A reusable heterogeneous catalyst without leaking palladium for highly-efficient Suzuki–Miyaura reaction in pure water under air

Abstract

Herein, we report a heterogenous catalyst (Pd@FSM) by immobilization of a novel Pd²⁺ sensor as promoter over mesoporous silica. Pd@FSM with a high palladium loading of ca. 11 mg g⁻¹ exhibited superior catalytic activity for Suzuki–Miyaura cross-couplings and a catalyst loading of 0.05 mol% is typically sufficient to achieve excellent reaction yields. Notably, the reaction is typically carried out in water without removing atmospheric oxygen. The catalyst is conveniently recycled and remains highly active even after being recycled 5 times. During this process, loss of palladium from the solid support of the catalyst is negligible. Furthermore, the catalyst can be stored in air for at least three months without loss of its catalytic activity. This work provides a new approach to developing heterogeneous palladium catalysts by combing materials and fluorescent sensors.

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1. Introduction

Palladium catalysts are widely employed in carbon–carbon bond formation and play an indispensable role in the synthesis of complex structures, such as natural products, pharmaceuticals, functional materials, polymers and supermolecules.^1–4 Homogeneous palladium catalysts are routinely employed in the Suzuki–Miyaura reaction. Though they have found great success, limitations such as high expenses and sensitivity to oxygen have been encountered.⁵ Recycling of a catalyst may greatly lower its cost and is particularly desired in industrial applications.⁶ Besides, contamination of the reaction products by palladium is not efficiently removed and represents an important concern of such processes.⁷ Recently, development of heterogeneous palladium catalysts have attracted considerable attention since they are conveniently recycled for reuse. They are typically constructed by covalent or supra-molecular immobilization^8,9 of metal catalysts on the surface of various materials through interactions, including silica,^10,11 graphene,^12,13 carbon nano tube,^14,15 and metallic oxide,¹⁶ and the organic matrix, such as polymers and dendrimers.^17,18

Various ligands that have been immobilized for chelating of palladium ions include thiol groups, heterocyclic ring structure, multi-oxygen or nitrogen groups and other groups.^11,19–23 In recent years, the fluorescent probes for the detection and separation of heavy metal ions, such as palladium ions, has gained extensive interest. These studies have inspired constructing multifunctional platforms for ion detection, separation and reusability onto host materials.^24–26 Recently, Bhalla group reported a multi-functional hetero-oligophenylene derivative, which could detect palladium ions and induce to form palladium nanoparticles as novel catalysts for carbon–carbon coupling.²⁷ In another aspect, various nanoparticles or micro-particles have been reported and widely used as the carrier of solid catalysts.^{10,11,16,19,20,28,29} Among those materials, the mesoporous silica nanoparticles is highly attractive by virtue of its large specific surface area, facile modification for diverse functions and heat- and hydro-stability.^30–32 Amini et al. reported a heterogeneous palladium catalyst by anchoring tridentate pyridine ligand to mesoporous silica, which showed good capacity in catalyzing Mizoroki–Heck and Suzuki–Miyaura reaction with 1 mol%.It could be recycled for four times but loss of catalytic activity after each recycle was noted.³³ Furthermore, Lin et al. reported a magnetic palladium catalyst, exhibiting much higher activity with only 0.02 mol% and excellent recyclability for more than 20 times without notable loss of activity. However, the leaking of palladium and requiring the use of organic co-solvent are still concerns.³⁴ Combination of selective and specific fluorescence probes with various matrixes is highly desirable endowing them excellent performance, such as broader linear detection range, convenience and reusability in separation or even lower detection limit.^24–26,35

We previously reported a fluorescent material FSM by anchoring a palladium fluorescent probe on mesoporous silica for detection and separation of palladium ions in various solutions.³⁵ Further investigation showed that the palladium ions were tightly bound with FSM, and could not be easily pulled down by the H⁺, EDTA or other chelating agents. The high stability of the complex has promoted us to test its potentials as a heterogeneous palladium catalyst. Herein, based on the palladium fluorescent probe FSM, we report a reusable heterogeneous catalyst Pd@FSM for Suzuki–Miyaura reaction. The catalyst exhibited excellent ability in catalyzing the Suzuki–Miyaura cross-coupling reactions of aryl halides with phenylboronic acids in water with only 0.05 mol% amount and kept its activity stable even after exposed to the air for three months or recycled for five times without palladium leaking.

2. Experimental

The synthesis of FSM was reported by our previous work.³⁵ Mainly by integrating the highly specific Pd²⁺ fluorescent probe with mesoporous silica through silicon oxygen bond.

2.1 Preparation of Pd@FSM

FSM (500 mg) and PdCl₂ solution in water (10 mM, 20 mL) were stirred for 3 h at room temperature. Then the mixture was filtered and washed with water for three times. After that, the residue was further refluxed in methanol for another 24 h. The solid catalysts were then filtered and washed with methanol and water for three times respectively. The final product Pd@FSM was dried under vacuum. The amount of palladium anchored to Pd@FSM was 11 mg g⁻¹ by the inductively coupled plasma atomic emission spectrometry (ICP-AES). The palladium ion was captured by alkynyl group and aminothiophene owing to their rich electron density as reported (Fig. 1),³⁶ which caused the decrease of fluorescence of FSM.³⁵

Fig. 1 Preparation of Pd@FSM and its application in suzuki coupling reaction.

2.2 General procedure for Suzuki–Miyaura reactions

Aryl halide (1 mmol), phenylboronic acid (1.5 mmol), K₂CO₃ (276 mg, 2.0 mmol), Pd@FSM (5.0 mg, 0.05 mol%) and water (5 mL) were mixed in 25 mL round-bottom flask and stirred at 80 °C for 10 h. After the reaction completed, the reaction mixture was extracted with CH₂Cl₂ (3 × 50 mL). The combined organic layers were dried over MgSO₄ and concentrated in vacuo. The remaining residue was purified by column chromatography on silica gel and confirmed with ¹H NMR, mass spectral data and melting point. In the recycle test, 4-bromoacetophenone (199 mg, 1.0 mmol), phenylboronic acid (183 mg, 1.5 mmol), K₂CO₃ (276 mg, 2.0 mmol), Pd@FSM (5.0 mg, 0.05 mol%) and water (25 mL) were used. After each cycle, the solution was extracted with CH₂Cl₂, and the combined organic layers were dried over MgSO₄ and concentrated in vacuo. The products were sent for ICP-MS analysis to detect the leached palladium. The water phase was centrifuged after extraction, washed with extensive methanol and Milli Q-water, then dried under vacuum and then used directly without any further treatment.

3. Results and discussion

As a safe and cost-effective solvent, water has been widely applied in catalyzing the Suzuki–Miyaura coupling reaction, as the solvent or a co-solvent.^34,37–39 In this research, the Pd@FSM catalyst performed excellent catalytic property in pure water under aerobic conditions.

Firstly, we examined the catalytic activity of Pd@FSM with a different amount of catalyst loading in water under air atmosphere. The results showed that Pd@FSM of 0.01 mol% can afford the product in 90% yield in 24 h. Raising the catalyst loading to 0.05 mol% led to improving the reaction yield to 97% but only in 10 h. These outcomes illustrate the much higher activity of Pd@FSM than those homogeneous or heterogeneous palladium catalysts under the condition of water solution and air atmosphere.^11,36,40 After that, the conversion rate had no significant increase even with much more catalyst (Table 1). Besides, the results also proved that the presence of oxygen does not inhibit the catalytic activity of Pd@FSM. This is an important feature in practical industrial application. Therefore, the following catalysis experiments were all carried out with 0.05 mol% of palladium under 80 °C in water for 10 h in ambient air.

Table 1 Catalytic activity evaluation of Pd@FSM^a

a Condition: 1.0 mmol B1, 1.5 mmol boronic acid B2, 2.0 mmol K2CO3 and Pd@FSM in 5 mL water solution under 80 °C.b Isolated yield, mean of three experiments.
Catalyst (mol%)	0.005	0.01	0.05	0.2
Yield (%)^b	27	90	97	98
Time (h)	24	24	10	10

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A broad substrate scope plays an essential role in evaluating the efficiency of a catalyst. Therefore, we screened different aryl halides with phenylboronic acid to further explore the catalyzing capability of Pd@FSM. As shown in Table 2, Pd@FSM had good performance for different substrates with high yields in water, especially for bromo- and iodo-benzenes. It could achieve uniformly high yields for a wide selection of substrates in pure water. And a lower catalyst loading is used compared with other palladium catalysts.^40,41

Table 2 Different aryl halides for Suzuki–Miyaura reaction^a

Entry	R1	R2–B(OH)2	Yield^b (%)
a Condition: 1.0 mmol R1–X, 1.5 mmol boronic acid, 2.0 mmol K2CO3 and Pd@FSM (0.05 mol% Pd) in 5 mL water solution under 80 °C for 10 h.b Isolated yield, mean of three experiments.
1			41
2			91
3			87
4			97
5			91
6			81
7			81
8			91
9			94
10			84
11			86

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Besides, the results in Table 2 showed that substitution on the ortho-/para of aryl halides had no obvious regular effect on the yields, no matter it was electron-drawing (acetyl-, nitro- and cyan-) or donating group (methoxy-, methyl-). The above phenomenon was further confirmed by the results in Table 3 (entries 12 and 13). However, we also found that the sterically demanding ortho-position on the phenylboronic acids would significantly lower the yields (Table 3, entries 14 and 15), considering the equal contribution of methoxyl group to electron density increase in ortho- and para-position. The steric hindrance from both the ortho-substituted substrates caused sharp reduction of the product (Table 3, entry 18).

Table 3 Steric hindrance effect of Suzuki–Miyaura reaction^a

Entry	R1–X	R2–B(OH)2	Yield^b (%)
a Condition: 1.0 mmol R1–X, 1.5 mmol boronic acid R2–B(OH)2, 2.0 mmol K2CO3 and Pd@FSM (0.05 mol% Pd) in 5 mL water solution under 80 °C for 10 h.b Isolated yield, mean of three experiments.
12			94
13			91
14			95
15			46
16			85
17			83
18			26

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Furthermore, we probed Pd@FSM catalyst in phenylboronic acids with various substitutions by reacting with 4-bromo-acetophenone which had relatively higher activity compared with other aryl halides (Table 2, entry 4). Phenylboronic acids substituted with methyl-, fluoro-and chloro-groups are all well tolerated even much higher yields (Table 4, entry 19–26), while the cyan-group in para-position came up with slight decrease of the yield (Table 4, entry 27). The formyl- and nitro-groups in the meta-position caused significant decrease of the yields of products (Table 4, entries 28 and 29). Besides, we also achieved the hydroxythio-group substituted product in the para-position for the first time.

Table 4 Widespread application of Pd@FSM in catalyzing Suzuki–Miyaura reaction with different phenylboronic acids^a

Entry	R1–X	R2–B(OH)2	Yield^b (%)
a Condition: 1.0 mmol 4-bromoacetophenone, 1.5 mmol boronic acid R2–B(OH)2, 2.0 mmol K2CO3 and Pd@FSM (0.05 mol% Pd) in 5 mL water solution under 80 °C for 10 h.b Isolated yield, mean of three experiments.
19			>99
20			>99
21			>99
22			>99
23			94
24			>99
25			99
26			96
27			91
28			32
29			69
30			48

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Heavy metal pollution to the products, like drugs and food additives, have been an important problem for palladium catalysts due to the difficulty in extraction of homogeneous catalysts from the solution or palladium leaking from heterogeneous catalysts which although could relieve that problem to a certain extent, not to mention the increasing costs.^42–45 Among those heterogeneous catalysts' advantages, easy separation and recyclability are the key solution to this issue, and naturally become the standard in assessing the performance of catalysts. Even though, Soomro once reported the dissolution and redeposition mechanism in the catalyzing process of heterogeneous palladium catalysts, which caused the palladium leaching and decrease of catalysis effcience.^46,47 In this research, the activity of Pd@FSM kept remained even after recycled for five times without the leaking of palladium observed in the product (Table 5). We supposed that the rich electron ligands (alkyne and thiophenemethylamine) and proper cavity size in FSM provided high combing ability for Pd²⁺. The post processing of prepared Pd@FSM by washing with methanol under reflux and difficulties in pulling Pd²⁺ down by other palladium chelating agents could also be good evidences.

Table 5 Recyclability and palladium leaking of Pd@FSM

a nd = not detected.
Run	1	2	3	4	5
Yield (%)	97	97	97	97	96
Leaking of Pd^2+	nd^a	nd	nd	nd	nd

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Stability of one catalyst in the air is another concern. Pd(PPh₃)₄, the most commonly applied homogeneous palladium catalyst, was limited in application due to its sensitivity to oxygen. Therefore, the protection by inert gas during the process is necessary and leads to a raise in cost. In this research, Pd@FSM could achieve high yield using even lower catalyst loading in water at 80 °C without argon protection. In comparison, the catalytic activity of Pd(PPh₃)₄ dropped markedly if the reaction is carried out without deoxygenation, and the PdCl₂ could only achieve 81% yield even with 5 mol% amount. Nevertheless, when the palladium ions were captured by the FSM from the water phase of PdCl₂ catalyzed solution after extracted with chloroform, they showed remarkable activity with only 0.05 mol%. These studies clearly confirmed the advantages of the specific and selective palladium fluorescence probe which could not only anchor the Pd²⁺ to the solid part, but also perform as the ligand assisting the catalytic process with significantly increased activity. Moreover, Pd@FSM could also remain its catalytic performance even after exposed to the air for three months (Table 6), which was unprecedented.⁴⁸

Table 6 Stability and high activity of Pd@FSM compared to the reported catalysts

a Pd@FSM was exposed to air for 3 months before used.
Catalyst	Pd@FSM	Pd@FSM^a	(Ph3P)4Pd	(Ph3P)4Pd	PdCl2	Pd@silica (ref. 11)
Yield (%)	97	97	58	99	81	96
Cat. (mol%)	0.05	0.05	0.1	0.1	5	0.2
Solvent	Pure water	Pure water	DMF	DMF	Water	Organic/water
Atmosphere	Air	Air	Air	Argon	Air	Not mentioned
Recyclability	Yes	Yes	No	No	No	Yes

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4. Conclusions

In summary, we have successfully designed and prepared a novel palladium catalyst by grafting highly selective and sensitive fluorescent sensor onto the surface of MSNs for anchoring Pd²⁺.The as-synthesized catalyst Pd@FSM displayed remarkable catalytic activity towards Suzuki–Miyaura coupling reaction in water with only 0.05 mol% of palladium and good recyclability without palladium leaking. The ultra-stability of the catalyst in the air also proved that the strategy described here provides an alternative choice for the development of green technology in heavy metal catalysis.

Acknowledgements

We thank the financial support from National High Technology Research and Development Program of China (863 Program, 2012AA061601), National Natural Science Foundation of China (Grants 21236002, 21476077), and Shanghai Pujiang Program. W. Zhu is grateful for the support from Chinese Scholarship Council.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra11736h

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