International Scholarly Research NetworkISRN Organic ChemistryVolume 2012, Article ID 928484, 9 pagesdoi:10.5402/2012/928484
Research Article
Chitosan as a Renewable Heterogeneous Catalyst for theKnoevenagel Reaction in Ionic Liquid as Green Solvent
Nam T. S. Phan, Ky K. A. Le, Thien V. Nguyen, and Nhan T. H. Le
Department of Chemical Engineering, Ho Chi Minh City University of Technology, VNU-HCM,268 Ly Thuong Kiet, District 10, Ho Chi Minh City 70350, Vietnam
Correspondence should be addressed to Nam T. S. Phan, [email protected]
Received 3 April 2012; Accepted 14 June 2012
Academic Editors: D. Chaturvedi, F. D’Anna, J. R. Hwu, and L. Novak
The combination of chitosan as a renewable heterogeneous catalyst and ionic liquid as a “green” solvent was employed for theKnoevenagel reaction. The chitosan catalyst was characterized by various techniques, including X-ray powder diffraction (XRD),scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier trans-form infrared spectroscopy (FT-IR), and elemental analysis. Excellent conversions were achieved under mild conditions withoutthe need for an inert atmosphere. There was no contribution from leached active species, and conversion was only being possiblein the presence of the solid catalyst. The chitosan catalyst as well as the ionic liquid solvent could be recovered in essentially pureform after being used in the reaction, and each of them could be reused several times without a significant degradation in efficiency.
1. Introduction
Room temperature ionic liquids have been considered aspotential green alternatives to conventional volatile organicsolvents during the last decade [1–5]. They exhibit severaladvantages such as negligible vapor pressure, excellent abilityto dissolve organic compounds, ease of separation fromproducts, and potential for recycling [6–8]. A variety of ionicliquids have been investigated, generally consisting of saltsof organic cations, for example, tetraalkylammonium, alkyl-pyridinium, 1,3-dialkylimidazolium, tetraalkylphospho-nium [2, 9]. During the past few years, several organic trans-formations have been carried out using ionic liquidsas environmentally benign solvents, such as hydrogena-tion [10], oxidation [11–14], Heck cross-coupling reaction[15, 16], Suzuki reaction [17], Sonogashira reaction [18],Diels-Alder reaction [19], aldol condensation [20], alkyla-tion [21–23], Micheal addition [24], oxa-Michael addi-tion [25], Schmidt reaction [26], ring-closing metathesis[27], esterification reaction [28, 29], and enzyme-catalyzedorganic reactions [30–33]. However, since the applicationof the first ionic liquid sample as solvent for organic trans-formations, research works have been mostly focused on
homogeneous catalysis in ionic liquids. Indeed, reports onorganic reactions using heterogeneous catalysts in ionicliquids as solvents have been very limited in the literature[34–38].
The Knoevenagel condensation between aldehydes orketones with activated methylene compounds is one ofimportant carbon-carbon forming reactions in organic syn-thesis [39, 40]. Conventionally, this reaction is catalyzed byalkali metal hydroxides or by organic bases under homoge-neous conditions with the attendant difficulties in catalystrecovery and recycling [41]. Over the last few years, severalsolid catalysts have been employed for this reaction suchas zeolites exchanged with alkylammonium cations [42],amine-functionalized mesoporous zirconia [43], meso-porous titanosilicate [44], basic MCM-41 silica [45–47],acid-base bifunctional mesoporous MCM-41 silica [48],nanocrytalline ceria-zirconia [49], amine-functionalizedsuperparamagnetic nanoparticles [50], organic-inorganichybrid silica materials [51], and metal-organic frameworks[52, 53]. Chitosan, a biomaterial derived from crustaceanshells, offers the advantages of being renewable and bio-degradable, as well as being relatively cheap and of low toxi-city [54]. It was used as a “green” catalyst support for several
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transitional metal-catalyzed reactions [55–58], and it wasalso used as a solid base catalyst for the aldol condensationreaction [59]. However, all of these processes were stillcarried out in conventional volatile organic solvents. In thispaper, we wish to report the combination of chitosan as arenewable heterogeneous catalyst and ionic liquid as a greensolvent for the Knoevenagel reaction. The chitosan catalyst aswell as the ionic liquid solvent could be recovered in essen-tially pure form after being used in the reaction. Both thecatalyst and the solvent could be reused several times withouta significant degradation in performance.
2. Experimental
2.1. Materials and Instrumentation. All reagents and startingmaterials were obtained commercially from Sigma-Aldrichand Merck, and they were used as received without anyfurther purification unless, otherwise, noted. Chitosan waskindly donated by MKVN Chemicals Company (autho-rized distributor of COGNIS-HENKEL, Germany). Nitrogenphysisorption measurements were conducted using a Quan-tachrome 2200e system. Samples were pretreated by heatingunder vacuum at 150◦C for 3 h. A Netzsch ThermoanalyzerSTA 409 was used for thermogravimetric analysis (TGA)with a heating rate of 10◦C/min from 30 to 900◦C in air. X-ray powder diffraction (XRD) patterns were recorded usinga Cu Kα radiation source on a D8 Advance Bruker powderdiffractometer. Scanning electron microscopy studies wereconducted on a JSM 740 Scanning Electron Microscope(SEM). Transmission electron microscopy studies were per-formed using a JEOL JEM 1400 Transmission ElectronMicroscope (TEM) at 100 kV. The chitosan samples were dis-persed on holey carbon grids for TEM observation. Fouriertransform infrared (FT-IR) spectra were obtained on aBruker TENSOR37 instrument, with samples being dis-persed on potassium bromide pallets. 1H and 13C NMR spec-tra were recorded using a Bruker AV 500 spectrometer. MSspectra were performed on a Thermo Finigan TSQ7000 triplequadrupole.
Gas chromatographic (GC) analyses were performedusing a Shimadzu GC 17-A equipped with a flame ionizationdetector (FID) and an DB-5 column (length = 30 m, innerdiameter = 0.25 mm, and film thickness = 0.25 μm). Thetemperature program for GC analysis heated samples from60 to 200◦C at 20◦C/min and held them at 150◦C for 1 min;then heated them from 150 to 160◦C at 1◦C/min and heldthem at 200◦C for 2 min; then heated them from 200 to300◦C at 50◦C/min and held them at 300◦C for 4 min.Inlet and detector temperatures were set constant at 300◦C.p-Xylene was used as an internal standard to calculatereaction conversions. GC-MS analyses were performed usinga Hewlett Packard GC-MS 5972 with an RTX-5MS col-umn (length = 30 m, inner diameter = 0.25 mm, and filmthickness = 0.5 μm). The temperature program for GC-MSanalysis heated samples from 60 to 280◦C at 10◦C/min andheld them at 280◦C for 2 min. Inlet temperature was set cons-tant at 280◦C. MS spectra were compared with the spectragathered in the NIST library.
2.2. Synthesis of Ionic Liquid. 1-Butyl-3-methylimidazoliumbromide ([BMIM][Br]) was prepared from the reaction ofN-methylimidazole and n-butyl bromide, according to aliterature procedure [60, 61]. A plastic conical flask con-taining a mixture of [BMIM][Br] (25.10 g, 0.115 mol) anddistilled water (50 mL) was immersed in an ice bath for30 min. Hexafluorophosphoric acid (HPF6) 60% (20 mL,0.147 mol) and water (50 mL) were then added dropwise toprevent the temperature from rising significantly. After stir-ring for 12 h at room temperature, the upper acidic aqueouslayer was separated by decantation and the lower ionic liquidphase was washed with cold water (10 × 50 mL) until thewashings were no longer acidic [61]. The ionic liquid wasthen heated under vacuum at 60◦C to remove any excesswater, affording 27.32 g of 1-butyl-3-methylimidazoliumhexafluorophosphate ([BMIM][PF6]) (83% yield).
Using a similar procedure, 1-hexyl-3-methylimidazoliumhexafluorophosphate ([HMIM][PF6]), and 1-octyl-3-meth-ylimidazolium hexafluorophosphate ([OMIM][PF6]) ionicliquids were synthesized in a yield of 83% and 85%, respec-tively.
2.3. Catalytic Studies. The Knoevenagel reaction betweenbenzaldehyde and malononitrile using the chitosan catalystwas carried out in a magnetically stirred round bottom flask.Unless, otherwise, stated, a mixture of chitosan (91 mg g,20 mol%), benzaldehyde (0.2 mL, 1.9 mmol), and p-xylene(0.2 mL) as an internal standard was placed into a 25 mL flaskcontaining 3 mL [BMIM][PF6]. The catalyst concentrationwas calculated with respect to the amino/benzaldehyde molarratio. The reaction vessel was stirred for 30 min to dispersethe chitosan catalyst in the liquid phase. Malononitrile
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Figure 1: SEM micrograph of the chitosan catalyst.
Figure 2: TEM micrograph of the chitosan catalyst.
(0.5 mL, 7.6 mmol) was then added, and the resulting mix-ture was stirred at room temperature for 6 h. Reactionconversion was monitored by withdrawing aliquots from thereaction mixture at different time intervals, quenching withacetone, filtering through a short silica gel pad, analyzingby GC with reference to p-xylene, and further confirmingproduct identity by GC-MS. The reaction mixture waswashed with diethyl ether (5 × 15 mL). The chitosan catalystwas then separated by simple centrifugation, washed withcopious amounts of anhydrous ethanol, dried at 60◦C over-night, and reused if necessary. For the leaching test, a catalyticreaction was stopped after 0.5 h, analyzed by GC, and cen-trifuged to remove the solid catalyst. The reaction solutionwas then stirred for further 5.5 h at room temperature.Reaction progress, if any, was monitored by GC as previouslydescribed.
3. Results and Discussion
3.1. Catalyst Characterization. The chitosan catalyst wascharacterized using a variety of different techniques, includ-ing SEM, TEM, XRD, FT-IR, TGA, nitrogen physisorptionmeasurements, and elemental analysis. The morphologyof the chitosan was observed from the SEM micrograph,exhibiting an uneven surface with straps and shrinkage(Figure 1). As expected, the TEM micrograph revealedthat the chitosan catalyst possessed a nonporous structure
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Figure 3: X-ray powder diffractogram of the chitosan catalyst.
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Figure 4: TGA analysis of the chitosan catalyst.
(Figure 2). No measurable mesoporosity was observed onthe nitrogen physisorption measurements. Indeed, severalapproaches have been developed to achieve a porous struc-ture for chotosan-based materials [62–66]. As inspired bygreen chemistry principles, unmodified chitosan was usedin this research. The crystallinity of the chitosan catalyst wasanalyzed by XRD. Two characteristic peaks [67] at 2θ = 10.5◦
and 2θ = 20.5◦ were observed on the XRD diffractogram ofthe catalyst (Figure 3). These two broad diffraction peaks arenormally considered as typical fingerprints of semicrystallinechitosan [68]. TGA result indicated that the chitosan catalystdegraded in two stages during the heating process from 30to 900◦C in air. The first weight loss of 12.5% was due tothe residual and physisorbed water. The second step startedat around 260◦C, with a decomposition peak temperatureof around 300◦C and a total weight loss of 68% (Figure 4).The thermal stability of the chitosan catalyst was, therefore,in good agreement with the literature [69], ensuring that thecatalyst could be used across a wide temperature range forliquid-phase reactions.
As expected, the FT-IR spectra of the catalyst indicatedcharacteristic bands of chitosan. Broad peaks near 3450 cm−1
were attributed to the O–H stretching vibration of thehydroxyl groups, as well as the inter- and extramolecularhydrogen bonding of chitosan molecules [70]. These broadbands were also indicative of the presence of physisorbedwater in the material. There would also exist the contributionof the –NH2 group for the band in the region of 3000–3400 cm−1, which was overlapped by the O–H stretchingvibration. The weak band near 2922 cm−1 was attributed to
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Chitosan
Ionic liquid
CHO CN
CN
CN
CNH2O+ +
Scheme 1: Knoevenagel reaction of benzaldehyde with malononitrile using the chitosan catalyst.
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Figure 5: FT-IR spectra of the chitosan catalyst.
the C–H stretching vibration. The band near 1646 cm−1 wasassigned to the vibration of amide one groups (Figure 5).Elemental analysis of the catalyst indicated a total nitrogenloading of 5.2 mmol/g. The degree of N-deacetylation of thechitosan (i.e., the average number of D-glucosamine unitsper 100 monomers, expressed as a percentage) was foundto be 87%, as estimated following Block’s method [71]. Theamino group loading in the chitosan catalyst was thereforecalculated to be 4.5 mmol/g. For the reason of simplicity, theamino group loading was used as an elemental tag for thecatalyst. However, it should be noted that not all of theseamino groups were accessible to the reactants during thecourse of the reaction.
3.2. Catalytic Studies. The chitosan catalyst was assessedfor its activity in the Knoevenagel condensation betweenbenzaldehyde and malononitrile to form benzylidene mal-ononitrile as the principal product (Scheme 1). As inspiredby green chemistry principles, it was decided to carry outthe reaction in the [BMIM][PF6] ionic liquid as solvent atroom temperature. The ionic liquid solvent was synthesizedand characterized according to a literature procedure [60,61]. Aliquots were withdrawn from the reaction mixtureat different time intervals and analyzed by GC, showingthe kinetic data during the course of the reaction. Wheninvestigating the chitosan-catalyzed Knoevenagel reaction inionic liquid, there would be several factors that should betaken into consideration. Initial studies addressed the effectof the benzaldehyde : malononitrile molar ratio on reactionconversions, having carried out the reaction at 20 mol% chi-tosan catalyst with molar ratios of 1 : 2, 1 : 3, and 1 : 4, respec-tively. It was found that the Knoevenagel reaction using thereagent molar ratio of 1 : 3 could afford a conversion of 98%after 6 h. More than 99% conversion was achieved after 3 h atthe reagent ratio of 1 : 4. As expected, decreasing the reagent
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Figure 6: Effect of benzaldehyde: malononitrile molar ratio onreaction conversion.
molar ratio to 1 : 2 resulted in a drop in reaction rate, though80% conversion was still observed after 6 h (Figure 6).
With this result in mind, it was then decided to inves-tigate the effect of catalyst concentration on the reactionconversion, having carried out the reaction at 10 mol%,15 mol%, and 20 mol% catalyst, respectively, at the reagentmolar ratio of 1 : 4. As mentioned earlier, the chitosan cata-lyst had a nonporous structure, and, therefore, not all ofamino groups in the polymer chain were accessible to thereactants during the course of the reaction. Indeed, furtherinvestigations would be needed to quantify the real activeamino groups in the Knoevenagel reaction carried out inionic liquid. However, for the reason of simplicity, the aminogroup concentration calculated from the total nitrogenloading and the degree of N-deacetylation was still used asan elemental tag for the chitosan catalyst. It was observedthat quantitative conversion of benzaldehyde was achievedafter 6 h for the reaction using 15 mol% catalyst. As expected,it was observed that increasing the catalyst concentration to20 mol% led to a significant reaction rate enhancement, withmore than 99% conversion being obtained after 3 h. TheKnoevenagel reaction at 10 mol% catalyst concentrationoccurred with slower rate, though 88% conversion was stillafforded after 6 h (Figure 7). Formentin and co-workers pre-viously employed more than one equivalent of KOH catalystfor the homogeneous Knoevenagel reaction between ben-zaldehyde and malononitrile carried out in ionic liquid [72].Tojo and coworkers previously employed 20 mol% glycineas a homogeneous catalyst for the Knoevenagel reaction inionic liquid [73]. Indeed, it was previously reported that con-centration of base catalysts used for the Knoevenagel reaction
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Figure 7: Effect of catalyst concentration on reaction conversion.
could be in the range from less than 1 mol% to 40 mol%,depending on the nature of the catalyst [43, 44, 74, 75]. Thecatalyst concentration used in this study was, therefore, ingood agreement with the literature.
The effect of different solvents on organic transfor-mations using heterogeneous catalysts could normally becrucial, depending on the nature of the catalyst material[50, 76]. Macquarrie and Jakson previously reported that theKnoevenagel reaction using silica-based catalysts could onlyproceed in a limited range of solvents, and the best reactionrate was observed in nonpolar solvents [77]. In contrast,Corma and coworkers previously showed that the reac-tion rate of the Knoevenagel reaction using solid catalystsdecreased significantly in nonpolar solvents, and higherconversions were achieved in more polar solvents [78–80]. Gascon and coworkers reported similar effect, wherepolar solvents favored the reaction rate of the heteroge-neous Knoevenagel condensation, and the reaction occurredwith difficulty in nonpolar solvents [52, 81]. Dong andcoworkers also demonstrated that the Knoevenagel reac-tion using a polymer-based catalyst proceeded readily inethanol [82]. It was, therefore, decided to investigate theeffect of different ionic liquid solvents on the Knoevenagelreaction using the chitosan catalyst. The reaction wascarried out using 20 mol% catalyst in there ionic liquids,including [BMIM][PF6], [HMIM][PF6], and [OMIM][PF6],respectively. It was found that the reaction rate decreasedwith the solvent order: [BMIM][PF6] > [HMIM][PF6] >[OMIM][PF6]. The reaction carried out in [HMIM][PF6]afforded more than 99% conversion after 5 h, while 99%conversion was observed for the reaction in [OMIM][PF6](Figure 8).
For a liquid-phase organic transformation using a solidcatalyst, an important problem that should be taken intoaccount is the possibility that some of active sites coulddissolve into the solution during the course of the reaction.In fact, these leached species might contribute significantlyto the catalytic reaction, and the reaction might not be truly
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Figure 8: Effect of solvent on reaction conversion.
heterogeneous with respect to the substrates and products.[50]. It should be noted that several amines previouslyexhibited high activity in the Knoevenagel reaction [83].However, it was apparent that these homogeneous catalystscould not be recycled and reused for the reaction, and, there-fore, they were practically undesirable. In order to determineif the Knoevenagel reaction using the chitosan catalyst inionic liquid was truly heterogeneous, an experiment wasperformed using a simple centrifugation during the courseof the reaction. After the chitosan catalyst was separated fromthe reaction mixture, if the catalytic reaction continued, thiswould indicate that the active species were from the solutionrather than from the solid catalyst. The organic phase wasseparated from the solid catalyst after 0.5 h reaction time bysimple centrifugation, having used 20 mol% of fresh chitosancatalyst. The reaction solution was then transferred to anew reactor vessel, stirred for an additional 5.5 h at roomtemperature with aliquots being sampled at different timeintervals, and analyzed by GC. It was found that, withinexperimental errors, no further reaction was observed afterthe solid chitosan catalyst was removed from the reactionmixture. The leaching test result indicated that the Knoeve-nagel reaction carried out in ionic liquid could only proceedin the presence of the solid chitosan catalyst, and there wasno contribution from active species dissolved in the reactionsolution during the course of the reaction (Figure 9).
When using solid catalysts for organic transformations,issues that should be considered are the ease of separa-tion as well as the deactivation and reusability of the catalyst.In fact, active lifetimes should be an important character-istic for both heterogeneous and homogeneous catalysts.Ionic liquids have been considered as green solvents notonly due to their nonvolatile nature, minimizing emissionof toxic organic compounds, but also because of their recy-clability. The chitosan catalyst and the ionic liquid solventwere, therefore, investigated for recoverability and reusabilityin the Knoevenagel reaction over five successive runs.The Knoevenagel reaction was carried out using 20 mol%
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With catalystLeaching test
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Figure 9: Leaching test indicated no contribution from homoge-neous catalysis of active species leaching into reaction solution.
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Figure 10: Recycling of both chitosan catalyst and ionic liquidsolvent.
chitosan catalyst in the [BMIM][PF6] ionic liquid at roomtemperature. Aliquots were withdrawn from the reactionmixture at different time intervals and analyzed by GC toobserve the kinetic data during the course of the reaction.After the reaction, product and unreacted starting materialswere separated from the reaction mixture by extraction withdiethyl ether. The mixture of chitosan catalyst and ionicliquid solvent was then washed several times with diethylether and reused in further reaction under identical condi-tions to those of the first run. Interestingly, it was found thatthe catalyst and solvent system could be reused without sig-nificant degradation in catalytic activity. Quantitative reac-tion conversion was still achieved at the fifth run using therecovered catalyst and solvent system (Figure 10).
As mentioned earlier, research works have been mostlyfocused on homogeneous catalysis in ionic liquids, and thenumber of reports covering the heterogeneous catalysis in
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Figure 11: Recycling of the chitosan catalyst with fresh ionic liquidsolvent for each run.
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Figure 12: Recycling of the ionic liquid solvent with fresh chitosancatalyst for each run.
ionic liquids are limited in the literature. Santamarta andcoworkers previously carried out the Knoevenagel reactionusing 20 mol% glycine as a homogeneous catalyst in ionicliquid [73]. The mixture of glycine and ionic liquid could berecycled and reused several times. Formentin and coworkersalso reported the recyclability of the mixture of KOH andionic liquid in the Knoevenagel reaction [72]. Indeed, it waspreviously reported that the mixture of homogeneous cata-lysts and ionic liquid solvents could be recycled and reusedin several organic transformations [3, 6–8]. However, itshould be emphasized that the homogeneous catalyst couldnot be separated from the mixture, and hence it could notbe recovered in essentially pure form after being used in thereaction. We, therefore, decided to investigate the recoveryof the chitosan catalyst from the reaction mixture, and its
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reusability in the ionic liquid-mediated Knoevenagel reac-tion. After the reaction, the catalyst was separated bysimple centrifugation, then washed with copious amountsof anhydrous ethanol to remove any physisorbed reagents,and dried at 60◦C overnight. The recovered chitosan catalystwas reused in further reaction using fresh ionic liquid solventfor each run under identical conditions to those of the firstrun. It was found that the catalyst could be reused withoutsignificant degradation in activity (Figure 11). The recoveryand recyclability of the ionic liquid were also investigated.After each run, the catalyst was separated by simple centrifu-gation, and the ionic liquid was washed several times withdiethyl ether to remove the product and unreacted startingmaterials. The recovered ionic liquid was then reused infurther reaction using fresh chitosan catalyst for each rununder identical conditions to those of the first run. It wasalso observed that the ionic liquid could be reused withoutloss of efficiency (Figure 12).
4. Conclusions
In conclusion, we have demonstrated the application ofchitosan as a renewable solid catalyst for the Knoevenagelcondensation between benzaldehyde with malononitrile toform benzylidene malononitrile as the principal product.The chitosan catalyst was characterized using a variety ofdifferent techniques, including FT-IR, TEM, SEM, XRD,TGA, and elemental analysis. The reaction was carried out inionic liquid as a “green” solvent. Excellent conversions wereachieved under mild conditions without the need for an inertatmosphere. The reaction could only proceed in the presenceof the solid chitosan catalyst, and there was no contributionfrom leached active species in the reaction solution. To thebest of our knowledge, the combination of chitosan asa renewable heterogeneous catalyst and ionic liquid as a“green” solvent for the Knoevenagel reaction was not pre-viously mentioned in the literature. The chitosan catalyst aswell as the ionic liquid solvent could be recovered in essen-tially pure form after being used in the reaction, and theycould be reused several times without a significant degra-dation in efficiency. Current research in our laboratory hasfocused on the application of several heterogeneous catalystsfor a wide range of organic transformations in ionic liquids.
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