Synthesis of 5-Hydroxymethylfurfural from Dehydration of Fructose And Glucose Using Ionic Liquids

A produção do 5-hidroximetilfurfural (HMF) a partir da desidratação de açúcares é uma alternativa para a obtenção de materiais de partida na produção de poliésteres, poliamidas e poliuretano a partir de fontes renováveis. Além disso, a oxidação do HMF leva ao ácido 2,5-furanodicarboxílico (FDCA) potencial substituto para o ácido tereftálico (TA), proveniente do petróleo, intensamente utilizado na produção de polímeros, tais como, o poli(tereftalato de etileno) (PET). A substituição do TA por materiais obtidos a partir de fontes renováveis é de grande interesse do ponto de vista de obtenção de produtos com elevado grau de sustentabilidade.


Introduction
Since the end of the 20 th century the interest in the use of raw materials from renewable resources for the production of a variety of petrochemical intermediates has been growing in order to develop the replacement of petroleum as a source of raw materials and energy.2][3] Several product classes are promising natural substitutes of petroleum derivatives, the biomass being the first one obtained from renewable sources.[6][7] Currently the sustainable industrial conversion of biomass still depends on the development of specific technologies involving processes for biomass conversion related to equipment for producing fuels, chemical products and energy. 1,4,8,9An example of this is the obtainment of 5-hydroxymethylfurfural (HMF), see structure in Figure 1, and furfural from cellulose or other carbohydrates as glucose, fructose and starch.[12][13] The catalytic oxidation of HMF produces 2,5-furandicarboxylic acid (FDCA), a material that can substitute the terephthalic acid (TA) in PET production or isophthalic acids in the manufacture of polyamides, polyesters and polyurethanes.The replacement of TA by FDCA constitutes an important step for sustainable processes development, thus FDCA production could represent a huge market.][16] The synthesis of HMF, shown in Scheme 1, comprises many problems, especially those associated with the formation of byproducts through parallel reactions.The formation of secondary products as levulinic acid (LA) and formic acid (FA) influence the overall efficiency of the process, as well as formation of humins polymers which is the main cause of low HMF yields reported in most of studies available in this area. 11,17,18MF produced with low yield and the high cost of industrial production are the factors that limit its availability.Some processes described in the literature produce HMF using acid catalysts for the conversion of fructose as substrate.However, the disadvantage in the use of these catalysts is that secondary reactions usually occur, burdening the process by the loss of material and the necessity of purifying the product.Moreover, HMF decomposes under acidic conditions in water. 19hen using glucose as substrate, the situation is more critical due to the low HMF yield and the production of larger amounts of byproducts.Using glucose implies the isomerization into fructose by selective methods, leading to an increase in yield of the desired final product. 18ifferent catalysts are employed for the synthesis of HMF, such as, ion exchange resins, [20][21][22] minerals and organic acids, [23][24][25] zeolites 6,26 and oxides. 27These catalytic systems, besides producing HMF with low yields and forming byproducts, high temperatures and longer reaction times are usually required. 28olid acid catalysts such as SO 4 2-/ZrO 2 -Al 2 O 3 present strong acidity and were used in the conversion of glucose and fructose to HMF yielding 47.6% and 68.2%, respectively in 4 h at 130 ºC.Nb 2 O 5 catalyst (calcined at 400 ºC) was effective for the production of HMF due to its Lewis acid sites.This catalyst showed a total fructose conversion with 86.2% HMF yield (2 h reaction at 120 ºC). 27,29i et al. 20 studied the catalytic dehydration of fructose into HMF using microwave heating and a solvent media composed by acetone-water, the catalyst being a strong acid cation exchange resin (Dowex 50wx8-100) that is insoluble in water.Yields of 73.4% for 5-HMF and a conversion of 94% at 150 ºC were obtained.The resin showed a good stability at high temperatures enabling its reuse 5 times without observing catalytic activity decrease.
An efficient strategy for the direct production of HMF from glucose and cellulose (from ligninocellulose) was proposed using ionic liquids (ILs) based in imidazolium in the presence of CrCl 3 by microwave radiations, yields behind 60-90% were obtained.This reaction was considered a significant advance in the use of ligninocellulose for the production of carbohydrates via a green process. 30The use ILs, besides leading to satisfactory results, provides an environmental alternative process where volatile organic solvents are substituted representing an attracted interest in different areas. 31u et al. proposed a mechanism employing SnCl 4 as catalyst for the glucose to HMF conversion in IL, 1-ethyl-3methylimidazolium tetrafluoroborate (EMI.BF 4 ), where the Sn +4 center interacts with a acyclic and five or six member ring intermediates. 32Zhao et al. 19 studied an alternative system, for which dehydration takes place more easily as the metallic halides catalyst (CrCl 2 , CrCl 3 , FeCl 2 , FeCl 3 , CuCl, CuCl 2 , VCl 3 , MoCl 3 , PdCl 2 , PtCl 2 , PtCl 4 or RuCl 3 ) is dissolved in the IL.With this method HMF is obtained in high yields (63 to 83%) and secondary reactions are minimized (for example, levulinic acid formation is 0.08%).Among the catalysts tested the highest HMF yield was achieved using CrCl 2 which reaches values around 70%.  Sidhpuria et al. used nanoparticles immobilized in ILs in the dehydration of fructose obtaining 63% HMF yield. 32,33nother alternative is employing an IL as catalyst and solvent.For example, the use of 1-H-3-methylimidazolium chloride (HMI.Cl) in the dehydration of fructose produced HMF with a yield of 92% after 45 minutes of reaction time.When this catalytic system was used with sucrose, a rapid cleavage of sucrose into fructose and glucose was observed.The fructose was then transformed quickly into HMF with high yield and without the formation of byproducts and on the other hand at the same time, only 3% of the glucose was converted in HMF.The low transformation of glucose is due the necessity of its previous isomerization into fructose before the dehydration reaction to produce HMF. 34,35urans produced from carbohydrates have high potential for the synthesis of monomers and then polymeric materials based on renewable sources.They can be obtained by synthesis which provides high yields and low production costs, but still should be investigated in order to optimize the process.A prime example is the use of ILs based on imidazolium in dehydration processes sugar (fructose or glucose) with satisfactory results related to the selectivity that can be improved in the case of the glucose and showed in this paper. 36,37his study reports results of HMF synthesis from dehydration of fructose or glucose using imidazolium based ILs as solvent and acid catalyst.
Were charged into the flask ionic liquid (4 g), fructose or glucose (0.4 g) and HCl acid (9%) (wt.%).The reaction system was placed in an oil bath adjusted to a range of 80 to 120 °C (according IL melting point), during 8 or 12 minutes. 40After reaction time, the reaction mixture was analyzed by high performance liquid chromatography (HPLC) equipped with UV and refractive index detectors.
The HPLC measurements are conducted using a Shimadzu LC-20AD with UV and refractive index detector.The column Aminex HPX-87H (300 mm × 7.8 mm) is employed to separate the reaction mixture.General HPLC conditions for analysis of sugars conversion and HMF yield: refractive index detector; column temperature: 65 ºC; eluent: 0.6 mL min -1 H 2 SO 4 pH 2; injection amount: 40 μL. 41The amount of fructose, glucose and HMF was determined by using calibration curves.Analysis chromatogram of a standard solution containing glucose, fructose and HMF by HPLC are shown in Figure 3.
The sugar conversion, HMF yield and HMF selectivity were defined as follows: Sugar conversion (mol% HMF Selectivity (mol%) HMF yield (mol%)   above 85%) than glucose (yields about 30%).The acid dissolved in the ILs is very selective in HMF formation (> 85%).The same performances are not observed when tests are performed with glucose as substrate.The poor conversion of glucose is linked to the need to isomerize glucose to fructose for subsequent dehydration, as described in literature. 40,42igure 4 and 5 repeat data of Table 1 evidencing the effect of the alkyl chain lengh of the ILs in dehydration of frutose and glucose respectively.The modification of ILs nature leads to considerable difference in selectivity and yield data for fructose reaction when the reaction time is 12 minutes, but not for 8 minutes reaction time (Figure 4).This results can indicate that with a higher reaction time decomposition of HMF occurs and ILs with a longer alkyl chain avoid the formation of byproducts (compare in Table 1, HMF selectivity in reaction 2 with reactions 6, 10 and 14).About the glucose reaction (Figure 5), conversion is observed only when C 12 MI.Cl and C 16 MI.Cl are employed and attains high value (ca.80%), but the corresponding HMF selectivities and yields remain low (< 50%).

Results and Discussion
Relating to fructose as substrate, when using C 4 MI.Cl at 80 °C, after 8 minutes, the yield is 91% (Table 1, reaction 1) and is reduced to 70% (Table 1, reaction 2) after 12 minutes of reaction time.This result indicates that the reaction is completed rapidly and that HMF decomposition occurs subsequently generating byproducts and decreasing the yield.In this IL (C 4 MI.Cl), HMF is not formed by dehydration of glucose (Table 1, reactions 3 and 4).The same occurs when C 8 MI.Cl (Table 1, reactions 7 and 8) and C 10 MI.Cl (Table 1, reactions 11 and 12) are employed.Reactions conditions: 4 g ionic liquid, 0.4 g sugar, 9% HCl (m/m).When C 12 MI.Cl is used in the fructose dehydration, (Table 1, reactions 13 and 14) the yield increases from 89% to 96% corresponding to 8 and 12 minutes respectively, indicating that after 8 minutes the reaction was not finished.For glucose (Table 1, reactions 15 and 16), the increase of the time reaction also leads to increasing the yield, but this one remains low (34%).This low yield obtained for glucose is not improved by the use of C 16 MI.Cl (Table 1, reactions 19 and 20).These low yields related to glucose indicate that its isomerization in this environment does not occur, probably due to the stability of its ring structure. 33esults of reactions 17 and 18 in Table 1, where fructose and C 16 MI.Cl are used, show that the change of the reaction time from 8 to 12 minutes does not affect the catalytic properties evidencing that no decomposition of HMF occurs as no byproducts are observed.
The set of these results show that, independently of IL used in this study, high HMF yields are obtained from dehydration of fructose in a relatively short reaction time (8 minutes).These results corroborate those described in the literature. 40,42cheme 2 shows a proposal for mechanism dehydration of fructose catalyzed by acid such as the systems developed in this work.Antal 43 and Newth 44 suggest that the formation of HMF easily occurs from fructose by cyclic intermediate enol, 2,5-anhydro-D-mannose, formed in tautomerization step. 42In this mechanism dehydration of fructose is initiated by protonation of the most basic hydroxyl group of the molecule that directly attached to the ring in a position alpha to the oxygen.The protonated form leading to spontaneous dehydration generates the intermediate enol that rearranges and then loses another water molecule, followed by deprotonation regenerating the catalyst and eliminating HMF.
It isn't surprising that the IL/HCl system catalyzed the dehydration of frutose due to the high acidity of the medium, as mechanism proposed, but also ensures the phase separation, in particular in the case of BMI.Cl IL, due to the lipophilic character coming from the chain length of the imidazolium ring.Balance of these different properties provides the best systems for avoiding decomposition of HMF from frutose and the conversion of glucose.In this

Figure 3 .
Figure 3. Example of a chromatogram showing separation of glucose, fructose and HMF.

Figure 4 .
Figure 4. Effect of ILs in the dehydration of fructose.

Figure 5 .Scheme 2 .
Figure 5.Effect of ILs in the dehydration of glucose.
Results of sugar conversion, HMF yield and selectivity using HCl acid and ILs (C 4 MI.Cl, C 8 MI.Cl, C 10 MI.Cl, C 12 MI.Cl or C 16 MI.Cl) are reported Table 1.These data show that it is easier to convert fructose into HMF (yields

Table 1 .
Dehydration of fructose and glucose in different ILs