Application of oxone immobilized on montmorillonite for an efficient oxidation of mannose thioglycoside

Article abstract of DOI:10.1007/s00706-013-0964-0

A new solid system based on montmorillonite supported oxone has been developed and used for the oxidation of thiomannoside. The oxidation properties of oxone immobilized on montmorillonite were affected by polarity of the solvent, resulting in the different sulfoxide to sulfone ratios as the products. Toluene was the only solvent favouring sulfone formation over sulfoxide. X-ray crystal structures of the starting compound as well as the corresponding sulfoxide (major epimer Rs) and sulfone are also reported. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-0964-0

Monatsh Chem (2013) 144:969–973
DOI 10.1007/s00706-013-0964-0
ORIGINAL PAPER
Application of oxone immobilized on montmorillonite
for an efficient oxidation of mannose thioglycoside
ˇ
Monika Polakova Lubos Jankovic
•
•
´
Lenka Kuckova Jozef Kozısek
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•
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Received: 13 December 2012 / Accepted: 10 March 2013 / Published online: 15 May 2013
Ó Springer-Verlag Wien 2013
Abstract A new solid system based on montmorillonite
supported oxone has been developed and used for the
oxidation of thiomannoside. The oxidation properties of
oxone immobilized on montmorillonite were affected by
polarity of the solvent, resulting in the different sulfoxide
to sulfone ratios as the products. Toluene was the only
solvent favouring sulfone formation over sulfoxide. X-ray
crystal structures of the starting compound as well as the
corresponding sulfoxide (major epimer Rs) and sulfone are
also reported.
sulfoxides have previously been widely used as glycosyl
donors [1, 2]. Although they are able to react under mild
conditions [3–5], their frequency of usage as glycosyl
donors has been decreased due to a development of the
thiol activation protocol that became a more convenient
glycosylation alternative [6–9]. Nevertheless, carbohydrate
sulfoxides still represent an interesting subject of choice in
the synthesis of new derivatives with biological effects
[10]. Sulfones have been synthesized for this purpose [10,
11], which moreover may function as the intermediates, for
example in C–C bond formation and stereocontrolled
group transformations [12, 13].
Keywords Carbohydrates Á Glycosides Á Oxidation Á
Solid support Á X-Ray structure determination
Due to the importance of sulfoxides as well as sulfones,
various methods for their synthesis have been developed
and reported. Both are prepared by an oxidation of the
corresponding thioglycoside. For this purpose a number of
oxidation agents have been employed. Among them the
most common agent is mCPBA [10, 14–16]. Its use,
however, is restricted by a limited solubility in dichloro-
methane and tedious removal of the reaction byproduct (m-
chlorobenzoic acid). Moreover, a strict temperature control
(below -30 °C) is required for sulfide oxidation to sulf-
oxide, i.e., to prevent overoxidation to sulfone. Various
sulfides have been transformed to sulfoxides by means of
other oxidation agents, e.g., magnesium monoperoxyphth-
alate (MMPP) [17], NaIO4 [17], tert-butyl peroxide [18],
oxone [18, 19], and hydrogen peroxide and AcOH or Ac2O
either in the presence or in the absence of urea [20].
Likewise, sulfones have been produced with the aid of
numerous oxidants, such as RuCl3/NaIO4 [21], dim-
ethyldioxirane [22], monoperoxyphthalic acid [23], oxone
[15], OsO4/tertiary amine N-oxide [24], KMnO4/
CuSO4Á5H2O [25], and HOFÁCH3CN complex [26].
Introduction
Thioglycoside derived compounds, glycosyl sulfoxides and
sulfones are valuable intermediates as well as target com-
pounds in the field of carbohydrate chemistry. The
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-0964-0) contains supplementary
material, which is available to authorized users.
´
´
M. Polakova (&)
Institute of Chemistry, Center for Glycomics, Slovak Academy
´
´
of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia
e-mail: monika.polakova@savba.sk
ˇ
L. Jankovic
ˇ
Institute of Inorganic Chemistry, Slovak Academy of Sciences,
´
´
Dubravska cesta 9, 845 36 Bratislava, Slovakia
´
ˇ´ˇ
L. Kuckova Á J. Kozısek
Institute of Physical Chemistry and Chemical Physics,
The use of many oxidation agents is restricted by their
solubility in polar solvent(s) only and/or poor oxidation
´
Slovak University of Technology, Radlinskeho 9,
812 37 Bratislava, Slovakia
123

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M. Polakova et al.
970
properties when used alone. These limitations can be
sometimes overcome by combining the agent with a ‘‘wet’’
solid support, which mediates oxidant reactivity in a rela-
tively non-polar solvent, such as dichloromethane [27].
Matrices having high specific surface area, in particular
aluminum oxide and silica, are often chosen as the oxidant
supports. Besides, bentonite [28], kaolin [29], and acidic
montmorillonite K-10 [29] have also been shown to
enhance the oxidant chemical reactivity.
previously been prepared by another procedure [10], were
used as the standards.
There was no reaction observed in the solvents lacking
either the substrate or the oxidation agent. Depending on
the oxidation conditions used, sulfide 1 afforded the cor-
responding sulfoxide 2 (as an epimeric mixture) and
sulfone 3 as products, accompanied with some amount of
unreacted starting material (Scheme 1). The results of the
conversion of sulfide 1 in the solvents used are summarized
in Table 1.
There are several applications of the use of solid sup-
ports for the oxidation of carbohydrate based sulfides. The
first one comprises an adsorption of MMPP, NaIO4, or
oxone on dry aluminum oxide or silica, followed by its
moistening with an appropriate amount of water before the
addition of sulfide solution [17]. Alternatively, the solid
support is fully swallowed with water followed by an
addition of the sulfide in an organic solvent and oxidant
(oxone or 70 % aq. tert-butyl peroxide) thereto [18]. In
addition, silica gel may be suspended in the organic solvent
intended to be used for the reaction, that is started by the
oxidant dissolved in water, e.g., 30 % hydrogen peroxide
[20].
As first, the reaction was screened in non-polar solvent
toluene. The absence of solid support led to a low yield of
the products (Table 1, entries 1, 2). Supported reagent
without water facilitated the reaction slightly better, pro-
viding 2 and 3 in a ratio of 3.8:1 in overall 24 % yield
(entry 3). Interestingly, addition of water (entry 4) signif-
icantly accelerated the oxidation, but also dramatically
changed its selectivity favouring formation of sulfone 3
(59 %) over sulfoxide 2 (37 %) (ratio 2:3 = 1:1.6). Pro-
longation of the reaction time (48 h) led to a further
increase in sulfone yield (entry 5) giving 2 and 3 in a ratio
of 1:3.6. Another examined solvent was polar aprotic
dichloromethane, which has only been employed in the
previous studies [14, 15]. When oxone alone was used,
sulfide 1 remained almost completely intact (entry 6).
Neither the presence of water (entry 7) nor supported
reagent alone (entry 8) promoted oxidation. The reaction
was enhanced by simultaneous addition of the supported
reagent and water when sulfoxide 2 along with sulfone 3
was yielded in a ratio of 5.1:1 and 3 % of unreacted 1 was
left (entry 9). In summary, the use of water immiscible
solvents resulted in an efficient oxidation only in the
presence of both water and the support.
Smectites, i.e., clay nanoparticles with a layer structure,
including montmorillonite, have specific surface areas
similar to that of silica and aluminum oxide. The smectites
are, thus, an interesting alternative to the more common
reagent supports, although so far there is no information
about their application as the support for oxidation agents
in the field of carbohydrate chemistry. In this paper we
report on a new solid phase system being prepared by
oxone adsorption from aqueous solution to montmorillon-
ite. For its evaluation, the mannoside having 2-phenylethyl
function as aglycone has been selected as a substrate since
the glycosides with phenylalkyl aglycone in its oxidized
forms are valuable compounds in a design of potential
glycosidase inhibitors [10, 30].
The course of oxidation reaction was also monitored in
other polar solvents. Water fully miscible polar solvent,
aprotic acetone, yielded an excellent conversion of start-
ing sulfide 1 to sulfoxide 2 as a predominant oxidation
product. In more detail, oxidation of 1 promoted by oxone
alone afforded products 2 and 3 in the ratios 5.2:1 (entry
10) and 3:1 (entry 11) depending on the presence of
water, which reduced the selectivity of the reaction and
favoured the sulfone formation. The use of ‘‘dry’’ sup-
ported reagent (entry 12) led to a ratio of 17:1, i.e., the
Results and discussion
The oxidation ability of montmorillonite supported oxone
(supported reagent) was evaluated in four distinct solvents
at rt for 24 h under an inert atmosphere, either without or in
the presence of a small amount of water to reveal an
influence of the solvent on the reaction course and the
product distribution. For comparison, the same conditions
were applied for the mixtures containing oxone alone as an
oxidant. Two types of solvents, i.e., non-polar (toluene)
and polar aprotic (THF, DCM, acetone) were chosen. The
2-phenylethyl 2,3,4,6-tetra-O-acetyl-1-thio-a-D-mannopy-
ranoside (1) was chosen as a model compound and its
oxidized products, sulfoxide 2 and sulfone 3, having
Scheme 1
OAc
O
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
AcO
AcO
AcO
a or b
+
SOR
SR
SO2R
1
2
3
Rs/Ss
R = CH2CH2Ph
123

Application of oxone immobilized on montmorillonite
971
Table 1 Influence of reaction solvent, moisture, and the presence of montmorillonite as the oxone support on the reaction mixture composition
Entry
Solvent
Support
Water
Yield/%
Sulfoxide
Sulfone
Sulfide
1
Toluene
-
-
?
?
?
-
-
?
?
-
-
?
?
-
-
?
?
-
?
-
?
?
-
?
-
?
-
?
-
?
-
?
-
?
19
2
81
98
76
4
2
3
19
37
21
3
5
59
76
4
5
Toluene/48 h
3
6
Dichloromethane
97
97
96
3
7
3
8
4
9
81
83
74
85
83
15
74
13
56
16
16
25
5
10
11
12
13
14
15
16
17
Acetone
THF
Trace
Trace
10
2
15
85
19
87
39
7
5
The reactions were carried out in duplicate for 24 h at rt under an inert atmosphere. Values are the mean of two independent experiments
highest selectivity of sulfoxide 2 formation over sulfone 3
from all examined conditions where supported reagent
was employed. In contrast, the oxidation promoted by
‘‘moist’’ supported reagent (entry 13) gave a comparable
selectivity (ratio 5.5:1) as the reaction promoted by oxone
alone. It was shown that the presence of the support
helped prevent overoxidation to sulfone (10 % reduction).
Besides, regarding the yield, the presence of water did not
seem to be important in a water fully miscible solvent,
aprotic acetone. On the other hand, another aprotic sol-
vent, THF, which is moderately miscible with water, gave
a distinct pattern. In this case, sulfoxide 2 was again a
predominant oxidation product, but its formation was
efficient only in the presence of added water (entries 15,
Fig. 1 X-ray of major epimer (Rs) of 2 with crystallographic
17) and not significantly affected by the support (entries
numbering. Displacement ellipsoids are shown at the 30 % probabil-
ity level
16, 17).
In summary, the use of supported reagent led in the most
cases to the increased yield of the products. Although the
oxidation was not selective, it might not be a limitation for
the use of supported reagent, since the system is convenient
to handle and the products are easily separable by column
chromatography.
interval of 10:1–8.1 and not significantly affected either
by solvent or by the support. Slight improvement in the
selectivity was observed for supported reaction in DCM
(entry 9) giving Rs/Ss ratio of 14:1. It was possible to
obtain the major epimer by the crystallization from eth-
anol [10], therefore, its structure was also solved and
confirmed by X-ray crystallographic analysis (Fig. 1).
Besides, sulfide 1 and sulfone 3 were obtained as crys-
talline products [10] and their X-ray characterization
was carried out as well (supplementary data, Figures S2
and S3).
Under all conditions tested, sulfoxide was obtained as a
mixture of Rs and Ss epimers, similarly as we observed
previously in oxidation of the same substrate 1 with
mCPBA [10]. The ratio of the epimers was distinguished
based on integration of selected signals in 1H NMR
spectra [10]. In accordance with previous results [10, 31],
the diasteromeric ratio Rs/Ss was found to be in an
123

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M. Polakova et al.
972
Conclusion
freeze-dried for 3 days. Dry powdered catalyst obtained
from a single batch was used in all catalytic tests.
In conclusion, this study was focused on the investigation
of the capacity of montmorillonite clay as a support in
oxidation of carbohydrate substrate. It was demonstrated
that a new system, montmorillonite supported oxone, is
compatible with the solvents of different polarity, which
greatly affected substrate reactivity and oxidation reaction
selectivity. Both supported reagent and moisture are
required for an efficient oxidation in water-immiscible
solvents, DCM and toluene. The non-polar solvent, tolu-
ene, is the only one favouring sulfone formation over
sulfoxide, which was a predominant oxidation product
under all other conditions used. Its most selective forma-
tion was observed in acetone in the presence of ‘‘dry’’
supported reagent. The choice of clays, such as montmo-
rillonite, in combination with an oxone provides a new,
cheap, and promising alternative for the combination of a
solid support and the oxidation agent.
Oxidation of 2-phenylethyl 2,3,4,6-tetra-O-acetyl-1-
thio-a-D-mannopyranoside (1)
To 5 cm3 solvent (which in some cases contained 15 mm3
H2O corresponding to 20 % quantity (w/W) of montmo-
rillonite supported oxone) 25 mg thioglycoside 1 (0.052
mmol, 1 eq) and 37.5 mg oxone (0.06 mmol, 1.15 eq) or
75 mg montmorillonite supported oxone were added. The
reaction slurry was stirred at rt for 24 h under an inert
atmosphere. The solid was then removed by filtration
through a Celite pad and washed with 20 cm3 EtOAc. The
organic phases were pooled, washed with 10 cm3 saturated
aq. FeSO4, dried (Na2SO4), filtered, and concentrated. The
1
mixture was analyzed by H NMR spectroscopy (supple-
mentary data, Figure S1).
Acknowledgments This work was supported by the APVV-51-
046505, APVV-0202/10, VEGA-2/0159/12, VEGA 1/0679/11 and
VEGA-1/0962/12 grants and the Slovak State Program Project No.
´
2003SP200280203. Dr. Vladimır Puchart is appreciated for helpful
discussion.
The study of montmorillonite to function as a support
for other agents designed for an efficient oxidation of
carbohydrate based substrates is in progress.
Experimental
References
1H NMR spectra were recorded at 25 °C with a VNMRS
400 MHz Varian spectrometer. Chemical shifts are refer-
1. Taylor JG, Li X, Oberthuer M, Zhu W, Kahne DE (2006) J Am
Chem Soc 128:15084
2. Mochizuki T, Kondo Y, Abe H, Taylor CW, Potter BVL, Mat-
suda A, Shuto S (2006) Org Lett 8:1455
3. Martin-Lomas M, Khiar N, Garcia S, Koessler J-L, Nieto PM,
Rademacher TW (2000) Chem Eur J 6:3608
4. Lichtenthaler FW, Oberthuer M, Peters S (2001) Eur J Org Chem
20:3849
5. Crich D, Vinod AU (2003) Org Lett 5:1297
¨
6. Mannerstedt K, Ekelof K, Oscarson S (2007) Carbohydr Res
1
enced to TMS (d = 0.00, CDCl3 for H). The TLC was
performed on aluminium sheets precoated with silica gel
60 F254 (Merck). Anhydrous acetone, tetrahydrofuran, and
toluene were purchased from Aldrich. Dichloromethane
was dried (CaH2) and distilled before use. All reactions
were carried out under argon atmosphere. Powdered
Kunipia clay was supplied by the Kunime, Japan. Per-
oxymonosulfate, which is available as a triple salt
2KHSO5ÁKHSO4ÁK2SO4 and commercially known as ox-
one, was obtained from Aldrich and used as an oxidant.
Fraction of the Na? saturated particles having diameter
lower that 2 lm was separated from Kunipia bentonite
(Japan). The obtained fraction identified by X-ray diffrac-
342:631
7. Kaethip S, Demchenko AV (2011) J Org Chem 76:7388
´
8. Moume-Pymbock M, Crich DJ (2011) Org Chem 77:8905
9. De Jong A-R, Hagen B, van der Ark V, Overkleeft HS, Codee
´
JDC, van der Marel GA (2011) J Org Chem 77:108
ˇ
´ ´ ˇ
10. Polakova M, Sestak S, Lattova E, Petrus L, Mucha J, Tvaroska I,
´ ˇ
´
Kona J (2011) Eur J Med Chem 46:944
´
ˇ
tion and FT-IR, corresponded only to
a
Na?-
11. Ayers B, Long B, Sim E, Smellie IA, Wilkinson BL, Fairbanks
AJ (2009) Carbohydr Res 344:739
12. Taylor RJK, McAllister GD, Franck RW (2006) Carbohydr Res
341:1298
13. Leon EI, Martin A, Perez-Martin I, Quintanal LM, Suarez E
(2010) Eur J Org Chem 27:5248
montmorillonite. Its structural formula was Na0.35K0.01Ca
0.02(Si3.89Al0.11)(Al1.60Mg0.32Fe0.08)O10(OH)2ÁnH2O.
Preparation of montmorilonite supported oxone
´
´
hydr Res 345:1339
´ˇ
´ ˇ ˇ ´
14. Polakova M, Belanova M, Petrus L, Mikusova K (2010) Carbo-
Montmorilonite supported oxone was prepared by a slow
addition of cold (2–4 °C) 1 % oxone solution in distilled
water (1 g/100 cm3) to stirred cold (2–4 °C) 1 % disper-
sion of sodium exchanged Kunipia clay (1 g/100 cm3) in
distilled water (weight ratio oxone:clay = 1:1). After
mixing, the viscous slurry was frozen to -20 °C and
15. Griffin FK, Paterson DE, Murphy PV, Taylor RJK (2002) Eur J
Org Chem 7:1305
16. Singer M, Lopez M, Bornaghi LF, Innocenti A, Vullo D, Supuran
CT, Poulsen S-A (2009) Biorg Med Chem Lett 19:2273
17. Chen M-Y, Patkar LN, Lin C-C (2004) J Org Chem 69:2884
18. Chen M-Y, Patkar LN, Chen H-T, Lin C-C (2003) Carbohydr Res
338:1327
123

Application of oxone immobilized on montmorillonite
973
19. Crich D, Cai W, Dai Z (2000) J Org Chem 65:1291
20. Kakarla R, Dulina RG, Hatzenbuhler NT, Hiu YW, Sofia MJ
(1996) J Org Chem 61:8347
21. Fernandez-Mayoralas A, Marra A, Trumtel M, Veyrieres A,
Sinay P (1989) Carbohydr Res 188:81
27. Kropp PJ, Breton GW, Fields JD, Tung JC, Loomis BR (2000) J
Am Chem Soc 122:4280
28. Hirano M, Ueno Y, Morimoto T (1995) Synth Commun 25:3125
29. Hirano M, Tomaru J, Morimoto T (1991) Bull Chem Soc Jpn
64:3752
´
30. Polakova M, unpublished results
31. Aversa MC, Barattucci A, Bilardo MC, Bonaccorsi P, Giannetto
´
22. Gervay J, Flaherty TM, Holmes D (1997) Tetrahedron 53:16355
23. Belica PS, Franck RW (1998) Tetrahedron Lett 39:8225
24. Priebe W, Grynkiewicz G (1991) Tetrahedron Lett 32:7353
25. Agnihotri G, Misra AK (2006) Carbohydr Res 341:275
26. Morais GR, Humphrey AJ, Falconer RA (2008) Tetrahedron
64:7426
¨
P, Rollin P, Tatiboet A (2005) J Org Chem 70:7389
123