Conversion of fructose and inulin to 5-hydroxymethylfurfural in sustainable betaine hydrochloride-based media

Article abstract of DOI:10.1039/c1gc16236e

We show here that betaine hydrochloride (BHC), a co-product of the carbohydrate industry, can be used for the design of cheap and safe media capable of promoting the dehydration of fructose and inulin to HMF. In particular, in these BHC-based media, HMF was obtained with up to 84% yield, thus offering a competitive route to the traditional imidazolium-based ionic liquids.

Full text of DOI:10.1039/c1gc16236e

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COMMUNICATION
Conversion of fructose and inulin to 5-hydroxymethylfurfural in sustainable
betaine hydrochloride-based media
Karine De Oliveira Vigier,* Adlene Benguerba, Joe¨l Barrault and Franc¸ois Je´roˆme
Received 5th October 2011, Accepted 17th November 2011
DOI: 10.1039/c1gc16236e
We show here that betaine hydrochloride (BHC), a co-
product of the carbohydrate industry, can be used for the
design of cheap and safe media capable of promoting the
dehydration of fructose and inulin to HMF. In particular, in
these BHC-based media, HMF was obtained with up to 84%
yield, thus offering a competitive route to the traditional
imidazolium-based ionic liquids.
Scheme 1 Chemical structure of BHC.
Nowadays, many studies are dedicated to the conversion of
carbohydrates to chemical platforms or transportation fuels.1–4
carbohydrates such as fructose and inulin while their acid
properties promote the dehydration of these carbohydrates to
5-hydroxymethylfurfural (HMF) with high yield. BHC is a solid
and cannot be directly used as a solvent. In order to circumvent
this problem, BHC was mixed with other renewable chemicals
such as glycerol, water and choline chloride with which a liquid
phase was readily obtained. These BHC-based media afford
similar results than those collected in imidazolium-based ionic
liquids while offering remarkable advantages such as low price
and low ecological footprint. Recyclability of these media as well
as extraction of HMF is also discussed.
In a previous article, we have shown that 1-butyl-4-
methylimidazolium chloride ([BMIM]Cl) can be partly sub-
stituted by glycerol, a renewably-sourced co-solvent, in the
dehydration of fructose to HMF.11 Although HMF was obtained
with 70% yield in a mixture glycerol/[BMIM]Cl (35/65), pres-
ence of toxic and expensive [BMIM]Cl still represents a serious
drawback of this process. Having these previous results in mind,
we first investigated the catalytic activity of a BHC/glycerol
mixture in the dehydration of fructose to HMF. Prior to catalytic
experiments, reactivity of glycerol with BHC was checked. To
this end, an equimolar mixture of glycerol and BHC was heated
at 110 ◦C. Under these conditions, no esterification reaction
occurred between BHC and glycerol.12 It is noteworthy that upon
prolonged reaction time, the reaction medium became slightly
yellow colored suggesting a partial degradation of glycerol.
Next, 2 g of fructose (40 wt%) was dissolved in 5 g of the
mixture glycerol/BHC (80/20) and heated at 110 ◦C. Reaction
progress was monitored by HPLC. Under these conditions,
HMF was produced with a maximum yield of 26% after 25 min
of reaction (Table 1, entry 2). With prolonged reaction time, the
HMF yield gradually decreased presumably due to its reactivity
with glycerol and to its acid-catalyzed degradation to humins
Although elegant works have been reported, one should mention
that these carbohydrate-based processes also generate some co-
products that need to be chemically valorized in order to limit
the economical and environmental impact of these bio-based
processes. In this context, glycine betaine also known as N,N,N-
trimethyl glycine, a metabolite of choline, is one of the main co-
products generated by the carbohydrate industry.5 In particular,
glycine betaine represents 27 wt% of molasse derived from sugar
beet6 itself industrially produced with more than 400 million
ton/year over the world.7 It should be noted that the value of
betaine rivals that of sugar contained in molasses making of
this co-product a highly valuable raw material for chemistry.8
Zwitterionic glycine betaine is also available under its acid
form and called betaine hydrochloride (BHC). Although glycine
betaine and BHC are cheap, biocompatible and biodegradable,
valorization of BHC for the chemical industry has been scarcely
investigated and betaine is nowadays mostly used for animal
feeding. To date, in the field of chemistry, glycine betaine and its
derivatives are essentially used as a polar heads for the synthesis
of safer and more biodegradable cationic surfactants.9,10 Clearly,
new applications are nowadays strongly researched for this by-
product in order to reduce the economic footprint of the sugar
beet industry.
Here we wish to show that BHC can be used as a very
promising derivative for the design of biorenewable solvent
mixture (Scheme 1). In particular, owing to its ionic structure,
its low pKa (1.9) and its low reactivity towards alcohols, we wish
to show here that BHC-based media are capable of dissolving
Laboratoire de Catalyse en Chimie Organique, CNRS Universite´ de
Poitiers, ENSIP, 1 rue Marcel Dore´, 86022, Poitiers, France.
E-mail: karine.vigier@univ-poitiers.fr; Fax: +33 5 49 45 33 49; Tel: +33
5 49 45 39 51
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Table 1 Dehydration of fructose to HMF in a BHC/glycerol systemsa
Table 2 Dehydration of fructose to HMF in a BHC/water systemsa
BHC Water
Entry (wt%) (wt%)
Fructose content
(wt%)
HMF yield
(%)b
t (min)
1
2
3
4
5
6
0
100
20
20
20
10
20
40
40
40
40
40
20
60
60
120
180
180
120
0
80
80
80
90
80
36
48
44
35
57
BHC
(wt%)
Glycerol
(wt%)
Fructose content
(wt%)
HMF yield
(%)b
Entry
1
2
3
4
5
6
0
100
80
50
20
50
50
40
40
40
40
20
10
0
a Reactions were performed in a biphasic system containing 5 g of a
BHC/water mixture and 20 mL of MIBK. b Determined by HPLC.
20
50
80
50
50
26
33
34
51
57
showing the great affinity of fructose for BHC-based medium.
Interestingly, as compared to the BHC/glycerol mixture, HMF
can be extracted in a larger extent from the BHC/water
medium. As shown in Table 2, in a BHC/water (80/20) mixture
containing 40 wt% of fructose, HMF was recovered with 48%
yield at 100 ◦C (entry 3). This maximum yield of HMF was
obtained after 120 min of reaction (entries 2–4). Analysis of the
MIBK phase by HPLC revealed that the purity of the recovered
HMF reached 95% further demonstrating the attractiveness of
the [BHC/water]/MIBK system. As compared to other reported
strategies, this is one of the highest yields of HMF obtained
starting from such highly concentrated solution of fructose. It is
noteworthy that an increase of the BHC content from 80 to 90%
results in a drop of the HMF yield from 48 to 35% (entries 3, 5).
In such conditions, BHC was not fully dissolved in water and
the reaction medium became heterogeneous which may explain
this lower yield obtained in the mixture BHC/water (90/10).
As observed above, a decrease of the fructose content from 40
to 20 wt% led to an increase of the HMF yield from 48 to 57%
(entries 3, 6).
Taken together, these results show that the mixture
BHC/water (80/20) is more convenient than the BHC/glycerol
(50/50) medium for the dehydration of fructose to HMF. Main
advantage of the BHC/water system stems from the possible
and selective extraction of HMF with MIBK allowing (1) a
convenient and selective recovery of HMF and (2) to limit the
reactivity of HMF with water.
With the aim of further improving the yield of HMF, we next
investigated the dehydration of fructose to HMF in a mixture
BHC/Choline chloride (ChCl). ChCl has recently attracted
considerable attentions as a reaction medium mainly because
of its low price, biodegradability and its ability to form deep
eutectic solvents in combination hydrogen bond donors such as
urea13 or carboxylic acid.14 Note that if ChCl can be extracted
from biomass, one should also comment that ChCl available on
the market is still synthesized from fossil carbon.
a Reactions were performed in 5 g of a BHC/glycerol mixture.
b Determined by HPLC.
as it was previously observed in the BMIMCl/glycerol media.11
Note that although fructose was completely dissolved in neat
glycerol, it remained unaltered confirming the effect of BHC on
the dehydration of fructose (Table 1, entry 1). With the aim of
limiting side reactions between glycerol and HMF, the content
of BHC was first increased from 20 to 50%. As shown in Table
1, an increase of the BHC content contributed to increase the
HMF yield from 26% to 33% (entries 2, 3). Note that a further
increase of the BHC content from 50 to 80% did not result in an
improvement of the HMF yield (entry 4) presumably because, in
these conditions, BHC became sparingly soluble in the glycerol-
fructose mixture.
A decrease of the fructose content from 40 wt% to 20 and
10 wt% has a clear beneficial effect on the HMF yield. As shown
in Table 1, whereas HMF was produced with 33% yield starting
from a BHC/glycerol (50/50) mixture containing 40 wt% of
fructose, a drop of the fructose content to 20 and 10 wt% led
to the production of HMF with 51 and 57% yield, respectively
(entries 3, 5, 6).
Next, extraction of HMF from the BHC/glycerol mix-
ture was explored. Inspired by our previous results, we per-
formed the reaction in a biphasic [BHC/glycerol(50/50)]/
methylisobutylketone (MIBK) system. Although we have pre-
viously reported that such approach was efficient in a biphasic
[glycerol/[BMIM]Cl]/MIBK system,11 all attempts to extract
HMF from the BHC/glycerol mixture with MIBK failed
since HMF was recovered with only 7% yield. Although the
difficult extraction of HMF from the BHC/glycerol (50/50)
mixture represents the main drawback of this process, it also
clearly highlights the great ability of the BHC/glycerol medium
to dissolve bio-based chemicals such as fructose and HMF.
Utilization of such medium for the dissolution of biomass is
now the topic of current investigations in our group.
With the aim of finding a suitable solution for the convenient
extraction of HMF, other BHC-based systems were explored.
In this context, dehydration of fructose to HMF was next
investigated in a mixture BHC/water. In order to (1) limit the
side rehydration of HMF to levulinic and formic acids and (2)
evaluate the possible extraction of HMF from the BHC/water
medium, all reactions were directly performed in a biphasic
[BHC/water]/MIBK system. In a mixture BHC/water (80/20),
we found that at least 40 wt% of fructose can be dissolved, further
Although ChCl is also known to create low-melting mixtures
with different carbohydrates (including fructose),15 formation
of a liquid phase from BHC, ChCl and fructose was difficult to
obtain. Indeed, from a mixture BHC/ChCl (90/10) containing
40 wt% of fructose, no transparent liquid phase was observed
after 15 min of stirring at 110 ◦C. Note that liquefaction
of the reaction medium was observed at 110 ◦C only upon
addition of a small amount of water. Hence, we decided to use a
ChCl/BHC/H2O system with a mass ratio of 10/1/2. It should
be noted that all attempts to increase the BHC content failed
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Table 3 dehydration of fructose to HMF in a ChCl/BHC systemsa
was partly due to the higher stability of HMF at this temperature.
For instance, when neat HMF was heated in ChCl/BHC/H2O
(10/0.5/2), only 4 mol% of HMF was degraded after 120 min of
reaction at 90 ◦C vs. 10 mol% and 13 mol% at 110 ◦C and 130 ◦C,
respectively. Note that a further decrease of the temperature from
BHC
(wt%)
Fructose content
(wt%)
HMF yield
(%)
Entry
t (min)
1
2
3
10
5
3.3
5
5
5
5
5
5
5
40
40
40
40
40
40
80
120
20
10
2
120
120
170
120
120
240
315
375
60
50
65
63
62
75
24
48
37
76
81
66
84
52
◦
90 ◦C to 70 C unfortunately dropped the reaction rate to an
unacceptable level since HMF was produced with only 24% yield
after 240 min of reaction (entry 6).
4b
5c
6d
7
In agreement with previous existing reports, the efficiency
of the ChCl/BHC/H2O (10/0.5/2) mixture is also strongly
dependent on the fructose content. As shown in Table 3, an
increase of the fructose content from 40 wt% to 80 and 120 wt%
resulted in a gradual drop of the HMF yield from 65% to
48% and 37%, respectively, due to the dominant acid-catalyzed
degradation of HMF to soluble and insoluble humins (entries 2,
7, 8). Conversely, a decrease of the fructose content from 40 wt%
to 20 and 10 wt% logically resulted in an improvement of the
HMF yield from 65% up to 81% (entries 2, 9, 10).
8
9
10
11e
12e
13f
60
120
60
5
5
5
10
15g
60
a Reactions were performed in 6.5 g of a ChCl/BHC/H2O mixture.
b Reaction performed at 130 ◦C. c Reaction performed at 90 ◦C.
d Reaction performed at 70 ◦C. e In a biphasic [ChCl/BHC]/MIBK
system. f Starting from inulin. g Inulin.
As in the case of the BHC/water medium, ChCl and BHC are
not soluble in MIBK. Therefore, we explored the possibility to
carry out the reaction in a biphasic [ChCl/BHC/H2O]/MIBK
system with the aim of continuously extracting HMF from the
catalytic phase. To this end, reactions were first performed at
110 ◦C starting from 40 wt% of fructose dissolved in a mixture
ChCl/BHC/H2O (10/0.5/2). Interestingly, in the presence of
MIBK, HMF can be selectively extracted and HMF was
recovered with 66% yield (entry 11). Thanks to the very low
solubility of ChCl and BHC in MIBK, HMF was obtained
with a purity higher than 95% (determined by HPLC). 1H
NMR also confirmed the high purity of recovered HMF (Fig.
1). To our delight, when the fructose content was dropped
from 40 wt% to 10 wt%, HMF was recovered with a yield
as high as 84% (entry 12), thus offering competitive results
with those commonly obtained in imidazolium-based ionic
liquids.
since in this case no formation of liquid phase was observed.
Therefore, in the following experiments, BHC was used in a
catalytic amount (30 mol% vs. fructose). In a typical procedure,
2 g of fructose (40 wt%) was heated at 110 ◦C in 6.5 g of a
ChCl/BHC/H2O mixture. In these experiments, the amount of
BHC was always maintained lower than 10 wt%. Results are
presented in Table 3.
In the mixture ChCl/BHC/H2O (10/1/2, i.e. 30 mol% of
BHC vs. fructose), HMF was obtained with a maximum yield
of 50% after 2 h of reaction (entry 1). When the amount of
BHC was decreased from 10 to 5 wt%, the yield of HMF was
unexpectedly improved from 50% to 65% after 2 h of reaction
(entries 1, 2). This result was ascribed to the initial lower viscosity
of the reaction medium. Indeed, using 10 wt% of BHC the
system is highly viscous and the reaction may be initially strongly
limited by diffusion problems.15 It should be noted that effect
of the reaction viscosity on the reaction rate only impacts the
initial stage of the reaction. Indeed, as we previously reported
in a mixture glycerol/[BMIM]Cl,10 the viscosity of the system
rapidly dropped after only few minutes of reaction due to the
release of water caused by the dehydration of fructose. Therefore,
no correlation between the reaction viscosity and reaction rate
has been clearly established. Similar conclusions can be also
drawn for the BHC/glycerol and BHC/water systems. When,
the amount of BHC was further decreased from 5 to 3.3 wt%,
the reaction time was then logically increased from 120 min to
170 min while the yield of HMF remained similar (63%) (entries
2, 3). This result shows that below 5 wt% of BHC the system is
no longer limited by diffusion problems and BHC normally acts
as a homogeneous catalyst.
Fig. 1 1H NMR spectra (300 MHz, 25 ◦C, DMSO-d6) of HMF
recovered with MIBK from ChCl/BHC/H2O (10/0.5/2) containing
40 wt% of fructose.
As researched, in the ChCl/BHC/H2O (10/0.5/2) mix-
ture, HMF was produced with higher yield (65%) than in
BHC/glycerol (33%) and BHC/water (48%) mixtures due to
the very low reactivity of HMF with ChCl.
Considering that HMF can be conveniently and selectively
extracted from the ChCl/BHC/H2O mixture with MIBK,
recyclability of the reaction medium was investigated. Recycling
experiments were performed at 100 ◦C using a fructose content
of 40 wt% which is, in our views, a good compromise between the
yield of HMF and the concentration of fructose. For recycling
experiments, the vessel was partly opened in order to contin-
uously remove water. Note that such a reactor configuration
Next, influence of the reaction temperature was investigated.
◦
At 130 C, the maximum yield of HMF was unchanged (62%,
entry 4). Conversely, a drop of the temperature from 110 ◦C to
90 ◦C resulted in a slight increase of the maximum yield of HMF
from 65% to 75% (entry 5). This higher yield observed at 90 ◦C
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also led also to a slight evaporation of MIBK (boiling point =
118 ◦C) which can be then further separated from water by liquid
phase decantation. At the end of the first catalytic cycle, 40 wt%
of fructose was directly reloaded to the recovered ChCl/BHC
mixture (no water was added) and the reaction was heated for
another 2 h at 100 ◦C. As shown in Fig. 2, the ChCl/BHC
mixture can be successfully reused at least 7 times without
appreciable loss of yield further demonstrating the effectiveness
of BHC-based medium for the synthesis of HMF. It should
be mentioned, however, that after 7 cycles, the HMF yields
started to decrease due to the unavoidable accumulation of
black materials (presumably humins) in the ChCl/H2O/BHC
medium.
extracted from the BHC/water and ChCl/BHC/H2O media by
liquid–liquid phase extraction allowing (1) isolation of HMF
with a purity higher than 95% and (2) the recycling of the
ChCl/BHC medium.
The authors are grateful to the French ministry of research
and the CNRS for their financial support.
Experimental
Analytical methods
Yields of HMF were determined by external calibration at 25 ◦C
using a HPLC equipped with a nucleosil 100–5 C18 column
(250 ¥ 4.6 mm), a Shimadzu LC-20AT pump, a Shimadzu RID-
10A detector and using a mixture acetonitrile/water (10 : 90)
as mobile phase (0.8 mL min-1). Fructose was quantified by
external calibration at 25 ◦C using a HPLC equipped with a
Varian NH2-column, a Varian Prostar RID detector, Varian
Prostar pumps (model 210) and a mixture acetonitrile/water
(90 : 10) as mobile phase (0.8 mL min-1).
General procedure for the dehydration of fructose to HMF
Fructose was dissolved in 5 g of a mixture BHC/glycerol or
BHC/water or BHC/ChCl/H2O. Then the mixture was heated
under air at 110 ◦C (or 100 ◦C in the case of water). During
the reaction, HMF was continuously extracted with 20 mL of
MIBK. The MIBK phase containing HMF was then separated
from the BHC-based medium by simple phase decantation.
Then, MIBK was removed under vacuum affording HMF as
a dark brown chemical. Because the extraction with MIBK is
highly selective to HMF, the distilled MIBK could be recycled
for other extraction cycles.
Fig. 2 Recycling of the ChCl/BHC system.
Finally, in a last set of experiments, we investigated the
capability of the ChCl/BHC/H2O system to directly promote
the conversion of inulin to HMF. Inulin is a biopolymer of
fructose. Inulin used in this work is commercially available and
was extracted from chicory roots. The degree of polymerization
of inulin is 46 and the water content is 15 wt%. Remark-
ably inulin is also soluble in the ChCl/BHC mixture further
demonstrating the efficiency of such medium for solubilizing
carbohydrates. Reaction was performed at 100 ◦C in a biphasic
[ChCl/BHC/H2O]/MIBK system and starting from 15 wt% of
inulin. As described above, the ChCl/BHC/H2O mass ratio was
initially 10/0.5/2. Here, initial addition of water not only helps
to solubilize chemicals but also to induce the hydrolysis of inulin
to fructose. Interestingly, under these conditions, HMF was
produced with 52% yield confirming that the ChCl/BHC/H2O
is also capable of promoting the tandem hydrolysis/dehydration
of inulin to HMF (Table 3, entry 13). As observed in other media,
no reaction took place from glucose in the ChCl/BHC/H2O
system. This result is in accordance with the current literature
suggesting that dehydration of glucose to HMF required the in
situ isomerization of glucose to fructose as a pre-requisite step.
Note that dehydration of glucose to HMF (40% yield) in the
ChCl/BHC/H2O medium required the assistance of 10 mol%
of AlCl3 which is known to promote the isomerization of glucose
to fructose.
Recycling experiments
Recycling experiments were performed in the ChCl : BHC : H2O
mixture (10 : 0.5 : 2) using a fructose content of 40 wt% (related to
the weight of ChCl + BHC). After the first extraction of HMF
with MIBK, fructose was directly reloaded to the recovered
BHC/ChCl mixture.◦No water was added. The reaction was then
heated again at 110 C for 2h. Similar procedure was repeated
up to the 7th cycle.
Notes and references
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7 M. D. Sutton and J. B. D. Peterson, J. Sugar Beet Res., 2001, 38, 19.
8 P. Ma¨kela¨, Sugar Tech, 2004, 6, 207.
In conclusion, we report here that BHC, a co-product of
the sugar beet industry, can be employed in combination with
glycerol or water or ChCl as a cheap and sustainable acid
media for the dehydration of fructose and inulin to HMF. These
BHC-based media affords similar yields (up to 84%) than those
commonly obtained in traditional imidazolium-based ILs while
offering notable economical and environmental advantages.
Except for the BHC/glycerol mixture, HMF can be conveniently
9 (a) M. Lever, W. Atkinson, P. M. George and S. T. Chambers, Clin.
Biochem., 2007, 40, 798–801; (b) R. B. Likes, R. L. Madl, S. H. Zeisel
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10 F. Goursaud and T. Benvegnu, Carbohydr. Res., 2009, 344, 136.
11 M. Benoit, Y. Brissonnet, E. Gue´lou, K. De Oliveira
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12 As previously observed by T. Benvegnu and co-workers, we observed
that esterification of BHC with glycerol only takes place after
exchange of the chloride by a sulfonate anion.
13 For recent examples please see (a) S. B. Phadtare and G. S.
Shankarling, Green Chem., 2010, 12, 458–462; (b) P. M. Pawar,
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