Preparation of halogenated furfurals as intermediates in the carbohydrates to biofuel process

Article abstract of DOI:10.1039/c6ra06050a

Lignocellulose derived halogenated furfurals are important chemicals that can serve as starting materials for diverse products such as drugs, polymers and fuels, including fuel additives. In this paper a protocol for the synthesis of 5-chloromethyl furfural (CMF) and 5-bromomethyl furfural (BMF) is put forward. The proposed process is based on a two liquid phases reaction composed of an aqueous hydrochloric or hydrobromic acid phase and 1,2-dichloroethane (DCE) organic phase. We have optimized and compared the yields of CMF and BMF in an open flask and in a closed reaction vessels. Utilization of the close reaction vessel resulted in not only higher yields in a shorter reaction time but also eliminated the necessity of the customary lithium salts additives previously advocated for this process. These additives were required in the open reaction systems in order to achieve reasonable yields. While a closed reaction vessel was previously reported for the production of CMF, and in this work its production was further improved, it is the first time a close vessel protocol for the production of BMF has been reported. In addition, improvement of the substrate to organic solvent ratio has been carried while yields of halogenated furfurals were maintained almost intact. NMR and UV-vis spectroscopy were used for identification and quantification of the products.

Full text of DOI:10.1039/c6ra06050a

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Page 1 of 18
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Preparation of halogenated furfurals as intermediates in the
carbohydrates to biofuel process
Elad Meller, Avishay Aviv, Zeev Aizenshtat*, Yoel Sasson
*
The Institute of Chemistry, Casali Institute for applied Chemistry, The Hebrew University
of Jerusalem Edmund Safra campus in Givat Ram 91904 Israel
Emails: zeev@ vms.huji.ac.il; yoel.sasson@gmail.com;
Elad.meller@mail.huji.ac.il; avishay.aviv@mail.huji.ac.il
Corresponding author: Elad Meller
The Hebrew University of Jerusalem. Institute of Chemistry, Casali Bld. room 208 B Edmund
Saphra Campus. Phone 972ꢀ2ꢀ6585561 Fax 972ꢀ2ꢀ6585318
Abstract
Lignocellulose derived halogenated furfurals are important chemicals that can serve as
starting materials for diverse products such as drugs, polymers and fuels, including fuel
additives. In this paper a protocol for the synthesis of 5ꢀchloromethyl furfural (CMF) and
5
ꢀbromomethyl furfural (BMF) is put forward. The proposed process is based on a two
liquid phases reaction composed of an aqueous hydrochloric or hydrobromic acid phase
and 1,2ꢀdichloroethane (DCE) organic phase. We have optimized and compared the
yields of CMF and BMF in an open flask and in a closed reaction vessels. Utilization of
the close reaction vessel resulted in not only higher yields in a shorter reaction time but
also eliminated the necessity of the customary lithium salts additives previously
advocated for this process. These additives were required in the open reaction systems in
order to achieve reasonable yields. While a closed reaction vessel was previously
reported for the production of CMF, and in this work its production was further
improved, it is the first time a close vessel protocol for the production of BMF has been
reported. In addition, improvement of the substrate to organic solvent ratio has been
carried while yields of halogenated furfurals were maintained almost intact. NMR and
UVꢀvis spectroscopy were used for identification and quantification of the products.

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Introduction
As a consequence of depleting petroleum resources and increasing demand for energy as
well as augmented awareness to the negative environmental impact of petroleum based
energy production, mankind is seeking for renewable green fuels that can replace fossil
1
fuels. Amongst the available renewable energy resources (solar, wind, geothermal etc)
only biomass can supply organic carbon in liquid form that may serve as fuel for
2
transportation. At present there are two industrial scale processes for biofuel production:
the first is the conversion of vegetable oils to fatty acid esters, known as biodiesel, via
3
,4
transesterification.
The second is the production of bioꢀethanol from glucose
5
,6
fermentation. However, these methodologies rely mainly on agricultural farmlands
utilized towards fuel production instead of food production. Furthermore, calculations
proved that even if all farmlands were exploited to produce oilꢀbased fuels it would not
7
cover even a small fraction of the annual energy consumption today. Therefore, other
nonꢀedible resources of biomass must be considered in order to supply the increasing
energy demand. Lignocellulose is a very attractive source for biofuels since it is the most
abundant material in plants. It is much more abundant in nature than lipid based
8
,9
biomass. In contrast to sugars and starch, using lignocellulose as a raw material for fuel
production does not compete with food production since it is not edible. Lignocellulose
1
0
consists of cellulose (40ꢀ50%), hemicellulose (20ꢀ40%) and lignin (20ꢀ30%). While the
first two macromolecules comprised of chains of 6 or 5 carbon sugar molecules, lignin is
1
1
composed from phenylpropane and methoxy groups. Lignocellulosic biomass can be
converted to ethanol by a twoꢀstep process; hydrolysis and a subsequent fermentation
(see Fig. 1 Scheme 1). In this process the hydrolysis step is performed on cellulose and
hemicelluloses, while the lignin fraction of lignocellulose is inert and must be separated
12
from the mixture. The first step of the process is the hydrolysis of the polyꢀsugars using
dilute acid or enzymatic system, and the second step involves of the monoꢀsugars
1
3,14
fermentation to ethanol using yeasts or bacteria.
.

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Fig. 1 Summary of several reactions and products from carbohydrates based biomass:
Scheme 1ꢀ Two step bioꢀethanol production from cellulose; first step includes the
catalytic hydrolysis of cellulose to glucose sugar monomers with dilute acid or enzyme as
catalyst following a step involves fermentation to ethanol and carbon dioxide using yeasts
or bacteria. Scheme 2ꢀ Conversion of sucrose to levulinic acid and the by product formic
acid using diluted hydrochloric acid (This is a multistep reaction). Scheme 3ꢀ The
chemical structure of 5ꢀhydroxymethyl furfural, 5ꢀchlormethyl furfural and 5ꢀ
bromomethyl furfural. Scheme 4ꢀ Possible fuels synthesized from CMF via etherifiaction
with ethanol or via catalytic hydrogenation.

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The conversion of cellulose to ethanol is not only expensive and time consuming (in
6
,15
addition to several additional limitations), but it also exhibits a poor atom economy.
From the original carbon atoms in the reactant only 2/3 are retained in the product and the
other 1/3 are removed in the form of CO . In addition, this process requires large vessels
2
and removal of large quantities of water that consumes energy.
In an alternative approach cellulose (or hemicellulose) is converted in a multistep
1
6,17
reaction to levulinic acid and formic acid (see Fig. 1 Scheme 2).
In this process 5/6 of
the reactant’s carbons are retained in the product, and the other 1/6 carbons are
discharged in the form of formic acid. It has been reported by Cha and Hanna that the
activity of mineral acids in the hydrolysis of carbohydrates to levulinic acid decrease in
1
4.
8
the following orderꢀ HBr>HCl>H SO Levulinic acid can be transformed into biofuels
2
in several routes. One route is the esterification with an alcohol thus producing levulinate
1
9,20
ester.
Alternatively, levulinic acid can undergo hydrogenation/deoxygenation to form
γꢀvalerolactone that can proceed in a following step to various valuable products and
fuels such as hydrocarbons, valeric esters and 2ꢀmethyltetrahydrofuran by hydrogenation
2
1,22,23
or esterification.
acid takes place via the intermediate 5ꢀhydroxymethyl furfural (HMF, Fig. 1 Scheme
It was found that the transformation of carbohydrates to levulinic
2
4,25
3
).
In the case of HMF all the carbon atoms originated from the reactant are retained,
and the carbon atom economy is 100%. In this spirit, researchers examined methods for
HMF production and utilization as a platform for biofuel synthesis such as 5ꢀ
2
6
alkoxymethylfurfural and 2,5ꢀdimethylfuran.
Ionic liquid systems were also
8
,27,28
demonstrated for this aim.
However, the most promising results were reported by
Mascal and Nikitin, who demonstrated the conversion of cellulose into 5ꢀchloromethyl
furfural (CMF, Fig.1 Scheme 3) in a biphasic system of aqueous hydrochloric acid phase
2
9
containing LiCl and an organic 1,2ꢀdichloroethane (DCE) phase. An important facet in
this approach is the continuous extraction of the aqueous phase with organic solvent. In
this manner CMF is removed from the aqueous phase and therefore it does not continue
to react and form levulinic acid and/or other products. However, the major drawbacks of
this protocol are the prolong reaction time (30h) and the utilization of lithium chloride,
which is expansive and call for further treatment steps.

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Mascal and Nikitin improved the above protocol by reducing the reaction time and
solvent amount along with eliminating of LiCl salt. These advancements were achieved
3
0
by working in a closed reaction apparatus. Kumari et al., demonstrated in another
interesting study the formation of 5ꢀbromomethyl furfural (BMF, Fig. 1 Scheme 3) from
cellulose and other carbohydrates using a biphasic system of aqueous layer containing
3
1
hydrobromic acid and LiBr and an organic layer of toluene. There are two potential
pathways to obtain a biofuel from BMF or CMF: reacting these intermediates with
alcohol to form an ester, or hydrogenating them to form methyl furfural (see Fig. 1
3
0,31
Scheme 4).
In the present study the formation of CMF and BMF was modified to be more applicable
industrially than previously reported. CMF and BMF preparation in an open reaction
apparatus was compared to a closed reaction apparatus. An optimization of reaction
parameters in a closed reaction system has been carried for both CMF and BMF and the
formation of BMF without assistance of LiBr is reported for the first time. In addition
several improvements in the synthesis of halogenated furfurals were demonstrated. It
should be noted here that in the results section we address only to CMF and BMF yields.
However, many side reactions can occur during CMF and BMF synthesis and byproducts
such as HMF, levulinic acid and humic substances can be found in the aqueous phase as
29,30
reported by Mascal and Nikitin.
Nonetheless, these compounds are found in low
amounts and we will not refer to them in this work since we intended to focus on the
improvements in CMF and BMF preparation.
Materials and methods
Materials
Cellulose microcrystalline powder, 1,2ꢀdichloroethane (DCE) 99%, hydrobromic acid
4
3
8% and hydrobromic acid 62% were purchased from Sigma Aldrich. Hydrochloric acid
7% was purchased from Holland Moran LTD. Table sugar was used as a source for
sucrose. In order to obtain HCl or HBr solutions in different concentrations, the
appropriate acid was diluted with deionized water. For column chromatography silica gel
6
0 (0.04ꢀ0.063mm) purchased from MerckꢀLTD and sand (50ꢀ70 mesh particle size)
purchased from Sigma Aldrich were used as stationary phase while dichloromethane AR

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6
purchased from BioꢀLab LTD was used as the eluent. DMSOꢀd purchased from
Cambridge Isotope Laboratories Inc was used for NMR spectroscopy.
CMF and BMF synthesis
For reaction in an open apparatus, 1g of the carbohydrate was placed in a round bottom
flask. 15ml of an aqueous HCl or HBr solution containing 0.5ꢀ4g of LiCl or LiBr,
respectively, was added. Then 35ml of organic solvent, DCE, was added. The aqueous
phase acidity was adjusted by diluting the appropriate acid to the desired concentration.
The round bottom flask was placed in an oil bath preheated to the desired temperature,
5
0ꢀ90°C, and the biphasic system was vigorously stirred. After 30min the reaction was
stopped, the organic phase was separated, and another 35ml of DCE was added before the
reaction vessel has been returned to the oil bath and the reaction proceeded for another
3
0min. This process was repeated for a total time of 4h. At the end of reaction the total
organics were dried over anhydrous magnesium sulfate, and the product was further
analyzed.
The procedure for a reaction in a close apparatus is quite similar. In this case 0.3ꢀ0.6g of
the carbohydrate was measured and placed in a pressure tube, which was used as the
reaction vessel. Then 7ml of an aqueous acid solution, adjusted to the desired acid
concentration, and 10ꢀ20ml of organic solvent, DCE, were added. The pressure tube was
sealed and located in an oil bath preheated to the desired temperature, 80ꢀ115°C. After 1ꢀ
2
h the vessel was removed from the heated oil bath and the organic phase was separated
from the aqueous phase. Then, the aqueous phase was extracted with DCE for 1ꢀ3 more
times, depends on the specific experiment (the acid kind, the solvent amount). The total
reaction time was between 3ꢀ4h. At the end of reaction the combined organic layer was
dried over anhydrous magnesium sulfate, and the product was further analyzed.
Product identification and quantification
The identification of CMF and BMF products at the end of reaction has been carried with
NMR spectroscopy. Once CMF and BMF have been identified calibration curves of the
UVꢀvis spectra for molar absorption coefficient of these materials were established and
used for yields calculations by means of CMF and BMF concentrations determination.
For identification with NMR, CMF and BMF have been isolated and purified. The
isolation process was carried, after the evaporation of the organic solvent, by standing

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column chromatography composed of silica gel 60 (0.040ꢀ0.063mm) and sand (50ꢀ70
mesh particle size). Dichloromethane was used as the mobile phase. Then
dichloromethane was evaporated and the isolated product was examined by NMR
spectroscopy, Bruker DRXꢀ400 instrument (see supporting information).
The product yield was calculated by measuring CMF and BMF concentrations using UVꢀ
vis spectroscopy. UVꢀvis spectra were recorded with Varian Cary 100 Bio
spectrophotometer, at a wavelength range of 800ꢀ200nm. The molar absorption
coefficients of CMF and BMF were calculated using calibration curves (see supporting
information).
Results and discussion
CMF and BMF formation in an open reaction vessel
Sucrose, glucose and cellulose were tested as starting materials for CMF preparation.
Table 1 summarizes the yields obtained with an open reaction system at 70°C, with 0.5g
LiCl, for CMF preparation from the above substrates.
Table 1. CMF yields obtained under different condition from various carbohydrates.
HCl
concentration
Reaction
time
Substrate
Yield
Sucrose, 1g
Glucose, 1g
Cellulose, 1g
Cellulose, 1g
10M
10M
12M
12M
4h
4h
4h
8h
35%
7.4%
5.5%
9.4%
*
Experiments for Table 1 have been carried out at 70°C with 0.5g LiCl, 15ml HCl
solution and 35ml DCE that was replaced every 30min.
The results in Table 1 clearly show that sucrose reacts with HCl to produce CMF faster
than glucose and cellulose. Solutions of 10M HCl were used for reactions with sucrose
and glucose. However, when a solution of 10M HCl was applied for the conversion of
cellulose to CMF, the reaction yield was so low that the maximal acid concentration,
1
2M, had to be used. We can see from Table 1 that CMF yield from cellulose after a

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reaction time of 4h was 5.5%, and that extending the reaction time to 8h improved the
yield to 9.4%.
The critical parameters for CMF production from sucrose in an open reaction system
were determined. Fig. 2 demonstrates the effect of temperature and HCl concentration on
CMF yield from sucrose.
Fig. 2 CMF yield from sucrose as a function of: (a) temperature, 60ꢀ90°C, with constant
HCl concentration of 10M and (b) HCl concentration, 6ꢀ12M, with constant temperature
of 80°C. All reactions were carried out with 1g of sucrose, 0.5g LiCl, 15ml HCl solution,
3
5ml DCE that was replaced every 30min and reaction time of 4h.
The results presented in Fig. 2 are for reactions in an open reaction system. In each run
.5g of LiCl was added and the organic solvent was replaced after every 30min. The
0
results reveal that the biphasic reaction is much more sensitive to HCl concentration than
to temperature. In Fig. 2 (a) the effect of temperature at constant acid concentration of
1
0M was determined, and in Fig. 2 (b) the effect of HCl concentration with constant
temperature of 80°C was determined. At HCl concentration of 6M CMF yield of 9.2% is
obtained, while at 10M CMF yield is about 35%. Higher acid concentrations give lower
CMF yields, probably as a consequence of increased polymerization to humic materials,
2
9,30
as reported in literature.
When different temperatures were applied, under constant
HCl concentration of 10M, the yields did not vary to a greater extent. The highest CMF
yield, 35.6%, was achieved when temperature of 80°C was employed. Lower and higher
temperatures lead to a small decrease in yields, utilizing reaction temperatures of 60°C
and 90°C resulted in yields of 31.3% and 32.2%, respectively.

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The same substrates, sucrose, glucose and cellulose, were examined also in BMF
synthesis with HBr (48%, 8.89M) reagent. Table 2 summarizes the results of experiments
with HBr 8.89M, at temperature of 70°C and with 0.5g LiBr, for the preparation of BMF.
Table 2. BMF yields obtained at different conditions from various carbohydrates.
Reaction
Substrate
Yield
time
Sucrose, 1g
Glucose, 1g
Cellulose, 1g
Cellulose, 1g
4h
4h
37.8%
41.9%
15.2%
37.7%
4h
10h
*
Experiments for Table 2 have been carried out at 70°C with 0.5g LiBr, 15ml 8.89M
HBr solution and 35ml DCE that was replaced every 30min.
Table 2 shows that under the above conditions the yield of BMF from sucrose is 37.8%,
almost the same as for CMF. However, as the results imply, glucose and cellulose are
more receptive to halogenated furfural formation with HBr than with HCl. Under similar
conditions, BMF yield from cellulose is 15.2%, while CMF yield is about 3 times lower,
5
.5%. For BMF formation from cellulose, extending the reaction time from 4h to 10h
resulted in a higher BMF yield of 37.7%. The difference in acid reactivity is very
pronounced with glucose as a substrate. At the same reaction time and temperature, BMF
yield from glucose is 41.9% while CMF yield is only 7.4%, even though the number of
LiCl moles used in reaction is twice the number of LiBr moles. The most important
factors in BMF preparation from cellulose are the temperature and the amount of LiBr
salt (see Fig. 3).

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Fig. 3 BMF yields from cellulose as a function of: (a) LiBr salt amount, 0.5ꢀ4g, with
constant temperature of 70°C and (b) temperature, 50ꢀ90°C, with constant LiBr amount
of 3.5g. All reactions were carried out with 1g of cellulose, 15ml 8.89M HBr solution,
3
5ml DCE that was replaced every 30min and reaction time of 4h.
The experiments presented in Fig. 3 (a) were carried out at constant temperature of 70°C
and for Fig. 3 (b) with constant amount of LiBr, 3.5g. For both, the acid concentration
was 8.89M. From Fig. 3 (a) we can see that increasing the amount of LiBr has an
immense impact on BMF yields from cellulose. BMF yield of 15.2% was obtained with
0
4
.5g LiBr (0.0057 mole), while with 3.5g LiBr (0.04 mole) the yield has been ascended to
5.3%. From Fig. 3 (b) we may conclude that the temperature has much stronger impact
on BMF formation than on CMF formation. Increasing the temperature from 50°C to 90°
increased the yield of BMF from 6% to 59.5% (reached already at 80°C).
These results show that HBr is more reactive than HCl in the conversion of cellulose and
glucose to halogenated furfural in an open reaction system. There are number of
reasonable explanations for the difference between HCl and HBr reactivity: first, the
9
6
acidity of HBr is higher than HCl acidity (Ka= 1×10 for HBr compared to Ka= 1×10 for
HCl) and as a consequence it is more reactive in this reaction. A second possible
explanation relates to the volatility of the above acids. HCl is more volatile than HBr
(with boiling points of about 50°C and of 122°C, respectively) and it may evaporate out
of the system before it reacts. The third explanation might relate to the mechanism of the
reaction. It is possible that under the above conditions CMF formation has a different
mechanistic path in comparison with BMF formation. It seems reasonable to conclude
from the above results that the isomerization step is the slow step when HCl/LiCl system

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is used. On the other hand, it does not seem to be the case when HBr/LiBr system is
applied. This conclusion originates not only by the higher yields of BMF as compared to
CMF yields from cellulose and glucose, but also by the fact that BMF yields from these
substrates are also higher then the yields obtained from sucrose.
CMF and BMF formation in a close reaction vessel
LiCl and LiBr play an important role in the conversion of carbohydrates to furfurals, and
discarding these lithium salts has a great economical and environmental advantages. In
order to eliminate LiCl and LiBr salts experiments were carried in a close reaction
system. This modification resulted in an enhancement of halogenated furfural yields from
the various carbohydrates. CMF and BMF formation were tested in a glass pressure tube
(a close reaction vessel). BMF and CMF preparation in the pressure tube from cellulose
were optimized as a function of temperature and acid concentration. Results are shown in
Fig. 4 and Fig. 5. CMF and BMF yields obtained in a close reaction system in the
absence of Li salts were higher than the yields of the corresponding experiments
performed in the presence of a Li salt in an open reaction vessel. For CMF preparation in
a close reaction system, temperatures of 90ꢀ110°C and HCl concentrations of 9ꢀ12M
were examined. These experiments were carried out with 0.3g of cellulose, 7ml of acid
solution and 20ml of DCE. After 2h the reaction was stopped and the organic solvent was
removed, the aqueous phase was extracted with 20ml of organic solvent and then another
2
0ml of DCE was added and the reaction vessel placed again in the heated oil bath for
another 2h. The results are presented in Fig. 4.

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Fig. 4 The effect of temperature (90ꢀ110°C) and HCl concentration (9ꢀ12M) on CMF
yields in a close reaction system. All reactions were carried out with 0.3g cellulose,
reaction time of 4h, 7ml HCl solution and 20ml DCE that was removed after 2h and
replaced with fresh portion of 20ml DCE. Before the addition of a new DCE portion the
aqueous phase was extracted once with 20ml DCE.
It should be emphasized again that the experiments presented in Fig. 4 were carried out in
the absence of LiCl. The highest CMF yield, 82.6%, was obtained with HCl
concentration of 10M and at temperature of 110°C. At the same reaction time and
without using LiCl we were able to achieve a significantly higher CMF yield from
cellulose in a close reaction system than in an open reaction system at 70°C with LiCl.
This phenomenon can be attributed to the higher acidity evolved at elevated
temperatures, an acidity which could not be achieved in an open reaction system at lower
temperatures. Increasing the temperature in the open reaction system was not effective as
a consequence of HCl volatility at high temperatures.
Similar approach was adapted for BMF formation with HBr as the acidic reagent, without
using LiBr. BMF production in a close reaction system was never reported. The total
amount of organic solvent used in BMF preparation was higher than for CMF preparation
since the aqueous phase was extracted twice (in contrast to one extraction for CMF
preparation) with 20ml DCE when the reaction was stopped after 2h and the organic
solvent was removed. The variations in HBr concentration here were subtler than for
HCl, namely 8.5ꢀ9M, because BMF yield was more sensitive to variations in HBr
concentration in a close reaction system. Temperatures between 80ꢀ105° were examined.
The results for BMF preparation in a close reaction vessel are presented in Fig. 5.

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Fig. 5 The effect of temperature (80ꢀ105°C) and HBr concentration (8.5ꢀ9M) on BMF
yields in a close reaction system. All reactions were carried out with 0.3g cellulose,
reaction time of 4h, 7ml HBr solution and 20ml DCE that was removed after 2h and
replaced with fresh portion of 20ml DCE. Before the addition of a new DCE portion the
aqueous phase was extracted twice with 20ml DCE.
The results shown in Fig. 5 demonstrate that the optimal temperature and HBr
concentration are 95°C and 8.89M (HBr 48%), respectively. Here, BMF yield at the
optimal point was 74.3%. We may conclude that BMF yields were improved significantly
when the reaction was carried out in a close reaction vessel. With the open reaction
system the highest yield was 59.5%, while with a close reaction system the highest yield
was 74.3%.
Substrate to solvent ratio
Closed reaction system was proven to be the most effective for high yield production of
halogenated furfurals, BMF and CMF. These systems also enable the elimination of LiCl
and LiBr, which were needed in the customary systems described in literature. However,
improving the ratio of the organic solvent volume to the substrate loading, i.e. using
minimum solvent amount and maximal substrate loading, is also highly desirable. In the
systems described in section 3.2 the overall amounts of organic solvent used were 80ml
DCE for CMF and 120ml DCE for BMF, or 266.7ml/1g cellulose for CMF and 400ml/1g
cellulose for BMF. Improving the organic solvent volume/substrateꢀloading ratio is a key
parameter in order to make the process industrially applicable. Experiments comparing
different solvent volume/substrateꢀloading ratio have demonstrated the effect of this ratio
on CMF and BMF yields. These experiments were performed with 0.3g of cellulose at
the optimal temperature and acid concentration (10M HCl and 110°C for CMF and
8
.89M HBr and 95°C for BMF). The results are summarized in Fig. 6.

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Fig. 6 The effect of the organic solvent, 1,2ꢀdichloroethane (DCE), volume on CMF and
BMF yield from cellulose. The volume described here is the initial volume of 1,2ꢀ
dichloroethane, and also the volume used in each extraction.
The results in Fig. 6 show that the optimal volume of DCE is 20ml. At this volume of
DCE the CMF yield is 82.6% and BMF yield is 74.3%. As the volume of the organic
solvent decreased, the yield of the product was lower, probably as a result of a lower
portion of product being able to dissolve in the organic solvent. In order to find
improvements in organic solvent volume/substrateꢀloading ratio optimization of reaction
parameters with lower ratio of organic solvent volume to substrate loading was
necessary. To test lower proportion of organic solvent volume to the substrate loading,
cellulose amount was doubled from 0.3g to 0.6g, and DCE volume in reaction and in
each extraction was reduced to 15ml. Fig. 7 summarizes the results of these experiments
for both CMF and BMF preparation.

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Fig. 7 The effect of temperature and acid concentration on: (a) CMF yield with HCl as an
acid in a close reaction system, and (b) BMF yield with HBr as an acid in a close reaction
system. All reactions were carried out with 0.6g cellulose, reaction time of 3h, 7ml HCl
or HBr solution and 15ml DCE that was removed after every 1h and replaced with fresh
portion of 15ml DCE. Before the addition of a new DCE portion the aqueous phase was
extracted once or twice with 15ml DCE for CMF and BMF, respectively.
In experiments carried out and presented in Fig. 7 the extraction time was reduced from
2
h to 1h, and the reaction time was reduced from 4h to 3h. After every hour the organic
solvent was removed and extraction of the aqueous phase with another portion of DCE
was performed once for CMF and twice for BMF. We can see from Fig. 7 (a) that an
optimal CMF yield of 77.3% was recorded when 10M HCl solution and temperature of
1
10°C were applied, and from Fig. 7 (b) that an optimal BMF yield of 66.8% was
recorded when 8.89M HBr solution and temperature of 100°C were applied. The decrease
in yields recorded for increased cellulose loading and reduced organic solvent volume
were 7.5% for BMF and 5.3% for CMF. In addition, although the reaction time was
reduced the number of extractions increased since the reaction was stopped and extracted
after every 1h in this case, instead of after every 2h. However, using volume of 15ml
DCE instead of 20ml in reaction and in each extraction brings to a net improvement in
the organic solvent volume/substrateꢀloading ratio. Now for 1g of cellulose we use a total
of only 150ml DCE for CMF preparation and 225ml DCE for BMF preparation. These
proportions are also much better in comparison with those reported in literature, namely
3
0,31
1
120ml DCE/1g cellulose for CMF and 585ml toluene/1g cellulose for BMF.
Conclusions
CMF and BMF preparation from various biomassꢀderived carbohydrates was studied and
optimized in a biphasic system of an aqueous HCl or HBr layer and an organic DCE
layer. An open reaction system showed that LiCl and LiBr are needed for the reaction in
order to receive reasonable yields of CMF and BMF, respectively. In addition, results
indicate that in an open reaction system HBr/LiBr system is more reactive than HCl/LiCl
system for the conversion of glucose and cellulose to halogenated furfural. CMF

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formation and BMF formation in a close reaction apparatus were demonstrated.
Experiments proved that operating in a close reaction system at higher temperatures have
three important advantageous over open reaction system: first, higher yields of 82.6%
CMF and 74.3% BMF were achieved at lower reaction time compared to the optimized
yields attained with an open reaction system. Second, LiCl and LiBr were no longer
needed for the reaction to proceed. This fact has a great impact on the possible
application of the process, since using lithium halides would make the process more
expansive and less environmentally friendly. Third, the total volume of the organic
solvent, DCE, was reducedꢀ instead of using 1120ml and 585ml of organic solvent per 1g
cellulose for CMF and BMF, respectively, as reported in literature, we needed only
2
66.7ml and 400ml of DCE per 1g cellulose for CMF formation and BMF formation,
respectively. Nonetheless, in order to make the process more efficient the organic solvent
volume/substrateꢀloading ratio was further improved. By performing more extractions at
shorter periods of time between extractions (extractions performed after every 1h with
total reaction time of 3h instead of after 2h and a total reaction time of 4h), while the
amount of cellulose substrate was increased from 0.3g to 0.6g and of the organic solvent
volume decreased from 20ml to 15ml. Then yields of 77.3% of CMF and 66.8% of BMF
were recorded. Now the efficacy of the system was improved since only 150ml and
2
25ml DCE per 1g cellulose were used for CMF and BMF preparation, respectively.
Acknowledgments
We thank the Israel Strategic Alternative Energy Fund (IꢀSAEF) for financial support of
this research. Special thanks for supporting in part the Ph.D. scholarship of E.M.
References
1
2
3
4
5
. I. Dincer, Renewable Sustainable Energy Rev. 2000, 4, 157ꢀ175.
. G. W. Huber, A. Corma, Angew. Chem., Int. Ed. 2007;45, 7184ꢀ7201.
. F. Ma, M. A. Hanna,. Bioresour. Technol. 1999, 70, 1ꢀ15.
. K. Narasimharao, A. Lee, K. Wilson, J. Biobased Mater. Bioenergy. 2007, 1, 19ꢀ30.
. M. O. S. Dias, A. V. Ensinas, S. A. Nebra, R. M. Filho, C. E. V. Rossell, M. R. W.
Maciel, Chem. Eng. Res. Des. 2009, 87, 1206ꢀ1216.
6
. M. Balat, H. Balat, C. Oz, Prog. Energy Combust. Sci. 2008, 34, 551ꢀ573.
7
. S. Lestari, I. Simakova, A. Tokarev, P. MakiꢀArvela, K. Eranen, D. Y. Murzin, Catal.
Lett. 2008, 122, 247ꢀ251.

Page 17 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA06050A
8
. O. O. James, S. Maity, L. A. Usman, K. O. Ajanaku, O. O. Ajani, T. O. Siyanbola, S.
Sahu, R. Chaubey, Energy Environ. Sci. 2010, 3, 1833ꢀ1850.
. J. A. Geboers, S. Van de Vyver, R. Ooms, B. Op de Beeck, P. A. Jacobs, B. F. Sels,
Catal. Sci. Technol. 2011, 1, 714ꢀ726.
9
1
1
3
1
1
1
1
1
1
1
9
1
1
0. H. Kobayashi, H. Ohta, A. Fukuoka, Catal. Sci. Technol. 2012, 2, 869ꢀ883.
1. C. N. Hamelinck, G. Van Hooijdonk, A. P. C. Faaij, Biomass Bioenergy. 2005, 28,
84ꢀ410.
2. P. Alvira, E. TomasꢀPejo, M. Ballesteros, M. J. Negro, Bioresour. Technol. 2010,
01, 4851ꢀ4861.
3. Y. Sun, J. Cheng, Bioresour. Technol. 2002, 83, 1ꢀ11.
4. M. Galbe, G. Zacchi, App. Microbiol. Biotechnol. 2002, 59, 618ꢀ628.
5. F. W. Bai, W. A. Anderson, M. MooꢀYoung, Biotechnol. Adv. 2008, 26, 89ꢀ105.
6. D. W. Rackemann, W. O. S. Doherty, Biofuels, Bioprod. Biorefin. 2011, 5, 198ꢀ214.
7. K. Yan, C. Jarvis, J. Gu, Y. Yan, Renewable Sustainable Energy Rev. 2015, 51, 986ꢀ
97.
8. J. Y. Cha, M. A. Hanna, Ind. Crops Prod. 2002, 16, 109ꢀ118.
9. K. Y. Nandiwale, S. K. Sonar, P. S. Niphadkar, P. N. Joshi, S. S. Deshpande, V. S.
Patil, V. V. Bokade, Appl. Catal., A. 2013, 460ꢀ461, 90ꢀ98.
0. D. R. Fernandes, A. S. Rocha, E. F. Mai, C. J. A. Mota, V. T. da Silva, Appl. Catal.,
A. 2012, 425ꢀ426, 199ꢀ204.
2
2
1
2
1. J. C. SerranoꢀRuiz, D. J. Braden, R. M. West, J. A. Dumesic, Appl. Catal., B. 2010,
00, 184ꢀ189.
2. J. M. Tukacs, D. Kiraly, A. Stradi, G. Novodarszki, Z. Eke, G. Dibo, T. Kegl, L. T.
Mika, Green Chem. 2012, 14, 2057ꢀ2065.
2
2
2
2
2
3. K. Yan, Y. Yang, J. Chai, Y. Lu, Applied Catalysis, B: Environmental 2015, 179,
92ꢀ304.
4. J. Horvat, B. Klaic, B. Metelko, V. Sunjic, Tetrahedron Lett. 1985, 26, 2111ꢀ2114.
5. M. Mascal, E. B. Nikitin, ChemSusChem. 2010, 3, 1349ꢀ1351.
6. R. J. van Putten, J. C. van der Waal, E. de Jong, C. B. Rasrendra, H. J. Heeres, J. G.
de Vries, Chem. Rev. 2013, 113, 1499ꢀ1597.
2
1
2
7. X. Qi, M. Watanabe, T. M. Aida, Smith Jr R. L. Smith Jr, Cellulose. 2011, 18, 1327ꢀ
333.
8. Y. J. PaganꢀTorres, T. Wang, J. M. R. Gallo, B. H. Shanks, J. A. Dumesic, ACS
Catal. 2012, 2, 930ꢀ934.
29. M. Mascal, E. B. Nilitin, Angew. Chem. 2008, 120, 8042ꢀ8044.
30. M. Mascal, E. B. Nikitin, ChemSusChem. 2009, 2, 859ꢀ861.
31. N. Kumari, J. K. Olesen, C. M. Pedersen, M. Bols, Eur. J. Org. Chem. 2011, 1266ꢀ
1270.

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Graphical abstract
Efficient processes for the production of CMF and BMF are demonstrated in a biphasic
system of aqueous acid and 1,2-dichloroethane.