Phenylboronic acid functionalized polyacrylonitrile fiber for efficient and green synthesis of bis(indolyl)methane derivatives

Haonan Zhang,Haotian Zhang,Minli Tao,2,*,Wenqin Zhang,2,*

1 Department of Chemistry,School of Science,Tianjin University,Tianjin 300072,China

2 Collaborative Innovation Center of Chemical Science and Engineering (Tianjin),Tianjin 300072,China

Keywords:Polymers Phenylboronic acid Catalyst support Friedel-Crafts alkylation Sustainability

ABSTRACT The use of fiber as a catalyst carrier to construct heterogeneous catalysts with good catalytic activity and recycling performance has received wide attention.In this study,three phenylboronic acid functionalized polyacrylonitrile fiber(PANF)catalysts were synthesized by amination and quaternization.Fourier transform infrared spectroscopy,X-ray diffractometry,scanning electron microscopy,and X-ray photoelectron spectroscopy were used to verify the successful grafting of phenylboronic acid and the structural integrity of the fiber catalyst after recycling.The activity of the catalysts was explored with the Friedel-Crafts alkylation between indole and aromatic aldehydes.The results indicate that the synthesized catalyst(PANp-BAF) in which the phenylboronic acid functional group was linked at the para position,exhibited the highest catalytic activity for the Friedel-Crafts alkylation.The substrate scope experiments confirmed that the catalyst has outstanding catalytic activity for most aromatic aldehydes,especially for those containing moderate electron donating groups.Moreover,the catalyst can be reused eight times in water without significant decrease in its catalytic activity.Further,the scale-up experiment confirmed that the fiber catalyst has a certain potential for industrial application.

1.Introduction

Bis(indolyl)methane derivatives are important organic compounds that are widely present in natural products [1].Owing to their special biological properties,these derivatives have been extensively investigated and applied in medicine,for example,as antihyperlipidemic [2],antitumor [3,4],and antileishmanial [5]agents.To date,one of the most convenient ways to synthesize bis(indolyl)methane derivatives is the Friedel-Crafts alkylation of indoles with aldehydes/ketones catalyzed by Br?nsted or Lewis acids.Many catalysts,such as BiVO4nanoparticles (NPs) [6],Fe3-O4@SiO2supported aza-crown ether complexcation ionic liquids[7],meglumine [8],[bnmim][HSO4] [9],Br2[10],I2[11],and enzymes [12] have high product yields.However,these catalysts also have disadvantages such as high toxicity,low recyclability,and high cost.Therefore,efficient,non-toxic,and recyclable catalysts for the synthesis of indole derivatives are in demand.

Arylboronic acids are extremely weak acids and show almost no Br?nsted acidity when dissolved in water.Since the discovery of the Suzuki(and related)coupling reactions catalyzed by transition metal catalysts,arylboronic acids and arylboronates have attracted much attention as coupling reaction substrates [13,14].However,in contrast to their use as substrates,the use of boronic acids as acid catalysts remains underexplored.To date,reactions catalyzed by phenylboronic acids include the Diels-Alder reaction [15,16],hetero-Michael reaction [17],amide condensation reaction [18-20],and esterification [21,22],with limited reports on the use of phenylboronic acids as catalysts for Friedel-Crafts alkylation reactions,making this an intriguing research area.

In recent years,the development of fiber materials and the investigation of their applications in chemistry has attracted increasing attention,and a large number of fibrous materials with new properties have been reported[23-26].Polyacrylonitrile fiber(PANF),known as ‘‘a(chǎn)rtificial wool”,has a unique appearance,elasticity,and thermostability,as well as other intriguing properties.In particular,PANF contains a large number and high density of cyano and ester groups.These groups can be modified to achieve different functionalities in the surface layers without affecting the integrity of the core of the fiber,which shows unique catalytic properties that other catalyst carriers do not possess.Previously,a range of homogeneous catalysts was successfully immobilized on PANF,includingN-heterocyclic carbene-Au complexes[27],sulfonic acid[28],prolinamide [29],lysine [30],4-dimethylaminopyridine [31],quaternary ammonium salts [32],and phosphoric acid [33].These reports show that PANF is an excellent carrier for heterogeneous catalysts.Thus,in this work,a new type of fiber catalyst containing immobilized phenylboronic acid moieties was prepared.Further,the optimum catalyst was used to catalyze the Friedel-Crafts alkylation of indoles and aromatic aldehydes to produce bis(indolyl)methane derivatives.

2.Materials and Methods

2.1.Reagents and instruments

Commercially available polyacrylonitrile fiber (The molecular weight is 53000-106000,with 93%acrylonitrile,6.5%methyl acrylate and 0.4%-0.5% sodium styrene sulfonate as the monomers,produced by Fushun Petrochemical Corporation of China) was cut into 10 cm segments and stored in a drying oven at 60 °C before use.All organic solvents,amines,aldehydes,indole,and bromomethylphenylboronic acid were commercially obtained from HEOWNS (China).Water is deionized water.

The mass of the fibers and chemicals were measured using an electronic analytical balance BSA124S (Sartorius,Germany).The model of the rotary evaporator is N-1300 (EYELA,Japan).The mechanical properties of the fibers were tested by an electronic single fiber strength tester YG(B)001A (Wenzhou Textile Instrument Company,China).The Fourier transform infrared spectra(FT-IR) were recorded by the AVATAR360 FT-IR spectrometer(Thermo Nicolet,America).The X-ray diffraction (XRD) patterns were recorded by the D/MAX-2500 X-ray diffractometer (Rigaku,Japan).The X-ray photoelectron spectra (XPS) were tested by the ESCALAB-250Xi (ThermoFisher,Britain).The morphology of fibers was recorded by scanning electron microscopy(SEM)using a Hitachi,S4800 or SU5000 (Hitachi,Japan).The1H NMR spectra of different products were tested with the AVANCE III HD400 MHz(Bruker,Germany) with TMS (tetramethylsilane) as the internal standard.

2.2.Fiber catalyst synthesis

2.2.1.Synthesis of PANTAF

To a three-necked flask with a magnetic stirring bar,30.0 ml ofN,N-dimethylethylenediamine,15 ml distilled water,and 1.00 g PANF were added and heated at 115 °C for 4 h.Then,the fibers were removed with a tweezer,placed in a Büchner funnel,and repeatedly washed with distilled water (60 °C) until the filtrate was neutral.The fiber was then dried in a vacuum drying oven(60 °C) overnight to obtain the tertiary-amine-functionalized fiber(PANTAF).

2.2.2.Synthesis of PANp-BAF,PANm-BAF,and PANo-BAF

Three different catalysts were prepared using 4-,3-,or 2-bromomethylphenylboronic acid,denoted PANp-BAF,PANm-BAF,and PANo-BAF,respectively.These catalysts were preparedviathe same procedures.Specifically,to a 50 ml round bottom flask equipped with a magnetic stirring bar,1.00 g of PANTAF,20.0 ml of acetonitrile,and 2.00 g of the corresponding bromomethylphenylboronic acid were added and refluxed with stirring for 2 h.Subsequently,the fibers were sequentially washed with cold ethanol (20 ml × 5) and distilled water (20 ml × 2).Finally,the fibers were dried in a vacuum drying oven (60 °C) for 12 h to a constant mass to obtain the functionalized fibers.

2.3.General catalytic reaction procedure

An aromatic aldehyde (0.5 mmol),indole (1 mmol),2.5 ml of water,and 10% (mol) of the fiber catalyst were added to a 10 ml sealed tube equipped with a magnetic stirring bar and stirred at 80 °C for 5.5 h.After the reaction was complete,the fiber catalyst was removed by suction filtration and washed with ethanol(3 ml × 5) in a Büchner funnel.The filtrates were combined and purified by column chromatography.

3.Results and Discussion

3.1.Preparation and characterization of phenylboronic acid modified fibers

As depicted in Fig.1,the phenylboronic acid modified fiber catalyst was prepared by amination and quaternization.Because of the high reactivity of tertiary amines with benzyl bromide,bromomethylphenylboronic acids were chosen for the reaction with PANTAF to prepare the phenylboronic acid functionalized fibers.Thus,this prevented the residual basic amine groups,which could affect the catalytic performance of the catalyst.

Fig.1.Preparation of the phenylboronic acid functionalized fibers.

The functionality of phenylboronic acid functionalized fibers was calculated by Eq.(1):

Here,Mis the molecular weight of the bromomethylphenylboronic acid,m0is the mass of PANTAF,andmis the mass of the phenylboronic acid functionalized fiber.The calculated values offfor PANp-BAF,PANm-BAF,and PANo-BAF are listed in Table 1.Because the catalytic tests showed that the PANp-BAF was the optimal catalyst(see Section 3.3.1),subsequent research focus on this catalyst.

Table 1Functionality of the phenylboronic acid functionalized fibers

3.2.Characterization of functionalized fibers

3.2.1.Fourier transform infrared spectroscopy

To explore whether the functionalized fibers had been successfully prepared and whether the functional groups of the fibers had been retained after recycling,FT-IR analysis was carried out.There are obvious absorption peaks at 2246 and 1731 cm-1(Fig.2),which correspond to the stretching vibrations of the C≡N and C=O groups in the methoxycarbonyl group,respectively[34].After the first (amination) modification step,a broad absorption band from 3700 to 3100 cm-1appeared,which corresponds to the N-H stretching vibration of the amide group.In addition,a strong peak at 1657 cm-1corresponds to the C=O stretching vibration of the amide group,while the new peak at 1577 cm-1can be attributed to the N-H bending vibration of the amide group.These new peaks demonstrate that the first step of the grafting reaction was successful.After the second step,in which 4-bromomethylphenylboronic acid was grafted onto PANTAF,a new peak appeared at 1373 cm-1,corresponding to the stretching vibration of the B-O bond [35].Lastly,the peak at 825 cm-1is related to the out-of-plane bending vibration of theparasubstituted benzene ring.Based on these results,it can be concluded that the functionalization of the fibers with phenylboronic acids was successful.Furthermore,after the first and eighth cycles of use of the catalyst (Fig.2(d) and (e)),the characteristic peaks remained,demonstrating the stability of the functionalized fibers.

Fig.2.FT-IR spectra of (a) PANF,(b) PANTAF,(c) PANp-BAF,(d) PANp-BAF-1,and (e)PANp-BAF-8.

3.2.2.X-ray diffraction

XRD measurements were used to determine the crystal structure of the fibers.The XRD pattern of PANp-BAF contains an obvious peak at 2θ=17.0° (Fig.3),which is consistent with the strong diffraction of the hexagonal lattice (1 0 0) planes of PANF [36].PANp-BAF also shows a weak peak at 2θ=29.5°,which corresponds to the weak diffraction of the (1 1 0) plane.After the fibers had been used once and eight times,the(1 0 0)and(1 1 0)planes were still present in the XRD patterns of PANp-BAF-1 and PANp-BAF-8,and the peak intensities showed no obvious attenuation.This result suggests that the core part of the fiber was not affected after grafting and reuse,and the crystal structure of functional fiber maintains good integrity.

Fig.3.X-Ray diffraction patterns of(a)PANF,(b)PANTAF,(c)PANp-BAF,(d)PANp-BAF-1,and (e) PANp-BAF-8.

3.2.3.Scanning electron microscopy

SEM was used to visualize the surface morphology of the fibers before and after modification (Fig.4).By comparing the SEM images of PANF,PANTAF,and PANp-BAF,it can be seen that the surface of unmodified PANF is smooth.After the amination and quaternization,the fiber surface became rougher than that of the original fiber,however,the overall structure was not damaged,which confirms the good mechanical strength of the modified fiber.Furthermore,after the first use,PANp-BAF-1 showed a bark-like morphology compared to that of the unused PANp-BAF,but the original morphology of the fiber was retained.After eight cycles of use,the surface of PANp-BAF-8 is significantly rougher than before.This to the magnetic stirring and slight peeling from the surface,which may lead to a slight decline in the catalytic activity of the fibers.

3.2.4.X-ray photoelectron spectroscopy

XPS was employed to ascertain if grafting was successful.Fig.5(a)shows the XPS spectra of PANTAF and PANp-BAF.For PANTAF,the four peaks with binding energies of 286.2,284.8,399.8,and 401.2 eV corresponding to C=O,C-C,C≡N,and O=C-N,respectively [37],suggest thatN,N-dimethylethylenediamine was successfully grafted onto the fibers (Fig.5(b) and (c)).Although some of the groups on the fiber changed upon exposure to amine,the structure did not fundamentally change.After the reaction of PANTAF with 4-bromomethylphenylboronic acid,two peaks with binding energies of 191.4 and 188.3 eV appeared in the B 1s spectrum (Fig.5(e)),which correspond to B-O and B-C,respectively[38-40].In addition,in the Br 3d spectrum (Fig.5(d)),there is a peak at 68.2 eV,which is as a result of the quaternization in the second grafting step [41].All evidence indicates that PANp-BAF has been successfully prepared.

3.2.5.Mechanical properties

The mechanical strength of the fibers is an important factor,which is indicative of the applicability of the fiber catalyst.Therefore,the mechanical properties,specifically,the breaking strengths of the single fibers of PANF,PANp-BAF,PANp-BAF-1,and PANp-BAF-8 were evaluated (Table 2).Compared with that of pristine PANF,the mechanical strengths of PANTAF and PANp-BAF slightly decreased because of the partial transformation of the cyano groups during the modification process.After two-step grafting,the strength retention of PANp-BAF (i.e.,the ratio of the breaking strength of pristine PANF to that of modified PANF) still reached 83%,indicating that the core structure of the fiber remained intact.Furthermore,after a single catalytic cycle,the mechanical strength of the fiber slightly decreased,but still remained at 74%.Moreover,only a slight decrease in the retention rate of PANp-BAF-8 from 74%to 71% was observed,showing that the fibers have good mechanical strength after eight cycles of use.

Fig.4.SEM images of (a) PANF,(b) PANTAF,(c) PANp-BAF,(d) PANp-BAF-1,and (e) PANp-BAF-8.

3.3.Catalytic experiments

3.3.1.Optimization of reaction conditions

The reaction temperature,catalyst dosage,solvent,and a suitable catalyst type for the Friedel-Crafts alkylation of indole and benzaldehyde were optimized (Table 3).In the absence of a catalyst (or in the presence of PANF),no product was detected,indicating that the above reaction is not a spontaneous reaction.Screening for the optimal reaction temperature revealed that the reaction cannot be carried out at room temperature as only a trace amount of product was detected.With the increase of the reaction temperature,the yield increased significantly.After that,the effect of the catalyst amount (5% and 10% (mol)) was tested,and the yield of product slightly decreased when using 5% (mol) catalyst compared to that at 10% (mol).The reaction solvents were also screened and most polar solvents,such as ethanol,methanol,and water,achieved good yields.Finally,10% (mol) catalyst,using ethanol as the solvent,and a temperature of 80 °C for 5.5 h were selected as optimal reaction conditions.

Table 2Mechanical strengths of PANTAF,PANp-BAF,PANp-BAF-1,and PANp-BAF-8

Table 3Condition optimization of Friedel-Crafts alkylation

Fig.5.XPS spectra of(a)PANTAF and PANp-BAF,(b)C 1s spectrum of PANTAF,(c)N 1s spectrum of PANTAF,(d)Br 3d spectrum of PANp-BAF,and(e)B 1s spectrum of PANp-BAF.

Based on this,the steric effects of the quaternary ammonium group and the boronic acid group on the catalytic efficiency were further investigated.As the quaternary ammonium group and the boronic acid group approach each other,the yield of the reaction sharply drops.When PANo-BAF was used as the catalyst in the model reaction,the catalyst loses its catalytic activity on the reaction,this phenomenon is unlike the previous report,in which steric ortho substituted phenylboronic acid exhibited the highest activity[15,16].This may be related to that this model reaction is more sensitive to steric effect.To verify that the boronic acid group played a role of the Lewis acid in the reaction,the fiber was soaked in sodium fluoride solution (0.6 mol·L-1) for 12 h before use.It is well known that F-,as a hard base,has a strong tendency to bind with boron,which will completely destroy the Lewis acidity of boron but enhance its Br?nsted acidity.As expected,the pretreated fiber completely did not show any catalytic activity.Apparently,the hard base F-occupied the Lewis center of boron and quenched its catalytic activity,this demonstrated that boronic acid group played a crucial role and acted as a Lewis acid catalytic site in the reaction.To further verify this point,the Pyridine-IR spectrum of PANp-BAF was obtained (Fig.S1).The obvious peak shown at 1450 cm-1confirmed that the fiber shows Lewis acidity.

3.3.2.Substrate scope

To further explore the applicability range of the reaction on substrates,different aromatic aldehydes were screened for the synthesis of bis(indolyl)methanes with PANp-BAF as the catalyst,moderate to high yields were obtained (Table 4).Among them,aromatic aldehydes with moderate electron-donating groups(EDGs) to weak electron-withdrawing groups (EWGs),i.e.,H,Cl,Br,hydroxy,methyl and methoxyl (1a-1g),perfectly fit the PANp-BAF catalyzed reactions.It is well known that aromatic aldehydes containing EWGs are more reactive,such as in the Knoevenagel and Henry reactions [30,33,42].This reversed activity sequence strongly suggests that the PANp-BAF catalysis undergoes a different mechanism.The rate-determining step in the reaction may be the coordination process of the carbonyl O atom with the empty 2p orbital of the B atom in the boronic group,which activates the carbonyl group.This is consistent with the observation that aromatics with EWGs,such as trifluoromethyl(1i)and nitro(1j),hindered thereaction,especiallyp-nitrobenzaldehyde.It demonstrated bad activity and poor yield (44%).However,it should be noted that easier substrate coordination with the boronic acid group does not ensure a better yield.Although the combination process with the boronic acid group is easier when the substrate has greater electron cloud density,the stable tendency of the formed carbocation intermediate A (see Fig.6) in turn hinders the subsequent nucleophilic attack,which also explains why moderate yields were obtained when 4-dimethylaminobenzaldehyde,3-indole formaldehyde,and furfural (1e,1 k,and 1 l) were used as substrates.

Table 4PANp-BAF catalyzed Friedel-Crafts alkylation of various substrates

Fig.6.Plausible mechanism for the PANp-BAF catalyzed Friedel-Crafts alkylation.

3.3.3.Recyclability

Recyclability is a crucial factor in catalyst evaluation.There cyclability of the catalyst PANp-BAF during the Friedel-Crafts alkylation was assessed on the synthesis of 3,3′-(phenylmethylene)bi s(1H-indole) through the reaction of indole and benzaldehyde as the model reaction,ethanol was used as the solvent,as it was the solvent of choice under optimized conditions (Section 3.3.1).However,the catalytic activity of the fiber catalyst started to decline after two cycles (Fig.7).Then,methanol,which exhibits a catalytic activity similar to that of ethanol,was employed and its recycling effect was investigated.However,the catalytic activity of the fiber catalyst started to decline from the fourth use.Considering the high reaction temperature,ethanol and methanol may have started to react with the hydroxyl group on the phenylboronic acid to form boronic acid esters during the reaction,which increases the steric hindrance and decreases the catalytic activity(Fig.S2).Finally,water was selected as the solvent for subsequent recyclability tests because it does not react with phenylboronic acid.Although the yield with water was slightly lower than that with ethanol,greater catalytic activity than with ethanol was observed after eight cycles of use.

Fig.7.The reusability of the PANp-BAF in methanol,ethanol,and water.

3.3.4.Gram-scale synthesis

To manifest the practical application of this fiber catalyst,the Friedel-Crafts reaction was carried out on a gram scale test for benzaldehyde (Fig.8).The benzaldehyde loading was increased to 10 mmol,and the corresponding product 3,3′-(phenylmethy lene)bis(1H-indole) was successfully obtained with comparable good yields(97%).The result suggests that PANp-BAF is a promising heterogeneous catalyst with certain utilization potential in industrial production.

Fig.8.Gram-scale synthetic promoted by the PANp-BAF.

3.3.5.Reaction mechanism

In the arylboronic acid,the boron is an electron-deficient center,its empty 2p orbital can accommodate electron pair and acts as a hard Lewis acid.As mentioned above,F-is a hard base,which has a strong tendency to coordinate with the electron-deficient boron atom.A reasonable mechanism is proposed (Fig.6) based on the results obtained,which are:(i)the NaF pretreated fiber catalyst completely lost its catalytic activity,and(ii)aromatic aldehydes with moderate electron-donating substituents are conducive for the reaction.The phenylboronic acid group first coordinates with the carbonyl group in the aromatic aldehyde to form a carbocation intermediate A,and the carbonyl carbon is activated to nucleophile.Then,A captures the indoleviaa hydrogen bond to give a H-bond associated complex B.In the next step,the C3 of indole carries out a nucleophilic attack on the carbocation and loses one molecule of water to generate intermediate C,which reacts with another molecule of indoleviaa H-bond associated complex D to form E,and liberates the catalyst.The catalyst then enters the next cycle.For the aromatic aldehydes with moderate to strong EDGs,the formation of the cationic intermediate A is the rate determining step.The more easily the aldehyde coordinates with the boron Lewis acid center,the higher yield will achieve.Owing to the strong electron deficiency,4-nitrobenzaldehyde is the most difficult substrate to coordinate with the boron Lewis acid center,therefore,its yield is poor (case 1j).For those highly electron rich substrates,the carbocation intermediate A is too stable,which hinders the nucleophilic attack of the indole.Therefore,the rate determining step changes into the formation of C.

4.Conclusions

In this work,three new phenylboronic acid functionalized fibers were successfully prepared.The fiber catalyst PANp-BAF with a para immobilized phenylboronic acid exhibited the highest activity for the Friedel-Crafts reaction between indole and aromatic aldehyde,where moderate to high yields were obtained.The scope expansion experiments indicate that this catalyst favors aromatic aldehydes that have moderate electron-donating to weak EWGs groups (Cl,Br,H,hydroxy,methyl and methoxyl)attached on them.A reasonable mechanism has been proposed to elucidate the different substrate activities.The rate determining step for those highly electron-rich aromatic aldehydes changes from the formation of cationic intermediate to the nucleophilic attack step.In regard to its practical application,the fiber catalyst PANp-BAF can be easily separated from the reaction system and reused eight times without significant yield loss in water.The gram-scale production also achieves an excellent yield of 97%.In brief,PANp-BAF requires a low catalyst dosage,and exhibits a high catalytic activity,nontoxicity,and an excellent scale-up performance.These characteristics pave the way for the industrial production of important indolecontaining compounds using fiber supported heterogenous catalyst which is greener,safer,and only mildly toxic.

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

This work was financially supported by the National Natural Science Foundation of China (21777111).

Supplementary Material

Supplementary data to this article can be found online at https://doi.org/10.1016/j.cjche.2021.08.029.