Mechanism of the dehydration of d-fructose to 5-hydroxymethylfurfural in dimethyl sulfoxide at 150 °C: an NMR study

Article abstract of DOI:10.1016/j.carres.2008.09.008

The anomeric composition of d-fructose in dimethyl sulfoxide changes when the solution is heated from room temperature to 150 °C, with a small increase in the α-furanose form at the expense of the β-pyranose tautomer. Additionally, a small amount of α-pyranose form was also observed at 150 °C. A mechanism is proposed for the dehydration of d-fructose to 5-hydroxymethylfurfural in DMSO at 150 °C, where the solvent acts as the catalyst. A key intermediate in the reaction was identified as (4R,5R)-4-hydroxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde by using ¹H and ¹³C NMR spectra of the sample during the reaction.

Full text of DOI:10.1016/j.carres.2008.09.008

Carbohydrate Research 343 (2008) 3021–3024
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Mechanism of the dehydration of D-fructose to 5-hydroxymethylfurfural
in dimethyl sulfoxide at 150 °C: an NMR study
*
Ananda S. Amarasekara , LaToya D. Williams, Chidinma C. Ebede
Department of Chemistry, Prairie View A&M University, Prairie View, TX 77446, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 April 2008
Received in revised form 8 September 2008
Accepted 9 September 2008
Available online 15 September 2008
The anomeric composition of
D
-fructose in dimethyl sulfoxide changes when the solution is heated from
-furanose form at the expense of the b-pyr-
-pyranose form was also observed at 150 °C. A mech-
-fructose to 5-hydroxymethylfurfural in DMSO at 150 °C,
room temperature to 150 °C, with a small increase in the
anose tautomer. Additionally, a small amount of
anism is proposed for the dehydration of
where the solvent acts as the catalyst. A key intermediate in the reaction was identified as (4R,5R)-4-
hydroxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde by using 1H and 13C NMR spectra of the
sample during the reaction.
a
a
D
Keywords:
D-Fructose
Ó 2008 Elsevier Ltd. All rights reserved.
5-Hydroxymethylfurfural
Dehydration
1. Introduction
The dehydration of D-fructose is a complex multistep process,
and there are several reports on the mechanistic investigations on
this industrially significant reaction.14–18 All these studies were
carried out on the aqueous media reaction with an added mineral
acid, which usually leads to further hydrolysis of HMF to levulinic
acid, lowering the yield of HMF. On the other hand, dehydration
in DMSO gives a cleaner reaction, and at a higher temperature,
this occurs without an added mineral or Lewis acid catalyst.19
All the earlier mechanistic studies14–18 were carried out by mea-
Acid-catalyzed hydrolysis, followed by dehydration of most of
the abundant biomass polysaccharides, produces furan derivatives
such as furfural and 5-hydroxymethylfurfural (HMF) as the major
products. These furans can be considered as practical renewable
resources-based feedstock materials useful in the replacement of
some fossil raw materials.1,2 5-Hydroxymethylfurfural is expected
to play a major role in this new generation of chemicals as it can be
used as a precursor for polymers and a number of useful materials.
As testimony to the importance of HMF, several extensive reviews
are reported in the literature about the preparation and applica-
tions of this versatile compound.3–5 The acid-catalyzed dehydr-
ation of hexoses in aqueous medium at elevated temperatures
produces levulinic acid in significant amounts in addition to
HMF. Ketohexoses are known to produce HMF more efficiently
and selectively than aldohexoses, and this may be due to the fact
that aldohexoses enolize to a much lower degree than ketohexoses.
In these reactions levulinic and formic acid formation is primarily
due to further hydrolysis of HMF in the aqueous acidic medium,
and this can be virtually suppressed by using a non-aqueous sol-
vent such as dimethyl sulfoxide (DMSO) and using certain Lewis
acid catalysts. In recent years, a number of methods have been
suring the rate of disappearance of D-fructose, which did not yield
insight into the intermediates involved in the reaction. In a ki-
netic investigation, Kuster and van der Baan showed17 that the
rate of disappearance of
essentially first order in
D
-fructose and formation of HMF are
-fructose concentration for reactions
D
carried out in 0.5–2 M aq HCl at 95 °C. Further, their studies sug-
gested the role of an unprotonated (uncharged) intermediate in
the two-step reaction sequence. Antal et al.20 later reported the
reaction in 2 mM aq H2SO4 medium at different temperatures
and pressures by monitoring the concentrations of
D-fructose
and the key products, levulinic acid, formic acid, furfural and
HMF, and proposed a mechanism involving a fructofuranosyl cat-
ion as a key intermediate. The mechanism of the dehydration
reaction in DMSO has not been investigated, and we have under-
taken to study this reaction using NMR methods, which give a
better insight into the structures of the intermediates. In this
developed for the efficient high-yield dehydration of
D-fructose
to HMF. These include the acidic ion-exchange resins6 in DMSO,
vanadium,7 niobium8 and zirconium9 phosphate catalysts, super-
critical fluids,10,11 and ionic liquid12,13 media.
communication, we report our study on the dehydration of
D-
fructose in DMSO at 150 °C without any added mineral or Lewis
acid catalyst by monitoring the 1H and 13C NMR spectra, and
the identification of a key intermediate involved in the reaction
using spectroscopic data.
* Corresponding author. Tel.: +1 936 261 3107; fax: +1 936 261 3117.
E-mail address: asamarasekara@pvamu.edu (A. S. Amarasekara).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.09.008

3022
A. S. Amarasekara et al. / Carbohydrate Research 343 (2008) 3021–3024
recorded using an identical experiment without adding biphenyl
2. Experimental
internal standard in order to maintain the clarity of the spectra
in the low-field region.
2.1. Instrumentation and materials
1H NMR spectra were recorded in DMSO-d6 on a Varian Mercury
Plus spectrometer operating at 400 MHz. Chemical shifts are given
in ppm downfield from TMS (d = 0.00). 13C NMR spectra in DMSO-
d6 were recorded on the same spectrometer operating at 100 MHz.
Chemical shifts are reported relative to DMSO-d6 and converted to
d (TMS) using d (DMSO) = 39.51. Anhyd DMSO-d6 (99.9% atom D)
2.3. Anomeric compositions of
D
-fructose at 23 °C and 150 °C
-fructose at 23 °C (room tem-
The anomeric compositions of
D
perature) and 150 °C were determined by the reported method21,22
of integrating the anomeric 2-OH 1H NMR signals of furanose and
pyranose tautomers in the t = 0.0, 1.0 and 3.0 min samples. These
results are shown in Table 1. All the D-fructose anomers are negli-
gibly small in the t = 6.0 spectra and completely disappeared at
later stages of the reaction.
was used as the reaction medium. (À)-
D-Fructose (>99.9%) and
biphenyl (99.5%) from Sigma–Aldrich were used without further
purification.
2.2. NMR kinetic investigation
3. Results and discussion
A solution of D-fructose (45.0 mg, 0.25 mmol) in 0.60 mL of an-
3.1. Anomeric composition of
D
-fructose in DMSO
-fructose in DMSO at 23 °C and
hyd DMSO-d6 was prepared in a 5-mm NMR tube. Biphenyl
(15.4 mg, 0.10 mmol) was added as an internal standard. The sam-
ple was allowed to stabilize at room temperature for 24 h, then, 1H
(rd = 2 s, NS = 8) and 13C (rd = 2 s, NS = 256) NMR spectra were re-
corded as the initial baseline data. Afterward the NMR tube was
heated in a thermostated oil bath at 150 1 °C for 1.0 min, and
then the reaction was quenched by immersing the NMR tube in
an ice-water bath. The tube was immediately transferred to the
NMR spectrometer, 1H and 13C NMR spectra were recorded using
conditions identical to the first t = 0 spectra. Further spectra were
recorded after heating 3.0, 6.0, 12.0, 18.0, 24.0, 30.0 and 36.0 min
The anomeric compositions of
D
150 °C from this work and selected 20 and 50 °C data from pub-
lished results are shown in Table 1. The results obtained at 23 °C
are comparable to the published22,23 anomeric compositions at
20 °C. The anomeric compositions at 150 °C show a small increase
in the a-furanose form at the expense of the b-pyranose tautomer.
Interestingly, a small amount of
a-pyranose form was also ob-
served at 150 °C.
3.2. Characterization of the intermediate and the mechanism of
the reaction
of total heating time at 150 1 °C. D-Fructose, reaction intermedi-
ate, and HMF amounts at different time intervals were measured
by manual integration of the 1H NMR peaks and comparison of
these areas with the area of the biphenyl internal standard. The
Figure 1 shows a time-progression stack of 1H NMR spectra,
illustrating the course of the dehydration of D-fructose to HMF.
variations in the amounts of
D-Fructose, reaction intermediate,
The spectra recorded after 1.0 min at 150 °C (t = 1.0 min) showed
only the four tautomers of fructose and no intermediates or prod-
ucts, whereas the t = 6.0 min, sample showed two new peaks in the
low-field region at 6.23 (d, J = 3.2 Hz) and 9.46 (s) ppm, indicating
and HMF during the 36.0-min reaction period are shown in
Figure 3. The changes in the 1H NMR spectra during the course
of the reaction are shown in Figure 1, and this set of spectra were
Figure 1. 1H NMR spectra of the -fructose sample (0.25 mmol in 0.6 mL of DMSO-d6) after 1.0, 6.0, 12.0, 18.0, 24.0, and 30.0 min of heating at 150 oC.
D

A. S. Amarasekara et al. / Carbohydrate Research 343 (2008) 3021–3024
3023
Table 1
Anomeric compositions of D-fructose in DMSO-d6 at different temperatures
0.25
Temperature
a
-Pyranose b-Pyranose
a-Furanose b-Furanose Reference
(°C)
(
a
-p)
(b-p)
(
a
-f)
(b -f)
0.2
0.15
0.1
20
20
50
23
—
—
—
—
26
29
21
27.7
16.1
21.9
20
20
23.5
20.7
24.9
25.9
55
46
51
51.6
54.5
48.9
23
22
22
This work
This work
This work
150 (1.0 min) 4.5
150 (3.0 min) 4.0
the formation of a reaction intermediate. The 13C NMR spectra of
this sample (not shown in the figures) showed two new alkene
peaks at 122.8 and 156.9 ppm and a peak in the carbonyl region
0.05
0
at 184.9 ppm corresponding to an a,b-unsaturated aldehyde func-
tional group. These new peaks in the 1H and 13C NMR spectra can
be explained as the formation of a dihydrofuran-2-aldehyde inter-
mediate in the dehydration reaction. The proposed mechanism for
the dehydration reaction in DMSO at 150 °C without any added
acid is shown in Figure 2. The dihydrofuran-2-aldehyde intermedi-
ate identified in the NMR study can be recognized as (4R,5R)-4-hy-
droxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde (4) in
the proposed mechanism. The 1H NMR signal at 6.23 ppm in the
spectra of the intermediate 4 was assigned to the C-3 olefinic
hydrogen, and this signal appears as a doublet (J 3.3 Hz) with cou-
pling to the C-4 hydrogen. 13C NMR signals of the dihydrofuran-2-
aldehyde intermediate 4 were observed at 122.8, 156.8, and
184.9 ppm, and these values are comparable to the chemical shifts
of a similar intermediate, 5-hydroxy-5-hydroxymethyl-4,5-dihy-
drofuran-2-carbaldehyde, where the corresponding peaks were
reported24 at 125.4, 153.5, and 192.2 ppm. In the proposed mech-
0
10
20
30
Time (min.)
D-Fructose
4
HMF
Figure 3. Changes in the amounts of
methyl-4,5-dihydrofuran-2-carbaldehyde (4) and 5-hydroxymethylfurfural (HMF)
during the reaction (0.25 mmol of -fructose in 0.6 mL of DMSO-d6 at 150 °C).
D-fructose, (4R,5R)-4-hydroxy-5-hydroxy-
D
evidence was seen for the intermediate 2 or the enol intermediate
3 (Fig. 2), probably because these compounds rapidly dehydrate to
give 4, which was identified by spectroscopic data. Attempts to iso-
late this important intermediate were not successful showing the
facile dehydration of 4 to HMF.
anism both furanose forms (a-f/b-f) can undergo DMSO-catalyzed
initial dehydration (Fig. 2 1?2). The 1H NMR spectra of the sample
after 12.0 min of reaction at 150 °C (Fig. 1) showed further increase
in the peaks corresponding to intermediate 4. Furthermore, this
sample showed another new set of small peaks at 6.57 (d, J
3.6 Hz), 7.46 (d, J 3.6 Hz), and 9.51 (s) ppm corresponding to the fi-
nal product HMF. The 13C NMR spectra of this sample further con-
firmed the production of HMF with the peaks at 58.6, 110.4, 125.0,
152.4, 162.8, and 178.7 ppm, identical to the reported 13C reso-
nance values.24 At t = 18.0 min, a further increase in the amounts
4. Conclusion
We have shown that the anomeric composition of
DMSO changes when heated from room temperature to 150 °C,
with a small increase in the -furanose ( -f) form at the expense
of b-pyranose (b-p) tautomer. Additionally, a small amount of
pyranose ( -p) form was also observed at 150 °C. We have pro-
posed a mechanism to explain the dehydration of the two furanose
forms of -fructose to HMF through the elimination of three water
D-fructose in
a
a
a
-
a
D
of intermediate
4 and HMF is observed, whereas beyond
molecules, where DMSO acts as the catalyst, and we identified a
key intermediate in the reaction based on spectroscopic methods.
The structure of this intermediate was established as (4R,5R)-4-hy-
droxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde (4) by
using a combination of 1H and 13C NMR data. This is the first direct
identification of an intermediate involved in the important dehy-
t = 24.0 min it shows a decrease in 4 with an increase in HMF
(Fig. 1). Finally, the intermediate 4 completely disappeared to give
HMF as the final product. Figure 3 shows the changes in the
amounts of D-fructose, intermediate 4, and HMF during the course
of the reaction, where the amounts were determined using a sam-
ple with a biphenyl internal standard. Furthermore, no direct NMR
dration process of D-fructose.
H3C
S O
H3C
H3C
H3C
S O
H
H
OH
OH
OH
OH
OH
OH
O
O
HO
2
3
O
HO
O
HO
O
CHO
O
5
CHO
OH
- H2O
- H2O
H3C
- H2O
4
H
OH
O
OH
OH
OH
OH
CH3
CH3
CH3
O S
HO S
5
4
CH3
S O
H3C
(α-f/ β-f)
1
2
3
Figure 2. Proposed mechanism for the dehydration of D-fructose furanose forms 1 (a-f/b-f) to 5-hydroxymethylfurfural (5) in dimethyl sulfoxide at 150 °C.

3024
A. S. Amarasekara et al. / Carbohydrate Research 343 (2008) 3021–3024
9. Asghari, F. S.; Yoshida, H. Carbohydr. Res. 2006, 341, 2379–2387.
Acknowledgments
10. Bicker, M.; Kaiser, D.; Ott, L.; Vogel, H. J. Supercrit. Fluids 2005, 36, 118–126.
11. Bicker, M.; Hirth, J.; Vogel, H. Green Chem. 2003, 5, 280–284.
12. Lansalot-Matras, C.; Moreau, C. Catal. Commun. 2003, 4, 517–520.
13. Moreau, C.; Finiels, A.; Vanoye, L. J. Mol. Catal. A: Chem. 2006, 253, 165–169.
14. McKibbins, S. W.; Harris, J. F.; Saeman, J. F.; Neill, W. F. Forest Prod. J. 1962, 17–
23.
The NMR spectrometer used in this study was obtained through
a NSF MRI Grant CHE-0421290. LDW and CCE thank NIH-NIGMS
RISE Grant R25 GM078361-01 for research fellowships.
15. Kuster, B. F. M.; Tebbens, L. M. Carbohydr. Res. 1977, 54, 158–164.
16. Kuster, B. F. M.; Temmink, H. M. G. Carbohydr. Res. 1977, 54, 185–191.
17. Kuster, B. F. M.; van der Baan, H. S. Carbohydr. Res. 1977, 54, 165–176.
18. Kuster, B. F. M. Carbohydr. Res. 1977, 54, 177–183.
19. Musau, R. M.; Munavu, R. M. Biomass 1987, 13, 67–74.
20. Antal, M. J., Jr.; Mok, W. S. L.; Richards, G. N. Carbohydr. Res. 1990, 199, 91–
109.
21. Schneider, B.; Lichtenthaler, F. W.; Steinle, G.; Schiweck, H. Justus Liebigs Ann.
Chem. 1985, 12, 2443–2453.
22. Nicole, D. J.; Gillet, B.; Eppiger, E. N.; Delpuech, J. J. Tetrahedron Lett. 1982, 23,
1669–1672.
References
1. Corma, A.; Iborra, S.; Velty, A. Chem. Rev. 2007, 107, 2411–2502.
2. Klass, D. L. Biomass for Renewable Energy, Fuels and Chemicals; Academic Press:
SanDiego, CA, 1998.
3. Lewkowski, J. Arkivok 2001, 1, 17–54.
4. Cottier, L.; Descotes, G. Trends Heterocycl. Chem. 1991, 2, 233–248.
5. Kuster, B. F. M. Starch-Stärke 1990, 42, 314–321.
6. Román-Leshkov, Y.; Chheda, J. N.; Dumesic, J. A. Science 2006, 312, 1933–1937.
7. Carlini, C.; Patrono, P.; Galletti, A. M. R.; Sbrana, G. Appl. Catal. A: Gen. 2004, 275,
111–118.
23. Jaseja, M.; Perlin, A. S.; Dais, P. Magn. Reson. Chem. 1990, 28, 283–289.
24. Horvat, J.; Klai, B.; Metelko, B.; Unji, V. Tetrahedron Lett. 1985, 269, 2111–2114.
8. Carniti, P.; Gervasini, A.; Biella, S.; Auroux, A. Catal. Today 2006, 118, 373–378.