Efficient isomerization of glucose to fructose over zeolites in consecutive reactions in alcohol and aqueous media

Article abstract of DOI:10.1021/ja400097f

Isomerization reactions of glucose were catalyzed by different types of commercial zeolites in methanol and water in two reaction steps. The most active catalyst was zeolite Y, which was found to be more active than the zeolites beta, ZSM-5, and mordenite. The novel reaction pathway involves glucose isomerization to fructose and subsequent reaction with methanol to form methyl fructoside (step 1), followed by hydrolysis to re-form fructose after water addition (step 2). NMR analysis with ¹³C-labeled sugars confirmed this reaction pathway. Conversion of glucose for 1 h at 120 C with H-USY (Si/Al = 6) gave a remarkable 55% yield of fructose after the second reaction step. A main advantage of applying alcohol media and a catalyst that combines Bronsted and Lewis acid sites is that glucose is isomerized to fructose at low temperatures, while direct conversion to industrially important chemicals like alkyl levulinates is viable at higher temperatures.

Full text of DOI:10.1021/ja400097f

Communication
pubs.acs.org/JACS
Efficient Isomerization of Glucose to Fructose over Zeolites in
Consecutive Reactions in Alcohol and Aqueous Media
Shunmugavel Saravanamurugan,†,§ Marta Paniagua,‡,§ Juan A. Melero,‡ and Anders Riisager*,†
†Centre for Catalysis and Sustainable Chemistry, Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby,
Denmark
‡Chemical and Environmental Technology Department, Universidad Rey Juan Carlos, C/Tulipan
́ ́
s/n, E-28933 Mostoles, Madrid,
Spain
S
* Supporting Information
and a high amount of byproducts are formed due to the side
reactions.6 Generally, Brønsted acids are not efficient catalysts for
aldose isomerization, although the efficacy may be a function of
ABSTRACT: Isomerization reactions of glucose were
catalyzed by different types of commercial zeolites in
methanol and water in two reaction steps. The most active
catalyst was zeolite Y, which was found to be more active
than the zeolites beta, ZSM-5, and mordenite. The novel
reaction pathway involves glucose isomerization to
fructose and subsequent reaction with methanol to form
methyl fructoside (step 1), followed by hydrolysis to re-
form fructose after water addition (step 2). NMR analysis
with 13C-labeled sugars confirmed this reaction pathway.
Conversion of glucose for 1 h at 120 °C with H‑USY (Si/
Al = 6) gave a remarkable 55% yield of fructose after the
second reaction step. A main advantage of applying alcohol
media and a catalyst that combines Brønsted and Lewis
acid sites is that glucose is isomerized to fructose at low
temperatures, while direct conversion to industrially
important chemicals like alkyl levulinates is viable at
higher temperatures.
reaction conditions.7 Roman
́
-Leshkov et al., however, provided
conclusive evidence via NMR that Lewis acidity can catalyze
sugar isomerization.6 Zeolites containing tetravalent metal atoms
in the tetrahedral positions are well-explored as solid Lewis acid
catalysts for many reactions and are widely used in the petroleum
industry.8 Recent studies have shown that the Lewis acid zeolite
Sn-BEA is particularly effective for catalyzing the isomerization of
a series of pentose and hexose sugars with activities comparable
to biological processes1,6,9 by a mechanism similar to enzymatic
catalysts.10 However, Sn-BEA is not commercially available,
comprises tina toxic heavy metaland is by traditional
methods cumbersome to synthesize, though improved synthetic
routes have very recently been devised.11
In this work, we report a new approach for getting
unprecedentedly high yields of fructose from glucose in alcohol
and aqueous media using commercially available zeolite catalysts
containing only silicon and aluminum. The isomerization
reaction was carried out in methanol following a two-step
batch mode procedure. The reaction pathway for the consecutive
reactions for the conversion of glucose to fructose is illustrated in
Scheme 1. In the first reaction step, glucose is isomerized to
lucose is the cheapest and the only abundant mono-
Gsaccharide available in nature among the isomeric hexose
sugars glucose, fructose, and mannose.1 Despite its lower
accessibility, fructose is widely used in the food industry as, for
example, a sweetener (high-fructose corn syrup), since it
contributes many useful physical and functional attributes to
food and beverage applications.2 Currently, the reversible
isomerization of glucose to fructose is carried out on large
industrial scale in aqueous phase with the enzyme D-glucose/
xylose isomerase (GI, EC 5.3.1.5), which possesses high reaction
specificity under benign pH conditions and relatively low
reaction temperature. However, major drawbacks of the process
are inactivation of GI at higher temperatures (above 60 °C),
narrow pH operation window, inhibition of GI in the presence of
Ca2+ ions (prerequisite for the action of amylase when
liquefaction, saccharification, and isomerization are carried out
simultaneously), requirement of Co2+ ions for enzyme activity,
and suboptimal concentrations of the product.3 For these
reasons, the enzyme activity is still low from an economic point of
view, and a large quantity of enzyme is thus needed to obtain
viable throughputs.4
Scheme 1. Reaction Pathway for Fructose Formation from
Glucose in Alcohol and Aqueous Media
As an alternative to GI, glucose can also be transformed into
fructose by aldose−ketose isomerization in the presence of a
base.5 However, monosaccharides are unstable in alkaline media,
Received: January 4, 2013
Published: March 18, 2013
© 2013 American Chemical Society
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Journal of the American Chemical Society
Communication
fructose in methanol, which immediately reacts with the reaction
media to form methyl fructoside. In a second reaction step, water
is added to hydrolyze the methyl fructoside in order to obtain
fructose. Notably, both reaction steps can be performed at the
same temperature.
One-pot synthesis of fructose from glucose was first examined
using different solvent mixtures containing up to 95 wt% of
methanol in water (Table S1). The initial presence of water in the
media led to low glucose isomerization (maximum yield of 8% of
fructose), and no methyl fructoside was formed. In line with this,
Johnson et al. reported that a large excess of alcohol is needed, as
well as removal of the water formed during the reaction, in order
to maximize the conversion of fructose into methyl fructoside.12
A way to circumvent the unfavorable water inhibition was to
perform the reaction as a two-step reaction sequence instead,
where the isomerization and etherification were first performed
in alcohol, followed by hydrolysis.
Table 1. Product Distribution (mol%) Obtained for Glucose
Conversion over Commercial Zeolites after the Two-Step
Reaction Sequence
a
product distribution
zeolite
H-Y
Si/Al ratio
2.6
step
glucose
fructose
methyl fructoside
1
2
1
2
1
2
1
2
1
2
1
2
56
54
30
28
63
63
29
30
39
43
90
89
16
20
22
55
26
24
23
40
21
29
0
19
18
33
4
H‑USY
6
30
<1
<1
22
8
H-beta
12.5
19
16
8
150
0
0
0
In the two-step process, different commercially available
zeolite catalysts were tested for the isomerization/etherification
of glucose to fructose/methyl fructoside at 120 °C and 1 h,
followed by hydrolysis after water addition for another hour. The
amount of water and the reaction time required to complete the
hydrolysis were found from a preliminary study (see Figure S1).
The best reaction results were attained using the large-pore
zeolites Y and BEA, with especially the H‑USY(6) and H-
beta(12.5) catalysts giving high fructose yields of 55 and 40%,
respectively. In addition to the pore size of the zeolite, the pore
structure was apparently an important factor, since the Y-zeolite
framework facilitated formation of a higher yield of methyl
fructoside in the first reaction step than the BEA framework. This
resulted in an overall improved fructose yield after hydrolysis of
the formed methyl fructoside in the second step. Notably,
USYa steamed zeolitemight have extra framework Al
compared to the beta zeolites, which could further improve the
formation of fructose during both reaction steps.
Basic zeolite catalysts Na-Y and Na-mordenite also isomerized
the glucose to a small extent. However, they were unable to
catalyze the etherification of fructose to methyl fructoside,
producing a maximum yield of 18% of fructose in the two-step
process (Table S3). With other acid zeolites (e.g., H-ZSM-5),
low glucose conversion was also achieved in the isomerization
reaction. Similar results have been obtained in other sugar
transformations.13
a
Step 1: 75 mg of catalyst, 125 mg of glucose, 4 g of methanol, 1 h,
120 °C. Step 2: 4 g of water, 1 h, 120 °C.
83% (Table 1). A significant product, eluting on HPLC between
the glucose and fructose (with retention time similar to that of
mannose), could account for the rest of the converted glucose. In
an attempt to identify the intermediate product and to examine
the equilibrium of the three isomeric sugarsglucose, fructose,
and mannosea time-course study was carried out for each
sugar over Na-mordenite under identical reaction conditions,
assuming that the basic zeolite would suppress the formation of
methyl fructoside during the first reaction step as well as the
intermediate product if it was not mannose. The results
confirmed that glucose isomerized to mannose and fructose to
some extent in the presence of basic zeolite in methanol and vice
versa (Figure S2). However, after isomerization reactions with
mannose or fructose in methanol using the acidic H‑USY(6) or
H-beta(12.5) zeolites, only traces of glucose were observed in
HPLC, implying that the formation of methyl fructoside
perturbed the equilibrium between the sugars. A complementary
reaction study with D-[1-13C]- and D-[2-13C]glucose and
mannose was further carried out in the presence of H‑USY(6)
in methanol-d4 and D2O. The results from 13C NMR analysis of
the reaction solutions revealed here no carbon signals
corresponding to formation of glucose from mannose or
mannose from glucose (Table S4; see Scheme S1 for the
tautomers). However, two new major peaks (δ/ppm = 102.7 and
109.0 ppm), which did not correlate with standards of methyl
glucosides, appeared in the experiments with the 1-13C-labeled
sugars. We speculate that these peaks originate from methyl
mannosides which account for the remainder of the converted
glucose. However, additional work is needed to establish this
identity positively. No other significant product peaks were
detected in the glucose reaction with this catalyst, thus implying
that there were no other degradation products formed.
Additionally, the reaction solution remained colorless after the
reaction, indicating that humins were not formed in significant
amounts. Importantly, it was also possible to get similar reaction
results (51% of fructose) and avoid sugar degradation by carrying
out the reaction at lower reaction temperature (80 °C) and
longer reaction time (24 h).
NH3-TPD analysis of the H‑USY(6) and H-beta(12.5)
catalysts revealed that they possessed moderate total acidity
and ratios of medium (type 1, Tdesorb = 100−270 °C) to strong
(type 2, Tdesorb = 270−500 °C) acid sites of 1:0.81 and 1:0.52,
respectively (Table S2). Notably, all of the other examined
zeolites, which gave lower fructose yields, exhibited significantly
different type 1:type 2 acid site ratios and/or number of total acid
sites. Previously, the Brønsted and Lewis acidity ratio of zeolites
has been determined from FT-IR, and here H‑USY(6) was
shown to possess a larger fraction of Lewis acid sites compared to
H‑USY(30).13 This suggests that the ratio of Lewis and
a
Brønsted acidity is a key factor to maximize the glucose
conversion. Moreover, glucose does not isomerize to fructose to
form ethyl levulinate over sulfonic acid-functionalized Brønsted
acid catalysts. Instead, glucose reacted with ethanol to form ethyl
glucopyranoside.13b,d These results confirm that Lewis acidity is
indeed necessary to carry out the glucose isomerization in
alcohol.
The influence of reaction time on fructose conversion in
methanol over H‑USY(6) was further studied at 80 °C to get
additional understanding of the reactivity and to ascertain the
reaction pathway proposed. In line with the initial experiments at
In the reactions of glucose with the Y and BEA catalysts, the
combined yields of fructose and glucose were between 70 and
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Communication
120 °C, methyl fructoside was practically the only product
formed (Figure S3), as also observed in previous work.12 When
water was added to the reaction solution during the second
reaction step, the initial fructose was recovered, as expected.
Moreover, 13C NMR analysis of reaction products formed with
D-[2-13C]fructose and methanol-d4 revealed the presence of
characteristic peaks of methyl fructoside (δ/ppm = 100.8, 104.5,
and 108.5). These three peaks were ascribed to methyl β-D-
fructopyranoside, methyl β-D-fructofuranoside, and methyl α-D-
fructofuranoside, respectively12 (tautomers shown in Scheme
S1). After the hydrolysis step, the three peaks were shifted to
lower chemical shift values (δ/ppm = 98.3, 101.9, and 104.7),
corresponding to the re-formation of fructose. In an experiment
starting with D-[2,5-13C]glucose, similar intermediate products
were identified unambiguously, confirming the proposed glucose
isomerization reaction pathway to fructose. Additionally, only
fructose and methyl fructoside (and trace glucose) were formed
when mannose was used as starting sugar, suggesting that the use
of methanol as solvent in the isomerization of glucose to fructose
is a way to impede establishment of the equilibrium of the C6
Figure 2. Effect of the initial glucose concentration for glucose
conversion. Step 1: 75 mg of H‑USY(6), 4 g of methanol, 1 h, 120 °C.
Step 2: 4 g of water, 1 h, 120 °C.
obtained yield of fructose from 55 to 27% when the glucose
concentration was changed from 3.0 to 16.7 wt%, probably as a
consequence of more water being formed during the ether-
ification step in the more concentrated systems. However, a
moderate fructose yield of 38% was obtained with up to about 9.1
wt% of initial glucose concentration. This yield increased further
to 46% at longer reaction time, thus approaching a result similar
to that achieved with lower initial glucose concentration.
Likewise, the yield of fructose could be enhanced from 27 to
38% when the reaction time was prolonged for the experiment
with 16.7 wt% glucose, while the presence of molecular sieves (4
Å) unexpectedly lowered the yield from 27 to 12%.
sugar isomers described in water.9
a
Changing the solvent from methanol to the higher alcohols
ethanol and 1-propanol led to the formation of the
corresponding alkyl fructoside. The same pathway as described
for methanol was observed, resulting in an increased amount of
fructose after addition of water in the second reaction step
(Figure 1). However, the fructose etherification with higher
The reaction system with H‑USY(6) and 3 wt% initial glucose
concentration in methanol was also examined with different
glucose-to-catalyst mass ratios between 1.7:1 and 12.5:1, and the
reaction time was optimized during each reaction step to achieve
high yields of fructose (Table 2). The results clearly
Table 2. Influence of the Mass Ratio of Glucose to H‑USY(6)
Catalyst on the Product Distribution (%) in the Two-Step
a
Reaction Sequence
product distribution
m
cat (mg)
10
mglu:mcat ratio
step
time (h)
glucose
fructose
Figure 1. Comparison of different solvents for the conversion of glucose
to fructose. Step 1: 75 mg of H‑USY(6), 125 mg of glucose, 4 g of
solvent, 1 h, 120 °C. Step 2: 4 g of water, 1 h, 120 °C.
12.5:1
1
2
1
2
1
2
1
2
1
2
21
3
39
37
40
38
32
33
32
33
30
28
20
51
18
52
19
53
20
55
22
55
15
25
50
75
8.3:1
5.0:1
2.5:1
1.7:1
5
3
4
alcohols seemed more difficult to accomplish, possibly due to
steric impediments. Therefore, less fructose and more by-
products were obtained here in comparison to reactions with
methanol. In the reaction with ethanol, formation of the
byproduct ethyl D-glucopyranoside was confirmed by GC-MS,
corroborating that glucose not only isomerized to fructose but
also reacted directly with the alcohol, resulting in decreased
fructose yield. Changing the reaction parameters did not
significantly improve the fructose yields for the ethanol
experiments. Importantly, the vital role of the alcohol for the
isomerization of glucose remained, however, clear compared to
aqueous media where no fructose formation occurred.
Another important aspect to examine is the viability of the
catalytic system for the isomerization reaction with increased
initial glucose concentration. Accordingly, experiments with
different initial concentrations of glucose were also carried out
over H‑USY(6). Figure 2 shows a progressive decrease in the
3
3
1
1
1
a
Step 1: 10−75 mg of H-USY(6), 125 mg of glucose, 4 g of methanol,
120 °C. Step 2: 4 g of water, 120 °C.
demonstrated that it was possible to achieve above 50% of
fructose for all the systems examined if the reaction times were
adjusted properly. Moreover, the combined yield of glucose and
fructose could be increased from 83% (1.7:1 mass ratio) to
between 88 and 91% at higher mass ratios, indicative of
suppression in the formed intermediates.
Catalyst reusability has also been evaluated for the most active
catalyst, H‑USY(6). Figure 3 depicts the results of five
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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, NMR and NH3-TPD data, and some
catalytic results. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
ar@kemi.dtu.dk
■
Author Contributions
§S.S. and M.P. contributed equally to the work.
Notes
The authors declare no competing financial interest.
Figure 3. Reuse of H‑USY(6) for glucose conversion. Step 1: glucose to
catalyst mass ratio = 1.7, 4 g of methanol, 1 h, 120 °C. Step 2: 4 g of
water, 1 h, 120 °C.
ACKNOWLEDGMENTS
M.P. and J.A.M. acknowledge support from the “Ministerio de
■
Ciencia e Innovacion
́
” of Spain through the project CTQ2011-
28216 and from the Regional Government of Madrid through
the project S2009-ENE1743. S.S. and A.R. thank the Danish
Council for Independent ResearchTechnology and Produc-
tion Sciences (project no. 10-081991) and The Catalysis for
Sustainable Energy initiative funded by the Danish Ministry of
Science, Technology and Innovation for financial support of the
work.
consecutive catalytic runs performed reusing the catalyst under
the optimal reaction conditions. After each catalytic run the
catalyst was recovered by filtration, washed thoroughly with
methanol, and dried overnight at 140 °C before being reused in
the following reaction. In all five consecutive catalytic runs, the
fructose yield remained constant at about 40−50% with a similar
product distribution. This clearly demonstrates that the catalytic
performance of the zeolite is preserved in the consecutive runs,
and that the catalyst system is highly suitable for reuse.
Furthermore, after the fifth reaction run, the catalyst was
calcined at 550 °C for 6 h and then subjected to surface area
analysis. The formal BET area and pore volume of H‑USY(6)
before use were measured to be 708 m2/g and 0.2436 cm3/g,
respectively. After the fifth reaction run, there were practically no
changes in the formal BET area (707 m2/g) and pore volume
(0.2463 cm3/g), thus corroborating that the structural integrity
of H‑USY(6) remained unchanged after the reaction cycles.
In conclusion, commercial large-pore zeolites have been
demonstrated to provide excellent catalytic performance in the
isomerization of glucose and subsequent etherification in
methanol. Applying these findings, a new two-step reaction
route to produce fructose from glucose was introduced, which
was ascertained by 13C NMR analyses using isotope-labeled
sugars. The best result for formation of fructose was obtained
using the zeolite H‑USY(6) with optimal levels and distribution
of Brønsted and Lewis acidity (Si/Al ratio = 6). Using this
catalyst, it proved possible to maintain a high fructose yield of
50−55%, with remaining 30−40% glucose even with low catalyst
loading (glucose-to-catalyst mass ratio = 12.5:1) at prolonged
reaction times. These values resembles the equilibrium yields
obtained of glucose (44−47%) and fructose (53−55%) in the
enzymatic isomerization reaction of glucose with glucose
isomerase.14 The solid catalyst could furthermore be reused in
five consecutive reaction runs, upholding the same initial activity
and structural integrity.
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