Environmentally benign preparation of benzylidene acetal of carbohydrate derivatives in PEG 600

Article abstract of DOI:10.1080/07328303.2011.585260

An environmentally benign preparation of benzylidene acetal of carbohydrate derivatives catalyzed by HClO₄-SiO₂ in PEG 600 as solvent has been developed. Yields were excellent in every case. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328303.2011.585260

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Environmentally Benign Preparation of
Benzylidene Acetal of Carbohydrate Derivatives in
PEG 600
Abhijit Sau & Anup Kumar Misra
To cite this article: Abhijit Sau & Anup Kumar Misra (2011) Environmentally Benign Preparation
of Benzylidene Acetal of Carbohydrate Derivatives in PEG 600, Journal of Carbohydrate
Chemistry, 30:1, 41-46, DOI: 10.1080/07328303.2011.585260
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Journal of Carbohydrate Chemistry, 30:41–46, 2011
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.585260
Environmentally Benign
Preparation of Benzylidene
Acetal of Carbohydrate
Derivatives in PEG 600
Abhijit Sau and Anup Kumar Misra
Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-
700054, India
An environmentally benign preparation of benzylidene acetal of carbohydrate deriva-
tives catalyzed by HClO4-SiO2 in PEG 600 as solvent has been developed. Yields were
excellent in every case.
Keywords Carbohydrate; Benzylidene acetal; HClO4-SiO2; PEG 600; Environmen-
tally benign
INTRODUCTION
Suitably functionalized monosaccharide derivatives act as useful intermedi-
ates in the synthesis of complex oligosaccharides. The choice of functional
groups for the protection of hydroxyl groups in carbohydrate skeleton plays
a significant role in the yield as well as stereo outcome of the glycoside for-
mation. Among several protecting groups used for simultaneous protection
of C-4/C-6 hydroxyl groups in carbohydrate derivatives, benzylidene acetal is
the one most frequently used.[1] The benzylidene acetal can be removed using
acidic hydrolysis[2] as well as neutral condition by hydrogenolysis.[3] One of the
important features of the benzylidene acetal is that it can be regioselectively
opened to generate a hydroxyl functionality for its application in oligosaccha-
ride synthesis.[4] A number of methods can be found in the literature for the
preparation of benzylidene acetal in carbohydrates. In most of the commonly
used methods benzaldehyde or its dimethylacetal derivative has been used for
Received February 4, 2011; accepted April 25, 2011.
Address correspondence to Anup Kumar Misra, Bose Institute, Division of Molec-
ular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata- 700054, India. E-mail: ak-
misra69@gmail.com
41

A. Sau & A.K. Misra
42
the acetal formation in the presence of a Lewis acid.[5–10] Benzylidene acetal
derivatives of carbohydrates have also been obtained under a basic condition
using dibromotoluene and pyridine.[11] Although the reported methods have
been used extensively, many of them have several shortcomings, such as long
reaction time, requirement of a large excess of reagents, use of a large quan-
tity of organic solvents, and chromatographic purifications. We envisaged that
the use of an eco-friendly solvent and stoichiometric amount of reagents could
offer a greener alternative for the preparation of benzylidene acetal of carbo-
hydrate derivatives. In recent years, polyethylene glycol (PEG) has been used
as an eco-friendly solvent in several organic transformations under green reac-
tion conditions.[12] We sought to explore the potential of PEG 600 as a reaction
medium for the preparation of benzylidene acetal derivatives using benzalde-
hyde dimethylacetal in the presence of an acidic catalyst. Since our aim is to
develop a clean reaction condition, we have used perchloric acid supported over
silica (HClO4-SiO2) as the heterogeneous solid catalyst,[13] which could be re-
moved from the reaction mixture by simple filtration. HClO4-SiO2 has been
developed by Chakraborti et al.[13] and used in several acid-catalyzed organic
transformations.[14] In this communication we describe the preparation of ben-
zylidene acetal of carbohydrate derivatives using benzaldehyde dimethylacetal
in the presence of HClO4-SiO2 as a catalyst in PEG 600 (Sch. 1).
OH
Ph
O
O
O
PhCH(OMe)2, HClO4-SiO2
PEG 600, r t, 6-7 h
HO
HO
O
HO
HO
HO
OR
OR
Scheme 1: Preparation of benzylidene acetal of carbohydrate derivatives using
benzaldehyde dimethylacetal in the presence of HClO4-SiO2 in PEG 600.
RESULTS AND DISCUSSION
In a set of initial experiments, methyl-α-D-glucopyranoside (1) was treated
with benzaldehyde dimethylacetal (1.1 mol equiv.) in the presence of a var-
ied quantity of HClO4-SiO2 (10–100 mg/mmol) in PEG 600 (1.0–2.0 mL/mmol)
at rt. After a series of reactions, it was observed that treatment of compound 1
with benzaldehyde dimethylacetal (1.1 equiv.) in the presence of HClO4-SiO2
(20 mg/mmol) in PEG 600 (2.0 mL/mmol) could furnish compound 2 in excel-
lent yield in 6 h at rt. After completion of the reaction, the pure product was
isolated by partitioning the reaction mixture with ethyl acetate and water. Fol-
lowing a similar reaction condition, a series of benzylidene acetal-containing
carbohydrate derivatives were prepared in excellent yield using PEG 600 as
reaction medium (Table 1). A large-scale preparation of benzylidene derivative

Carbohydrate Derivatives in PEG 600
43
Table 1: Preparation of benzylidene acetal of carbohydrate derivatives catalyzed
by HClO4-SiO2 in PEG 600 at room temperature
Entry
1
Substrates
Products
Time (h)
6
Yield (%)
90
Ref
[6]
OH
O
Ph
O
O
O
HO
HO
HO
OH
OMe
OH
OMe
1
HO
2
[15]
Ph
2
OH
6
76
O
O
O
HO
OMe
O
OH
HO
OMe
3
OH
4
Ph
[16]
[8]
3
4
6
6
70a
72
OH
O
HO
HO
HO
OH
O
O
O
HO
OMe
OSE
OMe
5
HO
6
Ph
OH
O
O
O
HO
O
OH
HO
OSE
7
OH
8
[17]
[8]
Ph
OH
O
5
6
6
7
70
68
O
O
O
HO
HO
HO
SEt
SEt
NPhth
NPhth
10
9
HO
Ph
OH
O
O
O
HO
OMp
O
OH
HO
OMp
11
OH
12
[18]
[19]
Ph
OH
O
7
8
6
6
77
72
O
O
O
HO
HO
HO
SPh
SPh
OH
OH
14
(4-MeO)Ph
13
OH
O
O
O
O
HO
HO
HO
OH
OMe
15
OH
OMe
1
[20]
[19]
(4-MeO)Ph
HO
9
6
70
OH
O
O
O
HO
OMe
O
OH
HO
3
OH
OMe
16
10
10
40b
OH
(4-MeO)Ph
O
O
O
O
HO
HO
HO
OH
OMe
15
OH
OMe
1
aTogether with some di-benzylidene derivative (∼15%).
bAt 80◦C.

A. Sau & A.K. Misra
44
of methyl α-D-glucopyranoside was also achieved using the optimized reac-
tion condition in excellent yield. The reaction condition has been successfully
extended for the preparation of 4-methoxybenzylidene acetal of carbohydrate
derivatives (Table 1, entry 8, 9). Uses of benzaldehyde in place of benzaldehyde
dimethylacetal require elevated temperature and did not produce satisfactory
yield (Table 1, entry 10). All known products gave acceptable spectral data that
matched the cited references.
In summary, an efficient eco-friendly reaction protocol has been devel-
oped for the preparation of 4,6-O-benzylidene acetal of carbohydrate deriva-
tives using benzaldehyde dimethylacetal in the presence of a catalytic amount
of HClO4-SiO2 in PEG 600. Use of HClO4-SiO2, a cheap heterogeneous cat-
alyst replacing hazardous, moisture-sensitive acidic catalysts, and PEG 600,
a biodegradable solvent, for the preparation of benzylidene derivatives will
certainly attract chemists for a practical eco-friendly alternative to existing
methods.
EXPERIMENTAL
General Methods
All reactions were monitored by thin layer chromatography over silica
gel-coated TLC plates. The spots on TLC were visualized by warming ceric
sulphate (2% Ce(SO4)2 in 2N H2SO4) sprayed plates in hot plate. Silica gel
1
230–400 mesh was used for column chromatography. H and 13C NMR were
recorded on Bruker Avance DRX 500 MHz using TMS as internal reference.
Chemical shift value is expressed in δ ppm. Optical rotations were measured
at 25◦C on a Jasco P-2000 polarimeter. Commercially available PEG 600 was
used in all reactions. HClO4-SiO2 was prepared following reported methods.
General Procedure for the Preparation of Benzylidene Acetal
of Carbohydrate Derivatives
To a mixture of substrate (1.0 mmol) in PEG 600 (2.0 mL) was added ben-
zaldehyde dimethylacetal (1.1 mmol) followed by HClO4-SiO2 (20 mg) and the
reaction mixture was allowed to stir at rt for the appropriate time (Table 1).
The reaction mixture was poured in water and the aqueous layer was extracted
with ethyl acetate. The organic layer was dried (Na2SO4) and evaporated to
dryness to give the desired product, which was crystallized from EtOH.
ACKNOWLEDGMENTS
A.S. thanks CSIR New Delhi for providing a Junior Research Fellowship. This
work was partly supported by Bose Institute, Kolkata.

Carbohydrate Derivatives in PEG 600
45
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