Green catalytic conversion of bio-based sugars to 5-chloromethyl furfural in deep eutectic solvent, catalyzed by metal chlorides

Article abstract of DOI:10.1039/c6ra00267f

5-Chloromethylfurfural (5-CMF), a biomass-derived platform chemical with great potential applications, was synthesized by a novel method from sugars, using metal chlorides as catalysts in a deep eutectic solvent (DES). AlCl₃·6H₂O was verified as the most effective catalyst among various metal chlorides, and provided a 5-CMF yield of 50.3% along with 8.1% 5-HMF yield at 120°C in 5 h. By this green, mild and cost-effective approach, the dependence of 5-CMF production on the large amount and high concentration of hydrochloric acid in previous studies was eliminated.

Full text of DOI:10.1039/c6ra00267f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: M. Zuo, Z. Li, Y.
Jiang, X. Tang, X. Zeng, Y. Sun and L. Lin, RSC Adv., 2016, DOI: 10.1039/C6RA00267F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Please do not adjust margins
RSC Advances
Page 1 of 6
View Article Online
DOI: 10.1039/C6RA00267F
Journal Name
COMMUNICATION
Green catalytic conversion of bio-based sugars to 5-chloromethyl
furfural in deep eutectic solvent catalyzed by metal chlorides
Received 00th January 20xx,
Accepted 00th January 20xx
Miao Zuo, Zheng Li, Yetao Jiang, Xing Tang, Xianhai Zeng*, Yong Sun, Lu Lin*
DOI: 10.1039/x0xx00000x
www.rsc.org/
5-Chloromethylfurfural (5-CMF),
a biomass derived platform solution was adopted for the generation of 5-CMF via
chemical with great potential applications, was synthesized by a hydrolysis, dehydration and halogenation process followed by
novel method from sugars using metal chlorides as catalyst in a simultaneous extraction with dichloromethane.13
deep eutectic solvent (DES). AlCl3∙6H2O was verified as the most Herein we proposed the “one-pot” conversion of
effective catalyst among various metal chlorides, which provided a carbohydrates to 5-CMF in a biphasic reaction system (Figure
5-CMF yield of 50.3% along with 8.1% 5-HMF yield at 120 oC in 5 h. S1), which was composed of methyl isobutyl ketone (MIBK)
15
By this green, mild and cost-effective approach, the dependence and deep eutectic solvent (DES)14,
. DES is widely
of 5-CMF production on the large amount and high concentration acknowledged as a new class of ionic liquid (IL), under mild
of hydrochloric acid in previous works was eliminated.
conditions without the utilization of concentrated acid. As
illustrated in Scheme 1, fructose which generated DES with
choline chloride (ChCl) is firstly dehydrated to 5-HMF in DES
phase with the catalysis of AlCl3·6H2O. The resulting 5-HMF is
rapidly extracted by MIBK from the DES phase. The following
halogenation of 5-HMF to 5-CMF in organic phase is catalyzed
by HCl, which was in-situ generated by the hydrolysis of
AlCl3·6H2O. In this work, a highest 5-CMF yield over 50% was
obtained with a high feed concentration (over 15 wt%) in a
DES-MIBK system in the absence of concentrated HCl. It is
noted that carbohydrates used here were both reactants and
part of DES.
Renewable lignocellulosic biomass has been utilized for the
production of fuels and chemicals in consideration of the
depletion of fossil resources worldwide.1-3 Much efforts have
been devoted to convert lignocellulose into versatile platform
chemicals, such as 5-hydroxymethylfurfural (5-HMF), which
can be produced by acid promoted dehydration of cellulose
and has been regarded as one of the most important cellulose-
derived products. However, 5-HMF is highly active and
instable, especially in the presence of acid catalysts which
could further promote the formation of humins and
degradation of 5-HMF to levulinic acid (LA).4, 5
5-Chloromethylfurfural (5-CMF), which can be directly
generated with a high yield up to 80% from cellulosic biomass,
is also acknowledged as a novel and promising platform
molecule owing to its higher stability compared with 5-HMF.4,
6-9
Moreover, highlighted by Mascal’s research, the chlorine
atom in 5-CMF is rather active for substitution reactions of 5-
CMF,4 which facilitates the conversion of 5-CMF into various
10
chemicals such as 5-aminolevulinic acid (5-ALA)
, 2,5-
dimethylfuran (DMF)11 and pharmaceutical chemicals.12
According to previous reports, 5-CMF was typically produced
in a biphasic reaction system, in which concentrated HCl
Scheme 1. Plausible mechanism for the conversion of fructose into
5-CMF in DES-MIBK system catalyzed by AlCl3·6H2O
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 2 of 6
View Article Online
DOI: 10.1039/C6RA00267F
COMMUNICATION
Journal Name
As moderate acids, metal chlorides were adopted in this study
to eliminate the dependence of 5-CMF production on
concentrated HCl. Various of metal chlorides were investigated
for the catalytic production of 5-CMF in DES-MIBK system
(Table S1). It is noted that the strength of Lewis acid greatly
affected the conversion of fructose and the selectivity to 5-
CMF and 5-HMF. Metal chlorides with high Lewis acid strength
provided much higher 5-CMF yields than 5-HMF. A highest 5-
CMF yield of 37% was obtained in the presence of AlCl3·6H2O
o
at 110 C in 2 h. Thus, AlCl3·6H2O was proven to be the most
effective among various metal chlorides and was applied for
further experiments.
When the reaction was performed in an isolated DES phase, a
severe coking process was observed and the yields of 5-CMF
and 5-HMF were quite low. Thus, several aprotic solvents
including acetonitrile (MeCN), methyl isobutyl ketone (MIBK),
γ-valerolactone (GVL), dimethyl formamide (DMF) and
dimethyl sulfoxide (DMSO) were introduced for the in-situ
extraction of products from DES reaction mixture to prevent
polymerization and coking. As shown in Table 1, the addition
of MeCN, DMF and DMSO effectively inhibited the coking
process and 44.9%-46.8% 5-HMF yield was achieved. However,
almost no 5-CMF was detected in the above mentioned cases.
As for GVL, a 5-CMF yield of 18.9% was obtained. Interestingly,
MIBK strongly facilitated the generation of 5-CMF and
provided a yield up to 37.1% at 110 oC in 2 h.
Table 1. Effects of extractants on the yields of 5-CMF and 5-
HMF
Extractant
Blankc
MeCN
MIBK
Y5-CMF a (%)
Y5-HMF b (%)
0
Figure 1. Effects of reaction time and temperature on the
conversion of fructose into 5-CMF (a) and 5-HMF (b); Reaction
conditions: 5 mmol fructose, 5 mmol AlCl3·6H2O, 25 mmol ChCl, 30
ml MIBK
0
3.7
37.1
18.9
0
44.9
16.7
GVL
32.0
The effect of the catalyst dosage was studied, as shown in
Figure 2. In a blank experiment, 20.9% of 5-HMF yield was
obtained and no 5-CMF was detected. 5-CMF yield of 23.6%
and 5-HMF yield of 13.4% were obtained when the mole ratio
of AlCl3·6H2O to fructose was 0.5. As the mole ratio of
AlCl3·6H2O to fructose increased to 1.0, a sharp increase of 5-
CMF yield from 0 to 50.3% was observed while 5-HMF yield
decreased from 20.9% to 8.1%. However, 5-CMF yield was
reduced to 40% as the mole ratio of AlCl3·6H2O to fructose was
further increased to 4.0, probably due to the overmuch acid
sites which would promoted the formation of undesired by-
products such as humins.
DMF
44.8
DMSO
0
46.8
Reaction conditions: 5 mmol fructose, 5 mmol AlCl3·6H2O, 25 mmol
ChCl, 30 ml extractant, 110 oC, 2 h. a: the yield of 5-CMF; b: the yield
of 5-HMF; c: extracted by 30 ml MIBK after the reaction mixture
cold down to room temperature.
The effects of temperature and reaction time on 5-CMF and 5-
HMF production in the biphasic system were also studied.
According to Figure 1(a), higher temperatures promoted the
generation of 5-CMF and a highest yield up to 50.3% was
achieved at 120 oC in 5 h. The yield was then decreased to
44.8% with a further increase of reaction time to 8 h, which
probably attributed to further conversion of 5-CMF into
humins and other by-products. Oppositely, the yield of 5-HMF
decreased as the reaction proceeded (Figure 1(b)), from which
we can deduce that fructose was firstly dehydrated into 5-HMF
and then halogenated into 5-CMF in the biphasic system. The
cascade generation of 5-HMF and 5-CMF was proved by GC-
MS detected product distribution, as shown in Figure S2.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 3 of 6
View Article Online
DOI: 10.1039/C6RA00267F
Journal Name
COMMUNICATION
function of 5-CMF production, as shown in Table S2. 5-CMF
was obtained with a best yield of 50% in the presence of ChCl
while the yield was only 6% and 0% in the cases of [BMIM]Cl
and [BMIM]BF4 respectively. It indicated that the composition of
DES reaction system was crucial for the production of 5-CMF
from fructose.
As our previous works shown, the fructose firstly converted
into 5-HMF rapidly, and then transformed into 5-CMF. In order
to investigate the forming process from 5-HMF to 5-CMF, a
series of experiments were conducted with 5-HMF as raw
material. As demonstrated in Table S3, low yield of 5-CMF and
5-HMF conversion were obtained with the addition of
independent AlCl3·6H2O or ChCl (entry 1, 4). However, around
100% 5-HMF conversion and 86% 5-CMF yield were obtained
in the presence of both AlCl3·6H2O and ChCl. Moreover, HCl
was detected from the MIBK extraction solvent, which formed
in the DES with the existence of both AlCl3·6H2O and ChCl. It
was inferred that 5-CMF could be produced from 5-HMF
catalyzed by HCl. Unfortunately, the source of chloride anions
in 5-CMF could not be exactly determined.
The continuous solvent extraction method which was
highlighted by Mascal has achieved an effective improvement
in the conversion of carbohydrates into 5-CMF.6 When MIBK
was used as the extractant and formed a biphasic system with
DES, as shown in Figure S3, 5-CMF yield decreased significantly
with an enhanced 5-HMF yield, whereas the total yield of
furfuran products was maintained at about 60%, corresponded
with our aforementioned work. This could be explained by that
the transfer of extraction solvent would lead to the loss of HCl
in the organic phase, which might affect the further
halogenation reaction of 5-HMF in MIBK. Moreover, those
experiment results indicated that the organic extraction
solvent was also participated in the process of 5-CMF
production.
Figure 2. Effect of catalyst loading on the conversion of fructose
into 5-CMF & 5-HMF; Reaction conditions: 5mmol fructose,
different amounts of AlCl3·6H2O, 25 mmol ChCl, 120 oC, 5 h.
Catalyst loading is relative to fructose.
As Table 2 showed, low concentration of ChCl helps to reduce
the costs of 5-CMF production which is desirable for the
practical production. Hence, the effect of the initial ChCl
concentration on 5-CMF and 5-HMF yields was studied at a
reaction temperature of 120 oC in 5 h with 5 mmol fructose
and 5 mmol catalyst. As demonstrated in Table 2, the equal
quality of fructose to ChCl content resulted in the
predomination of 5-HMF in the products. However, 5-CMF
yield gradually increased from 17.4% to 50.3% when the
weight ratio of ChCl to fructose increased from 1 to 4, and the
5-HMF yield sharply descended from 30.8% to 7.4%. This was
ascribed to that a suitable content of ChCl promoted the
conversion process from fructose to 5-CMF. It was also noted
that high content of ChCl have a promoting function on the
total yield of 5-HMF and 5-CMF.
To study the recycle performance of the catalyst, the catalyst
and ChCl were reused with water-washing and distillation after
separated from the reaction mixture (the HPLC analysis result
shown in Figure S4). A slight descending of 5-CMF yield was
observed in the successive 2 cycles. A 5-CMF yield of 41.3%
and a 5-HMF yield of 11.7% were still achieved after 5 h in the
3rd run.
Table 2. Effect of fructose concentration to the conversion of
fructose into 5-CMF & 5-HMF
Fructose : ChCl
weight ratio
Total
(%)
C fructose
(%)
Y5-CMF (%)
Y5-HMF (%)
87.3
1:1
1:2
1:3
1:4
1:5
17.4
25.8
32.6
50.3
50.2
30.8
21.9
18.6
8.1
48.2
47.7
51.2
58.4
57.9
95.5
100
100
100
7.4
Reaction conditions:
5
mmol (0.9g) fructose,
5
mmol
AlCl3·6H2O, 30 ml MIBK, 120 oC, 5 h
Other kinds of ionic liquids, such as [BMIM]Cl and [BMIM]BF4,
were applied to the comparison with ChCl-based DES in the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 4 of 6
View Article Online
DOI: 10.1039/C6RA00267F
COMMUNICATION
Journal Name
Figure 3. Performance of recycled catalyst mixture. Reaction
conditions: 5mmol (0.9g) fructose, 4.8g catalyst mixture (ChCl
and AlCl3·6H2O), 30ml MIBK, 120 oC, 5 h. The used catalysts
mixture were washed by deionized water and dried in a rotary
evaporator before reutilization
Figure 4. Conversion of various carbohydrates into 5-CMF & 5-
HMF in the presence of AlCl3·6H2O and ChCl. Reaction
conditions: 0.9 g different carbohydrate, 5 mmol AlCl3·6H2O, 25
mmol ChCl, 30 ml MIBK 120 oC, 5 h
In addition to fructose, other biomass derived carbohydrates
were also tested to produce 5-CMF in this MIBK/DES biphasic
system. As shown in Figure 3, 5-CMF yields of 16.93%, 22.66%
and 17.86% were obtained with glucose, inulin and sucrose as
substrates, respectively. Compared with the high yield of 5-
CMF achieved from fructose, these carbohydrates showed low
reaction activity in the production of 5-CMF. It was probably
due to that those carbohydrates could not convert into 5-HMF
easily in the DES-biphasic system, in which the isomerization
into fructose was not favored and the formation of 5-CMF was
further impeded. Thus, our further study would focus on the
conversion of different types of carbohydrates into 5-CMF with
high yields in a green DES-biphasic system.
Conclusions
In this work, 5-CMF was effectively produced in a DES/MIBK
biphasic reaction system. Although the 5-CMF yield obtained
in this work was lower than the yield reported by other
literatures, the major advantages of the present work was that
a combination of metal chlorides and ChCl was suitable for the
conversion of fructose into 5-CMF, without the large amount
of hydrochloric acid. This method provided a moderate and
green condition for the production of 5-CMF with a high yield.
In conclusion, this study presents a new green method to
efficiently produce important platform chemicals 5-CMF from
biomass derived carbohydrates under a one pot/two-step mild
biphasic reaction system.
Acknowledgements
This work was supported financially by the Natural Science
Foundation of China (No. 21506177), the Natural Science
Foundation of Fujian Province of China (2015J05034), the
Fujian province development and reform commission and the
Key Program for Cooperation between Universities and
Enterprises in Fujian Province (2013N5011) and the
Fundamental Research Funds for the Xiamen University
(20720160077).
Notes and references
1.
A. J. Ragauskas, C. K. Williams, B. H. Davison, G.
Britovsek, J. Cairney, C. A. Eckert, W. J.
Frederick, J. P. Hallett, D. J. Leak and C. L. Liotta,
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 5 of 6
View Article Online
DOI: 10.1039/C6RA00267F
Journal Name
COMMUNICATION
Science, 2006, 311, 484-489.
Y. Román-Leshkov, J. N. Chheda and J. A.
Dumesic, Science, 2006, 312, 1933-1937.
J. B. Binder and R. T. Raines, J. Am. Chem. Soc.,
2009, 131, 1979-1985.
2.
3.
4.
5.
M. Mascal, ChemSusChem, 2015, 8, 3391-3395.
F. Liu, J. Barrault, K. De Oliveira Vigier and F.
Jérôme, ChemSusChem, 2012, 5, 1223-1226.
M. Mascal and E. B. Nikitin, Angew. Chem.,
2008, 120, 8042-8044.
M. Mascal and E. B. Nikitin, ChemSusChem,
2009, 2, 423-426.
M. Brasholz, K. von Kanel, C. H. Hornung, S.
Saubern and J. Tsanaktsidis, Green Chem.,
2011, 13, 1114-1117.
6.
7.
8.
9.
J. Howard, D. W. Rackemann, Z. Zhang, L.
Moghaddam, J. P. Bartley and W. O. Doherty,
RSC Adv., 2016, 6, 5240-5248.
10.
11.
M. D. Mascal, Saikat, Green Chem., 2011, 13,
40-41.
M. Mascal and S. Dutta, in Selective Catalysis
for Renewable Feedstocks and Chemicals,
springer, 2014, pp. 41-83.
12.
13.
S. Dutta, L. Wu and M. Mascal, Green Chem.,
2015, 17, 3737-3739.
S. Breeden, J. Clark, T. Farmer, D. Macquarrie, J.
Meimoun, Y. Nonne and J. Reid, Green Chem.,
2013, 15, 72-75.
14.
15.
A. P. Abbott, D. Boothby, G. Capper, D. L. Davies
and R. K. Rasheed, J. Am. Chem. Soc., 2004,
126, 9142-9147.
E. L. Smith, A. P. Abbott and K. S. Ryder, Chem.
Rev., 2014, 114, 11060-11082.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

RSC Advances
Page 6 of 6
View Article Online
DOI: 10.1039/C6RA00267F
Graphical Abstract
5-Chloromethylfurfural (5-CMF) was effectively prepared from fructose and other
carbohydrates, in a biphasic reaction system, which was composed of methyl isobutyl
ketone (MIBK) and deep eutectic solvent (DES) with catalyst of AlCl3·6H2O.