5-(Chloromethyl)furfural production from glucose: A pioneer kinetic model development exploring the mechanism

Article abstract of DOI:10.1002/kin.21485

Conversion of glucose to 5-(chloromethyl)furfural (CMF) is one of the well-known high yield unit processes in lignocellulosic biomass valorization. A kinetic modeling study was not reported for the reaction, owing to the complexity in quantification of CMF. Herein we have successfully developed a rapid, sensitive, and specific HPLC method (reverse phase) to quantify the generated CMF (range: 10–650?μg/mL) in a dichloroethane solvent. The Box–Behnken design of experiment method employed for the statistical optimization. A kinetic model was developed based on the homogeneous first-order kinetic model, and the results are in good agreement with the experiment data. The formation of CMF, 5-(hydroxymethyl)furfural, formic acid, levulinic acid, and humins from glucose and HCl were modeled using a serial parallel reaction mechanism. The apparent activation energy (E_a) for glucose decomposition and CMF formation is 99 and 31 kJ/mol.

Full text of DOI:10.1002/kin.21485

Received: 28 January 2020
DOI: 10.1002/kin.21485
Revised: 11 January 2021
Accepted: 15 February 2021
A RT I C L E
5-(Chloromethyl)furfural production from glucose:
A pioneer kinetic model development
exploring the mechanism
Churchil A. Antonyraj1,2
Amal J. Chennattussery2,3
Ajit Haridas2
1 Department of Chemistry, PSG College
of Arts & Science, Coimbatore, India
Abstract
2 Environmental Technology Division,
CSIR-National Institute for
Interdisciplinary Science and Technology,
Council of Scientific and Industrial
Research, Thiruvananthapuram, India
3 Department of Biochemistry and
Biochemical Engineering, Sree Chitra
Thirunal College of Engineering,
Thiruvananthapuram, India
Conversion of glucose to 5-(chloromethyl)furfural (CMF) is one of the well-
known high yield unit processes in lignocellulosic biomass valorization. A
kinetic modeling study was not reported for the reaction, owing to the complexity
in quantification of CMF. Herein we have successfully developed a rapid, sensi-
tive, and specific HPLC method (reverse phase) to quantify the generated CMF
(range: 10–650 μg/mL) in a dichloroethane solvent. The Box–Behnken design of
experiment method employed for the statistical optimization. A kinetic model
was developed based on the homogeneous first-order kinetic model, and the
results are in good agreement with the experiment data. The formation of CMF,
5-(hydroxymethyl)furfural, formic acid, levulinic acid, and humins from glucose
and HCl were modeled using a serial parallel reaction mechanism. The apparent
activation energy (Ea) for glucose decomposition and CMF formation is 99 and
31 kJ/mol.
Correspondence
Churchil A. Antonyraj, Departmentof
Chemistry, PSG CollegeofArts & Science,
Coimbatore 641014, India.
Email:churchilangel@psgcas.ac.in;
churchilangel@gmail.com
K E Y WO R D S
5-(chloromethyl)furfural, design of experiment, glucose dehydration, kinetic model, nonlinear
least-squares method
1
INTRODUCTION
ate produced from cellulose/lignocellulosic biomass using
concentrated HCl.4,5 Like conversion of CMF to feed-
Lignocellulose from agro-industrial waste is a key biomass
resource, which has highest availability (200 × 109
tons/year) and nonedible.1,2 Ecofriendly production of
feedstock chemicals from such biomass resources remains
a challenge owing to the complexity of biomass struc-
ture and the need of technical knowledge in reaction
engineering.3 The intention of developing a kinetic model
for glucose to 5-(chloromethyl)furfural (CMF) conversion
to understand the reaction network in the acid catalyst
medium. CMF is one of the high yielding intermedi-
stock chemicals, conversion to fuel is also a well-studied
reaction.6,7 Well-established industrial production of HCl
and recovery of used HCl using membrane techniques
renders it a potential catalyst.8–10 CMF has been used as
an intermediate chemical for the synthesis of drugs like
ranitidine.11,12 Chang etal. used CMF as an intermediate
for the synthesis of prothrin, a synthetic insecticide, in a
six-step synthesis with 65% yield.13 Three US companies
have succeeded in the commercial synthesis of CMF for
the production of fuels, fuel additives, and p-xylene.6,14
CMF can also be utilized for the synthesis of highly pure
5-(acetoxymethyl)furfural under mild reaction conditions
in a continuous reaction.15
Abbreviations: CMF, 5-(chloromethyl)furfural; DCE, dichloroethane;
FA, formic acid; HMF, 5-(hydroxymethyl)furfural; LA, levulinic acid;
MIBK, methyl isobutyl ketone
Int J Chem Kinet. 2021;1–9.
wileyonlinelibrary.com/journal/kin
© 2021 Wiley Periodicals LLC
1

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ANTONYRAJ et al.
also formed during the reaction. Kinetic analysis of main
reaction (CMF formation) as well as all intermediate reac-
tions was performed. Different control experiments were
also performed to understand the basic reaction mecha-
nism.
The chemical kinetic model was implemented using
MATLAB, a matrix-based mathematical software pack-
age, for a first-order reaction involving concentrated HCl
both as a reactant and a catalyst in a water–DCE biphasic
medium. The resultant kinetic studies and models are con-
sistent with the proposed mechanism.
2
EXPERIMENTAL
Materials
S C H E M E 1 Possible reaction pathways for conversion of
glucose to CMF [Color figure can be viewed at
wileyonlinelibrary.com]
2.1
d-(+)-Glucose (97.5%, EMPARTA ACS), d-(−)-fructose
(EMPARTA), formic acid (FA; 98–100%; EMPARTA ACS),
LA, 1,2-dichloroethane (EMPARTA ACS), and hydrochlo-
ric acid (35% EMPLURA) were purchased from Merck
chemicals, Germany, and used without any further purifi-
cation. 5-(Hydroxymethyl)furfural (≥99% FG) and furfural
(99%) were purchased from Sigma Aldrich chemicals.
HPLC solvents were acquired from Merck chemicals, Ger-
many, and hydrochloric acid (38%) was purchased from
Fisher Chemical, and solutions were prepared using Milli
Q water.
CMF production is a biphasic reaction, and the possi-
ble reaction pathway involves multiple unitary reactions
as given in Scheme 1. The kinetic analysis of conversion of
glucose to CMF by exploring the underlying mechanism
has few reports in contrast to other feedstock chemicals
like 5-(hydroxymethyl)furfural (HMF) or levulinic acid
(LA).16–19 This might be due to the unavailability of analyt-
ical methods for the quantification of CMF, that is, in the
literature, the CMF was quantified by complex procedures
like solvent evaporation followed by column chromatogra-
phy (to remove other furan-based soluble polymers). In a
kinetic study, time/temperature variation may lead to mild
deviation in the yield/conversion, and it should be quanti-
fied accurately to develop a well-defined kinetic model. So,
the above-reported method is cumbersome for the quan-
tification of CMF yield. Yet other reports have employed
a NMR-based method and an UV–vis spectroscopy based
method for the quantification of CMF.20,21 Consequently,
the development of a sensitive, specific, and valid analyti-
cal method for the routine analysis of CMF remains a pri-
mary requisite.
The Box–Behnken design of experiment (DOE) method
employed here circumvented the customary steps, thereby
reducing the number of reactions to be performed to
15. Time, temperature, and acid concentration are three
important reaction parameters in the conversion of glucose
to CMF. As mentioned in Scheme 1, conversion of glucose
to CMF may involve multiple steps. A reverse-phase HPLC
technique has been successfully developed for quantitative
assay of CMF in dichloroethane (DCE) solvent. It must be
mentioned here that DCE is the commonly employed sol-
vent for CMF production from mono/polymeric carbohy-
drates.
2.2
Experimental procedure
Reactions were carried out in a round-bottomed glass reac-
tor with magnetic stirring in a preheated oil bath. For a
typical reaction, 150 mg of glucose was added in a reactor
tube to which 6 mL of DCE and then selected volume of
acid was added. This was placed in a preheated oil bath at
desired reaction temperature and stirred at 600 rpm for a
specified reaction time. After each reaction, a glass reac-
tor was cooled to room temperature, to which calculated
volume of water and DCE was added to obtain a solvent
ratio of 6 : 12 mL (water: DCE ratio). This solvent ratio was
retained after each reaction to make HPLC analysis simple.
This was shaken well to extract all CMF into the organic
layer (DCE), and both aqueous as well as organic layer
were collected separately. The aqueous layer was diluted
and analyzed for glucose conversion along with the yield
of LA, FA, and HMF. The aqueous layer was analyzed in
a Shimadzu HPLC spectrometer (LC-10AD with RID 6A
RI detector) using 0.008N H2SO4 buffer, Bio-Rad Aminex
HPX-87H (300 × 7.8 mm) column at 50◦C, and results were
analyzed using Autochro-3000 software. The organic layer
was diluted and analyzed for CMF and HMF yield using
Apart from the main product CMF, the other possible
intermediates like fructose, HMF, LA, humins, etc. were

ANTONYRAJ et al.
3
TA B L E 1 Factors selection for optimization of CMF formation
by the Box–Behnken design
a DIONEX HPLC (Ultimate 3000) chromatograph using a
reversed-phase C18 column (150 × 4.6 mm). The optimized
mobile phase consists of methanol and 0.5 % acetic acid
solvents with 7:3 ratio at 30◦C, and the results were ana-
lyzed using Chormelon software. The conversion and the
yield of the products can be defined by the following
equation:
Independent
Level
(1)
37.2
80
2
Level
(0)
24.8
60
1
Level
Factors
Unit
mmol
◦C
(−1)
Acid concentration
Temperature
Time
12.4
40
h
0.5
Conversion %
( )
3
RESULTS AND DISCUSSION
moles of initial reactant – moles of final reactant
(
)
=
moles of initial reactant
(
)
CMF is a low melting solid (pure state) at room tem-
perature and is freely soluble in organic solvents like
methanol and acetonitrile. Different solvent proportions
of methanol, acetonitrile, and 0.1–2% acetic acid solutions
were screened to obtain a CMF yield peak with tailing
factor >2.22 Acetic acid sharpens the HMF peak, which
was broader due to the hydroxyl group, whereas increased
methanol ratio resulted in drastic reduction of CMF peak
tailing. CMF in DCE was quantitated by a rapid reversed-
phase HPLC method (sensitivity: 650–10 μg/mL).
The isocratic elution of CMF and HMF was done as
mentioned in the Experimental Procedure (Figure S2 in
the Supporting Information). Moreover, the residual con-
centration of HMF can also be quantitatively determined
under the above conditions. HPLC analysis has shown
linearity in CMF concentrations ranging from 650 to
10 μg/mL as shown in Figure S3 in the Supporting Informa-
tion. The linear regression coefficient obtained using the
least square method is 0.991. Temperature, time, and acid
volume/concentration are the three crucial factors which
influence glucose to CMF conversion using the biphasic
medium. Table 1 shows the values of these parameters
tested in the Box–Behnken design. The selection criteria of
these factors were based on the results reported in the liter-
ature. To reduce the complexity of this reaction, the effect
of salt addition like LiCl, LiBr, or NaCl was not included
in this study. The results obtained from the 17 experimen-
tal runs, which were carried out according to the Box–
Behnken design with three variable factors, are summa-
rized in Table S1 in the Supporting Information.
∗ 100
moles of product
(
)
Yield %
=
∗ 100
( )
moles of initial reactant
(
)
2.3
Synthesis of CMF
180 mg of HMF ((≥99% Aldrich) added in the glass reac-
tor was dissolved in 6 mL of DCE and placed in an oil
bath at 70◦C for 5 min to which 12.4 mmol of concentrated
HCl was added, and the reaction was continued for 1 h
with stirring. After the reaction, 5 mL of water and another
6 mL of DCE were added, and the organic layer was sepa-
rated. Anhydrous sodium sulfate was added to remove the
moisture and DCE removed under reduced pressure. The
yellow viscous liquid obtained was dissolved in minimum
amount of CH2Cl2 and purified by column chromatogra-
phy using silica gel (60–120) and CH2Cl2 as eluent. This
CMF was further characterized using mass spectral anal-
ysis, and the result is given in Figure S1 in the Supporting
Information.
2.4
System suitability
The system suitability of HPLC method was analyzed by
six replicate analyses of the CMF at a concentration of
210 μg/mL. The acceptance criterion was 2% for the per-
cent coefficient of variation (%CV) for the peak area and
retention times for CMF.
The (0,0,0) condition was repeated five times; 1% vari-
ation in the conversion and selectivity was observed (Table
S1). Temperature has a major influence in the conversion of
glucose on increasing the temperature, glucose conversion
as well as CMF selectivity increased. Under all conditions,
reactions at 80◦C showed three times higher glucose con-
version than at 40◦C. The maximum glucose conversion
(77.2%) and CMF selectivity (38.1%) was seen for 24.8 mmol
acid at 80◦C for 3 h reaction time, whereas 37.2 mmol acid
at 80◦C for 2 h showed 72.6% conversion with 38% CMF
yield (entries 8 and 4, Table S1). The cumulative influence
of different parameters on the reaction can be expressed by
2.5
Determination of the kinetic
parameters
The kinetic parameters were determined based on mini-
mization of the errors between the experimental data and
the kinetic model. Error minimization to determine the
best estimate of the kinetic parameters was performed
using the built-in MATLAB function lsqnonlin, a non-
linear least-squares method based on the Trust- Region-
Reflective algorithm.

4
ANTONYRAJ et al.
a quadratic equation as given below:
Glucose conversion
= 24.39 − 2.5 × (Acid Conc) + 26.8 × (Temp)
+ 5.2475 × (Time) + 3.56 × (Acid Conc × Temp)
+ 3.4625 × (Acid Conc × Time) + 5.4225
× (Time × Temp) + 3.108 × (Acid Conc)2
+ 14.008 × (Temp)2 + 2.15 × (Time)2
CMF yield
= 9.24 − 0.32 × (Acid Conc) + 17.96 × (Temp)
+ 4.32 × (Time) + 0.21 × (Acid Conc × Temp)
+ 0.07 × (Acid Conc × Time) + 2.04
× (Time × Temp) + 2.58 × (Acid Conc)2
+ 7.04 × (Temp)2 + 0.79 × (Time)2
F I G U R E 1 Response surface plot for cumulative influence of
different parameters on glucose conversion and CMF yield obtained
by the Box–Behnken design [Color figure can be viewed at
wileyonlinelibrary.com]
The cumulative influence of different parameters on
glucose conversion and CMF yield obtained by means
of Box–Behnken design (response surface methodology
[RSM] analysis) using SAS JMP11 software is given in
Figure 1. In all different combinations, elevated temper-
ature leads to high glucose conversion and thereby high
CMF yield. Humins (furan-based polymer) formation also
increased simultaneously with increased temperature. The
presence of high humin levels made the product mixture
darker in color, thus confirming high humin formation
throughout our study (our studies were done without any
added salt).
model is smaller than 0.002, whereas R2 values of 0.99 for
glucose conversion and 0.98 for CMF yield, respectively,
reveals the statistically significant relationship between
the variables.
To comprehend the underlying mechanism of the CMF
formation, different control experiments were carried out
and the results are given in Table 2. Glucose dehydra-
tion performed in aqueous medium without addition of
organic solvent produced no CMF; on the contrary HMF,
LA, and FA were formed. Similarly, glucose dehydration
performed with conc. HCl in the absence of additional
water or organic solvent attained only 0.5% CMF along
with FA (10.7%), LA (5.9%), and humins. Accordingly,
under these reaction conditions, formation of degrada-
tion products like LA and FA dominates than the furanic
compounds. Owing to no CMF formation, we may have
neglected the possibility of direct formation of CMF from
glucose for kinetic studies. Chlorination of HMF in DCE
yielded the maximum of 75% CMF along with the forma-
tion of LA and FA, whereas a similar reaction of HMF
in water alone might have generated CMF which possi-
bly could have migrated to organic layer (Table 2. entries
3 and 4). Consequently, no CMF was found in the analysis
of the water layer by HPLC. We did not find any CMF in the
water layer under biphasic conditions we cannot do kinetic
studies for HMF to CMF conversion in the water layer and
Glucose conversion has a linear relationship with fac-
tors like temperature and acid concentration. Regard-
less of the acid concentration, glucose conversion was
high at 80◦C. Glucose conversion increased with increas-
ing temperature/acid concentration. However, the acid
concentration showed lesser influence than tempera-
ture (Figure 1(A)). A trend was observed in CMF
yield (Figure 1(B)); at 40◦C, no CMF was formed at
any of the applied levels of acid concentration and
time. Both temperature and time have remarkable influ-
ence on glucose conversion/CMF yield; conversion and
yield increased with increasing time/temperature. RSM
showed that 98% glucose conversion and 53% CMF yield
were the maximum possible conversion/selectivity with
the different parameters optimized in 24.8 mmol acid
concentration.
Correlation between predicted and experimental values
of glucose conversion and CMF yield shows that the model
is significant and acceptable (Figure 2). The P value of the

ANTONYRAJ et al.
5
F I G U R E 2 Correlation between predicted and experimental values of (A) glucose conversion and (B) CMF yield [Color figure can be
viewed at wileyonlinelibrary.com]
TA B L E 2 Control experiments for the CMF formation mechanism
Glucose
conversion (%)
CMF
yield (%)
HMF
yield (%)
LA yield
(%)
FA yield
(%)
S. No
Reactants
1
150 mg Glucose, 24.8 mmol HCl, 4 ml H2O
150 mg Glucose, 24.8 mmol HCl
126 mg HMF, 6 mL DCE, 24.8 mmol HCl
126 mg HMF, 4 mL H2O, 24.8 mmol HCl
150 mg Glucose, 6 mL MIBK, 24.8 mmol HCl
17
28
–
–
46
0
2.1
0.7
5.9
9.4
21.4
0
3.8
2
3
4
5
0.5
74.5
0
2.3
5.3
54.2
7.0
10.7
10.5
33.2
0
0.13
Condition: Temperature 70◦C, time 1 h, rpm 650.
its migration without knowing the concentration (Table 2).
HMF extracted in the organic phase immediately was con-
verted to CMF. Utilization of nonchlorinated organic sol-
vents like (methyl isobutyl) ketone yielded no CMF from
HMF. Chlorinated solvent (DCE) is one of the important
conditions for the formation of CMF.
a reaction mechanism for CMF formation from glucose in
Scheme 2. The kinetic model proposed has the following
key steps: (1) glucose dehydration to HMF, (2) HMF phase
transfer, (3) HMF chlorination to CMF in DCE, (4) HMF
degradation to FA and LA in water, (5) decomposition of
HMF in water layer to humins, (6) glucose decomposition
to degradation products (FA, furfural, and humins). Here,
k1 is the rate constant for the formation of HMF from glu-
cose; k2 and k3 are the rate constants for mass transfer of
HMF between water and DCE layer; k4 is the rate constant
It is necessary to be mentioned here that the forma-
tion of HMF from glucose is well-studied in the literature,
and the possible formation of fructose, reversion products,
and levoglucosan from glucose was also reported.19,23–25
On the contrary, no levoglucosan was found to be pro-
duced during our reaction and less than 1% fructose was
obtained. Henceforth, we assume that glucose has under-
gone irreversible reactions like dehydration to HMF as
well as degradation to polymers in concurrent to other
reports in the literature.19,24 HMF undergoes a reversible
phase transfer between water and DCE layers. HMF could
possibly be degraded to LA and FA in the water layer;
whereas in DCE, HMF was easily converted to CMF rather
than undergoing degradation. The amount of FA formed
in the water layer is not stoichiometrically equal to that of
LA; this leads to the probable conclusion that HMF was
degraded to FA and humins via the intermediate furfural
as reported in the literature.18
S C H E M E 2 Mechanism for CMF formation from glucose
[Color figure can be viewed at wileyonlinelibrary.com]
Based on the above products obtained from control reac-
tions including the stoichiometric excess of FA, we propose

6
ANTONYRAJ et al.
F I G U R E 3 Comparison of CMF production from glucose (A) 80◦C as a function of time and (B) 70◦C as a function of time, (glucose
(blue spheres), FA (black spheres), LA (green spheres), CMF (red spheres), HMF in DCE (yellow spheres), and HMF in H2O (purple spheres),
# Conditions: Glucose 150 mg, HCl 24.8 mmol, DCE 6 mL [Color figure can be viewed at wileyonlinelibrary.com]
for the formation of CMF from HMF in DCE layer; k5 is the
rate constant for the degradation of HMF to LA and FA in
aqueous phase; k6 is the rate constant for the degradation
to FA and humins; k7 is the rate constant for the formation
of degradation products from glucose.
CMF formation was modeled based on the simplified
reaction mechanism given in Scheme 2. Since the concen-
tration of HCl is far greater than the other reactant glucose,
all reactions are considered as first order.
concentration, and kinetic parameters were determined
with the same acid concentration. Experimental results
were fitted to the kinetic model to calculate the kinetic
parameters with the proposed mechanism in Scheme 2.
Kinetics of possible reactions involved in CMF formation
were independently studied at two different temperatures,
and the variable products formed were modeled to fit with
experimental results (Figure 3 and Table 3).
Figure 3(A) shows the experimental results of glucose
conversion studied at 80◦C with 24.8 mmol HCl, 70% glu-
cose conversion was achieved within 1 h, and LA or FA
formation was detected within 0.5 h. FA remains as the
major product throughout the reaction at 80◦C, which has
higher concentration than LA. This confirms the possi-
ble formation of humins immediately after the onset of
reaction which leads to excess FA. Maximum CMF for-
mation was observed at 2 h and thereafter the CMF con-
centration decreased this might be due to back extrac-
tion of CMF to aqueous layer followed by hydrolysis to
HMF and ultimately undergoing decomposition. HMF was
present in both water and DCE phases; after 0.5 h, high
HMF concentration was obtained. It needs to be men-
tioned here that a small amount of furfural (<1%) was also
detected under these reaction conditions. With the pro-
gression of time, the initially formed HMF present in both
aqueous layer and organic layer decreased which might
be due to the formation of LA, FA, or humins. The effect
of both acid concentration and temperature on the glu-
cose conversion, CMF, LA, and FA yield was given in Fig-
ure S4 in the Supporting Information. At 70◦C, the glu-
cose concentration slowly decreased simultaneously with
the formation of CMF, LA, and FA. Up to 1.5 h reac-
tion time, LA and FA showed equal concentrations and
thereafter FA dominates. This confirms that up to 1.5 h,
HMF prefers to degrade into LA and FA rather than as
The overall rate equation for the biphasic production of
CMF from glucose is given below:
ꢀ Glu
(
)
1
7
= −ꢂ × Glu − ꢂ × Glu
(1)
(2)
[
]
[
]
ꢀꢁ
ꢀ CMF
(
)
4
= ꢂ × HMFo
[
]
ꢀꢁ
ꢀ HMFw
(
)
2
6
= ꢂ1 × Glu − ꢂ × HMFw − ꢂ
[
]
[
]
ꢀꢁ
5
3
× HMFw − ꢂ × HMFw + ꢂ HMFo
[
]
[
]
[
]
(3)
ꢀ HMFo
(
)
2
3
= ꢂ × HMFw − ꢂ × HMFo
[
]
[
]
ꢀꢁ
4
−ꢂ × HMFo
[
(4)
(5)
(6)
]
ꢀ LA
(
)
5
= ꢂ × HMFw
[
]
ꢀꢁ
ꢀ FA
(
)
5
6
= ꢂ × HMFw + ꢂ × HMFw .
[
]
[
]
ꢀꢁ
Kinetic studies of all the reactions were modeled by
assuming the first-order reaction with respect to the acid

ANTONYRAJ et al.
7
TA B L E 3 Kinetic parameters for the formation of CMF from glucose in the bi-phasic medium
Entry No
1
2
3
Temperature
80
70
k1
0.70
0.26
k2
k3
k4
3.00
2.19
k5
k6
5.96
3.84
k7
0.44
0.28
95.43
79.99
–
50.74
24.31
–
10.01
5.60
58.37
Ea (kJ/mol)
98.99
31.47
44.12
43.30
F I G U R E 4 Comparison of CMF production from glucose (A) 80◦C as a function of time and (B) 70◦C as a function of time, glucose
(blue spheres), FA (black spheres), LA (green spheres), CMF (red spheres), HMF in DCE (yellow spheres), and HMF in H2O (purple spheres)
along with model predictions (lines). # Conditions: Glucose 150 mg, HCl 12.4 mmol, DCE 6 mL [Color figure can be viewed at
wileyonlinelibrary.com]
FA and humins. After 1.5 h, both the degradations were
possible which leads to excess LA, the formation of CMF
increased up to 3 h. Results obtained from the experi-
ments were fitted to the kinetic model proposed to calcu-
late the kinetic parameters. Moreover, it needs to be men-
tioned here that the experimental values agreed relatively
with the modeling results which validates the proposed
mechanism. The activation energy calculated for HMF for-
mation from glucose is 98.99 kJ/mol, whereas formation
of HMF directly from glucose was reported 108 and 160
kJ/mol higher than other report.19,26 Similar reports on
conversion in water using H2SO4 and H3PO4 acids were
128 and 121 kJ/mol, respectively, which was higher than our
observed activation energy.27–29 But reactions using ionic
liquids and heterogeneous catalysts showed lower acti-
vation energy between 22 and 64 kJ/mol.30–32 The lower
activation energy favors the reaction toward the product-
specific pathway. The mass transfer of HMF between aque-
ous and organic layers can be expressed by a distribution
coefficient Keq = k2/k3 = 95.43/50.74 = 1.88. Formation of
CMF from HMF showed minimum activation energy of
31.47 kJ/mol proves it to be the most likely reaction than
other competitive reactions.
Formation of FA and humins in the water layer from
HMF showed activation energy of 44.12 kJ/mol, previ-
ous reports on this conversion using AlCl3 had an activa-
tion energy of 90 kJ/mol.18 The degradation of glucose to
humins, furfural, and FA has the activation energy of 43.30
kJ/mol; it needs to be mentioned here that the humins
and other degradation products formation from glucose is
a well-studied conversion with high activation energy 89
kJ/mol.18
To study the influence of acid concentration on this
kinetic model, similar reaction modeling was done using
12.4 mmol acid concentration and the results are given
in Figure 4. Higher initial concentration of glucose was
due to the lower volume of the water layer during the
reaction. 80◦C reaction exhibited a trend similar to the
24.8 mmol acid reaction, and LA remains as the major
product. However, at 70◦C, CMF prevailed as a major
product up to 1 h reaction time, later other products pre-
dominated. It needs to be mentioned here that at low
acid concentrations, the formation of by-products like
LA, FA, and humins was low compared to higher acid
concentrations.
To validate the present kinetic model, parity plots were
constructed for glucose conversion as well as CMF yield
and the corresponding result is shown in Figure 5. Good
agreement between prediction and experimental values
has been established for all products.
HMF degradation in an aqueous layer to LA and FA has
an activation energy of 58.37 kJ/mol. Reports showed that
the H2SO4-, H3PO4-, and HCl-catalyzed reactions had acti-
vation energies of 57, 56, and 95 kJ/mol, respectively.19,33,34

8
ANTONYRAJ et al.
F I G U R E 5 Parity plot with experimental and model values at (A) 80◦C and (B) 70◦C at 24.8 mmol acid concentration [Color figure can
be viewed at wileyonlinelibrary.com]
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4
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AC K N OW L E D G E M E N T S
A. Antonyraj thanks Anita Amaladas for professional
English corrections and the Department of Science and
Technology, New Delhi for financial assistance (research
project sponsored under DST-SERB for young scientist
award – SERB/F/1856/2015-16).
DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are avail-
able in the Supporting Information of this article.
O RC I D
ChurchilA. Antonyraj https://orcid.org/0000-0002-
6381-7603
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S U P P O RT I N G I N FO R M AT I O N
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How to cite this article: Antonyraj CA,
Chennattussery AJ, Haridas A
5-(Chloromethyl)furfural production from glucose:
a pioneer kinetic model development exploring the
mechanism. Int J Chem Kinet. 2021;1-9.