Catalyst and Process Design for the Continuous Manufacture of Rare Sugar Alcohols by Epimerization–Hydrogenation of Aldoses

Article abstract of DOI:10.1002/cssc.201600755

Sugar alcohols are applied in the food, pharmaceutical, polymer, and fuel industries and are commonly obtained by reduction of the corresponding saccharides. In view of the rarity of some sugar substrates, epimerization of a readily available monosaccharide has been proposed as a solution, but an efficient catalytic system has not yet been identified. Herein, a molybdenum heteropolyacid-based catalyst is developed to transform glucose, arabinose, and xylose into less-abundant mannose, ribose, and lyxose, respectively. Adsorption of molybdic acid onto activated carbon followed by ion exchange to the cesium form limits leaching of the active phase, which greatly improves the catalyst stability over 24 h on stream. The hydrogenation of mixtures of epimers is studied over ruthenium catalysts, and it is found that the precursor to the desired polyol is advantageously converted with faster kinetics. This is explained by density functional theory on the basis of its more favorable adsorption on the metal surface and the lower energy barrier for the addition of a hydrogen atom to the primary carbon atom. Finally, different designs for a continuous process for the conversion of glucose into mannitol are studied, and it is uncovered that two reactors in series with one containing the epimerization catalyst and the other containing a mixture of the epimerization and hydrogenation catalysts increases the mannitol/sorbitol ratio to 1.5 from 1 for a single mixed-bed reactor. This opens a prospective route to the efficient valorization of renewables to added-value chemicals.

Full text of DOI:10.1002/cssc.201600755

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DOI: 10.1002/cssc.201600755
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Catalyst and Process Design for the Continuous
Manufacture of Rare Sugar Alcohols by Epimerization–
Hydrogenation of Aldoses
Giacomo M. Lari,[a] Olivier G. Grçninger,[a] Qiang Li,[b] Cecilia Mondelli,*[a] Nfflria López,*[b] and
Javier PØrez-Ramírez*[a]
Sugar alcohols are applied in the food, pharmaceutical, poly-
mer, and fuel industries and are commonly obtained by reduc-
tion of the corresponding saccharides. In view of the rarity of
some sugar substrates, epimerization of a readily available
monosaccharide has been proposed as a solution, but an effi-
cient catalytic system has not yet been identified. Herein, a mo-
lybdenum heteropolyacid-based catalyst is developed to trans-
form glucose, arabinose, and xylose into less-abundant man-
nose, ribose, and lyxose, respectively. Adsorption of molybdic
acid onto activated carbon followed by ion exchange to the
cesium form limits leaching of the active phase, which greatly
improves the catalyst stability over 24 h on stream. The hydro-
genation of mixtures of epimers is studied over ruthenium cat-
alysts, and it is found that the precursor to the desired polyol
is advantageously converted with faster kinetics. This is ex-
plained by density functional theory on the basis of its more
favorable adsorption on the metal surface and the lower
energy barrier for the addition of a hydrogen atom to the pri-
mary carbon atom. Finally, different designs for a continuous
process for the conversion of glucose into mannitol are stud-
ied, and it is uncovered that two reactors in series with one
containing the epimerization catalyst and the other containing
a mixture of the epimerization and hydrogenation catalysts in-
creases the mannitol/sorbitol ratio to 1.5 from 1 for a single
mixed-bed reactor. This opens a prospective route to the effi-
cient valorization of renewables to added-value chemicals.
Introduction
Sugar alcohols, particularly those with C5 and C6 backbones,
are an important class of carbohydrate derivatives. Pentose-de-
rived polyols include arabitol, xylitol, and ribitol, whereas man-
nitol and sorbitol are the most relevant representatives of
hexose-derived alcohols, which comprise a higher number of
molecules owing to the presence of an additional stereocenter.
All these molecules have multiple uses in the fine chemical,
pharmaceutical, and food industries.[1] Specifically, they im-
prove the nutritional profile of food preparations, as they are
often incompletely absorbed by the intestine,[2] marginally
alter blood sugar levels,[3] and appear to limit the formation of
body fat.[4] They are also added to toothpaste and chewing
gum formulations for their anticaries effect, as oral bacteria
cannot ferment them.[5] Additionally, they are relevant and ver-
satile monomers for the manufacture of highly performing bio-
degradable and biocompatible materials[6] and renewable feed-
stocks for the preparation of chemicals[7] and fuels.[8] Notably,
arabitol has recently entered the list of the top-12 biobased
chemicals.[9]
Sugar alcohols are rarely isolated from natural products and
are more commonly obtained by hydrogenation of the corre-
sponding carbohydrates. This has mostly been achieved by
means of enzymes,[10] although chemocatalytic technologies
have also been proposed.[11] The latter systems feature a lower
environmental and economic impact owing to the possibility
of processing reactants at higher concentrations and of operat-
ing over wider pH and temperature ranges.[12] Aldoses are the
substrates of choice,[13] as the formation of a hydroxyl group
from a primary carbonyl function does not generate a stereo-
center and the reaction can proceed with high selectivity. Nev-
ertheless, the very low availability of certain sugars (e.g., man-
nose and ribose) limits the feasibility of obtaining some of the
polyols at a large scale.[14] Two approaches have been pro-
posed to overcome this problem. The first comprises the use
of a suitable ketose, as in the case of fructose for the prepara-
tion of mannitol.[15] Here, the drawback is the formation of ap-
proximately equimolar mixtures of mannitol and sorbitol,
which have to be separated by costly crystallization or chroma-
tography techniques.[16] Indeed, attempts to increase the selec-
tivity to mannitol by modification of the catalyst[17] or by the
addition of a chiral organic co-catalyst[18] have only led to mod-
erate success. Alternatively, the abundant epimeric form of
[a] G. M. Lari, O. G. Grçninger, Dr. C. Mondelli, Prof. J. Pꢀrez-Ramꢁrez
Institute for Chemical and Bioengineering
Department of Chemistry and Applied Biosciences
ETH Zurich
Vladimir-Prelog-Weg 1, 8093 Zurich (Switzerland)
E-mail: cecilia.mondelli@chem.ethz.ch
jpr@chem.ethz.ch
[b] Q. Li, Prof. N. Lꢂpez
Institute of Chemical Research of Catalonia, ICIQ
The Barcelona Institute of Science and Technology
Av. Pa¨ısos Catalans 16, 43007 Tarragona (Spain)
E-mail: nlopez@iciq.es
Supporting Information and the ORCID identification number(s) for the
author(s) of this article can be found under http://dx.doi.org/10.1002/
cssc.201600755.
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a rare sugar could be chosen as the starting material, and the
desired polyol could be obtained by combining epimerization
and hydrogenation steps.[19] Remarkably, this strategy could be
applied to sugars such as pentoses, for which the ketonic form
is infrequent. Raney nickel and Ru/C have been shown to be
effective hydrogenation catalysts,[11] whereas the best hetero-
geneous epimerization materials reported so far have shown
limitations with respect to the concentration of the
substrate owing to the requirement of using metha-
nol as the medium (Sn-b)[20] or to their level of activi-
ty (layered niobium molybdate).[21] Besides, only few
catalytic data are available for solids prepared by im-
mobilizing the highly active but water-soluble[22]
phosphomolybdic heteropolyacid (HPA) through ad-
sorption onto activated charcoal[23] or by precipita-
tion in the form of an insoluble salt.[24] Most relevant-
ly, the combination of the two reactions has never
been studied in detail, and the application of indus-
trially more amenable reactors in flow mode instead
of vessels in batch mode has not been explored.
Results and Discussion
Design of the epimerization catalyst
Bulk and supported molybdenum-based catalysts were pre-
pared to evaluate their activity and stability in sugar epimeriza-
tion (Scheme 1). The first group included phosphomolybdic
Herein, we target the preparation of rare sugar al-
Scheme 1. Preparation of bulk and supported heteropolyacid catalysts.
cohols by epimerization followed by hydrogenation.
In particular, we focus on the synthesis of mannitol
from glucose, ribitol from arabinose, and arabitol
from xylose. We initially confront various methods for the im-
mobilization of HPA by evaluating the epimerization activity of
the silica-supported, carbon-supported, and ion-exchange-
resin-supported materials obtained and by investigating their
compositional and structural changes upon use in continuous-
flow catalytic runs. After selecting an efficient and stable hy-
drogenation catalyst based on ruthenium, we investigate the
relative hydrogenation rates of the starting sugars and their
epimers by combining kinetic tests and density functional
theory (DFT) simulations. Finally, we study the overall per-
formance of a continuous process by comparing different ar-
rangements of the catalysts in single and series reactor config-
urations.
acid in its protonic form and as its silver and cesium salts.[24]
The second set was obtained by adsorption of the acid or the
salt on silica, activated carbon,[23] or an ion-exchange resin
(IER).[25] Compositional data (Table 1) confirmed the expected
molybdenum contents in the bulk solids. In the case of the
supported catalysts, high metal loadings were observed that
corresponded to up to 75% uptake of the precursor applied in
the preparation. The Mo/P ratio was used to estimate the pres-
ervation of the heteropolyacid nature (Scheme 1) of the active
phase upon synthesis. The typical value of phosphomolybdic
acid (12) was obtained in most cases. A notable exception was
the material prepared by using the IER, which lost part of the
phosphoric acid groups. This was ascribed to the limited stabil-
ity of the heteropolyacid at pH>3, which resulted in depletion
of its Keggin-type structure and the formation of molybdate
and phosphate ions.[26] Finally, the Mo/M ratio (M=Ag, Cs) was
considered to evaluate the efficiency of the proton exchange.
Table 1. Characterization data and epimerization activity of the molybdate-based catalysts.[a]
[d]
[e]
[g]
Catalyst
Mo[b]
[wt%]
Mo/P[c]
Mo/M[c]
SBET
Vpore
TOF[f]
[hꢀ1
SM
Mo leaching[b]
[%]
[m2 gꢀ1
]
[mLgꢀ1
]
]
[%]
MoO3
H-HPA
Ag-HPA
Cs-HPA
H-HPA/IER
H-HPA/SiO2
H-HPA/C
Ag-HPA/C
Cs-HPA/C
73.5
65.6
48.1
49.7
12.2
18.6
25.5
20.1
16.1
–
–
–
3.5
3.8
–
–
–
5.2
5.5
15
7
41
61
21
105
581
629
654
0.21
0.06
0.18
0.16
0.07
0.35
0.41
0.45
0.42
1.8
28.9
31.1
29.1
15.4
35.4
51.8
60.7
55.4
95.7
93.6
89.9
89.4
91.5
95.1
93.4
92.8
90.2
100
100
21
13
3
61
16
4
12.8
10.9
11.5
15.9
11.8
12.4
12.6
13.1
2
[a] Reaction conditions: T=333 K, [glucose]=0.28m, glucose/Mo=50, t=30 min. [b] ICP-OES. [c] XRF. [d] BET method. [e] Volume of N2 adsorbed at p/p0 =
0.99. [f] Based on Mo. [g] Selectivity to mannose.
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This was close to the theoretical value of 4 for the bulk Ag-
HPA and Cs-HPA, whereas it was significantly higher for the
carbon-supported materials, indicating that part of the ex-
changed metal was lost (Table 1). This can be explained by the
ionic nature of the interaction between the support and the
active phase, as hinted by previous reports describing that
positively charged sites on the carbon surface act as cations
displacing the Ag+ and Cs+ species.[23] The porous properties
of the catalysts were determined by nitrogen sorption. The
data evidence that H-HPA possessed an even lower specific
surface area (SBET) than the reference material MoO3, whereas
the SBET values of Ag-HPA and Cs-HPA were markedly higher.[27]
Carbon-supported catalysts displayed high porosity (Vpore) and
total surface areas (SBET) greater than 500 m2 gꢀ1. Nevertheless,
it should be noted that these values are substantially lower
than those of the bare carbon (Vpore =0.61 mLgꢀ1 and
S
BET =1100 m2 gꢀ1). This points to significant pore blockage
upon deposition of large quantities of the heteropolyacid. The
same was observed in the case of the silica-supported material.
Incorporation of the active phase reduced the SBET of the bare
support by 20 m2 gꢀ1 and its Vpore by 0.15 mLgꢀ1. In the case of
the IER-supported solid, no differences were observed relative
to the pristine carrier. H-, Ag-, and Cs-HPA deposited on
carbon were amorphous, as no distinctive reflections were ob-
served by X-ray diffraction (Figure S1a in the Supporting Infor-
mation). On the other hand, H-HPA/SiO2 and the bulk materials
showed typical reflections of the Keggin-type phosphomolyb-
dic acid. The very sharp diffraction lines point to crystals
>100 nm in size Taking into account the substantially different
loadings of the elements, energy-dispersive X-ray spectroscopy
(EDS) mapping of the Cs-HPA/C catalyst (Figure 1a) displayed
homogeneous distributions of Cs, Mo, and P on the carbon
support, in line with a high dispersion of the active phase. Ad-
ditionally, the absence of areas enriched in Mo or P pointed to
a preserved heteropolyacid structure.
Figure 1. EDS mapping of Mo, Cs, P, and C for Cs-HPA/C in (a) fresh and
(b) used forms.
nisms likely play a role in the deposition of HPA on carbon,[23]
which rationalizes the intermediate leaching observed by
using this carrier. Immobilization of the ion-exchanged HPAs
produced catalysts showing activities and selectivities compa-
rable to those shown by H-HPA/C, in line with the testing of
the bulk materials featuring different counterions. Still, these
solids were more stable, as metal depletion was similar to that
of the robust H-HPA/IER. Also in this case, the presence of a dif-
ferent counterion did not significantly alter the activity or se-
lectivity. On the basis of its high activity and robustness, Cs-
HPA/C was chosen to investigate the temperature dependence
of the reaction and the catalyst stability upon repeated use.
Regarding the first aspect, a negligible glucose conversion was
observed below 313 K, whereas it steadily increased between
333 and 373 K (Figure 2a). The Mo leaching over 10 cycles was
higher than 80% in the case of H-HPA/C but was limited to
only 35% in the case of Cs-HPA/C (Figure 2b). Notably, in both
cases, the Mo/P ratio did not change, which likely indicates
that the Keggin-type structure was maintained. On the basis of
these results, Cs-HPA/C was tested in continuous mode under
industrially relevant, that is, high-conversion, conditions (Fig-
ure 2c). A minor activity loss was observed over the first 12 h
on stream, whereas deactivation became more pronounced in
the subsequent 12 h of the test. The major reason for the ac-
tivity loss seems to be the substantial (45%) depletion of the
Mo content, as determined by elemental analysis. It should be
noted that, despite significant deactivation, the stability of this
optimized catalyst was found to be greatly superior to that of
The catalytic activities of the prepared materials were tested
in the batch epimerization of glucose to mannose. The hetero-
polyacid-based catalysts exhibited better performances than
the bulk molybdenum oxide (Table 1 and Table S1), as expect-
ed on the basis of previous evidence.[22] Interestingly, the ex-
change of protons by cesium or silver cations did not influence
the reaction rate significantly, in line with the fact that protons
do not partake in the reaction,[28] but the material became less
soluble and only 13–21% of the molybdenum leached from
the solids into the reaction mixture.
The immobilization of molybdic acid onto solid supports led
to inferior (IER carrier), similar (SiO2 carrier), or doubled (C carri-
er) activity. The enhancement in the turnover frequency (TOF)
in the latter case (Table 1) is possibly due to a better dispersion
of the active phase. The amount of Mo leached varied over
a very broad range. Specifically, the maximum (61%) was ob-
served in the case of the silica-supported solid and the mini-
mum (3%) for H-HPA/IER. This indicates that ionic interactions,
which were expected to be the only means for immobilization
onto the IER, are most beneficial to anchor the active phase in
a stable manner, whereas weak dipolar interactions, such as
those acting in the case of silica, are ineffective. Both mecha-
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Table 2. Performance of Cs-HPA/C in the epimerization of arabinose and
xylose.[a]
[b]
[d]
Reaction
Xeq
TOF[c]
[hꢀ1
Sepimer
[%]
[%]
]
arabinose$ribose
xylose$lyxose
41.2
52.7
54.3
48.2
96.6
98.1
[a] Reaction conditions: T=333 K, [arabinose, xylose]=0.28m, (arabinose,
xylose)/Mo=50, t=30 min. [b] Equilibrium conversion obtained at t=
16 h. [c] Based on Mo. [d] Selectivity to ribose or lyxose from arabinose
and xylose, respectively.
carbon has been reported to display the highest activity in this
reaction, although its selectivity to mannitol is limited by the
sustained formation of the epimeric alcohol sorbitol. A more
selective process has been attained by alloying this element
with other metals.[17] To choose the most suitable material, we
thus prepared a 5 wt% Ru/C catalyst as well as bimetallic sys-
tems comprising the same amount of Ru and 1 wt% Sn, Cr, La,
or Pd by incipient wetness. As shown in Table 3, the actual
Table 3. Characterization data of the ruthenium-based catalysts.
[c]
[d]
[e]
Catalyst
Ru[a]
[wt%]
M[b]
[wt%]
Vpore
SBET
DCO
[%]
[mLgꢀ1
]
[m2 gꢀ1
]
Ru/C
4.8
5.1
4.9
4.8
5.0
–
0.58
0.61
0.53
0.55
0.57
912
956
988
973
934
61
54
58
60
67
RuSn/C
RuCr/C
RuLa/C
RuPd/C
1.0
0.9
1.0
1.0
[a] ICP-OES. [b] XRF. [c] Volume of N2 adsorbed at p/p0 =0.99. [d] BET
method. [e] Ru dispersion determined by CO pulse chemisorption.
Figure 2. (a) Glucose conversion (relative to the equilibrium) as a function of
temperature over Cs-HPA/C. (b) Variation in the molybdenum content and
the molar molybdenum-to-phosphorous ratio upon consecutive batch runs
over H-HPA/C and Cs-HPA/C at 333 K. (c) Glucose conversion (relative to the
equilibrium) versus time-on-stream during continuous experiments over Cs-
HPA/C at 363 K.
metal loadings were determined to be close to the nominal
values. The porous properties of the support were not sub-
stantially modified upon deposition of the active phase. No re-
flections attributed to any of the metals were observed in the
XRD patterns of the solids (Figure S1b), which was indicative
of high dispersion. The latter was determined for Ru to be in
the 54–67% range on the basis of CO chemisorption. Addition-
ally, TEM analysis of Ru/C (Figure 3a) visualized very small met-
allic particles with diameters less than 5 nm.
previously reported materials. The used catalyst was analyzed
by transmission electron microscopy (TEM)-EDS (Figure 1b),
which showed that the fine distribution of the active phase
was preserved. The slightly decreased intensity of the Cs, Mo,
and P signals in the map of the used sample is in line with
leaching (Table 1). Finally, Cs-HPA/C was evaluated in the epi-
merization of arabinose to ribose and of xylose to lyxose. In
both cases, high selectivities were attained (Table 2), and the
turnover frequencies were similar to that obtained in the con-
version of glucose, which confirmed the versatility of this cata-
lyst with respect to the nature of the saccharide substrate.
Testing of these catalysts in the hydrogenation of fructose
surprisingly revealed that the presence of any of the second
metals did not improve the mannitol/sorbitol ratio (Figure 3b)
and reduced the activity. The discrepancy between our data
and earlier evidence may originate from the different reaction
conditions applied.[17] On the basis of these results, further
studies were conducted over the simple Ru/C catalyst. Firstly,
the dependence of mannitol selectivity on the temperature
and hydrogen pressure was explored. Although very different
operating conditions were investigated (Figure 3c), only slight
changes in the mannitol selectivity were observed, which was
the highest below 0.7 MPa and at 313–343 K. On the other
hand, the conversion increased monotonously with the tem-
Design of the hydrogenation catalysts
For the hydrogenation of glucose/mannose, xylose/lyxose, and
arabinose/ribose mixtures obtained by epimerization of the
first more naturally abundant sugar over molybdate-based ma-
terials, the catalyst selection relied on literature studies on the
reduction of fructose to mannose. Ruthenium supported on
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