Integrating enzymatic and acid catalysis to convert glucose into 5-hydroxymethylfurfural

Article abstract of DOI:10.1039/b921306f

A convenient and cost-efficient method featuring the integration of enzymatic and acid catalysis has been developed for the selective conversion of glucose into HMF, which provides a new strategy for HMF production from glucose.

Full text of DOI:10.1039/b921306f

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Integrating enzymatic and acid catalysis to convert glucose
into 5-hydroxymethylfurfuralw
Renliang Huang, Wei Qi,* Rongxin Su and Zhimin He
Received (in Cambridge, UK) 13th October 2009, Accepted 4th December 2009
First published as an Advance Article on the web 24th December 2009
DOI: 10.1039/b921306f
5,10
or to protect rigorously from moisture and oxide impurities,
A convenient and cost-efficient method featuring the integration
of enzymatic and acid catalysis has been developed for the
selective conversion of glucose into HMF, which provides a
new strategy for HMF production from glucose.
which is unfavorable for biomass transformation since bio-
mass contains much water and ash. In contrast, water is a
convenient solvent and could increase the economic feasibility
of producing HMF from sugars (or biomass). Therefore,
it is highly desirable to develop a cost-efficient approach to
transform glucose to HMF in aqueous phase systems.
Fossil resources have created unprecedented social prosperity
over the past decades. However, it has entered a dilemma
between the increasing energy need and the depleting fossil
fuel reserves, which has stimulated tremendous efforts towards
finding sustainable sources for the production of fuels
The proposed reaction mechanism for glucose transforma-
tion in the chromium(II) chloride/ionic liquid system is
4
depicted in Scheme 1 (Route A). It shows that the critical
1
and chemicals. Biomass, especially lignocellulose (the most
3
role of [EMIM]CrCl is to induce the glucose–fructose
abundant renewable biomass), is currently regarded as an
alternative source of carbon for both fuels and chemical
isomerization reaction. Once fructose is formed, dehydration
of fructofuranose to HMF is straightforward in the presence
of mineral or Lewis acid catalysts. Thus, the isomerization step
is essential to produce HMF in high yields from glucose.
Recently, Ebitani and co-workers had published a study
in which HMF was produced from glucose (or sucrose,
cellobiose) by isomerization and dehydration reactions using
2
,3
intermediates. In this respect, non-fermentative pathways
to biomass transformation that exploit all of the available
carbon present have become the focus of the world’s attention.
One of the most attractive directions for this research is
towards furan derivatives, such as 5-hydroxymethylfurfural
1
1
(
HMF), a sustainable precursor for the preparation of non-
4
petroleum-derived polymeric materials and fine chemicals.
solid base and acid catalysts. Herein, we selected borate-
assisted isomerase as catalyst for the isomerization of glucose
to fructose (Scheme 1, Route B). In this study, nearly 90% of
glucose was converted into fructose by immobilized glucose
isomerase (Sweetzyme IT) in the presence of sodium tetra-
borate. The supernatant after recycling of glucose isomerase
and adding dilute hydrochloric acid was introduced into a
reaction chamber containing an extracting organic layer
(1-butanol). A 63.3% HMF yield from glucose was achieved
when the mixture was heated in an oil bath at 463 K for 45 min
(Fig. 1, Run III).
–8
Current processes to produce HMF generally involve the
use of acid catalysts in biphasic systems and metal chlorides in
4
–8
ionic liquid solvents.
Dumesic and co-workers demon-
strated that high yields (approximately 75%) of HMF could
be obtained from fructose in aqueous/organic reaction
7
,8
media.
However, such a system exhibited low ability
(
HMF yield less than 25%) to transform from glucose, which
is a more stable and abundant sugar source. To achieve high
HMF yield from glucose, Zhang and co-workers developed a
metal chloride/ionic liquid (1-ethyl-3-methylimidazolium
Glucose isomerase, as one of the largest-volume commercial
chloride, [EMIM]Cl) system that gave good HMF yields
4
about 68% with CrCl ). The ionic liquid system for HMF
enzymes, is used almost exclusively for the conversion of
12,13
(
starches to high-fructose syrup.
Compared with chemical
2
preparation was further improved by using NHC/metal
5
catalysis, the enzyme-catalyzed process provides remarkable
advantages for isomerization of glucose, including its high
selectivity and environmental friendliness. However, there
exists a thermodynamic equilibrium of the isomerization
between glucose and fructose, in which fructose is derived
(
NHC = N-heterocyclic carbene) complexes as catalysts.
Recently, Binder and Raines reported that cellulose and
untreated lignocellulosic biomass could be directly converted
to HMF in mixed solvent of DMA–LiCl (DMA = N,N-
1
3
dimethylacetamide) and [EMIM]Cl with addition of CrCl
6
2
from glucose at low conversion (about 50%). In this case, the
HMF yield was only 28.2% (Fig. 1, Run II) due to the low
reactivity of glucose (2.4% yield, Fig. 1, Run III). Therefore,
how to shift the equilibrium to achieve high yield of fructose is
a key issue in the synthesis of HMF.
3
or CrCl as catalysts. They also showed that ionic liquid
systems could enable the conversion of glucose or cellulose
to high-yield HMF, but ionic liquids themselves were so
3
,9
expensive that they were difficult to apply commercially.
Moreover, ionic liquids are necessary to purify after recycling
We selected sodium tetraborate as an agent to shift the
1
4
isomerization equilibrium of glucose. As shown in Fig. 2a,
just 52.7% of glucose was converted to fructose in the absence
of sodium tetraborate. The presence of borate induced a
significant shift of the equilibrium to the fructose side. The
yield of fructose increased to about 87.8% when the isomeri-
zation reaction carried out at a borate-to-glucose ratio of 0.5.
State Key Laboratory of Chemical Engineering, School of Chemical
Engineering and Technology, Tianjin University, 300072, Tianjin,
China. E-mail: qiwei@tju.edu.cn; Fax: (+86) 22-2740-7599
w Electronic supplementary information (ESI) available: Experimental
details and supporting figures. See DOI: 10.1039/b921306f
This journal is ꢀc The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 1115–1117 | 1115

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Scheme 1 Catalytic conversion of glucose into HMF.
In aqueous solution, borate ions reacted with glucose and
13
1
fructose to form ionized esters (determined by B and
1
C
nuclear magnetic resonance (NMR) spectroscopy). Our
NMR study showed unambiguously that both 1 : l
(
(
1
molecule boron : 1 molecule sugar, B–L) and 1 : 2
1 molecule boron : 2 molecules sugar, B–L ) species were
2
formed concurrently in every borate–sugar system (ESI,
Fig. S5 and S6w). The formed sugar–borate complexes can
shift the equilibrium since they did not participate in
the reaction. Generally, ketose complexes exhibited higher
association constants than the aldoses in the equilibrium
1
4
between borate and borate esters. Therefore, the higher
affinity of borate to D-fructose than to D-glucose explained
the equilibrium shift toward the fructose side in the isomeriza-
tion reaction.
Fig. 1 Glucose conversion to HMF in a water–butanol biphasic
reactor. Runs I–III represent direct glucose dehydration (I), dehydra-
tion after isomerase (II) and borate-assisted isomerase (III) treatment,
respectively. Isomerization reactions were carried out at 70 1C for 8 h
with 0.5 g immobilized glucose isomerase as catalyst; dehydration
reactions (the reaction conditions for Runs II and III were optimized)
were carried out at 190 1C for 20 min with 0.25 M HCl aqueous
solutions (Runs I and II), or 45 min with 0.35 M HCl aqueous
Once a high yield of fructose was obtained, the key step that
followed was to produce HMF efficiently. Previous studies
have developed numerous catalytic systems to produce HMF
in high yields from fructose, including homo- and hetero-
geneous acid catalysts, and single phase and biphasic
15,16
systems.
Among these, biphasic reaction systems with
dilute hydrochloric acid and low boiling extraction solvent
exhibited desirable features for HMF production, due to their
ability to reach a high yield of HMF without requiring the
solutions (Run III). Other default conditions unless otherwise noted:
À1
1.00 g glucose (50 mg mL ), 20 mL deionized water, glucose/sodium
tetraborate molar ratio = 0.5 : 1, 50 mg MgSO
0 mL 1-butanol.
4
Á7H
2
O, 2.00 g NaCl,
1
6,17
energy-intensive isolation operation.
In this study, we also
3
selected dilute hydrochloric acid as a catalyst to convert sugar
mixtures obtained after isomerization. The HMF product was
simultaneously extracted with 1-butanol from the aqueous
phase, which generated 88.2% sugar conversion and 63.3%
HMF yield (Fig. 3, 45 min). The HPLC results showed that
very few soluble by-products (such as levulinic acid or formic
acid) were formed (ESI, Fig. S4w), therefore, the decrease in
HMF selectivity with increasing reaction time may be caused
by the formation of insoluble humins (or solid waste) during
However, further addition of the borate would result
in a slight decrease of the conversion yield. In addition,
immobilized glucose isomerase is a stable and highly active
catalyst in aqueous solution, leading to rapid isomerization of
glucose to fructose (Fig. 2b).
7
the fructose dehydration. The results of the by-product
analysis indicated that our process was suitable for HMF
production because levulinic acid was particularly difficult to
separate from HMF.
To develop an efficient catalytic system for converting
glucose to HMF, the strategy of an integrated biological and
chemical process was introduced in our work. The most
remarkable advantage of this process is its ability to produce
a high yield of HMF from glucose in aqueous/organic media,
leading to its feasibility of large-scaled HMF production.
Meanwhile, continuous isomerization of glucose in fixed bed
reactors also offers the possibility of lower operating cost.
Other processes such as ionic liquid systems, however, have
Fig. 2 Effects of the molar ratio of borate to glucose (a) and reaction
time (b) on the yield of fructose. Default conditions unless otherwise
À1
noted: 1.00 g glucose (50 mg mL ), 20 mL deionized water, 0.5 g
immobilized glucose isomerase, glucose : sodium tetraborate molar
ratio = 0.5 : 1, 50 mg MgSO
4
Á7H
2
O, pH 7.7, 70 1C 12 h (the time is
sufficient for isomerization reaction).
1
116 | Chem. Commun., 2010, 46, 1115–1117
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and Technology Cooperation Program (2006DA62400), the
Program for New Century Excellent Talents in Chinese
University (2008), and the Program for Changjiang Scholars
and Innovative Research Team in University of China
(
IRT0641).
Notes and references
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Fig. 3 Changes in sugar conversion and HMF yield with reaction
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integration of enzymatic and acid catalysis has been developed
for the selective conversion of glucose into HMF. In this
process, borate-assisted isomerase was used to convert glucose
into fructose, leading to high fructose yield (87.8%). The
resulting sugar mixtures were dehydrated in water–butanol
media to produce HMF (63.3% yield). Our results suggested
that this green, cost-efficient approach had the potential to
produce large-scale HMF from glucose. In view of the
importance of HMF in renewable chemical industry, this
process may provide a new avenue for HMF production,
and further accelerate the commercial application of HMF.
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Chem. Commun., 2010, 46, 1115–1117 | 1117