Highly reactive and reusable heterogeneous activated carbons-based palladium catalysts for Suzuki-Miyaura reaction

Yifan Jiang,Bingqi Xie,Jisong Zhang

State Key Lab of Chemical Engineering,Department of Chemical Engineering,Tsinghua University,Beijing 100084,China

Keywords:Suzuki-Miyaura reaction Heterogeneous palladium catalysts Activated carbon Thiol-and amino-functionalization Catalyst support Packed bed

ABSTRACT Suzuki-Miyaura reaction of aryl halides with phenylboronic acid using a heterogeneous palladium catalyst based on activated carbons(AC)was systematically investigated in this work.Two different reaction modes (batch procedure and continuous-flow procedure) were used to study the variations of reaction processing.The heterogeneous catalysts presented excellent reactivity and recyclability for iodobenzene and bromobenzene substrates in batch mode,which can be attributed to stabilization of Pd nanoparticles by the thiol and amino groups on the AC supports.However,significant dehalogenation in the reaction mixture and Pd leaching from the heterogeneous catalysts were observed in continuous-flow mode.This unique phenomenon in continuous-flow mode resulted in a dramatic decline in reaction selectivity and durability of heterogeneous catalysts comparing with that of batch mode.In addition,the heterogeneous Pd catalysts with thiol-and amino-modified AC supports exhibited different reactivity and durability in batch and continuous-flow mode owing to the difference of interaction between Pd species and AC supports.

1.Introduction

There is no doubt that the transition-metal-catalyzed crosscoupling reaction is the most attractive procedure to construct the C-C bond in organic chemistry [1].Suzuki-Miyaura reaction has gradually become the most popular coupling reaction over the past decades,due to high functional group tolerance and water stability of organic boric acid in this reaction[2,3].The precious Pd component is commonly used as a catalytic active center for this reaction.In this context,the homogeneous Pd catalyst with phosphine ligands (e.g.,triphenylphosphine,PPh3) is a common catalytic system for Suzuki-Miyaura reaction [4,5].However,shortcomings in existing homogeneous Pd catalysts,e.g.,the complicated separation and recycling of the noble Pd component from reaction products,have hindered the development of these homogeneous catalysts [6,7].On the other hand,the heterogeneous Pd catalysts with excellent reaction activity and durability could readily address these drawbacks by the filtration after reaction.

Immobilizing Pd species onto diverse solid materials,such as silica [8],metal oxides [9],resins [10],metal-organic frameworks[11],and carbon [12] is a common approach for designing heterogeneous Pd catalysts.In particular,for these Pd supported catalysts,ligands play a predominantly large role for stabilizing Pd species when ligands participated in the reaction,which is related to the usually accepted mechanism for Suzuki-Miyaura reaction.During the transformation process of Suzuki-Miyaura reaction,the quasi-homogeneous reaction pathway demonstrates that the Pd0species are transformed into soluble PdIIspecies;when this reaction is over,the Pd0species can redeposit onto the solid materials.The solid support in heterogeneous catalysts is actually regarded as a ‘‘reservoir” of active Pd species [13].This reservoir constantly releases and captures the active Pd species during the transformation process of Suzuki-Miyaura reaction.Therefore,porous solid materials can be conducive to re-adsorb the Pd species onto the support phase of heterogeneous catalysts.In addition,appropriate selection of ligand immobilized on supports,has beneficial effect in capturing Pd species sufficiently fast from reaction mixture and improving stability of heterogeneous catalysts [14].

Compared with the classical batch process,continuous-flow procedure has already be used for Suzuki-Miyaura reaction for process intensification.In this mode,the heterogeneous catalysts are filled in a packed-bed reactor and the reaction mixture pass through the reactor at the proper flow rate [15].Therefore,as a flow chemistry technique,it has shown certain advantages including simplified separation step for catalysts,integrated multistep synthesis,improved safety,and rapid mass transfer [16,17].However,the Pd leaching from heterogeneous catalyst in the continuous-flow procedure is more significant than that in the batch procedure [18].This effect eventually leads to deactivation of the heterogeneous catalysts and contamination of the target product.In this context,there are two suitable approaches to alleviate the problem of Pd leaching in Suzuki-Miyaura reaction: (i)designing the leaching-resistant heterogeneous catalysts based on the porous solid support;(ii) developing the ‘‘release and capture”technologies for recycling of the precious metal.For the porous solid support,activated carbon(AC)may be a suitable selection owing to its surface chemical characteristics,great attrition resistance,and low-cost[19].Although ligand-free AC support has been used for cross-coupling reaction,they usually exhibit obvious Pd leaching especially in the continuous-flow procedure,owing to the absence of ligands on the support.Modification of AC surface with various ligands is a promising application for catalytic reaction.For example,the Mn catalysts modified with salen or Schiff base complexes based on AC as support present high efficiency and selectivity for the epoxidation reaction [20,21].In addition,Pd species stabilized by amino-or thiol-functionalized groups have been used for dehydrogenation reaction,in which organic groups improves the stability of heterogeneous catalysts by inhibiting the aggregation of Pd species [22,23].However,there are few investigations of surface-modified AC catalysts for cross-coupling reactions,especially for Suzuki-Miyaura reaction in continuousflow mode.

In this study,we prepared two heterogeneous Pd/AC catalysts functionalized with thiol and amino groups as the Pd species reservoir for Suzuki-Miyaura reaction.A detailed comparison of batch and continuous-flow procedures was shown in order to explore the feasibility of practical applications using the heterogeneous Pd/AC catalysts for Suzuki-Miyaura reaction in the future.The lifetime of the two heterogeneous Pd/AC catalysts was studied in a packed-bed reactor.In addition,the discrepancy of catalytic activity between the two heterogeneous Pd/AC catalysts for Suzuki-Miyaura reaction is discussed in detail.

2.Experimental

2.1.Materials

The nitric acid(HNO3,65%-68%),methylbenzene(C7H8,99.9%),and ethanol (EtOH,99.7%) was purchased from Sinopharm Chemical Reagent Co.,Ltd;the palladium chloride (PdCl2,99.9%) was purchased from Shanghai Jiuling Chemical Co.,Ltd;the AC materials,3-aminopropyl trimethoxysilane (APTMS,99%),3-mercaptopropyl trimethoxysilane (MPTMS,99%),phenylboronic acid (C6H7BO2,99%),potassium carbonate (K2CO3,99%),bromobenzene (C6H5Br,99%),iodobenzene (C6H5I,98%),chlorobenzene (C6H5Cl,99%),4′-bromoacetophenone (C8H7BrO,99%),4-bromophenol (C6H5BrO,99%),and 4-bromoaniline (C6H6BrN,99%)was purchased from Bide Pharmatech Ltd.All materials were used as received without further purification.

2.2.Catalyst preparation

The AC was refluxed with a 40% (mass) HNO3solution for 6 h.The oxidized AC obtained was washed using distilled water until pH=6-7 and dried in an oven at 80°C for 24 h.Then,the oxidized AC(3.0 g) was added to a solution containing 0.005 mol of APTMS or MPTMS in 40 ml of toluene,respectively.The mixture was refluxed at 60 °C for 24 h.The solid was filtered and washed with EtOH.The SH/AC and NH2/AC support were obtained after drying in an oven at 60 °C for 6 h.Afterwards,the SH/AC and NH2/AC support were added to a PdCl2(0.035 mol.L-1) solution,respectively.The mixture was stirred at room temperature for 24 h,then filtered and washed with distilled water.Finally,the SH-Pd/AC and NH2-Pd/AC heterogeneous catalysts were obtained after drying in an oven at 60 °C for 6 h.

2.3.Suzuki-Miyaura reaction

In batch experiments,the SH-Pd/AC or NH2-Pd/AC catalysts(40 mg),substrate (1 mmol),phenylboronic acid (1.5 mmol),and K2CO3(2 mmol)were mixed into 20 ml of EtOH-H2O(1:1,volume ratio).The above mixture was refluxed at given temperature (e.g.,80°C)for a predetermined time(e.g.,1 h)under inert atmosphere.Appropriate amount of reaction mixture was diluted with EtOH and filtered,then was analyzed with gas chromatography(GC,Agilent,HP-5,capillary column,FID detector).In addition,the solid catalyst was washed with distilled water and EtOH,and reused in the next batch experiment.

In continuous-flow experiments,the SH-Pd/AC or NH2-Pd/AC catalysts (1 g) were filled in a stainless steel column(100 mm × 3.18 mm ID) as shown in Fig.1.The mixture of EtOH-H2O(1:1,volume ratio)was first pumped through the stainless steel column.Then,a freshly prepared solution containing substrate (0.05 mol.L-1),phenylboronic acid (1.5 equivalent) and K2CO3(2 equivalent) in EtOH-H2O (1:1,volume ratio) passed through the system at given temperature and flow rate.The outflowing solution was collected,and then analyzed by GC-FID system (GC,Agilent,HP-5,capillary column,FID detector).After determined time on stream,the packed-bed reactor was flushed with EtOH-H2O solution (1:1,volume ratio).

Fig.1.Schematic representation of the continuous-flow experiments.

2.4.Materials characterization

The elemental analysis was carried out by vario EL III.The composition analysis was carried out by inductively coupled plasma optical emission spectrometry (ICP-OES,Varian 720) and X-ray photoelectron spectroscopy (XPS,ThermoFischer,ESCALAB 250Xi,Al Kα,hv=1486.6 eV).Chemical bonding information was analyzed with Fourier-transform infrared spectroscopy(FT-IR,Thermo IS50).The catalyst morphologies were characterized with transmission electron microscopy (TEM,FEI Talos 200X,200 kV).

3.Results and Discussion

3.1.Characterization of the catalysts

The results obtained from the elemental analysis of support materials suggest the significant increase of S and N content in AC due to the successful grafting of thiol and amino groups.The functionalization of AC leaded to an approximate loading of 0.93 mmol.g-1of MPTMS and 0.77 mmol.g-1of APTMS onto AC support,respectively (Fig.2(a)).Moreover,Fig.2(b) shows the remarkable features for the modified AC in FT-IR spectroscopy,such as Si-O-Si stretching vibrations (1126 cm-1) and Si-OH stretching vibrations (900 cm-1) [14].These features also confirm the successful grafting of amino and thiol groups to the AC support.

Fig.2.(a) Elemental analysis of the pristine and modified AC support.(b) FT-IR spectra of pristine and modified AC materials.

As shown in Fig.3(a)-(b),the noticeable S 2p XPS peaks for SHPd/AC at 163.8 eV and N 1s XPS peaks for NH2-Pd/AC at 400.4 eV can be attributed to the thiol and amino groups on the AC,respectively.The chemical state of Pd species in the SH-Pd/AC and NH2-Pd/AC catalysts was determined by the XPS spectra.For the SH-Pd/AC catalysts,two major peaks at 337.8 and 343.1 eV were observed,which can be explained by the Pd2+ion bounded to sulfur atom (Fig.3(c)).The Pd2+binding energies for the NH2-Pd/AC catalysts shift towards higher binding energies (338.2 and 343.5 eV)compared with that of the SH-Pd/AC catalysts.This slight variation in binding energy might be due to difference of interaction between Pd species and support.In addition,the Pd loading was measured to be 3.48% (mass) and 2.38% (mass) for the SHPd/AC catalysts and NH2-Pd/AC catalysts by the ICP-OES analysis,respectively.

Fig.3.XPS spectra for SH-Pd/AC catalysts ((a),(c)) and NH2-Pd/AC catalysts ((b),(d)).

3.2.Batch experiments

The catalytic reactivity of prepared SH-Pd/AC and NH2-Pd/AC catalysts were examined for Suzuki-Miyaura reaction between aryl halides and phenylboronic acid(Table 1).As expected,the high reactive iodobenzene led to an excellent yield of biphenyl using SH-Pd/AC and NH2-Pd/AC catalysts.However,the two catalysts exhibited inferior catalytic reactivity for the less reactive chlorobenzene even if expanding the reaction time to 5 h.In addition,for moderately reactive aryl bromides,NH2-Pd/AC catalysts led to higher yield than that of SH-Pd/AC catalysts under the same reaction conditions.The electron-withdrawing (COCH3) substituents in favor of the oxidative addition process,achieving high yield of the substrate.However,for the electron-donating (OH,NH2) substituents,the relatively low selectivity was observed within 1 h of reaction.

Table 1 Suzuki-Miyaura reactions catalyzed by the SH-Pd/AC and NH2-Pd/AC catalysts under batch conditions

To further reveal the difference in catalytic performance between the SH-Pd/AC and NH2-Pd/AC catalysts,the Suzuki-Miyaura reaction of bromobenzene with phenylboronic acid was selected as a model for batch experiments.Fig.4(a) shows the conversion versus reaction time over SH-Pd/AC and NH2-Pd/AC catalysts under the same conditions.As expected,NH2-Pd/AC catalysts exhibited higher reaction rate than that of SH-Pd/AC catalysts,which may be related to the lower interaction between support and PdIIion.Because the interaction between S atoms and PdIIion is stronger than that between N atoms and PdIIion,the difference of interaction may results in different reactivity of heterogeneous catalysts for Suzuki-Miyaura reaction [22,24].The thiolfunctionalized supports can also be used as selective poisons of active Pd species through excessive coordination,which may lead to partial deactivation of heterogeneous catalysts [25,26].In addition,we investigated the effect of temperature on the catalytic reactivity of the two catalysts in batch experiments (Fig.4(b)).The lower temperature (e.g.,40 °C) was unfavorable for catalytic reaction in batch process.The reusability of heterogeneous catalysts is a critical factor considered for their practical application.Considering the reaction rate of SH-Pd/AC catalysts,the reaction time was prolonged to 3 h in reusability test.Fig.4(c) shows the results of reusability test over SH-Pd/AC and NH2-Pd/AC catalysts in Suzuki-Miyaura reaction.Both catalysts presented high stability without significant performance deterioration in batch procedures within 8 cycles.In addition,TEM was used to investigate the morphology of fresh and recovered Pd catalysts.As shown in Fig.5(a)and(b),no evident Pd nanoparticles or nanoclusters were observed for fresh SH-Pd/AC and NH2-Pd/AC catalyst.However,for the recycled catalyst,slight agglomeration of Pd species can be detected after 8 recycles (Fig.5(c) and (d)).This observation suggests that thiol and amino-modified AC could effectively inhibit the formation of Pd nanoparticles or nanoclusters,and promote the stability or recyclability of heterogeneous Pd catalysts.

Fig.4.(a)Conversion of bromobenzene versus time over SH-Pd/AC and NH2-Pd/AC catalysts at 80°C.(b)The effect of temperature on the catalytic reactivity of SH-Pd/AC and NH2-Pd/AC catalysts for 1 h.(c) Reusability test of SH-Pd/AC and NH2-Pd/AC catalysts at 80 °C for 3 h.

3.3.Continuous-flow processing using the heterogeneous catalysts

To better understand the difference in cross-coupling reactions between batch and continuous-flow processes,the Suzuki-Miyaura reaction of bromobenzene with phenylboronic acid was chosen as a model in this context.As is known to all,the variation of flow rate can lead to a remarkable impact on the conversion of bromobenzene in flow experiments.As can be seen from Table 2,when the flow rate was increased from 0.2 to 0.8 ml.min-1,the residence time was reduced from about 1 min to 0.26 min.The conversion of bromobenzene dropped from 100% to 96.12% when using the SH-Pd/AC catalysts at 80 °C.In addition,the temperature parameters in flow process also notably affects the conversion of bromobenzene in Suzuki-Miyaura reaction.With the drop of temperature,the conversion of bromobenzene decreased rapidly when using the SH-Pd/AC catalysts at the same flow rate (Table 2,entries 2,4,5 and 6).This also accords with the results obtained in batch experiments.However,when we examined the catalytic performance of the NH2-Pd/AC catalysts in flow experiments,one unanticipated finding was that the full conversion of bromobenzene can not be accomplished at 80 °C at a flow rate of 0.5 ml.min-1.In this context,lower conversions were observed even when the flow rate was reduced to 0.2 ml.min-1(Table 2,entries 1 and 2).Contrary to expectations,the temperature parameter resulted in a prominent difference of catalytic performance between SH-Pd/AC and NH2-Pd/AC catalysts in continuous-flow experiments.Lower temperature in continuous-flow process instead achieved higher conversion of bromobenzene when using the NH2-Pd/AC catalysts (Table 2,entries 2,4,5 and 6).An explanation for these results may be the high Pd leaching in the NH2-Pd/AC catalysts.Higher temperature was expected to release more activated Pd species from the AC support.After the reaction,however,more Pd0species may aggregate into the Pd nanoparticles,which usually leads to the reduction of catalysts activity.In addition,in a shorter retention time,the amino-functionalized AC did not have ample time to capture the Pd species in solution back to the AC supports,which led to a large amount of Pd flowing out of the catalyst cartridge outlet with the reaction mixture.ICP-OES analyses show that the Pd mass concentrations in the reaction mixture were 1×10-6and 1×10-7at 80°C and 25 °C,respectively,when the NH2-Pd/AC catalyst was used at the same flow rate in the flow experiment.In contrast,for SH-Pd/AC catalysts,high temperature was required to minimize the energy barrier for oxidative addition owing to the strong interaction between S atom and Pd atom.Therefore,when the SH-Pd/AC catalyst was used at 80 °C at the same flow rate,only 5×10-7of Pd species in the reaction mixture was determined by ICP-OES.

Table 2 Suzuki-Miyaura reactions catalyzed by the SH-Pd/AC and NH2-Pd/AC catalysts under continuous-flow conditions

Another interesting finding in Table 2 was that a great deal of dehalogenation byproducts under continuous-flow conditions appeared in the reaction mixture compared to the batch experiments.Fig.6 displays the reaction conversion over time for the continuous-flow reaction catalyzed by SH-Pd/AC and NH2-Pd/AC catalysts.The variations of substrate (bromobenzene),product(biphenyl),and by-product (benzene and methylbenzene) in the continuous-flow process could be clearly observed in the Fig.6.In the case of SH-Pd/AC catalysts,complete conversion was reached within a residence time of about 0.4 min,as shown in Fig.6(a).However,the occurrence of about 55% benzene in the reaction mixture resulted in the low selectivity in continuousflow mode.The amount used of heterogeneous catalyst in continuous-flow mode is 25 times that in batch mode (1 gversus0.04 g),which always bring about the high local concentrations of active Pd species in continuous-flow experiment.In this case,the ratio of ArPdII(i.e.,Ar-Pd-X) species/ phenylboronic acid in the flow experiments can be increased through the (quasi)homogeneous pathways.Therefore,some ArPdIIspecies were not combine with the partner (phenylboronic acid),and can be reduced to benzene.The hydrogen source for dehalogenation may be water added to the reaction system.In addition,the dehalogenation sidereaction may also occur heterogeneously on the surface of supported Pd metal particles [27,28].Compared with the SH-Pd/AC catalysts,the NH2-Pd/AC catalysts exhibited relative high selectivity (Fig.6(b)).Although full conversion of substrate was not obtained under current reaction conditions,the mild conditions(i.e.,room temperature) may be an advantage.In addition,several different substrates were tested under continuous-flow conditions,and obvious dehalogenation still existed (Table 3).Similar to the batch mode,the transformation of electron-donating substituents was troublesome in continuous-flow owing to their lower reactivity.

Table 3 Substrate conversion using the SH-Pd/AC and NH2-Pd/AC catalysts under continuous-flow conditions

Fig.6.Conversion profiles catalyzed by SH-Pd/AC catalysts (a) at 80 °C and NH2-Pd/AC catalysts (b) at 25 °C and 0.5 ml.min-1 (Reaction conditions: 0.05 mol.L-1 bromobenzene in EtOH-H2O (1:1,volume ratio),1.5 equivalent of phenylboronic acid,2 equivalent of K2CO3).

When continuous-flow experiments are operated for a long time,the catalytic activity of heterogeneous catalysts generally drops dramatically due to the continuous Pd leaching.With this in mind,a long-run(24 h)experiment was conducted to determine the stability of SH-Pd/AC and NH2-Pd/AC catalysts in a continuousflow process.As shown in Table 4,the SH-Pd/AC catalyst system maintained a high substrate conversion during the first ten hours of continuous operation.However,when the system was operated for 24 h,we observed the significate drop of substrate conversion.For the NH2-Pd/AC catalyst,after 24 h working time,dropped markedly to a conversion of ＜50%,indicating that the heterogeneous catalysts were rapidly inactivated during reaction.These results demonstrate that durability of SH-Pd/AC catalyst is better than that of the NH2-Pd/AC catalyst in continuous-flow conditions because of the strong interaction between S atom and PdIIion.

Table 4 Durability of the SH-Pd/AC and NH2-Pd/AC catalysts under continuous-flow conditions

The SH-Pd/AC catalyst and NH2-Pd/AC catalyst present better reactivity and durability compared with other ligand-free catalysts in continuous-flow conditions.For example,ligand-free Pd/monolith catalyst only process 1 mmol substrate(4′-bromoacetophenone)within 24 h,such low catalytic efficiency is obviously contrary to the high efficiency principle of flow chemistry [29].In addition,the PPh3-Pd/SiO2catalyst retain relatively high conversion of substrate within only 4 recycling of catalyst in batch mode [30].One key factor maybe the low loading of PPh3onto SiO2(0.18 mmol.g-1).It is difficult for PPh3to get into the micropores of SiO2due to the large size of PPh3,therefore the most PPh3-Pd complex are kept on the surface of support.The low loading of PPh3on support cannot efficiently capture the Pd species in the solution,which leads to the performance deterioration of the PPh3-Pd/SiO2catalyst after 4 recycling of the catalyst.

4.Conclusions

Recycling of heterogeneous Pd catalysts is more efficient than that of homogeneous Pd catalysts for Suzuki-Miyaura reaction.Two heterogeneous Pd catalysts with thiol-and amino-modified AC supports were synthesized for Suzuki-Miyaura reaction.Compared with the SH-Pd/AC catalysts,the NH2-Pd/AC catalysts exhibited better reactivity in batch and continuous-flow mode.However,the SH-Pd/AC catalysts presented superior durability with respect to the NH2-Pd/AC catalysts especially in continuousflow mode.These diversities caused in reactivity and durability during this reaction can be attributed to the interaction between support and Pd species.Therefore,the selection of suitable ligands for covalent grafting on support should be considered carefully in the future.In addition,incorporation of tailor-made ligands to the AC or other porous materials for Suzuki-Miyaura reaction in batch and continuous-flow mode are currently in progress.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We gratefully acknowledge the support of the National Natural Science Foundation of China(20222809,21978146)and Tsinghua-Foshan Innovation Special Fund (2021THFS0214) in this work.