The effect of microwave irradiation on Mo(VI) catalyzed transformations of reducing saccharides

Article abstract of DOI:10.1016/j.carres.2006.05.007

Efficient microwave-assisted Mo(VI)-catalyzed transformations of the 10 most common aldoses are described. Both pentoses and hexoses were converted to the corresponding epimers in considerably shorter reaction times. The yields were comparable, or better compared to conventional synthetic methods.

Full text of DOI:10.1016/j.carres.2006.05.007

Carbohydrate Research 341 (2006) 2131–2134
Note
The effect of microwave irradiation on Mo(VI)
catalyzed transformations of reducing saccharides
*
´
´
Zuzana Hricovıniova
Institute of Chemistry, Slovak Academy of Sciences, SK-845 38 Bratislava, Slovakia
Received 3 February 2006; received in revised form 6 April 2006; accepted 8 May 2006
Available online 5 June 2006
Abstract—Efficient microwave-assisted Mo(VI)-catalyzed transformations of the 10 most common aldoses are described. Both pen-
toses and hexoses were converted to the corresponding epimers in considerably shorter reaction times. The yields were comparable,
or better compared to conventional synthetic methods.
Ó 2006 Elsevier Ltd. All rights reserved.
Keywords: Microwave; Isomerization; Saccharide; Mo(VI)-catalysis; Aldose/epialdose; Ketose/2-C-branched aldose
Microwave activations have been employed to accelerate
various organic reactions, including alkylations, nucleo-
philic substitutions, condensations, cycloadditions, pro-
tection and deprotection reactions with the advantages
of optimal use of material and energy, short reaction
times, high stereoselectivity and increased yields com-
pared to conventional methods.1,2 In particular this
approach has opened-up the possibility of optimizing
chemical reactions where equilibria were reached in a
very short time.
We have previously reported convenient synthetic
methods for the preparation of some rare carbohydr-
ates.3–6 The approach was based on molybdic acid-
catalyzed reactions7 and showed that the application
of a catalytic amount of molybdate ions significantly
simplified the synthesis of these compounds.4,5 The typ-
ical feature of Mo(VI)-catalyzed interconversions of
reducing sugars is both high stereoselectivity and yield.
We now further examine methodologies to optimize
the reaction conditions. The knowledge of structure of
Mo(VI) complexes8–11 and mechanism of isomerization
of aldose/epialdose12 and 2-ketose/2-C-(hydroxy-
methyl)branched aldose3,4 lead us to the idea that micro-
wave irradiation might have a considerable effect on
Mo(VI)-catalyzed saccharide transformations. The pres-
ent investigation is thus devoted to examining the effect
´
of microwave irradiation on the Bılik reaction in which
Mo(VI) complexes play a crucial role in isomerization of
reducing sugars.
A series of monosaccharides were isomerized in
aqueous media with catalytic amounts of molybdic acid
under the influence of microwave irradiation. These
substrates were chosen to allow the comparison of
microwave-assisted reactions with conventionally
heated reactions, with respect to stereo/chemoselectivity
as well as isomerization processes. The reactions were
performed under standardized reaction conditions to
permit the rigorous comparison of results and are sum-
marized in Table 1.
Table 1 shows the results of Mo(VI)-catalyzed isomer-
ization of aldoses under both conventional and micro-
wave heating. The comparison of equilibrium mixtures
obtained by conventional and microwave heating shows
that microwave irradiation markedly accelerated the
isomerization process and resulted in different equilibria
of the products.
Applying microwave irradiation of moderate power
and using a catalytic amount of molybdic acid resulted
in the reaction time decreasing from hours to minutes,
that is 60- to 200-fold shorter than with conventional
oil-bath heating. At the same time, improved yields were
*
Fax: +421 2 5941 0222; e-mail: chemhric@savba.sk
0008-6215/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.05.007

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Z. Hricovı´niova´ / Carbohydrate Research 341 (2006) 2131–2134
Table 1. Compositions of reaction mixtures of aldoses/epialdoses obtained by Mo(VI)-catalyzed isomerizations under conventional heating and
microwave irradiationg
Aldose
Conventional heatinga
MW filedb
Aldose/epialdose
Epialdose
Time (min)
Aldose/epialdose
Time (min)
Yieldh (%) aldose/epialdose
Ara
Rib
Xyl
Lyx
Glc
Man
Gal
Tal
Allo
Altro
Rib
Ara
Lyx
Xyl
Man
Glc
360
360
360
360
180
180
600
600
180
180
2:1c
3
3
3
3
3
3
3
3
3
3
2:1
1:1
65/30
47/45
62/31
30/63
69/27
27/65
73/22
53/40
50/42
70/24
1:2c
1.4:1c
1:1.4c
3:1d
1.9:1
1:1.9
2.5:1
1:2.5
3.2:1
1.4:1
1.2:1
2.8:1
1:3d
Tal
4:1e
Gal
Altro
Allo
1:4e
1.5:1f
1:1.5f
a Heating was carried out by conventional method.
bHeating was carried out by microwave irradiation.
c Ref. 13.
d Ref. 7.
e Ref. 14.
f Ref. 15.
g Reactions were performed in Pyrex tubes essentially following the literature procedures.
h Semi-preparative scale.
obtained for instance in the D-Gal/D-Tal conversion.
The microwave-enhanced Mo(VI)-catalyzed transfor-
mation of aldoses occurred with full stereospecificity
resulting in the formation of the corresponding epial-
dose. The catalytic system survived microwave irradia-
tion and conversion was achieved in a few minutes in
higher yields.
and epialdose at equilibrium was the same regardless of
the starting sugar. The microwave-assisted isomeriza-
tion reached thermodynamic equilibrium after 2–3
min. However, the true thermodynamic equilibrium
was not reached in several cases, because the prolonged
microwave irradiation (more than 10 min) led to the
decomposition of saccharides.
Microwave thermal effects originate from dielectric
heating as the consequence of intermolecular friction
and collisions. The latter phenomena result from polari-
zation in molecules due to dipole–dipole interactions be-
tween polar molecules and the electromagnetic field. As
water and alcohols are polar molecules, having high
dielectric losses, carbohydrates dissolved in water are
suitable systems for microwave irradiation and, conse-
quently, the reaction rate increased considerably. On
the other hand, two heating techniques yielded different
ratios of stereoisomers. So, there must be some differ-
ence in the susceptibility of the transition state of the
two stereoisomers to microwave heating. This would
be caused by differences in dipole moment or polari-
zability of the complex in the transition states. However,
details of the latter mechanism are not clear and would
require thorough theoretical study.
The comparative study of the progress of aldose/epi-
aldose isomerization under classical and microwave-
assisted conditions has shown the potential advantage of
this approach. There are also differences in the composi-
tion of the reaction products. The equilibria were shifted
to the aldose with the lower value of conformational
instability (e.g., during D-Glc/D-Man interconversion,
a larger amount of D-glucose was present). Under clas-
sical conditions, the equilibrium mixture of two isomeric
saccharides was obtained in 3–10 h. The ratio of aldose
In both cases the reaction equilibrium was shifted to
the saccharide with the lower value of conformational
instability, but the yield of the corresponding epialdose
was different. The results suggest that the ability of
molybdate ions to form complexes with reducing sugars
and promote the isomerization processes during micro-
wave irradiation are maintained and improved. Fast
complex formation, subsequent intramolecular rear-
rangements and release of the epialdoses from the
molybdate complexes resulted in good yields (Table 1).
The most studied example, D-Glc/D-Man and D-Man/
D-Glc epimerizations, was 60 times faster than the con-
ventional approach7 and the yield slightly improved in
favour of D-mannose (1:2.5 compared to 1:3). The same
is valid for the D-Gal/D-Tal system. However, the reverse
epimerization, D-Tal/D-Gal, was found to be less efficient
(1.4:1, compared to 1:4), thus D-galactose was formed in
considerably smaller amounts (though this type of inter-
conversion is less synthetically interesting). Different
final concentrations of epimers, obtained under
microwave-assisted interconversions, were also observed
for other aldose/epialdose conversions, namely, D-Ara/
D-Rib–D-Rib/D-Ara,
D-Allo/D-Altro–D-Altro/D-Allo
and D-Gal/D-Tal–D-Tal/D-Gal. Interestingly, a charac-
teristic feature of these aldoses is that they have cis con-
figuration of hydroxyl groups at C-3 and C-4. In
contrast, those that reached the same final concentration

Z. Hricovı´niova´ / Carbohydrate Research 341 (2006) 2131–2134
2133
after interconversion (epimers D-Xyl/D-Lyx–D-Lyx/
D-Xyl and D-Glc/D-Man–D-Man/D-Glc), have trans
configuration of hydroxyl groups. It thus appears, that
configuration at C-3 and C-4 carbons is an important
factor that influences the final equilibria of the products
obtained under microwave conditions. The reason for this
effect is not fully understood at present, but might origi-
nate in lower stability of cis-configured aldoses due to
steric effects at C-3 and C-4 carbons leading to easier
decomposition under microwave irradiation. In fact,
when attempting to reach the expected equilibria in cis-
configured saccharides using longer irradiation times
(15 min), partial decomposition was observed.
The efficiency of the method was also demonstrated in
the semi-preparative scale, where 1 g of compounds and
molybdic acid were dissolved in 50 mL of water. The
transformation occurred in 5 min reaching comparable
final concentrations. The yields and recovery of starting
material are listed in Table 1. The advantages of per-
forming these reactions under microwave heating are
evident in all cases in terms of shorter reaction times,
(reaction rate enhancements of up to 200 times as com-
pared to conventional methods), better yields, stereo-
selectivity and purity of obtained products. This
approach opens the way for the preparation of many
interesting sugar derivatives. Preliminary experiments
with mutual interconversions of 2-ketoses and 2-C-
hydroxymethyl aldoses under microwave irradiation
showed that these transformations were markedly faster
as well. For example, about 15% conversion to the
branched chain saccharide, D-hamamelose, was ob-
served after 3 min in the case of D-Fru/D-Ham intercon-
version. This is a considerably higher yield than that
obtained under classical conditions (about 7% after
4 h).3 It appears therefore that even branched chain sac-
charides can be prepared successfully under microwave
heating and further experiments with 2-ketoses are in
progress.
time and the selectivity of isomerization were studied.
Reactions were performed in Pyrex glass vessels. The
reaction volume filled not more than 1/5th of the total
volume of the vessel, allowing head space for pressure
build-up during the microwave treatment. Reaction
mixtures were irradiated in microwave field for different
lengths of time. The ratio of saccharides in the products
at equilibrium was determined from high-resolution
NMR spectra. The purity of isolated saccharides was
checked by NMR spectroscopy and by measuring of
optical rotation. NMR spectra were recorded on a
Bruker DPX 300 spectrometer equipped with a 5 mm
inverse broadband probe with a shielded z-gradient.
The experiments were carried out at 40 °C in D2O.
The proton and carbon chemical shifts were referenced
to external TSP. One-dimensional 1H and 13C NMR
spectra and two-dimensional COSY and HSQC were
used to determine 1H and 13C chemical shifts. All chem-
icals were of reagent grade and used without further
purification.
1.2. Reaction of the saccharide with Mo(VI) ions under
microwave irradiation
Aldose (10 mg, 0.056 mmol) was dissolved in D2O
(0.5 mL), and molybdic acid (1 mg, 0.006 mmol) was
added. The tube was exposed to microwave irradiation
for 3 min. The reaction mixture was analyzed by
NMR spectroscopy measurements and the ratio of
aldose/epialdose was determined by integration of
1
selected resonances in H NMR spectra.
1.3. Reaction of the saccharide with Mo(VI) ions with oil-
bath heating
Aldose (10 mg, 0.056 mmol) was dissolved in D2O
(0.5 mL), and molybdic acid (1 mg, 0.006 mmol) was
added. The tube was sealed and heated in an oil-bath
at 90–95 °C according to the literature data.7,13–15 The
reaction mixture was analyzed by NMR spectroscopy
measurements and the ratio of aldose/epialdose was
In summary, microwave heating has been shown to be
a very useful method for preparation of epimeric
aldoses. Dramatically shorter reaction times (about two
orders) were observed compared to conventional meth-
ods and yields were comparable (or higher), where short
reaction time also prevented decomposition. Such reac-
tion times in combination with the easy performance
and work-up also make the method attractive and appli-
cable on a semi-preparative scale.
1
determined by integration of selected resonances in H
NMR spectra.
1.4. Reaction of the saccharide with Mo(VI) ions under
microwave irradiation on a semi-preparative scale
A solution of saccharide (D-glucose) (1 g, 5.6 mmol),
molybdic acid (100 mg, 0.6 mmol) in water (50 mL)
was exposed to microwave irradiation. Samples
(0.5 mL) were taken at selected intervals (0.5, 1, 2, 3, 4
and 5 min) and treated with Amberlite IRA-400 in the
HCO3À form (3 mL) to remove the catalyst. The compo-
sition of the reaction mixture was determined by 1H
NMR spectroscopy to determine the ratio of sugars
present in equilibrium mixture. The rest of the reaction
1. Experimental
1.1. General methods
Experiments were conducted using domestic microwave
oven producing continuous irradiation operated at
0–800 W. The influence of power output upon the reaction

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3. Hricovıniova, Z.; Hricovıni, M.; Petrus, L. Chem. Papers
mixture was also treated batchwise with an excess of the
ion-exchange resin, filtered, washed with water and the
combined filtrates evaporated. The syrupy residue was
fractionated by column chromatography on Dowex
50 W X8 (200–400 mesh) in Ba2+ form with water as
eluent. Fractionization of the syrupy residue afforded
D-glucose (0.69 g, 69%) and D-mannose (0.27 g, 27%).
1998, 52, 692–698.
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4. Hricovıniova-Bılikova, Z.; Hricovıni, M.; Petrusova, M.;
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This research was supported by VEGA Grant No. 2/
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