Mono- and multifold C–C coupling reactions catalyzed by a palladium complex encapsulated in MIL-Cr as a three dimensional nano reactor

Abstract

The organic palladium complex (trans-dichlorobis(4-iodoaniline-κN)palladium(II)) was encapsulated into a porous metal–organic framework MIL-Cr (Pd complex@MIL-Cr) using ship-in-a-bottle strategy. The novel catalyst as a three dimensional nanoreactor was fully characterized using different techniques such as XRD, BET, XPS, SEM, EDX, TEM and ICP. The Pd complex@MIL-Cr is isostructural to the parent MIL-Cr framework, with a high surface area and pore volume of ca. 1418 m² g⁻¹ and 0.87 cm³ g⁻¹, respectively. The nanoreactor was highly efficient in the catalytic conversion of aryl halides, showing extraordinarily higher activity than the homogeneous Pd counterparts. Surprisingly, high yields were achieved in Suzuki–Miyaura and Heck coupling reactions of chloroarenes bearing a wide range of substituents. Besides, this protocol could be extended to the cross-couplings of 2-bromo and 2,6-dibromopyridine with arylboronic acids in excellent yields at room temperature. The Pd complex@MIL-Cr was also used as an efficient and convenient catalyst for the preparation of a series of C₃-symmetric molecules with benzene, pyridine or pyrimidine units as the central core. Moreover, the catalyst could be recovered easily and reused several times without any considerable loss of its catalytic activity. Investigation of the nature of the recovered catalyst showed that the catalyst is converted to Pd nanoparticles.

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Introduction

Metal complexes have widespread applications in different fields such as modern chemistry, biotechnology, materials science and light-harvesting systems.^1–4 In the last decade, the use of transition metal complexes as homogeneous catalysts has rapidly increased for a wide variety of transformations.^5,6 However, they have some disadvantages such as difficulty of separating them from the products or solvents that limit the applicability of these homogeneous catalysts in large scale operations, and since most of them cannot be reused, causes serious economic, environmental and safety issues.^7,8 Hence, many efforts have been devoted to overcome these drawbacks and limitations, in which immobilization of metal complexes on solid support is a more hopeful and promising approach.^9–13

Among the various solid supports, porous materials such as zeolites family, metal oxides and metal–organic frameworks (MOFs) are found as exclusive classes of materials for highly convenient encapsulation of organometallic compounds and transition metal complexes (“ship-in-a-bottle” hybrids).^14–16 Moreover, these fascinating encapsulated complexes have been appropriate stability and catalytic activity, because the complex cannot ‘leak out’ through the pores without destruction of the framework.¹⁷

Palladium species have long been found as efficient catalysts in a variety of chemical transformations, especially in C–C bond-forming processes such as Suzuki–Miyaura cross-coupling and Heck reactions.^18–22 In this way, different palladium complexes were synthesized and encapsulated in porous materials as heterogeneous catalysts.^23,24

MOFs are compounds consisting of metal ions or clusters that connected by organic linkers to form three-dimensional porous structures.^25–27 Due to their high surface area, porosity, high thermal stability and resistance to water steam and moisture can act as suitable hosts for a wide range of ions, molecules, nanoparticles and metal complexes especially such as palladium species.^28,29 Up to now, palladium nanoparticles are often immobilized on MOFs using different methods.³⁰ However, little attention has been paid to the immobilization or encapsulation of palladium ions in MOFs as heterogeneous catalysts. Recently some reports have shown that palladium ions are immobilized on the walls of MOF through direct or post-synthesis incorporation methods as single-site catalysts.^31–34 Nevertheless, they are elegant catalysts; suffer from some disadvantages such as agglomeration of metal ions which decreases the catalytic activity.³⁵

The concept of green chemistry in different technology has been defined as the design of protocol or method for producing of diverse chemical products by reducing or eliminating the use and generation of hazardous solvents and was developed in principle to guide the chemists in their search for greenness.^36,37 In recent years, aqueous media is widely used as green solvent in variety organic reactions.^38–40 However, some of these synthetic methods suffer from disadvantages such as expensive starting materials, long reaction times, and use of large amounts of palladium and organic solvents. Therefore, there is still considerable room for development of simple and eco-friendly protocols of C–C cross-coupling reactions.

Encouraged by the unique properties of MOFs and in continuation of our efforts to develop novel heterogeneous catalytic systems,^41–44 herein, we wish to report preparation and characterization of a palladium catalyst by encapsulation of palladium complex into MOF. The catalytic activity of this catalyst as a highly efficient and reusable catalyst was investigated in the Suzuki–Miyaura and Heck C–C coupling reactions under green conditions (Scheme 1). It is worth mentioning that we chose the MIL-Cr MOF for the encapsulation of palladium complex because of its high specific surface areas and porosity with extraordinary stability.^45,46

Scheme 1 C–C coupling reaction catalyzed by Pd complex@MIL-Cr.

Experimental

General remarks

All materials were commercial reagent grade. Compounds were obtained from Merck or Fluka chemical companies. FT-IR spectra were recorded from potassium bromide pellets in a special range of 400–4000 cm⁻¹ using a JASCO 6300D spectrophotometer. The scanning electron micrographs were taken on a Hitachi S-4700 field emission-scanning electron microscope (FE-SEM). The XRD analysis was carried out a D8 Advanced Bruker anode X-ray diffractometer with Cu Kα (λ = 1.5406 Å) radiation. Substances were identified and quantified by gas chromatography (GC) on an Agilent GC 6890 equipped with a 19096C006 80/100 WHP packed column and a flame ionization detector (FID). In GC experiments anisole was used as internal standard. The X-ray photo-electron spectroscopy (XPS) measurements were performed using a Gammadata-scienta ESCA200 hemispherical analyzer equipped with an Al (Kα = 1486.6 eV) X-ray source. X-ray data for Pd(II) complex was collected on a STOE IPDS-II diffractometer with graphite monochromated Mo Kα radiation. Specific surface area was measured by adsorption–desorption of N₂ gas at 77 K with ASAP 2000 Micromeritics instrument. The transmission electron microscopy (TEM) was carried out on a Philips CM10 transmission electron microscope operating at 100 kV. The Pd content of the catalyst was determined by a Jarrell-Ash 1100 ICP analysis.

Catalyst preparation

Synthesis of MIL-Cr. The MOF was synthesized and purified according to a procedure reported by Férey and coworkers.⁴⁶ For MIL-Cr, chromium(III) nitrate Cr(NO₃)₃·9H₂O (400 mg, 1 mmol (Aldrich, 99%)), CrO₃ (35 mg, 0.35 mmol) and terephthalic acid (58 mg, 0.35 mmol) were dissolved in 4.8 mL H₂O (4 mL) and the mixture was stirred at room temperature. The obtained mixture was placed in a Teflon-lined stainless steel autoclave and heated at 220 °C for 8 h. The solid MOFs were washed with fresh DMF, chloroform and methanol three times every 12 hours. Then it was activated at 150 °C under vacuum for 6 hours.

Synthesis of Pd(II) complex. A mixture of PdCl₂ (240 mg, 1.36 mmol) and NaCl (88 mg, 1.52 mmol) in methanol (8 mL) was stirred at room temperature for 24 h. The mixture was filtered and Na₂[PdCl₄] solution was formed. Then, the solution of Na₂[PdCl₄] (5 mL) was added to 4-iodoaniline (0.132 g) in methanol (5 mL) and stirred at room temperature for 2 h. The desired palladium complex was collected by filtration and purified by recrystallization. The yield of yellow product was 87%.

Synthesis of palladium complex encapsulated in MIL (palladium complex@MIL-Cr). In a round-bottomed flask equipped with a condenser and a magnetic stirrer, a mixture of MIL-Cr (0.3 g) and Pd(II) complex (0.03 g) in DMF (12 mL) was stirred at 100 °C under N₂ atmosphere for 24 h. The reaction mixture was filtered and the resulting solid was washed with DMF several times for removing excess Pd(II) complex.

General procedure for Suzuki cross-coupling reaction catalyzed by Pd complex@MIL-Cr. Typically, a mixture of aryl halide (1 mmol), phenylboronic acid (1.5 mmol), K₂CO₃ (2 mmol) and the Pd complex@MIL-Cr catalyst (0.06 mol% Pd) in a 2 : 1 solution of EtOH/H₂O (2 mL) was stirred at room temperature under air atmosphere. The progress of the reaction was monitored by GC. After completion of the reaction, the catalyst was separated by filtration and the desired products were extracted with ethyl acetate (3 × 10 mL). The organic phase was collected and dried over anhydrous Na₂SO₄. The solvent was evaporated under reduced pressure and the residue was dissolved in the minimum amount of hot ethyl acetate. Next, cold petroleum ether was added dropwise to the solution to form the crystals of the desired product.

Genera procedure for synthesis of C₃-symmetric molecules via Suzuki–Miyaura cross-coupling catalyzed by Pd complex@MIL-Cr. A mixture of 1,3,5-tribromobenzene, 2,4,6-trichloropyrimidine or 2,4,6-trichlorotriazine (1 mmol), arylboronic acid (4 mmol), K₂CO₃ (3 mmol) and Pd complex@MIL-Cr (0.1 mol% Pd) in 6 mL of EtOH/H₂O (2 : 1, 6 mL) was stirred at room temperature. The work-up was performed as described for Suzuki–Miyaura cross-coupling and the pure product was obtained by recrystallization of the crude product from ethyl acetate and petroleum ether (1 : 1).

General procedure for Heck reaction catalyzed by Pd complex@MIL-Cr. Typically, a mixture of aryl halide (1 mmol), styrene (1.5 mmol), K₂CO₃ (1.5 mmol) and the Pd complex@MIL-Cr catalyst (0.5 mol% Pd) in a 2 : 1 solution of DMF/H₂O (2 mL) was stirred at 80 °C under air atmosphere. The reaction progress was monitored by GC. After completion of the reaction, the catalyst was separated by filtration and washed with DMF, and reused for next cycle.

Synthesis of 1,3,5-tristyrylbenzenes (C₃f and C₃g) via Heck reaction catalyzed by Pd complex@MIL-Cr. The 1,3,5-tribromobenzene (1 mmol), styrene (4 mmol), K₂CO₃ (3.5 mmol) and Pd complex@MIL-Cr (1.2 mol% Pd) were mixed in DMF/H₂O (2 : 1, 6 mL). The reaction mixture was stirred at 80 °C. The reaction progress was monitored by TLC (eluent: ethyl acetate/petroleum ether, 1 : 6). After completion of the reaction, the mixture was cooled to room temperature, ethyl acetate (15 mL) was added and the catalyst was separated by centrifugation. The organic phase was washed with water (2 × 10 mL), dried over anhydrous MgSO₄, and evaporated. The organic phase was evaporated and the residue was recrystallized from n-hexane to afford the pure product.

Results and discussion

Preparation and characterization of Pd complex@MIL-Cr

The schematic preparation of catalyst is shown in Scheme 2. The palladium complex, was prepared by the reaction of Na₂[PdCl₄] with 4-iodoaniline. After preparation and characterization of the complex by different techniques especially with single crystal X-ray diffraction, we found that this complex has been synthesized by a different method (CCDC-881454).⁴⁷ However, our reported procedure was easier and more applicable. Then, the Pd complex@MIL-Cr catalyst was synthesized by encapsulating of Pd complex, into MIL-Cr in DMF. Desired powder was separated by filtration and washed with DMF several times for removing excess Pd(II) complex.

Scheme 2 (a) Schematic procedures for preparation of the Pd complex@MIL-Cr structure, and (b) schematic diagram of the Pd complex@MIL-Cr.

According to channel diameter of MIL-Cr⁴⁶ and the size of the Pd(II) complex,⁴⁷ the Pd complex can be encapsulated using ship-in-a-bottle strategy. The prepared catalyst was characterized by XRD, BET, TEM, XPS and FE-SEM methods.

The XRD pattern of synthesized MIL-Cr matches well with the reported patterns of the MOF⁴⁶ (Fig. 1a). Moreover, the sharp peaks indicate the excellent crystallinity of the framework. As can be seen, the crystallinity of the catalyst was studied (Fig. 1b). The pattern of MIL-Cr, indicating that Pd complex@MIL-Cr is very stable and sustainable during the encapsulating of Pd complex and is isostructural with XRD pattern of MIL-Cr, thus which is also obvious from the similarity between their XRD patterns.

Fig. 1 XRD patterns of (a) MIL-Cr and (b) Pd complex@MIL-Cr.

The morphology and crystalline size of the samples were examined using field emission scanning electron microscopy (FE-SEM) (Fig. 2). As can be seen the morphology of MIL-Cr is octahedral and its structure form maintains during encapsulation of Pd complex.

Fig. 2 FE-SEM image of: (a) MIL-Cr, (b) Pd complex@MIL-Cr and (c) reused catalyst.

The energy dispersive X-ray (EDX) results, obtained from FE-SEM analysis for the Pd complex@MIL-Cr is shown in Fig. 3, which clearly show the presence of Pd in catalyst texture. EDX elemental mapping was also performed for the Pd complex@MIL-Cr (Fig. 4). The distributions of elements from the area mapping showed a uniform scattering of Pd, N, I, Cl, O and Cr elements in the catalyst, which highly indicated that the catalyst was formed. Also, as can be seen, the Pd(II) complex was homogeneously dispersed on the MIL-Cr pores without any aggregation (Fig. 4).

Fig. 3 SEM-EDX spectrum of Pd complex@MIL-Cr.

Fig. 4 Energy dispersive X-ray (EDX) mapping analysis of Pd complex@MIL-Cr.

To confirm and determine the coordination environment of Pd complex@MIL-Cr, we performed X-ray photoelectron spectroscopy (XPS) analysis (Fig. 5).

Fig. 5 The XPS spectrum of: (a) Pd complex@MIL-Cr, (b) the elemental survey scan of Pd complex@MIL-Cr, (c) the recovered catalyst.

In XPS of Pd complex@MIL-Cr, Pd 3d_3/2 (343.08 eV) and 3d_5/2 (337.64 eV), split each individual peak into two peaks at 341.39 eV and 343.08 eV for Pd 3d_3/2 whereas 336.45 eV and 337.64 eV for Pd 3d_5/2; corresponding to Pd(II) in the square planar palladium complex and chloride-coordinated Pd(II) states (Fig. 5a).⁴⁸ The peaks corresponding to oxygen, carbon, chromium and nitrogen are also clearly observed in XPS elemental survey of the catalyst (Fig. 5b).

The structure of MIL-Cr and Pd complex@MIL-Cr was further studied by transmission electron microscopy (TEM). The TEM image of MIL-Cr showed well-defined octahedral structures for MIL-Cr (Fig. 6). Also, the TEM image of Pd complex@MIL-Cr showed that the Pd(II) complex was homogeneously dispersed on the MIL-Cr support and no obvious Pd(0) nanoparticle was observed (Fig. 6b). On the other hand, in the case of the reused catalyst (in the Suzuki reaction), no obvious change, which represents the aggregation, was observed (Fig. 6c). The surface areas and pore volumes of MIL-Cr and Pd complex@MIL-Cr, were measured by N₂ physisorption at 77 K (Fig. 7). The N₂ adsorption/desorption isotherm measurement indicated that MIL-Cr exhibited a Brunauere–Emmette–Teller (BET) surface area about 2730 m² g⁻¹. After encapsulation of Pd(II) complex, the specific surface area decreased to 1418 m² g⁻¹. Besides, the pore volume of MIL-Cr after encapsulation of Pd(II) complex decrease from 1.35 to 0.87 cm³ g⁻¹ (Fig. 7B). The decrease of surface area and pore volume is attributed to the occupying and/or blocking of MIL-Cr pores by the palladium(II) complex.^49,50 All these observations and remarks clearly indicate that the MIL-Cr is an elegant and appreciate host for encapsulation of palladium(II) complex.

Fig. 6 TEM image of: (a) MIL-Cr; (b) and (c) Pd complex@MIL-Cr and (d) reused catalyst.

Fig. 7 N₂ isotherms at 77 K (A) and pore size distributions (B) of MIL-Cr (a) and Pd complex@MIL-Cr (b).

Also, to verify the Pd content in MIL-Cr, the catalyst was treated with a mixture of concentrated HCl and HNO₃ (3/1 ratio of HCl and HNO₃) at room temperature to digest the Pd species and then was analyzed by ICP analysis. The Pd content was estimated about 1.4% for Pd complex@MIL-Cr.

Suzuki–Miyaura cross-coupling of aryl halides with arylboronic acids catalyzed by Pd complex@MIL-Cr

After, synthesis and characterization of Pd complex@MIL-Cr as a three dimensional nanoreactor catalyst, the catalytic activity was investigated in C–C bond-forming processes that have much lured researchers in modern organic synthesis.⁷ Hence, the catalytic activity of Pd complex@MIL-Cr was evaluated for Suzuki–Miyaura cross-coupling reactions using as model substrates 4-iodoanisole and phenylboronic acid. In order to obtain the most appropriate conditions, we set out to study variety parameters such as the base and solvent types, temperature and catalyst loading. The obtained results are showed in Table 1.

Table 1 Optimization of the Suzuki–Miyaura cross-coupling of 4-iodoanisole with phenylboronic acid catalyzed by Pd complex@MIL-Cr^a

Entry	Base	Catalyst (mol% Pd)	Solvent	Time (min)	Yield^b (%)
a Reaction conditions: 4-iodoanisole (1 mmol), phenylboronic acid (1.1 mmol), base (1.5 mmol), solvent (2 mL), room temperature.b Isolated yield.c The reaction was performed under Ar atmosphere.d trans-Dichlorobis(4-iodoaniline-κN)palladium(II).e MIL-Cr was used as catalyst.
1	Na2CO3	0.06	DMF/H2O (2 : 1)	15	70
2	Na2CO3	0.06	MeCN/H2O (2 : 1)	15	65
3	Na2CO3	0.06	DMSO/H2O (1 : 1)	30	52
4	Na2CO3	0.06	Dioxane/H2O (1 : 1)	30	37
5	Na2CO3	0.06	EtOH/H2O (2 : 1)	15	86
6	Na2CO3	0.06	H2O	15	41
7	Na2CO3	0.06	EtOH/H2O (1 : 2)	15	63
8	K2CO3	0.06	EtOH/H2O (2 : 1)	15	97
9	NaOH	0.06	EtOH/H2O (2 : 1)	15	35
10	K3PO4	0.06	Dioxane/H2O	30	48
11	NEt3	0.06	EtOH/H2O (2 : 1)	30	17
12	K2CO3	0.08	EtOH/H2O (2 : 1)	15	97
13	K2CO3	0.04	EtOH/H2O (2 : 1)	15	46
14^c	K2CO3	0.06	EtOH/H2O (2 : 1)	15	97
15^d	K2CO3	0.06	EtOH/H2O	30	25
16^e	K2CO3	5 mg	EtOH/H2O	30	0

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With consideration of economy, safety and environment problems and according to previously reported papers,^41–44 aqueous–organic mixtures are the best solvents in theses transformations. Due to the ability of water for dissolving of base and activating the arylboronic acids, the reaction accelerates in aqueous media.⁵¹ Among them, EtOH/H₂O (2 : 1) was proved to be the best reaction media. Subsequently, a series of bases including NEt₃, NaOH, K₃PO₄, Na₂CO₃ and K₂CO₃ were then screened, with optimum results obtained using K₂CO₃ (up to 97% isolated yield, Table 1). Additionally, to study the effect of the amount of catalyst on the model reaction was also explored; the best result was obtained using 0.06 mol% Pd catalyst. Therefore, it was concluded that the optimum reaction conditions involved 4-iodoanisole (1 mmol), phenylboronic acid (1.1 mmol), K₂CO₃ (1.5 mmol) and catalyst (0.06 mol% Pd) in EtOH/H₂O (2 : 1) at room temperature (Table 1, entry 8). The model reaction was also performed in the presence of MIL-Cr but no product was obtained. This observation shows that that catalytic activity can be attributed to Pd complex in the nanopores of MIL-Cr. On the other hand, the C–C cross coupling was also carried out in the presence of 0.06 mol% of homogeneous Pd complex under the same reaction conditions and the desired product was obtained in 25% yield. Under these conditions, the palladium complex was converted to palladium black and deactivated. It seems that the MIL-Cr plays tow important role in this catalytic system: (i) isolation of catalytic active sites by their dispersion on its high surface area and (ii) prevention of conversion of palladium species to palladium black.

The scope of the reaction was subsequently expanded to several substrates including a range of aryl halides with phenylboronic acid (Table 2). Results summarized in Table 3 obviously show that the protocol was amenable to various substrates (iodo, bromo and chloro derivatives), containing electron-donating and electron-withdrawing substituents providing very good to excellent yields to afford the desired cross-coupling products. As can be seen, aryl iodides were found to be more reactive than aryl bromides and aryl chlorides. Aryl chlorides are inexpensive and abundantly available but less reactive than their bromides and iodide counterparts. Due to lower reactivity, the coupling reactions with aryl chlorides have been generally investigated by using harder conditions.^52,53

Table 2 Suzuki–Miyaura cross-coupling of aryl halides with phenylboronic acid catalyzed by Pd complex@MIL-Cr^a

Entry	R^1	R^2	X	Time (min)	Yield^b (%)
a Reaction conditions: aryl halide (1 mmol), arylboronic acid (1.1 mmol), K2CO3 (1.5 mmol), Pd complex@MIL-Cr (0.06 mol% Pd), EtOH/H2O (2 : 1, 2 mL), room temperature.b Isolated yield.
1	H	H	I	15	95
2	H	4-MeO	I	15	97
3	4-Ac	H	I	18	96
4	4-Me	H	I	15	95
5	4-Ac	4-MeO	I	15	96
6	H	H	Br	25	95
7	H	4-MeO	Br	25	94
8	4-MeO	4-MeO	Br	25	95
9	4-Ac	4-MeO	Br	25	95
10	4-CHO	4-MeO	Br	25	92
11	3-CN	H	Br	25	94
12	H	H	Cl	45	82
13	H	4-MeO	Cl	45	86
14	4-Ac	H	Cl	45	82
15	4-Ac	4-MeO	Cl	45	87
16	4-CHO	H	Cl	45	85

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Table 3 Optimization of the Heck reaction of 4-iodoanisole with styrene catalyzed by Pd complex@MIL-Cr^a

Entry	Base	Catalyst (mol% Pd)	Solvent	T (°C)	Time (h)	Yield^b (%)
a Reaction conditions: 4-iodoanisole (1 mmol), styrene (1.1 mmol), base (1.5 mmol), solvent (2 : 1, 2 mL).b Isolated yield.
1	K3PO4	0.5	DMF/H2O (2 : 1)	80	6	60
2	Et3N	0.5	DMF/H2O (2 : 1)	80	6	31
3	Na2CO3	0.5	DMF/H2O (2 : 1)	80	6	57
4	NaOH	0.5	DMF/H2O (2 : 1)	80	6	41
5	K2CO3	0.5	DMF/H2O (2 : 1)	80	4	94
6	K2CO3	0.5	DMF/H2O (1 : 1)	80	6	86
7	K2CO3	0.5	EtOH/H2O (2 : 1)	75	6	60
8	K2CO3	0.5	MeOH/H2O (2 : 1)	68	6	48
9	K2CO3	0.5	CH3CN/H2O (2 : 1)	80	6	60
10	K2CO3	0.5	EtOAc/H2O (1 : 1)	60	8	19
11	K2CO3	0.5	DMF	80	6	78
12	K2CO3	0.5	DMF/H2O (2 : 1)	95	4	92
13	K2CO3	0.5	DMF/H2O (2 : 1)	65	8	73
14	K2CO3	0.25	DMF/H2O (2 : 1)	80	8	62
15	K2CO3	0.75	DMF/H2O (2 : 1)	80	4	91
16	K2CO3	0.5	DMF/H2O (2 : 1)	80	3	85

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It is also interesting that this procedure can be scaled-up. When 10 mmol of chlorobenzene was reacted with 11 mmol of phenylboronic acid in the presence of 15 mmol K₂CO₃ and 0.01 mol% of Pd complex@MIL-Cr, the yield of produced biphenyl was 75% yield (1.15 g) after 6.5 h.

Suzuki–Miyaura cross-coupling of 2-bromo- and 2,6-dibromopyridine with arylboronic acids catalyzed by Pd complex@MIL-Cr

In order to expand the scope of the reaction substrates, 2-bromo- and 2,6-dibromopyridine as heteroaromatic substrate were also examined (Scheme 3, P_a and P_b). This transformation is quite more important owing to wide application of aryl pyridine compounds in materials chemistry and advanced technologies such as light-emitting devices.⁵⁴ As far as we know, Suzuki–Miyaura cross-coupling reaction of heterocycle-containing substrates usually performs in harsh conditions in the presence of high loading of palladium due to its low reactivity.^55,56 As revealed in Scheme 3, this C–C cross coupling reaction was carried out smoothly with phenylbronic acid and 4-methoxyphenylbronic acid in the presence of Pd complex@MIL-Cr under mild and green conditions in high yields.

Scheme 3 Suzuki–Miyaura cross-coupling of 2-bromo and 2,6-dibromopyridine catalyzed by Pd complex@MIL-Cr.

Synthesis of C₃-symmetric molecules via Suzuki–Miyaura cross-coupling catalyzed by Pd complex@MIL-Cr

C₃-Symmetric molecules are indeed an attractive and significant feature due to their wide variety of applications such as components of organic light-emitting devices (OLEDs), chemical sensors and optical switches.⁵⁷ The cross coupling reactions are a suitable method for preparation of symmetric aromatic compounds. It is well known that these molecules can be synthesized by use of cross coupling reaction as a key step. However, it is not a trivial task, due to difficulties in purifying these molecules by column chromatography. In this way, we intended to use tribromo-substituted benzene and heteroaromatic substrates for Suzuki–Miyaura cross coupling reaction. As shown in Scheme 4, the triarylbenzens, triarylpyridine and triarylpyrimidines were obtained in high yields at room temperature under green conditions in the presence of Pd complex@MIL-Cr catalyst.

Scheme 4 Synthesis of C₃-symmetric aromatic molecules via Suzuki–Miyaura coupling reaction catalyzed by Pd complex@MIL-Cr.

Heck reaction of aryl halides with styrene catalyzed by Pd complex@MIL-Cr

Inspired by the obtained results in the Suzuki–Miyaura cross-coupling, in other part of this study, we evaluated the catalytic activity of Pd complex@MIL-Cr catalyst in the Heck reaction. To survey the possibility of the Heck reaction using Pd complex@MIL-Cr, the reaction of 4-iodoanisole with styrene was selected as model substrates for optimization study. The obtained results are summarized in Table 3. As can be seen, under thermal conditions, the best result was obtained using 4-iodoanisole (1 mmol), styrene (1.1 mmol), K₂CO₃ (1.5 mmol) and Pd complex@MIL-Cr (0.5 mol% Pd) in aqueous DMF at 80 °C (Table 3, entry 5). To determine the scope of this protocol, various stilbenes were synthesized under the optimized conditions, and the results are summarized in Table 3. The results in Table 3 disclose that Pd complex@MIL-Cr an active and efficient three dimensional nano-reactor catalytic system for the Heck reaction in aqueous DMF media.

The reaction conditions are quite broad with respect to the substrates examined, providing the desired stilbenes with good to excellent yields. As clearly shown in Table 4, this catalytic system can be used for various aryl halides with electron-withdrawing and electron-donating groups. It is worth mentioning that based on NMR spectra; all of the products were obtained in trans form, demonstrating extremely high trans selectivity for the catalyst in Heck reaction. The selectivity in these reactions can be related to the size of the cavity in the MIL-Cr. When the size of the cavity is large, the trans-product is produced.⁵⁸

Table 4 Heck reaction of aryl halides with styrene catalyzed by Pd complex@MIL-Cr^a

Entry	R^1	R^3	X	Time (h)	Yield^b (%)
a Reaction conditions: aryl halide (1 mmol), styrene (1.1 mmol), K2CO3 (1.5 mmol), DMF/H2O (2 : 1, 6 mL), Pd complex@MIL-Cr (0.5 mol% Pd), 80 °C.b Isolated yield.
1	H	H	I	4	94
2	H	4-Me	I	3	97
3	4-Me	4-Me	I	3	97
4	4-Ac	H	I	4	96
5	4-Ac	4-Me	I	4	91
6	H	H	Br	7	90
7	H	4-Me	Br	6	89
8	4-MeO	4-Me	Br	6	97
9	4-F	H	Br	7	90
10	4-F	4-Me	Br	7	86
11	4-Me	H	Br	6	93
12	4-Ac	4-Me	Br	6	90
13	4-Ac	H	Br	6	94
14	4-CHO	H	Br	6	85
15	H	H	Cl	12	86
16	4-MeO	H	Cl	10	91
17	4-Ac	H	Cl	12	88
18	4-Ac	4-Me	Cl	12	89
19	4-CHO	H	Cl	12	92

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Synthesis of C₃-symmetric molecules via Heck reaction catalyzed by Pd complex@MIL-Cr

Finally, in order to further widen the applicability of this catalytic system was surveyed for the synthesis of C₃-symmetric molecules by Heck reaction. As shown in Scheme 5, the reaction of 1,3,5-tribromobenzene with styrene or 4-methylstyrene was performed efficiently in the presence of Pd complex@MIL-Cr at 80 °C and the corresponding symmetric molecules (C₃f and C₃g) were obtained in high yields within 6 h.

Scheme 5 Synthesis of C₃-symmetric molecules by Heck reaction.

In order to show the quality and the reactivity of Pd complex@MIL-Cr system compared to other catalysts, a comparison with some previously reported palladium immobilized on MOF catalysts for the Suzuki–Miyaura cross-coupling is presented in Table 5. As shown in Table 5, our catalytic system is superior to the previously reported methods in terms of reaction condition, reaction time and yield. Furthermore, the amount of the catalyst required is lower and the turnover frequency (TOF) of is clearly higher, indicating the efficiency and superiority of this protocol. The high catalytic activity of this catalytic system can be attributed encapsulation of nanoparticles in the pores of the MIL-Cr. While supporting of the nanoparticles on the outer surface give lower catalytic activity.^59,60

Table 5 Comparison of the results obtained in the Suzuki–Miyaura coupling reaction of chlorobenzene with phenylboronic acid catalyzed by Pd complex@MIL-Cr with those obtained by the recently reported catalysts

Catalyst	Condition	Yield^a (%)	TOF (h^−1)	(Ref.)
a Isolated yield.b TBAB = tetrabutylammonium bromide.
Pd/MIL-53(Al)–NH2 (0.5 mol% Pd)	H2O/EtOH, Na2CO3, 80 °C, 24 h, N2	36	3	61
Pd/MIL-Cr (0.9 mol% Pd)	NaOMe, TBAB^b, H2O, 80 °C, 20 h, N2	97	5.4	62
Pd(II) doped UiO-67 (0.46 mol% Pd)	KOH, DMF/EtOH (20 : 1) 100 °C, 20 h, N2	90	9.8	63
Pd/UiO-66–NH2 (0.25 mol% Pd)	H2O/DMF, K2CO3, 80 °C, 41 min	80	467.8	41
Pd complex@MIL-Cr (0.06 mol% Pd)	EtOH/H2O, K2CO3, rt, 45 min	82	1822	Present work

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Catalyst recycling and reuse

The recovery and reusability of a heterogeneous catalyst is a significant attribute from practical, economical and safety points of view. For this purpose and sensible application of this catalytic system, the reusability of Pd complex@MIL-Cr was investigated using the model reaction of Suzuki–Miyaura cross-coupling under optimized conditions. The results showed that the catalyst could be reused in Suzuki–Miyaura reaction at least six times without any treatment in its catalytic activity (Fig. 8).

Fig. 8 Reusability of Pd complex@MIL in Suzuki–Miyaura cross-coupling reaction. Reaction conditions: 4-iodoanisole (1 mmol), phenylboronic acid (1.1 mmol), K₂CO₃ (1.5 mmol), Pd complex@MIL-Cr (0.06 mol% Pd), EtOH/H₂O (2 : 1, 2 mL), room temperature.

It is important to note that leaching of the Pd complex from the MIL-Cr is an environmental concern. Additionally, it makes the catalyst inactive within a very short time. Thus, leaching of Pd complex from MIL-Cr was checked. After six times of reuse, we checked the Pd content of the Pd complex@MIL catalyst using ICP analysis, and the results indicated that less than 2% of Pd was leached. The hot filtration test was also performed for the model reaction at 70 °C.^64,65 The reaction mixture was filtered after 5 min the reaction was continued to 15 min. The results showed no further progress. These observations proved the low leaching of the palladium species.

Comparison of SEM image of recovered catalyst with fresh catalyst showed no obvious changes in the morphology and structure of MIL-Cr which showed the stability of the nanoreactor during the catalytic cycles. But the TEM image of recovered catalyst (Fig. 6d) showed that the Pd complex is converted to Pd nanoparticle. The XPS analysis confirmed this observation (Fig. 6c). The presence of the peaks at 335.4 (3d_5/2) and 339.8 (3d_3/2) proved the formation of Pd(0).

Conclusion

In conclusion, the trans-dichlorobis(4-iodoaniline) palladium(II) complex encapsulation in MIL-Cr (Pd complex@MIL-Cr) was prepared and applied as a highly active and reusable catalyst for the Suzuki–Miyaura cross-coupling and the Heck reaction of aryl halides with arylboronic acids and styrene, respectively. This catalytic system was also used efficiently for the synthesis of arylpyridine derivatives and C₃-symmetric molecules. In addition, high yields, short reaction times, use of green solvent such as EtOH/H₂O and simple work-up procedure make this method a valid contribution to the existing methodologies for C–C coupling reactions. Moreover, the prepared catalyst was easily recoverable and reusable makes this method an economic and environmentally-benign process. Such an efficient design for three dimensional nanoreactor catalysts with encapsulating of palladium complex, as well as excellent recyclability and negligible metal leaching could coincide with the concepts of green chemistry. During the catalytic cycles, palladium complex is converted to Pd nanoparticles. Simply encapsulation of palladium complex into MOFs might bring new opportunities in the improvement of highly active heterogeneous palladium catalysts for C–C couplings which can be extended to other Pd-catalyzed transformations.

Acknowledgements

The authors thank the Research Council of the University of Isfahan.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra11212a

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