Catalytic dehydration of fructose to 5-hydroxymethylfurfural (HMF) in low-boiling solvent hexafluoroisopropanol (HFIP)

Article abstract of DOI:10.3390/molecules23081866

A mixture of hexafluoroisopropanol (HFIP) and water was used as a new and unknown monophasic reaction solvent for fructose dehydration in order to produce HMF. HFIP is a low-boiling fluorous alcohol (b.p. 58^?C). Hence, HFIP can be recovered cost efficiently by distillation. Different ion-exchange resins were screened for the HFIP/water system in batch experiments. The best results were obtained for acidic macroporous ion-exchange resins, and high HMF yields up to 70% were achieved. The effects of various reaction conditions like initial fructose concentration, catalyst concentration, water content in HFIP, temperature and influence of the catalyst particle size were evaluated. Up to 76% HMF yield was attained at optimized reaction conditions for high initial fructose concentration of 0.5 M (90 g/L). The ion-exchange resin can simply be recovered by filtration and reused several times. This reaction system with HFIP/water as solvent and the ion-exchange resin Lewatit K2420 as catalyst shows excellent performance for HMF synthesis.

Full text of DOI:10.3390/molecules23081866

molecules
Article
Catalytic Dehydration of Fructose to
5-Hydroxymethylfurfural (HMF) in Low-Boiling
Solvent Hexafluoroisopropanol (HFIP)
Sarah Tschirner, Eric Weingart, Linda Teevs and Ulf Prüße *
Thünen Institute of Agricultural Technology, Bundesallee 47, 38116 Braunschweig, Germany;
sarah.tschirner@thuenen.de (S.T.); eric.weingart@thuenen.de (E.W.); linda.teevs@thuenen.de (L.T.)
* Correspondence: ulf.pruesse@thuenen.de; Tel.: +49-531-596-4270
Academic Editor: Michela Signoretto
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 28 June 2018; Accepted: 23 July 2018; Published: 26 July 2018
Abstract: A mixture of hexafluoroisopropanol (HFIP) and water was used as a new and unknown
monophasic reaction solvent for fructose dehydration in order to produce HMF. HFIP is a low-boiling
fluorous alcohol (b.p. 58 ◦C). Hence, HFIP can be recovered cost efficiently by distillation.
Different ion-exchange resins were screened for the HFIP/water system in batch experiments.
The best results were obtained for acidic macroporous ion-exchange resins, and high HMF yields up
to 70% were achieved. The effects of various reaction conditions like initial fructose concentration,
catalyst concentration, water content in HFIP, temperature and influence of the catalyst particle size
were evaluated. Up to 76% HMF yield was attained at optimized reaction conditions for high initial
fructose concentration of 0.5 M (90 g/L ). The ion-exchange resin can simply be recovered by filtration
and reused several times. This reaction system with HFIP/water as solvent and the ion-exchange
resin Lewatit K2420 as catalyst shows excellent performance for HMF synthesis.
Keywords: HMF; HFIP; fructose; ion-exchange resin; Lewatit K2420
1. Introduction
Diminishing fossil resources, growing world population and increasing importance of global
warming make it necessary to find alternative sources for energy and chemicals. Biomass offers a
promising alternative for a sustainable supply of energy and valuable chemicals. One of the most
interesting organic compounds that can be obtained from biomass is 5-hydroxymethylfurfural (HMF).
Because of its functionalities, HMF is a very important key intermediate with a wide variety of
products, such as furan-based polymers, fuels, fine chemicals and pharmaceuticals [1–4]. One product
with great potential is furandicarboxylic acid (FDCA). Due to the structural similarity to terephthalic
acid (TA), FDCA serves as possible alternative in the production of plastics. In combination with
ethylene glycol it can be polymerized to bio-based poly(ethylene-2,5-furanoate) (PEF), an alternative to
the petrochemical-based polyethylene terephthalate (PET). The PET market volume of 50 million t/a
demonstrates the high potential of FDCA and the importance of HMF production. Therefore, in the
last 30 years the dehydration of fructose to HMF, which is the most efficient synthetic route, received
increasing attention. The main problem in the production of HMF is the instability of HMF. In the
presence of water and acid the formed HMF is rehydrated and different condensation products are
formed. As a result, levulinic and formic acid in a subsequent rehydration reaction, as well as soluble
and insoluble polymers (humins) in parallel condensation reactions, are generated (Scheme 1).
Molecules 2018, 23, 1866; doi:10.3390/molecules23081866
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Scheme 1. Reaction pathway from fructose to 5-hydroxymethylfurfural (HMF) and its decomposition.
To overcome HMF condensation and rehydration reactions, different approaches such as the use
of biphasic reaction systems or organic solvents are investigated. In biphasic systems, the reaction
takes place in an acidic aqueous phase and the formed HMF is extracted in situ into the organic phase.
Typically applied extracting solvents are methyl isobutyl ketone (MIBK), 2-butanol or mixtures of
different solvents. With a 2-butanol–water biphasic system, HMF yields up to 89% were observed [5,6]
Yang et al. achieved the HMF yield of 89% with the biphasic mixture of water and 2-butanol (2:3 v/v)
for the dehydration of fructose and the use of hydrated niobium pentoxide as catalyst [ ]. With a
combination of MIBK and 2-butanol as extraction solvent, HMF yields of 69% up to 82% were
observed [ ]. The HMF yield of 69% with a fructose conversion of 86% was obtained with the
biphasic solvent system water–MIBK–2-butanol and HCl as catalyst [ ]. The replacement of a part of
the water phase by dimethyl sulfoxide (DMSO) with MIBK and 2-butanol as extraction solvents led to
an increase of the HMF yield to 82% with a fructose conversion of 95% [ ]. However, small partition
coefficients for HMF of 1.6–1.9 [ ], high amounts of solvent and high boiling points of the solvents
.
5
7,8
7
8
7
(b.p. (MIBK) = 116 ◦C, b.p. (2-butanol) = 100 ◦C) lead to difficulties in HMF production and isolation.
In previous investigations we showed that hexafluoroisopropanol (HFIP, Scheme 2) solves these
problems in an excellent way [9,10].
Scheme 2. Structure of 1,1,1,6,6,6-hexafluoroisopropanol (HFIP).
In biphasic systems, HFIP showed a very good extraction capacity and an extraordinarily high
◦
partition coefficient for HMF of >10. In combination with the low boiling point of 58 C it is a superior
extraction solvent for the HMF production.
Good results in the dehydration of fructose to HMF are also achieved with the use of monophasic
reaction systems. Organic solvents, like dimethyl sulfoxide (DMSO), dimethylformamide (DMF)
and 1,4-dioxane or ionic liquids were applied [11–14]. Shimizu et al. reported for DMSO as reaction
solvent and the acidic ion-exchange resin Amberlyst 15 as catalyst an HMF yield of 92% at 120 ◦C
under reduced pressure and 2 h reaction time [11]. For fructose dehydration, either in DMSO or in
[BMIM]Cl, high HMF yields of around 95% were described at 120 ◦C with a chromium-exchanged
K-10 clay as catalyst [15]. The high boiling point or no boiling point of these solvents leads to the
problem of isolation of the thermally labile HMF. With the use of low-boiling HFIP in combination
with water as monophasic reaction solvent instead, a very good result was achieved. After 360 min
for 0.1 M fructose, 12.5 vol % water in HFIP, 18 g/L Amberlyst 15 and 87 ◦C, an HMF selectivity of

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79% at a fructose conversion of 98% was received [
9
]. Based on this result, further investigations on
the influence of different reaction parameters on fructose dehydration were carried out. In this paper
we present a monophasic reaction system with HFIP and water as reaction solvent and strong acidic
ion-exchange resins as catalysts. Excellent performance in view of HMF synthesis from fructose was
observed. An HMF yield up to 76% at high initial fructose concentrations of 0.5 M can be achieved at
optimized reaction conditions, and the recyclability of the catalyst was proven.
2. Results and Discussion
2.1. Screening of Different Ion-Exchange Resins for Dehydration of Fructose
Cation-exchange resins are known as suitable solid acid catalysts for HMF synthesis [1,16]
Six different commercially available acidic ion-exchange resins (properties of the used
cationic-exchange resins are summarized in Table S1) were tested for the catalysis of fructose
dehydration. Most of the chosen catalysts are strongly acidic macroporous polystyrene- and
divinylbenzene copolymer-based ion-exchange resins, except for Amberlite IR-120 (H), which is
a microporous gel-type strong acid ion-exchange resin. Gel-type resins have smaller pore diameters
than macroporous resins. The copolymer matrix of polystyrene and divinylbenzene of the macroporous
resins are cross-linked in comparison to gel-type resins, leading to different pore systems with varying
pore diameters and volumes (Table S1). The effect of the different catalysts on fructose conversion,
maximum HMF yield and maximum HMF selectivity was investigated and is shown in Figure 1.
.
Figure 1. Screening of different ion-exchange resins and their influence on fructose conversion,
maximum HMF yield and maximum HMF selectivity. Reaction conditions: 0.5 M fructose, 12.5 vol %
◦
water in HFIP, 20 g/L (21.6 mol % (acid sites/substrate)) catalyst and 105 C.
Under screening reaction conditions, the highest HMF yields in the range of 69–70% were obtained
for Lewatit-type resins. With Amberlyst resins, an HMF yield of 62% was achieved. The lowest HMF
yield of 51% was reached with Amberlite IR-120 (H). Amberlite IR-120 (H) has a poor accessibility of
the acid sites, due to its small pore diameters (<0.5 nm). Therefore, the macroporous ion-exchange
resins obtained superior results compared to the gel-type resin, based on the better availability of the
active sites for fructose [17]. Additionally, the larger acid-site concentration of Lewatit-type resins led
to a faster fructose conversion. In comparison to the literature, higher HMF yields were generated
with ion-exchange resins as catalyst in HFIP than in other low-boiling solvents [18
isopropyl alcohol as reaction solvent for HMF production. At 120 C and with Amberlyst 15 as catalyst,
,
19]. Lai et al. used
◦

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a total furfural yield (including HMF, ether and acetalization products) of 60% was observed after
4 h [19]. Only in high-boiling reaction solvents like DMSO and DMF can HMF yields over 80% be
achieved [11,12]. A high HMF yield was obtained with Lewatit K2420. Additionally, this catalyst
provides a good thermostability up to 150 ◦C. Hence, Lewatit K2420 was selected as catalyst for the
dehydration of fructose in the following experiments.
2.2. Examination of Different Reaction Parameters
The influence of various reaction parameters, like initial fructose concentration,
catalyst concentration, water content in HFIP, temperature and effect of the catalyst particle
size on fructose dehydration were evaluated.
2.2.1. Effect of Initial Fructose Concentration
High initial fructose concentrations are an important aspect in the development of an industrial
HMF production process. Hence the influence of five different initial fructose concentrations on the
dehydration of fructose to HMF were investigated using 22 g/L (23.8 mol %) Lewatit K2420, 15 vol %
water in HFIP and a temperature of 110 ◦C. The fructose concentrations were varied between 0.1 M and
2 M (18–360 g/L). The effect of the initial fructose concentration on the HMF yield is shown in Figure 2.
Figure 2. Effect of fructose concentration on the HMF yield. Reaction conditions: 0.1–2 M fructose,
◦
15 vol % water in HFIP, 22 g/L (23.8 mol %) Lewatit K2420 and 110 C.
The largest HMF yield of 79% was achieved with the lowest initial fructose concentration of
0.1 M after 75 min and a fructose conversion of 99%. The HMF yield was reduced to 75% and 70% at
a fructose conversion of 99% by rising the fructose concentration to 0.25 M and 0.5 M, respectively,
whilst the reaction time increased to 77 min and 129 min, respectively. Further increase of the fructose
concentration led to decreased HMF yields of 61% and 41% at 99% fructose conversion for 1 M and
2 M fructose, respectively. The content of the unknown side products (humins), which was defined
as amount of undetectable products by carbon balance, increased with the fructose concentration
(0.1–2 M) from 7 to 37%. The summarized yields of levulinic and formic acids had also risen from 14 to
23% with increasing fructose concentration from 0.1 M to 2 M. Nevertheless, Lewatit K2420 was an
effective catalyst for the fructose dehydration at high initial fructose concentrations, in comparison to
the literature, which only delineates high HMF yields in high-boiling reaction solvents like DMSO and
DMF at low initial concentrations [11
,12]. Ohara et al. reported for the fructose dehydration in DMF
an HMF yield of 90%, with a fructose concentration of 33 g/L (0.18 M) and a reaction temperature of

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100 ◦C as well as total fructose conversion [12]. A 0.5 M (90 g/L ) fructose concentration was selected
for further reactions, because of the high HMF yield at large fructose concentrations.
2.2.2. Effect of Catalyst Concentration
Figure 3 shows the effect of different catalyst concentrations (5–40 g/L ; 5.4–43 mol %) on the
HMF yield with equal reaction conditions.
Figure 3. Effect of catalyst concentration on the HMF yield. Reaction◦conditions: 0.5 M fructose,
15 vol % water in HFIP, 5–40 g/L (5.4–43 mol %) Lewatit K2420 and 110 C.
First, the fructose dehydration was performed without catalyst. In the absence of catalyst, no
HMF was formed. With increasing amount of catalyst, the HMF yield rose from 60% for 5 g/L
(5.4 mol %) and 94% fructose conversion to 68–70% for a catalyst concentration in the range of
10 g/L (10.8 mol %) to 22 g/L (23.8 mol %) and 99% fructose conversion. At a higher catalyst
concentration (40 g/L , 43 mol %), slightly lower HMF yield of 66% at a fructose conversion of 99%
was observed. The side reactions of HMF were favored due to the larger amount of accessible acid
sites, which promote the rehydration and condensation reactions to levulinic acid, formic acid and
humins. A catalyst concentration of 22 g/L (23.8 mol %) was chosen as an optimal amount of catalyst
for further experiments, because this concentration allowed a fast fructose conversion.
2.2.3. Effect of Water Content
The addition of different amounts of water to HFIP and its effect on the maximum HMF yield
was investigated. The results are illustrated in Figure 4.
The highest maximum HMF yield of 69–70% was achieved for 12.5–17.5 vol % water in HFIP as
reaction solvent. With a water content <10 vol % and
≥
25 vol %, the HMF yield declined significantly.
An HMF yield of 25% was observed in pure HFIP solution and an HMF yield of 16% in pure water
as reaction solvent. The addition of water to HFIP led to a slower conversion of fructose. With
increasing water content the rehydration of HMF to levulinic acid and formic acid was favored.
The summarized yield of levulinic and formic acids rose from 15 to 50% when the water content
in HFIP was increased from 15 to 100 vol %. For decreasing water contents from 15 to 0 vol %,
the amount of fructose condensation products (e.g., difructose anhydrides), which were not quantified,
increased. H2O (15 vol %) in HFIP was selected as optimal water content, due to the high achieved
HMF yield.

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Figure 4. Effect of water content in HFIP on maximum HMF yield. Reaction conditions: 0.5 M fructose,
◦
0–100 vol % water in HFIP, 22 g/L (23.8 mol %) Lewatit K2420 and 110 C.
2.2.4. Effect of Reaction Temperature
Seven different reaction temperatures in the range of 90 to 120 ◦C were examined, in order to
determine their influence on fructose conversion, HMF selectivity and HMF yield. The results are
shown in Table 1.
Table 1. Effect of temperature on fructose conversion, HMF selectivity and HMF yield. Reaction
◦
conditions: 0.5 M fructose, 15 vol % water in HFIP, 22 g/L (23.8 mol %) Lewatit K2420 and 90–120 C.
Temperature
HMF
Selectivity (%)
HMF
Yield (%)
Reaction Time (min)
Fructose Conversion (%)
◦
( C)
90
95
405
315
225
137
129
105
90
95
98
97
98
99
99
99
67
69
72
72
71
67
68
64
67
70
71
70
66
67
100
105
110
115
120
◦
At 90 C, an HMF yield of 64% was achieved after 405 min. With increasing temperature, the HMF
yield rose to a maximum of 71% at 105 ◦C after 137 min. At even higher temperatures, the HMF yield
◦
dropped to 67% at 120 C. As expected, the fructose dehydration rate increased with rising temperature.
When the temperature was increased from 90 to 120 ◦C, the summarized yield of levulinic and formic
acids rose from 7 to 23%. Consequently, the amount of unknown side products (humins) decreased
with rising temperature.
A reaction temperature of 105 ◦C was chosen for following investigations, due to the high HMF
yield and low reaction time.
2.2.5. Kinetic Analysis
Additionally, the kinetic analysis of fructose dehydration in the HFIP/water system and Lewatit
K2420 as catalyst was performed. The reaction order of one was adopted for fructose dehydration
in HFIP, as described in the literature [20
,21]. The logarithm of 1–X (X = conversion of fructose)
was plotted versus the reaction time for each reaction temperature, and the first-order reaction

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constants were determined. Afterwards, the reaction constants were applied in the Arrhenius equation.
The obtained Arrhenius plot is shown in Figure 5.
Figure 5. Arrhenius plot for the dehydration of fructose in 15 vol % water in HFIP, 22 g/L (23.8 mol %)
Lewatit K2420 and 0.5 M fructose.
An activation energy of 92.6 kJ/mol was calculated, which is comparable to the ones described
in previous works [14,22]. Qi et al. determined an activation energy of 103 kJ/mol for fructose
dehydration in acetone–water mixture and 60.4 kJ/mol in acetone–DMSO mixture, both with addition
of an acidic ion-exchange resin as catalyst [22].
2.2.6. Effect of Catalyst Particle Size
The influence of the catalyst particle size on the fructose dehydration at optimized reaction
conditions was investigated. The fructose conversion, HMF selectivity and HMF yield for different
catalyst sizes are summarized in Table 2.
Table 2. Effect of catalyst particle size on fructose conversion, HMF selectivity and HMF yield. Reaction
◦
conditions: 0.5 M fructose, 15 vol % water in HFIP, 22 g/L (23.8 mol %) Lewatit K2420 and 105 C.
Reaction Time
(min)
HMF
Selectivity (%)
HMF
Yield (%)
Particle Size (µm)
Fructose Conversion (%)
Original (>500)
150–300
137
120
120
98
99
99
72
76
77
71
75
76
25–100
When Lewatit K2420 particles in their original size distribution were used, a fructose conversion
of 98% and an HMF yield of 71% were achieved. 90% of the catalyst particles had a particle size in
the range of 500–710
150–300 m led to a faster fructose conversion and an HMF yield of 75%. For 25–100
particles, an HMF yield of 76% at a fructose conversion of 99% was observed. Therefore, crushing the
catalyst particles from the original size to 25–100 m led to a faster HMF formation and a reduction
µm, 10% were even larger. The crushing of the ion-exchange resin particles to
µ
µm catalyst
µ
of the reaction time to achieve maximum HMF yield from 137 to 120 min. A further reduction of the
catalyst particle size resulted in a negligible increase of the HMF yield. In the literature, similar results
were described [23]. The higher HMF yield and faster HMF formation for smaller catalyst particles
can be attributed to the shorter diffusion pathway to and from acid sites of the catalyst. This results

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in a lower internal mass transfer limitation. The lower pore diffusion limitation is beneficial for the
selective production of HMF. Since HMF is an intermediate product of the reaction, the diffusion of
HMF out of the pores has to be fast, in order to avoid a subsequent rehydration reaction, which is also
catalyzed by acid sites. Consequently, the amount of the rehydration products decreased with the
reduction of particle size. The summarized yield of levulinic and formic acids was reduced from 15.5%
at original particle size to 11.8% at particle sizes of 25–100 µm. Therefore, smaller catalyst particles in
the range of 25–100 µm were used in the following experiments.
2.3. Recyclability of the Catalyst
The reuse of the catalyst plays an important role for the development of economic processes.
The recyclability test of Lewatit K2420 was performed under the previously optimized reaction
conditions in five consecutive runs. Between each run, Lewatit K2420 was separated from the reaction
solution by filtration and washed with HFIP. The fructose conversion, HMF yield and HMF selectivity
after 135 min for each catalytic run are shown in Figure 6.
Figure 6. Recyclability of Lewatit K2420 (25–100
water in HFIP, 22 g/L (23.8 mol %) Lewatit K2420 (25–100 µm), 105 C and 135 min.
µ
m). Reaction conditions: 0.5 M fructose, 15 vol %
◦
The HMF yield slightly decreased from 76 to 72%, as well as the fructose conversion from 99 to
98%. The catalytic activity showed almost constant performance over five successive runs. The fructose
dehydration reaction rate dropped slightly for each catalytic run. In comparison to the literature,
a very weak deactivation of the ion-exchange resin for successive runs was noticed [23,24]. In DMF as
reaction solvent in combination with Amberlyst 15 as catalyst, a strong decline in HMF yield from
64 to 0% in five successive catalytic runs was observed [23]. A poor reusability in combination with a
low HMF yield of 46 mol % was achieved for fructose dehydration with Amberlyst 70 in water under
microwave heating. Over three reaction cycles, the HMF yield decreased by about 10% [24].
The good reusability, the high fructose concentration and the short reaction time enable high
space-time yields, which are necessary for an efficient continuous HMF production. Consequently,
further investigations will focus on the continuous HMF production [25].

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3. Materials and Methods
3.1. Materials
Fructose (99.5% p.a. Carl Roth, Karlsruhe, Germany), HFIP (99% Fluorochem, Hadfield, UK),
HMF (98%, Sigma-Aldrich, Munich, Germany), levulinic acid (99%, Merck, Darmstadt, Germany),
formic acid (98% p.a., Carl Roth, Karlsruhe, Germany), Lewatit K2420 (Lanxess, Cologne, Germany),
Lewatit K2430 (Lanxess, Cologne, Germany), Lewatit K2620 (Lanxess, Cologne, Germany), Amberlyst
15 (dry) (Acros Organics, Geel, Belgium), Amberlyst 16 (wet) (Fluka, Munich, Germany), Amberlite
IR-120(H) (Alfa Aesar, Heyshem, UK). All chemicals were used as received. Lewatit K2420, Lewatit
K2430, Lewatit K2620, Amberlyst 16 (wet) and Amberlite IR-120 (H) were washed with water
(Merck Milli-Q, Darmstadt, Germany) until the permeate is colourless and dried overnight at 100 ◦C
◦
prior to use. HFIP was recycled by atmospheric evaporation distillation (b.p. 58 C). No contamination
in the distilled HFIP was found. HFIP was reused in subsequent reactions. Further information on
HFIP is provided in Table S2 under Supplementary Materials.
3.2. Catalytic Conversion of Fructose into HMF
The dehydration reactions were carried out in a 1-L pressure-resistant reactor with a Teflon inlet
from Parr Instrument Company. 0.5 L of the mixture of water, HFIP and fructose was filled in the
reactor. Afterwards, the corresponding amount of catalyst was added to the reaction mixture and
the reactor was heated to reaction temperature. The heat-up phase of the reactor was included in the
reaction time. Samples were taken with a glass syringe via a septum at different times and analyzed
via HPLC. For recyclability studies the catalyst was washed with HFIP, stored overnight in HFIP,
filtered and reused in the following reaction. We observed little loss of catalyst (1 wt %) between each
catalytic run. No fresh catalyst was added to the used catalyst.
3.3. Analytical Methods
Quantitative analysis was performed by HPLC (CBM-20 A, Shimadzu, Kyoto, Japan), equipped with
an Animex HPX-87H column, refraction index detector (RID-6A, Shimadzu, Kyoto, Japan) and UV detector
(SPD-10AV, Shimadzu, Kyoto, Japan). The reaction components were quantified by HPLC measurement
at 60 ◦C, 0.7 mL min−1 flow rate of 5 mM sulfuric acid. Calibration was realized with external standards.
All samples were diluted at least 10 times with water (Merck Milli-Q) prior to analysis. The fructose
conversion, HMF selectivity and HMF yield were determined by Equations (1)–(3):
nfructose,initial − nfructose,final
fructose conversion (%) =
HMF selectivity (%) =
× 100,
(1)
nfructose, initial
nHMF
× 100,
(2)
(3)
nfructose,initial − nfructose,final
nHMF
HMF yield (%) =
× 100
nfructose,initial
4. Conclusions
The use of HFIP/water as reaction solvent shows excellent performance for HMF synthesis.
Several heterogeneous catalysts were screened and the highest HMF yield was achieved by using
the ion exchanger Lewatit K2420. The influence of different reaction conditions, like initial fructose
concentration, catalyst concentration, water content in HFIP, temperature and effect of the catalyst
particle size on fructose dehydration, was evaluated. At optimized reaction conditions and an initial
fructose concentration of 0.5 M (90 g/L ), an excellent HMF yield of 76% was achieved. Comparable
results were only described for high-boiling reaction solvents, in which the isolation of thermally
◦
instable HMF is complicated. HFIP (b.p. 58 C), on the other hand, can easily be separated from

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HMF by distillation. Additionally, Lewatit K2420 demonstrated a good recyclability over five repeated
batch experiments.
Supplementary Materials: The supplementary materials are available online. Table S1. Properties of applied
dry cationic ion-exchange resins. All data were provided by the manufacturer. Table S2. Chemical and physical
characteristics as well as safety parameters of 1,1,1,6,6,6-hexafluoroisopropanol (HFIP).
Author Contributions: S.T., E.W. and U.P. conceived and designed the experiments; S.T. and L.T. performed the
experiments and analyzed the data; S.T., E.W., L.T., U.P. wrote the paper.
Funding: This research received no external funding
Conflicts of Interest: The authors declare no conflicts of interest.
References
1.
Van Putten, R.J.; van der Waal, J.C.; de Jong, E.; Rasrendra, C.B.; Heeres, H.J.; de Vries, J.G.
Hydroxymethylfurfural, A Versatile Platform Chemical Made from Renewable Resources. Chem. Rev.
2013, 113, 1499–1597. [CrossRef] [PubMed]
2.
Hu, L.; Lin, L.; Wu, Z.; Zhou, S.; Liu, S. Recent advances in catalytic transformation of biomass-derived
5-hydroxymethylfurfural into the innovative fuels and chemicals. Renew. Sustain. Energy Rev. 2017
74, 230–257. [CrossRef]
,
3.
4.
5.
6.
7.
8.
9.
Kang, S.; Fu, J.; Zhang, G. From lignocellulosic biomass to levulinic acid: A review on acid-catalyzed
hydrolysis. Renew. Sustain. Energy Rev. 2018, 94, 340–362. [CrossRef]
Wang, T.; Nolte, M.W.; Shanks, B.H. Catalytic dehydration of C6 carbohydrates for the production of
hydroxymethylfurfural (HMF) as a versatile platform chemical. Green Chem. 2014, 16, 548–572. [CrossRef]
Yang, F.; Liu, Q.; Bai, X.; Du, Y. Conversion of biomass into 5-hydroxymethylfurfural using solid acid catalyst.
Bioresour. Technol. 2011, 102, 3424–3429. [CrossRef] [PubMed]
Yang, F.; Tong, X.; Xia, F.; Zheng, C.; Qin, L.; Jiang, X. Efficient Hydroxymethylfurfural Production over
Phosphoric Carbon Solid Acids. Catal. Lett. 2018, 148, 1848–1855. [CrossRef]
Román-Leshkov, Y.; Chheda, J.N.; Dumesic, J.A. Phase Modifiers Promote Efficient Production of
Hydroxymethylfurfural from Fructose. Science 2006, 312, 1933–1937. [CrossRef] [PubMed]
Chheda, J.N.; Román-Leshkov, Y.; Dumesic, J.A. Production of 5-hydroxymethylfurfural and furfural by
dehydration of biomass-derived mono- and poly-saccharides. Green Chem. 2007, 9, 342–350. [CrossRef]
Vorlop, K.-D.; Prüße, U.; Krieg, R.; Teevs, L. Improved 5-Hydroxymethylfurfural Production Using a
Multi-Fluorinated Alcohol Compound. U.S. Patent 10,005,748, 26 June 2018.
10. Weingart, E.; Teevs, L.; Krieg, R.; Prüße, U. Hexafluoroisopropanol as low boiling extraction solvent for
5-hydroxymethylfurfural production. Energy Technol. 2017, 6, 432–440. [CrossRef]
11. Shimizu, K.-I.; Uozumi, R.; Satsuma, A. Enhanced production of hydroxymethylfurfural from fructose with
solid acid catalysts by simple water removal methods. Catal. Commun. 2009, 10, 1849–1853. [CrossRef]
12. Ohara, M.; Takagaki, A.; Nishimura, S.; Ebitani, K. Syntheses of 5-hydroxymethylfurfural and levoglucosan
by selective dehydration of glucose using solid acid and base catalysts. Appl. Catal. A Gen. 2010, 383, 149–155.
[CrossRef]
13. Wang, F.; Shi, A.-W.; Qin, X.-X.; Liu, C.-L.; Dong, W.-S. Dehydration of fructose to 5-hydroxymethylfurfural
by rare earth metal trifluoromethanesulfonates in organic solvents. Carbohydr. Res. 2011, 346, 982–985.
[CrossRef] [PubMed]
14. Qi, X.; Watanabe, M.; Aida, T.M.; Smith, R.L., Jr. Efficient process for conversion of fructose to
5-hydroxymethylfurfural with ionic liquids. Green Chem. 2009, 11, 1327–1331. [CrossRef]
15. Fang, Z.; Liu, B.; Luo, J.; Ren, Y.; Zhang, Z. Efficient conversion of carbohydrates into
5-hydroxymethylfurfural catalyzed by the chromium-exchanged montmorillonite K-10 clay.
Biomass Bioenergy 2014, 60, 171–177. [CrossRef]
16. Agirrezabal-Telleria, I.; Gandarias, I.; Arias, P.L. Heterogeneous acid-catalysts for the production of
furan-derived compounds (furfural and hydroxymethylfurfural) from renewable carbohydrates: A review.
Catal. Today 2014, 234, 42–58. [CrossRef]

Molecules 2018, 23, 1866
11 of 11
17. Li, Y.; Liu, H.; Song, C.; Gu, X.; Li, H.; Zhu, W.; Yin, S.; Han, C. The dehydration of fructose to
5-hydroxymethylfurfural efficiently catalyzed by acidic ion-exchange resin in ionic liquid. Bioresour. Technol.
2013, 133, 347–353. [CrossRef] [PubMed]
18. Brown, D.W.; Floyd, A.J.; Kinsman, R.G.; Roshan-Ali, Y. Dehydration Reactions of Fructose in Non-aqueous
Media. Chem. Tech. Biotechnol. 1982, 32, 920–924. [CrossRef]
19. Lai, L.; Zhang, Y. The Production of 5-Hydroxymethylfurfural from Fructose in Isopropyl Alcohol: A Green
and Efficient System. ChemSusChem 2011, 4, 1745–1748. [CrossRef] [PubMed]
20. Bicker, M.; Hirth, J.; Vogel, H. Dehydration of fructose to 5-hydroxymethylfurfural in sub- and supercritical
acetone. Green Chem. 2003, 5, 280–284. [CrossRef]
21. Kuster, B.F.M.; van der Baan, H.S. The influence of pH and weak-acid anions on the dehydration of d-fructose.
Carbohydr. Res. 1977, 54, 165–176. [CrossRef]
22. Qi, X.; Watanabe, M.; Aida, T.M.; Smith, R.L., Jr. Selective Conversion of D-Fructose to 5-Hydroxymethylfurfural
by Ion-Exchange Resin in Acetone/Dimethyl sulfoxide Solvent Mixtures. Ind. Eng. Chem. Res. 2008, 47, 9234–9239.
[CrossRef]
23. Sampath, G.; Kannan, S. Fructose dehydration to 5-hydroxymethylfurfural: Remarkable solvent influence on
recyclability of Amberlyst-15 catalyst and regeneration studies. Catal. Commun. 2013, 37, 41–44. [CrossRef]
24. Antonetti, C.; Raspolli Galetti, A.M.; Fulignati, S.; Licursi, D. Amberlyst A-70: A surprisingly active catalyst
for the MW-assisted dehydration of fructose and inulin to HMF in water. Catal. Commun. 2017, 97, 146–150.
[CrossRef]
25. Weingart, E.; Tschirner, S.; Teevs, L.; Prüße, U. Conversion of Fructose to HMF in a Continuous Fixed Bed
Reactor with Outstanding Selectivity. Molecules 2018, in press. [CrossRef] [PubMed]
Sample Availability: Samples of the compounds are not available from the author.
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