DOI: 10.1002/cctc.

201200111

On the Mechanism of Lewis Acid Catalyzed Glucose Transformations in Ionic Liquids

Evgeny A. Pidko,* Volkan Degirmenci, and Emiel J. M. Hensen*[a]
A complementary computational and experimental study of the reactivity of Lewis acidic CrCl2, CuCl2 and FeCl2 catalysts towards glucose activation in dialkylimidazolium chloride ionic liquids is performed. The selective dehydration of glucose to 5hydroxymethylfurfural (HMF) proceeds through the intermediate formation of fructose. Although chromium(II) and copper(II) chlorides are able to dehydrate fructose with high HMF selectivity, reasonable HMF yields from glucose are only obtained with CrCl2 as the catalyst. Glucose conversion by CuCl2 is not selective, while FeCl2 catalyst does not activate sugar molecules. These differences in reactivity are rationalized on the basis of in situ X-ray absorption spectroscopy measurements and the results of density functional theory calculations. The reactivity in glucose dehydration and HMF selectivity are determined by the behavior of the ionic liquid-mediated Lewis acid catalysts towards the initial activation of the sugar molecules. The formation of a coordination complex between the Lewis acidic Cr2 + center and glucose directs glucose transformation into fructose. For Cu2 + the direct coordination of sugar to the copper(II) chloride complex is unfavorable. Glucose deprotonation by a mobile Cl ligand in the CuCl42 complex initiates the nonselective conversion. In the course of the reaction the Cu2 + ions are reduced to Cu + . Both paths are prohibited for the FeCl2 catalyst.

Introduction
Declining fossil fuel resources and growing concerns about climate change are the main drivers for intensive studies both in industry and academia aiming at the development of new and improved ways to utilize renewable resources for an adequate and sustainable supply of energy and chemicals.[1, 2] Biomass is considered as one of the most promising renewable and carbon-neutral feedstocks for the production of bulk chemicals and transportation fuels. Carbohydrates are major constituents of lignocellulosic biomass,[3] which can be isolated from lignocellulose by conventional acid hydrolysis[4] or by more recently developed methodologies involving the use of ionic liquids.[5] One of the attractive routes to the valorization of carbohydrates involves their conversion to 5-hydroxymethylfurfural (HMF). HMF is considered a potential platform chemical, which can be used as a starting material for a wide range of chemical processes such as production of high-value polymers, solvents, pharmaceuticals and biofuels.[1, 2] HMF can be readily produced from the dehydration of fructose by a wide variety of homogeneous and heterogeneous catalysts ranging from mineral acids[6, 7] and modified mesoporous silicas[8] to metal-organic frameworks.[9] Brnsted and Lewis acids are effective catalysts in such different reaction media as ionic liquids,[10] organic solvents,[11] and biphasic systems.[7] Compared to fructose, the selective conversion of glucose, which is the most abundant monosaccharide in biomass, is much more difficult. This is probably associated with the higher stability of the glucopyranose ring structure. Typically, dehydration of glucose over Brnsted and Lewis acid catalysts efficient for fructose dehydration result in very low HMF yields. In their pioneering work, Zhang and co-workers[12] demonstratChemCatChem 2012, 4, 1263 1271

ed a significant HMF yield of 70 % from glucose by use of CrCl2 in 1-ethyl-3-methylimidazolium chloride (EMImCl) ionic liquid. This work was followed by many reports about the use of ionic liquid media for the conversion of glucose to HMF.[10, 13, 14] In addition to Cr salts, boric acid[15] and tin chloride[16] were shown to be able to catalyze glucose dehydration to HMF in ionic liquids albeit with substantially lower HMF yield compared to the Cr-based systems. In all these systems the initial glucose isomerization to fructose is the key step determining the overall efficiency of the catalytic process.[1517] It has been demonstrated that the ability of CrCl2 in EMImCl ionic liquid to catalyze this isomerization step is related to the transient self-organization of catalytic Cr2 + complexes into dimers in the course of the reaction.[17] A subsequent computational study showed that the reaction mechanism for the CrIII chloride catalyst is very similar to that originally proposed for CrII.[18] The isomerization reaction involves a number of anionic intermediates that are stabilized by their interaction with the cationic Cr2 + centers. More efficient stabilization of the anionic reaction intermediates by the stronger Lewis acidic Cr3 + ions substantially lowers the barrier for the rate-limiting hydrogen-shift step. As a result chromium(III) chloride shows a higher catalytic activity than its bivalent counterpart. It was concluded that the Lewis acidity of the cat[a] Dr. E. A. Pidko, Dr. V. Degirmenci, Prof. Dr. E. J. M. Hensen Inorganic Materials Chemistry, Schuit Institute of Catalysis Eindhoven University of Technology P.O. Box 513, NL-5600 MB, Eindhoven (The Netherlands) Fax: (+ 31) 40-245-5054 E-mail: e.a.pidko@tue.nl e.j.m.hensen@tue.nl

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E. A. Pidko, V. Degirmenci, and Dr. E J. M. Hensen alytic metal center is one of the key factor for the high activity in glucose isomerization.[18] This suggests that a wider range of ionic liquid-mediated metal chlorides exhibiting stronger Lewis acidity and being more environmentally benign than chromium should in principle be able to efficiently promote the isomerization of glucose to fructose. For example, both the coordination properties and the Lewis acidity of the ionic liquid-mediated CuII and FeII chlorides are expected to be similar to those of CrCl2.[19, 20] Nevertheless, their behavior towards glucose activation is very different. Although complete conversion of glucose with very low selectivity to HMF was reported to occur in the presence of CuCl2, FeCl2 is inactive towards glucose activation.[12] The actual mechanism of sugar activation by copper(II) chloride and the origin of the low reactivity of the iron(II) catalyst remain unclear. Understanding the factors that govern the catalytic performance of ionic liquid-mediated metal chlorides in glucose dehydration is necessary for further development of green and sustainable catalytic processes for the conversion of lignocellulosic biomass. This work is a continuation of our previous mechanistic studies on activation of carbohydrates by chromium salts in imidazolium-based ionic liquids.[1719] Herein we combine experimental and computational approaches in a complementary manner to unravel the main factors that determine the selectivity and activity of glucose dehydration by CrCl2, CuCl2, and FeCl2 in an ionic liquid medium. with low HMF yield. The reactivity of glucose in the absence of Lewis acidic catalysts is negligible. The introduction of CrCl2 and CuCl2 promotes fructose conversion to HMF with the latter catalyst showing the highest reaction selectivity. The HMF yields for CrCl2 and CuCl2 after 3 h at 353 K are 67 and 84 %, respectively. The activity of FeCl2 under these conditions is much lower with a very low HMF yield. In contrast, with glucose as the substrate, only CrCl2 shows a high HMF yield. The HMF selectivity in this case is close to that observed for fructose dehydration by the same metal chloride. Despite the high activity of CuCl2, it produces only small amounts of HMF. FeCl2 exhibits very low activity for the dehydration of glucose. The reactivity in this case is close to that of pure EMImCl suggesting that the IL-mediated FeII species do not specifically interact with carbohydrates. Mechanism of glucose isomerization To obtain high HMF selectivity, the catalyst should be able to isomerize glucose to fructose. In an attempt to explain differences between copper and chromium, we compared the DFTcomputed reaction energy diagrams for glucose isomerization to fructose over CrII and CuII chloride complexes in MMImCl model ionic liquid (Figure 1). Chromium is predominantly present as mononuclear anionic CrCl42 complexes in a CrCl2/EMImCl solution.[19] The reaction is initiated by the direct coordination of glucose with the Lewis acidic Cr2 + center (GluCr, Figure 2). This facilitates the deprotonation of the O1H moiety of the carbohydrate and formation of the deprot-O1-GluCr intermediate.[17] The subsequent protonation of O6 opens the glucopyranose ring (open-GluCr). Model DFT calculations predict these initial transformations to be very facile (Glu!open-Glu, mononuclear path, Figure 1 b). This is in line with the experimentally observed rapid interconversion of a-d-glucose to b-d-glucose in the presence of the Cr catalyst at conditions under which glucose is not converted.[12, 17] The free energy barrier for opening of the glucopyranose ring is only 14 kJ mol1. The resulting open-GluCr complex is the precursor for the formation of fructose. The isomerization reaction begins with the deprotonation of the coordinated open form of glucose at O2H, resulting in an activated deprot-O2-open-Glu sugar intermediate (Figure 1 a). This intermediate then undergoes an H-shift between the C1 and C2 carbon atoms of the carbohydrate yielding a fructose precursor (deprot-O1-open-Fru). Subsequent protonation of this species at the anionic O1 site and closure of the furanose ring yields fructose. The key H-shift step of the isomerization reaction involves the migration of the negative charge from the O2 site of carbohydrate to O1. Efficient interaction of the migrating anionic center with the Lewis acidic Cr2 + center is required for the stabilization of the activated reaction intermediates. The coordination with a single cationic center is not sufficient to promote the H shift reaction. When the open form of glucose is coordinated to one Cr center (mononuclear path, Figure 1 b), the formation of the activated deprot-O2-open-Glu intermediate is endothermic (+ 68 kJ mol1) and the subsequent H shift
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Results and Discussion

Catalytic sugar conversion A set of fructose and glucose dehydration experiments was performed in the presence of CuCl2, FeCl2, and CrCl2 catalysts in EMImCl ionic liquids (ILs). The results of the catalytic tests both in the presence and in the absence of the metal chloride catalysts are summarized in Table 1. In line with previous reports,[12, 21] fructose can be converted in pure EMImCl albeit

Table 1. Dehydration of carbohydrates by selected metal chlorides (MeCl2) in EMImCl ionic liquids and the influence of ionic liquid solvents on glucose dehydration.[a] Catalyst CuCl2 CuCl2 CuCl2 FeCl2 FeCl2 CrCl2 CrCl2 CrCl2 Solvent EMImCl EMImCl EMImCl EMImCl EMImCl EMImCl EMImCl EMImCl EMImCl EMImCl Hexose fructose glucose Me-a-d-GP[b] fructose glucose fructose glucose Me-a-d-GP[b] fructose glucose Conversion [%] 90 82 0 18 4 100 100 0 22 6 Yield HMF [%] 84 5 0 3 0 67 68 0 2 0

[a] Reaction conditions: 500 mg solvent, 50 mg carbohydrate, MeCl2/ hexose = 0.06, 373 K for glucose dehydration, 353 K for fructose dehydration, 3 h. [b] Me-a-d-GP = methyl-a-d-glucopyranoside

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Lewis Acid Catalyzed Glucose Transformations sugar-Cr complex equals 120 kJ mol1. This barrier decreases strongly when the deprotonated glucose intermediate interacts with two Cr centers (binuclear path, Figure 1 b). The deprotonation of the O2H hydroxyl group of the open form of glucose bound to a single Cr center (open-GluCr) favors the complexation of a second chromium chloride species with the activated sugar intermediate. In the resulting deprot-O2-openGlu2xCr complex, the carbonyl O1 moiety bridges two Cr ions with one of Cr2 + additionally coordinating to the anionic O2 group (Figure 2). The interaction with the two metal cations substantially stabilizes the anionic reaction intermediates involved in the H shift reaction. The free energy barrier for the H shift from C2 to C1 in this binuclear complex is only 9 kJ mol1. The product of this elementary step is a stable anionic fructose intermediate, in which the negative charge on the O1 site is compensated by the direct coordination with two Cr2 + ions (deprot-O1-open-Fru2 xCr, Figure 2). Subsequent protonation of this complex by O1 leads to a complex with the open form of fructose. This step is slightly unfavorable. The associated energy losses are compensated by the decomposition of the binuclear complex and the closure of the furanose ring resulting in the formation of a fructose molecule. Thus, the favorable route (min(DG8) path, Figure 1 b) for glucose isomerization to fructose catalyzed by ionic liquid-mediated chromium chloride complexes involves the transient self-organization of the catalytic Cr2 + centers into binuclear complexes with the activated sugar intermediates (Figure 2). This lowers substantially the activation barrier of the rate-controlling H shift.[17, 18] The reaction free-energy diagram for the same mechanism catalyzed by CuII is shown in Figure 1 c. The initial glucopyranose ring opening proceeds via a proton transfer from O1H to O6 site in a complex of a-d-glucose with a single Cu2 + center (GluCu!open-GluCu, Figure 3). The calculated reaction free energies for the elementary steps involved (Figure 1 c) are slightly higher than those computed in the case of Cr. The introduction of a second copper chloride species into the reactive intermediate complex is favored at the stage of the formation of the O2-deprotonated activated glucose intermediate (open-Glu!deprot-O2-open-Glu, Figure 1 c). The corresponding binuclear Cu complex is 40 kJ mol1 more stable than its mononuclear counterpart. In contrast to the case of Cr, the two Cu centers in the deprot-O2-open-Glu2xCu complex do not have shared ligands (Figure 3). The coordination in this complex can be described as two independent complexes of CuCl3 species with O1 and O2 sites of the activated glucose intermediate. Despite the Cu species are initially not correlated, the coordination of two Lewis acids substantially decreases the activation energy for the H-shift reaction and additionally stabilizes the resulting activated fructose intermediate. Compared to mononuclear case, the activation free energy barrier for the binuclear Cu case is lower by 38 kJ mol1. The reaction product is also stabilized by more than 74 kJ mol1. The developing negative charge on the O1 site brings the two Cu species together (Figure 3). The structures of the TS-H-shift2xCu and deprot-O1-open-Fru2xCu complexes resemble those found for Cr2 + , although the development of the delocalized p-elec-

Figure 1. a) Mechanism of glucose to fructose isomerization as a first step towards the selective glucose dehydration to HMF and the corresponding DFT-computed free energy diagrams for glucose isomerization over monoand binuclear b) Cr2 + [17] and c) Cu2 + chloride complexes in a MMImCl model ionic liquid.

has an activation free energy barrier of 51 kJ mol1. Thus, the overall free energy barrier for the H shift for a mononuclear
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E. A. Pidko, V. Degirmenci, and Dr. E J. M. Hensen

Figure 2. Optimized structures of chromium(II)-sugar complexes involved in the minimum free energy reaction path of glucose isomerization to fructose.

tron system upon the H-shift is much less pronounced (TS-Hshift, Figure 2 and 3). The protonation of the H-shift product by O1 is only slightly unfavorable (DG8 ,IL373K = 12 kJ mol1) and results in the open form of fructose coordinated to two Cu centers effectively sharing two Cl ligands and the O1H hydroxyl group of the sugar. Subsequent closure of the fructofuranose ring proceeds with a free energy increase of 18 kJ mol1 and results in the loss of the direct interaction between one of the Cu centers and the carbohydrate, although the effective binuclear structure of the Cu complex remains unchanged (Fru2xCu, Figure 3). The energy difference between the mono- (FruCu) and binuclear Cu (Fru2xCu) complexes with fructofuranose is only 12 kJ mol1. Thus, our model DFT calculations suggest that glucose to fructose isomerization by ionic liquid-mediated copper(II) chlorides may proceed through the same mechanism as the one identified for chromium. The favorable reaction route involves the transient self-organization of Lewis acidic CuCln species, which substantially stabilize the reaction intermediates and the transition state involved in the rate-controlling H-shift step. The overall free energy barrier for the reaction is 71 kJ mol1. This barrier is only 8 kJ mol1 higher than the barrier computed for the case of chromium(II) catalyst (Figure 1 a and b). Comparable activation energies of reaction steps in the same reaction mechanism imply that CuCl2 and CrCl2 in dialky-

limidazolium chloride ionic liquids should exhibit similar activity and selectivity in the isomerization of glucose to fructose. This hypothesis clearly contradicts the experimental observations shown in Table 1. One reason could be the assumption in our DFT calculations that at the initial stage of the reaction the metal chloride species specifically activate the O1H hydroxyl group through direct coordination followed by deprotonation. An explanation for high but unselective conversion of glucose observed for copper(II) chloride could be the ability of CuCl2 to activate other hydroxyl groups of the sugar molecule. This could lead to condensation-type side-reactions instead of the desirable ring opening and isomerization to fructose. To verify this proposition, the dehydration of O1-methylated a-d-glucopyranose was studied. Neither CuCl2 nor CrCl2 convert this reactant (Table 1). This evidences that glucose can only be activated at the O1H position, which will lead to opening of the glucopyranose ring. Thus, we expect that the differences in the catalytic performance of chromium(II) and copper(II) chlorides are associated with the different mechanisms of glucose activation after the initial O1H deprotonation. State and structure of catalytic complexes To obtain more detailed insight into the differences in the behavior of the selected Lewis acidic catalysts towards sugar activation, the state and structural properties of the ionic liquidChemCatChem 2012, 4, 1263 1271

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Lewis Acid Catalyzed Glucose Transformations

Figure 3. Optimized structures of copper(II)-sugar complexes involved in the minimum free energy reaction path of glucose isomerization to fructose.

mediated CuII, CrII, and FeII coordination complexes and their interaction with glucose were investigated by X-ray absorption spectroscopy. Listed in Table 2 are the EXAFS fit parameters and edge positions in XANES spectra for CrCl2, CuCl2, and FeCl2 dissolved in EMImCl ionic liquid at 353 K prior to and after addition of glucose, as well as after 3 h reaction with glucose at 373 K. In the absence of glucose, the metal cations are surrounded by four Cl ligands at a distance of 2.39, 2.28, and 2.32 , respectively, for Cr2 + , Cu2 + , and Fe2 + . In our earlier communication[17] we have reported that the introduction of glucose to the Cr-containing solution leads to the substitution of one of the chlorine ligands in the coordination sphere of chromium by one of the hydroxyl groups of the carbohydrate (Table 2). The resulting CrO coordination bond is characterized by r(Cr O) = 2.13 . The remaining CrCl coordinations remain unchanged (r(CrCl) = 2.38 ). The edge position in the Cr K-edge XANES spectra in both cases (5993.1 eV) is very close to the value for the pure CrCl2 (5994.9 eV). Already after 10 min of the reaction with glucose at 373 K, the coordination environment of Cr changes significantly. Each chromium ion at this stage is surrounded by two oxygen ligands and two chlorine ligands (r(CrO) = 2.04 and r(CrCl) = 2.36 ). In line with the theoretical predictions of the binuclear structure of the reaction inChemCatChem 2012, 4, 1263 1271

termediates in the CrCl2-catalyzed reaction (Figure 2), an additional CrCr shell is detected (Table 1). The edge position in the respective XANES spectrum is significantly shifted to higher energies and equals 5999.1 eV. This value is close to that for the reference pure Cr(OAc)2 (6000.2 eV). This shift of the edge position is associated with the formation of a CrO bond with anionic sugar intermediates rather than with the oxidation of Cr2 + species. This is in agreement with the observed shortening of the CrO distance. When the reaction is completed, the coordination environment of Cr contains on average 1.4 O ligands at 2.02 and 2.4 Cl ligands at 2.35 , while no additional CrCr coordination is detected. A very different behavior is observed for copper(II) and iron(II) chlorides. The addition of the sugar at 353 K and the subsequent heating of the solution for 3 h at 373 K does not result in any notable change of the coordination environment of Fe centers and the edge position in the Fe K-edge XANES spectra (Table 2). The initial FeCl42 complexes remain unchanged in the course of the experiment. This coheres well with the absence of a catalytic effect of FeCl2 in sugar dehydration. Similarly, no changes in the metal coordination are observed upon the introduction of glucose to the CuCl2-containing solution (Table 2). Instead, part of the bivalent Cu cations is re-

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E. A. Pidko, V. Degirmenci, and Dr. E J. M. Hensen Glucose activation We propose that the differences in the behavior of CrCl2, CuCl2, and FeCl2 catalysts for the conversion of glucose are already determined at the initial step of the reaction. The ability of the catalytic complex to promote the isomerization of glucose to fructose and therefore to open the pathway for its selective dehydration is directly related to its ability to form a direct coordination complex with the substrate. To further validate this proposal we compared the DFT-computed thermodynamics of the initial glucose activation via the formation of such a direct coordination complex and via the deprotonation by O1H site indirectly catalyzed by the ionic liquid-mediated metal chloride catalysts. The respective DFT results are summarized in Figure 4. In agreement with the EXAFS data, the introduction of glucose into the first coordination sphere of the IL-mediated CrCl42 complex is favorable (DEZPE = 10 kJ mol1, Figure 4). Under the reaction conditions an equilibrium is established (DG8 ,IL353K = 0 kJ mol1) between the coordinated (CrGlu) and non-coordinated H-bonded complexes (Cr + Glu). The replacement of a Cl ligand by the O1H group of the substrate does not substantially change the coordination properties of the Cr center. The resulting CrGlu complex is characterized by a distorted square-planar configuration of the metal ion. The geometry of the initial structure corresponding to the product of the alternative activation path via direct deprotonation of the sugar in the hydrogen bonded-complex was optimized. This leads to the opening of the glucopyranose ring and the formation of an under-coordinated CrCl3 species. This path is thermodynamically unfavorable (Cr + Glu ! CrUopen-Glu, Figure 4) most likely because of the low stability of the tricoordinated chromium chloride species.[19] A different behavior follows from similar considerations for the CuCl42 complex. The substitution of a Cl ligand by an O1H group of glucose alters the coordination of the Cu ion leading to a distorted square-planar CuGlu configuration (Figure 4). This transformation is strongly unfavorable (DG8 ,IL353K = + 43 kJ mol1). Thus, to initiate the selective glucose isomerization (Figure 1 a and c) an overall free energy barrier of 65 kJ mol1 has to be overcome. The alternative direct proton abstraction path, resulting in the glucopyranose ring opening and the formation of a three-coordinated CuCl3 species, is preferred (Cu + Glu!CuUopen-Glu). The corresponding calculated free energy differences with (DG8 ,IL353K) and without (DG8353K) correction for bulk solvent effects are small (+ 21 and + 3 kJ mol1, respectively, Figure 4). For FeCl2, both the formation of the coordination complex with glucose (Fe + Glu! FeGlu) and the direct deprotonation path (Fe + Glu! FeUopen-Glu) involve substantially larger free energy changes than those predicted for CuCl2 (Figure 4). The direct interaction between the cationic metal center and the hydroxyl groups of glucose is necessary for the efficient stabilization of the anionic reaction intermediates involved in the isomerization reaction. DFT calculations and EXAFS measurements demonstrate that only for the CrCl2/EMImCl system oxygen neighbors are found in the coordination sphere of the
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Table 2. The evolution of edge positions in XANES spectra and EXAFS fit parameters of the CrCl2/EMImCl,[17] CuCl2/EMImCl, and FeCl2/EMImCl systems upon the reaction with glucose. Backscatter N[a] R [][b] Ds2 [][c] 0.008 0.007 0.015 0.004 0.004 0.006 0.005 0.003 0.016 0.011 0.018 0.013 0.015 0.013 DE0 [eV][d] 8.4 3.4 Edge [eV] 5993.1 5993.1

CrCl2/EMImCl CrCl 3.9 2.39 Glucose/CrCl2/EMImCl, 0 min CrCl 2.9 2.38 CrO 1.0 2.13 Glucose/CrCl2/EMImCl, 10 min CrCl 2.4 2.36 CrO 2.0 2.04 CrCr 0.6 3.45 Glucose/CrCl2/EMImCl, 180 min CrCl 2.4 2.35 CrO 1.4 2.02 CuCl2/EMImCl[19] CuCl 4.1[e] 2.28 Glucose/CuCl2/EMImCl, 0 min[19] CuCl 2.0,[e] 2.23 4.0[f] CuO Glucose/CuCl2/EMImCl, 180 min CuCl 4.8[f] 2.24 CuO FeCl2/EMImCl FeCl 3.9 2.32 Glucose/FeCl2/EMImCl, 0 min FeCl 3.8 2.33 FeO Glucose/FeCl2/EMImCl, 180 min FeCl 4.0 2.33 FeO

7.4

5999.3

5.2

5999.3

0.0 5.5 8.27 7.19 7.99 7.51

8984.8 8984.6

8981.7

7118.4 7118.5

7118.6

[a] Coordination number (N) 20 %; [b] coordination distance (R) 0.02 ; [c] Debye-Waller factor (Ds2) 10 %; [d] Inner potential (DE0); [e] under the assumption that copper is present as Cu2 + ; [f] - under the assumption that copper is present as Cu + .

duced to the + 1 state.[19] The reduction is complete after 3 h of reaction at 373 K. The edge position in the Cu K-edge XANES spectrum shifts to the value observed for a solution of CuCl in EMImCl (8981.6 eV). The coordination environment of these Cu + ions is made up from four chlorine ligands at a distance of 2.24 . No oxygen neighbors were detected in the course of the reaction. Thus, despite its inability to form a direct coordination complex with the sugar, the ionic liquid-mediated copper(II) chloride catalyst converts glucose although with very low HMF selectivity. Similar to CrII, the glucose transformations promoted or initiated by the CuII catalyst involve the ring-opening and mutarotation processes. Taking into account that the sugar oxidation by CuII requires the presence of the open form of glucose and water in the reaction medium, it appears that partial glucose dehydration takes place before the catalyst is reduced to Cu + . This is in line with the fact that the stoichiometric oxidation path alone cannot explain the almost complete conversion of glucose by CuCl2 because of the much lower concentration of the catalyst compared to the sugar substrate.

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Lewis Acid Catalyzed Glucose Transformations the carbohydrate. The initial sugar activation in this case proceeds via deprotonation of the O1H site by CuCl42 species resulting in transient formation of under coordinated CuCl3 complex and HCl. Subsequent reprotonation of the anionic sugar intermediate by O6 results in the open form of glucose and the regeneration of the initial CuCl42 complex. We propose that partial sugar dehydration and other non-selective glucose reactions proceed via this mechanism. Water formed in the course of the partial sugar dehydration accelerates the reduction of Cu2 + ions with the aldose. The resulting oxidized products and transient reactive Brnsted and Lewis acidic species probably contribute to the overall non-selective glucose conversion by CuCl2 in EMImCl. The low reactivity of the FeCl2/EMImCl system is attributed to the inability of iron(II) chloride complexes to coordinate glucose as well as to promote its direct deprotonation. As a result neither selective glucose isomerization followed by fructose dehydration nor the non-selective paths initiated by direct proton abstraction will occur, in line with the experiment.

Figure 4. Optimized structures of hydrogen bonded (Me + Glu for which Me is Cr, Cu, or Fe) and coordination (MeGlu for which Me is Cr, Cu, or Fe) complexes, as well as of the products of the direct deprotonation (MUopen-Glu) of glucose by metal chloride catalysts in MMImCl model ionic liquid. ZPE-corrected energies (DEZPE) and free energies at 353 K with (DG8353K) and without implicit solvent correction (DG8 ,IL353K) calculated for the respective interconversions are given in kJ mol1.

metal center in the presence of glucose. The reversibility of the sugar to Cl ligand exchange in the initial CrCl42 catalytic complexes is important to obtain high selectivity to isomerization. One can speculate that irreversible glucose binding to a Lewis acidic site would initiate a range of non-selective conversion paths by activating the sugar molecules at various OH sites. When a complex between Cr and glucose at the O1H site is formed, a sequence of favorable sugar transformations initiates that involves transient formation of binuclear Cr complexes at the rate-determining step and leads to the selective formation of fructose that is further rapidly dehydrated to HMF. The exchange of Cl ligand by glucose in both CuCl42 and FeCl42 species is endothermic and characterized by positive Gibbs free energy changes (Figure 4). Although there is a possibility for the copper catalyst to promote the isomerization reaction via a mechanism similar to that postulated for CrCl2 and with comparable activation energy, glucose conversion by CuCl2/EMImCl is not selective (Table 1). The reduction of Cu2 + to Cu + requires that the presence of the open form of glucose and water. The latter is formed by the partial dehydration of
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Conclusions
Catalytic activity and selectivity of glucose dehydration to 5-hydroxymethylfurfural by Lewis acidic CrCl2, CuCl2, and FeCl2 catalysts in dialkylimidazolium chloride ionic liquids is determined by their different behavior towards the initial activation of the sugar substrate. The selective transformations of glucose proceed via the formation of fructose as an intermediate. Among the catalysts considered, chromium(II) chloride shows an exceptional ability to efficiently promote glucose to fructose isomerization and its subsequent dehydration to HMF. Glucose conversion by copper(II) chloride shows very low selectivity to HMF, while iron(II) chloride is completely inactive towards sugar activation. The initial attack by O1 resulting in the glucopyranose ring opening is necessary for both the selective and nonselective transformations in the presence of chromium(II) and copper(II) chlorides, respectively. In the case of Cr, the reactive metal chloride species are able to directly coordinate the substrate at

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E. A. Pidko, V. Degirmenci, and Dr. E J. M. Hensen the O1H site. The formation of the coordination complex with glucose initiates the isomerization reaction that involves the transient formation of binuclear Cr complexes that substantially stabilize the activated anionic sugar intermediates. The thus formed fructose is then rapidly dehydration to HMF. Nonselective conversions are also initiated by the O1H activation indirectly catalyzed by the copper(II) chloride catalyst. In this case the initial O1H deprotonation proceeds via a proton abstraction by one of the chlorine ligands of the ionic liquid-mediated copper(II) choride complexes. The promotion effect of CuCl2 is attributed to the high mobility of Cl ligands in the catalytic CuCl42 species. Subsequent sugar transformations are no longer determined by the site of the initial activation by the metal chloride complex and, therefore, contribute to the paths of non-selective conversions. In the course of the reaction, bivalent copper species are reduced to the + 1 formal oxidation state. When FeCl2 is used as a catalyst, both reaction channels initiated by the formation of a coordination complex with glucose and by the direct deprotonation by O1H are unfavorable. This explains the very low reactivity of the iron(II) chloride catalyst.
set was used for the remaining C, H, and N atoms of the 1,3-dimethylimidazolium (MMIm) cation of the model ionic liquid solvent. This approach has been successfully employed in our previous mechanistic studies of sugar transformations by ionic liquid-mediated Lewis acid catalysts.[1719] Based on previous work[1719] and test calculations on molecular models involving different spin states, all calculations were performed with the complexes in a high spin state (S = 4/2 and S = 8/ 2 for mononuclear and binuclear Cr complexes, respectively; S = 1/ 2 and S = 3/2 for mononuclear and binuclear Cu complexes, respectively; and S = 4/2 for the mononuclear Fe complexes). At least two MMImCl ion pairs per a metal center were explicitly included in the models to account for the influence of the ionic liquid on the catalytic reaction. The remaining part of the medium was approximated using the polarizable continuum model (PCM) within the conductor reaction field (COSMO) approach.[24] Free energy values (DG8T) were computed using the results of the normal-mode analysis within the ideal gas approximation at a pressure of 1 atm and temperatures of 298, 353, and 373 K. To reduce potential errors associated with the non-uniform stabilization and charge compensation of the MMIm + ions at the outer part of the molecular models, their contributions were removed from the Hessian matrix for all the reaction intermediates and transition states in this case. Higher-level SCF and PCM corrections were then applied to yield the Gibbs free energies in solution (DG8 ,ILT). More extensive description of the employed computational procedures can be found in Refs [1719].

Experimental Section
Catalytic tests
d-glucose (99.5 %), d-fructose (99 %), methyl-a-d-glucopyranose (98 %), CrCl2 (99.99 %), CuCl2 (99.995 %), and FeCl2 (99.998 %) were purchased from SigmaAldrich. 1-Ethyl-3-methylimidazolium chloride (EMImCl, 98 %) was obtained from Merck. The catalytic activity experiments were performed in 4 mL batch glass vials (15 45 mm). The reactor vials were heated in an oil bath placed on top of a magnetic stirrer. In a standard experiment, 500 mg EMIMCl was mixed with 50 mg of sugar (glucose or fructose). An amount of metal chloride catalyst corresponding to 6 mol % by sugar was added to the vial under inert atmosphere. After closing the vial, the reactor was placed in the preheated oil bath. The reaction was quenched by placing the vial in an ethylene glycol bath at 273 K. Analytes were extracted with 2 mL of water for HPLC analysis. The extracted samples were analyzed by a Shimadzu HPLC system equipped with UV and ELSD detectors. Hexoses were detected by an ELSD detector with a Prevail Carbohydrate ES (Grace) column. The mobile phase (1 mL min1) was acetonitrile/water (83:17 v/v) and the column temperature 323 K. HMF was detected by a UV detector (320 nm) on a Pathfinder PS C18 reversed phase column. The mobile phase (0.6 mL min1) was methanol/water (20:80 v/v) and the column temperature was 303 K.

X-ray absorption spectroscopy

X-ray absorption spectroscopy (XAS) experiments were performed in a home built in situ cell, which is designed to retain the liquid between two Kapton windows and can be heated up to 473 K. XAS spectra were collected in fluorescence mode at the Cr, Cu, and Fe K edges at the Dutch Belgium Beamline (DUBBLE) equipped with a Si(111) monochromator at the European Synchrotron Radiation Facility (ESRF). EXAFS analysis was then performed with EXCURV98[25] on k3-weighted unfiltered raw data by using the curved wave theory. Phase shifts were derived from ab initio calculations using HedinLundqvist exchange potentials and Von Barth ground states as implemented in EXCURV98. Energy calibrations were performed with Cr, Cu, and Fe foils. The amplitude reduction factor S02 associated with central atom shake-up and shake-off effects was set at 0.87, 0.80, and 0.83 for Cr, Cu, and Fe, respectively, based on data obtained for reference CrCl2, CuCl2, and FeCl2 compounds. In a typical experiment, 500 mg of EMImCl was mixed with 8 mg metal chloride and 50 mg glucose at 333 K in a nitrogen-flushed glovebox. 3 mL of this mixture was transferred into the XAS cell and closed under inert atmosphere. The cells were then transferred to the beamline and EXAFS spectra of the liquid were recorded at 353 K.

Density functional theory calculations

Density functional theory (DFT) calculations were performed with the PBE0 (also denoted as PBE1PBE and PBEh)[22] hybrid exchangecorrelation functional using Gaussian 03 program.[23] The full electron 6-31 + G(d) basis set was used for Cr, Cu, Fe, Cl, and O atoms, while the C, N and H atoms were treated with the 6-31G(d) basis set. The resulting SCF energies were corrected by computing single point energies for the optimized structures employing an extended combination of basis sets, in which Cr, Cu, and Fe atoms were treated using the 6-31 + G(d) basis set. The Cl, C, H, and O atoms of the carbohydrate molecule and its derivatives were described with the 6-311 + + G(d,p) basis set. The 6-311G(d,p) basis

Acknowledgements
This research has been performed within the framework of the CatchBio program. The authors gratefully acknowledge the support of the Smart Mix Program of the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science. NWO-NCF and NWO-Dubble are acknowledged for access to computing and XAS facilities, respectively.
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Lewis Acid Catalyzed Glucose Transformations

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Keywords: biomass catalysis calculations ionic liquids Lewis acid

density

functional

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Received: February 23, 2012 Published online on April 18, 2012

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