyst.

Catalytic application of
Finally, in order to examine the generality of this nanocatalyst for the synthesis of 2,4,6-triarylpyridine derivatives, a number of aromatic aldehydes and acetophenones with electron-withdrawing and electron-releasing substitutions, were employed and a variety of products were synthesized under the optimized conditions the results are summarized in Table 1.
Mechanistic evaluation. The plausible mechanism for the formation of 2,4,6-triarylpyridines is shown in Fig. 6

Recyclability of LPSF magnetic nanocatalyst.
In order to investigate the possibility of several recycling runs for LPSF magnetic nanocatalyst, the solid catalyst was separated from the reaction mixture by using an external magnet. It was washed two times with ethanol and water, dried and reused in subsequent reactions. The catalyst can be reused seven times without any significant decrease in yield of the products (Fig. S1). Finally, as can be seen in Figs S2 and S3, we have characterized the recycled nanocatalyst by FT-IR spectroscopy and FE-SEM image which showed suitable retention of its structure and morphology.

Experimental
General. All the solvents, chemicals and reagents were purchased from Merck, Sigma and Aldrich. Melting points were measured on an Electro thermal 9100 apparatus and are uncorrected. Fourier transforms infrared spectroscopy (FT-IR) spectra were recorded on a Shimadzu IR-470 spectrometer by the method of KBr pellet. 1 H and 13 C NMR spectra were recorded on a Bruker DRX-300 Avance spectrometer at 500 and 125 MHz, respectively. Field-emission scanning electron micrograph (FE-SEM) images were taken with Sigma-Zeiss microscope with attached camera. Elemental analysis of the nanocatalyst was carried out by energy-dispersive X-ray (EDX) analysis recorded Numerix DXP-X10P. Thermal analysis was taken by Bahr-STA 504 instrument under argon atmosphere. General procedure for preparing 2,4,6-triarylpyridines. A mixture of acetophenones (2 mmol), aromatic aldehyde (1.0 mmol), ammonium acetate (1.5 mmol) and 0.01 g LPSF nanocatalyst was stirred at 60 °C under solvent-free conditions for an appropriate time. The completion of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, hot ethanol was added to the mixture added to the mixture and the catalyst was separated easily by an external magnet. The pure products were obtained from the reaction mixture by recrystallization from hot EtOH and no more purification was required. All the product were known compounds which were identified by characterization of their melting point with those authentic literature samples and also in some cases their 1 H and 13 C NMR spectral data.

Conclusions
In summary, LPSF magnetic nanocatalyst was prepared and used as a novel, green, magnetically recyclable, environmentally-friendly and efficient composite nanocatalyst for the synthesis of chemically and biologically important 2,4,6-triarylpyridines by a simple, clean, eco-friendly and inexpensive method. The novel magnetic nanocatalyst can be easily separated by an external magnet and recycled for several times without any significant loss of activity. We used FT-IR, EDX, TGA and FE-SEM to confirm that the nanocomposite was formed, and 1 H and 13 C NMR analyses were performed for the confirmation of the synthesized products. TGA result revealed that it is stable up to 200 °C for using as a catalyst in organic reactions. FE-SEM image of the synthesized nanocatalyst showed that it has nearly core-shell spherical shape and uniform size distribution with an average size about 80 nm. This study is the first report on design, synthesis, functionalization and characterization of the novel magnetic nanocomposite and also performance as a heterogeneous catalyst in organic reactions.