Utilization of bio-based glycolaldehyde aqueous solution in organic synthesis: Application to the synthesis of 2,3-dihydrofurans

Article abstract of DOI:10.1039/c8gc04000a

Glycolaldehyde is a biomass-derived chemical compound available from cellulose or glucose. Until now, little attention has been devoted to its use towards value-added chemicals. To explore novel transformations of glycolaldehyde, in this work, a three-com

Full text of DOI:10.1039/c8gc04000a

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DOI: 10.1039/C8GC04000A
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ARTICLE
Utilization of bio-based glycolaldehyde aqueous solution in
organic synthesis: application to the synthesis of 2,3-
dihydrofurans
Received 00th January 20xx,
Accepted 00th January 20xx
Jing Xu,a Wenbo Huang,a Rongxian Bai,a Yves Queneau,d Francois Jerome*c and Yanlong Gu*a,b
DOI: 10.1039/x0xx00000x
www.rsc.org/
Glycolaldehyde is a biomass-derived chemical compound available from cellulose or glucose. Until now, little attention has
been devoted to its use towards value-added chemicals. To explore novel transformations of glycolaldehyde, in this work,
a three-component reaction of glycolaldehyde, indole and 1,3-dicarbonyl compound was developed to synthesize a class
of 3-(indol-3-yl)-2,3-dihydrofurans. Using glycolaldehyde diethyl acetal as glycolaldehyde source, the reaction can be
performed in organic solvents, and two catalytic systems were proved to be effective: (a) Sc(OTf)3/nitromethane; and (b)
.
Ni(ClO4)2 6H2O/acetonitrile. However, these conditions applied to the direct use of the bio-based glycolaldehyde aqueous
solution did not provide the dihydrofurans efficiently. To enable the use of the aqueous solution of glycolaldehyde, a
.
hitherto unreported deep eutectic solvent (DES) was developed by using FeCl3 6H2O and meglumine (N-methylglucamine)
.
as precursors. The FeCl3 6H2O/meglumine DES was characterized by FTIR, TGA and DSC, and the obtained results
demonstrated unambiguously the formation of a DES. This DES was found to be an efficient and a water-compatible
promoting medium for the above mentioned three-component reaction. A variety of 3-(indol-3-yl)-2,3-dihydrofuranfurans
.
were synthesized in good yields. The FeCl3 6H2O/meglumine DES system can also be recycled without significant loss of
activity.
condensation.3 Nowadays, glycolaldehyde is mostly used as food
browning agent.4 It was also proved to be an intermediate in the
formation of ethylene glycol or ethanolamine from glucose or
Introduction
In consideration of environmental issues and economic stress,
biomass conversion has become more attractive because energy,
fuels and chemicals/materials can be co-produced in the process
called biorefinery. Therefore, strategies and processes devoted to
the conversion of biomass have been the focus of intense research
by chemists recently.1 However, most of the biomass conversion
reactions involve the formation of water. For example, pyrolysis oil
derived from biomass contains 15-25 wt% water.2 In some cases,
the amount of water is so significant that it can affect notably the
quality of the main product. Glycolaldehyde is one of the valuable
biomass-derived platform molecules, and it can be produced by
hydrolysis of cellulose or glucose followed by a selective retro-aldol
cellulose.5 Because of its unique reactivity, bio-based
glycolaldehyde exhibits a great potential to be used in the synthesis
of fine chemicals. However, owing to the difficulty of removing
water in the bio-sourced product, it is necessary to consider using
directly the aqueous solution of glycolaldehyde in the downstream
value-added transformations.6 In this context, water-compatible
catalytic systems and water-compatible media, such as DES, should
be the best choices.
DESs (deep eutectic solvents) are generally composed of two or
three cheap and safe compounds. Intermolecular interaction of all
the components lead to the formation of deep eutectic mixtures
with one melting point lower than that of each individual
component. Most of present widely-used DESs is choline chloride
(ChCl)-based DESs.7 It is a cheap and biodegradable quaternary
ammonium salt which can be extracted from biomass. In
combination with hydrogen bond donors such as carboxylic acid,
polyols/sugars and amides, ChCl is liable for rapidly forming a DES.
The physico-chemical properties and applications of these DESs in
some areas, such as dissolution, extraction process,
electrochemistry and material chemistry, have been extensively
explored.8 DESs formed by zinc chloride are also reported. These
DESs are acidic, can thus be applied in organic synthesis as dual
solvents/catalysts.9 Some other metal halides were also used to
a. Key Laboratory of Energy Conversion and Storage, Ministry of Education, School
of Chemistry and Chemical Engineering, Huazhong University of Science and
Technology, Wuhan 430074, China. E-mail: klgyl@hust.edu.cn
b. State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute
of Chemical Physics, 730000, Lanzhou, China.
c. Institut de Chimie des Milieux et Matériaux de Poitiers, Ins Université de Poitiers,
ENSIP, 1 rue Marcel Dore, 86073 Poitiers cedex 9, France. E-mail:
francois.jerome@univ-poitiers.fr
d. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS),
Université de Lyon, CNRS, Université Lyon 1, INSA Lyon, CPE Lyon, UMR 5246,
Université Claude Bernard, Bâtiment Lederer, 1 Rue Victor Grignard, 69622
Villeurbanne, France.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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prepare DESs. However, until now, little attention has been devoted
to the rational design of task-specific DESs that allows an
individualization of their catalytic uses. We focused on designing
task-specific DESs for synthesis and catalysis uses.
6). Then, the effect of solvent was explored. Among all the
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solvents screened, nitromethane cleDarOlyI: 10s.1t0o3o9d/C8oGuCt040w0i0thA
acetonitrile in a near second place (entries 2 and 7). The
reaction proceeded sluggishly in 1,2-dichloroethane and
toluene, producing 4a only in moderate yields (entries 8 and
9). Ethanol was proven to be inappropriate for this reaction
(entry 10).
Among possible targets are the very interesting five-
membered furan and dihydrofuran rings which can be found in
a
fascinating array of bioactive natural products and
pharmaceutical compounds.10 Therefore, efficient synthesis of
these derivatives is of high interest and consequently many
procedures have been developed.11 We have paid much
attention to the ring embellishment and transformations of
furan or dihydrofuran derivatives in the past decade.12
Particularly, by combining a bifunctional aldehyde and a
nucleophilic indole together, some interesting approaches to
heterocyclic derivatives can be achieved.13 Glycolaldehyde
being a bifunctional nucleophilic and electrophilic species, it
can therefore be possibly used as precursor for synthesizing
some five-membered dihydrofurans. Considering also the bio-
based origin of glycolaldehyde, if a new synthesis reaction
forming a specific class of heterocycles were established, it
would provide suitable routes and options for value-added
transformation of biomass. Hence, we focused our effort on
this topic by investigating the direct use of glycolaldehyde
aqueous solution towards furans and we report herein our
preliminary results obtained in this endeavor.
Although the target dihydrofuran 4a can be synthesized in
good yield, owing to the use of nitromethane, which is a toxic
and
an
explosive
solvent,16
the
greenness
of
Sc(OTf)3/nitromethane system is thus far from satisfactory.
The significant solvent effect observed over Sc(OTf)3 catalyst
led us to scrutinize the catalytic activities of some other acids
in different solvent systems. From the viewpoint of industrial
uses, acetonitrile is much better than nitromethane although it
is still toxic. This can be witnessed by the wide uses of
acetonitrile in pharmaceutical synthesis.17 We therefore paid
our attention particularly to acetonitrile. It was found that, by
.
using Ni(ClO4)2 6H2O as catalyst (20 mol%), the reaction
proceeded very well at 80 °C. And 4a could be obtained in 79%
yield after 6 h of reaction (entry 11). But, the formation of 5a
was unavoidable. The reaction over Ni(OTf)2 catalyst
proceeded also smoothly. However, perhaps due to the easy
formation of 5a, the yield of 4a reached only 61% (entry 12).
.
For the reaction over Ni(ClO4)2 6H2O catalyst, solvent effect is
also significant, which can be verified by the results obtained
with toluene and ethanol, and those are inappropriate for this
reaction (entries 13 to 15). At this stage of our study, two
systems were identified to be suitable to implement the
synthesis of 4a: (A) Sc(OTf)3 (5 mol%)/nitromethane, with this
Results and discussion
Although glycolaldehyde is
a
commercially available
compound, but it is very expensive. Considering also the fact
that it is not stable under acidic conditions, we used
glycolaldehyde acetal, an easily available and inexpensive
system, the reaction can be performed at room temperature,
.
and finished within
1
h; and (B) Ni(ClO4)2 6H2O (20
reagent, as
a source of glycolaldehyde. Under acidic
mol%)/acetonitrile, with this system, the reaction has been
performed at 80 °C, and 6 h are needed to get a good reaction
yield (optimization of the reaction parameters, such as
temperature and reaction time, is given in SI, Table S1).
conditions, glycolaldehyde can be released via deacetalization
reaction.14 Initially, a mixture of glycolaldehyde diethyl acetal
1a, ethyl acetoacetate 2a and indole 3a was treated under the
conditions tabulated in Table 1. Theoretically speaking, the
molar ratio of 1a/2a/3a was 1/1/1 for the synthesis of the
target dihydrofuran 4a. Taking into account that a by-product,
ethyl 2-methyl-3-furancarboxylate 5a, might be formed
through a reaction of 1a and 2a,15 and the molar ratio of
1a/2a/3a was temporarily fixed at 2/2/1 with the aim of
obtaining higher 4a yields.
Table 1. Three-component reaction of 1a, 2a and 3a.a
OEt
+
OH
N
EtO
OEt
H
O
O
O
O
H
N
OEt
OEt
3a
1a
catalyst
solvent
+
O
O
+
5a
2a
4a
In the absence of catalyst, no reaction occurred after 1 h of
reaction at 80 °C in acetonitrile or nitromethane (Table 1,
entry 1). When Sc(OTf)3 was used as catalyst in conjunction
with using nitromethane as solvent, 3a consumed rapidly at
room temperature, and 4a was isolated in 81% yield after 1 h
of reaction (entry 2). Al(OTf)3 and Fe(OTf)3 were also able to
catalyze this reaction, but the yields of 4a were inferior as
compared with Sc(OTf)3 (entries 3 and 4). The formation of a
by-product 5a could be clearly observed in these cases, which
was partially responsible for the insufficient synthesis of 4a.
yield (%)b
entry
catalyst and specified conditions
4a
0
5ac
1
catalyst-free, in CH3CN or CH3NO2, 80 °C, 1 h
Sc(OTf)3 (5 mol%), CH3NO2, r.t., 1 h (method A)
Al(OTf)3 (5 mol%), CH3NO2, r.t., 1 h
0
2
81
50
63
0
0
3
16
14
0
4
Fe(OTf)3 (5 mol%), CH3NO2, r.t., 1 h
.
5
Ni(OTf)2 or Ni(ClO4)2 6H2O (5 mol%), CH3NO2, r.t., 1 h
PTSA (5 mol%), CH3NO2, r.t.,1 h
6
0
0
7
Sc(OTf)3 (5 mol%), CH3CN, r.t., 1 h
Sc(OTf)3 (5 mol%), DCE, r.t., 1 h
73
47
39
0
8
.
When Ni(OTf)2 and Ni(ClO4)2 6H2O were used, only unreacted
8
14
17
0
starting materials were recovered (entry 5). A strong Brønsted
acid, p-toluenesulfonic acid (TsOH), was also examined under
the identical conditions, but no product can be detected (entry
9
Sc(OTf)3 (5 mol%), Toluene, r.t., 1 h
Sc(OTf)3 (5 mol%), EtOH, r.t., 1 h
10
11
.
Ni(ClO4)2 6H2O (20 mol%), CH3CN, 80 °C, 6 h (method
79
12
2 | J. Name., 2012, 00, 1-3
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that a small amount of water has already induced intVoietwhAertriceleaOctniloinne
B)
DOI: 10.1039/C8GC04000A
system as the hydrate of the Ni(II) salt in method B. It should be
12
13
14
15
Ni(OTf)2 (20 mol%), CH3CN, 80 °C, 6 h
61
57
13
11
15
16
0
.
Ni(ClO4)2 6H2O (20 mol%), DCE, 80 °C, 6 h
mentioned that water is immiscible with nitromethane, and as a
result, a biphasic system can be formed after adding some amounts
of water with method A (the left picture in Figure 2). But, the
reaction with method B is still a homogeneous system (the right
picture in Figure 2). Whatever happens, after adding 7 mmol (0.13
g) of water into the reaction system, the yield of 4a sharply reduced
to < 20%. These results imply that methods A and B are both unable
to implement the synthesis of 4a by using an aqueous solution of
.
Ni(ClO4)2 6H2O (20 mol%), Toluene, 80 °C, 6 h
.
Ni(ClO4)2 6H2O (20 mol%), EtOH, 80 °C, 6 h
0
a: 1a (0.4 mmol), 2a (0.4 mmol), 3a (0.2 mmol), solvent (1.0 mL). b: Isolated yield, and
calculated with respect to 3a. c: Isolated yield, and calculated with respect to 1a.
The effect of catalyst amount on the model reaction was
then investigated. As shown in Figure 1, the performance of
the model reaction was influenced quite notably by the
bio-based glycolaldehyde as precursor. Therefore,
a water-
.
amount of Sc(OTf)3 or Ni(ClO4)2 6H2O. Increasing the
compatible catalytic system that enables the use of bio-based
glycolaldehyde is still appealingly needed.
concentration of these acid catalysts in general led to
improvement of the reaction yield. For Sc(OTf)3/nitromethane
system, this tendency is quite obvious when the amount of
Sc(OTf)3 is lower than 2.0 mol% (Figure 1, a). While the yield of
4a can be improved from 15% to 67% by increasing the loading
of Sc(OTf)3 catalyst from 0.5 mol% to 2.0 mol%, an increase of
the scandium loading from 2.0 mol% to 5.0 mol% gained only
14% of yield increase. Taking together with the mild conditions
and the short reaction time (1 h) of the method A, these
results imply that the catalytic activity of Sc(OTf)3 is quite high,
and a small amount of Sc(OTf)3 is sufficient enough to initiate
the reaction. Indeed, when 0.5 mol% of Sc(OTf)3 was used, the
yield of 4a can be improved to the same level by elongating
the reaction time to 12 h (See SI, Table S2). This was because
small reaction rate than deactivation of catalyst. In method B,
100
80
60
40
20
b
a
0
0
2
4
6
8
Water amount (mmol)
Figure 2. Effect of the water amount on the model reaction. (a)
.
Sc(OTf)3/nitromethane, r.t., 1 h (method A). (b) Ni(ClO4)2 6H2O/acetonitrile, 80
°C, 6 h (method B).
.
with Ni(ClO4)2 6H2O catalyst/acetonitrile system, 5.0 mol% of
On the other hand, DESs have gained much attention in the
past decade.18 Like ionic liquids19, DESs are generally less-
volatile and their properties can be finely tuned by changing
the component structures and the ratio of different
components. But they have notable advantages, such as easy
preparation, low cost and good recyclability. Therefore, DESs
have been widely used as eco-friendly and sustainable
alternatives to the conventional organic solvents in synthetic
chemistry. Some of DESs can be synthesized by using metal
halides as hydrogen bond acceptors (HBAs) in conjunction with
the uses of amides, carboxylic acids or polyols as hydrogen
bond donors (HBDs).20 This class of DESs are acidic, can thus be
applied in organic synthesis as dual solvents/catalysts. We
conjectured that acidic DESs might be suitable promoting
media for aforementioned three-component reaction with
high efficiency. To verify our hypothesis, a novel deep eutectic
catalyst is sufficient enough to provide over 60% of yield under
the standard conditions. Different from method A, the yield
cannot be improved further by simply elongating the reaction
(See SI, Table S2). Changing of the catalyst amount from 5.0
mol% to 20.0 mol% led to only 17% of yield increase.
(b)90
(a)100
80
80
60
40
20
0
70
60
50
0
1
2
3
4
5
0
5
10
15
20
25
Catalyst amount (mol%)
Catalyst amount (mol%)
Figure 1. Effect of the catalyst amount on the model reaction. (a)
.
.
Sc(OTf)3/nitromethane, r.t., 1 h (method A). (b) Ni(ClO4)2 6H2O/acetonitrile, 80
solvent (DES) was synthesized from FeCl3 6H2O and meglumine
°C, 6 h (method B).
at a molar ratio of 1:2 at 60 °C until a homogeneous liquid was
obtained.21
Given that bio-based glycolaldehyde is generally produced in
water, and is rather difficult to obtain in an anhydrous form with a
high degree of purity, a water-compatible system should be
preferable for updating bio-based glycolaldehyde to value-added
products. To this end, we then investigated the effect of water to
methods A and B for the synthesis of 4a. As evidenced by the
results in Figure 2, in a reaction in 0.2 mmol scale, addition of water
resulted in dramatic decrease of the reaction yield.
Sc(OTf)3/nitromethane seems more sensitive toward water than
The thereby obtained the DES was characterized by Fourier
Transform Infrared (FTIR) spectroscopy (Figure 3A). The FTIR
spectra of both DES and their two precursors (FeCl3 6H2O and
.
meglumine) were recorded and put together in order for us to
find any changes. The bottom blue line is for DES, the top black
.
line is for FeCl3 6H2O, and the meddle red line is for
meglumine. The peaks at about 2950 cm-1, 2850 cm-1 and 1450
cm-1 can be ascribed to C–H symmetric stretching, C–H
asymmetric stretching and the CH2 bending vibration,
respectively.22 The peaks at about 3327 cm-1 and 3239 cm-1
can be assigned to stretching vibration of N–H band and O–H
.
Ni(ClO4)2 6H2O/acetonitrile. It is reasonable considering the fact
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bond of meglumine.23 An intermolecular interaction between a glass transition temperature was observed at about -30 °C
View Article Online
.
.
DOI: 10.1039/C8GC04000A
FeCl3 6H2O and meglumine can be verified by the broaden for FeCl3 6H2O/meglumine DES.
peaks at around these areas. And the peaks at about 1087 cm-1
and 1054 cm-1 can be assigned to C–O stretching vibration of indole, glycolaldehyde diethyl acetal and ethyl acetoacetate as
meglumine. In FeCl3 6H2O/meglumine system, a slight red shift dual solvents/catalysts. Some well-known DESs were also
occurred, and the peaks appeared at 1078 cm-1 and 1038 cm-1, examined. In order to check the water compatibility of the
respectively. This result suggested that the DES are indeed newly developed DES catalytic system, water was also added
We then used the DES in the three-component reaction of
.
.
formed by the coordination between FeCl3 6H2O and (50 wt% with respected to the weight of DES). The reaction
meglumine. Moreover, at a loading below 50 wt%, the amount was performed at 60 °C in the presence of 5 mol% of DES-
of water has no significant effect on the formation of DES (see water mixtures. The obtained results were tabulated in Table
SI, Figure S1).24
2. No reaction occurred when ChCl/ethylene glycol (1:2)-H2O
was used (entry 1). This is quite reasonable as ChCl/ethylene
glycol DES was known as a neutral DES.28 When ZnCl2/ethylene
glycol (1:2)-H2O was used, 4a can be isolated in 14% yield
(A)
a
(B)
100
1615
3516
.
75
50
25
0
(entry 2). The reaction with FeCl3 6H2O/ethylene glycol (1:2)-
b
3239
3327
a
b
H2O gave nearly the same result (entry 3). In these DESs-
mediated reactions, the formation of 5a can be clearly
observed. A significant yield improvement was observed by
changing the HBD component from ethylene glycol to glycerol.
1087
1054
c
1038
1078
3359
4000
3000
2000
1000
0
200
400
600
800
.
-1
Temperature (C)
The reaction with FeCl3 6H2O/glycerol (1:2)-H2O gave the
Wavenumber (cm
)
desired 4a in 43% yield (entry 4). The side reaction toward the
formation of 5a was also improved, but not as much as the 4a-
(D)
(C)
b
a
1606
1460
forming
reaction.
A
novel
DES-water
mixture,
1
2
1029
1080
.
FeCl3 6H2O/meglumine (1:2)-H2O, can also promote the
reaction efficiently, and a fairly good yield of 4a, 46%, can be
obtained (entry 5). In order to further improve the reaction
3362
3362
1606
1460
1029
1080
yield,
we
tried
to
increase
the
loading
of
.
FeCl3 6H2O/meglumine (1:2)-H2O. When it was used in 15
mol%, the yield of 4a can be improved to 63% (entry 6). By
performing the reaction at 80 °C, a yield up to 73% can be
achieved (entry 7). In these cases, the formation of by-product
5a proceeded also inevitably. Fortunately, this side reaction
consumed only a small part of substrate, thus the 4a-forming
reaction remains to be predominant. The molar ratio of
HBA/HBD is also an important parameter to determine the
4000
3000
2000
1000
-60 -50 -40 -30 -20 -10
0
Wavenumber (cm-1)
Temperature (C)
.
Figure 3. FTIR spectroscopy of (a) FeCl3 6H2O by liquid film; (b) meglumine by
.
KBr; (c) FeCl3 6H2O/ meglumine DES by liquid film (A); TGA analysis of (a) fresh
.
.
FeCl3 6H2O/meglumine DES; (b) recovered FeCl3 6H2O/meglumine DES under
.
Argon atmosphere (B); DSC of FeCl3 6H2O/meglumine DES (line 1: the first scan,
.
line 2: the second scan) (C); FTIR spectroscopy of (a) fresh FeCl3 6H2O/meglumine
.
DES by liquid film; (b) recovered FeCl3 6H2O/meglumine DES by liquid film (D).
.
catalytic activity of FeCl3 6H2O/meglumine-H2O. The optimal
.
molar ratio of FeCl3 6H2O/meglumine was proved to be 1:2
Thermal stability of the DES was investigated by TGA
analysis, and the results are depicted in Figure 3B. Under mild
conditions, a temperature ranging from 25 °C to 80 °C, the
.
(entries 7, 8 and 9). Additionally, we have tested FeCl3 6H2O in
.
the model reaction. When 15 mol% FeCl3 6H2O was directly
used, a complex messy mixture was obtained, in which the
desired product 4a was hardly observed by TLC detection after
10 h of reaction at 80 °C. So we think the DES structure is
indeed pivotal in the catalysis.29 On the basis of all these
studies, a DES-based method C was established to implement
.
weight of FeCl3 6H2O/meglumine DES keeps nearly unchanged.
The weight loss from 80 °C to about 200 °C can be ascribed to
the evaporation of moisture and the decomposition of crystal
water in FeCl3 6H2O.25 The weight loss from 200 °C to about
330 °C can be linked to the decomposition of meglumine as
meglumine starts to decompose about 200 °C.26 The obtained
TGA data indicated that FeCl3 6H2O/meglumine DES has a quite
.
.
the synthesis of 4a: FeCl3 6H2O/meglumine (1:2)-H2O (50 wt%
with respect to the weight of DES) (15 mol%), 80 °C, and 10 h.
It should be noted that, without adding water component,
.
good thermal stability under mild conditions (< 80 °C), and can
thus be applied as solvent or catalyst in a reaction. The
differential scanning calorimeter (DSC) was used to investigate
.
FeCl3 6H2O/meglumine DES can also catalyze the reaction very
well, and the yield of 4a reached 72% under the identical
conditions (entry 10). In fact, even 300 wt% of water was
added, the reaction still proceeded very well with the aid of
.
the thermal behavior of FeCl3 6H2O/meglumine DES, and the
DSC curves from -60 °C to 0 °C are given in Figure 3C. Only one
endothermic peak or exothermic peak in DSC curve can be
observed and they are located in nearly the same temperature
range. It may be connected with higher rates of relaxation of
the structure of DES from liquid to grass state while cooling.27
This result indicated that no phase change appeared and only
.
FeCl3 6H2O/meglumine DES, and the yield of 4a reached 67%
(see SI, Figure S2). This result manefasted that
.
FeCl3 6H2O/meglumine DES might be indeed
a suitable
catalytic system to update bio-based water-containing
glycolaldehyde to value-added products.
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Table 2. Three-component reaction of 1a, 2a and 3a in DES-water mixtures.a
and moderately electron-poor indoles readily participated in
View Article Online
the reaction. However, those containDinOgI: 1s0t.r1o0n39g/lCy8GeCle0c4t0r0o0nA-
withdrawing groups, such as 5-cyanoindole and 5-nitroindole,
failed to participate in the reaction. Different from the results
obtained in extending the scope of 1,3-dicarbonyl component,
the performance of method A is not always superior to
method B. In the synthesis reactions of 4x and 4y, the yields
obtained with method B are even twice higher than that of
method A. In many cases, the yields obtained with method C
are comparable with that obtained with organic solvent
systems. However, when 2-phenylindoles were used, method
C was found to be invalid perhaps due to the strong
hydrophobicity of the indole compounds. Then we continued
to explore the reactivity of glycolaldehyde analogues in the
model reaction. When (4R)-2,2-dimethyl-1,3-dioxolane-4-
carboxadehyde was used, the desired dihydrofuran 4ad was
obtained with method A and method C in quite good yield.
Method A slightly displayed superior catalytic ability than
method B. And 2,5-dihydroxy-1,4-dithiane was also applicable
in this reaction to obtain 2,3-dihydrothiophene derivative.
It should be noted that the dihydrofuran ring system is
found prevalently at the central position of diverse classes of
OEt
+
OH
N
EtO
OEt
H
O
O
O
O
H
N
OEt
OEt
3a
1a
Catalyst
+
Solvent-free, 10 h
O
O
+
5a
2a
4a
yield (%)b
entry
catalyst and specified conditions
4a
0
5ac
1
2
3
4
5
6
7
ChCl/ethylene glycol (1:2)-H2O (5 mol%), 60 °C
0
ZnCl2/ethylene glycol (1:2)-H2O (5 mol%), 60 °C
14
16
43
46
63
73
17
21
24
22
26
25
.
FeCl3 6H2O/ethylene glycol (1:2)-H2O (5 mol%), 60 °C
.
FeCl3 6H2O/glycerol (1:2)-H2O (5 mol%), 60 °C
.
FeCl3 6H2O/meglumine (1:2)-H2O (5 mol%), 60 °C
.
FeCl3 6H2O/meglumine (1:2)-H2O (15 mol%), 60 °C
.
FeCl3 6H2O/meglumine (1:2)-H2O (15 mol%), 80 °C
(method C)
.
8
FeCl3 6H2O/meglumine (1:1)-H2O (15 mol%), 80 °C
0
0
.
9
FeCl3 6H2O/meglumine (1:3)-H2O (15 mol%), 80 °C
12
72
0
15
23
0
.
10
11
FeCl3 6H2O/meglumine (1:2) (15 mol%), 80 °C
.
FeCl3 6H2O (15 mol%), 80 °C
a: 1a (0.4 mmol), 2a (0.4 mmol), 3a (0.2 mmol), water (50 wt%) was added in DESs.
Isolated yield, and calculated with respect to 3a. c: Isolated yield, and calculated with
respect to 1a.
b
:
naturally occurring and biologically active heterocycles.30
A
plenty of syntheses of dihydrofurans are available which offers
a variety of intermediates and reaction conditions.31 A large
majority of synthetic approaches have been accomplished via
ionic32 or radical pathways33 through oxidative addition of 1,3-
dicarbonyl compounds to appropriate olefins. Although all of
these methodologies afford the dihydrofuran moiety in a
reasonable yield, simple and efficient synthetic approaches
still remain scarce.34 The present reaction offered thus an
expedient method to synthesize dihydrofurans with an indo-3-
yl substituent, which cannot be attained with the other
methods.
Having three different methods in hand, we studied the
scope of substrate, and the results are given in Scheme 1. A
wide range of -ketoesters were used to assemble with 1a and
indole 3a. Three methods are all effective to promote the
reactions, and the corresponding dihydrofurans were obtained
in generally good yields (4b–d, 4g–m, and 4o–q). When the
reactions were performed in organic solvents, as evidenced by
the results in Scheme 1, method A displayed superior catalytic
ability than method B. Double and triple bonds, ether and
acrylate moiety can all be delivered uneventfully into the
product molecules (4g–4i, 4q). An acid-liable cyclopropyl-
containing
component reaction, affording the desired product 4m in >
53% yield. -Ketoesters with a heterocyclic group, such as
-ketoeaster is also amenable to this three-

furan-2-yl and thiophene-2-yl, are also applicable in this
reaction, and the desired dihydrofurans 4o and 4p were
obtained in quite good yield. In all the reactions of
-
ketoesters, method C that involves the use of DES as dual
solvent/catalyst seems slightly less effective compared with
method A and B. This can also be verified by the reactions of
1,3-diketones. While the expected products can be obtained in
at maximum moderate yields with methods A and B, only by-
product furans were isolated with method C. (4e–f, 4n).
However, limitations of this three-component reaction were
also observed. Attempts to use ethyl trifluoroacetoacetate and
ethyl 4-chloroacetoacetate as substrate failed.
We also probe the scope of the reaction with respect to
indole component. In most of the cases, three methods were
used in order for us to find the best system for each individual
reaction. As shown in Scheme 1, indoles with different
substituents smoothly reacted with 1a and 2a, producing
dihydrofuran products in fairly good yields. Both electron-rich
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Green Chemistry
Page 6 of 9
ARTICLE
Journal Name
R3
N
can be trapped by 3a through a Michael addition.VTiehweArrtieclseuOlntleinde
intermediate III underwent an intramolecular dehydration,
R4
OEt
O
O
O
O
R2
R1
+
N
OH
DOI: 10.1039/C8GC04000A
R2
R1
EtO
O
R3
+
R4
affording thus 4a as the final product. The last step should be
very fast, otherwise this three-component reaction wouldn’t
be successful. Michael addition of 3a to intermediate II may be
crucial, and if it is insufficient, the equilibria of the reaction will
channelize to the formation of 5a. Considering together with
the reactant scope, we found that indoles with moderate and
strong electron-withdrawing including 5-cyanoindole and 5-
nitroindole, failed to participate in the reaction, because of
their weakly nucleophilicity.
O
+
4a-4ac
R1
R2
H
R = OMe 81%,a 71%c
N
O
H
N
4b
O
O
O
OMe
t
R = O Bu 75%,a 55%c
R
4c
4d
4e
4f
i
R = O Pr 83%,a 81%,b 83%c
R = Me 55%,a 21%,b 0c
R = 2-Br-C6H4 33%,a 0c
O
84%,a 67%,b 64%c
4g
H
O
N
H
H
N
O
N
OMe
R
O
O
O
O
O
i
R = Pr 45%,a 30%c
O
4j
77%,a 53%c
85%,a 74%,b 70%c
OH
O
O
R = nPr 67%,a 52%,b 49%c
R = Ph 60%,a 31%c
4i
4h
4k
4l
HO
OEt
nucleophilic attack of indole on C=O
N
H
H
2a
O
N
N
+
O
N
H
- H2
O
O
N
OMe
OMe
O
IV
S
H
HO
3a
Lewis acid
O
O
OMe
59%,a 57%,b 53%c
O
N
+
44%,a 25%,b 0c
4m
4n
82%,a 70%c
O
OEt
O
OH
4o
Lewis acid
OH
OH
O
EtO
H
H
N
HO
O
1c
H
H
O
O
N
O
N
O
4a
1a
1b
OMe
O
O
O
O
O
- H2
OEt
O
aldol
OEt
O
O
2a
O
O
N
R
H
75%,a 63%,b 59%c
3a
Lewis acid
Michael addition
76%,a 61%c
4q
4p
O
O
O
R = OMe 56%,a 59%,b 57%c
R = CH3 54%,b 37%c
4r
- H2
O
HO
O
O
OEt
O
O
OEt
OH
H
H
H
4s
4t
O
O
N
N
N
H
R = CO2Me 24%,a 32%,b 23%c
R = Cl 41%,b 36%c
OMe
OMe
II
I
III
R
4u
4v
R = Br 39%,b 38%c
O
O
R
Scheme 2. Proposed mechanism of a three-component reaction.
R = H 38%,a 86%,b 76%c
R = Br 66%,b 30%c
R = F 43%,b 41%c
R = Br 29%,a 63%,b 34%c
4y
4z
4w
4x
H
O
N
OMe
In fact, the real advantages of using the DES as dual
solvent/catalyst in the title reaction came from considering the
following factors: (i) recyclability and (ii) feasibility of using an
aqueous solution of glycolaldehyde. To investigate the
recyclability, the progress of a three-component reaction
Ph
O
Ph
O
N
N
OMe
OMe
O
c
MeO
b
4ac
O
c
60% , 52%
O
c
b
b
4aa
51% , 0
4ab
50% , 0
H
H
O
O
N
N
OMe
OMe
.
driven by FeCl3 6H2O/meglumine was recorded by a camara,
HO
O
and the pictures were collected in Figure 4. The DES is a dark
brown fluid (Fig. 4a). After adding all of the starting materials,
owing to the high viscosity of the DES at room temperature, a
biphasic system could be visually observed (Fig. 4b). During the
reaction, a homogeneous liquid was formed (Fig. 4c). At the
end of the reaction, the formed products can be isolated
through extraction with a mixture compose of heptane and
ethyl acetate (H/Ev/v = 5:1) (Fig. 4d). The DES can thus be
recovered and reused. Then we investigated the recycling
performance of DES in the model reaction. The results are
shown in Table 3. After four consecutive runs, the
S
60%,a 49%c
43%,e 17%c
4ae
4ad
a: 1a (0.4 mmol), 2a (0.4 mmol), 3a (0.2 mmol), method A: Sc(OTf)3 catalyst (5
mol%), r.t., nitromethane (1.0 mL), 1 h. : 1a (0.4 mmol), 2a (0.4 mmol), 3a (0.2
b
.
mmol), method B: Ni(ClO4)2 6H2O catalyst (20 mol%), 80 °C, acetonitrile (1.0 mL),
c
6
h.
.
:
1a (0.4 mmol), 2a (0.4 mmol), 3a (0.2 mmol), method C:
e
FeCl3 6H2O/meglumine-H2O (15 mol%), 80 °C, 10 h. : 1a (0.2 mmol), 2a (0.4
mmol), 3a (0.2 mmol), method C: MnBr2 catalyst (20 mol%), 80 °C, acetonitrile
(1.0 mL), 12 h.
Scheme 1. Substrate scope of three-component reaction of indoles,
glycolaldehyde acetal and 1,3-dicarbonyl compounds.
.
FeCl3 6H2O/meglumine is still capable of catalyzing the model
reaction in 64% yield. TGA analysis revealed that the weight
losses of fresh and recovered FeCl3 6H2O/meglumine DES
A mechanism was also proposed as depicted in Scheme 2.
Initial event of the reaction should be an acid-catalyzed
deacetalization of 1a, leading to the formation of
glycolaldehyde 1b. This species can be trapped by 3a or 2a. It
can also be converted reversibly to its dimer 1c. Assembly of
1b with 2a through an aldol-type reaction occurred, and
resulting in the generation of an intermediate I (the bottom
pathway). An intramolecular hydrogen bond between the
hydroxyl group and the ketone carbonyl may be formed in this
intermediate. This increased the stability of I, conferring thus
2a a priority to interact with 1b compared with 3a (the upper
pathway). A Knoevenagel product II was then formed, which
.
remained consistent (Figure 3B). By comparing FT-IR spectra of
.
fresh and recovered FeCl3 6H2O/meglumine DES (Figure 3D), it
can be found that the absorption peaks almost had no change.
.
The DSC curves of fresh and recovered FeCl3 6H2O/meglumine
DES exhibited the same glass transition temperature (see SI,
.
Figure S3). The results indicate that FeCl3 6H2O/meglumine
DES is indeed stable and recyclable in the model synthesis
reaction.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 9
Green Chemistry
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Journal Name
ARTICLE
Conclusions
View Article Online
DOI: 10.1039/C8GC04000A
To update the use of bio-based glycolaldehyde, a hydrolysis
product of cellulose or glucose, as a platform molecule
towards value-added products, we first developed an
expedient three-component reaction of indole, glycolaldehyde
acetal and 1,3-dicarbonyl compound in organic solvent
.
systems. Both Sc(OTf)3 and Ni(ClO4)2 6H2O are able to catalyze
the reaction efficiently, providing a hitherto unreported class
of 3-(indol-3-yl)-2,3-dihydrofurans in good to excellent yields.
We then turned to aqueous systems for which the previous
conditions were not giving satisfactory results. To enable the
use of aqueous solution of glycolaldehyde, we developed a
.
Figure 4. Progress of the model reaction in the DES. (a) FeCl3 6H2O/meglumine
DES; (b) after adding all of the starting materials; (c) at the end of the reaction;
(d) product extraction with organic solvent.
.
Table 3. Reusability of FeCl3 6H2O/meglumine DES.a
.
novel DES, FeCl3 6H2O/meglumine. This system was proved to
be an efficient and a water-compatible promoting medium for
the synthesis of dihydrofuran derivatives via the three-
component reaction. The use of bio-based glycolaldehyde as
starting material is also very successful. The system can also be
recycled without significant loss of its activity. This work may
give an inspiration to organic chemists that bio-based
glycolaldehyde should be a useful C2 building block, which has
unique reactivities and can be hopefully applied in many
organic transformations. In the future, much effort should be
paid to (i) explore suitable methods for large scale synthesis of
bio-based glycolaldehyde, and (ii) develop appropriate
catalytic systems for enabling the use of water-containing bio-
based glycolaldehyde.
Run
1
2
3
4
Yield (%) 4a
73
67
65
64
.
a: Method C: 1a (0.4 mmol), 2a (0.4 mmol), 3a (0.2 mmol), FeCl3 6H2O/meglumine DES
(15 mol%), 80 °C, 10 h.
To investigate the feasibility of using bio-based
glycolaldehyde, commercially available glycolaldehyde was
dissolved in water to prepare two solutions with different
concentrations (25 wt% and 50 wt%) and then utilized in the
three-component reaction. As shown in Scheme 3, the
reaction with an aqueous solution of glycolaldehyde (25 wt%)
.
proceeded very well with the aid of FeCl3 6H2O/meglumine
DES, producing 4a in 51% yield after 10 h of reaction at 80 °C.
When a concentrated solution of glycolaldehyde (50 wt%) was
used, the yield keeps almost constant. However, in an organic
system, Sc(OTf)3/nitromethane, the aqueous solution of
glycolaldehyde can be hardly used, and the yield of 4a reached
Experimental
Unless otherwise noted, all reagents were purchased from
.
commercial suppliers and used without purification. 1H and 13
C
only 8%. And Ni(ClO4)2 6H2O/acetonitrile worked slightly, and
the yield of 4a can be improved to 26%. These results
demonstrated that using FeCl3 6H2O/meglumine as dual
NMR spectra were recorded on a Bruker AV-400. Chemical
shifts are expressed in parts per million relative to Me4Si in
CDCl3 or DMSO-d6. IR spectra were recorded with a FT-IR
Bruker (EQUINOX 55) spectrometer using KBr pellets or neat
liquid. The thermal stability of the samples was characterized
by thermogravimetric analysis (TGA, TGA-7, Perkin-Elmer, USA)
at a heating rate of 10 °C min-1 in an argon flow (20 mL min-1).
Differential scanning calorimetry (DSC) measurements were
.
solvent/catalyst indeed enabled the utilization of bio-based
glycolaldehyde in the model three-component assembly
reactions. We found also that the DES can be recycled and
reused in this reaction, and the catalytic activity remained
perfect in the second run.
O
conducted in
a DSC Q2000 (Thermal Analyst Co., TA
+
OH
N
H
H
H
O
O
O
O
FeCl3.6H2O/meglumine DES
Instruments, USA) to determine the glass transition
temperature (Tg) of DESs. All experiments were performed
from 30 °C to -60 °C at a heating rate 10 °C min-1 in an argon
atmosphere at 50 mL min-1.
N
3a
1b
OEt
OEt
C
(15 mol%) (method
)
+
O
O
80 oC, 10 h
+
OEt
5a
2a
4a
Yield (%)
4a 5a
Entry
1a
Glycolaldehyde
Synthesis of 3i, 3o and 3p: a solution of methyl acetoacetate (2
mmol) in toluene was mixed with propargyl alcohol (2 mmol)
and triphenylphosphine (0.2 mmol) to obtain (2-propynyl) 3-
oxobutanoate (3i).35 The mixture was then refluxed for 6 h.
The progress of the reactions was monitored by TLC. After the
reaction, the reaction mixture was cooled to room
temperature, and the product was obtained in 83% yield by
isolation with preparative TLC (eluting solution: petroleum
ether/ethyl acetate = 5/1 (v/v)). Synthesis of the other
compounds was performed by an analogous procedure.
25 wt% aqu.
25 wt% aqu.
25 wt% aqu.
50 wt% aqu.
8
0
2b
3
26
51
47
27
13
15
4
5c
25 wt% aqu.
50
10
a
A
Sc(OTf)3/nitromethane(method ).
b Ni(ClO4)2 6H2O/acetonitrile (method ).
c Recovered DES was used.
.
B
Scheme 3.
A
three-component reaction of using bio-based glycolaldehyde
.
aqueous solution in the FeCl3 6H2O/meglumine DES.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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Green Chemistry
Page 8 of 9
ARTICLE
Journal Name
4
5
R. Flamini, A. D. Vedova, J. Agric. Food Chem., 2003, 51,
Synthesis of 4a and 5a: the reaction was conducted in a 10 mL
V-type flask equipped with a triangular magnetic stirring bar. A
solution of ethyl acetoacetate (0.4 mmol) in CH3NO2 (1.0 mL)
was mixed with glycolaldehyde diethyl acetal (0.4 mmol),
indole (0.2 mmol) and Sc(OTf)3 (0.01 mmol) to obtain target
product (4a). The mixture was then stirred at room
temperature for 1 h. After the reaction, the product was
obtained in 81% by isolation with preparative TLC (eluting
solution: petroleum ether/ethyl acetate = 5/1 (v/v)). All tests
for substrate scope were performed with an analogous
procedure (method A). And a solution of ethyl acetoacetate
(0.4 mmol) in CH3CN (1.0 mL) was mixed with glycolaldehyde
diethyl acetal (0.4 mmol), indole (0.2 mmol) and
View Article Online
2300–2303.
(a) G. F. Liang, A. Q. Wang, L. Li, T. ZhDaOngI:,1A0.n10g3e9w/C.8CGhCe0m40. 0In0tA.
Ed., 2017, 56, 3050–3054; (b) N. Ji, T. Zhang, A. Q. Wang, X.
D. Wang, Angew. Chem. Int. Ed., 2008, 47, 8510–8513; (c) K.
Usami, A. Okamoto, Org. Biomol. Chem., 2017, 15, 8888–
8893.
6
7
G. Cassone, J. Sponer, J. E. Sponer, F. Saijia, Chem. Commun.,
2018, 54, 3211–3214.
(a) W. F. Zhao, X. P. Chi, H. Li, J. He, S. Yang, Green Chem.,
2019, 21, 567–577; (b) S. Ranganathan, S. Zeitlhofer, V.
Sieber, Green Chem., 2017, 19, 2576–2586; (c) A. P. Abbott,
A. Z. M. Al-Bassam, A. Goddard, R. C. Harris, M. Wieland,
Green Chem., 2017, 19, 2225–2233; (d) F. Sebest, L.
Casarrubios, H. S. Rzepa, A. J. P. White, S. Díez-González,
Green Chem., 2018, 20, 4023–4035.
(a) D. Carriazo, M. C. Serrano, M. C. Gutierrez, M. L. Ferrer,
Chem. Soc. Rev., 2012, 41, 4996–5014; (b) E. J. Smith, A. P.
Abbott, K. S. Ryeder, Chem. Rev., 2014, 114, 11060–11082;
(c) H. G. Cruz, N. Jordăo, L. C. Branco, Green Chem., 2017, 19,
1653–1658; (d) J. Y. Jiang, C. Y. Yan, X. H. Zhao, Z. M. Xue, T.
C. Mu, Green Chem., 2017, 19, 3023–3031.
(a) A. Wang, P. Xing, X. Zhang, H. Cao, G. Yang, RSC. Adv.,
2015, 5, 59022–59026; (b) P. H. Tran, H. T. Nguyen, P. E.
Hansen, RSC. Adv., 2016, 6, 37031–37038; (c) K. H. Kim, T.
Dutta, J. Sun, B. Simmons, S. Singh, Green Chem., 2018, 20,
809–815; (d) L. Cicco, N. R. Lombardía, M. J. R. Álvarez, J. G.
Sabín, ACS Sustainable Chem. Eng., 2018, 20, 3468–3475.
.
Ni(ClO4)2 6H2O (0.08 mmol) to obtain target product (4a). The
8
9
mixture was then stirred at 80 °C for 6 h. After the reaction,
the mixture was cooled to room temperature, and the product
was obtained in 79% by isolation with preparative TLC (eluting
solution: petroleum ether/ethyl acetate = 5/1 (v/v)). All tests
for substrate scope were performed with an analogous
procedure (method B). And a solution of ethyl acetoacetate
(0.4 mmol) was mixed with glycolaldehyde diethyl acetal (0.4
.
mmol), indole (0.2 mmol) and FeCl3 6H2O/meglumine-H2O
(0.03 mmol) to obtain target product (4a). The mixture was
then stirred at 80 °C for 10 h. After the reaction, the mixture
was cooled to room temperature, and the product was
obtained through extraction with a mixture compose of
heptane and ethyl acetate (H/Ev/v = 5:1). And then the formed
products can be isolated with preparative TLC (eluting solution:
petroleum ether/ethyl acetate = 5/1 (v/v)) (method C).
10 For selected examples, see: (a) A. T. Merrit, S. V. Ley, Nat.
Prod. Rep., 1992, 9, 243–287; (b) J. P. Michael, Nat. Prod.
Rep., 2000, 17, 603–620; (c) T. Koike, T. Takai, Y. Hoashi, K.
Hirai, O. Uchikawa, J. Med. Chem., 2011, 54, 4207–4218; (d)
M. J. Somerville, P. L. Katavic, L. K. Lambert, M. Gavagnin, M.
G. Banwell, M. J. Garson, J. Nat. Prod., 2012, 75, 1618–1624;
(e) K. Sugimoto, K. Tamura, N. Ohta, C. Tohda, N. Toyooka, H.
Nemoto, Y. Matsuya, Bioorg. Med. Chem. Lett., 2012, 22,
449–452; (f) Y. Zhang, H. Zhong, T. Wang, D. Geng, M. Zhang,
K. Li, Eur. J. Med. Chem., 2012, 48, 69–80; (g) M. R. Lambu, Z.
M. A. Judeh, Green Chem., 2019, 21, 821–829.
11 For reviews, see: (a) J. Iqbal, B. Bhatia, N. K. Nayyar, Chem.
Rev., 1994, 94, 519–584; (b) B. B. Snider, Chem. Rev., 1996,
96, 339–364; (c) B. Godoi, R. F. Schumacher, G. Zeni, Chem.
Rev., 2011, 111, 2937–2980; (d) J. Le Bras, J. Muzart, Chem.
Soc. Rev., 2014, 43, 3003–3040; (e) R. Zimmer, H. U. Reissig,
Chem. Soc. Rev., 2014, 43, 2888–2903.
12 (a) W. Huang, C. H. Liu, Y. L. Gu, Adv. Synth. Catal., 2017,
359, 1811–1818; (b) Z. F. Jia, K. W. Wang, B. E. Tan, Y. L. Gu,
Adv. Synth. Catal., 2017, 359, 78–88; (c) C. H. Liu, L. Zhou, D.
Jiang, Y. L. Gu, Asian J. Org. Chem., 2016, 5, 367–372; (d) C.
H. Liu, L. Zhou, W. B. Huang, M. Wang, Y. L. Gu, Adv. Synth.
Catal., 2016, 358, 900–918; (e) C. Cheng, C. H. Liu, Y. L. Gu,
Tetrahedron, 2015, 71, 8009–8017; (f) A. Taheri, B. Lai, C.
Cheng, Y. L. Gu, Green Chem., 2015, 17, 812–816.
Conflicts of interest
The authors declare no competing financial interest
.
Acknowledgements
The authors thank the National Natural Science Foundation of
China (2171101076 and 21872060) and the Fundamental
Research Funds for the Central Universities of China
(2016YXZD033) for the financial support. The Cooperative
Innovation Center of Hubei Provinceand is also
acknowledgeds.
13 See a review: (a) P. Ravichandiran, B. Lai, Y. L. Gu, Chem.
Rec., 2017, 17, 142–183. See some examples: (b) Y. L. Gu, F.
Wu, J. Yang, Adv. Synth. Catal., 2018, 360, 2727–2741; (c) J.
Yang, F. Mei, S. Fu, Y. L. Gu, Green Chem., 2018, 20, 1367–
1374; (d) C. H. Liu, W. B. Huang, M. Wang, B. Pan, Y. L. Gu,
Adv. Synth. Catal., 2016, 358, 2260–2266; (e) S. Sun, C.
Cheng, J. Yang, A. Taheri, D. Jiang, B. Zhang, Y. L. Gu, Org.
Lett., 2014, 16, 4520–4523.
14 (a) A. T. Nielsen, G. W. Lawrence, J. Org. Chem., 1977, 42,
2900–2902; (b) W. M. Koppes, M. E. Sitzmann, H. G. Adolph,
J. Chem. Eng. Data, 1986, 31, 119–123.
15 Hydroxycarbonyl compounds can react with C-H acids, such
as malononitrile and 1,3-dicarbonyl compounds, to form
furans: (a) L. Tan, Z. Zhang, D. Gao, J. Luo, X. Ren, K. Ding, J.
Med. Chem., 2016, 59, 6807–6825; (b) Z. J. Ding, F. Zhang, T.
References
1
(a) S. Wang, G. Dai, H. Yang, Z. Luo, Prog. Energy Combust.
Sci., 2117, 62, 33–86; (b) J. F. Jenck, F. Agterberg, M. J.
Droescher, Green Chem., 2004, 6, 544–556; (c) Y. Zhang, Z. G.
Yuan, B. Hu, J. Deng, Y. Fu, Q. Lu, Green Chem., 2019, 21,
812–820.
(a) A. Demirbas, Energy Convers. Manage., 2009, 50, 2782–
2801; (b) C. R. Vitasari, G. W. Meindersma, A. B. De Haan,
Bioresour. Technol., 2011, 102, 7204–7210; (c) C. R. Vitasari,
G. W. Meindersma, A. B. De Haan, Green Chem., 2012, 14,
321–325; (d) D. Mohan, C. U. Pittman, P. H. Steele, Energy
Fuels, 2006, 20, 848–889.
2
3
G. Xu, A. Q. Wang, J. F. Pang, T. Zhang, Appl. Catal. A–Gen,
2015, 502, 65–70.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 9
Green Chemistry
Please do not adjust margins
Journal Name
ARTICLE
X. Xu, W. B. Wang, L. Jin, N. Y. Huang, Chin. J. Struct. Chem., 34 (a) M. E. Jung, L. J. Street, J. Am. Chem. Soc., 1994, 106,
View Article Online
2017, 36, 1124–1129; (c) E. Nagy, Y. Liu, K. J. Prentice, K. W.
8327–8329; (b) D. D. Sternbach, D. M. Rossana, Tetrahedron
DOI: 10.1039/C8GC04000A
Sloop, P. E. Sanders, B. Batchuluun, C. D. Hammond, M. B.
Lett., 1982, 23, 303–306.
Wheeler, T. B. Durham, J. Med. Chem., 2017, 60, 1860–1875. 35 J. S. Yadav, B. V. S. Reddy, A. D. Krishna, A. V. Narsaish, J.
16 Y. Ren, M. Li, J. Yang, J. Peng, Y. Gu, Adv. Synth. Catal., 2011,
Mol. Catal. A–Chem., 2007, 261, 93-97.
353, 3473–3484.
17 (a) R. Gani, P. A. Crafts, M. J. Powell, L. Powell, J. H. Atherton,
J. L. Cordiner, Chem. Eng., 2006, 113, 30–43; (b) D. J. C.
Constable, R. K. Henderson, Org. Proc. Res. Develop., 2007,
11, 133–137; (c) C. Wu, H. J. Xiao, S. W. Wang, M. S. Tang, W.
F. Li, Z. Cao, W. M. He, ACS Sustainable Chem. Eng., 2019, 7,
2169–2175.
18 C. Wu, L. H. Lu, A. Z. Peng, G. K. Jia, C. Peng, Z. Cao, W. X. He,
X. H. Xu, Green Chem., 2018, 20, 3683–3688.
19 (a) C. J. Li, Acc. Chem. Res., 2002, 35, 533–538; (b) M. J. Earle,
S. P. Katdare, K. R. Seddon, Org. Lett., 2004, 6, 707–710; (c)
Q. H. Zhang, S. G. Zhang, Y. Q. Deng, Green Chem., 2011, 13,
2619–2637; (d) J. R. Hyde, P. Licence, M. Poliakoff, Appl.
Catal. A–Gen, 2001, 222, 119–131; (e) N. Azizi, M. Khajeh, M.
Alipour, Ind. Eng. Chem. Res., 2014, 53, 15561–15565; (f) J.
Cao, L. Y. Chen, M. H. Li, F. L. Cao, E. Su, Green Chem., 2018,
20, 1879–1886.
20 (a) F. J. Liu, Z. M. Xue, X. H. Zhao, H. Y. Mou, J. He, T. C. Mu,
Chem. Commun., 2018, 54, 6140–6143; (b) T. J. Park, S. H.
Lee, Green Chem., 2017, 19, 910–913.
21 (a) A. P. Abbott, G. Capper, D. L. Davies, R. Rasheed, Inorg.
Chem., 2004, 43, 3447–3452; (b) A. P. Abbott, G. Capper, D.
L. Davies, R. Rasheed, Chem–Eur. J., 2004, 10, 3769–3774.
22 (a) M. Hayyan, A. Abo-Hamad, M. A. AlSaadi, M. A. Hashim,
Nanoscale Res. Lett., 2015, 10, 324–350; (b) H. M. Badawi,
W. Förner, Spectrochim. Acta A, 2011, 78, 1162–1167.
23 (a) R. Ullah, M. Atilhan, B. Anaya, S. Aparicio, Phys. Chem.
Chem. Phys., 2015, 17, 20941–20960; (b) S. L. Perkins, P.
Painter, C. M. Colina, J. Chem. Eng. Data, 2014, 59, 3652–
3662.
24 DESs maintain its structure in water up to solutions of 50 %
(v/v): (a) O. S. Hammond, D. T. Bowron, K. J. Edler, Angew.
Chem. Int. Ed., 2017, 56, 9782–9785; (b) C. Y. Ma, A.
Laaksonen, C. Lu, X. Y. Ji, Chem. Soc. Rev., 2018, 47, 8685–
8720.
25 M. Agrawal, S. Gupta, A. Pich, N. E. Zafeiropoulos, M. Stamm,
Chem. Mater., 2009, 21, 5343–5356.
26 L. Moradi, M. J. Tadayon, Saudi Chem. Soc., 2018, 22, 66–75.
27 A. A. Samarov, M. A. Smirnov, M. P. Sokolova, E. N. Popova,
A. M. Toikka, Fluid Phase Equilibria, 2017, 448, 123–127.
28 Q. H. Zhang, S. Royer, F. Jérôme, Chem. Soc. Rev., 2012, 41,
7108–7146.
29 The use of FeCl3 as catalyst in aqueous solutions has been
reported: T. V. Stein, P. M. Grande, W. Leitner, P. D. de
Maria, ChemSusChem, 2011, 4, 1592–1594.
30 (a) J. Lee, J. H. Li, S. Oya, J. K. Snyder, J. Org. Chem., 1992, 57,
5301–5312; (b) P. A. Jacobi, H. G. Selnick, J. Org. Chem.,
1990, 55, 202–209; (c) B. H. Lipshutz, Chem. Rev., 1986, 86,
795–819.
31 (a) Y. Fukude, H. Shiragami, K. Utimoto, H. Nozaki, J. Org.
Chem., 1991, 56, 5816–5819; (b) K. Shishido, K. Umimoto, M.
Shibuya, Heterocycles, 1990, 31, 597–598; (c) S. P. Tanis, M.
C. McMills, T. A. Scahill, D. A. Kloosterman, Tetrahedron
Lett., 1990, 31, 1977–1980; (d) R. L. Danheiser, E. J. Stormer,
H. Koyama, D. S. Yamashita, C. A. Klade, J. Am. Chem. Soc.,
1989, 111, 4407–4413;
32 (a) Y. R. Lee, J. K. Suk, Tetrahedron, 2002, 58, 2359–2367; (b)
N. Aso, A. Ojida, G. Yang, O. J. Cha, E. Osawa, K. Kamematsu,
J. Org. Chem., 1993, 58, 3960–3968.
33 J. Iqbal, B. Bhatia, N. K. Nayyar, Tetrahedron, 1991, 47,
6457–6468.
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