A rapid and facile preparation of methyl 4,6-O-benzylidene-α-D-glucopyranoside and some related compounds

Article abstract of DOI:10.1081/SCC-120015781

A simple and rapid benzylidenation procedure for preparing the title compound and other related derivatives using tin(II) triflate and other triflate salts as catalysts is described.

Full text of DOI:10.1081/SCC-120015781

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A Rapid and Facile Preparation of Methyl 4,6- O -
Benzylidene-α-d-glucopyranoside and Some Related
Compounds
a
a
a b
Cosam C. Joseph , Prof. Binne Zwanenburg & Gordon J. F. Chittenden
a
Department of Organic Chemistry , NSR Center , University of Nijmegen , Toernooiveld,
Nijmegen, The Netherlands
b
Department of Chemistry , University of Dar es Salaam , P.O. Box 35061, Dar es Salaam,
Tanzania
Published online: 17 Aug 2006.
To cite this article: Cosam C. Joseph , Prof. Binne Zwanenburg & Gordon J. F. Chittenden (2003) A Rapid and Facile
Preparation of Methyl 4,6- O -Benzylidene-α-d-glucopyranoside and Some Related Compounds, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:3, 493-497, DOI: 10.1081/SCC-120015781
To link to this article: http://dx.doi.org/10.1081/SCC-120015781
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 3, pp. 493–497, 2003
A Rapid and Facile Preparation of Methyl
4
,6-O-Benzylidene-a-D-glucopyranoside
and Some Related Compounds
Cosam C. Joseph, Binne Zwanenburg,*
#
and Gordon J. F. Chittenden
Department of Organic Chemistry, NSR Center, University of
Nijmegen, Toernooiveld, Nijmegen, The Netherlands
ABSTRACT
A simple and rapid benzylidenation procedure for preparing the title
compound and other related derivatives using tin(II) triflate and
other triflate salts as catalysts is described.
A benzylidene acetal function is the group of choice for protecting
the C-4/C-6 hydroxyl groups of glycopyranosides when subsequent reac-
*
Correspondence: Prof. Binne Zwanenburg, Department of Organic Chemistry,
NSR Center, University of Nijmegen, Toernooiveld, 6525 ED Nijmegen, The
Netherlands; E-mail: zwanenb@sci.kun.nl.
#
Current address: Department of Chemistry, University of Dar es Salaam,
P.O. Box 35061, Dar es Salaam, Tanzania.
4
93
DOI: 10.1081/SCC-120015781
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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4
94
Joseph, Zwanenburg, and Chittenden
[
1]
tion of the remaining functions is required, e.g., 2,3-anhydro formation.
Methyl 4,6-O-benzylidene-a-D-glucopyranoside (1) is one of the most
frequently used intermediates in synthetic carbohydrate chemistry,
especially as a model substrate. The protecting function can be removed
easily under neutral conditions by hydrogenolysis.
Most of the procedures used for the introduction of this protecting
[
2]
function are based on the original method using benzaldehyde in the
presence of zinc chloride. Many of these are time consuming often requir-
ing reaction periods in excess of 24 h. There have been some improvements
[
3–6]
[3]
described
The use of benzaldehyde dimethyl acetal (a ,a -dimethoxy toluene) in the
presence of p-toluenesulfonic acid for the preparation of 1 and its corre-
and a brief history of the reaction has been presented.
0
0
[
7,8]
sponding b-D-anomer 2 has been recommended.
A more general
[
9]
procedure uses camphorsulfonic acid as a catalyst. These procedures
result in considerably shortened reaction periods but require careful
control of the conditions.
In this communication we describe a very rapid and simple method
for the synthesis of 1 which requires a very short reaction time (4–6 min)
and a minimum of workup. The reaction was also applied to some other
glycosides.
Treatment of a stirred mixture of methyl-a-D-glucopyranoside (3)
and benzaldehyde dimethylacetal (1.05 equiv.) in boiling 1,4-dioxane

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4
,6-O-Benzylidene-a-D-glucopyranoside
495
with tin(II) triflate (0.30 mol%) resulted in the rapid dissolution of the
substrate 3 (4–6 min), when analysis (TLC) indicated consumption of 3.
The cooled neutralized mixture was concentrated in vacuo and the resi-
due recrystallized to give pure 1 (78%). Compound 1 was not produced
when benzaldehyde was used in place of the dimethylacetal. Various
other triflate salts were also effective in the formation of 1; Sc(Tf )3
(
72%), In(Tf ) (76%), Yb(Tf ) (79%), and Lu(Tf ) (70%). There has
3 3 3
[
10,11]
been increasing use of these salts as powerful Lewis acids.
application in a very wide variety of organic reactions.
They find
The use of other solvents, e.g., ethyl acetate and 1,2-dimethoxyethane
resulted in longer reaction times and decreased yields.
[
14]
The reaction was then applied to the glycosides 2 and 4.
The
corresponding benzylidene derivatives 5 (81%) and 6 (75%), respectively,
were successfully obtained. Attempts to apply the reaction for the selec-
tive benzylidenation of the mannoside 7 were not successful. Analysis
(TLC) of the product obtained indicated that it was a mixture of
unreacted 7, a monoacetal, and diastereoisomeric diacetals and offered
no improvement over pre-existing procedures for benzylidenating this
glycoside.
[14–19]
No attempts were made to separate the mixture.
The crude, uncrystallized compound 1 was sufficiently pure to
continue with the preparation of routine derivatives. Treatment of
crude 1 with acetic anhydride/pyridine gave the diacetate 8 (67%) and
with p-toluenesulfonyl chloride/pyridine the bis-tosylate 9 (70%) was
obtained.
The modifications described provide a simple and rapid route to
these useful intermediates.
EXPERIMENTAL
Optical rotations were determined with a Perkin Elmer automatic
polarimeter, model 241, on 1% solutions in chloroform. Melting
points were determined using a Buchi B-545 melting point apparatus,
¨
and are uncorrected. Thin layer chromatography (TLC) was performed
on pre-coated plates of silica gel 60 (Merck) using cyclohexane-1,2-
dimethoxyethane, (3:2) as irrigant. Detection was effected by 3%
ꢀ
H SO in ethanol followed by charring at 140 C. Compounds 2, 3, and
2
7
4
ꢀ
were obtained fromAcros and were dried at 100 C in vacuo prior
to use. All other reagents were of commercial quality and were used as
such.

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Joseph, Zwanenburg, and Chittenden
Methyl 4,6-O-Benzylidene-a-D-glucopyranoside (1)
A stirred mixture of compound 3 (9.70 g, 5 mmol) and benzaldehyde
dimethylacetal (7.9 mL, 5.25 mmol) in boiling 1,4-dioxane (60 mL) was
treated with tin(II) triflate (0.3 mol%). A clear solution was obtained in
ca 4–6 min whereon it was cooled, neutralized by addition of conc.
NH OH (1 mL) and concentrated in vacuo. The resultant material was
4
recrystallized fromwater–propan-2-ol (3:1, 28 mL ) containing 2 drops
ꢀ
of conc. NH OH to give compound 1 (11.0 g, 78%), m.p. 164–166 C,
4
ꢀ
[3,4,7]
ꢀ
ꢀ
[
ꢀ] þ108.6 , lit.
m.p. 166–167 C, [ꢀ] þ110 .
D
D
In another experiment, treatment of
the crude product with acetic anhydride-pyridine in the usual manner
a
portion (2 g) of
ꢀ
gave the diacetate 8 (1.9 g, 67%), m.p. 107–109 C (aq. EtOH),
ꢀ
ꢀ
[20]
ꢀ] þ70.3 ; lit. m.p. 109–110 C, [ꢀ] þ72 .
ꢀ
[
D
D
Treatment of another portion dissolved in dichloromethane (10 mL)
with a mixture of pyridine (10 mL) and p-toluenesulfonyl chloride (4.0 g) at
ꢀ
[5]
0
(
[
C and then at roomtemperature for 5 days
ꢀ
gave the bis-tosylate 9
ꢀ
ꢀ
[21]
2.33 g, 70%), m.p. 145–147 C (EtOH), [ꢀ] þ11.4 , lit.
147–148 C,
D
ꢀ
ꢀ] þ13 .
D
Methyl 4,6-O-Benzylidene-b-D-glucopyranoside (5)
Treatment of the glycoside 2 (1.94 g) in the manner described above
ꢀ
ꢀ
gave compound 5 (2.28 g, 81%), m.p. 204–207 C (EtOH), [ꢀ] ꢁ74.5 ,
D
[
8]
ꢀ
ꢀ
lit. m.p. 205–207 C, [ꢀ] ꢁ76 .
D
Benzyl 4,6-O-Benzylidene-b-D-galactopyranoside (6)
[12]
Compound 6 (2.97 g, 74%) was obtained fromcompound 4 using
ꢀ
ꢀ
[13]
the described procedure, m.p. 206–209 C (acetone), [ꢀ] ꢁ61 , lit. m.p.
D
ꢀ
ꢀ
2
09–210 C [ꢀ] ꢁ62.4 .
D
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. Freudenburg, K.; Toepffer, H.; Andersen, C.C. Ber. 1928, 61, 1758.
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Received in the USA February 21, 2002

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