Efficient and rapid experimental procedure for the synthesis of furan diol from d-glucal using ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2007.09.070

A new efficient and rapid experimental method and product isolation procedure as well as easy recyclable reaction media is expected to contribute to the development of a green strategy for the synthesis of furan diol from d-glucal. We determine the best conditions of reaction, minimizing the toxicity and finding an environmentally more acceptable process, using [Bmim][MSO₄]/InCl₃·3H₂O as a new solvent system under extremely mild conditions, providing high yields with a dramatic enhancement of reaction rate.

Full text of DOI:10.1016/j.tetlet.2007.09.070

Tetrahedron Letters 48 (2007) 7926–7929
Efficient and rapid experimental procedure for the synthesis
of furan diol from D-glucal using ionic liquid
Marta Teijeira,* Yagamare Fall, Francisco Santamarta and Emilia Tojo
Departamento de Quı´mica Orga´nica, Facultad de Quı´mica, Universidad de Vigo, 36200 Vigo, Spain
Received 9 July 2007; revised 4 September 2007; accepted 11 September 2007
Available online 15 September 2007
Abstract—A new efficient and rapid experimental method and product isolation procedure as well as easy recyclable reaction media
is expected to contribute to the development of a green strategy for the synthesis of furan diol from D-glucal. We determine the best
conditions of reaction, minimizing the toxicity and finding an environmentally more acceptable process, using [Bmim][MSO4]/
InCl3Æ3H2O as a new solvent system under extremely mild conditions, providing high yields with a dramatic enhancement of reaction
rate.
Ó 2007 Elsevier Ltd. All rights reserved.
2-(D-glycero-1,2-dihydroxyethyl)furan (2) is a potential
chiral building block used as an intermediate in the
organic synthesis of biologically significant products.1,2
Monosaccharides are extremely acid-labile and under
hydrolytic conditions lead to furans. Thus, in 1966 the
first transformation of D-glucal (1) to optically active
furan diol 2 (Scheme 1) was reported, using H2O/HOAc
at 170 °C of temperature in moderate yield (50%).3,4
zation to a five-membered ring and dehydration fur-
nished the furan ring.6 More recently, relatively less
toxic and efficient catalysts have been reported.7 The
use of InCl3Æ3H2O on D-glucal or its epimer D-galactal
in acetonitrile for 2.5 h at room temperature led to the
same product 2 in 82% yield.
At present, this reaction continues receiving wide atten-
tion. Thus, in 2004 perchloric acid supported on silica
gel as a new reagent system was introduced,8 but during
this reaction there appeared to be some furan diol race-
mization. Finally in 2005, montmorillonite KSF clay in
acetonitrile for 5–7 h at room temperature was reported
as a promoter for the conversion of glycals into furan
diols with high selectivity,9 searching for environmental
compatibility and recyclable catalyst.
Similarly, in 1975 this transformation obtained the high-
est yield for catalysis by toxic metal salt HgSO4 in con-
centrated H2SO4; its possible mechanism of elimination
was also discussed.5 Subsequently, by using Sm(OTf)3 or
RuCl2(PPh3)3 in the presence of H2O, which requires
relatively higher temperature (80–100 °C), the research-
ers suggested the probable nucleophilic attack of H2O
on D-glucal, opening of pyranose ring followed by cycli-
All of these synthetic procedures explained above have
been carried out or worked-up in classical volatile
organic compounds (VOCs) such as dichloromethane,
acetonitrile, ethyl acetate, hexane and methanol. How-
ever, in recent times, the room temperature ionic liquids
(RTILs) have a significant interest as new solvents in
the area of green synthesis.10,11 They have emerged as
a set of green designer solvents with unique properties
such as negligible vapour pressure, tuneable polarity,
high thermal stability and they can be easily recycled
without any significant loss of activity. They are excel-
lent media for catalytic processes12 and it has been
demonstrated that some reactions in RTILs show rate
acceleration and increased yield compared to VOCs.13
OH
OH
cat/solvent
OH
OH
O
O
OH
1
2
Scheme 1.
Keywords: Diols; Ionic liquids; Furans; Green-chemistry; Solvent
effects.
*
Corresponding author. Fax: +34 986 81 22 62; e-mail:
qomaca@uvigo.es
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.070

M. Teijeira et al. / Tetrahedron Letters 48 (2007) 7926–7929
7927
In view of the emerging importance of the RTILs used
-
as solvent systems,14 as novel alternative reaction media
for the immobilization of transition metal based cata-
lysts and Lewis acids,15 or more recently as clean reagent
and catalyst,16 our purpose in this Letter is to explore
the effect of RTILs for the synthesis of 2-(D-glycero-
1,2-dihydroxyethyl)furan 2 from D-glucal.
+
PF6
+
-
MeSO4
N
N
N
N
[Bmim][MSO4]
[Bmim][PF6]
Cl-
-
+
MeSO4
N
N
+
N
N
As part of our ongoing program on the synthesis of nat-
ural products using the oxidation of a furan ring with
singlet oxygen, we used chiral furan diol 2 as starting
material towards the synthesis of optically active bute-
nolide 317 (Scheme 2).
[Bnmim][Cl]
[Mmim][MSO4]
Scheme 3. RTILs structures with cations imidazolium derivatives.
The results presented in Table 1 show a dramatic
enhancement of the transformation rate of D-glucal to
optically active furan diol 2, compared to the method
reported without ionic liquids7 (entry 1) or to any other
classical procedures;3–6,8 besides similar high yields were
obtained (73–78% yields). It should be noticed that the
reaction time was reduced by 5 times with [Bmin][PF6]
(entry 2) and it was possible to reduce it up to 15 times
with [Bnmim][Cl] (entry 5). However, the fastest reac-
tion rate was observed with methylsulfate derivatives
(entries 3 and 4), where the transformation was almost
instantaneous in both RTILs. Therefore, we can say that
this new synthetic procedure described above—using
RTILs—contribute to better results of reaction rate
than the procedures previously reported, under extre-
mely mild conditions and high yields.
In our laboratory we synthesized 2 using D-glucal in the
presence of 10% InCl3Æ3H2O in acetonitrile at room
temperature.7
We selected the following RTILs: 1-butyl-3-methyl-
imidazolium hexafluorophosphate [Bmim][PF6], 1-butyl-
3-methylimidazolium methylsulfate [Bmim][MSO4],
1,3-dimethylimidazolium methylsulfate [Mmim][MSO4],
1-benzyl-3-methylimidazolium chloride [Bnmim][Cl]. All
these were synthesized and characterized in our labora-
tories18,19 (Scheme 3).
In a first study, the influence of RTILs in this transfor-
mation as catalyst promoter was established. We used
10% InCl3Æ3H2O and acetonitrile as catalyst and solvent
respectively at room temperature, under synthetic proce-
dures reported in the literature;7 nevertheless, an addi-
tional catalytic amount of RTIL (10%) was included
(entries 2–5; General procedure 1).20 The spectral data
of furan diol 2 were in accordance with the reported
data.7
On the other hand, we explored the absence of InCl3Æ
3H2O to establish the potential catalysis use of RTILs
in this reaction (entries 10–13; General procedure 2).21
The results clearly show an absence of catalytic effect,
even maintaining 48 h of reaction time.
Next, in order to evaluate RTILs as recyclable solvent
systems in this transformation, we substituted aceto-
nitrile for these green solvents (entries 6–9; General pro-
cedure 3).22 The treatment of D-glucal with InCl3Æ3H2O
(10%) in corresponding RTIL at room temperature
OTBDPS
OTBDPS
OH
O
O
O
3
2
OH
Scheme 2.
Table 1. Study of various RTILs in the synthesis of 2-(D-glycero-1,2-dihydroxyethyl)furan (2) from D-glucal
Entry
RTIL
Catalyst
Solvent
Reaction time
Yielda (%)
1
2b
—
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
InCl3Æ3H2O
—
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
—
—
—
—
CH3CN
CH3CN
CH3CN
CH3CN
2 h 30 min
30 min
Few seconds
Few seconds
10 min
15 min
15 min
6 h 30 min
24 h
48 h
48 h
48 h
48 h
82
73
78
77
75
5
79
70
68
—
—
—
—
[Bmin][PF6]
[Bmim][MSO4]
[Mmim][MSO4]
[Bnmim][Cl]
[Bmim][PF6]
[Bmim][MSO4]
[Mmim][MSO4]
[Bnmim][Cl]
[Bmim][PF6]
[Bmim][MSO4]
[Mmim][MSO4]
[Bnmim][Cl]
3b
4b
5b
6c
7c
8c
9c
10d
11d
12d
13d
—
—
—
a Yield refers to isolated furan diol 2 after purification by column chromatography. The structure of product 2 was characterized by 1H NMR and it
was in accordance with the reported data.7
b According to procedure 1.20
c According to procedure 3.22
d According to procedure 2.21

7928
M. Teijeira et al. / Tetrahedron Letters 48 (2007) 7926–7929
afforded furan diol 2 in 5–79% yields. Except for the
reaction in hydrophobic [Bmin][PF6] ion liquid—which
was the least efficient of all (yields 5%)—reactions of
the other ionic liquids (entry 7–9) proved to have high
yields, comparable to VOCs.3–8 The instability of the
PF6À anion towards hydrolysis in contact with moisture,
forming volatiles, including HF, POF3, etc. is well estab-
lished.23 Taking into account that indium salt must be
hydrated to react as catalyst in this reaction, the
above-mentioned effect undergone by hexafluorophos-
phate anion derivatives could be the reason of the low
yield obtained in procedure 3 (entry 6; yield 5%) when
compared to procedure 1 (entry 2; yield 73%). More-
over, the reaction time was reduced from 2 h 30 min,
when using acetonitrile as the solvent, to 15 min when
1-butyl-3-methylimidazolium derivatives (entries 6 and
7) were used. Yet, the substitution of cation 1-butyl-3-
methylimidazolium for 1,3-dimethylimidazolium (entry
8), increases the reaction time (6 h 30 min) considerably.
This could be due to the fact that dimethylimidazolium
cations have a more compact ionic structure than butyl-
methylimidazolium cations; the former being comprised
of two hydrogen-bonded cation–anion chains aligned in
opposite directions, hydrogen bonded together to form
ribbons.24 Probably, this effect makes RTIL’s co-
catalyst role difficult and so, a good connection between
InCl3ÆH2O–RTIL is not established. Nevertheless, it
should be necessary to report more examples to help
us explain this special behaviour of imidazolium cations
with alkyl substituents in methylsulfate derivatives.
Moreover, we observed that the high viscosity of
chloride derivative makes the stirring more difficult
and increases the reaction time (entry 9). Thus,
[Bmim][MSO4]/InCl3Æ3H2O solvent system proved to
be a more effective reaction medium for the synthesis
of furan diol 2 from D-glucal by playing the dual role
of the solvent as well as promoter, maintaining room
temperature and high yields.
ing an environmentally more acceptable process, using
[Bmim][MSO4]/InCl3Æ3H2O as a new solvent system.
This medium reaction was proved to be a more effective
reaction medium for the synthesis of furan diol 2 from
D-glucal 1 than the others previously reported, by play-
ing the dual role of the solvent as well as promoter under
extremely mild conditions and providing high yields.
Acknowledgements
We gratefully acknowledge financial support from
Xunta de Galicia (PGIDIT04BTF301031PR) and
´
the Spanish Ministerio de Educacion
y Ciencia
(MEC) (Project CTQ2004-0045). We acknowledge the
comments and suggestions of the referees who helped
to improve the quality of this manuscript and the
attention received from the editor.
References and notes
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17. Teijeira, M.; Lois Suarez, P.; Gomez, G.; Teran, C.; Fall,
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18. Pereiro, A. B.; Santamarta, F.; Tojo, E.; Rodriguez, A.;
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Finally, in seeking to explore the potential environmen-
tal benefits of our system, we next examined solvent
recycling. The recycling of the remaining oily RTIL
was possible by employing a non-aqueous work-up
(simple extraction of the furan diol 2 with THF or ethyl
ether) followed by removal of any traces of volatiles
from RTILs in vacuo. These ionic liquids can be
recycled and reused three times for subsequent reactions
without any loss of activity. For example, treatment of
D-glucal with [Bmim][MSO4]/InCl3Æ3H2O afforded
furandiol 2 in 79%, 77% and 77% yields over three runs.
Therefore, we also avoided a chlorinated solvent
(CH2Cl2), used in extraction process in classical proce-
dure,3–8 so that it could have an additional environmen-
tal benefit.
20. General procedure 1: To a stirred mixture of InCl3Æ3H2O
(0.27 mmol) and RTIL (0.27 mmol) in acetonitrile, was
added D-glucal (2.27 mmol) at room temperature. Stirring
was continued for the appropriate time. After completion
of the reaction as indicated by TLC, the reaction mixture
was concentrated in vacuo. The residue was suspended
into H2O and extracted with tBuOMe. The combined
organic extract was dried over Na2SO4, concentrated and
purified by column chromatography. Yields ranged from
73% to 78%.
In summary, this Letter describes a new experimental
method and product isolation procedure for transforma-
tion of D-glucal 1 to optically active furan diol 2, using
imidazolium RTILs. The notable feature of this proce-
dure is the dramatic enhancement of reaction rate when
RTILs are included in classical procedure with acetoni-
trile as the solvent. Moreover, we determined the best
conditions of reaction, minimizing the toxicity and find-

M. Teijeira et al. / Tetrahedron Letters 48 (2007) 7926–7929
7929
21. General procedure 2: A mixture of RTIL (2 ml) and D-
glucal (2.27 mmol) in acetonitrile was stirred at room
temperature. The reaction was stirred for 48 h. The
absence of reaction evolution was indicated by TLC.
The ionic liquid was recycled by washing with tBuOMe or
THF and drying under vacuum. The combined organic
extracts were concentrated to afford D-glucal.
was indicated by TLC. The residue was extracted with
tBuOMe or THF. The combined organic extracts were
concentrated and purified by column chromatography.
Yields ranged from 5% to 80%. The ionic liquid was
recycled by drying under vacuum.
23. Swatloski, R. P.; Holbrey, J. D.; Rogers, R. D. Green
Chem. 2003, 5, 361.
22. General procedure 3: To a stirred mixture of InCl3Æ3H2O
(0.27 mmol) in RTIL (2 ml), was added D-glucal
(2.27 mmol) at room temperature. Stirring was continued
for the appropriate time. The completion of the reaction
24. Holbrey, J. D.; Reichert, W. M.; Swatloski, R. P.; Broker,
G. A.; Pitner, W. R.; Seddon, K. R.; Rogers, R. D. Green
Chem. 2002, 4, 407.