PdCl2 Immobilized on Poly(styrene-co-maleimide) as an Effective Heterogeneous Catalyst for Suzuki Cross-Coupling Reaction

Poly(styrene-co-maleic anhydride) (SMA) was reacted with 4-amino-6-methyl-3-thioxo-1,2,4-triazine-5-one to obtain the corresponding imide [SMI] which was used as a substrate for immobilization of PdCl2 and preparation of palladium nanoparticles (PdNPs). The supported PdNPs were fully characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDAX) and FTIR spectroscopy, and inductively coupled plasma spectrometry (ICP). The catalytic efficiency of the PdNPs was evaluated examined successfully in one the established and useful reaction so-called the Suzuki cross-coupling reaction involving the reaction of various aryl halides with phenylboronic acid in water. The advantages of this procedure include easy recovery and efficient reusability of the expensive PdNPs, high yields of the cross coupled products, short reaction times, and use of water as a green solvent for a wide range of substrates.

DOI: 10.1134/S1070428020050231 The Suzuki cross-coupling reaction is widely used in the synthesis of natural products [1][2][3]. Recently, this reaction has drawn special attention due to successful use of intramolecular Suzuki cross-coupling for cyclizations and heterocyclizations [4]. Introduction of new catalysts to promote the cross coupling reactions is considered a signifi cant objective in organic chemistry. Many efforts have been focused on the development of nanocatalysts due to the high and unique activities in the fi eld of catalytic organic transformations [5]. Along with the high effi ciency, the advantages of nanocatalysts include cost-effectiveness, low chemical waste, low heat and energy consumption, high safety, and optimal use of starting chemicals [6]. Metal nanoparticles, in particular, palladium nanoparticles (PdNPs), are among the most useful catalysts for both organic and inorganic transformations. The immobilization of PdNPs on different mesopours and polymeric supports provides heterogeneous catalysts with a well-established capability for easy separation and reusability without considerable loss in catalytic activity [7]. Applications of PdNPs catalysts have always been one of the most fascinating research fi elds in green chemistry [8]. The most important Pd-catalyzed reactions include Suzuki [9], Sonogashira [10], Heck [11], Kumada [12] and Stille reactions [13]. Although, Pd catalysts are very useful in academia and industry, their utilization suffers from some disadvantages. They are rather expensive and cannot be easily separated from the reaction mixture. In these cases, using immobilized PdNPs on an appropriate support decreases their backdraws, making them desirable as a catalyst from the economical point of view. In recent decades, poly(styrene-co-maleic anhydride) [SMA] is known as a commercially available and sensitive co-polymer which can be modifi ed using various nucleophilic agents. Moreover, it is used as an attractive support for designing different reagents and catalysts [14]. The SMA polymer can be modifi ed to an N-substituted maleimide [SMI] [15].
Proceeding with our studies regarding organic reactions and preparation of catalysts [16], in the present work we synthesized a modifi ed SMA using a simple coordinating agent, 4-amino-6-methyl-3-thioxo-1,2,4triazine-5-one, and explored the activity of this newly synthesized substrate for preparing a Pd-supported catalyst. The effi ciency, reusability, and recyclability of this catalyst were checked in the Suzuki coupling reaction under green conditions. The modifi cation of SMA (1) with 4-amino-6-methyl-3-thiouxo-1,2,4-triazine-5-one (2) was successfully performed in two steps following the procedure of Lee et al. [17] (Scheme 1). In the 1 H NMR spectrum of SMI in DMSO, the triazine NH and CH 3 protons appeared as two singlets at 12.09 and 1.92 ppm, respectively. The aromatic proton signals were observed in the range 6.61-7.92 ppm and the aliphatic proton signals, in the range 0.70-2.28 ppm. Such 1 H NMR spectrum confi rms the proposed polymer structure (Fig. 1).
Furthermore, the conversion of the maleic anhydride moiety in SMA to maleimide in SMI was monitored by FTIR spectroscopy. Figure 2 shows that, after the reaction of SMA with 4-amino-6-methyl-3-thiouxo-1,2,4-triazine-5-one, a new imide band appeared at 1732 cm -1 , and no NH 2 band was observed at 3500 cm -1 .
In the FTIR spectrum of the polymer-supported palladium complex, the ν(C=C), ν(C=N), and ν(C=S) bands were slightly shifted to the longwave region, implying chelation of palladium to the triazine nitrogen atom. Therefore, the polymer support can act as a multidentate chelate, increasing the amount of palladium in the catalyst. Indeed, according the ICP-AES analysis, the concentration of palladium in SMI-PdCl 2 is high (17.34 wt %).
The scanning electron micrographs (Fig. 3) of the supported Pd catalyst clearly showed the morphological changes in the SMI surface produced by the loading with palladium (different size of formations and surface roughness).
The EDAX spectrum of the Pd catalyst ( Fig. 4) displayed strong signals of Cl and Pd and weaker signals of N, C, and O atoms, thereby providing evidence to Scheme 1.  show the nano catalyst was composed of Pd and SMI (Fig. 4).
To test the potency of Pd-supported catalyst, we made use of the Suzuki coupling reaction between phenylboronic acid (5) and various aryl halides 6. The effects of base, solvent, and reaction temperature were screened to optimize the reaction conditions for the coupling of iodobenzene (1.0 mmol) with phenylboronic acid (1.5 mmol) to form biphenyls 7 as the model reaction (Scheme 2, Table 1).
In the Suzuki coupling reaction, the solvent plays a crucial role in the rate and product distribution. As shown by Bedford et al. [18], water profoundly increases the activity of Suzuki-Miyaura catalysts. Therefore, we used H 2 O and MeOH-H 2 O (3 : 1, v/v) as green and conditionally green solvents, respectively. Even though the experimental results showed that the reaction time in MeOH-H 2 O (3 : 1 v/v) was shorter, ( Table 1, entry 1), we chose straight H 2 O (Table 1, entries 2, 6-15) as an inexpensive, green, readily available, non-infl ammable, and non-toxic solvent [19]. In addition, using water as the solvent not only minimizes homocoupling of phenylboronic acid, but also allows easy separation of the desired product from the homo coupled product, due to the different water solubility of these two products [18]. Furthermore, the best results were obtained with 0.02 g of the catalyst under refl ux (Table 1, entries 6-8). As expected, in the absence of any base, virtually no reaction took place (Table 1, entry 9). For selecting appropriate base, such bases as K 2 CO 3 , Na 3 PO 4 , NaOAc, NaOH, pyridine, and NEt 3 were tested. As a result, we found that inorganic bases were more effective than organic bases. K 2 CO 3, as an easily available and inexpensive chemical, was selected as an optimal base (Table 1, entries [10][11][12][13][14]. To discriminate the effect of the polymer supported catalyst SMI-PdCl 2 , the reaction was performed with PdCl 2 under the same reaction conditions. In this case, 2 m 10 m a signifi cantly lower activity was observed (Table 1, entry 15). Therefore, the Suzuki cross-coupling reaction of various aryl halides (1.0 mmol) and phenylboronic acid (1.5 mmol) were performed in the presence of K 2 CO 3 (5 mmol), using 0.02 g of the SMI-PdCl 2 catalyst (Pd-aryl halide molar ratio 0.018) in water under refl ux ( Table 2).
We analyzed the electronic and steric effects of electron-donor and electron-acceptor substituents in aryl halides, focusing on the yields and the time required   for conversion. According to the data in Table 2, both aryl iodides and bromides with both electron-donor and electron-acceptor substituents (entries 1-9) afforded excellent yields of coupling products in reasonable times. However, the couplings of 2-iodotoluene and 2-iodo-5-nitrotoluene with phenylboronic acid resulted in moderate yields of 72 and 65%, respectively (entries 5 and 6, respectively), which can be explained by steric reasons. As known, aryl chlorides are less reactive than aryl iodides and bromides in the Suzuki coupling reactions [20]. In our case, too, the yield and reaction time with chlorobenzene (entry 10) are lower that the respective parameters for bromo-and iodobenzenes (entries 9 and 1, respectively). The turnover frequency (TOF), defi ned as the mol product/mol catalyst per hour, was calculated from the isolated yield of the product, the amount of palladium, and reaction time. In all reactions, the TOF parameter determined SMI-PdCl 2 as a good catalyst for this kind of reaction (Table 2).
In order to demonstrate the suitability of the catalyst, we compared the results obtained in the synthesis of biaryls with SMI-PdCl 2 with the results of the same reaction with some other catalysts ( Table 3). The data in the table show that each method has its own advantages, but SMI-PdCl 2 offers some benefi ts in terms of low reaction temperature, simple separation, as well as use of a green solvent and no use of additional instruments like a microwave oven. Therefore, we consider our system a better choice.

Br
Varian 730-ES instrument. The SEM images of the catalyst were obtained on a TeScan-Mira III scanning electron microscope. The X-ray diffraction analysis was performed at room temperature on a PANalytical X'Pert PRO MPD X-ray diffractometer. The chemical composition was determined by energy dispersive X-ray (EDX) elemental analysis on a Lecia Cambridge S 360 scanning electron microscope equipped with EDX probe.

Preparation of SMI (3).
Poly(styrene-co-maleic anhydride) (1), prepared as described in [14], (1.00 g), 4-amino-6-methyl-3-thiouxo-1,2,4-triazine-5-one (2) (1.64 g, 16 mmol), and 15 ml of dry DMF were loaded into a 100-mL three-necked fl ask, and the mixture was stirred for 3.5 h at 35°C (heating on an oil bath) under nitrogen. Sodium acetate (0.33 g), acetic anhydride (sodium acetate, 0.6 mL), and 0.3 mL of triethylamine were then added to the reaction mixture with syringe. The temperature was raised to 75°C and stirring was continued for an additional 3.5 h. After cooling to room temperature, 300 mL of rotating methanol was slowly added. The precipitated polymer was washed several times with methanol, and dried at 70°C. For further purifi cation polymer 3 was reprecipitated twice. The amine content of the product was measured by back titration with 0.2 N NaOH [19]. Preparation of SMI-PdCl 2 (4). A mixture of SMI polymer 3 (1.0 g), PdCl 2 (1.0 g, 3 mmol), and 10 mL DMF was heated at 80°C for 15 h. After completion of the reaction, the precipitated brown polymer was fi ltered off, washed with acetonitrile (2 × 20 mL), and dried under vacuum at 60°C to give SMI-PdCl 2 4. To estimate of the palladium extent, SMI-PdCl 2 (30 mg) was reacted with 5 mL of a mixture of hydrochloric and nitric acids (3 : 1, v/v) at 100°C for 4 h. The mixture was then fi ltered, and the recovered polymer was washed with distilled water (6 × 2.5 mL), poured with 50 mL of distilled water and analyzed by ICP-OES.
General procedure for the Suzuki coupling reaction 7a-7h. A mixture of aryl halide 6 (1.0 mmol), phenylboronic acid 5 (1.5 mmol, 0.18 g), K 2 CO 3 (5.0 mmol, 0.69 g), H 2 O (5 mL), and 0.02 g of SMI-PdCl 2 was stirred under refl ux. Reaction progress was monitored by TLC in hexane-ethyl acetate (2 : 5). After completion of the reaction, the precipitate that formed was fi ltered off, washed with several portions of acetone, and dried under reduced pressure at 70°C for 3 h. The product was extracted with CH 2 Cl 2 (3 × 5 mL), and the solvent was removed on a rotary evaporator. The crude product was purifi ed by fl ash column chromatography (hexane or hexane-ethyl acetate). Biaryls 7a-7h were characterized by their melting points and IR and 1 H NMR spectra and comparison of their physical data with the literature [23,24].
The IR and 1 H NMR data for selected compounds are as follows.

CONCLUSIONS
To conclude, we synthesized a novel effi cient and green polymer-supported palladium catalyst for the Suzuki reaction. The catalyst exhibited not only high activity, but also afforded a wide range of coupling products in good to excellent yields. In addition, the catalyst is stable in the reaction conditions and can be used without preactivation and recycled in at least fi ve consecutive cycles without appreciable loss of activity. These benefi ts make the synthesized supported palladium catalyst an interesting and promising alternative to other heterogeneous palladium catalytic systems.