5-hydroxymethylfurfural synthesis from hexoses is autocatalytic

Article abstract of DOI:10.1021/cs400099a

Many researchers and articles have reported the development of synthesis methods for 5-hydroxymethylfurfural, one of the top 12 biobased building blocks listed by the U.S. Department of Energy. The focus has especially been on the development of efficient catalytic systems for this synthesis. In contrast, we report here a process that does not require any added catalysts, yet leads to interesting yields and selectivities. Moreover, we demonstrate that the process is autocatalytic involving formic acid, the byproduct.

Full text of DOI:10.1021/cs400099a

Letter
pubs.acs.org/acscatalysis
5‑Hydroxymethylfurfural Synthesis from Hexoses Is Autocatalytic
Adeline Ranoux, Kristina Djanashvili, Isabel W. C. E. Arends, and Ulf Hanefeld*
†Technische Universiteit Delft, Afdeling Biotechnologie, Gebouw voor Scheikunde, Julianalaan 136, 2628 BL Delft, The Netherlands
ABSTRACT: Many researchers and articles have reported the development
of synthesis methods for 5-hydroxymethylfurfural, one of the top 12 biobased
building blocks listed by the U.S. Department of Energy. The focus has
especially been on the development of efficient catalytic systems for this
synthesis. In contrast, we report here a process that does not require any
added catalysts, yet leads to interesting yields and selectivities. Moreover, we
demonstrate that the process is autocatalytic involving formic acid, the
byproduct.
KEYWORDS: HMF, 5-hydroxymethylfurfural, autocatalysis, aqueous media, water, fructose, glucose
conversion and selectivity has yet been published in purely
aqueous media.
5-Hydroxymethylfurfural (HMF) is a biobased platform
chemical with high potential.1 It is formed through elimination
of three molecules of water from hexoses, and therewith, it is a
straightforward and easy way to upgrade sugars to molecules
with a higher energy density. HMF serves as starting material
for a wide variety of biobased chemical intermediates (e.g.,
levulinic acid, furandicarboxylic acid, dimethyl furan, γ-
valerolactone, and dihydroxymethylfuran). Therefore, it is the
key entrance to a whole range of products (solvents, polymers,
biofuels) derived from all types of lignocellulosic biomass.2
The awareness that it will become necessary to produce
materials from renewable resources rather than from fossil raw
materials has led to an enormous increase in research efforts
dedicated to the production and utilization of platform
molecules, including HMF;3 however, it is important to realize
that the first report on the acid-catalyzed synthesis of HMF
Scheme 1. Fructose Conversion into HMF and Its In Situ
Rehydration/Degradation
from sugars stems from 1895 by Dull.4 The acid-catalyzed
̈
conversion of sugars (e.g., fructose, glucose, sucrose) into HMF
has since then been implemented in many different media:
aqueous,5 organic, biphasic,6 and ionic liquids.7 Originally,
oxalic acid-catalyzed reactions were described.4,8 Since then,
many different acidic catalysts have been reported, such as
organic or inorganic acids5d,6 and salts,9 Lewis acidic metals,10
zeolites,11 and organic resins.12 The proposed processes are
generally complex and often involve toxic (such as chromium
derivatives13) or corrosive (H2SO4, HCl) catalysts and harmful
solvents (dichloromethane as the extracting solvent,14 ionic
liquids such as [BMIM]/[EMIM][Cl]/[Br]7a); in the case of
biphasic mixtures, especially when DMSO6 is used as solvent
(for complete review see2a), hard-to-handle separation
procedures are required.
Several articles have reported the synthesis of HMF without
a catalyst in the presence of DMSO12a,15 or ionic liquids.16 In
these systems, the solvent also plays the role of promoter,
coordinating and activating intermediates. Older articles
reported a possible autocatalysis of fructose in aqueous media
with interesting yields when starting from a low concentration
of the sugar (less than 5 wt %),5a or from sucrose, glucose, or
sorbose with lower yields.17
In line with these early results, we report here high
selectivities that can lead to the implementation of a highly
improved and sustainable autocatalytic process for the synthesis
of HMF in water. This process can be operated without any
added catalyst and starts from a highly concentrated feed of
sugar (30 wt %). In addition, experiments were carried out to
The development of a more sustainable process, especially in
an aqueous medium, is highly desirable. It is, however, limited
by the partial degradation of HMF by rehydration. In the
presence of water, levulinic acid (LA) and formic acid (FA) are
formed (Scheme 1). To our knowledge, no report of high
Received: February 6, 2013
Revised: March 8, 2013
© XXXX American Chemical Society
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ACS Catalysis
Letter
study the mechanism and verify the potential of this
autocatalytic reaction.
Table 2. HMF Synthesis from Sugars in Water without Any
Added Catalyst
Systematic evaluation of the reaction parameters led us to
identify temperature and reaction time as the most critical
parameters. To obtain high yields, a compromise must be
reached between conversion and selectivity. A too high
temperature or too long reaction time leads to the degradation
of the product and the formation of humins. The formation of
the dehydration products LA and FA increases exponentially
with time and temperature of the reaction, as shown in Table 1.
concn
a
time
temp
conv
b
selec Y (FA) Y (LA)
b
b
b
sugar
wt %
(min) (°C)
(%)
(%)
(%)
(%)
fructose
glucose
sucrose
Glu/Fru
30
10
20
20
40
80
40
40
190
195
200
195
70
19
39
40
61
38
56
51
3.2
0.4
2.2
<0.1
1.0
4.85
2.2
0.4
a
b
2 mL experiments, carried out in Ace pressure tubes. Determined by
HPLC analysis, in mol % (conv, conversion; selec, selectivity HMF; Y,
yield calculated from HPLC analysis, not isolated).
Table 1. HMF Synthesis from Fructose (30 wt %) in Water
without Any Added Catalyst
Scheme 2. Two-Step Glucose Conversion into HMF
concn
a
time
temp
conv
b
selec Y (FA) Y (LA)
b
b
b
sugar
wt %
(min) (°C)
(%)
(%)
(%)
(%)
<0.1
0.15
fructose
fructose
fructose
fructose
fructose
fructose
fructose
fructose
fructose
fructose
fructose
30
30
30
30
30
30
30
30
30
30
30
40
60
170
170
170
170
200
200
200
200
200
190
190
13
25
47
84
19
46
66
94
97
35
70
26
41
56
51
44
58
58
50
44
61
61
0.2
0.65
2.2
5.9
0.3
1.3
2.7
6.1
6.7
0.95
3.2
120
180
20
1.05
6.85
<0.1
30
0.4
1.6
9.3
7.4
0.2
2.2
40
50
60
20
40
a
b
2 mL experiments, carried out in Ace pressure tubes. Determined by
degradation products. One hypothesis is that these acidic
byproducts are involved in the catalysis of HMF formation.
This autocatalysis was suggested for the first time in 194717
and again in 1977.5a To prove the involvement of the acidic
byproducts, the reactions were first carried out in different
organic and inorganic buffers (to eliminate any possible salt
effect) at various concentrations (Table 3).
HPLC analysis, in mol % (conv, conversion; selec, selectivity HMF; Y,
yield calculated from HPLC analysis, not isolated).
With 30 wt % fructose, up to 70% conversion was obtained
with a selectivity of 61% (Table 1). This result is one of the
highest reported in a neutral, salt-free aqueous solution
(compared, for example, with 52% conversion and 63%
selectivity obtained at 200 °C from fructose at 27 wt % in
the presence of HCl and under microwave irradiation18) and is
comparable to the results obtained in many biphasic systems.19
This result is exceptional, considering the high concentration of
fructose used and the absence of a catalyst.
It should be noted that the literature on HMF synthesis
reports only a few “blank” experiments (without cata-
lyst).5a,9,10b,17,20 For example, Wu et al. in their study on the
effect of different salts on HMF formation and degradation21
obtained up to 75% conversion of fructose with a selectivity of
42% after 60 min at 180 °C in their blank reaction.
We then extended our study to other sugars, such as glucose
or sucrose. The formation of HMF from pyranoses as glucose is
more challenging. Much lower conversions than in the case of
fructose were achieved (Table 2). A catalyst is then
indispensable to promote the required first step, the isomer-
ization of the sugar (Scheme 2).
A mixture of glucose and fructose at a ratio 50/50, similar to
the composition of a high fructose corn syrup (industrial
product issued from the isomerization of glucose), was also
tested. The fructose was then converted in the same proportion
as described previously (around 40% yield), but the glucose
remained unconverted (Table 2). This conversion of fructose
in the absence of any catalyst or any possible promoter led to
the question of the mechanism involved in HMF formation.
Although no acid was added during this reaction, the final pH
was unexpectedly low (around 3). This acidity can be explained
by the formation of levulinic acid (LA) and formic acid (FA) as
Using concentrated buffers, regardless of their type, the pH
was maintained around 7, and no HMF formation occurred,
whereas at a lower concentration of buffer, the formation of
HMF was accompanied by a drop in pH. Obviously,
neutralization of these acidic compounds leads to inhibition
of the reaction. This result verifies our hypothesis by
demonstrating that neutralization of the acidic byproducts,
LA and FA, prohibits the formation of HMF. Large quantities
of humins are then produced in these cases as a result of the
degradation of the sugars. At low buffer concentrations, FA and
LA catalyze and redirect the overall reaction away from humins.
To test the potential of LA and FA as catalysts of the
reaction, experiments were carried out in their presence (Table
4). A net acceleration of the reaction when adding FA
compared with the blank was demonstrated. After only 20 min,
45% yield was reached. LA has a much more limited effect.
Only a slight increase in the conversion and yield could be
observed. Thus, the reaction without added catalyst gives
results essentially equally as good as with the FA catalyst.
The difference in acidities of LA (pKa 4.59) and FA (pKa
3.74) explains why the latter is a better catalyst for HMF
synthesis. Thus, the observed formation of HMF in the absence
of any added catalyst is mainly due to the “auto” catalysis
mediated by FA.
It could also be noticed that the addition of FA at the
beginning of the reaction dramatically increases the formation
of degradation products, such as LA and humins. At 190 °C and
40 min, more than 8% of LA is formed in the presence of the
initial FA. If no FA is initially added, only 2% of LA is detected.
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Table 3. Buffered Media for the Synthesis of HMF
concn wt
time
(min)
temp
(°C)
concn buff.
pH
beg.
conv
b
Y (HMF)
selec
b
Y (FA)
b
Y (LA)
b
a
b
sugar
%
buffer
(M)
pH end
(%)
(%)
(%)
(%)
(%)
fructose
fructose
fructose
fructose
fructose
30
30
30
30
30
40
40
40
40
40
190
190
190
190
190
Tris/HCl
Glygly
0.05
0.2
1
7.5
7.5
7.0
7.3
7.0
∼3
∼4−5
∼7
∼5−6
∼4−5
79
69
98
98
92
48
23
4
61
33
4
4.05
1.4
4.7
1.3
0.8
0.2
0.45
phosphate
Glygly
10.4
1.4
0.5
0.1
5
5
phosphate
28.5
31
2.8
a
b
2 mL experiments, carried out in Ace pressure tubes. Determined by HPLC analysis, in mol % (conv, conversion; selec, selectivity HMF; Y, yield
calculated from HPLC analysis, not isolated).
a
Table 4. HMF Synthesis from Sugars in Water with or without Added Catalyst
a
b
b
b
b
b
sugar
concn wt %
time (min) temp (°C) catalyst mol ratio % conv (%)
Y (HMF) (%)
selec (%) ¶ Y (FA) (%)
Y (LA) (%)
fructose
fructose
fructose
fructose
fructose
fructose
30
30
30
30
30
30
20
40
20
40
20
40
190
190
190
190
190
190
35
70
44
93
70
96
21
43
27
49
45
47
61
61
61
53
64
49
0.95
3.2
0.2
2.2
c
LA
LA
FA
FA
50
50
50
50
1.1
+0.6
c
3.4
+2.1
c
+4.8
2.7
8.1
c
+5.9
a
b
2 mL experiments, carried out in Ace pressure tubes. Determined by HPLC analysis, in mol % (conv, conversion; selec, selectivity HMF; Y, yield
c
calculated from HPLC analysis, not isolated). Calculated in addition to the amount initially introduced.
The excellent selectivity results obtained for the reaction
without any added catalyst can be thus explained by the slow
formation of FA under these conditions (cf. Table 1). The
small quantity of FA then present is enough to catalyze the
HMF synthesis but also such that it limits HMF degradation.
Therefore, it is logical to notice that the highest yield and
selectivity results in the absence of any added catalyst are
obtained for an “ideal” amount of FA between 2 and 4% (cf
Table 1, 2, or 3). As for temperature and time, a compromise
must be found between FA-catalyzed HMF formation and the
equally FA-catalyzed HMF degradation. Furthermore, because
FA formation depends mainly on time and temperature, these
two parameters remain the two critical parameters for an
efficient HMF synthesis.
In light of these findings on the effective autocatalyzed
dehydration by release of FA in solution, we recommend the
stringent evaluation of future potential catalysts for HMF
formation in aqueous media against the blank reaction.
In conclusion, starting from a highly concentrated fructose
solution containing only sugar and water, without any
cosolvent, extracting phase, or coproduct (salts), good HMF
yields can be achieved. This autocatalyzed reaction may
facilitate the development of a very simple and sustainable
process. Combined with an efficient isomerization step, it could
also lead to a new HMF synthesis from glucose. To avoid the
virtually impossible isolation of HMF,22 the sugar and HMF-
containing reaction mixture could be used as substrate. For
instance, in the fermentative conversion of HMF to the stable
and isolable 2,5-furandicarboxylic acid, FDCA.23
times by adding 8 mL of 5 mM H2SO4. Two milliliters of this
diluted solution was placed in an Eppendorf tube and
centrifuged, and the supernatant was analyzed by HPLC.
HPLC Analysis. The concentrations of HMF, fructose,
glucose, sucrose and the degradation products in the aqueous
phases were determined on a HPLC equipped with a CarboSep
Coregel column, Shimadzu RI and UV detectors (210 nm), and
a Perkin-Elmer series 200 autosampler. Samples were diluted by
a factor of 10 or 20 with an aqueous solution of 5 mM H2SO4.
Ten microliters of the diluted samples was measured by HPLC.
The used eluent was an aqueous solution of 5 mM H2SO4. The
method lasted 35 min with a flow rate of 0.8 mL/min. Both UV
(for HMF and furaldehyde, Fal) and RI (for HMF, fructose,
LA, FA, and Fal) detections were used. The column was
maintained at 60 °C. A calibration was established by
preparation of standard solutions of the different sugars,
HMF, and organic acids, LA, and FA. Retention times (min),
RI: glucose, 6.7; fructose, 7.3; sucrose, 6.7; FA, 10.3; LA, 11.5;
HMF, 21.7; Fal, 32.6. UV (min): HMF, 21 min; Fal, 32 min.
AUTHOR INFORMATION
■
Corresponding Author
*Fax: +31 (0) 15 2781415. E-mail: u.hanefeld@tudelft.nl.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The work presented was executed within the BE-Basic program
and was funded (in part) by the Dutch Ministry of Economic
Affairs. The authors gratefully acknowledge Dr. Harald
Ruijssenaars (Bird Engineering) for fruitful and valuable
discussions about this work.
EXPERIMENTAL SECTION
■
Chemicals. Commercially available chemicals were used
without further purifications.
General Procedure. A 600 mg portion of fructose was
weighed and added to an Ace pressure 15 mL-glass tube. The
solution was brought up to 2 mL by adding demiwater (pH
6.7) and placed in an oil bath at 190 °C. After 40 min, the tube
was removed from the oil bath and allowed to cool to room
temperature (∼5 min). The aqueous phase was diluted 10
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