Proline-functionalized chitosan–palladium(II) complex, a novel nanocatalyst for C–C bond formation in water

Abstract

An environmentally friendly palladium-based catalyst supported on proline-functionalized chitosan was successfully prepared and evaluated as a heterogeneous nanocatalyst in the Suzuki cross-coupling reaction of various aryl halides with phenylboronic acid. The catalyst was characterized by FT-IR, FE-SEM, TEM, XRD, SEM-EDX, ICP and TGA techniques and exhibited reasonable catalytic activity in the reaction system, producing substituted biaryls in good to excellent yields. In addition, the catalyst could be recovered in a facile manner from the reaction mixture and recycled several times.

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Introduction

In recent years, many efforts have been focused on the development of green synthetic routes which minimize contamination and pollution in chemical synthesis. The goal is to use green reagents in producing materials. To reach this goal, highly active immobilized metal catalysts^1–3 have been used to facilitate reactions. Such heterogeneous catalysts are often readily removed by filtration and can be successfully recycled several times. Polysaccharides have been widely applied as a suitable architecture for solid catalysts. Chitosan (CS), the N-deacetylated derivative of chitin, is an example of a polysaccharide that is widely distributed in living organisms. Due to the presence of a free amino group, CS and its Schiff base derivatives are considered to be suitable solid supports for the immobilization of metal catalysts.⁴ A limiting factor in the use of CS is its poor chemical resistance and mechanical strength, which significantly reduces the recyclability of this biopolymer. Physical and chemical modifications have been used to alter the properties of fresh CS. In order to improve pore size, mechanical strength, chemical stability, hydrophilicity and biocompatibility, modifications using cross-linking agents such as glutaraldehyde, epichlorohydrin, diisocyanates or ethylene glycol glycidyl ether have been reported.^5–13 Amino acids, pyridine, alkaloids, biguanidine and piperidine are some of the most common catalysts supported on solid substrates.^14–19 Proline is a green and applicable amino acid in catalytic systems,²⁰ especially for the modification of various supports. Recently, there has been a widespread trend for the use of heterogeneous nanocatalysts modified with amino acids such as proline,²¹ and also for using CS as a green support for the preparation of heterogeneous nanocatalysts. These procedures result in faster reaction times, lower temperatures and greener media in comparison with conventional methods, and can give rise to interesting nanostructures.^22,23 In continuation of our recent investigations on the synthesis and applications of palladium-based catalysts,²⁴ we present a novel synthetic method for the preparation of a CS-proline-Pd(II) complex in the form of a recyclable solid catalyst (Scheme 1).

Scheme 1 Preparation of the nanocatalyst.

The NH₂ functional group in CS was reacted with esterified proline, yielding proline-functionalized chitosan via an amide bond formation. Then, the resulting proline-functionalized chitosan was treated with Pd(OAc)₂ to form the complex shown in Scheme 1.

The synthesis of CS-supported Pd(II) has already been reported in the literature, as well as CS-imine derivatives used in C–C coupling reactions.^25,26 A study on the structure of CS supported ligand-free Pd(II) has already been reported.²⁷ However, to the best of our knowledge, only a few reports refer to the application of such complexes in coupling reactions, especially by employing amino acids such as proline.²⁸

The palladium-catalyzed Suzuki cross-coupling reaction is a powerful method for carbon–carbon bond formation, especially for the synthesis of biaryl derivatives, which are used as building blocks for many natural products, pharmaceuticals and advanced materials.²⁹ Phosphine ligands are toxic and sensitive to air and moisture,^30,31 so phosphine-free catalysts are highly valuable.

Result and discussion

The XRD pattern in Fig. 1a was measured for the palladium(II) complex spread on the amorphous modified chitosan support. The presence of palladium in the catalyst was confirmed by SEM-EDX analysis (Fig. 1b).

Fig. 1 XRD pattern (a) and SEM-EDX spectrum (b) of the CS-proline-Pd(II) complex.

The field emission scanning electron microscopy (FE-SEM) image in Fig. 2 demonstrates the phase morphology of CS-proline-Pd(II). Fig. 3 shows TEM (transmission electron microscopy) images of the catalyst. The TEM micrographs show the distribution of particles, confirming that the nano-sized particles are well-distributed throughout the polymer matrix. The black spots and translucent parts correspond to the nanoparticles and the polymer, respectively.

Fig. 2 FE-SEM image of the CS-proline-Pd(II) complex.

Fig. 3 TEM images of the CS-proline-Pd(II) complex.

The amount of palladium in the catalyst was determined by ICP to be 2 wt%. We propose that the complex is formed randomly on the support surface between CS-proline and Pd(II) ions, and this helps the system to form a better nanostructure.

The TGA thermogram of weight loss as a function of temperature for the CS-proline-Pd(II) nanocatalyst is shown in Fig. 4. The TGA analysis results illustrate that the catalyst is stable at over 200 °C, and the total weight loss of 52.7% is due to the decomposition of the polysaccharide chain.

Fig. 4 TGA thermogram.

To explore the activity of the nanocatalyst, we used it in the Suzuki cross-coupling reaction (Scheme 2). The reusability of the nanocatalyst was also investigated. A model reaction of 4-bromonitrobenzene with phenylboronic acid was used to optimize the reaction conditions. The activity of the catalyst in different amounts was studied, and comparable yields were obtained (Table 1).

Scheme 2 Suzuki cross-coupling reaction catalyzed by CS-proline-Pd(II).

Table 1 Optimization of main parameters in the Suzuki cross-coupling reaction using the CS-proline-Pd(II) nanocatalyst^a

Entry	Solvent	Temperature (°C)	Base	Catalyst (mol%)	Time (min)	Yield^b
a Reaction conditions: 4-bromonitrobenzene (1 mmol), phenylboronic acid (1.2 mmol), CS-proline-Pd(II) catalyst, solvent (4 ml).b GC yield.
1	PEG-200	70	K2CO3 (1 eq)	0.8	40	97
2	CH3OH	70	K2CO3 (1 eq)	0.8	30	80
3	EtOH/H2O (1 : 1)	70	K2CO3 (1 eq)	0.8	47	99
4	H2O	70	K2CO3 (1 eq)	0.8	45	99
5	EtOH/H2O (2 : 1)	70	K2CO3 (1 eq)	0.8	50	88
6	EtOH/H2O (1 : 2)	70	K2CO3 (1 eq)	0.8	56	73
7	EtOH/H2O (1 : 1)	70	KOH (1 eq)	0.8	35	81
8	EtOH/H2O (1 : 1)	70	Na2CO3 (1 eq)	0.8	55	87
9	EtOH/H2O (1 : 1)	70	K2CO3 (0.5 eq)	0.8	60	45
10	EtOH/H2O (1 : 1)	70	K2CO3 (2 eq)	0.8	50	88
11	EtOH/H2O (1 : 1)	rt	K2CO3 (1 eq)	0.8	50	40
12	EtOH/H2O (1 : 1)	40	K2CO3 (1 eq)	0.8	60	80
13	EtOH/H2O (1 : 1)	70	K2CO3 (1eq)	0.4	47	100
14	EtOH/H2O (1 : 1)	70	K2CO3 (1 eq)	0.2	47	91
15	EtOH/H2O (1 : 1)	70	K2CO3 (2 eq)	0.4	47	97

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We investigated the efficiency of different bases in the Suzuki reaction (Table 1, entries 6–8). Among the selected bases, K₂CO₃ was found to be the most effective base. Several different solvents were examined, and among the tested solvents a 1 : 1 mixture of H₂O/EtOH gave the best result. We also optimized the catalyst concentration, employing various amounts of catalyst for the cross-coupling reaction. The best result was obtained when the Suzuki coupling reaction was carried out with 0.4 mol% of the catalyst (Table 1, entry 13). Temperature was also optimized for this catalytic system, and 70 °C gave the best result, in which the reaction time of the model reaction was significantly reduced in comparison with other reports.³²

The optimized parameters were applied to the reaction of various aryl halides with phenylboronic acid. The results are shown in Table 2. Electronic effects on the yield and conversion time of the reaction were examined. The nanocatalyst was compatible with a wide range of functional groups.

Table 2 Suzuki cross-coupling reaction of various aryl halides with phenylboronic acid catalyzed by the CS-proline-Pd(II) nanocatalyst^a

Entry	Aryl halide	Product	Time (min)	Yield^b
a Reaction conditions: aryl halide (1 mmol), phenylboronic acid (1.2 mmol), K2CO3 (1 mmol), 1 : 1 EtOH/H2O (4 ml), CS-proline-Pd(II) catalyst (0.4 mol%), 70 °C.b GC yield.
1			8	100
2			30	100
3			36	99
4			60	81
5			10	100
6			30	100
7			39	100
8			3 h	89
9			40	99
10			60	89
11			60	93
12			53	95
13			69	68
14			60	87
15			69	85

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Aryl halides with electron-donating groups, in comparison with aryl halides with electron-withdrawing groups, showed better conversions and shorter reaction times. As shown in Table 2, aryl halides with the iodide leaving group reacted faster than aryl bromides (Table 2, entries 1 and 2). Aryl bromides required longer reaction times, and lower yields were obtained.

The achievability of recycling the catalyst was also examined (Fig. 5). After the reaction, the catalyst was easily recovered by filtration and washed with water and acetone, then dried at room temperature and used in the next catalytic cycle under the optimized conditions. However, no significant decrease in activity was observed until the fifth reuse.

Fig. 5 Reusability of the CS-proline-Pd(II) catalyst.

The supported Pd nanocatalyst exhibited moderate activity in the Suzuki cross-coupling reaction in aqueous ethanolic solvent. The catalyst displayed good activity at low Pd loading and in aqueous medium. The amino acid-modified chitosan support plays an essential stabilizing role for the supported catalyst in the coupling reaction. The heterogeneous catalyst could be easily separated and recovered from the reaction mixture by filtration and reused several times. The combination of advantages displayed by the supported catalyst, such as ease of preparation, reasonable catalytic activity, stability, reusability and versatility, mean that this catalyst may be considered as a viable alternative in cross-coupling reactions on efficiency, environmental and economic grounds.

The use of chitosan beads as a catalyst reservoir allowed the loading of palladium because of the metal ion sorption capacity of chitosan.

Experimental

All chemical reagents were purchased from Merck and were used without further purification. Chitosan was purchased from Acros Organics and its molecular weight was 100000–300000. ¹H-NMR spectra were recorded on a Bruker 400 spectrometer using tetramethylsilane as an internal standard in CDCl₃, and FT-IR spectra were obtained using KBr pellets on a JASCO 680-Plus spectrophotometer. We also used gas chromatography (GC) (BEIFIN 3420 gas chromatograph equipped with a Varian CP SIL 5CB column: 30 m, 0.32 mm, 0.25 mm), field emission scanning electron microscopy (FE-SEM, HITACHI (S-4160)), and inductively coupled plasma (Perkin Elmer Optima 7300 DV) for determining reaction conversions.

General procedure for the Suzuki cross-coupling reaction catalyzed by CS-proline-Pd(II) nanocatalyst

The aryl halide (1 mmol) and phenylboronic acid (1.1 mmol, 0.13 g) were dissolved in H₂O/EtOH 50 : 50 (4 ml). The CS-proline-Pd(II) nanocatalyst and K₂CO₃ (1 mmol, 0.14 g) were added. The mixture was stirred continuously at 70 °C (see Table 1) using conventional heating, and the reaction was monitored by both TLC and GC. After the reaction was completed, the mixture was cooled to room temperature, 30 ml water was added and the product was extracted with n-hexane (3 × 10 ml). The organic phase was dried over CaCl₂, concentrated under vacuum and purified by column chromatography on silica gel (n-hexane/EtOAc, 9 : 1). The products were characterized by comparing their melting points, FT-IR spectra and ¹H-NMR spectra with those reported in the literature.³³

General procedure for the synthesis of chitosan modified by methyl prolinate (CS-proline)

Methyl prolinate (5 mmol, 0.64 g) and chitosan (0.5 g) were refluxed in DMF (20 ml) in a round-bottom flask for 3 days under a N₂ atmosphere. The reaction mixture was cooled to room temperature, followed by filtration to separate the proline-functionalized chitosan. After that, the product was collected, washed with methanol several times to remove impurities, and dried.

General procedure for the synthesis of CS-proline-Pd(II) nanocatalyst

The proline-functionalized chitosan (0.026 g) and Pd(OAc)₂ (0.02 g) were stirred in 10 ml acetone in a round-bottom flask for 3 days. Then, the powder was filtered and washed with acetone. The CS-proline-Pd(II) catalyst was obtained as a brown powder.

Conclusions

In this work we reported the use of a chitosan-proline-Pd(II) complex nanocatalyst for the Suzuki coupling carried out in aqueous medium. Excellent yields were achieved in relatively short reaction times for a wide range of iodo- and bromo-arenes bearing both electron-donating and electron-withdrawing groups. The conversion of aryl bromides depended slightly on the electronic effect of the substituent in the position para to the bromine. Remarkably advantageous conditions, such as the low catalyst loading, the use of an eco-friendly support (chitosan), and the green solvent, provide the method with great benefits in terms of safety, economy and sustainability. In addition, the use of water as part of the solvent mixture proved to be particularly advantageous for its ability to dissolve boron side-products coating the catalyst surface. Consequently, we believe that this method can compete with the most efficient known protocols, and due to its simple operating procedure we anticipate that it will find wide applicability. Further applications of this new catalytic system are under investigation in our laboratory.

Acknowledgements

We gratefully acknowledge the funding support received for this project from the Isfahan University of Technology (IUT), IR of Iran, and Isfahan Science and Technology Town (ISTT), IR of Iran. Further financial support from the Center of Excellence in Sensor and Green Chemistry Research (IUT) is gratefully acknowledged.

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Footnote

† Electronic supplementary information (ESI) available: Characterization data of products. See DOI: 10.1039/c5ra01187f

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