Selective Synthesis of 2,5-Diformylfuran by Sustainable 4-acetamido-TEMPO/Halogen-Mediated Electrooxidation of 5-Hydroxymethylfurfural

Article abstract of DOI:10.1002/asia.201600801

A new method was developed for the selective gram-scale synthesis of 2,5-diformylfuran (DFF), which is an important chemical with a high application potential, via oxidation of biomass-derived 5-hydroxylmethylfurfural (HMF) catalyzed by 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-AcNH-TEMPO) in a two-phase system consisting of a methylene chloride and aqueous solution containing sodium hydrogen carbonate and potassium iodide. The key feature of this method is the generation of the I₂ (co-)oxidant by anodic oxidation of iodide anions during pulse electrolysis. In addition, the electrolyte can be successfully recycled five times while maintaining a 62–65 % yield of DFF. This novel method provides a sustainable pathway for waste-free production of DFF without the use of metal catalysts and expensive oxidants. An advantage of electrooxidation is utilized in the preparation of demanding chemical.

Full text of DOI:10.1002/asia.201600801

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Selective Synthesis of 2,5-Diformylfuran by Sustainable 4-acetamido-
TEMPO/Halogen Mediated Electrooxidation of 5-Hydroxymethylfurfural
Authors: Vera P. Kashparova; Victor A. Klushin; Daria V. Leontyeva; Nina V.
Smirnova; Victor M. Chernyshev; Valentine P. Ananikov
This manuscript has been accepted after peer review and the authors have elected to
post their Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by using the Di-
gital Object Identifier (DOI) given below. The VoR will be published online in Early
View as soon as possible and may be different to this Accepted Article as a result
of editing. Readers should obtain the VoR from the journal website shown below
when it is published to ensure accuracy of information. The authors are responsible
for the content of this Accepted Article.
To be cited as: Chem. Asian J. 10.1002/asia.201600801
Link to VoR: http://dx.doi.org/10.1002/asia.201600801
A Journal of
A sister journal of Angewandte Chemie
and Chemistry – A European Journal

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
Selective Synthesis of 2,5-Diformylfuran by Sustainable
4-acetamido-TEMPO/Halogen Mediated Electrooxidation of
5-Hydroxymethylfurfural
Vera P. Kashparova,[a] Victor A. Klushin,[a] Daria V. Leontyeva,[a] Nina V. Smirnova,[a] Victor M.
Chernyshev,[a] Valentine P. Ananikov*[a, b]
Abstract: A new method was developed for the selective gram-
scale synthesis of 2,5-diformylfuran (DFF), which is an important
chemical with a high application potential, via oxidation of biomass-
derived 5-hydroxylmethylfurfural (HMF) catalyzed by 4-acetylamino-
Therefore, HMF is a beneficial starting compound for the
5]
preparation of new sustainable materials and polymers.[4a,
Because the HMF molecule contains two nonequivalent
functional groups, initial modification of this compound is
required for the preparation of many functional materials and
polymers (Scheme 1). Most valuable HMF-derived building
blocks for materials chemistry are symmetrically functionalized
furan compounds, such as 2,5-furandicarboxylic acid (FDCA),
2,5-diformylfuran (DFF) and 2,5-bishydroxymethyl furan
(BHMF).[5] FDCA is currently produced using environmentally
friendly methods from the direct oxidation of HMF,[1, 3b, 6] and
BHMF is typically prepared in good yields by the selective
catalytic[1, 7] or electrochemical[8] reduction of the formyl group in
HMF or by the Cannizzaro reaction with HMF.[9]
2,2,6,6-tetramethylpiperidine-1-oxyl (4-AcNH-TEMPO) in
a two-
phase system consisting of a methylene chloride and aqueous
solution containing sodium hydrogen carbonate and potassium
iodide. The key feature of this method is the generation of the I2
(co-)oxidant by anodic oxidation of iodide anions during pulse
electrolysis. In addition, the electrolyte can be successfully recycled
five times while maintaining a 62-65% yield of DFF. This novel
method provides sustainable pathway for waste-free production of
DFF without the use of metal catalysts and expensive oxidants. An
advantage of electrooxidation is utilized in the preparation of
demanding chemical.
Introduction
The worldwide rapid decrease in fossil resources has
prompted ongoing research on renewable alternatives for the
production of chemicals and fuels to achieve a sustainable
society.[1] Currently, biomass is considered to be the most
important carbon-containing renewable resource and the most
promising alternative to petroleum, natural gas, coal and other
fossil carbon resources.[2] Therefore, the development of
efficient and greener processes (i.e., “biorefinery technologies”)
for the conversion of biomass into useful chemicals and valuable
fuels has received much attention in recent years.[3]_
Scheme 1. Pathways from biomass to biorenewable materials through HMF
and HMF-derived key monomers.
DFF is a versatile compound[4a] that can be used as a
monomer for the production of urea resins[10], electroconductive
polymers[11] and imine-linked porous organic frameworks, which
are useful for CO2 adsorption.[12] Moreover, DFF is a valuable
building block for the preparation of fluorescent materials,[13]
One of the fastest emerging pathways for the conversion of
biomass-derived carbohydrates involves their dehydration into
furan
derivatives.[1-3]
Among
these
derivatives,
5-
hydroxymethylfurfural (HMF) is considered to be a key platform
molecule for the production of a wide variety of valuable
pharmaceuticals,[14]
macrocyclic[15]
and
coordination[16]
compounds. DFF is indefinitely stable in its crystalline form,
which makes it a more convenient compound for storage and
transportation than low-melting and hygroscopic HMF.[17] In
contrast to highly water soluble HMF, DFF is less hydrophilic
and can be easily isolated from aqueous reaction mixtures by
extraction with various organic solvents.[14a] In this context, much
[a]
[b]
Dr. V.P. Kashparova, Dr. V.A. Klushin, Dr. D.V. Leontyeva, Prof. Dr.
N.V. Smirnova, Prof. Dr. V.M. Chernyshev, Prof. Dr. V.P. Ananikov
Platov South-Russian State Polytechnic University (NPI),
Novocherkassk 346428 (Russia)
Prof. Dr. V.P. Ananikov
Zelinsky Institute of Organic Chemistry,
Russian Academy of Sciences,
Leninsky pr. 47
attention has been focused on the synthesis of DFF from
18]
HMF.[4a,
However, in contrast to the preparation of FDCA,
Moscow 119991 (Russia)
E-mail: val@ioc.ac.ru
selective oxidation of HMF to DFF is a challenge because the
oxidation of the hydroxyl group in HMF proceeds much slower
than the oxidation of the aldehyde moiety by a majority of the
available oxidizing agents.[19] Therefore, 5-hydroxymethyl-2-
furan carboxylic acid (HMFC), 5-formyl-2-furan carboxylic acid
Supporting information for this article is is available on the WWW
under http://dx.doi.org/10.1002/asia.201xxxxxx.
chemicals and fuels through specific transformations.[4]
1

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
(FFCA) and FDCA are considered to be typical byproducts of
the oxidation of HMF to DFF (Scheme 2).[18, 20] Moreover, the
oxidative or hydrolytic cleavage of the furan ring in HMF could
occur, resulting in acyclic compounds, such as succinic acid
(SA), 2-oxoglutaric acid (OGA), maleic acid (MA), fumaric acid
(FA), levulinic acid (LA) and formic acid (Scheme 2).[21] In
addition, most methods for the preparation of DFF from HMF via
18, 22]
oxidation require the use of expensive oxidants[4a,
generate large amounts of inorganic wastes.[19, 22-23]
or
Waste-free methods for the preparation of DFF from HMF
are limited to catalytic oxidation of HMF in the presence of O2.[4a]
Various procedures for aerobic oxidation of HMF in
24]
14a, 25]
homogeneous[4a,
and heterogeneous[4a,
catalytic
systems based on transition metals have been reported.
Moreover, nonmetal organic catalysts for aerobic HMF oxidation
are regularly published in the literature. In addition, fermentative
aerobic oxidation of HMF was recently reported as a promising
approach but the optimized procedure required a long reaction
time (~ 96 h) and was very susceptible to the reaction
conditions.[26] 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO)
and related nitroxides immobilized on various supports[27] and
nanosized graphene oxide in the presence of TEMPO[28] have
been reported to be effective catalysts. Regardless of the high
yields of DFF, metal-based catalysts often suffer from
deactivation or do not satisfy the current demands for green
technology. In addition, the proposed nonmetal catalysts are
expensive or still not easily accessible. Therefore, the
development of novel efficient methods for the selective
oxidation of HMF to DFF is important.
Scheme 2. Typical products of HMF oxidation.
Scheme 3. 4-AcNH-TEMPO/halogen mediated electrochemical oxidation of
HMF.
The electrochemical oxidation of HMF is an alternative
approach for the waste-free synthesis of DFF. According to the
electrochemical concept, a change in the interfacial potential or
current density may be used to control the selectivity. In
electrochemical oxidation, the electric current plays the role of
an oxidant, and in aqueous electrolytes, hydrogen and oxygen
are the main byproducts. Recently, direct[29] and TEMPO-
mediated[30] electrochemical oxidations of HMF in aqueous
electrolytes have been studied, and FDCA was the major
product in both processes. It is important to note that selective
TEMPO-catalyzed oxidation of alcohols to aldehydes is typically
performed in nonaqueous organic solvents or in two-phase
systems.[31] In addition, biphasic electrochemical HMF oxidation
in the (KBr + NaHCO3 + TEMPO radicals)aq./CH2Cl2 system has
been previously studied. However, the reported yields of DFF
were only 20-53% for various radicals and did not exceed 34%
in most cases.[32] In recent years, iodine was found to be an
effective redox catalyst with a good capacity for electron transfer
in numerous oxidative reactions of organic substances.[33] We
propose that iodine can be used rather than bromine as a milder
terminal oxidant, which will enhance the selectivity of the
TEMPO-catalyzed electrochemical oxidation of HMF to DFF.
Herein, we describe electrochemical oxidation of HMF
mediated by 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxyl
(4-AcNH-TEMPO, the low-cost, readily accessible TEMPO
derivative)[34] in the presence of bromine and iodine anions in
both aqueous solutions and a biphasic system consisting of
aqueous electrolyte/CH2Cl2 (Scheme 3). We developed a new
efficient method for the electrochemical synthesis of DFF from
HMF. Sustainable pathway via electrooxidation and the absence
of by-products (cf. Schemes 2 and 3) are important practical
advantages of the developed methodology.
Results and Discussion
Electrochemical behavior of HMF and DFF on Pt electrode
Prior to investigating the electrochemical oxidation of HMF in a
biphasic medium, we compared the electrochemical behavior of
the main reaction participants using cyclic voltammetry on a Pt
electrode in a supporting electrolyte containing 0.5 М NaHCO3
(as a buffering system, рН 8.7) + 0.5 М Na2SO4 (as an additive
to enhance conductivity). These experiments were performed to
answer the following questions: How does the nature of the
halogen anion influence the oxidation of HMF in the presence of
4-AcNH-TEMPO? Is it possible to selectively obtain DFF by the
4-AcNH-TEMPO/halogen-mediated electrochemical oxidation of
HMF in an aqueous solution without the addition of an organic
phase?
The anodic scans of the CV curves of HMF and DFF
oxidation without 4-AcNH-TEMPO and KI or KBr (Figure 1a)
indicate that both HMF and DFF are irreversibly oxidized in the
same potential region of ~0.15-0.70 V with very low rates.
However, the rate of DFF oxidation is three times higher than
that of HMF.
The CV curve recorded in a solution consisting of 4-AcNH-
TEMPO without HMF and DFF (Figure 1b, blue line) contained
nearly symmetric anodic (+0.66 V) and cathodic (-0.60 V) peaks,
which correspond to the oxidation of 4-AcNH-TEMPO to the
oxoammonium cation (4-AcNH-TEMPO+) and the reverse
reduction of 4-AcNH-TEMPO+ to 4-AcNH-TEMPO.[30] It is
2

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
important to note that the rate of 4-AcNH-TEMPO to 4-AcNH-
TEMPO+ oxidation is an order of magnitude greater than the
oxidation rates for HMF and DFF (Figure 1a). The CV curves for
the oxidation of 4-AcNH-TEMPO+HMF and 4-AcNH-
TEMPO+DFF (Figure 1b) indicate that the oxidation rates for
HMF and DFF in the presence of 4-AcNH-TEMPO are nearly the
same and sufficiently higher than the oxidation rates in the
absence of 4-AcNH-TEMPO. The disappearance of the cathode
peak at 0.60 V in the 4-AcNH-TEMPO+HMF and 4-AcNH-
TEMPO+DFF curves confirmed the complete reduction of 4-
AcNH-TEMPO+ to 4-AcNH-TEMPO by HMF and DFF,
respectively. Therefore, under these conditions, HMF and DFF
were oxidized by 4-AcNH-TEMPO+ at nearly equal rates.
Figure 1c shows the CV curves measured in the solutions
containing HMF (green line) and DFF (red line) in the presence
of 4-AcNH-TEMPO+KI as well as the CV curve for only KI (blue
line) in the supporting electrolyte. The CV curve for KI (blue line)
indicates that I- was oxidized to I2 without an overvoltage at
potentials higher than 0.35 V, and the liberated I2 formed a film
on the anode surface, as previously described for iodide
oxidation in alkaline solutions.[35] A substantial increase in the
current was observed in a potential range from 0.4 to 0.9 V in
the KI+4-AcNH-TEMPO+HMF (green line) and KI+4-AcNH-
TEMPO+DFF (red line) systems compared to the same systems
without KI (Fig. 1b). Therefore, the increase in the current was
primarily determined by the oxidation of iodide anions, and both
rates for HMF and DFF oxidation were small and nearly equal.
Thin polymeric films that consist of molecular iodine and organic
polymers were formed during oxidation of HMF or DFF and
detected on the surface of the working electrode using scanning
electron microscopy. EDX analyses of the electrode surface
after the CV measurements indicated a high content of carbon
(~ 48%) and oxygen (~20%) in the formed films in addition to
iodine (~21%) (See supplementary material).
Replacement of KI with KBr significantly changes the CV
curves (Figure 1d). Bromine anions suffer oxidation at ~0.5 V
higher potentials than iodide ones. Large current densities at
potentials higher than 1.1 V are caused by oxidation of HMF
(green line) and DFF (red line) with nearly equal rates that are
sufficiently higher than the rates of the analogous processes in
the presence of KI (Figure 1c). It is important to note that the
selectivity of oxidation of organic molecules at the electrode
surface typically decreases with increasing potential, and
anodically generated bromine (Br2) and hypobromite anions
(BrO-) that form in basic medium are stronger oxidizers than
iodine (I2) or I3- anions.
Figure 1. CV curves for the Pt electrode in a supporting electrolyte consisting
of 0.5 M NaHCO3 + 0.5 M Na2SO4 (carbonate buffer, pH= 8.7) at 10 mVs-1 in
solutions containing: a) supporting electrolyte (blue line); 0.05 M HMF (green
line) and 0.05 M DFF (red line); b) 0.01 M 4-AcNH-TEMPO (blue line); 0.01 M
4-AcNH-TEMPO + 0.05 M HMF (green line) and 0.01 M 4-AcNH-TEMPO +
0.05 M DFF (red line); c) 0.2 M KI (blue line); 0.2 M KI + 0.01 M 4-AcNH-
TEMPO + 0.05 M HMF (green line); 0.2 M KI + 0.01 M 4-AcNH-TEMPO + 0.05
M DFF (red line); d) 0.2 M KBr (blue line); 0.2 M KBr + 0.01 M 4-AcNH-
TEMPO + 0.05 M HMF (green line); 0.2 M KBr + 0.01 M 4-AcNH-TEMPO +
0.05 M DFF (red line).
Based on these CV results, the electrochemical oxidation of
HMF in aqueous solutions is inappropriate for the selective
synthesis of DFF because the potentials and rates of oxidation
of HMF and DFF are very similar in the absence or presence of
4-AcNH-TEMPO and KI or KBr. Therefore, the concentration of
HMF and DFF in the aqueous solution for the electrochemical
generation of halogens (terminal oxidant of 4-AcNH-TEMPO)
should be minimized to avoid their undesirable oxidation in
aqueous solutions on the anode. Ideally, the electrochemical
oxidation of halogen anions should be separated from HMF
oxidation by 4-AcNH-TEMPO+, as previously reported for
mediated oxidations of alcohols.[36] Biphasic systems consisting
of non-miscible organic solvent and aqueous electrolyte were
shown to be beneficial for some processes of electrocatalytic
oxidations of organic compounds, anodic C–H functionalizations
and heterocyclisations, allowing for operation in an undivided
cell under galvanostatic conditions within a wide range of current
densities and simplifying product isolation.[37]
As it will be shown further, the selectivity of electrochemical
HMF to DFF oxidation may be enhanced significantly by
performing electrolysis in biphasic system.
Electrochemical oxidation of HMF to DFF in a two-phase
system
The conclusions from the CV measurements were examined
by the experimental investigation of the electrochemical 4-
AcNH-TEMPO-mediated oxidation of HMF in a two-phase
system consisting of CH2Cl2/(aqueous electrolyte) in the
presence of potassium bromide or iodide. The choice of CH2Cl2
3

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
as a solvent for organic phase is based on the numerous
examples of its successful application for the selective TEMPO-
mediated oxidation of alcohols to aldehydes in biphasic
processes including simplicity of isolation of resulting
aldehydes.[31c, 36, 38]
We were unable to obtain DFF yields higher than 30% for
the 4-AcNH-TEMPO/KBr electrochemical oxidation of HMF
under any of the conditions investigated (Table 1). Polymers
with undetermined structures that were isolated by extraction of
the aqueous electrolyte with ethyl acetate at pH 2-3 were the
main byproducts in these processes (Table 1). It is important to
note that electrolysis in an undivided electrolysis cell afforded
nearly the same results. Therefore, bromine-mediated
electrolysis is not effective for DFF preparation.
Scheme 4. 4-AcNH-TEMPO/KI mediated electrochemical oxidation of HMF
(for the discussion of the proposed reaction mechanism, see Supporting
Information).
Table 1. Effect of the charge passed during the conversion of HMF and the
selectivity and yield of DFF in the 4-AcNH-TEMPO/KBr-mediated
electrochemical oxidation of HMF.
First, the effect of the pH on the yield of DFF was
investigated (Table 2). As for the 4-AcNH-TEMPO-catalyzed
chemical oxidation of HMF with I2 in a biphasic medium, a
sufficient change in the pH resulted in a decrease in the DFF
yield. Therefore, NaHCO3 was considered to be the most
suitable buffer system. A NaHCO3 concentration of 0.3-0.8 M
has no appreciable effect on the DFF yield. Therefore, a 0.5 M
concentration of NaHCO3 (entry 3) was determined to be the
most appropriate.
Charge
[F mol-1]
Conversion
[%]
Selectivity
[%]
DFF yield
[%]
Polymers
yield [%][d]
Entry
1
2
3
4
5
6
7
8
9
0.7[a]
1.5[a]
1.9[a]
1.9[b]
2.2[a]
3.0[a]
3.7[a]
4.5[a]
2.5[c]
35
47
57
68
63
72
83
94
87
80
54
32
32
27
22
17
13
28
28
25
18
22
17
16
14
12
24
41
Table 2. Effect of the electrolyte composition on the conversion of HMF and
the selectivity and yield of DFF[a]
.
Buffer concentration in
Entry
Conversion
[%]
Selectivity
[%]
Yield
[%]
рН
aqueous solution [M]
63
78
1
2
3
4
5
6
Na2HPO4 (0.5)
NaHCO3 (0.8)
NaHCO3 (0.5)
NaHCO3 (0.4)
NaHCO3 (0.3)
Na2CO3 (0.5)
7.8
8.7
8.7
8.7
8.7
11.3
22
90
89
83
85
100
56
50
51
51
45
15
12
45
45
42
39
15
[a] Current density 5 mA сm-2. [b] Current density 10 mA сm-2. [c] Current
density 10 mA сm-2. [d] Calculated from the ratio of the mass of the
polymers isolated to the mass of converted HMF.
[a] Reaction conditions: concentration of KI in aqueous solution is 0.2 M; dc,
current density 80 mA сm-2, charge 2.5 F per mole of HMF.
During the investigation of HMF oxidation in the presence of
KI (Scheme 4), previously published conditions for the
electrochemical oxidation of benzyl and aliphatic alcohols (10
mol % 4-AcNH-TEMPO, 20 mol % KI, concentration of NaHCO3
0.9 M, current density 25 mA cm-2, charge 2.5 F/mole)[38a] were
initially tested. Under these conditions, the DFF yield was 37%,
which demonstrates the advantage of the iodide mediator
system over bromide mediator system. To optimize this method,
we investigated the effects of the electrolyte composition (i.e.,
pH, concentrations and molar ratios of reagents) and the
electrolysis parameters (i.e., current density, charge passed,
reaction time, continuous or pulse regimes of electrolysis) on the
HMF to DFF oxidation process in the two-phase system.
The effect of the concentrations of HMF and KI on the DFF
yield is more complex and dependent on other parameters, such
as the current density and ton: toff with regards to the pulse
current. Therefore, based on the results from a majority of the
experiments, an increase in the HMF concentration higher than
0.2 M (in CH2Cl2 solution being charged to the electrolysis cell)
resulted in decreasing selectivity (especially at concentrations
higher than 0.5 M) due to increased contributions from the direct
oxidation of HMF on the anode surface, which is known to afford
FDCA as the main product.[29-30] When the KI concentration was
below 0.2 M (in aqueous electrolyte being charged to the
electrolysis cell), a moderate decrease in the selectivity was
observed, and an increase in the KI concentration either
decreased the selectivity (especially at high current densities) or
did not appreciably influence the yield.
4

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
The addition of Na2SO4 to the electrolyte was employed to
enhance the conductivity and reduce ohmic losses. Under
otherwise equal conditions, the addition of Na2SO4 enhanced the
conversion of HMF by 1.5-1.7 times (Table 3). Moreover, sodium
sulfate supports the “salting out” of HMF and DFF from the
aqueous phase to the organic phase. This effect reduces
undesirable reactions in the aqueous electrolyte. Therefore, the
partition coefficients were enhanced by 4 and 3 times for HMF
and DFF, respectively, after the addition of Na2SO4 at a
concentration of 0.5 M (see Supporting Materials). However, a
further increase in the Na2SO4 concentration to 0.8 M decreased
the DFF yield.
40
1.7
94
89
45
42
39
45
30
80
0.85
0.43
51
68
160
[a] Reaction conditions: concentrations of KI, NaHCO3 and Na2SO4 in
aqueous solution are 0.2 M, 0.5 M, and 0.4 M, correspondingly; dc, charge
2.5 F per mole of HMF.
Therefore, high concentrations of I2 in the electrolyte are
undesirable for the synthesis of DFF. We propose that an
electrolysis pulse regime will enable an increase in the DFF yield.
Pulsating current is applied as powerful technique for controlling
mass transfer parameters and selectivity in various
electrochemical processes.[39] For example, pulse mode is used
to suppress the formation of non-conducting polymer films and
Table 3. Effect of Na2SO4 on the conversion of HMF and selectivity and yield
of DFF[a]
.
Concentration of Na2SO4
[M]
Conversion
[%]
Selectivity
[%]
Yield
[%]
anode passivation in the electrochemical fluorination of organic
compounds,[39d,
to avoid poisoning of electrodes and to
39e]
0
48
82
89
51
59
50
24
48
44
enhance C2H4 yield in the electrochemical reduction of CO2,[39f]
to control the composition and morphology of the polymers
obtained by the electropolymerization of organic compounds.[39g-
0.4
0.8
i]
We hypothesized that the pulse mode will provide sufficient
[a] Reaction conditions: concentrations of KI and NaHCO3 in aqueous solution
are 0.2 M and 0.5 M, correspondingly; dc, current density 80 mA сm-2, charge
2.5 F per mole of HMF.
time for nearly complete conversion of the electrochemically
formed iodine in the “slow” chemical 4-AcNH-TEMPO/iodine
oxidation of HMF in the organic phase during the pulse-of time
(toff). Therefore, the pulse mode will provide an opportunity to
perform the process at relatively high current densities, which
would prevent the formation of high iodine concentrations in the
reaction medium.
After a series of optimization experiments, we determined
the parameters for the pulse electrolysis that enable
enhancement of the DFF yield by ~ 16-20% relative to that of the
continuous mode (Table 5, entry 3).
The current density is an important parameter that influences
the DFF yield. At the same passed charge, the enhancement of
the current density up to 80 mA сm-2 resulted in an increase in
the DFF yield due to increasing selectivity (Table 4). However, a
further increase in the current density decreased the yield due to
decreasing selectivity. At low current densities, the low
selectivity was caused by gradual decomposition of HMF and
DFF due to their instability in the reaction medium and long
duration of the syntheses (after termination of electrolysis, DFF
concentration in the reaction mixture decreased by ~ 29% within
2.5 h at 22 °C). An increase in the current density from 20 mA
сm-2 to 80 mA cm-2 resulted in a four-fold reduction in the
reaction time (at the constant charge passed) and an increase in
the DFF yield from 32 to 45% (Table 4). However, a further
increase in the current density caused intensive liberation of
iodine and coloration of the electrolyte. Presumably, the
oxidation of HMF by the oxoammonium cation becomes a rate-
limiting step at high current densities. Excess I2 in the reaction
medium accelerates the decomposition of HMF and DFF.
Moreover, at high current densities, I2 forms low conductive films
on the electrode surface, which accounts for the additional
ohmic losses.
Table 5. Effect of the durations of the ton and toff pulse periods and the
charges passed during the conversion of HMF as well as the selectivity and
yield of DFF in the pulse electrolysis [a]
.
Entry
Charge
ton: toff
Total
Conversion Selectivity
Yield
[%]
[F mol-1] [min : min] reaction
time [h]
[%]
[%]
1
2
3
4
5
6
2.5
2.5
2.5
5
dc
0.85
1.70
2.55
1.70
3.40
5.10
68
91
92
96
71
66
69
52
45
38
48
60
64
50
45
38
1:1
1:2
dc
5
1:1
1:2
100
100
5
[a] Reaction conditions: concentrations of KI, NaHCO3 and Na2SO4 in
aqueous solution are 0.2 M, 0.5 M, and 0.4 M, correspondingly; current
density 80 mA сm-2.
Table 4. Effect of current density on the conversion of HMF and selectivity
and yield of DFF [a]
.
The optimized conditions were applied for the preparative
gram-scale electrochemical synthesis of DFF from HMF. The
isolated yield of DFF was 61-63%. The purity of the crude
product was 91-92% based on HPLC analyses. The total yields
of purified DFF (crystallization from water) were 55-58%.
Current density Reaction
Conversion
[%]
Selectivity
[%]
Yield [%]
32
[mA сm-2]
time [h]
20
3.4
99
32
5

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
Exhaust electrolyte can be recycled after addition of 10% 4-
AcNH-TEMPO relative to the initial quantity of 4-AcNH-TEMPO
loaded into the reaction mixture. We were able to perform five-
fold recycling of the electrolyte without a significant decrease in
the DFF yield (Table 6).
AcNH-TEMPO do not exceed 1 molar % relative to HMF
converted. Moreover, this process has several advantages,
including simple product separation and purification, mild
reaction conditions and a simple electrochemical setup.
Experimental Section
Table 6. Effect of electrolyte recycling on the yield of DFF.
Materials and Methods
Cycle number
Yield of DFF [%]
Unless otherwise noted, materials were obtained from commercial
sources and were used as supplied. Melting points were determined with
an open capillary tubes in a Thiele apparatus. 1H and 13C NMR spectra
were recorded on a Bruker DRX 500 instrument at 500 MHz and 125
MHz, respectively, as solutions in CDCl3 with tetramethylsilane (TMS) as
an internal standard. The percentage yields of all products were
calculated by dividing the amount of the desired product obtained after
purification by the theoretical yields.
1
2
3
4
5
65
64
62
63
62
The concentrations of HMF and DFF in the reaction mixtures were
determined by HPLC using an Agilent 1260 Infinity LC system equipped
with a reversed-phase Eclipse PAH column (250 × 4.6 mm), detection
wavelength of 284 nm. The mobile phase was constituted of acetonitrile
and water (V:V = 70: 30) at 0.5 mL min-1. The column oven temperature
was kept at 30 ºC. The content of HMF and DFF in samples was
calculated by the external standard calibration curve method, which was
constructed based on the pure compounds.
Cyclic voltammetry measurements were performed at room temperature
using potentiostat/galvanostat P-30J (Elins) in an undivided three-
electrode glass cell. The platinum foil (1 cm2) was used as a working
electrode, a Pt wire and Ag/AgCl (saturated KCl) were used as a counter
and reference electrodes, respectively. Cyclic voltammograms were
measured between -0.7 and 1.3 V at a sweep rate of 10 mV s-1 in 0.5 M
NaHCO3 + 0.5 M Na2SO4 (pH = 8.7) aqueous solution.
Conclusions
The 4-AcNH-TEMPO/halogen-mediated electrochemical
oxidation of HMF on a Pt electrode in an aqueous solution was
ineffective for the synthesis of DFF because the potentials and
rates of oxidation of HMF and DFF were very similar in the
absence or presence of 4-AcNH-TEMPO and KI or KBr.
The selectivity of the electrochemical oxidation of HMF to
DFF can be significantly enhanced by performing the electrolysis
in a biphasic system. The organic phase provides an opportunity
to minimize the concentration of DFF in the aqueous electrolyte
due to extraction and reduce its further oxidation and
decomposition in the aqueous phase. The iodide/iodine system
is a more effective mediator than the bromide/bromite system
due to the lower potentials required for the oxidation of the
iodide anions. Anodic oxidation of the iodide anions occurs at a
lower potential than anodic oxidation of DFF and HMF.
Therefore, direct nonselective electrochemical oxidation of HMF
was suppressed by the preferential oxidation of iodide and the
formation of I2 films on the electrode surface, and the low
conductivity of these films requires a higher power consumption
due to ohmic losses. Pulse electrolysis was shown to be an
effective approach for increasing the DFF yield in the 4-AcNH-
TEMPO/KI-mediated electrochemical oxidation of HMF. The
pulse mode enables an increase in the current density and a
decrease in the total reaction time. In addition, this mode
provides sufficient time for the “slow” chemical 4-AcNH-
TEMPO/iodine oxidation of HMF in the organic phase during the
cut-off time between the pulses, thus preventing an undesirable
increase in the I2 concentration in the electrolyte and organic
phase.
Studies of 4-AcNH-TEMPO/KBr mediated electrochemical oxidation of
HMF in biphasic media (general procedure)
Experiments were performed in a diaphragm thermostated glass cell
equipped with two platinum electrodes (each of 10.0 cm2 area, the inter
electrode distance was 3.5 cm) and a mechanical stirrer in the anodic
compartment (300 rpm). A solution of HMF (1.26 g, 10 mmol) and 4-
AcNH-TEMPO (0.213 g, 1 mmol) in CH2Cl2 (20 mL) was placed in an
anodic compartment. Then, 25% aqueous solution of KBr saturated with
NaHCO3 was added (100 ml to the anodic compartment and 120 mL to
the cathodic compartment). Then whole mixture was submitted to the
constant current electrolysis at 20–21 ºC (Table 1). Then organic and
aqueous phases from anodic compartment were separated and analyzed
by HPLC. To determine the yield of polymeric products, aqueous
electrolyte was acidified by concentrated hydrochloric acid to pH 2-3 and
then extracted by ethyl acetate (5×40 mL). The extract was dried by
anhydrous Na2SO4 and evaporated to dryness under reduced pressure.
The obtained resinous residue was dried at 20 °C to constant weight in
vacuo then analyzed for HMF content by HPLC. The mass of polymers
formed was calculated by subtraction of the mass of HMF (determined in
the residue by HPLC) from the total mass of the residue.
Studies of 4-AcNH-TEMPO/KI mediated electrochemical oxidation of
HMF in biphasic media (general procedure)
Therefore, we have developed an effective synthesis of DFF
using the 4-AcNH-TEMPO/KI-mediated oxidation of HMF via
pulse electrolysis in a two-phase system. The overall process
represents a green and sustainable synthesis because it does
not require the use of metal-based catalysts. In addition, this
process uses an electric current as a green oxidizer, a less toxic
inexpensive mediator system (4-AcNH-TEMPO/KI) and
recyclable nontoxic electrolyte. During recycle, losses of 4-
Experiments were performed in an undivided thermostated glass cell
equipped with two platinum electrodes (each of 1.0 cm2 area, the inter
electrode distance was 1.5 cm) and a mechanical stirrer. A solution of
appropriate amount of KI in aqueous buffer of appropriate pH (10 mL)
was added to a solution of HMF (0.126 g, 1 mmol) and 4-AcNH-TEMPO
(0.021 g, 0.1 mmol) in CH2Cl2 (5 mL). The whole solution was stirred at a
rate of 300 rpm to form an emulsion. The electrolysis was conducted at
6

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
1998, 41, 3872-3878; c) M. Del Poeta, W. A. Schell, C. C. Dykstra, S.
Jones, R. R. Tidwell, A. Czarny, M. Bajic, M. Bajic, A. Kumar, D. Boykin,
J. R. Perfect, Antimicrob. Agents Chemother. 1998, 42, 2495-2502.
[15] D. T. Richter, T. D. Lash, Tetrahedron Lett. 1999, 40, 6735-6738.
[16] O. W. Howarth, G. G. Morgan, V. McKee, J. Nelson, J. Chem. Soc.,
Dalton Trans. 1999, 2097-2102.
appropriate parameters of current at the 20–21 ºC. Then organic and
aqueous phases were separated and analyzed by HPLC.
Electrochemical synthesis of DFF (preparative procedure)
[17] A. Gandini, M. N. Belgacem, Prog. Polym. Sci. 1997, 22, 1203-1379.
[18] X. Tong, Y. Ma, Y. Li, Appl. Catal., A 2010, 385, 1-13.
[19] X. Liu, H. Ding, Q. Xu, W. Zhong, D. Yin, S. Su, J. Energy Chem. 2016,
25, 117-121.
[20] S. Dutta, S. De, B. Saha, ChemPlusChem 2012, 77, 259-272.
[21] S. Li, K. Su, Z. Li, B. Cheng, Green Chem. 2016.
[22] V. P. Kashparova, E. A. Khokhlova, K. I. Galkin, V. M. Chernyshev, V.
P. Ananikov, Russ. Chem. Bull. 2016, 64, 1069-1073.
[23] a) C. Laugel, B. Estrine, J. Le Bras, N. Hoffmann, S. Marinkovic, J.
Muzart, ChemCatChem 2014, 6, 1195-1198; b) Q. Girka, B. Estrine, N.
Hoffmann, J. Le Bras, S. Marinkovic, J. Muzart, React. Chem. Eng.
2016.
[24] a) X. Jia, J. Ma, M. Wang, Z. Du, F. Lu, F. Wang, J. Xu, Appl. Catal., A
2014, 482, 231-236; b) T. S. Hansen, I. Sádaba, E. J. García-Suárez, A.
Riisager, Appl. Catal., A 2013, 456, 44-50; c) X. Tong, Y. Sun, X. Bai, Y.
Li, RSC Adv. 2014, 4, 44307-44311; d) M. O. Kompanets, O. V. Kushch,
Y. E. Litvinov, O. L. Pliekhov, K. V. Novikova, A. O. Novokhatko, A. N.
Shendrik, A. V. Vasilyev, I. O. Opeida, Catal. Commun. 2014, 57, 60-
63; e) H. Zhao, W. Sun, C. Miao, Q. Zhao, J. Mol. Catal. A: Chem. 2014,
393, 62-67; f) C. Fang, J.-J. Dai, H.-J. Xu, Q.-X. Guo, Y. Fu, Chin.
Chem. Lett. 2015, 26, 1265-1268.
[25] a) Y. Guo, J. Chen, ChemPlusChem 2015, 80, 1760-1768; b) X. Liu, J.
Xiao, H. Ding, W. Zhong, Q. Xu, S. Su, D. Yin, Chem. Eng. J. 2016, 283,
1315-1321; c) Y. Zhu, X. Liu, M. Shen, Y. Xia, M. Lu, Catal. Commun.
2015, 63, 21-25; d) J. Chen, J. Zhong, Y. Guo, L. Chen, RSC Adv. 2015,
5, 5933-5940; e) J. Artz, S. Mallmann, R. Palkovits, ChemSusChem
2015, 8, 672-679; f) Y. Zhu, M. Shen, Y. Xia, M. Lu, Catal. Commun.
2015, 64, 37-43; g) R. Fang, R. Luque, Y. Li, Green Chem. 2016,
dx.doi.org/10.1039/C1035GC03051J; h) D. Baruah, F. L. Hussain, M.
Suri, U. P. Saikia, P. Sengupta, D. K. Dutta, D. Konwar, Catal. Commun.
2016, 77, 9-12.
Synthesis was carried out in an undivided glass cell equipped with two
platinum electrodes (each of 10 cm2 area, the inter electrode distance
was 3.5 cm), water cooling jacket and a mechanical stirrer. A solution of
NaHCO3 (4.20 g, 50 mmol) and KI (3.32 g, 20 mmol) in water (100 mL)
was added to a solution of HMF (1.26 g, 10 mmol) and 4-AcNH-TEMPO
(0.21 g, 1 mmol for fresh electrolyte (aqueous phase); 0.021 g, 0.1 mmol,
if a recycled electrolyte is used) in CH2Cl2 (50 mL). The whole solution
was stirred at a rate of 300 rpm to form an emulsion. The electrolysis was
carried out at the galvanostatic conditions using square wave pulses, an
anode pulse current density was 80 mA cm-2, durations of the pulse-on
time ton and the pulse-of time toff were 1 and 2 min, respectively. The total
time of electrolysis was 2.5 h while maintaining the temperature at 20–25
ºC. After passing 2400 C (2.5 F charge per mole of HMF), the magnetic
stirring was stopped. Then organic phase was separated, and aqueous
phase was extracted with CH2Cl2 (2× 25 mL). The combined organic
phase was treated with a saturated solution of sodium thiosulfate (3 mL)
to complete discoloration, dried with anhydrous Na2SO4, then passed
through a short column of Al2O3 (4×5 cm) and evaporated to dryness to
give crude DFF of 91-92% purity according to HPLC analysis (yield 61-
63%). The product was recrystallized from water to give 0.68-0.72 g
(yield 55-58%) of pure DFF with mp 109-110 ºC (lit. 108-110 ºC).[14a]
Acknowledgements
[26] Y.-Z. Qin, Y.-M. Li, M.-H. Zong, H. Wu, N. Li, Green Chem. 2015, 17,
3718-3722.
[27] a) B. Karimi, H. M. Mirzaei, E. Farhangi, ChemCatChem 2014, 6, 758-
762; b) N. Mittal, G. M. Nisola, J. G. Seo, S.-P. Lee, W.-J. Chung, J.
Mol. Catal. A: Chem. 2015, 404–405, 106-114.
[28] G. Lv, H. Wang, Y. Yang, T. Deng, C. Chen, Y. Zhu, X. Hou, Green
Chem. 2016.
[29] K. R. Vuyyuru, P. Strasser, Catal. Today 2012, 195, 144-154.
[30] H. G. Cha, K.-S. Choi, Nat. Chem. 2015, 7, 328-333.
[31] a) R. A. Miller, R. S. Hoerrner, Org. Lett. 2003, 5, 285-287; b) J. C. Qiu,
P. P. Pradhan, N. B. Blanck, J. M. Bobbitt, W. F. Bailey, Org. Lett. 2012,
14, 350-353; c) J. M. Bobbitt, C. BrüCkner, N. Merbouh, in Organic
Reactions, John Wiley & Sons, Inc., 2009, pp. 103-424.
This work was financially supported by the Russian Science
Foundation (grant no. 14-23-00078). The authors also thank the
Shared Research Center “Nanotechnologies” of the Platov
South-Russian State Polytechnic University and the Department
of Structural Studies of Zelinsky Institute of Organic Chemistry
for analytical services.
Keywords: 4-Acetylamino-2,2,6,6-tetramethylpiperidine-1-oxyl •
2,5-Diformylfuran • Electrochemistry • HMF • Oxidation
[32] L. Cottier, G. Descotes, E. Viollet, J. Lewkowski, R. Skowroñski, J.
Heterocyclic Chem. 1995, 32, 927-930.
[33] a) S. Tang, K. Liu, Y. Long, X. Qi, Y. Lan, A. Lei, Chem. Commun. 2015,
51, 8769-8772; b) S. Tang, K. Liu, Y. Long, X. Gao, M. Gao, A. Lei, Org.
Lett. 2015, 17, 2404-2407; c) D. Liu, A. Lei, Chem. Asian. J. 2015, 10,
806-823; d) M. S. Yusubov, V. V. Zhdankin, Resource-Efficient
Technologies 2015, 1, 49-67; e) D. Beukeaw, K. Udomsasporn, S.
Yotphan, J. Org. Chem. 2015, 80, 3447-3454.
[1]
[2]
M. Besson, P. Gallezot, C. Pinel, Chem. Rev. 2014, 114, 1827-1870.
B. R. Caes, R. E. Teixeira, K. G. Knapp, R. T. Raines, ACS Sustainable
Chem. Eng. 2015, 3, 2591-2605.
a) L. Wang, F.-S. Xiao, Green Chem. 2015, 17, 24-39; b) R. A. Sheldon,
J. Mol. Catal. A: Chem.,
[3]
[34] M. Rafiee, K. C. Miles, S. S. Stahl, J. Am. Chem. Soc. 2015, 137,
http://dx.doi.org/10.1016/j.molcata.2016.1001.1013.
14751-14757.
[4]
a) 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, 1499-1597; b) P. K.
Rout, A. D. Nannaware, O. Prakash, A. Kalra, R. Rajasekharan, Chem.
Eng. Sci. 2016, 142, 318-346.
a) A. Gandini, T. M. Lacerda, A. J. F. Carvalho, E. Trovatti, Chem. Rev.
2016, 116, 1637-1669; b) D. Esposito, M. Antonietti, Chem. Soc. Rev.
2015, 44, 5821-5835.
a) J. Zhang, J. Li, Y. Tang, L. Lin, M. Long, Carbohydr. Polym. 2015,
130, 420-428; b) Z. Zhang, K. Deng, ACS Catal. 2015, 5, 6529-6544.
W. Hao, W. Li, X. Tang, X. Zeng, Y. Sun, S. Liu, L. Lin, Green Chem.
2016, 18, 1080-1088.
[35] S. Chen, W. Huang, Z. Niu, Z. Li, Chem. Phys. Lett. 2006, 421, 161-165.
[36] T. Inokuchi, S. Matsumoto, S. Torii, J. Org. Chem. 1991, 56, 2416-2421.
[37] a) B. A. Frontana-Uribe, R. D. Little, J. G. Ibanez, A. Palma, R.
Vasquez-Medrano, Green Chem. 2010, 12, 2099-2119; b) R. Francke,
R. D. Little, Chem. Soc. Rev. 2014, 43, 2492-2521; c) A. J. Bosco, S.
Lawrence, C. Christopher, S. Radhakrishnan, A. A. Joseph Rosario, S.
Raja, D. Vasudevan, J. Phys. Org. Chem. 2015, 28, 591-595.
[38] a) E. S. Kagan, V. P. Kashparova, I. Y. Zhukova, I. I. Kashparov, Russ.
J. Appl. Chem. 2010, 83, 745-747; b) R. A. Sheldon, Catal. Today 2015,
247, 4-13.
[5]
[6]
[7]
[39] a) D. T. Chin, J. Electrochem. Soc. 1983, 130, 1657-1667; b) S. Roy,
Ind. Eng. Chem. Res. 2012, 51, 1756-1760; c) N. Monk, S. Watson, Int.
J. Hydrogen Energy 2016, 41, 7782-7791; d) T. Fuchigami, S. Inagi,
Chem. Commun. 2011, 47, 10211-10223; e) T. Fuchigami, S. Inagi, in
Fundamentals and Applications of Organic Electrochemistry, John
Wiley & Sons Ltd, 2014, pp. 83-128; f) J. Yano, T. Morita, K. Shimano,
Y. Nagami, S. Yamasaki, J. Solid State Electrochem. 2007, 11, 554-
557; g) J. Wang, Y. Xu, J. Wang, X. Du, F. Xiao, J. Li, Synth. Met. 2010,
160, 1826-1831; h) J. Wang, Y. Xu, J. Zhu, Y. Bai, S. Mao, L. Xiong, J.
Solid State Electrochem. 2016, 20, 1413-1420; i) H. Karami, A. R.
Nezhad, Int. J. Electrochem. Sci. 2013, 8, 8905-8921.
[8]
[9]
J. J. Roylance, T. W. Kim, K.-S. Choi, ACS Catal. 2016, 1840-1847.
Z. Miao, Y. Zhang, X. Pan, T. Wu, B. Zhang, J. Li, T. Yi, Z. Zhang, X.
Yang, Catal. Sci. Technol. 2015, 5, 1314-1322.
[10] A. S. Amarasekara, D. Green, L. D. Williams, Eur. Polym. J. 2009, 45,
595-598.
[11] T.-L. Choi, K.-M. Han, J.-I. Park, D. H. Kim, J.-M. Park, S. Lee,
Macromolecules 2010, 43, 6045-6049.
[12] J. Ma, M. Wang, Z. Du, C. Chen, J. Gao, J. Xu, Polym. Chem. 2012, 3,
2346-2349.
[13] C. Mallet, C. Moussallem, A. Faurie, M. Allain, F. Gohier, W. G. Skene,
P. Frère, Chem. Eur. J. 2015, 21, 7944-7953.
[14] a) G. A. Halliday, R. J. Young, V. V. Grushin, Org. Lett. 2003, 5, 2003-
2005; b) K. T. Hopkins, W. D. Wilson, B. C. Bender, D. R. McCurdy, J.
E. Hall, R. R. Tidwell, A. Kumar, M. Bajic, D. W. Boykin, J. Med. Chem.
7

Chemistry - An Asian Journal
10.1002/asia.201600801
FULL PAPER
FULL PAPER
A process for the efficient synthesis of
2,5-diformylfuran, which is an
important biobased chemical with a
high application potential, via pulse
electrolysis of 5-hydroxymethylfurfural
was developed.
Vera P. Kashparova,[a] Victor A. Klushin,[a]
Daria V. Leontyeva,[a] Nina V. Smirnova,[a]
Victor M. Chernyshev,[a] Valentine P.
Ananikov*[a, b]
Page No. – Page No.
Selective Synthesis of
2,5-Diformylfuran by Sustainable
4-acetamido-TEMPO/Halogen Mediated
Electrooxidation of
5-Hydroxymethylfurfural
8