One-pot conversions of raffinose into furfural derivatives and sugar alcohols by using heterogeneous catalysts

Article abstract of DOI:10.1002/cssc.201300939

Inedible and/or waste biomass reserves are being strongly focused upon as a suitable new energy and chemical source. Raffinose, which is an indigestible trisaccharide composed of glucose, galactose, and fructose, is found abundantly in beet molasses, sugar cane, and seeds of many leguminous plants. Herein, we demonstrate the one-pot synthesis of furan derivatives and sugar alcohols from raffinose by using heterogeneous acid, base, and/or metal-supported catalysts. The combination of Amberlyst-15 and hydrotalcite (HT) showed a high activity (37% yield) for 5-hydroxymethyl-2-furaldehyde (HMF) through continuous hydrolysis, isomerization, and dehydration reactions. In addition, the use of a hydrotalcite-supported ruthenium catalyst (Ru/HT) successfully afforded 2,5-diformylfuran (DFF, 27% yield) from HMF produced by raffinose, directly. Moreover, the hydrogenation of hexoses obtained by raffinose hydrolysis into sugar alcohols (galactitol, mannitol, sorbitol) was also achieved in a high yield (91 %) with Amberlyst-15 and Ru/HT catalysts. Thus, we suggest that raffinose has great potential for the synthesis of important industrial intermediates under mild reaction conditions.

Full text of DOI:10.1002/cssc.201300939

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DOI: 10.1002/cssc.201300939
One-Pot Conversions of Raffinose into Furfural Derivatives
and Sugar Alcohols by Using Heterogeneous Catalysts
Saumya Dabral,[a, b] Shun Nishimura,[a] and Kohki Ebitani*[a]
Inedible and/or waste biomass reserves are being strongly fo-
cused upon as a suitable new energy and chemical source.
Raffinose, which is an indigestible trisaccharide composed of
glucose, galactose, and fructose, is found abundantly in beet
molasses, sugar cane, and seeds of many leguminous plants.
Herein, we demonstrate the one-pot synthesis of furan deriva-
tives and sugar alcohols from raffinose by using heterogene-
ous acid, base, and/or metal-supported catalysts. The combina-
tion of Amberlyst-15 and hydrotalcite (HT) showed a high ac-
tivity (37% yield) for 5-hydroxymethyl-2-furaldehyde (HMF)
through continuous hydrolysis, isomerization, and dehydration
reactions. In addition, the use of a hydrotalcite-supported
ruthenium catalyst (Ru/HT) successfully afforded 2,5-diformyl-
furan (DFF, 27% yield) from HMF produced by raffinose, direct-
ly. Moreover, the hydrogenation of hexoses obtained by raffi-
nose hydrolysis into sugar alcohols (galactitol, mannitol, sorbi-
tol) was also achieved in a high yield (91%) with Amberlyst-15
and Ru/HT catalysts. Thus, we suggest that raffinose has great
potential for the synthesis of important industrial intermedi-
ates under mild reaction conditions.
Introduction
Recently, there have been efforts to develop renewable bio-
mass resources to reduce the load on existing nonrenewable
fossils. The use of biorenewable resources allows the explora-
tion of opportunities that will
composed of galactose, glucose, and fructose sugar units (see
Scheme 1) and is one of the most abundant oligosaccharides
found in plants and agricultural products, such as beet molass-
partly contribute to secure the
domestic supply of energy, sup-
port agricultural economics, and
produce energy from renewable
resources in
a carbon-neutral
way.[1–4] Because the utilization
of edible biomass leads to the
evident drawback of competi-
tion with food production, the
focus is being shifted towards
inedible and/or waste biomass
reserves as suitable new energy
and chemical sources.[5]
Raffinose (O-a-d-galactopyra-
nosyl-(1!6)-O-a-d-glucopyrano-
syl-(1$2)-O-b-d-fructofurano-
side) is a naturally occurring indi-
gestible trisaccharide[6] that is Scheme 1. Pathway for the hydrolysis of raffinose into monosaccharides.
[a] S. Dabral, Dr. S. Nishimura, Prof. Dr. K. Ebitani
es, sugar cane, honey, eucalyptus manna, cottonseed meal,
School of Materials Science
leaves of the yew, potatoes, grapes, and the seeds of many le-
guminous plants.[7–10] Recently, raffinose has gained interest as
a potential excipient in stabilizing biomolecules because its
specific stabilizing properties are reported to be superior to
other sugars, such as lactose, maltose, and sucrose.[11] Raffinose
can be completely converted into three hexoses, namely, gal-
actose, glucose, and fructose, through hydrolysis, which are
economical and suitable for use as chemical feedstocks
(Scheme 1).[2]
Japan Advanced Institute of Science and Technology (JAIST)
1-1 Asahidai, Nomi, 923-1292 (Japan)
Fax: (+81)761-51-1149
E-mail: ebiatni@jaist.ac.jp
[b] S. Dabral
M. Tech, C.S.P.T, Department of Chemistry
Faculty of Science, University of Delhi (DU)
University Road, Delhi, 110007 (India)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201300939.
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Previous works have studied the enzymatic hydrolysis of raf-
finose into d-galactose and sucrose by a-galactosidase[6,12,13] or
into melibiose and fructose by invertase.[13] Although enzymati-
cally hydrolysis is possible from either side of the glucose unit,
the b-anomer of fructose reacts faster than the a-anomer of
galactose due to structural angle strain, that is, hydrolysis of
raffinose into melibiose and fructose is a dominant route. This
hydrolytic cleavage of the b-1,2-glycosidic bond between meli-
biose and fructose is of fundamental interest because it paves
the way for other catalytic transformations.[14] Apart from ex-
pensive enzymes, various homogeneous acids, for example,
HCl, H2SO4, and H3PO4, can also catalyze the hydrolysis of raffi-
nose into melibiose and fructose at 298 K;[13] however, these
mineral acids are not environmentally benign because of their
corrosive properties and difficulty in isolation from the prod-
uct.[3] Numerous reviews have been published on the conver-
sion of biomass with heterogeneous catalysts that have the in-
herent advantage of easy handling and isolation, thereby
giving them a large role in the evolution of utilization for bio-
mass.[14–19]
biomass-derived sugars into furan derivatives in a one-pot
manner by using heterogeneous catalysts are very attractive
from the viewpoint of environmental chemistry.
Hydrogenation of hexoses into the corresponding C6 sugar
alcohols, such as sorbitol and mannitol, is also an interesting
topic for biorefinery. Sugar alcohols find their application in
various pharmaceuticals as carriers of therapeutic agents, as an
unmodified sweetener in consumer products such as tooth-
paste, and as low-calorie sweeteners in the food industry.
Hexoses form precursors to important compounds such as vi-
tamin C and surfactants.[43,44] In particular, d-sorbitol is an im-
portant platform chemical reported to be added to the list of
top-twelve value-added chemicals derived from biomass by
the US Department of Energy.[45] d-Mannitol is widely distribut-
ed in nature and can be used as an osmotic diuretic and laxa-
tive.[46,47] These sugar alcohols have been synthesized from
monosaccharides, such as glucose and fructose;[48,49] cellu-
lose;[50] inulin;[51] and hemicellulose[52] by using Ru/Al2O3, Ru/C,
Ru/Y-zeolite, Ni/SiO2, and CuO–ZnO catalysts in the presence of
pressurized hydrogen.
One-pot synthesis is an attractive methodology to make
multistep reactions requiring isolation and purification of inter-
mediates into a simpler process: it reduces product loss at
every stage and saves energy, solvent, and time. One-pot syn-
thesis with heterogeneous catalysts further enables the se-
quential conversion of unstable intermediates into the target
Herein, we report the one-pot syntheses of HMF and DFF
and sugar alcohols (sorbitol, mannitol, and galactitol) from raf-
finose by using Amberlyst-15, HT, and Ru/HT as reusable heter-
ogeneous catalysts.
product with minimum loss in the final yield by site isola- Results and Discussion
tion.[20,21]
One-pot synthesis of HMF from raffinose
The conversion of biomass sources into 5-hydroxymethyl-2-
furaldehyde (HMF) with heterogeneous catalysts is an attrac-
tive process because HMF is a versatile and key renewable
platform chemical. The two functional groups in HMF, hydroxyl
and aldehyde, afford various transformations for the produc-
tion of notable intermediates for plastics, polymers, pharma-
ceuticals, and fuel.[22–27] Traditionally, HMF is obtained through
a dehydration reaction of hexoses, such as fructose,[22,23] glu-
cose,[24] and sucrose,[25] with the elimination of three water
molecules or the hydrolysis/dehydration reactions of various
biomass-derived carbohydrates, such as starch, inulin, cellulose,
and lignocelluloses, by using a variety of catalysts, such as min-
eral acids,[26–29] Lewis acids,[30] citric acid, oxalic acid,[31] strong-
acid cation-exchange resin,[32–34] and H-form zeolite.[35,36] Previ-
ously, we adopted an efficient method for the production of
HMF in a one-pot approach by using a combination of solid-
acid and -base catalysts through the isomerization of glucose
into fructose and a consecutive dehydration of fructose into
HMF.[37–39] This system can decrease the reaction temperature
compared with the direct dehydration of glucose into HMF
and is applicable for disaccharides such as sucrose, cellobiose,
and lactose as a substrate. Moreover, the innovative one-pot
synthesis of 2,5-diformylfuran (DFF), which is a useful inter-
mediate for the synthesis of antifungal agents, drugs, ligands,
as well as cross-linking agents for poly(vinyl alcohol),[40,41]
through the selective oxidation of HMF following the one-pot
conversion of glucose was also successfully carried out with
solid-acid Amberlyst-15, solid-base hydrotalcite (HT), and HT-
supported ruthenium (Ru/HT) catalysts.[42] These conversions of
The one-pot synthesis of HMF from raffinose is composed of
the following three steps: 1) hydrolysis of raffinose into glu-
cose, fructose, and galactose; 2) isomerization of these aldo-
hexoses into fructose and tagatose; and 3) their successive de-
hydration into HMF (Scheme 2).
Table 1 shows the results for the synthesis of HMF from raffi-
nose by using heterogeneous catalysts. The use of Amberlyst-
15 alone gave >99% conversion of raffinose and melibiose
with 20% yield of HMF (Table 1, entry 2). On the other hand,
Nafion NR50 and Nafion SAC13 catalysts exhibited low yields
of HMF (12 and 6%, respectively) with low melibiose conver-
sion, although they showed high conversions of raffinose (>
94%; Table 1, entries 3 and 4). It was supposed that the surface
acidities of these three catalysts were enough for the hydroly-
sis of raffinose into melibiose and fructose; however, the un-
availability of acidic sites in the small pores, as a result of pore
locking after the initial step of raffinose hydrolysis, blocked the
smooth raffinose and melibiose hydrolysis reactions in the case
of Nafion catalysts (Figure S1 in the Supporting Information).
Moreover in acidic media, the oligomerization of sugars and/or
HMF lead to the appearance of insoluble humins on the sur-
face of Amberlyst-15; this caused a decrease in the mass bal-
ance. On the other hand, no HMF production and no raffinose
conversion were observed for the HT catalyst alone (Table 1,
entry 5). The one-pot synthesis of HMF from raffinose over the
combination of Amberlyst-15 acid and HT base catalysts dis-
played good activity (30% yield, 29% selectivity) at 373 K
(Table 1, entry 1). The use of less Amberlyst-15 (50 mg, acidic
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Scheme 2. One-pot synthesis of HMF from raffinose by using Amberlyst-15 and HT catalysts.
Table 1. Synthesis of HMF from raffinose by using ion-exchange resins as solid-acid catalysts and HT as a solid-base catalyst.[a]
Entry
Catalyst
Raffinose
conv. [%]
Yield [%]
fructose+galactose
HMF selectivity
[%]
acid
base
melibiose
glucose
HMF
1
2
3
4
5
Amberlyst-15
Amberlyst-15
Nafion NR50
Nafion SAC13
–
HT
–
–
–
HT
>99[a,b,c]
17[a], 20[b], 6[c]
7[a], 4[b], 2[c]
10
2
2
0
6[a], 2[b] ,5[c]
8.8
9
4
0
30,[a] 26,[b] 37[c]
20
12
6
29,[a] 26,[b] 37[c]
20
13
7
>99
94
95
0
1
62
79
0
0
0
[a] Reaction conditions: raffinose (0.2 g, 0.33 mmol), acid catalyst (0.2 g), base catalyst (0.4 g), DMF (5 mL), 373 K, 6 h, 500 rpm, N2 flow (30 mLminꢀ1).
[b] Amberlyst-15 (50 mg), HT (0.3 g). [c] 393 K.
sites; 0.24 mmol) in combination with HT (0.3 g, basic sites;
0.21 mmol) also gave a good yield of HMF (26%; Table 1,
entry 1b). Figure S2 in the Supporting Information shows the
dependence of HMF yield on the reaction temperature. HMF
formation was enhanced upon increasing the temperature
from 373 to 393 K; maximum yields were obtained at 6 h;
thereafter, the yields of HMF became constant. The highest
yield and selectivity (37% yield, 37% selectivity) were achieved
at 393 K for a 6 h reaction (Table 1, entry 1c). Therefore, raffi-
nose also proved to be a good biomass source that was as effi-
cient as cellobiose and lactose, which gave 34.8 and 30.5%
yield for HMF, respectively, in a one-pot synthesis, as reported
Figure 1. Effect of solvent on the one-pot synthesis of HMF from raffinose.
Reaction conditions: raffinose (0.2 g, 0.33 mmol), Amberlyst-15 (0.2 g), HT
(0.4 g), solvent (5 mL), 393 K, 6 h, 500 rpm, N2 flow (30 mLminꢀ1).
previously.[37,39]
Figure 1 shows the effect of solvent for the one-pot synthe-
sis of HMF from raffinose with Amberlyst-15 and HT at 393 K
for 6 h. Water and some polar aprotic solvents, such as DMF,
DMSO, and MeCN, were investigated. Almost all raffinose (>
99%) was consumed in all of these solvents; however, they ex-
hibited large differences in the yield of HMF. The highest yield
of HMF was observed in DMF (37%). For the other polar aprot-
ic solvents, DMSO and MeCN, the HMF yields were 27 and 2%,
respectively, whereas no HMF was produced in water. No levu-
linic acid was observed in any of the solvents as a rehydration
product of HMF, but small amounts of formic acid were detect-
ed in DMF, DMSO, and MeCN (trace).
Figure 2. At the initial stage of the reaction (0.5 h), melibiose
formation was clearly observed (44% yield) with >99% con-
version of raffinose, which indicated that raffinose was first hy-
drolyzed into melibiose and fructose over protic acid sites of
Amberlyst-15; thereafter, the yield of melibiose gradually de-
creased with increasing HMF yield. It was supposed that the
hydrated water of raffinose pentahydrate and/or a small
amount of water absorbed on the catalysts was enough for
the initial hydrolysis of raffinose and the hydrolysis steps of raf-
finose and/or melibinose were further smoothed by the water
molecules formed in the progressive dehydration steps. During
The time course of HMF formation from raffinose in the
presence of Amberlyst-15 and HT catalysts is shown in
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Figure 3. Recyclability of acid and base catalysts in the one-pot synthesis of
HMF from raffinose. Reaction conditions: raffinose (0.2 g, 0.33 mmol), Am-
berlyst-15 (0.2 g), HT (0.4 g), DMF (5 mL), 393 K, 6 h, 500 rpm, N2 flow
(30 mLminꢀ1).
Figure 2. Time course in the one-pot synthesis of HMF from raffinose by
using Amberlyst-15 and HT. Reaction conditions: raffinose (0.2 g, 0.33 mmol),
Amberlyst-15 (0.2 g), HT (0.4 g), DMF (5 mL), 393 K, 500 rpm, N2 flow
(30 mLminꢀ1).
from raffinose through acid-catalyzed hydrolysis, base-cata-
lyzed isomerization, acid-catalyzed dehydration, and successive
selective oxidation was examined in a one-pot manner.
the hydrolysis of melibiose into glucose and galactose, and
their subsequent isomerization and dehydration to HMF
(Scheme 2), the increase in the yields of these intermediates
were not observed; thereby confirming that melibiose hydroly-
sis was the rate-determining step for the one-pot synthesis of
HMF from raffinose. Results obtained from the time courses
over Nafion catalysts also supported that melibiose hydrolysis
was a key step for the one-pot synthesis of HMF (Figure S1 in
the Supporting Information).
Table 2 lists the results of DFF formation from raffinose
when using heterogeneous catalysts. As mentioned above,
Amberlyst-15 and HT catalysts gave 37% yield of HMF in
a one-pot process from raffinose (Table 2, entry 3). The addition
of Ru/HT as an oxidation catalyst afforded DFF from raffinose
To check the recyclability of the acid and base catalysts, they
were simply recovered by centrifugation, washed with DMF,
dried in vacuum, and recycled for further reactions. The
amount of acidic and basic sites present in the reaction mix-
ture, to check their recyclability, were estimated to be 0.96 and
0.28 mmol for Amberlyst-15 (0.2 g) and HT (0.4 g), respectively.
The one-pot conversion of 0.33 mmol of raffinose into HMF in-
cluded the hydrolysis of 0.66 mmol of glycosidic bonds in raffi-
nose and isomerization/dehydration processes of 0.99 mmol of
produced monosaccharides (intermediates) in theory. Thus, we
conclude that both Amberlyst-15 and HT are effective and re-
usable catalysts, at least three times, for the one-pot synthesis
of HMF, without any significant loss in their catalytic activity
and selectivity (Figure 3).
Table 2. One-pot synthesis of DFF from raffinose by using Amberlyst-15,
HT and Ru/HT catalysts under atmospheric pressure.[a]
Entry
Catalyst
base
Raffinose
conv. [%]
Yield [%]
HMF DFF
acid
oxidation
1[b]
2[c]
3[d]
4[d]
5[b]
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
–
HT
HT
HT
–
Ru/HT
Ru/HT
–
Ru/HT
Ru/HT
>99
>99
>99
>99
42
<1
1
37
28
0
12
27
–
0
0
–
[a] Reaction conditions: raffinose (0.2 g, 0.33 mmol), Amberlyst-15 (0.2 g),
HT (0.4 g), 4 wt% Ru/HT (0.15 g), DMF (5 mL), 393 K, 500 rpm. [b] O2 flow
(20 mLminꢀ1) for 12 h. [c] Two-step reaction without catalyst separation.
After 6 h under a flow of N2 (30 mLminꢀ1), Ru/HT (0.15 g) was added
under
(30 mLminꢀ1) for 6 h.
a ) for 6 h. [d] Under a flow of N2
flow of O2 (20 mLminꢀ1
One-pot synthesis of DFF from raffinose
in the presence of both solid-acid Amberlyst-15 and solid-base
HT catalysts (Table 2, entries 1 and 2). The coexistence of three
catalysts from the initial stage of the reaction gave 12% yield
of DFF under a flow of O2 (Table 2, entry 1), whereas the two-
step reaction without separation of the catalyst improved the
DFF yield from 12 to 27% (Table 2, entry 2). This improvement
was due to the prohibition of side reactions of raffinose by the
Ru/HT catalyst because 42% of raffinose was converted by Ru/
HT under a flow of O2 (Table 2, entry 5). In the absence of
oxygen (under a flow of nitrogen), 28% of HMF was formed by
Ru/HT and Amberlyst-15, which indicated that Ru/HT could cat-
alyze glucose–fructose and galactose–tagatose isomerization in
the same manner as HT, but with a low yield and selectivity
(Table 2, entry 4).
DFF has been synthesized from carbohydrates such as fruc-
tose[32] and glucose[40] in a one-pot, two-step approach or by
selective oxidation of the hydroxy group of HMF with classical
oxidants and metal-based catalysts, such as Pt/C,[41] V2O5,[53] Co/
Mn/Zr/Br,[54] VOPO4·2H2O,[55] MnIII–Salen,[56] and various inorgan-
ic vanadium compounds. HT has been reported as a support
for dispersing ruthenium species[57,58] and is an important cata-
lyst for selective oxidations and reductions.[20,59] According to
our previous report,[42] the Ru/HT catalyst afforded a remarkable
activity for the synthesis of DFF through the selective oxidation
of HMF in the presence of molecular oxygen under mild reac-
tion conditions. Therefore, by using a combination of Amber-
lyst-15, HT, and Ru/HT catalysts, the direct production of DFF
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These results indicate that, for the one-pot synthesis of DFF
from raffinose, the combination of Amberlyat-15, HT, and Ru/
HT catalysts with atmospheric control achieved the best activi-
ty. The sequential reactions were confirmed by measuring
a time course for the formation of DFF by the successive addi-
tion of Amberlyst-15, HT, and Ru/HT into the solution
(Figure 4). The addition of Ru/HT under an oxygen flow result-
ed in the rapid consumption of HMF and the simultaneous for-
mation of DFF through the selective oxidation of HMF. The
achieved 27% yield of DFF from raffinose was also comparable
to that obtained from glucose (25%), as reported in our previ-
ous paper.[42]
for the one-pot synthesis of sugar alcohols (Table 3, entries 1–
3). The hydrolysis of melibiose occurred easily in the presence
of Amberlyst-15, compared with Nafion catalysts (see Table 1,
entries 2–4). Further investigations into the hydrogenation re-
action were performed with Ru-, Pt-, Pd-, and Au-supported HT
catalysts in the presence of Amberlyst-15. As shown in Table 3,
only the pairing of Amberlyst-15 and Ru/HT gave the sugar al-
cohols in a high yield (91%; Table 3, entries 1 and 4–6). The
Ru/HT catalyst also exhibited good activities for the hydrogena-
tion of fructose, glucose, and galactose into the corresponding
sugar alcohols (Table 3, entries 10–12). The absence of either
Amberlyst-15 or Ru/HT did not produce any sugar alcohols
(Table 3, entries 7 and 8). The reaction in the absence of both
Amberlyst-15 and Ru/HT also did not result in any sugar alco-
hols (Table 3, entry 9). In all cases, the formation of HMF was
not observed by HPLC.
The product distribution upon the hydrogenation of raffi-
nose was not equimolar, which would have been expected.
This result can be explained by considering that fructose (acy-
clic) in water is in equilibrium with its four different cyclic
forms. The hydrogenation of fructose gave mannitol and sorbi-
tol (Table 3, entry 10). The ratio of b/a-d-fructofuranose in solu-
tion may determine the ratio of mannitol/sorbitol formed
through the hydrogenation of fructose. Glucose and galactose
gave only one major hydrogenation product, sorbitol and ga-
lactitol, respectively (Table 3, entries 11 and 12).
The reaction temperature had a significant effect on the
yield of sugar alcohols: the yield increased linearly over the
temperature range of 333 to 383 K. At 383 and 393 K, the yield
of sugar alcohols reached a plateau and beyond a reaction
temperature of 393 K the yields decreased (Figure S3 in the
Supporting Information).
Figure 4. Time course in the one-pot synthesis of DFF from raffinose by
using Amberlyst-15, HT, and Ru/HT catalysts. The Ru/HT catalyst was added
after 6 h under a flow of O2 (10 mLminꢀ1). Reaction conditions: raffinose
(0.2 g, 0.33 mmol), Amberlyst-15 (0.2 g), HT (0.4 g), 4 wt% Ru/HT (0.15 g),
DMF (5 mL), 393 K, 500 rpm.
One-pot synthesis of sugar alcohols from raffinose
Sugar alcohols are formed by
the reduction of carbonyl
groups of the hexose units ob-
tained by raffinose hydrolysis. In
the case of trisaccharide raffi-
nose, the hydrolysis of the glyco-
sidic bonds is necessary before
(or parallel with) hydrogenation
of the aldohexoses into the
sugar alcohols, namely, sorbitol,
mannitol, and galactitol. Accord-
ingly, the current one-pot
system includes a two-step cas-
cade reaction (Scheme 3).
Table 3 shows the results for
the one-pot synthesis of sugar
alcohols from raffinose by using
heterogeneous acid and metal-
supported catalysts in the pres-
ence of H2 and isopropanol. A
comparison of the acidic resins
suggested that the Ambelyst-15
was also the best acid catalyst Scheme 3. One-pot synthesis of sugar alcohols from raffinose by using Amberlyst-15 and Ru/HT catalysts.
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tained without H2 gas under our
experimental conditions (Table 4,
entry 4b). Therefore, interesting-
ly, both isopropanol and H2 gas
were important factors for the
effective hydrogenation of hexo-
ses.[61]
Table 3. The effect of the catalyst on the one-pot hydrolytic hydrogenation of raffinose into sugar alcohols.[a]
Entry
Substrate
Catalyst
hydrogenation
Yield [%]
galactitol+sorbitol
hydrolysis
mannitol
total
1
2
3
4
5
6
7
8
raffinose
raffinose
raffinose
raffinose
raffinose
raffinose
raffinose
raffinose
raffinose
fructose
glucose
Amberlyst-15
Nafion NR50
Nafion SAC13
Amberlyst-15
Amberlyst-15
Amberlyst-15
–
Ru/HT
Ru/HT
Ru/HT
Pt/HT
Pd/HT
Au/HT
Ru/HT
–
15
6
0
0
0
0
0
0
0
76
20
0
0
0
0
0
0
0
91
26
0
0
0
0
0
0
0
Experiments were performed
to check the reusability of the
Amberlyst-15 and Ru/HT catalyst.
The catalysts were separated
from the reaction mixture by
centrifugation. As shown in
Figure 6, the Amberlyst-15 and
Ru/HT catalysts demonstrated
excellent recyclability for more
than three consecutive runs.
Amberlyst-15
9
–
–
–
–
–
10
11
12
Ru/HT
Ru/HT
Ru/HT
44
–
–
53[b]
89[b]
87[c]
97
89
87
galactose
[a] Reaction conditions: substrate (0.16 mmol), acid catalyst (0.1 g), metal/HT (25 mg, metal 3 wt%), water
(3 mL), isopropanol (2 mL), H2 (0.3 MPa), in a 50 mL Teflon-lined autoclave reactor, 383 K, 3 h. [b] Yield of sorbi-
tol. [c] Yield of galactitol.
The time course for the reaction showed that the reaction
was complete after 3 h, with a high yield and conversion (91%
yield, 99% conversion; Figure 5); thereafter, the sugar alcohols
remained stable even after 6 h of reaction time. The turnover
number (TON) for the sum of the sugar alcohols was calculated
to be 0.91 for Amberlyst-15 and 59 for Ru/HT catalysts
(Table 3, entry 1).
Table 4. The effect of the ratio of isopropanol to water on the yields of
the sugar alcohols.[a]
Entry
Isopropanol Water
Yield [%]
[mL]
[mL]
mannitol galactitol+sorbitol total
1
2
3
4
5
6
0
1
2
3
4
5
5
4
3
2
1
0
5
13
15
15, 0[b]
13
23
62
76
75, 0[b]
66
28
75
91
90, 0[b]
79
0
0
0
[a] Reaction conditions: raffinose (0.1 g, 0.16 mmol), Amberlyst-15 (0.1 g),
3 wt% Ru/HT (25 mg), water, isopropanol, H2 (0.3 MPa) in a 50 mL Teflon-
lined autoclave reactor, 383 K, 3 h. [b] In the absence of H2 gas (0.3 MPa
Ar atmosphere).
Figure 5. Time course for the one-pot hydrolytic hydrogenation of raffinose.
Reaction conditions: raffinose (0.1 g, 0.16 mmol), Amberlyst-15 (0.1 g),
3 wt% Ru/HT (25 mg), water (3 mL), isopropanol (2 mL), H2 (0.3 MPa), in
a 50 mL Teflon-lined autoclave reactor, 383 K.
To study the role of the additive isopropanol, various ratios
of water and isopropanol were employed as the solvent
system. The yield of sugar alcohols depended on the ratio of
water and isopropanol, as shown in Table 4. In the case of
pure water and H2 gas (without isopropanol), the yield of
sugar alcohols was very low (28%; Table 4, entry 1), whereas
no product was obtained in pure isopropanol as a solvent
(Table 4, entry 6). When the water to isopropanol ratio was 2:3
or 3:2, the yield of sugar alcohols was around 90% (Table 4,
entries 3 and 4). In previous reports, isopropanol was used as
a hydrogen transferring agent for the hydrogenation reaction
at 463[60] and 413 K.[52] However, no sugar alcohols were ob-
Figure 6. Recyclability of the Amberlyst-15 and Ru/HT catalysts in the one-
pot synthesis of sugar alcohols from raffinose. Reaction conditions: raffinose
(0.1 g, 0.16 mmol), Amberlyst-15 (0.1 g), 3 wt% Ru/HT, water (3 mL), isopro-
panol (2 mL), H2 (0.3 MPa), in a 50 mL Teflon-lined autoclave reactor, 383 K,
3 h.
Conclusions
We have successfully proved that raffinose is a potentially
useful source of inedible biomass feedstock that can be effi-
ciently converted into three industrially important intermedi-
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to HPLC analysis. The solid catalyst thus obtained was washed with
DMF (25 mL) and dried in vacuo overnight before reuse.
ates, namely, HMF, DFF, and sugar alcohols (sorbitol, mannitol,
and galactitol), in a one-pot manner by using reusable hetero-
geneous catalysts, such as Amberlyst-15, HT, and Ru/HT. The
Ru/HT catalyst was an efficient heterogeneous catalyst for both
the oxidation of HMF and the hydrogenation of aldohexoses.
Moreover, solid-acid, solid-base, and metal catalysts can work
together in the same reactor without destruction of their
active sites by site isolation.
Synthesis of DFF: The reaction was performed by using raffinose
pentahydrate (0.2 g, 0.33 mmol), Amberlyst-15 (0.2 g), HT (Mg/Al=
3, 0.4 g), and DMF (5 mL) at 393 K for 6 h under a flow of N2
(30 mL·minꢀ1) followed by the addition of 4 wt% Ru/HT (0.15 g)
catalyst at 393 K under a flow of O2 (20 mLminꢀ1) for another 6 h.
At the end of the reaction, the reactor was cooled to room temper-
ature and the reaction mixture was diluted 20 times with water fol-
lowed by separation of the solid catalyst from the solution by cen-
trifugation. The solution was then filtered by using a Milex-LG
0.20 mm filter and subjected to HPLC analysis.
Experimental Section
Synthesis of sugar alcohols: One-pot conversion of raffinose was
performed in a 50 mL Teflon-lined autoclave. The reactor was
charged with raffinose pentahydrate (0.1 g, 0.16 mmol), Amberlyst-
15 (0.1 g), 3 wt% Ru/HT catalyst (25 mg), isopropanol (2 mL), water
(3 mL), and H2 gas (0.32 MPa). The reactor was heated to 383 K in
a silicon oil bath and maintained at this temperature for 3 h with
magnetic stirring at 500 rpm. After the reaction, the reactor was
cooled to room temperature. The reaction mixture was diluted
with water (50 mL) followed by separation of the solid catalyst
from the solution by centrifugation. The solution was then filtered
by using a Milex-LG 0.20 mm filter and subjected to HPLC analysis.
Because the resin was denser, it settled at the bottom of the centri-
fuge tube and because Ru/HT was lighter it dispersed itself in the
washing solution; thus, the catalyst could be separated and
washed individually with distilled water (25 mL) followed by over-
night drying in vacuo.
Materials: d-(+)-Raffinose pentahydrate, ruthenium (III) chloride·n-
hydrate (99.9% purity), and isopropanol (dehydrated, 99.5% purity)
were purchased from Wako Pure Chemicals. Amberlyst-15 cation-
exchange resin (acid sites; 4.8 mmolgꢀ1), Nafion SAC13 (acid sites;
0.13 mmolgꢀ1), Nafion NR50 (acid sites; 0.9 mmolgꢀ1), and HMF
were purchased from Sigma–Aldrich, Inc. HT (Mg/Al=3; base sites;
0.7 mmolgꢀ1 [62]
was supplied by Tomita Pharmaceuticals Co., Ltd.
)
d-Mannitol (ꢁ99% purity), d-sorbitol (ꢁ97% purity), galactitol (ꢁ
98% purity), and DFF were purchased from Tokyo Chemical Indus-
try. DMF, DMSO, and MeCN were purchased from Kanto Chemicals
Co., Inc. All solvents were purified before use.[63]
Preparation of Ru/HT: HT (Mg/Al=3, 1.0 g) was added to an aque-
ous solution containing RuCl3·nH2O and stirred for 1 h at room
temperature.[20,58] The resulting solid was filtered and washed with
water (300 mL). Finally, a gray solid was obtained after drying in
vacuo at room temperature overnight. The synthesized Ru/HT cata-
lyst retained the original MgꢀAl layered HT structure, as deter-
mined by XRD measurements (Figure S4 in the Supporting Infor-
mation). The extended X-ray absorption fine structure (EXAFS) fea-
ture of synthesized Ru/HT showed the same profile to that of previ-
ous studies,[57,58] which supported the presence of RuIV species (Fig-
ure S5 in the Supporting Information). Inductively coupled plasma
(ICP) analysis indicated that the 4 wt% Ru/HT catalyst contained
3.94 wt% Ru metal, and the 3 wt% Ru/HT catalyst contained
3.0 wt% Ru metal. The preparation of Pd/HT, Pt/HT, and Au/HT fol-
lowed procedures reported previously.[64,65]
Product analysis: The conversions and yields of HMF and DFF were
estimated by using a high-performance liquid chromatograph
(WATERS 600 Pump) with an Aminex HPX-87 H column from Bio-
rad laboratories, Inc. The analysis conditions were set as follows:
eluent,
a
10 mm aqueous solution of H2SO4; flow rate,
0.5 mL·minꢀ1; column temperature, 323 K. The products were ana-
lyzed by using a refractive index detector (WATERS 2414). Authen-
tic samples were used as standards and a calibration curve was
used for quantification. The yield of sugar alcohols was determined
by liquid chromatography (LC; Shimadzu LC-20AT, refractive index
detector RID-10A). The column was a Shodex Sugar SC1211
column (6.0 mm ID x 250 mmL, mobile phase: MeCN/water (40/
60), 0.6 mLminꢀ1, 323 K). A typical HPLC chromatogram is shown
in Figure S6 in the Supporting Information. The peaks of galactitol
and sorbitol were not well resolved. Therefore, we showed the
sum of the yields of galactitol and sorbitol in Tables 3 and 4. Reac-
tant conversions and product yields were calculated from the con-
centrations obtained by HPLC using standard curves. All data were
based on repeated runs and the standard deviation was less than
2%.
Characterization: The catalyst was characterized by XRD with
a Rigaku Smartlab X-ray diffractometer using CuKa radiation (l=
0.154 nm) and a power of 40 kV and 20 mA. Inductively coupled
plasma atomic emission spectroscopy (ICP-AES) was obtained by
using a Shimadzu ICPS-7000 ver.2 instrument to estimate the wt%
of Ru in the Ru/HT catalyst. X-ray adsorption fine structure (XAFS)
measurements were performed at the BL01B1 station in the
SPring-8 synchrotron radiation facility, Japan. Ru K-edge XAFS spec-
tra was recorded at room temperature by the transmission method
using a Si(311) monochromator.
Synthesis of HMF: The one-pot conversion of raffinose was per-
formed in a 30 mL Schlenk flask equipped with a reflux condenser.
The reaction was typically performed by using raffinose pentahy-
drate (0.2 g, 0.33 mmol), Amberlyst-15 (0.2 g), HT (Mg/Al=3, 0.4 g),
and DMF (5 mL) at 393 K for 6 h under a flow of N2 (30 mLminꢀ1).
After the temperature of the thermostatic oil bath rose to the de-
sired reaction temperature (393 K) and remained constant, the re-
action chamber was then put into the oil bath. The reaction mix-
ture was magnetically stirred at 500 rpm. At the end of the reac-
tion, the reactor was cooled to room temperature and the reaction
mixture was diluted 20 times with water followed by separation of
the solid catalyst from the solution by centrifugation. The solution
was then filtered by using a Milex-LG 0.20 mm filter and subjected
Acknowledgements
S.D. gratefully acknowledges support from a grant from the dual
masters program between JAIST and DU. S.N. is thankful for sup-
port from the Intellectual Property Highway Promotion of the
Japan Science and Technology Agency (JST), Japan. K.E. appreci-
ates a Grant-in-Aid for Scientific Research(C) (no.22560764) sup-
ported by the Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Japan. The synchrotron radiation experi-
ments were performed at the BL01B1 in the SPring-8 with the ap-
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Published online on November 5, 2013
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