Microwave-assisted rapid deacetalation of carbohydrates

Article abstract of DOI:10.1081/SCC-200066667

A simple and fast procedure to deprotect carbohydrate 4,6-di-O-benzylidene acetals was accomplished by using domestic microwave-oven irradiation in solvent-free conditions and with silica-gel-supported reagents. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200066667

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Microwave‐Assisted Rapid
Deacetalation of Carbohydrates
Mara Rubia C. Couri a , Erúzia A. Evangelista a
,
Rosemeire B. Alves a , Maria Auxiliadora F. Prado b
, Rossimiriam P. F. Gil a , Mauro V. De Almeida c
Délio S. Raslan a
&
a Departamento de Química, Instituto de Ciências
Exatas, Universidade Federal de Minas Gerais, Belo
Horizonte, Brazil
b Departamento de Produtos Farmacêuticos,
Faculdade de Farmácia, Universidade Federal de
Minas Gerais, Belo Horizonte, Brazil
c Departamento de Química, Instituto de Ciências
Exatas, Universidade Federal de Juiz de Fora, Juiz
de Fora, Brazil
Published online: 16 Aug 2006.
To cite this article: Mara Rubia C. Couri , Erúzia A. Evangelista , Rosemeire B. Alves ,
Maria Auxiliadora F. Prado , Rossimiriam P. F. Gil , Mauro V. De Almeida & Délio S.
Raslan (2005): Microwave‐Assisted Rapid Deacetalation of Carbohydrates, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:15, 2025-2031
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Synthetic Communicationsw, 35: 2025–2031, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200066667
Microwave-Assisted Rapid Deacetalation
of Carbohydrates
´
Mara Rubia C. Couri, Eruzia A. Evangelista, and
Rosemeire B. Alves
´ ˆ
Departamento de Quımica, Instituto de Ciencias Exatas, Universidade
Federal de Minas Gerais, Belo Horizonte, Brazil
Maria Auxiliadora F. Prado
ˆ ´
Departamento de Produtos Farmaceuticos, Faculdade de Farmacia,
Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Rossimiriam P. F. Gil
´ ˆ
Departamento de Quımica, Instituto de Ciencias Exatas, Universidade
Federal de Minas Gerais, Belo Horizonte, Brazil
Mauro V. De Almeida
´ ˆ
Departamento de Quımica, Instituto de Ciencias Exatas, Universidade
Federal de Juiz de Fora, Juiz de Fora, Brazil
´
Delio S. Raslan
´ ˆ
Departamento de Quımica, Instituto de Ciencias Exatas, Universidade
Federal de Minas Gerais, Belo Horizonte, Brazil
Abstract: A simple and fast procedure to deprotect carbohydrate 4,6-di-O-
benzylidene acetals was accomplished by using domestic microwave-oven
irradiation in solvent-free conditions and with silica-gel-supported reagents.
Keywords: Deacetalation, microwave, solvent-free
Received in the USA December 6, 2004
Address correspondence to Mara Rubia C. Couri, Departamento de Quımica,
ˆ ˆ
Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio
´
Carlos, 6627, 31270-901 Belo Horizonte, Brazil. E-mail: mrcouri@yahoo.com.br
2025

2026
M. R. C. Couri et al.
Protective groups play an important role in organic synthesis, mainly in the
field of carbohydrate chemistry. Carbohydrate hydroxyl groups are usually
protected by conversion into acetals, esters, and ethers. Efficient selective pro-
tection–deprotection is required for the appropriate manipulation of hydroxyl
groups in synthesis procedures.[1] Because faster and simpler methods are
always needed in organic synthesis, since 1986 microwave irradiation has
been increasingly used as a laboratory method to accelerate synthetic trans-
formations[2] in a clean, effective, and convenient way. Additionally,
heating reactants often results in higher yields and shorter reaction times.[3]
Reactions under “dry conditions” (in the absence of a solvent on solid
support with or without catalysts) were originally developed in the late
1980s.[4] Microwave heating has been proven to be of benefit, in particular
for reactions without solvents, which are often expensive, toxic, and difficult
to remove, specifically solvents with high boiling points.[4] Moreover, the
absence of solvent reduces explosion hazards in microwave-oven reactions.
During microwave-induced reactions under “dry conditions,” the reactants
are adsorbed onto the surface of alumina, silica gel, clay, and other
supports. Consequently, supported reagents afford safe and simple reaction
conditions and an opportunity to work with open vessels in domestic
microwave-oven rather than in expensive laboratory microwave systems.
Some papers on protecting-group chemistry have been published, but most
of them involve solvent-free techniques of deprotection of different protecting
groups.[5] We herein describe a method for fast deacetalation of carbohydrates
assisted by domestic microwave-oven heating and using silica gel as a solid
support with good yield.
The reactions were carried out by simply mixing 4,6-di-O-benzylidene
acetals with H2O/AcOH 1 : 1 (Scheme 1). The mixtures were adsorbed onto
silica gel and then heated in a domestic microwave oven in an open vessel
for 7 min. The results are summarized in Table 1. Deacetalation of the carbo-
hydrate shown in entry 2 (Table 1) with microwave heating in these conditions
was also tried, but it did not afford the deprotected product in a good yield in a
short reaction time. Thus, the deacetalation product was obtained by reaction
without support with a yield of 71%, as described in Table 1.
The workup procedure is reduced to the treatment with an appropriate
solvent (e.g., methyl alcohol or acetone), simple filtration, solvent
Scheme 1.

Table 1. Deacetalation of carbohydrates under microwave irradiation
AcOH/H2O1 : 1
(mL)
Carbohydrate/SiO2
(mmol : g)
Yield
(%)
Entry
Acetal carbohydrates
Products
1
4.50
0.56
1.44
0.355/2.0
93
71
2
3
0.042/a
0.114/1.0
81
(continued)

Table 1. Continued
AcOH/H2O1 : 1
(mL)
Carbohydrate/SiO2
(mmol : g)
Yield
(%)
Entry
Acetal carbohydrates
Products
4
9.56
2.72
2.72
0.757/2.0
0.216/2.0
0.216/2.0
90
83
81
5
6
aWithout support.

Deacetalation of Carbohydrates
2029
evaporation, and the removal of excess acetic acid and water under reduced
pressure. The products were obtained with good yields and purity for use in
1
the subsequent reactions. All products were confirmed by H NMR.
To the best of our knowledge, there is only one example of debenzylide-
nation of carbohydrates using microwave-oven irradiation in the literature.[2,5]
It describes the deacetalation of methyl 4,6-O-benzilidene-a-D-glucopyrano-
side with an 89% yield using MeOH/H2O at 1508C for 2 min. Heating was
performed with a laboratory microwave system and the reaction was carried
out in a closed vessel. In the method reported here, deacetalation of six carbo-
hydrates was accomplished by using a domestic microwave oven as an
irradiation source and an open vessel. Benzylidene removal was also
achieved with high yields and short time. It should also be noticed that the
deprotection reaction condition used in the present work was efficiently
selective. Although the carbohydrates used presented different substituting
groups, no secondary products were formed in any case.
In conclusion, we have developed a simple carbohydrate deacetalation
method in the absence of any organic solvent. This procedure furnished
“one-spot” TLC reactions with satisfactory yields and purity. Further-
more, heating with domestic microwave-oven irradiation has led to faster
deprotection than conventional heating.[6,7]
EXPERIMENTAL
1H NMR spectra were recorded using a BRUKER AVANCE DRX/400 in
CDCl3, CD3SO, or D2O with TMS as an internal standard. Melting points
were determined on a Mettler FP80HT apparatus and are uncorrected.
Microwave irradiation was carried out with a domestic microwave oven,
General Electric JEI 1145 AWA, at 2450 MHz.
General Carbohydrate Deacetalation Procedure
A mixture of carbohydrate and H2O/AcOH 1 : 1 (1 mmol/12.5 mL) adsorbed
onto silica gel (Table 1) was heated in a domestic microwave oven in an open
flask for 7 min. Subsequently, the reaction mixture was washed while stirred
with either methyl alcohol or acetone depending on the carbohydrate, and
silicagel was removed by filtration. Finally, the solvent and excess H2O/AcOH
were evaporated under reduced pressure to afford the deprotection product.
Compound (1b), methyl a-D-glucopyranoside. Mp: 165–1668C (lit.[8]
1
1698C); H NMR (D2O, 400 MHz): d 4.76 (1H, d, H-1, J1,2 ¼ 3.6 Hz), 3.82
(1H, dd, H-6a, J6a,5 ¼ 1.6 Hz, J6a,6b ¼ 12.3 Hz), 3.70 (1H, dd, H-6b,
J6b,5 ¼ 5.4 Hz, J6a,6b ¼ 12.3 Hz), 3.60 (2H, m, H-3 and H-5), 3.51 (1H, dd,
H-2, J2,3 ¼ 9.7 Hz), 3.71 (3H, s, OCH3), 3.32 (1H, t, H-4, J3,4
J4,5 ¼ 9.7 Hz).
¼

2030
M. R. C. Couri et al.
Compound (2b), methyl 2,3-di-p-toluenesulphonyl-a-D-glucopyranoside.
(This compound could not be crystallized).[9] 1H NMR (CDCl3, 400 MHz): d
0
0
0
0
7.76; 7.04 (2H, d, J2 ,3 ¼ 8.2 Hz; -OTs); 7.65; 7.32 (2H, d, J3 ,4 ¼ 8.2 Hz; -
OTs); 4.89 (1H, t, H-3, J3,4 ¼ 9.2 Hz); 4.77 (1H, d, J1,2 ¼ 3.4 Hz); 4.31
(1H, dd, H-2, J2,3 ¼ 9.2 Hz); 3.91–3.78 (1H, m, H-5); 3.76 (1H, t, H-6b,
J6b–6a ¼ 9.2 Hz); 3.64 (1H, t, H-6a, J6a–6b ¼ 9.2 Hz); 3.41 (1H, t, H-4);
3.26 (3H, s, OCH3); 2.44 (3H, s, H3C-Ph); 2.43 (3H, s, H3C-Ph).
Compound (3b), methyl 2,3-anhydro-a-D-allopyranoside. Mp: 98–1008C
1
(lit.[10] 103–1058C); H NMR (CD3SO, 400 MHz): d 5.20 (1H, d, -CHOH,
JOH,H-4 ¼ 6.5 Hz); 4.85 (1H, d, H-1, J1,2 ¼ 3.0 Hz); 4.55 (1H, t, –CH2OH,
JOH, H-6 ¼ 5.7 Hz); 3.70–3.49 (2H, m, H-4, H-6a); 3.50–3.40 (4H, m, H-2,
H-3, H-5, H-6b); 3.35 (3H, s, OCH3).
Compound (4b), methyl 2,3-anhydro-a-D-mannopyranoside. Mp: 83–
848C (lit.[11,12] 81–828C) 1H NMR (CD3SO, 400 MHz): d 5.20 (1H, d,
CHOH, JOH,H-4 ¼ 6.0 Hz); 4.77 (1H, broad singlet, H-1); 4.62 (1H, t,
CH2OH, JOH, H-6 ¼ 6.0 Hz); 3.46–3.32(2H, m, H-3, H-5), 3.46–3.38 (5H,
m, H-3, H-4, H-5, H-6a, H-6b); 3.41 (3H, s, OCH3); 3.26 (1H, d, H-2,
J2,3 ¼ 3.7 Hz).
Compound (5b), methyl 2,3-di-O-benzyl-a-D-galactopyranoside. Mp:
81–838C (lit.[13] 83–868C); 1H NMR (CDCl3, 400 MHz): d 7.41–7.24
(10H, m, 2 ꢀ C6H5); 4.80 (2H, d, 2 ꢀ PhCH, J ¼ 11.8 Hz); 4.67 (3H, m,
2 ꢀ PhCH,H-1); 4.03–3.74 (6H, m, H-2, H-3, H-4, H-5, H-6a and H-6b);
3.36 (3H, s, OCH3).
Compound (6b), methyl 2,3-di-O-benzyl-a-D-glucopyranoside. Mp: 78–
1
798C (lit.[1] 75–768C); H NMR (CDCl3, 400 MHz): d 7.36–7.24 (10H, m,
2 ꢀ C6H5); 4.99 (1H, d, PhCH, J ¼ 11.5 Hz); 4.73 (1H, d, PhCH,
J ¼ 12 Hz); 4.71 (1H, d, PhCH, J ¼ 11.5 Hz); 4.63 (1H, d, PhCH,
J ¼ 12 Hz); 4.59 (1H, d, H-1, J1,2 ¼ 3.5 Hz); 3.80–3.73 (3H, m, H-2, H-3,
H-4); 3.60-3.46 (3H, m, H-5, H-6a and H-6b), 3.35 (3H, s, OCH3).
ACKNOWLEDGMENT
´
The authors thank Conselho Nacional de Desenvolvimento Cientıfico e
´
Tecnologico (CNPq) for financial support.
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