c3gc41324a 24..38szolcsanyi/education/files... · advances in 5-hydroxymethylfurfural production...

Green Chemistry

CRITICAL REVIEW

Cite this: Green Chem., 2014, 16, 24

Received 6th July 2013,Accepted 24th September 2013

DOI: 10.1039/c3gc41324a

www.rsc.org/greenchem

Advances in 5-hydroxymethylfurfural productionfrom biomass in biphasic solvents

Basudeb Saha*a,b and Mahdi M. Abu-Omar*a,b

Biomass derived 5-hydroxymethylfurfural (HMF) has emerged as an important platform chemical for the

production of value added chemicals and liquid fuels that are currently obtained from petroleum.

Although a significant amount of research has been performed over the past decade, the high production

cost of HMF is still a bottleneck for its sustainable utilization for making other value added chemicals and

fuels on a commercial scale. Among several factors, low product selectivity and high purification cost are

major constraints. To address these drawbacks, HMF production methodology in recent years has been

directed towards utilization of biphasic media for concurrent extraction of HMF into an organic phase

immediately after its formation in the reactive phase. As a result, several dozens of journal and patent

articles have appeared, demonstrating the benefit of biphasic media for effective HMF extraction. This

review article summarizes the findings of the most recent research articles with critical discussion on the

factors that enhance the performance of biphasic media. Particular emphasis has been given to the devel-

opment of more effective extracting solvents and their beneficial effect in enhancing HMF yield and

selectivity, improvement of partition coefficient, mechanistic role of the bi-functional acid catalysts and

factors that control high HMF selectivity for solid catalysts.

1. Introduction

The awareness of climate change and rapid depletion of non-renewable fossil sources, such as petroleum, and the high vola-tility in crude oil price caused by the imbalance in demand

Basudeb Saha

Dr Basudeb Saha, born inCalcutta (India), graduated inchemistry at Calcutta Universityand received his Ph.D. from theIndian Association for the Culti-vation of Science (India). He didpostdoctoral research with Pro-fessor James Espenson at IowaState University (USA), and thenmoved to the polyurethanebusiness R&D division of DowChemical Company (USA) wherehe led several breakthrough andimplementation research pro-

jects. Currently, he is an Associate Research Scientist at PurdueUniversity and is pursuing research on utilization of bio-renewablefeedstocks for chemicals and fuels production via effective cata-lysis. Prior to joining Purdue University, he worked at Delhi Uni-versity (India) as an Associate Professor.

Mahdi M. Abu-Omar

Mahdi is a native of Jerusalem,Palestine. He moved to the U.S.in 1988 to pursue higher edu-cation. He completed his Ph.D.in Inorganic Chemistry in 1996from Iowa State University underthe guidance of James Espenson.After a postdoc at Caltech in thegroup of Harry Gray, Mahdistarted his independent aca-demic career at UCLA and movedto Purdue University in 2003,where he is now professor ofchemistry and chemical engi-

neering. Mahdi’s research interest is in the design and develop-ment of transition-metal catalysts for renewable energy andenvironmental applications.

aBrown Laboratory, Department of Chemistry and School of Chemical Engineering,

Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.

E-mail: [email protected], [email protected] Center for Direct Catalytic Conversion of Biomass to Biofuels (C3Bio),

Discovery Park, Purdue University, West Lafayette, IN 47907, USA

24 | Green Chem., 2014, 16, 24–38 This journal is © The Royal Society of Chemistry 2014

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and supply, have put enormous pressure on the globaleconomy.1 Thus, the development of environmentally andeconomically viable synthetic routes and related technologiesfor producing chemicals and fuels from non-fossil carbonsources has been reenergized in recent years after the U.S.Department of Energy published a list of “top ten biobasedchemicals”.1 In this context, lignocellulosic biomass-derived5-hydroxymethylfurfural (HMF) and furfural have emerged asimportant platform chemicals to meet the chemical and fuelneeds of the next generation.1,2 The driving factors for thisinitiative from biorenewable sources are not only limited todeveloping new energy platforms and CO2 minimization, butalso creating opportunities to secure the local supply of energyand support agricultural economics.3,4

The production of chemicals and fuels from lignocellulosicbiomass requires effective pretreatment and hydrolysis of cel-lulose and hemicellulose polymers of the biomass to thecorresponding pentose and hexose sugar units, followed bycatalytic dehydration of sugars to the corresponding furfuraland HMF products. The production of HMF from mono- andpolysaccharides, including pretreated biomass substrates,using homogeneous mineral acid, Brønsted acidic ionicliquids (IL), Lewis acidic metal halides and recyclable hetero-geneous catalysts in pure organic or aqueous solvents hasbeen reported.5–7 The subsequent transformation of HMF intoother value added chemicals, such as promising next gen-eration polyester building block monomers (2,5-furandicar-boxylic acid (FDCA),8,9 2,5-bis(hydroxymethyl)furan (BHMF),10

and 2,5-bis(hydroxymethyl)tetrahydrofuran (BHMTF)) andpotential biofuel candidates (2,5 dimethylfuran (DMF),11,12

5-ethoxymethylfurfural (EMF),13 ethyl levulinate (EL) andγ-valerolactone (gVL))2 (Fig. 1) has also been explored bydifferent researchers using HMF as a starting substrate ordirectly from biomass in a one-pot process.

Additionally, HMF also functions as an anti-sickling agentfor intermolecular sickle haemoglobin without inhibition byplasma and tissue proteins or other undesirable sequences.14

Experimental results show that HMF forms stable high-affinitySchiff base adducts with intramolecular hemoglobin andhence pre-treatment of transgenic sickle mice with HMF inhi-bited the formation of sickle cells. Despite the versatile appli-cation of HMF, the high production cost of HMF, owing to lowproduct selectivity and high separation cost, is a major draw-back to its sustainable utilization as a potential replacementfor petroleum feedstock.

Besides the effectiveness of the catalyst for high yield andhigh selective in HMF production, solvents also play an impor-tant role in enhancing HMF yields; its purity and ease of separ-ation make the process economically and environmentallycompetitive. Although the chemistry and engineering aspectsof HMF production and its effective separation technologyhave advanced in recent years, most research efforts over thepast decade were limited to achieving higher carbohydrate con-versions in high boiling point organic solvents. These solventsinclude dimethylsulfoxide (DMSO), N,N-dimethylformide(DMF), N,N-dimethylacetamide (DMA), methyl isobutyl ketone(MIBK) and ILs. Several catalytic systems have been employedfor the conversion of mono-, di-, polysaccharides and celluloseinto HMF by utilizing the DMSO solvent system. Tong et al.reported fructose dehydration with Brønsted acidic ILcatalysts, N-methyl-2 pyrrolidonium methyl sulfonate([NMP]+[CH3SO3]

−) and N-methyl-2-pyrrolidonium hydrogensulfate ([NMP]+[HSO4]

−) in DMSO, enabling maximum 72 mol%HMF yield with 87% selectivity from a reaction between5.8 mmol fructose and 0.44 mmol [NMP]+[CH3SO3]

− catalystfor 2 h at 90 °C.15 Other homogeneous and heterogeneous cata-lytic systems including SnCl4/tetra-butyl-ammonium bromidein DMSO,16 Amberlyst-70 in DMSO and N,N-demethyl-

Fig. 1 HMF production and its utilization routes for chemicals and liquid fuels.

Green Chemistry Critical Review

This journal is © The Royal Society of Chemistry 2014 Green Chem., 2014, 16, 24–38 | 25

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formamide,17 sulfonic acid (–HSO3) and IL functionalizedmesoporous NPs in DMSO,18 1-hydroxyethyl-3-methylimidazo-lium tetrafluoroborate ([C2OHMIM]BF4) IL in DMSO,19 sup-ported Sn-catalyst in DMSO,20 metal halides in DMSO andILs,21 bifunctional SO4

2−/ZrO2–Al2O3 catalyst in DMSO–H2O,22

GeCl4 in DMSO–IL,23 CrCl2 in DMA–1-ethyl-3-imidazoliumchloride ([EMIM]Cl),24 combined CuCl2–CrCl2 catalyst inILs,25 and Brønsted–Lewis-surfactant-combined heteropolyacid(HPA), Cr[(DS)H2PW12O40]3, catalyst in ILs26 have shown mo-derate to high catalytic activity in HMF production. The mostrecent publication in this area of research showed the for-mation of 99 and 91 mol% HMF from fructose using Ti-containing and Ti-free sulfonated carbonaceous catalysts inDMSO.27,28 However, a potential drawback of the ILs solventmediated process is that ILs are expensive and the separationof HMF from high boiling ILs is energy intensive. Besidesthe cost factor, ILs also deactivate by water, which isformed during the dehydration reaction. The high boilingpoints of DMSO and DMF also pose similar challenges forHMF separation, and therefore these processes are eco-nomically unfavorable on a commercial scale. Additionally,high concentrations of oligomeric species, humins, also formas by-products in organic solvent mediated dehydrationreactions.29

To overcome these challenges, HMF production has beenattempted in pure water. Zhu and co-workers have used aLewis acidic ZnCl2 catalyst for the conversion of mono- anddisaccharides into HMF in pure water.30 Mineral acid catalyzedhydrolysis and dehydration of carbohydrates in subcriticalwater was ineffective due to high reaction temperature (320 °C)and poor HMF selectivity.31 The aluminosilicate catalyzeddehydration of fructose in pure water suffered because ofthe low selectivity of the desired product, producing only20–32 mol% HMF at 145 °C, perhaps due to rapid rehydrationof HMF with Brønsted acidic aluminosilicate catalyst.32 In thiscontext, Lewis and Brønsted acidic niobic acid, niobium orvanadium phosphate catalysts certainly claimed higher HMFyield (50 mol%) in pure water from fructose and inulin.33 Thisis perhaps the highest HMF yield reported to date in purewater without using any extracting solvent. The mesoporousTiO2 and H3PO4 treated Nb2O3 catalysts are reported toproduce poor HMF (∼30%) in pure water.34,35 Thus, HMFproduction in monophasic solvent using pure water is nota viable option either, presumably due to the slow rate ofHMF formation and rapid rehydration to furan ringopening products, levilininc acid (LA) and formic acid36,37

(Fig. 2).

2. Advantages of biphasic solvents

Because of the aforementioned disadvantages of the mono-phasic solvent system using high boiling point organic solvents,ILs or pure water, current research efforts for HMF productionhave been directed towards the utilization of biphasic reactionsystems in batch or continuous biphasic reactors. Aqueous ormodified aqueous solution is used as the reactive phase foracid catalyzed conversion of starting substrates to HMF. Theorganic layer of the biphasic system acts as an extracting phasefor continuous accumulation of HMF into the organic phaseimmediately after its formation in the reactive phase. Thus,lower concentration of HMF in the aqueous phase limits therate of side reactions and thereby improves HMF yields.38 Thismethod allows easy separation and reusability of the reactiveaqueous phase containing spent homogeneous or hetero-geneous catalysts. The partition coefficient (R), which is theratio of HMF in the organic phase to that in the aqueousphase, is an important parameter in determining overall effec-tiveness of the biphasic media. Higher partitioning of HMFinto the organic layer improves effective extraction and henceincreases HMF selectivity. Besides the nature of the organicsolvents in determining effective extraction, the presence of in-organic salt, e.g. NaCl, in the aqueous phase also plays animportant role in improving the partition coefficient of HMF.

Dumesic and co-workers measured the R values for HMFextraction using several organic solvents as the extractingphase in biphasic reaction systems in the presence andabsence of NaCl in the reactive phase.39,40 A test reaction forfructose dehydration with a mineral acid catalyst at 150 °C andpH 0.6 shows that the R values for all organic solventsincreased in the presence of NaCl in the aqueous phase andthe relative increase of the R value depends on the solventnature (Fig. 3). For example, 1-butanone showed a two-foldincrease in the R-value from 1.6 to 3.2, whereas 2-butanonerevealed a three-fold increase from 1.8 to 5.4. This significantimprovement in the R value can be explained by the salting-out effect41,42 in which electrolytes alter the intermolecularbonding interactions between liquid components and decrease

Fig. 2 Rehydration of HMF with water.

Fig. 3 Effect of NaCl on the partition coefficient R of HMF extraction inrepresentative biphasic systems. Black bars correspond to systems satu-rated with NaCl, while white bars represent systems without NaCl(modified from Fig. 2 of ref. 39).

Critical Review Green Chemistry


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the mutual solubility of the aqueous and organic phases. Theextent of the salting-out effect depends on the nature of ionicinteractions between all components, nature of salts, concen-trations, temperature and pressure.42

To further test the extent of the salting-out effect on thenature of salts, the authors further studied fructose dehy-dration in 1-butanol by varying the charge and size of cationsand anions.39 Among several chloride salts, Na+ and K+ saltsgenerated the highest partition coefficient and consequentlyproduced HMF with maximum selectivity. This observation isattributed to the fact that smaller hydrated ions have the stron-gest influence on the salting out effect.43 Interestingly, Na2SO4

is found to be most effective at salting-out HMF in 1-butanol,giving a surprisingly high R-value of 8.1. Under comparablereaction conditions, a maximum of 68 wt% HMF yield isrecorded in the 2-propanol and 2-butanone systems. The THF,1-butanol and biorenewable Me–THF systems produced amaximum of 60, 59 and 66 wt% HMF, respectively. The pres-ence of NaCl in the reactive aqueous phase also influencedhigher partitioning of HMF into the organic phase in 0.25 MHCl catalyzed dehydration of fructose.11 In addition to a sig-nificant improvement of the R value from 1.5 to 3.5 with anincrease of NaCl concentrations from 0 to 30 wt% in thewater–2-butanol biphasic system, the selectivity of the HMFproduct also increased from 65 to 90% (Fig. 4), indicatinga more efficient removal of HMF from the aqueous phaseprevents undesired side products.

3. Scope

Because of the several benefits of the biphasic reactionsystems, namely (i) high HMF yield and selectivity bypreventing undesired side reactions, (ii) easy separation and

reusability of the reactive phase containing spent catalysts and(iii) cost-effective separation of the desired product from lowerboiling point extracting solvents, current research efforts inthis area are directed towards the design and implementationof more effective biphasic solvents as well as reactor systems.As a result, dozens of journal and patent articles have beenpublished over the past few years describing the beneficialeffect of biphasic solvents on homogeneous and hetero-geneous catalyzed carbohydrates and lignocellulosic biomassconversions, advancement of extracting organic phase frompetroleum based solvents to environmentally friendly bio-renewable solvents and the role of Lewis and Brønsted acidicsites of the catalyst on HMF yield and selectivity. The presentreview article is devoted exclusively to the latest advancementof HMF production technology in biphasic media with descrip-tive illustration of the results obtained by using different cata-lytic systems consisting of Brønsted acids, Lewis acids and acombination of both. Attention is paid to discussing thekinetic and mechanistic aspects of HMF formation, especiallyfrom glucose, which includes a very important step of isomeri-zation of glucopyranose to fructofuranose.

4. HMF production usinghomogeneous catalysts

To address the limitation of the HMF production technologysuffered by poor product selectivity and separation issue,Dumesic et al.44 designed a modified biphasic reaction system(Fig. 5) using high boiling point polar aprotic solvents modi-fied aqueous medium as a reactive phase for mineral acid(HCl) catalyzed dehydration of concentrated fructose solution(30–50 wt%). The modified reactive phase containing DMSO orpoly(1-vinyl-2-pyrrolidinone) (PVP) or a combination of bothDMSO–PVP as an additive with total mass up to 50%, based onmass of water, showed a noticeable increase in HMF yield incomparison to the reactive phase without a modifier. Amongseveral organic solvents, such as methyl isobutyl ketone

Fig. 5 Schematic diagram of a biphasic reactor for HMF production viaconcurrent extraction and evaporation steps. The aqueous phase con-tains fructose, DMSO, PVP, and catalyst, and the organic phase containsMIBK and 2-butanol (modified from ref. 44).

Fig. 4 A correlation of partition coefficient of different organic solventsfor HMF extraction from fructose dehydration versus HMF selectivity.Experiments without NaCl in the aqueous phase are represented byopen symbols. Experiments with 30% NaCl in the aqueous phase arepresented by solid symbols (modified from Fig. 3 of ref. 11).



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(MIBK), 1-butanol, 2-butanol, 1-hexane, MIBK–2 butanolmixture (7/3 w/w) and toluene–2 butanol mixture (5/5 w/w),that were tested as the organic phase, the modified systemcomprising water–DMSO–PVP (∼4 : 1 : 2 weight ratio) as a reac-tive phase and MIBK–2 butanol (7 : 3 volume ratio) as anextracting phase offered the best HMF yield (76%) with 85%selectivity at 180 °C. The authors extended the application ofthe modified water–organic biphasic systems to HCl catalyzedconversions of mono-, di- and polysaccharides of C6/C5 sugarunits to the corresponding furfural products.45 Under compar-able reaction conditions, a biphasic system containing awater–DMSO mixture as the aqueous phase and MIBK–2butanol (7 : 3 w/w) as the organic phase produced a maximumof 23, 50, 26, 27 and 75 wt% HMF from glucose, sucrose,starch, cellobiose and inulin, respectively at 170 °C (Table 1).

Using this continuous reactor for subsequent hydrogen-ation of extracted HMF to the promising biofuel candidate,DMF46,47 via hydrogenolysis of C–O bonds to HMF over aRuCu/C catalyst, the authors demonstrated that the formationof undesired side products was suppressed to a significantextent in the presence of a modifier in the reactive aqueousphase. The reason for suppression of by-products formationcan be explained by more efficient HMF extraction facilitatedby higher partition coefficient in the presence of a modifier.High extraction of HMF in the organic phase, induced by highconcentration of the ZnCl2 catalyst (68 wt%) as well as theDMSO modifier in the aqueous phase, is also seen in the caseof cotton cellulose conversion.48 Additionally, this process ofHMF production does not require the separation of extractingorganic solvents (2-butanol, 1-butanol, 1-hexanol, MIBK, andtoluene–MIBK mixture) from HMF because of inherent fuelproperties of the solvent themselves. The only disadvantage ofthis process is the complex and energy intensive separation ofHMF from the high boiling point modifier as the modifyingagent also expects to accumulate in the organic phase. Aspenmodel simulation for predicting the energy requirement forthe separation of HMF from a low-boiling point solvent (pureMIBK) and from a high boiling point solvent (pure DMSO)shows that the vacuum evaporation method would evaporate99.5% MIBK at 13 mbar and 70 °C with a 2.5% loss of HMF,whereas DMSO evaporation under similar conditions would

cause 30% HMF loss.49 The simulation also predicts that HMFseparation from DMSO with minimal loss would require amore expensive vacuum distillation process and 40% moreenergy than that from MIBK.

In a subsequent communication, Okano et al. used anacidic ionic liquid, 1-methyl-3-(butyl-4-chlorosulfonyl) imida-zolium chlorosulfate ([MBCIm]SO3Cl) as a modifier for phaseseparation between water and acetonitrile in the water–aceto-nitrile biphasic system.50 In this process, a [MBCIm]SO3Clmodifier also acted as a dehydration catalyst for the conversionof fructose. The water–[MBCIm]SO3Cl–acetonitrile biphasiccomposition is reported to improve HMF yield and selectivity,enabling 81% HMF at 80 °C for 3 h. To claim the benefit ofthis biphasic system, control experiments were conducted inmonophasic solvents using acetonitrile–[MBCIm]SO3Cl andwater–[MBCIm]SO3Cl–HCl compositions. Significantly lowerHMF yields from the monophasic systems (48 and 26 mol%HMF from acetonitrile–[MBCIm]SO3Cl and water–[MBCIm]-SO3Cl–HCl compositions, respectively) suggest an involvementof secondary side reactions in the monophasic system. Amongseveral varying compositions of water, acetonitrile and[MBCIm]SO3Cl in the biphasic system, the composition shownin the following phase diagram (Fig. 6) accounted formaximum HMF yields (89%). A larger scale reaction underoptimized conditions produced 82% HMF, which is slightlylower than the test tube scale reaction due to mass transferlimitation of the liquid–liquid system. While [MBCIm]SO3Cl ILis an effective phase separator and an acid catalyst, its con-tamination with HMF in the organic phase is imminent andhence, possess the problem of expensive separation of thishigh boiling point IL from HMF.

To avoid the disadvantages of expensive separation of ahigh boiling point modifier from HMF, Hu et al. developed abiphasic system based on deep eutectic solvent, such aschlorine chloride (ChoCl)–malonic acid, ChoCl–oxalic acid,ChoCl–citric acid, as the reactive phase and ethyl acetate as the

Fig. 6 An experimental pseudo ternary phase diagram for the water–acetonitrile–[MBCIm]SO3Cl biphasic system with tie lines at room temp-erature (point A is the composition of a typical experiment and point B isthe composition providing the highest yield of HMF in the acetonitrilephase). This figure is obtained from ref. 50.

Table 1 Results for HMF yields from HCl catalyzed dehydration ofC6-carbohydrates at 170 °C using water–DMSO as the reactive phaseand MIBK–2 butanol as the extracting phase

SubstratesReactive phasecomposition pH

Time(min)

Conv.(%)

HMFselectivity (%)

Glucose Water 1.0 50 17 28Glucose 4 : 6 H2O : DMSO 1.0 10 43 53Glucose 5 : 5 H2O : DMSO 1.5 60 48 34Glucose 5 : 5 H2O : DMSO 1.0 17 50 47Xylose 5 : 5 H2O : DMSO 1.0 12 71 91Inulin 5 : 5 H2O : DMSO 1.5 5 98 77Sucrose 4 : 6 H2O : DMSO 1.0 5 65 77Cellobiose 4 : 6 H2O : DMSO 1.0 10 52 52Starch 4 : 6 H2O : DMSO 1.0 11 61 43Xylan 5 : 5 H2O : DMSO 1.0 25 100 66



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organic phase.51 Deep eutectic solvents have characteristicssimilar to those of ILs, but are less expensive and less toxicthan most ILs, and are sometimes biodegradable. Amongseveral of these biorenewable ILs tested as the reactive phaseas well as the catalyst for fructose conversion in a batchreactor, the ChoCl–citric acid reaction system enabledmaximum fructose conversion (97%) and HMF selectivity(92%) in 1 h under reactive to organic phase mass ratio of 1.0and mild reaction temperature (80 °C). A comparative studyshows a 9% higher HMF yield in the biphasic system than thecorresponding monophasic solvent (ChoCl–citric acid) withoutusing ethyl acetate. Although ethyl acetate accounts for a slightincrease in yield of the desired product, it facilitated easy sepa-ration of the reactive phase from the organic layer and henceallowed the recycling of the reactive phase up to 8 cycles withconsistent HMF yields. In a subsequent communication, theauthors extended the benefit of the ChoCl–citric acid–ethylacetate and ChoCl–oxalic acid–ethyl acetate biphasic systemsfor the production of HMF from inulin.52 The kinetic profile ofinulin conversion shows the formation of fructose as an inter-mediate, followed by its subsequent conversion to HMF. Undercomparable reaction conditions, the ChoCl–citric acid–ethylacetate and ChoCl–oxalic acid–ethyl acetate biphasic systemsproduced ∼55 and 64% HMF, respectively, which are 8–9%higher than the respective monophasic reaction systemswithout using ethyl acetate as an extracting solvent. In contrastto a previous report showing higher HMF yield from inulinthan that from fructose in the water–DMSO–MIBK–2 butanolbiphasic system,45 both ChoCl–citric acid–ethyl acetate andChoCl–oxalic acid–ethyl acetate biphasic systems producedlower HMF from inulin than that from fructose. This differ-ence may be due to lower partitioning of HMF into the organicphase in the present biphasic medium, thus causing rapidrehydration of HMF with water. Separate experiments to testthe effect of water on HMF selectivity indeed show a rapiddecrease in yield upon increasing the molar ratio of addedwater to fructose units in inulin above 20 (Fig. 7).

As direct conversion of inexpensive and abundant rawbiomass to HMF is the focus of many biorenewable researchprograms, Amiri and co-workers tested the effectiveness of

biphasic reaction systems for the production of HMF from ricestraw, a cheap, abundant and mainly unused agriculturalwaste.53 Rice straw contains 21% xylan, 37.5% glucan and 12%lignin. Because of the presence of xylan and glucan, simul-taneous hydrolysis and dehydration of rice straw with 0.5 wt%H2SO4 produced HMF and furfural as major products in abiphasic medium consisting of 30 wt% NaCl saturatedaqueous medium as the reactive phase and an organic solventfrom the list of THF, 1-butanol, MIBK, 2-propanol and acetoneas the extracting phase. The results showed a 2–3 fold increasein HMF yield in the biphasic system compared to the corres-ponding monophasic aqueous solvent. Depending on thenature of organic solvents and temperatures in the range of120–180 °C, HMF yields varied in the range of 45–60 g per kgof rice straw. Among all organic solvents tested, THF and1-BuOH were the most effective extracting solvents, giving 60 gHMF per kg of rice straw. These results are consistent withother literature data showing THF and 1-BuOH as good extract-ing solvents for HMF in HCl catalyzed dehydration offructose.39

One aspect of process technology development is continu-ous operation rather than batch mode. To translate the benefitof the biphasic reaction system from a batch reactor to a con-tinuous reactor, Brasholz et al. designed54 and implemented acontinuous biphasic flow reactor for HCl catalyzed conversionof fructose to HMF using 0.25 M aqueous HCl as the reactivephase and MIBK as the organic phase (Fig. 8). This flowreactor was designed in such a way that a flow of 10 wt% fruc-tose solution in aqueous HCl is mixed with a flow stream ofthe extracting phase (MIBK) in defined alternating segmentsin a heated PFA flow coil of 10 mL volume and 1 mm innerdiameter. A back pressure regulator of 8 bar was connected tothe reactor outlet to ensure continuous flow of the liquidstream. Among other reaction parameters, the flow rates of thereactive and extracting phases are found to have a significantinfluence on overall HMF yield and selectivity. The best resultswere obtained when the flow rate of MIBK stream is adjustedat 3 times higher than the flow rate of fructose stream and theresulting flow stream is heated at 140 °C for 15 min. A reactionunder the optimized condition produced 74 wt% HMF with

Fig. 7 Effect of water on HMF yield from inulin in ChoCl–citric acid–ethyl acetate and ChoCl–oxalic acid–ethyl acetate biphasic systems(modified from Fig. 2 of ref. 52). Fig. 8 Biphasic continuous flow reactor for fructose dehydration.54



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88% selectivity. It is possible to further improve the selectivityof HMF by tuning the flow rates of both streams. Thus, thiscontinuous biphasic flow reactor offers a simple, efficient andpractical device for high HMF yield in reasonable reactiontime. It should be noted that translating this flow reactorwhich uses homogeneous fructose solution to a reactor thatemploys biomass constitutes a significant challenge becauseof expected plugging of liquid flow streams by solid biomassresidue. Perhaps, a modified flow reactor with a higher innerdiameter may resolve the plugging issue.

The water–MIBK biphasic solvent system is also used foranhydrous AlCl3 catalyzed dehydration of carbohydrates undermicrowave assisted heating at 120 °C.55 Among several experi-ments carried out for fructose conversion at varying reactionconditions in pure water and biphasic media, water–MIBKsolvent combination accounted for 11% more HMF than thatobtained from monophasic reactions in pure water. Therespective HMF yields in water–MIBK and pure water were 62and 51 mol% for 5 min. Consistent with previous studies, THFappears to be a better extracting solvent resulting in compar-able yield (58 mol%) of the desired product at significantlylower temperature (100 °C). Because of the inherent benefits ofthe microwave assisted heating, this method allows reducingthe reaction time from hours to minutes and also improvesHMF yield and selectivity when compared with results for fruc-tose dehydration under conventional oil-bath heating. Thelatter reaction under oil-bath heating produced only 33 mol%HMF in 1 h. A Lewis acidic AlCl3 catalyst also produced moder-ate HMF (24–43 mol%) from difficult carbohydrate substrates,such as glucose, starch and inulin, which require sequentialhydrolysis, isomerization and dehydration steps. However,product selectivity is an issue in this process as 30% HMFexists in the form of chlorinated species, 5-chloromethylfur-fural (CMF). 1H NMR spectrum of the isolated oily productconfirms the presence of HMF and CMF in 2 : 1 molar ratio.CMF, a precursor to promising biofuel component 5-ethoxy-methylfurfural (EMF), can easily be converted to EMF via asimple etherification reaction with ethanol.56

However, CMF formation was not an issue when Yanget al.57 investigated the catalytic activity of hydrated AlCl3 forthe conversion of glucose by using the water–THF (1 : 3 v/v)biphasic system, where THF is a better extracting solvent thanMIBK. Under microwave assisted heating at 160 °C and AlCl3to glucose molar ratio of 2.5 : 1, the water–THF biphasicsystem produced 30 mol% more HMF than the monophasicsystem in pure water (Table 2). Additionally, high partitioncoefficient of the biphasic system led to a continuous separ-ation of HMF into the THF phase. As a result, HMF recovery inthe biphasic system reached as high as 94% with a significantdecrease in by-products (lactic acid and LA) formation. As seenin Table 2, a further increase in HMF yield and selectivity isrecorded in the presence of 35 wt% NaCl in the aqueous phasedue to further increase of the R value because of the salting-out effect.41,42

While the exact pathway for HMF formation has beendebated over the years, the kinetic profile of AlCl3 catalyzed

dehydration of glucose shows direct evidence for fructose for-mation as an intermediate species, followed by its rapid dis-appearance to HMF (Fig. 9). This result supports the fact thatHMF formation with the Lewis acid catalyst occurs via isomeri-zation of glucose to fructose. Analysis of relevant kineticmodels for the observed intermediate and product formationrevealed that the rate of HMF formation is approximately 4times faster than the glucose isomerization to fructose. In aprevious study,55 glucose dehydration with a AlCl3 catalyst hasbeen monitored by 1H NMR spectroscopy to gain a betterunderstanding of the mechanism of isomerization. 1H NMRspectra showed a line broadening of –OH proton signals ofglucose in the beginning of the reaction. This line broadeningof –OH protons indicated H-bonding interaction between theCl atom of AlCl3 and –OH protons of glucose forming anAlCl3–glucose adduct. The line broadening of –OH protonscorresponding to –H⋯Cl– interaction disappeared uponheating the reaction mixture at 100 °C for 40 min, with appear-ance of a new signal at 9.49 ppm corresponding to the –CHOproton signal of HMF. Similar line broadening of the –OHproton signals of glucose has been observed in the case ofSnCl4,

55,58 Yb(OTf)3 (OTf = trifluoromethanesulfonate)55 andZr(O)Cl2

59 catalyzed dehydration of glucose. Based on theseobservations, the authors proposed a catalytic cycle for glucoseisomerization to fructose in which Al[(OH)(H2O)5]

2+ is formedby hydrolysis of AlCl3 with water (Fig. 10). This active catalyticspecies, Al[(OH)(H2O)5]

2+ acts as a potential electrophile and

Table 2 Glucose conversion with AlCl3 catalyst in different media

SolventConv.(%)

HMFyield (%)

Lactic acidyield (%)

LA yield(%)

Single phase (water) 98 22 17 10Biphasic (water–THF) 99 52 13 TraceSingle phase (water–NaCl) 98 17 — 29Biphasic (water–NaCl/THF) 99 61 — 1Biphasic (water–NaCl/THF) 30 12 — 2

Fig. 9 Conversion of glucose as a function of time using hydrated AlCl3catalyst in water–NaCl/THF biphasic medium (obtained from ref. 57).



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reacts with α-glucopyranose to form intermediate A, as shownin Fig. 10. Intermediate A is possibly converted to fructofura-nose via a hydride transfer, followed by cyclization.60 Thetransformation of fructofuranose to intermediate E occurs viaa cyclic pathway assisted by a proton that is generated duringAlCl3 hydrolysis. In agreement with earlier findings,24 thetransformation of oxonium ion (intermediate C) to intermedi-ate D is proposed to occur via two pathways in which Cl− actsas a base as well as a nucleophile for abstracting proton fromthe oxonium ion.

The potential of the combined AlCl3/water–NaCl–THFbiphasic system has been further demonstrated for the conver-sion of intact lignocellulosic biomass (corn stover, pinewood,switchgrass, and poplar).61 Because of the presence of hemi-cellulose and cellulose biopolymers in the biomass, both HMFand furfural were produced concurrently upon catalysis(Table 3). However, the relative yield of HMF (19–26 mol%)was significantly lower than that of furfural (51–66 mol%)based on the literature values of total hexose and pentoseunits by weight.62,63 This difference in HMF and furfural yieldsmay be due to the fact that cellulose is more recalcitrant thanhemicellulose.64 The complex structure of lignocellulose, con-taining cross-linkers of hemicellulose with cellulose fibers intomicrofibrils and cellulose with lignin,65 makes it harder toconvert intact biomass to the reactive sugar components of

cellulose. In this context, the water–LiCl/dichloroethane bipha-sic system has yielded promising results for HCl catalyzed con-version of pure microcrystalline cellulose and lignocellulosicbiomass, e.g., filter paper cotton, newsprint, wood, corn stoverand straw.56 An integrated one-pot reaction between 10 gbiomass substrates (filter paper, cotton and newspaper werecut into 0.25–1 cm2 pieces; wood, corn stover and straw weremade into sawdust or smaller pieces and then ball-milled topowder) and 75 mL concentrated HCl in the presence of 10 gLiCl in a batch reactor at 65 °C for 30 h and continuous extrac-tion of organic fragments into the extracting phase resulted in72, 72, 60, 45, 43 and 36 wt% furanic product from filter

Table 3 Furfural and HMF yields from various sources of lignocellulosicbiomass

BiomassTemp(°C)

Furfural(%)

Xylose(%)

HMF(%)

Glucose(%)

Corn stover 160 55 <1 14 1Pinewood 160 38 <1 42 1Switchgrass 160 56 1 13 <1Poplar 160 64 <1 15 <1Cellulose/xylan 160 66 0 14 1Pinewood 180 61 <1 35 1Cellulose 180 — — 37 <1

Fig. 10 Proposed mechanism for glucose dehydration to HMF with AlCl3 catalyst.



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paper, cotton, newsprint, wood, corn stover and straw, respect-ively. However, high concentration of chloride ions in the reac-tion medium is perhaps the reason for substitution of thehydroxyl group of HMF giving CMF as a major fraction alongwith small amount of HMF, furan monocarboxylic acid andLA. Furthermore, ball-milling renders the biomass more amen-able to hydrolysis, but such pretreatment is not scalable toindustrial scale production.

THF has also been reported as an effective extractingsolvent in the THF–tetraethyl ammonium chloride (TEAC)/fructose/NaHSO4·H2O melt biphasic system for the productionof HMF from fructose.66 This biphasic medium containing amixture of 50 wt% fructose, TEAC and CrCl3 catalyst and 5 mol%of NaHSO4 (with respect to glucose) as the reactive phaseproduced 93.5 wt% HMF at 120 °C in 70 min. Low viscosity ofthe reactive melt at 120 °C favored mass transfer and easy sepa-ration of HMF from the reactive phase into the organic phase.Although this biphasic medium is beneficial in improvingHMF yield by about 13 wt% as compared to the correspondingmonophasic system without THF, the selectivity of HMF didnot improve by this method.

Dumesic et al. also investigated the conversion of glucoseto HMF using combined HCl/metal chloride catalysts, includ-ing AlCl3, to elucidate the mechanistic role of both Brønstedand Lewis acidic catalytic materials in the said conversionprocess by carrying out the reactions in water–NaCl/2-sec-butyl-phenol (SBP) and water–NaCl/THF solvent systems (organic toaqueous mass ratio = 2).67 In the absence of Lewis acidic metalchlorides, glucose conversion with Brønsted acidic HCl at pH2.5 produced HMF with very low yield and selectivity. Thisresult agrees well with Abu-Omar’s findings showing very lowHMF yield and selectivity from glucose conversion with theHCl catalyst alone.57 Consistent with AlCl3 catalyzed reaction,a significant improvement in HMF yield is noted in the pres-ence of Lewis acidic metal chlorides. Depending on the natureof the metal chloride, HMF yields varied in the range of

60–38% (Table 4). Most importantly, the kinetic profile for pro-gression of glucose conversion with a combined HCl/metalchloride catalyst showed the formation of fructose as an inter-mediate, the concentration of which varied depending on themetal chloride salt used. Al3+, being the hardest Lewis acidamong all metal ions studied, strongly interacts with theoxygen atoms of the hydroxyl groups of glucose, and henceaccounts for higher fructose concentration and consequentlyhigher HMF yields. It should be noted here that glucose con-version with HCl alone did not show the formation of fructoseintermediates, which suggested an involvement of a differentmechanism for direct conversion of glucose to HMF with theBrønsted acid catalyst. It has been suggested that a carbocationis formed at the C-2 position of open-chain glucose, whichreacts with the hydroxyl group of glucose at the C-5 position toform a tetrahydro-3,4-dihydroxy-5-(hydroxymethyl)-2-furanalde-hyde intermediate.68 As shown in Fig. 11, HMF is formed viasequential removal of water from the latter intermediate.

As mentioned above, bi-functional HCl/metal chloride cata-lyzed dehydration of glucose progresses via two routes, namely(i) isomerization of glucose to fructose and (ii) direct conver-sion of glucose with the formation of tetrahydro-3,4-dihydroxy-

Table 4 Conversion of glucose to HMF with HCl and bi-functionalHCl/metal chloride catalysts in water–NaCl/SBP biphasic solvent at pH1.8 and 170 °C

Catalyst Time (min) Conv. (%) HMF selectivity (%)

HCl 30 15 52HCl 420 91 30HCl/AlCl3 40 91 68HCl/SnCl4 45 90 58HCl/VCl3 90 92 53HCl/GaCl3 120 90 50HCl/InCl3 150 86 52HCl/YbCl3 120 93 46HCl/DyCl3 160 93 41HCl/LaCl3 240 87 44

Fig. 11 Reaction scheme for Brønsted acid catalyzed dehydration of glucose to HMF.67,68



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5-(hydroxymethyl)-2-furanaldehyde intermediate. To explorethe role of Lewis acidic metal chloride catalyst alone, the con-version of glucose and other carbohydrate substrates with thelanthanide based metal chloride catalysts (YbCl3, DyCl3 andLaCl3) has been reinvestigated at pH 5.5 in the water–NaCl/SBPbiphasic solvent system.69a Using SBP to aqueous phase massratio of 2, glucose dehydration at pH 5.5 without an isomeriza-tion catalyst showed a small conversion of the substrate(20 mol%) for 80 min. A similar reaction using a 25 mM YbCl3catalyst improved both glucose conversion (90 mol%) andHMF yield (41 mol%) to the same extent as that observed withthe bi-functional catalyst, HCl (pH 1.8)/YbCl3.

67 This compari-son suggests that the glucose to fructose isomerization stepdominates in glucose dehydration with both catalytic systems.Interestingly, the bi-functional Brønsted/Lewis acid, HCl(pH 1.8)/YbCl3, catalysis reaction took twice the time(150 min) that of the YbCl3 catalysis reaction (80 min) toachieve a similar glucose conversion and HMF yield. While thereasons for the slower reaction with the LnCl3 catalyst athigher HCl concentrations are unclear, the above comparisonreveals that the LnCl3 catalysis at pH 5.5 is more practical fromboth economical and environmental points of view. Thekinetic isotope labeling and NMR spectroscopic data for theinteraction of catalytic species and substrate reveals the invol-vement of an intra-molecular H-transfer from C-2 to C-1 inglucose/fructose isomerization,69b,70 and supports the pro-posed mechanism observed for AlCl3 catalyzed conversion ofglucose.55

Biomass derived SBP solvent demonstrating higher HMFyield (68%) with better HMF extraction (97%) than the THFsolvent (57% yield, 93% HMF extraction) under comparablereaction conditions is indeed attractive as environmentallyfriendly extracting solvents gain ground in biorefinery pro-cesses.67 The use of an SBP solvent having high R values (90and 50 with and without NaCl saturation in the aqueousphase)71 is advantageous because of (i) fast HMF extraction,(ii) low amounts of mineral acids dissolved in SBP therebyeliminating energy intensive separation of mineral acid fromthe product layer, and (iii) SBP can be derived from biomass

lignin. While the authors list SBP’s higher boiling point thanthat of the HMF product as an advantage, this feature can beinterpreted as a drawback because it requires intensive energyto remove the product via distillation.

One aspect of HMF process technology development isminimization of operational temperature (i) to reduce pro-duction cost by lowering energy requirement and (ii) toimprove HMF selectivity by eliminating undesired secondaryreactions. A biphasic system consisting of imidazolium basedIL ([BMIM]Cl) as the reactive phase and THF as the organicphase has addressed this issue by demonstrating effective fruc-tose dehydration with WCl6 catalyst at lower temperatureranging from room temperature to 50 °C.72 A test reactionbetween fructose and WCl6 catalyst in a biphasic reactorhaving capability of concurrent extraction of the desiredproduct and evaporation of the organic phase results in 72%HMF at 50 °C in 1 h. One of the problems of biphasic systemscontaining high viscous IL is poor mixing between the reactiveand organic phases, which hinders HMF extraction and hencecan often give lower HMF yield. This is exactly observed infructose dehydration with WCl6 catalyst in the [BMIM]Cl–toluene solvent system where HMF yield was suppressed by25% in comparison to the [BMIM]Cl–THF system under com-parable reaction conditions. A summary of HMF yields underbest reaction conditions using different homogeneous cata-lysts in biphasic solvent systems is shown in Table 5.

5. HMF production usingheterogeneous catalysts

Collective research efforts of HMF production technology overthe past decade and better understanding of the mechanisticroles of the Brønsted and Lewis acids has contributed signifi-cantly to developing a more effective homogeneous catalysisstrategy, process design and extraction methodologies for highselective HMF formation by minimizing undesired side reac-tions. However, energy intensive separation of HMF from thereaction media remains an issue. Although this issue has been

Table 5 A summary of HMF yields using homogeneous catalysts in biphasic solvent systems

Entry (ref.) Substrate Reactive phase Organic phase Catalyst Temp (°C) Time (min) HMF yield (%)

139 Fructose H2O–Na2SO4 1-Butanol HCl 180 20 68244 Fructose H2O–DMSO–PVP (4 : 1 : 2) MIBK–2-butanol (7 : 3) HCl 180 3 77345 Inulin H2O–DMSO (5 : 5) MIBK–2-butanol (7 : 3) HCl 170 5 75450 Fructose H2O–[MBCIm]SO3Cl Acetonitrile [MBCIm]SO3Cl 80 180 89552 Fructose ChoCl–citric acid Ethyl acetate Citric acid 80 60 89652 Inulin ChoCl–oxalic acid Ethyl acetate Oxalic acid 80 60 64753 Rice straw H2O THF H2SO4 180 180 16854 Fructose H2O–NaCl MIBK HCl 140 15 74955 Fructose H2O MIBK AlCl3 120 5 621057 Glucose H2O–NaCl THF AlCl3 160 5 611161 Cellulose H2O THF AlCl3 140 60 371266 Fructose H2O–TEAC–NaHSO4 melt THF CrCl3 120 70 93.51367 Glucose H2O–NaCl 2-sec-Butylphenol HCl–AlCl3 170 40 611469a Glucose H2O–NaCl 2-sec-Butylphenol YbCl3 170 80 411572 Fructose [BMIM]Cl THF WCl6 50 60 72



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addressed by developing biphasic reaction systems, partial dis-solution of mineral acids and metal halides in the productphase and hence their contamination with the crude productstill requires energy intensive separation of HMF from con-taminants. To avoid this disadvantage, several heterogeneouscatalytic materials having controlled acid sites and shape havebeen tested in recent years by utilizing biphasic media. Unlikethe homogeneous catalyst, several factors of heterogeneouscatalysts such as preparation condition of the catalyst, struc-tural properties, accessibility of acid sites, surface area, porevolumes and nature of acid sites play important roles in deter-mining the efficiency of solid catalyzed conversion of hexoserich carbohydrates to HMF. For example, a strong Brønstedacidic cation exchange resin, Dowex 50wx8–100 of50–100 mesh beads, was prepared from sulfonated copolymerand divinyl benzene, and used for fructose conversion in thewater–acetone biphasic system.73 Using the water to acetoneweight ratio of 7 : 3, recyclable Dowex 50wx8–100 catalystyielded 73 mol% HMF with 91% fructose conversion at 150 °C.To compare the partition efficiency of the water–acetone bipha-sic system, the authors performed another experiment in purewater which produced only 34 mol% HMF yield with 83% fruc-tose conversion, suggesting that the investigated biphasicsystem has a high partition coefficient. Although continuousextraction of HMF into the extracting phase eliminated HMFrehydration to a significant extent, formation of humin oligo-mers catalyzed by strong Brønsted acidic sulfonate groups isthe reason for the difference in observed HMF yield and fruc-tose conversion.

In contrast to the disadvantage of Brønsted acidic Dowex50wx8–100 catalyst in humins formation, Lewis acidic zeolitebeta topology (Sn-beta) and Brønsted acidic HCl combinationseems beneficial to achieve higher HMF selectivity.74 Usingwater–NaCl/THF biphasic media, Sn-beta catalyzed glucosedehydration shows 79 wt% conversion with 72% HMF selecti-vity under glucose to Sn molar ratio of 200. While the biphasicmedia itself accounted for 66% higher HMF selectivity and34 wt% higher glucose conversion than the correspondingmonophasic system without THF, the bi-functional HCl/Sn-beta catalyst resulted in a further increase in HMF selectivitycompared to the Sn-beta catalyst alone. Similar to xylose dehy-dration with the Sn-beta catalyst in which the reaction pro-gressed via isomerization of xylose to xylulose intermediate,75

glucose conversion with Lewis acidic Sn also takes place viathe formation of a fructose intermediate. Besides dehydrationvia a isomerization pathway, a parallel pathway for direct

conversion of glucose to HMF in the presence of HCl catalystis perhaps the reason for higher HMF selectivity with thebi-functional Sn-beta/HCl catalyst.67

While the dehydration reaction requires an acid catalyst,acid density of the catalyst is not only the critical parameter indetermining overall effectiveness of the catalyst as well as HMFselectivity. To justify this fact, Zhao et al. have used a series ofrecyclable solid acid catalysts for the conversion of concen-trated fructose solution (30–50 wt%) to HMF in water–MIBKbiphasic solvent.76 As seen in Table 6, heteropolyacid,Cs2.5H0.5PW12O40, catalyst having lower acid density(1.52 mmol g−1) than the Brønsted acidic Amberlyst-15 (aciddensity = 2.9 mmol g−1) or sulfated zirconia (acid density =1.87) mmol g−1 is more effective, giving 95% HMF selectivitywith 74% overall yield. However, a longer reaction time isfound to have a negative effect on HMF selectivity due to itsrehydration with water. Such rehydration predominantlyoccurrs with the Brønsted acidic catalytic materials (Amberlyst-15 and sulfated zirconia) resulting in a significantly lowerselectivity of the desired product. Besides rapid rehydration,the high rate of oligomerization by the Amberlyst-15 and sul-fated zirconia catalysts can also contribute to their low productselectivity. The higher catalytic activity of solid catalysts havinglower acid density is also demonstrated by Yang et al.77 Forexample, modified hydrated niobium oxide (NA-p), preparedby treating niobium oxide (NA) with 1 M phosphoric acid, fol-lowed by calcination of the resultant sold at 300 °C for 3 h, isfound to have a higher surface area (214.9 m2 g−1) and aciddensity (4.4 mmol g−1) than the parent NA material. A modi-fied hydrated tantalum oxide (TA-p) catalyst, prepared by asimilar phosphoric acid treatment and calcination method,has a lower surface area (141.5 6 m2 g−1) and acid density(1.5 mmol g−1) than the NA-p material.78 However, catalyticactivities of both NA-p and TA-p materials were comparable forfructose conversion, giving 89 and 91 wt% HMF, respectively,in water–2-butanol biphasic media. Interestingly, NA-p cata-lyzed conversion of glucose and inulin produced significantlylower HMF than the corresponding reactions with the TA-pcatalyst; respective HMF yields from glucose with NA-p andTA-p catalysts are 49 and 70 wt% and those from inulin are 54and 95 wt%. A comparative analysis of these results revealsthat the NA-p catalyst is less effective even though it hashigher acid density and surface area than the TA-p catalyst.Although the authors neither elucidated the reasons for loweractivity of the NA-p catalyst nor gave any data for by-productsformation, it is presumed that the higher acid density of the

Table 6 Fructose conversion, HMF selectivity and yield with different solid catalysts at 105 °C in water–MIBK solvent

CatalystsAcid density(mmol g−1)

Reactiontime (h)

Conversion(%)

Selectivity(%)

Yield(%)

TOF(h−1)

Zeolite 1.94 1 58 92 54 3.47Cs2.5H0.5PW12O40 1.52 1 78 95 74 3.66

2 95 82 77 2.25SO4

2−/ZrO2 1.87 1 79 62 49 4.67Amberlyst-15 2.9 1 100 48 48 6.00



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NA-p catalyst could accelerate HMF rehydration36,79 andhumin formation in the reactive aqueous phase. Differences inother material properties, e.g., pore diameter, could also bethe reason for lower activity of the NA-p catalyst. In a recentpublication,27 biorenewable glucose supported sulfonatedcarbonaceous material having total Brønsted acid density of2.0 mmol g−1 is shown to be less effective in HMF selectivitythan a similar carbonaceous catalysts containing Lewis acidicTiO2 mesoporous sites (0.071 mmol g−1) as well as signifi-cantly lower Brønsted acid density (0.027 mmol g−1).28

Although total acidity of the Ti-containing carbonaceousmaterial is significantly lower than the Ti-free carbonaceouscatalyst, the superior HMF selectivity in the product by theTi-containing catalyst has been explained by the presence of itsLewis acidic sites as well as higher surface area (42.5 m2 g−1)than the Ti-free material (<1 m2 g−1).

Because of the benefit of biphasic media as well as ease ofrecyclability of a solid catalyst, several researchers haveadopted this method for HMF production in recent years. Inthis direction, a self-assembled Lewis acidic mesoporous TiO2

nanoparticulate catalyst of particle size 10–20 nm has beenprepared using sodium salicylate as a templating agent.80 Thiscatalyst, having acid density of 0.45 mmol g−1 but high surfacearea of 326 m2 g−1, showed moderate activity for hydrolysisand dehydration of a number of carbohydrate substrates intoHMF in water–MIBK biphasic solvent. Using the water to MIBKvolume ratio of 1 : 2 and at mild reaction temperature of130 °C, maximum reported HMF yields from fructose andglucose are 40 and 26 mol%, respectively, which are about10 mol% higher than the corresponding yields in single phaseusing pure water as a solvent. A similar HMF yield (35 mol%)from fructose in water–MIBK biphasic solvent is also reportedin a subsequent publication using the Lewis acidic titaniumphosphate nanoparticle catalyst (MTiP-1).81 MTiP-1, preparedby using Pluronic P123 as a structure directing agent andhaving large pore diameter of 7 nm, was separated by a simplecentrifugal method and recycled for several cycles without asignificant loss in its catalytic activity. Recently biopolymersodium alginate templated porous TiO2 nanocatalysts (Fig. 12),containing strong Lewis acidic sites as determined by pyri-dine-IR and NH3-TPD methods, have been prepared for the

production of HMF from unutilized abundant sugar deriva-tives, such as D-mannose, D-galactose and lactose, in water–MIBK biphasic solvent.82 Total acid density of the TiO2 NPsmaterial prepared under three different conditions (roomtemperature, 0 °C and hydrothermal at 60 °C), varied as a func-tion of their synthetic conditions. Among these three varieties,the material prepared under hydrothermal condition (rep-resented as TiO2–H) is most effective even though its total aciddensity (1.10 mmol g−1) is lower than the TiO2–R catalysthaving a total acid density of 1.21 mmol g−1.

The role of organic solvents of the biphasic media inimproving the HMF yield and selectivity by minimizing the de-activation of the external pore volume of zeolites and amor-phous aluminosilicate catalysts has been investigated byOrdomsky et al.83 In the absence of organic solvent (e.g.,MIBK), fructose dehydration with zeolite and aluminosilicatecatalysts having Si/Al ratio in the range of 11–16 and acid den-sities in the range of 0.2–1.1 mmol g−1, achieved 80–100% con-version in 5 h at 165 °C. However, poor HMF selectivity(maximum 50%) and very low LA/formic acid in the isolatedproduct suggested the formation of a significant amount ofhumins by-product. The initial induction period in the kineticprofile of fructose conversion and decrease in HMF selectivityas a function of fructose conversion for all zeolite catalysts ledto the hypothesis that fructose transformation takes placeinside the pores of the catalyst and that HMF or its precursorcyclic intermediate84 forms humin inside the pore before HMFcan desorb from the pore. One way to validate this hypothesisis to test fructose dehydration with these catalysts in a biphasicsolvent system for concurrent extraction of HMF as it isformed in the aqueous phase. As expected, HMF selectivityimproved to almost 98% in the beginning of the reaction at20% conversion, but slowly decreased to ∼60% as the conver-sion increased to almost 100%. An initial increase in HMFselectivity is attributed to the fact that HMF was readily de-sorbed from the pore of the catalyst by MIBK, and thereby sup-pressed humins formation inside the pore. This argumentsupports the result of aluminosilicate catalysis reactionshaving lower acid density. While lower acid density of the alu-minosilicate catalyst explains its lower catalytic activity, thiscatalyst without any micropores showed no improvement inHMF selectivity in the presence of MIBK solvent such as thatobserved for zeolite catalyzed reactions. This observation sup-ports the fact that fructose dehydration occurs inside the poreof the catalyst.

To further elucidate the role of the pore diameter in HMFselectivity as well as its secondary transformation to unwantedside products, Ordomsky et al. prepared a series of hetero-geneous materials with different pore diameters and differentamount of Lewis and Brønsted acid density (Table 7) for fruc-tose dehydration.85 While the catalytic activity of fructose con-version correlates with the strength of the Lewis acidity of thecatalysts, the MOR zeolite containing highest acid density(1.1 mmol g−1) exhibits the lowest fructose conversion, whichis due to the smallest pore diameter of this material. On theother hand, HMF selectivity in the product correlated with the

Fig. 12 Conversion of mannose to HMF using alginate derived TiO2

NPs catalyst.



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Brønsted acid density of the catalyst. Thus, maximum selecti-vity in HMF yield is seen with the MOR and Amberlyst-15catalysts having strong Brønsted acidity, whereas the alumino-silicate catalyst with weak Brønsted acidity shows lower HMFselectivity. This behavior of the Lewis and Brønsted acidic sitesin the dehydration reaction also reflected their activity patterntowards by-products formation via secondary HMF transform-ations (Fig. 13). For example, Brønsted acid sites of the MORand Amberlyst-15 catalyst strongly interacts with the carbonylgroup of HMF, facilitating its desorption in the presence oforganic solvents. As a result, HMF selectivity improved toabout 75–80% with the Amberlyst-15 catalyst in the water–MIBK biphasic solvent (water–MIBK volume ratio = 5). Whilethe authors explain that the Brønsted acidity of Amberlyst-15 isthe reason for its high selective HMF formation, this obser-vation can be interpreted by the high pore diameter of theAmberlyst-15 catalyst. On the other hand, Lewis acid sites ofthe alumina, aluminosilicate, niobic acid and zirconium phos-phate catalysts tend to adsorb fructose on the surface of thecatalyst by multiple surface interactions of carbonyl andhydroxyl groups with Lewis acid sites before HMF can be de-sorbed. Thus, fast cross-oligomerization between fructose andHMF takes place on the catalyst surface and forms huminby-products.

6. Conclusions

HMF is a promising biomass derived platform chemical forthe production of high value chemicals and liquid fuels that

are currently obtained from petroleum feedstock. Developmentof effective catalysts and reactors designed to achieve highyield and selectivity of HMF from abundant biomass contain-ing C6-sugars is a viable strategy for the modern biorefinery.HMF production technology over the past decade has primarilyfocused on the utilization of homogeneous mineral acids andmetal halide catalysts in pure water or high boiling point sol-vents (DMSO, DMF, and ILs) alone or in modified high boilingpoint solvents mixed with aqueous media. These reactionssuffered from low conversion and selectivity of the desiredproduct due to the involvement of secondary reactions leadingto the degradation of HMF to undesired side products via re-hydration and oligomerization pathways. Besides low yield andselectivity, energy intensive separation and purification ofHMF from high boiling point solvents and by-products areamong the reasons for its high production cost, which createsa bottleneck for its sustainable utilization for making othervalue chemicals and fuels on commercial scale.

Leveraging the learning from these drawbacks and betterunderstanding of the mechanistic roles of both Brønsted andLewis acidic sites for HMF and by-products formation hasdirected the current research efforts of HMF productiontowards development of biphasic reaction systems as well asheterogeneous catalysts containing balanced Brønsted andLewis acid sites. As a result, several improvements have beennoted on a laboratory scale for continuous extraction of HMFinto the organic phase by using solvents having a high par-tition coefficient as well as by modifying the reactive phasewith inorganic salts. Among several organic solvents tested,biomass derived 2-MeTHF and petroleum based THF,2-butanol and 2-butanone solvents are found to have high par-tition coefficient values. While continuous improvement ofbiphasic media has enhanced HMF yield and selectivity byminimizing secondary reactions, there are fewer reports on thedevelopment of continuous reactors design or testing of thelaboratory scale processes on a larger scale reaction to examinetheir production viability, particularly from intact biomassfeedstock. Investigation of solid acid catalysts containing vari-able pore diameters and Lewis and Brønsted acid densitiessuggest that the mesoporous materials having large pore size,high surface area and balanced Lewis to Brønsted acid den-sities perform the best for high selective HMF production. Acombination of both chemistry and engineering approaches todevelop more effective catalytic systems and process chemistry,and cost-effective purification of the desired product arenecessary to lower HMF production costs.

Acknowledgements

The authors acknowledge financial support from the Centerfor direct Catalytic Conversion of Biomass to Biofuels (C3Bio),an Energy Frontier Research Center funded by the U.S. Depart-ment of Energy, Office of Science, and Office of Basic EnergySciences under Award Number DE-SC0000997.

Fig. 13 Fructose dehydration and HMF oligomerization routes.

Table 7 Properties of heterogeneous catalysts having different Lewisand Brønsted acid densitiesa

SampleSurface area(m2 g−1)

Pore size(nm)

TDP NH3(mmol g−1) L/B

SiO2–Al2O3 327 9.5 0.012 2Al2O3 262 9.8 0.072 —ZrPO4 93 8.5 0.11 2Nb2O3 108 8.0 0.24 2.4MOR 420 0.5–0.8 1.1 0.2Amberlyst-15 53 30 — —

a B = Brønsted acidity; L = Lewis acidity.



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