SPION-A-Pd(EDTA) (superparamagnetic iron oxide nanoparticles-A-ethylendiamine tetraacetic acid) as a robust nanocatalyst for Buchwald-Hartwig C-N Coupling Reaction

Document Type: Research Paper

Authors

1 Department of Chemistry, University of Isfahan, Isfahan, Iran

2 Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan

Abstract

During thelast20-30 years, palladium-catalyzed reactions have witnessed tremendous advances in the industrial and organic reactions such as hydrogenation, coupling, cyanation and amination. Despite the wide utility of Pd-catalysts in these reactions, they suffer from a number of drawbacks such as recovery, reuse of catalyst and remain as  a contaminant in the products at the end of the reaction.
A powerful and convenient reaction procedure for the C-N coupling reaction (the Buchwld-Hartwig reaction), yielding products of N-arylanilines and N-arylamines in conventional heating has been reported. The protocol utilized an high stable Pd(EDTA)2- salt by counter cation of N-methylimidazolium bounded to 1,3,5-triazine-tethered SPIONs (superparamagnetic iron oxide nanoparticles). The reaction products were produced under conventional heating at extremely low catalyst loading (as low as 0.003 mol% Pd).Finally, we also examined the reusability of the catalyst.  It was found that the catalyst could be recovered by external magnetic field and be reused for five times without obvious loss in catalytic activity.

Keywords


INTRODUCTION

Palladium-catalyzed reactions have emerged as powerful and selective tools for synthetic organic chemistry [1-3] such as carbonylation [4-8], cyanation [9,10], hydrogenation [11-13], coupling reactions [14-16], and amination [17].

Despite the wide utility of Pd-catalysts in these reactions, they suffer from a number of drawbacks such as recovery, reuse of catalyst and remain as  a contaminant in the products at the end of the reaction.

Magnetic nanoparticles (MNPs) serve as an effective support for the metals in various organic transformations [18-20].

Buchwald-Hartwig type C-N coupling reaction is one of the most efficient tools to prepare  nitrogen-containing arylamines [21,22]. This reaction involves the coupling of amines and aryl halides, using palladium as the catalyst.

The formation of the C-N bond has  wide applications in biology, biochemistry, pharmaceutics, pigments, conducting polymers, electronic materials, and other organic synthesis [23-32].

In this work, we hope to report a powerful and efficient nanocatalyst for the N-arylation of various amines. This catalyst could be satisfactory recovered by a simple external magnet, and reused without loss of its reactivity.

 

EXPERIMENTALS

Materials and methods

All chemicals purchased from Merck chemical company. Fe3O4 nanocomposite and silica-coated magnetite nanoparticles (SiO2@Fe3O4) were synthesized according to the literature respectively [33]. Na2Pd(EDTA) complex was prepared by dissolution of Pd(OAc)2 (Aldrich),  Na2CO3 and Na2H2EDTA (MERCK) in water (pH 9) as found in the literature [34]. All known organic products were identified by comparison of their physical and spectral data with those of authentic samples. Thin layer chromatography (TLC) was performed on UV-active aluminum-backed plates of silica gel (TLC Silica gel 60 F254). 1H, and 13C NMR spectra were measured on a Bruker DPX 400 MHz spectrometer in CDCl3 with chemical shift (d) given in ppm. Coupling constants are given in Hz. The FT-IR spectra were taken on a Nicolet-Impact 400D spectrophotometer in KBr pellets and reported in cm-1.

 

Synthesis of SPION-A-Pd(EDTA)

Na2CO3 (0.2 mmol, 0.021 g) was added to a mixture of Na2EDTA (0.1 mmol, 0.037 g) and PdCl2 (0.1 mmol, 0.018 g) in water (5 ml) at 25 ˚C, and was stirred magnetically for 5 h. In an argon atmosphere, SPION-ACl2 (0.53 g) in EtOH (5 ml) was added dropwise to the solution and the resulting mixture was stirred for a further 12 h at room temperature. Finally, the catalyst was collected by external permanent magnet and washed with CH2Cl2 (3×10 ml) and H2O, and dried under vacuum.

 

General Procedure for Buchwald-Hartwig Reaction under Thermal Conditions

A round-bottom flask was charged under argon with aryl halide (2 mmol, 1 equiv), amine (1 mmol, 1 equiv), DMSO (1 mL), tBuO-Na+ (2 mmol, 2 equiv) and SPION-A-Pd(EDTA) (0.094g, 0.003mol % of Pd).  The reaction mixture was stirred and heated at 120 ˚C for several hours (thin layer chromatography monitoring). After completion of the reaction, the reaction mixture was cooled to room temperature; the mixture was diluted with Et2O, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silicagel.

 

RESULT AND DISCUSSION

The SPION-A-Pd(EDTA) was successfully prepared (scheme 1) and characterized by means of  Fourier transform infrared spectroscopy (FT-IR),inductively coupled plasma atomic emission spectroscopy (ICP), thermal gravimetric analysis(TG), and high resolution transmission electron microscopy (HR-TEM).

Fig. 1 illustrates the FT-IR spectrums of Fe3O4 (a), silica-encapsulated Fe3O4 (b), and nanocatalyst SPION-A-Pd(EDTA) (c) respectively.

The FT-IR spectrum of SPION-A-Pd(EDTA) (Fig.1, c) showed absorption bands at 3421 cm-1 (N-H stretching vibration), 2930 cm-1 (C-H), 1622 cm-1 (C=N) and 635-587 cm-1 (Fe-O) SPIONs.

The thermal stability of SPION-A-Pd(EDTA) was also evaluated by TGA-DTG. According to these curves, the weight loss below 600 ºC was approximately 8.87%. So, these results approved that SPION-A-Pd(EDTA) has almost high thermal stability below 600 ˚C (Fig. 2).

For  studying the morphology characteristics of SPION-A-Pd(EDTA), HR-TEM image was also investigated (Fig. 3).

HR-TEM images of SPION-A-Pd(EDTA) revealed that it appears to have almost a spherical structure with the average size about 10-13 nm (Fig. 3, b). Then, enormous active sites of this nanoparticle may present excellent activity in organic transformations.

Inductively coupled plasma atomic emission spectroscopy (ICP) determined the amount of palladium in SPION-A-Pd(EDTA) as 3.41wt%.

In continue, catalytic activity of this complex was investigated in Buchwald-Hartwig reaction.

Hence, we initially examined reaction between morpholine and bromobenzene as model substrate to optimize the reaction conditions such as solvents, bases, temperature, and catalyst source.

In order to investigate the best solvent for this reaction, a series of solvents such as Dioxan, Toluene, DMF, and DMSO were selected (Table 1).

We observed that more polar solvents such as DMSO, and DMF (Table 1. Entries 3, 4) were favorable for the reaction. On the contrary, less polar solvents such as Dioxan, and Toluene (Table 1, entries 1, 2) provided slightly lower yields. Therefore, among the solvents tested, DMSO was the best choice.

Next, various bases were investigated. We found that using tBuONa as base in DMSO gives the N- arylated product with an excellent yield (Table 2, entry 5). The other inorganic bases such as K2CO3, K3PO4, and CS2CO3 and organic bases like NEt3 only afford moderate to low yields of N-arylated products (Table 2, entries 1-4). No product was achieved in the absence of any bases.

Among the four Pd-sources used as a catalyst, SPION-A-Pd(EDTA) gave the highest yield (Table 3, entry 5). Use of Pd(OAc)2, nanoSiO2@Pd(OAc)2, and nanoFe3O4@Pd(OAc)2 as catalyst gave low yield of product (Table 3, entries 2-4 ). The reaction in the absence of any catalyst did not give any product at all (Table 3, entry 1).

We also found that this reaction is sensitive to the reaction temperature. A temperature 120 ˚C was found to be the best temperature for the model reaction (Table 4, entry 3). A further increase in temperature could not enhance the product yield (Table 4, entry 4). Decrease in the temperature to 90 ˚C led to a decrease in yield (Table 4, entry 1).

When bromobenzene was reacted with morpholine under air atmosphere, no coupling reaction was observed to take place. Whereas, in the presence of inert atmosphere, products were obtained with an excellent yield. With the optimized conditions in hand, the Buchwald-Hartwig cross-coupling reactions were examined by varying both the amines including aromatic, aliphatic, and cyclic and a variety of aryl bromides. The results are summarized in Table 5.

In general, the presence of electron donating groups on N-nucleophiles and electron withdrawing groups on aryl halides enhanced the N-arylated product yield. Aniline substituted with electron donating group, such as 4-methoxy aniline, gave the product with a good yield (Table 5, entry 1). The reaction of aryl halides with heterocyclic amines such as morpholine, piperidine (Table 5, entries 5-10) resulted in a desired product in an excellent yield. The high nucleophilicity of these heterocyclic amines can be due to their reactivities.

The recyclability of the SPION-A-Pd(EDTA) system was also investigated. Catalyst recovered by a simple external magnet and reused for five times. Results are represented in Fig. 4.

 

CONCLUSION

In summary, we have developed a novel, air-moisture, easily recoverable Pd-complexe.

We believe that this catalyst can catalyze amination of aryl halides in the presence of inorganic bases with an excellent recycling efficiency.

 

ACKNOWLEDGMENT

The authors are grateful to the Center of Excellence of Chemistry of University of Isfahan (CECUI) and also the Research Council of the University of Isfahan for financial support of this work.

 

CONFLICT OF INTEREST

The authors declare that there is no conflict of interests regarding the publication of this manuscript.

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