Bis-sulfonic acid ionic liquids for the conversion of Fructose to 5-Hydroxymethyl-2-furfural

Article abstract of DOI:10.3390/molecules171112804

Homogenous bis-sulfonic acid ionic liquids (1 mol equiv.) in DMSO (10 mol equiv.) at 100 °C efficiently mediated the conversion of D-fructose into 5-hydroxymethyl-2-furfural in 75% isolated yield, which was roughly a 10% increment compared to the case of the mono-sulfonic acid ionic liquids.

Full text of DOI:10.3390/molecules171112804

Molecules 2012, 17, 12804-12811; doi:10.3390/molecules171112804
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
Bis-sulfonic Acid Ionic Liquids for the Conversion of Fructose
to 5-Hydroxymethyl-2-furfural
Sang Eun Sim 1, Sunjeong Kwon 1 and Sangho Koo 1,2,
*
1
Department of Nano Science and Engineering, Myong Ji University, San 38-2, Nam-Dong, Yongin,
Kyunggi-Do 449-728, Korea; E-Mails: longberk@hanmail.net (S.E.S.); kksj1675@hanmail.net (S.K.)
Department of Chemistry, Myong Ji University, San 38-2, Nam-Dong, Yongin,
Kyunggi-Do 449-728, Korea
2
* Author to whom correspondence should be addressed; E-Mail: sangkoo@mju.ac.kr;
Tel.: +82-31-330-6185; Fax: +82-31-335-7248.
Received: 10 September 2012; in revised form: 26 October 2012 / Accepted: 29 October 2012 /
Published: 31 October 2012
Abstract: Homogenous bis-sulfonic acid ionic liquids (1 mol equiv.) in DMSO
(10 mol equiv.) at 100 °C efficiently mediated the conversion of D-fructose into
5-hydroxymethyl-2-furfural in 75% isolated yield, which was roughly a 10% increment
compared to the case of the mono-sulfonic acid ionic liquids.
Keywords: biomass conversion; D-fructose; 5-hydroxymethyl-2-furfural; acid ionic liquid;
sulfonic acid
1. Introduction
Generating a sustainable energy source from the readily available natural resources is one of the
most important and urgent challenges of mankind. Much attention has focused on the biomass
conversion into the platform chemical such as 5-hydroxymethyl-2-furfural (5-HMF) (2) [1,2], which
can be further transformed to bio-fuels or other commodity chemicals [3,4]. D-Fructose (1) is the basic
and the most widely studied biomass, whereby dehydration with elimination of three water molecules
directly produces 5-HMF (2) (Scheme 1) [5]. Biomass conversion in ionic liquids has been extensively
studied due to their strong solvent power as well as good thermal stability, in which acids were
normally added to the reaction media in order to facilitate the dehydration step [6–14].

Molecules 2012, 17
12805
Scheme 1. D-Fructose (1) conversion to 5-HMF (2).
We were interested in ionic liquids containing an acid moiety in the expectation of the synergistic
effect on the acidity as well as the solubility [15]. There have been several reports on the biomass
conversion into 5-HMF utilizing the ionic liquids containing mono-sulfonic acid as reaction media or
as catalysts [16–19]. Sulfonic acids seemed to be suitable promoters for the dehydration of sugars due
to their ideal pKa values for the dehydration [20]. The preparation and measurement of the pKa values
of the bis-sulfonic acid ionic liquids has been recently published, which were efficiently utilized as
catalysts in the esterification of glycerol and Fischer indole synthesis [21,22]. It appeared that the
bis-sulfonic acid ionic liquids might as well be better promoters for the biomass conversion into
5-HMF, and we herein demonstrated the efficiency of the bis-sulfonic acid ionic liquids as efficient
promoters for the fructose conversion into 5-HMF, together with the comparison with the
mono-sulfonic acid ionic liquids.
2. Results and Discussion
The zwitterionic salts 3 and 5 containing a sulfonate anion were prepared by the reaction of
propanesultone with 1-methylimidazole and 1-(trimethylsilyl)imidazole, respectively [20,22]. Strong
acids (HX) which were selected among the groups of methanesulfonic acid (pKa −1.9), sulfuric acid
(pKa −2.8), para-toluenesulfonic acid (pKa −2.8), trifluoromethanesulfonic acid (pKa −13.6), and
chlorosulfonic acid (pKa −6.0) should be added to protonate the sulfonate anion, thereby forming the
ionic liquids 4 and 6 containing mono- and bis-sulfonic acids, respectively (Scheme 2). The zwitterion
5 itself is an ionic liquid containing a sulfonic acid.
Scheme 2. Preparation of mono- and bis-sulfonic acid ionic liquids 4 and 6.

Molecules 2012, 17
12806
The ionic liquids 4 were easily prepared by heating the mixture of the acid and the salt 3 at 80 °C
for 1~2 h. On the other hand, solvent (toluene or water) was required for the generation of the ionic
liquids 6 due to their high melting points. It is much convenient to use toluene as a solvent to prepare
the ionic liquids 6 as pure white solid forms, whereas a longer reaction time as well as thorough drying
was required from the aqueous solutions [22]. When DMSO was used as a reaction medium for the
fructose conversion, the isolation of the ionic liquids 6 was not necessary. The acid and the salt 5 in
DMSO were heated at 100 °C for 2 h before fructose was added, which gave almost identical results
with the cases where the isolated ionic liquids 6 were used in DMSO.
The effects of acid, acid ionic liquid, and solvent on the conversion of fructose to 5-HMF was
examined first and the results are summarized in Table 1. The reaction was carried out at 100 °C
for 1 h using 0.5 g of D-fructose. Methanesulfonic acid (MsOH) alone contributed little effect on the
formation of 5-HMF regardless of the amount of acid added (entries 1–2). Ten mol equiv. of acid ionic
liquid 4a prepared by the addition of MsOH to the zwitterionic salt 3 produced 5-HMF in 31% yield
(entry 4). The amount of acid ionic liquid 4a can be reduced to 1 mol equiv. by the use of organic
solvent, among which DMSO is better than any other solvent (entries 5–8). DMSO is known to be a
favorable solvent for fructose dehydration due to its ability to prevent the formation of by-products,
levulinic acid and humins, from the resulting 5-HMF [16]. On the other hand, water is conceived to
have a negative effect on the dehydration of sugars to 5-HMF, because 5-HMF may react with water to
generate levulinic acid and formic acid or furfural under acidic conditions [18,19,23,24]. Therefore,
excessive water should be avoided from the reaction medium (entry 6). It is also important to use the
right amount of solvent to give the optimum concentration (ca. 1.4 M solution) for the fructose
conversion. A slight decrease in the yield of 5-HMF was noticed for diluted solutions (ca. 0.14 M and
0.28 M) of fructose in DMSO (entries 8–10). When one mol equiv. of acid ionic liquid 4a is used for
fructose (0.5 g), ten mol equiv. of DMSO (2 mL) provides the optimum concentration, in which 100%
conversion of fructose and 66% yield of 5-HMF were obtained (entry 10).
Table 1. The effect of the acid ionic liquid 4a and solvent on the conversion of D-fructose
(1) into 5-HMF (2) a.
3
MsOH
(equiv.)
Solvent
(mL)
EtOAc (10)
-
Conversion
(%) b
96.3
Yield 2
(%) c
5.0
3.0
5.0
30.8
41.0
0.7
41.3
59.8
59.3
Selectivity
(%)
5.2
Entry
(equiv.)
1
2
3
4
5
6
7
8
9
-
-
1
10
1
1
1
1
1
1
1
10
1
10
1
1
1
1
1
81.5
99.5
95.6
99.6
17
92.7
100
100
3.7
5.0
-
-
32.2
41.2
4.1
44.6
59.8
59.3
65.6
EtOAc (10)
H2O (10)
MeCN (10)
DMSO (10)
DMSO (20)
DMSO (2)
10
1
100
65.6
a
b
The reactions were carried out at 100 °C for 1 h using 0.5 g of D-fructose (1); The conversion was
calculated based on the recovered D-fructose in aqueous layer by HPLC analysis (2:8 H2O/MeCN; flow rate
1~2 mL/min; PDA detector at 195 nm) using the Waters Carbohydrate Analysis Column (3.9 × 300 mm);
c
The Yield (%) was calculated based on 5-HMF in organic layer by HPLC analysis (5:5 H2O/MeOH; flow
rate 2 mL/min; PDA detector at 285 nm) using Watchers 120 ODS (4116B) column (4.6 × 250 mm).

Molecules 2012, 17
12807
The effects of the amount of acid ionic liquid, reaction temperature and time, and the types of
sulfonic acid ionic liquids on the fructose conversion to 5-HMF were then studied systematically under
the above solvent conditions (2 mL DMSO for 0.5 g D-fructose), and the results are summarized in
Table 2. Since the dehydration of fructose was reported to proceed in high boiling DMSO even without
acid catalysts, the blank experiment was carried out first [9]. D-Fructose in DMSO was heated to
100 °C for 1 h to produce 5-HMF in only 15% yield (entry 1). The mono-sulfonic acid ionic liquid 4a
was then selected again for the optimization study. The yield of 5-HMF was continuously increased as
the amount of 4a was increased up to one mol equiv., and then decreased back (entries 2–7). This
phenomenon can be explained based on the following contrasting facts that sufficient active site from
the ionic liquid should be available for the facile fructose dehydration and that the acidic ionic liquids
promote degradation of 5-HMF at elevated temperature [9,18,20]. We set the optimum temperature
and time as 100 °C and 1 h, even though almost identical result was obtained in 2 h at 100 °C
(entries 8–11). However, humin and insoluble polymers were obtained after a prolonged reaction time.
Table 2. The conversion of D-fructose (1) into 5-HMF (2) under the acidic ionic liquids in DMSO a.
Ionic liquid
(equiv.)
-
Temp.
(°C)
100
100
100
100
100
100
100
80
Time
(h)
1
Yield 2
(%) b
15
Entry
1
2
4a (0.1)
4a (0.3)
4a (0.5)
4a (0.7)
4a (1.0)
4a (2.0)
4a (1.0)
4a (1.0)
4a (1.0)
4a (1.0)
4b (1.0)
4c (1.0)
4d (1.0)
4e (1.0)
5 (1.0)
1
48
3
1
51
4
1
59
5
1
62
6
1
66
7
1
50
8
1
54
9
120
100
100
100
100
100
100
100
100
100
100
100
100
1
54
10
11
12
13
14
15
16
17
18
19
20
21
0.5
2
52
66
1
65
1
67
1
63
1
23
1
57
6a (1.0)
6b (1.0)
6c (1.0)
6d (1.0)
6e (1.0)
1
75
1
72
1
64
1
55
1
33
a
b
The reactions were carried out using 0.5 g of D-fructose (1 equiv.) in 2 mL of DMSO; Isolated
yield after silica gel column chromatography.
The efficiencies of various mono- and bis-sulfonic acid ionic liquids for the fructose conversion to
5-HMF were then compared under the above optimized conditions (entries 12–21). The pKa of the
sulfonic acids (or the counter anions of the ionic liquids) did not make much differences in the product
yield (~60% isolation of 5-HMF) for the mono-sulfonic acid ionic liquids 4a–d except for the case of

Molecules 2012, 17
12808
chlorosulfonic acid in 4e (entries 12–15). The zwitterionic salt 5 can be regarded as a mono-sulfonic
acid ionic liquid, in which the counter ion is tethered by the propylene bridge. An almost similar yield
of 5-HMF (57%) was obtained for 5 as the other mono-sulfonic acid ionic liquids 4a–d (entry 16). The
bis-sulfonic acid ionic liquid 6e prepared from the strong super acid was not effective in converting
D-fructose into 5-HMF (entry 21) like in the case for the monosulfonic acid ionic liquid 4e. It was
reported that strong acids afford undesirable by-products such as humins. The mildest sulfonic acids,
methanesulfonic acid and sulfuric acid, provided the best yield (~75%) of 5-HMF (entries 17–18). The
homogeneity of the reaction media (the acid ionic liquid and DMSO) may be the most important issue in
these bis-sulfonic acid ionic liquids. It is obvious that the bis-sulfonic acid ionic liquids 6 are generally
better promoters than the mono-sulfonic acid ionic liquids 4 in converting fructose to 5-HMF.
3. Experimental
3.1. General
1H-NMR spectra were recorded on a Varian 400 MHz NMR spectrometer in deuterated water
(D2O) for ionic liquids and deuterated chloroform (CDCl3) for 5-HMF. Solvents for extraction and
chromatography were reagent grade and used as received. The column chromatography was performed
by the method of Still with silica gel 60, 70–230 mesh ASTM supplied by Merck using a gradient
mixture of EtOAc/hexanes. Reactions were performed in a flask open to the air unless noted otherwise.
HPLC analysis for the sugar in aqueous layer was carried out using the Waters Carbohydrate Analysis
Column (3.9 × 300 mm) with H2O/MeCN (2:8) as a mobile phase (flow rate 1~2 mL/min), while
5-HMF in organic layer was analyzed using Watchers 120 ODS (4116B) column (4.6 × 250 mm) with
H2O/MeOH (5:5) as a mobile phase (flow rate 2 mL/min). PDA detector was used to measure each
compound either at 195 nm (D-fructose) or at 285 nm (5-HMF).
3.2. Preparation of 3
To a stirred solution of 1-methylimidazole (7.93 mL, 100 mmol) in acetone (100 mL) at 0 °C was
added propanesultone (12.21 g, 100 mmol) in acetone (80 mL). The mixture was then warmed to and
stirred at room temperature for 1 day. The crude product was filtered, rinsed thoroughly with acetone,
1
dried under reduced pressure to give 3 (19.61 g, 96 mmol) in 96% yield as a white solid. H-NMR
(D2O)  2.31 (m, 2H), 2.89–2.93 (m, 2H), 3.89 (s, 3H), 4.36 (t, J = 7.2 Hz, 2H), 7.44 (d, J = 2.0 Hz,
1H), 7.52 (d, J = 2.0 Hz, 1H) ppm.
3.3. Representative Procedure for the Preparation of 4a
The imidazolium sulfonate 3 (0.30 g, 1.48 mmol) and methanesulfonic acid (0.10 mL, 1.48 mmol)
were heated at 80 °C for 2 h. The homogeneous mixture was then cooled to room temperature, rinsed
with Et2O, and concentrated under reduced pressure to give 4a (0.43 g, 1.44 mmol) in 97% yield.
1H-NMR (D2O)  2.31 (m, 2H), 2.80 (s, 3H), 2.89–2.93 (m, 2H), 3.89 (s, 3H), 4.36 (t, J = 7.2 Hz, 2H),
7.44 (s, 1H), 7.52 (s, 1H), 8.75 (s, 1H) ppm.

Molecules 2012, 17
3.4. Preparation of 5
12809
To a stirred solution of 1-(trimethylsilyl)imidazole (1.49 g, 10.6 mmol) in MeCN (20 mL) was
added propanesultone (2.60 g, 21.25 mmol). The mixture was stirred at room temperature for 1 day.
The crude product was filtered, rinsed thoroughly with acetone, and dried under reduced pressure to
1
give 5 (2.95 g, 9.43 mmol) in 89% yield as a white solid. H-NMR (D2O)  2.33 (m, 4H), 2.89–2.95
(m, 4H), 4.38 (t, J = 7.2 Hz, 4H), 7.57 (s, 2H), 8.82 (s, 1H) ppm.
3.5. Representative Procedure for the Preparation of 6a
The imidazolium sulfonate 5 (0.87 g, 2.78 mmol) and methanesulfonic acid (0.18 mL, 2.78 mmol)
in toluene (10 mL) were heated at 100 °C for 2 h. The homogeneous mixture was then cooled to room
temperature and concentrated under reduced pressure. The crude product was rinsed with Et2O and
1
then dried in a vacuum oven to give 6a (1.10 g, 2.70 mmol) in 97% yield. H-NMR (D2O)  2.33
(m, 4H), 2.80 (s, 3H), 2.89–2.96 (m, 4H), 4.38 (t, J = 7.2 Hz, 4H), 7.57 (s, 2H), 8.82 (s, 1H) ppm.
3.6. Representative Procedure for 5-HMF (2) Using the Acid Ionic Liquid 6a
The imidazolium sulfonate 5 (0.87g, 2.78 mmol) and methanesulfonic acid (0.18ml, 2.78mmol)
were mixed in DMSO, and the mixture was heated at 100 °C for 2 h. D-Fructose (0.5 g, 2.78 mmol)
was then added to the mixture, and heated for 1 h. The color of the mixture turned to dark brown. The
mixture was cooled to room temperature, quenched with water, extracted with EtOAc, dried over
sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by
1
SiO2 flash column chromatography to give 5-HMF (0.26 g, 2.08 mmol) in 75% yield. H-NMR
(CDCl3)  2.24 (br s, 1H), 4.73 (s, 2H), 6.52 (s, 1H), 7.22 (s, 1H), 9.61 (s, 1H) ppm.
4. Conclusions
We demonstrated that the homogenous bis-sulfonic acid ionic liquids 6 are efficient mediators for
the conversion of D-fructose to 5-HMF. Up to 75% yield of 5-HMF was isolated in DMSO at 100 °C
for 1 h using the bis-sulfonic acid ionic liquid 6a prepared by the addition of methanesulfonic acid
to the zwitterionic salt 5, which was ~10% higher than the yield obtained from the use of the
mono-sulfonic acid ionic liquid 4a. Studies on the other biomass (e.g., glucose and cellulose)
conversion to 5-HMF and further conversions to the other useful chemicals using the bis-sulfonic acid
ionic liquids 6a–b are currently underway together with an effort for efficient recycling of the ionic
liquids from the highly polar and high boiling DMSO solution.
Acknowledgments
This research was supported by Basic Science research Program (No. 2012-000702) and by Priority
Research Centers Program (No. 2012-0006693) both through the National Research Foundation of
Korea funded by the Ministry of Education, Science and Technology (MEST).

Molecules 2012, 17
12810
References
1. Ragauskas, A.J.; Williams, C.K.; Davison, B.H.; Britovsek, G.; Cairney, J.; Eckert, C.A.;
Frederick, W.J. Jr.; Hallett, J.P.; Leak, D.J.; Liotta, C.L.; et al. The path forward for biofuels and
biomaterials. Science 2006, 311, 484–489.
2. Roman-Leshkov, Y.; Chheda, J.N.; Dumesic, J.A. Phase modifiers promote efficient production
of hydroxymethylfurfural from fructose. Science 2006, 312, 1933–1937.
3. Roman-Leshkov, Y.; Barrett, C.J.; Liu, Z.Y.; Dumesic, J.A. Production of dimethylfuran for
liquid fuels from biomass-derived carbohydrates. Nature 2007, 447, 982–986.
4. Lichtenthaler, F.W. Unsaturated O- and N-heterocycles from carbohydrate feedstocks.
Acc. Chem. Res. 2002, 35, 728–737.
5. Binder, J.B.; Raines, R.T. Simple chemical transformation of lignocellulosic biomass into furans
for fuels and chemicals. J. Am. Chem. Soc. 2009, 131, 1979–1985.
6. Zhao, H.; Holladay, J.E.; Brown, H.; Zhang, Z.C. Metal chlorides in ionic liquid solvents convert
sugars to 5-hydroxymethylfurfural. Science 2007, 316, 1597–1600.
7. Yong, G.; Zhang, Y.; Ying, J.Y. Efficient catalytic system for the selective production of
5-hydroxymethylfurfural from glucose and fructose. Angew. Chem. Int. Ed. 2008, 47, 9345–9348.
8. Sievers, C.; Musin, I.; Marzialetti, T.; Olarte, M.B.V.; Agrawal, P.K.; Jones, C.W. Acid-catalyzed
conversion of sugars and furfurals in an ionic-liquid phase. ChemSusChem 2009, 2, 665–671.
9. Stahlberg, T.; Sorensen, M.G.; Riisager, A. Direct conversion of glucose to 5-(hydroxymethyl)furfural
in ionic liquids with lanthanide catalysts. Green Chem. 2010, 12, 321–325.
10. Takagaki, A.; Ohara, M.; Nishimura, S.; Ebitani, K. A one-pot reaction for biorefinery:
Combination of solid acid and base catalysts for direct production of 5-hydroxymethylfurfural
from saccharides. Chem. Commun. 2009, 6276–6278.
11. Huang, R.; Qi, W.; Su, R.; He, Z. Integrating enzymatic and acid catalysis to convert glucose into
5-hydroxymethylfurfural. Chem. Commun. 2010, 46, 1115–1117.
12. Hu, S.; Zhang, Z.; Song, J.; Zhou, Y.; Han, B. Efficient conversion of glucose into
5-hydroxymethylfurfural catalyzed by a common Lewis acid SnCl4 in an ionic liquid.
Green Chem. 2009, 11, 1746–1749.
13. Tong, X.; Li, Y. Efficient and selective dehydration of fructose to 5-hydroxymethylfurfural
catalyzed by Brønsted-acidic ionic liquids. ChemSusChem 2010, 3, 350–355.
14. Tong, X.; Ma, Y.; Li, Y. An efficient catalytic dehydration of fructose and sucrose to
5-hydroxymethylfurfural with protic ionic liquids. Carbohydr. Res. 2010, 345, 1698–1701.
15. Fei, Z.; Zhao, D.; Geldbach, T.J.; Scopelliti, R.; Dyson, P.J. Brønsted acid ionic liquid and their
zwitterions: Synthesis, characterization and pKa determination. Chem. Eur. J. 2004, 10, 4886–4893.
16. Bao, Q.; Qiao, K.; Tomida, D.; Yokoyama, C. Preparation of 5-hydroxymethylfurfural by
dehydration of fructose in the presence of acidic ionic liquid. Catal. Commun. 2008, 9, 1383–1388.
17. Jiang, F.; Zhu, Q.; Ma, D.; Liu, X.; Han, X. Direct conversion and NMR observation of cellulose
to glucose and 5-hydroxymethylfurfural (HMF) catalyzed by the acidic ionic liquids. J. Mol.
Catal. A 2011, 334, 8–12.
18. Tao, F.; Song, H.; Chou, L. Efficient conversion of cellulose into furans catalyzed by metal ions
in ionic liquids. J. Mol. Catal. A 2012, 357, 11–18.

Molecules 2012, 17
12811
19. Tao, F.; Song, H.; Chou, L. Catalytic conversion of cellulose to chemicals in ionic liquid.
Carbohydr. Res. 2011, 346, 58–63.
20. Tao, F.; Song, H.; Chou, L. Hydrolysis of cellulose in SO3H-functionalized ionic liquids.
Bioresour. Technol. 2011, 102, 9000–9006.
21. Liu, X.; Ma, H.; Wu, Y.; Wang, C.; Yang, M.; Yan, P.; Welz-Biermann, U. Esterification of
glycerol with acetic acid using double SO3H-functionalized ionic liquids as recoverable catalysts.
Green Chem. 2011, 13, 697–701.
22. Xu, D.-Q.; Wu, J.; Luo, S.-P.; Zhang, J.-X.; Wu, J.-Y.; Du, X.-H.; Xu, Z.-Y. Fischer indole
synthesis catalyzed by novel SO3H-functionalized ionic liquids in water. Green Chem. 2009, 11,
1239–1246.
23. Qi, X.; Watanabe, M.; Aida, T.M.; Smith, R.L., Jr. Catalytic dehydration of fructose into
5-hydroxymethylfurfural by ion-exchange resin in mixed-aqueous system by microwave heating.
Green Chem. 2008, 10, 799–805.
24. Hu, S.; Zhang, Z.; Zhou, Y.; Han, B.; Fan, H.; Li, W.; Song, J.; Xie, Y. Conversion of fructose to
5-hydroxymethylfurfural using ionic liquids prepared from renewable materials. Green Chem.
2008, 10, 1280–1283.
Sample Availability: Samples of the compounds 5 and 6 are available from the authors
© 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).