Accepted Manuscript

Title: Synthesis of 2,5-diformylfuran from

5-hydroxymethylfurfural in ethyl acetate using
4-acetamido-TEMPO as a recyclable catalyst

Authors: Mei Cui, Renliang Huang, Wei Qi, Rongxin Su,

Zhimin He

PII: S0920-5861(18)30323-7
DOI: https://doi.org/10.1016/j.cattod.2018.03.054
Reference: CATTOD 11337

To appear in: Catalysis Today

Received date: 11-11-2017

Revised date: 29-1-2018
Accepted date: 26-3-2018

Please cite this article as: Cui M, Huang R, Qi W, Su R, He Z,

Synthesis of 2,5-diformylfuran from 5-hydroxymethylfurfural in ethyl acetate
using 4-acetamido-TEMPO as a recyclable catalyst, Catalysis Today (2010),
https://doi.org/10.1016/j.cattod.2018.03.054

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Synthesis of 2,5-diformylfuran from 5-hydroxymethylfurfural in ethyl

acetate using 4-acetamido-TEMPO as a recyclable catalyst

Mei Cui a, Renliang Huang b*, Wei Qi a,c,d*, Rongxin Su a,c,d, Zhimin He a

a
State Key Laboratory of Chemical Engineering, School of Chemical Engineering

T
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and Technology, Tianjin University, Tianjin 300072, China

R
Tianjin Engineering Center of Bio Gas/Oil Technology, School of Environmental

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Science and Engineering, Tianjin University, Tianjin 300072, China

c
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin),

Tianjin 300072, China U

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d
Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin
A
M

University, Tianjin 300072, China

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* Corresponding author
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E-mail address: tjuhrl@tju.edu.cn (R. Huang); qiwei@tju.edu.cn (W. Qi)

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Graphical abstract
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1
Highlights

 ·A green method for the synthesis of 2,5-DFF from 5-HMF in ethyl acetate is developed.

 ·High yield of 2,5-DFF is achieved using 4-acetamido-TEMPO as catalyst at 40 oC.

 ·4-acetamido-TEMPO can be easily recovered and shows good recyclability.

Abstract:

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2,5-Diformylfuran (2,5-DFF) is an important furan-based chemical with broad

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application potential. To address the difficulties in isolating/purifying the product and

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recycling the 2,2,6,6- tetramethylpiperidine-1-oxy (TEMPO)-based catalysts, we

employed a solvent with a low boiling point in which TEMPO has a low solubility to

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investigate the effects of TEMPO and its analogs on catalyzing the oxidation of
N
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5-hydroxymethylfurfural (5-HMF). The results indicated that in ethyl acetate with the
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substitution of one H of TEMPO at the C4 position with either an acetamido

(-NH-Ac), methoxy (-OCH3), hydroxy (-OH) or isothiocyanato (-N = C = S) group,

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the resulting compound had a product selectivity similar to that of TEMPO (> 86%),
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except for the 4-isothiocyanato-TEMPO-catalyzed reaction. However, after two Hs

were substituted with an oxo group (= O), the catalytic efficiency significantly
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decreased (product yield 16%, selectivity 52%). Based on both the catalytic efficiency
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and catalyst solubility, a highly efficient method for preparing 2,5-DFF was
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established using ethyl acetate as the solvent, 4-acetamido-TEMPO as the catalyst and

Fe(NO3)3 and NaCl as cocatalysts. At 40 C with a substrate concentration of 0.125

mol/L, 5-HMF was completely converted in 2 h, and the yield of 2,5-DFF was 89%.

Moreover, when the substrate concentration increased to 0.25 mol/L, the yield of

2
2,5-DFF was 87%. When 4-acetamido-TEMPO was recovered by centrifugation, the

product yield remained as high as 86% after three cycles, demonstrating good

recyclability.

Keywords: TEMPO; 5-hydroxymethylfurfural; 2,5-DFF; ethyl acetate; biomass

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1. Introduction

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The preparation of high value-added chemicals from bio-based saccharides has

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attracted much attention in recent years [1-6]. As an important bio-based platform

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chemical, 5-hydroxymethylfurfural (5-HMF) can be converted to various high

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value-added products through subsequent steps including hydrogenation, oxidation
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and hydration [1, 7-11]. 2,5-Diformylfuran (2,5-DFF) is one of the important products
A

derived from 5-HMF via selective oxidation [12-15]. 2,5-DFF contains two rather
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reactive aldehyde groups and one furan ring, and this chemical can be converted into
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other high value-added chemicals and new polymer materials including

pharmaceutical intermediates, organic conductors, fluorescers and macrocyclic ligand,

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using various chemical reactions, such as hydrogenation, oxidation, polymerization

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and hydrolysis [16-18].

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In recent years, 2,5-DFF has been primarily prepared through the oxidation of

5-HMF and the direct dehydration and further oxidation of fructose. Numerous efforts
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have focused on this field including some studies that was recently reported by our

group [19, 20]. Currently, several catalytic systems have been established for 2,5-DFF

production via 5-HMF oxidation, and the necessary catalysts can be divided into

3
several categories including vanadium-based catalysts, manganese-based catalysts,

noble metal-based catalysts and non-metal catalysts. The vanadium-based catalysts

are commonly used due to their low price. In 1997, Moreau et al. [21] achieved a 91%

conversion of 5-HMF with a selectivity of 93% for 2,5-DFF using V2O5 on a TiO2

carrier as a catalyst and methyl isobutyl ketone (MIBK) and toluene as solvents in a

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the reaction at 80 C and 1.6 MPa. However, in this process, the amount of catalyst

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was twice that of the substrate, and the reaction required a high pressure. We achieved

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complete HMF conversion and an 85.7% 2,5-DFF yield in 5 h using a reaction set up

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with V2O5 on a ceramic carrier as the catalyst in dimethylsulfoxide (DMSO) at 140 C

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under 0.1 MPa of oxygen in a one-pot synthesis using fructose as the starting material,
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and the 2,5-DFF yield was 68.4% [22]. Recently, the vanadium (V)-containing
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all-silica beta-zeolites (VSi-Beta) developed by Zhang et al. [23] demonstrated high

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activity in the one-pot conversion of fructose into 2,5-DFF in the presence of sulfuric
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acid, affording a high yield of 86.3%. Manganese-based catalysts, which are another

group of inexpensive catalysts, have also been extensively investigated. Yang et al.
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[24] applied porous manganese dioxide K-OMS-2 to catalyze the synthesis of

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2,5-DFF from 5-HMF in DMSO at 110 C, and the yield of 2,5-DFF was as high as
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99% in 6 h. Nie et al. [25] and Yadav et al. [26] used a manganese-based molecular

sieve and Ag-doped Ag-OMS-2, respectively, to establish reaction systems with good
A

catalytic properties. Recently, Biswas et al. [27] reported a promising catalytic

protocol for the oxidation of 5-HMF to 2,5-DFF using the mesoporous manganese

doped cobalt oxide as catalyst and air as the sole oxidant. Noble metal catalysts have

4
exhibited high activity as well as high selectivity for the selective oxidation of 5-HMF

[28-31]. Antonyraj et al. [29] used RuCl3/Al2O3 as a catalyst in a reaction at 130 C in

toluene to achieve a final 5-HMF conversion of 99% and a 2,5-DFF selectivity of

97%. Zhu et al. [30] employed Au loaded onto a MnO2 microspheroidal carrier at 120

C under atmospheric oxygen using dimethyl formamide (DMF) as the solvent to

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obtain a final 5-HMF conversion of 82% and a 2,5-DFF selectivity of 99% in 8 h.

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Although these methods can efficiently produce 2,5-DFF, some challenges remain

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including the high boiling point of the reaction solvent, stringent reaction conditions

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and difficulties in isolating the product, which are not conducive to large-scale

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applications. Therefore, a green reaction system with the mild operating conditions
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where the product can be easily isolated is desired. Recently, Ning et al. [32] also
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reported the catalytic synthesis of 2,5-DFF from 5-HMF under mild conditions (80
M

o
C ) with a cobalt-based catalyst (CoxOy-N@TiO2).
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Based on these requirements, TEMPO and its analogs (N-oxyl radical catalysts),

which are a group of mild non-metal catalysts, have emerged as potential reaction
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components. These mild oxidation catalysts can efficiently and highly selectively
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catalyze the oxidation of alcohols to produce the corresponding aldehydes or ketones

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[33, 34]. Currently, only a few studies have applied N-oxyl radicals to catalyze the

oxidation of 5-HMF. In 1995, Cottier et al. studied the application of N-oxyl radical
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catalysts to 5-HMF oxidation in different reaction systems and demonstrated that in

the presence of Ca(ClO)2 in a biphasic system of water-dichloromethane, a 2,5-DFF

conversion rate of 81% can be achieved in 10 min at 10-15 C. In addition, Hansen et

5
al. [35] achieved a 2,5-DFF yield of 95% in 24 h at room temperature under

atmospheric oxygen pressure in acetonitrile using TEMPO as the catalyst, CuCl as the

cocatalyst and 2,2-bipyridine (bipy) as an additive. Recently, Li et al. [36] reported

that the benzoic acid/TEMPO afforded an efficient catalytic system for the oxidation

of 5- HMF into 2,5-DFF and obtained the maximum conversion of 86.7 % for 5-HMF

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with a 77.8 % 2,5-DFF yield at 0.4 MPa O2 in acetonitrile. Because TEMPO is

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difficult to recycle, Karimi et al. [37] synthesized a magnetic and recyclable TEMPO

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catalyst (Fe3O4 @ SiO2-TEMPO) that achieved a 2,5-DFF yield of 99% in 24 h at 50

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C under atmospheric oxygen pressure using toluene as the solvent in the presence of

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t-butyl nitrite and acetic acid. Mittal et al. [38] immobilized TEMPO on SBA-15 and
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achieved a 2,5-DFF yield of 73% in 1 h using ethyl acetate as the solvent at 40 C
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under atmospheric oxygen pressure in the presence of [bis(acetoxy)iodo] benzene

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(BAIB) and acetic acid. As previously mentioned, some studies have employed the
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immobilization of TEMPO to recycle the catalyst. Herein, we report the successful

production and isolation of 2,5-DFF as well as catalyst recycling using ethyl acetate
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as a low boiling point solvent and 4-acetamido-TEMPO as the catalyst.

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First, we investigated the effect of six different TEMPO-type catalysts on the

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oxidation of 5-HMF to produce 2,5-DFF in ethyl acetate. 4-Acetamido-TEMPO,

which has a low solubility in ethyl acetate, was used as the catalyst, and Fe(NO3)3 and
A

NaCl were used as cocatalysts to produce 2,5-DFF at room temperature and

atmospheric pressure and investigate the effect of various reaction parameters (e.g.,

the amount of catalyst, amount of cocatalyst, reaction time, temperature and oxygen

6
flow rate) on the catalytic performance. In addition, the recycling properties of the

catalyst were evaluated, and the mechanism of the catalytic reaction was analyzed.

2. Experimental

2.1 Materials

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5-HMF was purchased from Beijing Huawei Ruike Chemical Co., Ltd.

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2,5-Furandicarboxylic 4-OH-TEMPO, 4-O-TEMPO, sodium chloride, cobalt nitrate,

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sodium nitrate, ferric chloride, DMF and acetonitrile were purchased from Shanghai

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Aladdin Biochemical Technology Co., Ltd. 5-Formyl-2-furancarboxylic acid and

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4-NCS-TEMPO were purchased from TCI (Shanghai) Chemical Industry Co., Ltd.
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DMSO, iron sulfate, copper nitrate, anhydrous methanol, MIBK and magnesium
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nitrate were obtained from Tianjin Guangfu Technology Development Co., Ltd.
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4-Acetamido-TEMPO, 4-OCH3-TEMPO, TEMPO, ethyl acetate and ferric nitrate

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were purchased from Tianjin Heowns Biochem LLC. All reagents were used without

further purification.
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2.2 Oxidation of 5-HMF

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To test the catalytic performance of different catalysts, 0.04 mmol of

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4-acetamido-TEMPO, 4-OCH3-TEMPO, TEMPO, 4-OH-TEMPO, 4-NCS-TEMPO

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or 4-O-TEMPO was added to a glass reactor supplied with a total reflux condenser,

and then, 63 mg (0.5 mmol) of 5-HMF, 10.1 mg (0.025 mmol) of Fe(NO3)3, 1.5 mg

(0.025 mmol) of NaCl and 4 mL of ethyl acetate were added to the reactor. Oxygen

was supplied at a flow rate of 10 mL/min. The glass reactor was placed in an oil bath

7
at 40 C with stirring using a magnetic bar. After the reaction was complete, the

reaction mixture was transferred to a volumetric flask. Then, the reactor was rinsed

with ethyl acetate, and the final volume was adjusted to 10 mL. The product was

quantitatively analyzed via gas chromatography.

To optimize the reaction conditions, the previously described reaction was

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performed using various solvents, types of cocatalyst, amounts of catalyst, amounts of

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cocatalyst, oxygen flow rates, temperatures and substrate concentrations.

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2.3 Catalyst recycling

In the 4-acetamido-TEMPO catalyst system, the reaction mixture was collected in a

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centrifuge tube and centrifuged to remove the supernatant after completion of the
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A
reaction. After two rinses with ethyl acetate, the catalyst pellet was dried and added to
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an aspirated glass reactor. Then, 63 mg of 5-HMF, 10.1 mg of Fe(NO3)3, 1.5 mg of

NaCl and 4 mL of ethyl acetate were added, and oxygen gas was supplied. The reactor
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was incubated in an oil bath at 40 C, and the reaction was initiated and timed. After
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the reaction was complete, the reaction product was cooled to room temperature and

transferred to a volumetric flask. Then, the reactor was washed with ethyl acetate, and
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the final volume was adjusted to 10 mL for analysis.

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2.4 Product analysis

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The concentrations of 5-HMF and 2,5-DFF were determined using gas

chromatography (GC, AgiIem 6890/5973Ms, HP-5, 30 * 0.32 mm (id)) and a flame

ionization detector (detection temperature: 300 C; injection outlet temperature: 220

8
C), and prior to loading, the samples were filtered using a 0.22-μm membrane.

3. Results and discussion

3.1 Effect of catalysts in the aerobic oxidation of 5-HMF in EtOAC

In recent years, methods for the selective catalytic oxidation of 5-HMF using

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N-oxyl radical catalysts have been reported where 4-acetamido-TEMPO,

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4-OH-TEMPO and TEMPO have been used in various solvents to generate 2,5-DFF

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by oxidizing 5-HMF with good results (Table S1) [39-41]. We selected six different

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N-oxyl radical catalysts and used Fe(NO3)3 and NaCl as cocatalysts to produce

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2,5-DFF in ethyl acetate via catalytic oxidation. As shown in Table 1, the results
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indicate that under the same conditions, 4-acetamido-TEMPO, 4-OH-TEMPO,
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TEMPO and 4-OCH3-TEMPO exhibited very similar 5-HMF conversion rates (i.e.,
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95-100%). However, 4-NCS-TEMPO resulted in a slightly lower conversion rate of

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84%. Nevertheless, the selectivity for 2,5-DFF of the five N-oxyl radical catalysts was

similar (i.e., 85-89%). When 4-O-TEMPO was used as the catalyst, the conversion of
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5-HMF was only 31%, and the 2,5-DFF selectivity was only 52%. These results did
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not exhibit a significant correlation with the reduction potentials of the six N-oxyl
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radicals, which are very similar to those of the nitrogen radicals employed in an

alcohol oxidation process reported by Markus et al. [42]. When one H at the C4
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position of TEMPO was substituted by an acetamido group (-NH-Ac), methoxy group

(-OCH3), hydroxyl group (-OH) or isothiocyanato group (-N = C = S), the product

selectivity was similar to that of TEMPO. However, when two Hs were substituted by

9
an oxo group (= O), the catalytic efficiency decreased significantly, which is most

likely due to the C = O bond that formed at the C4 position pulling the lone-pair

electrons further toward the six-member ring. Therefore, the activity of the free

electrons of the N-oxyl radicals decreased, reducing the catalytic performance. In

subsequent experiments, 4-acetamido-TEMPO and 4-OCH3-TEMPO were used

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because they exhibited better catalytic performance.

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To examine the role of a cocatalyst in the reaction, we selected several trivalent

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iron salts and metal nitrates as cocatalysts, and the results are shown in Table 2.

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Among the seven inorganic salts, Fe(NO3)3 as a cocatalyst led to the highest 5-HMF

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conversion rate (i.e., 100%) with a 2,5-DFF yield of 88% in 2 h. When FeCl3 and
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Fe2(SO4)3 were used, no 2,5-DFF was produced, indicating that when NO3- is absent,
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the coupling among Fe3+, 4-OCH3-TEMPO and NaCl cannot perform the selective
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oxidation of 5-HMF to generate 2,5-DFF. When metal nitrates were used as

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cocatalysts, Cu(NO3)2 led to a 2,5-DFF yield at 56.5% with a 5-HMF conversion rate

of 72.8%. However, these results were significantly lower than those of Fe(NO3)3.
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Mg(NO3)2, Co(NO3)2 and NaNO3, which exhibited small amount of 5-HMF

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conversion (10.4%, 25.8% and 8.4%, respectively) with the highest 2,5-DFF yield
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being only 10.2%. This result was most likely due to these metal ions not being able

to promptly re-oxidize the reduced 4-OCH3-TEMPO to its N-oxyl radical state,

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leading to a low conversion and low yield. These results indicated that both Fe3+ and

NO3- determine the effect of co-catalyst, while the other ions, e.g., Fe2+, Mg2+, Cl-,

SO42-, exhibited poor performance. Therefore, the use of Fe(NO3)3 and NaCl as

10
cocatalysts achieved the best performance for the catalytic conversion of 5-HMF to

2,5-DFF.

3.2 Effect of solvent on the aerobic oxidation of 5-HMF

In this study, six solvents were used to test the effect of different solvents on the

conversion of 5-HMF to 2,5-DFF. As shown in Fig. 1, in acetonitrile, the 5-HMF

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conversion and 2,5-DFF selectivity were 56% and 82%, respectively. When MIBK,

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DMF, DMSO and methanol were used as the reaction solvent, the catalytic

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performance was very poor, with a 5-HMF conversion rate less than 33% and a

maximum 2,5-DFF yield of 20%. Although the reaction performance did not exhibit a

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linear relationship with the polarity of the solvent (in terms of polarity, ethyl acetate <
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MIBK < acetonitrile < DMF < methanol < DMSO), less polar solvents performed
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slightly better.

3.3 Optimization of reaction conditions

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Table 3 summarizes the changes in 5-HMF conversion and 2,5-DFF yield as the
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amount of catalyst was varied. When 0.01 mmol of 4-acetamido-TEMPO was used as
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the catalyst, only 86% of HMF was converted with a 2,5-DFF selectivity of 81%. As
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the amount of 4-acetamido-TEMPO increased to 0.02 mmol, the HMF conversion

rate increased to 99%, and the 2,5-DFF yield increased to 81%. With a further
A

increase in the amount of 4-acetamido-TEMPO to 0.03 mmol or 0.04 mmol, the HMF

was completely converted with 2,5-DFF yields of 85% and 89%, respectively.

Similarly, using 0.01 mmol of 4-OCH3-TEMPO achieved a 5-HMF conversion of

11
84.2% with a 2,5-DFF selectivity of only 77%. A further increase in the amount to

0.05 mmol led to complete 5-HMF conversion, and the 2,5-DFF selectivity increased

to 88%. Therefore, the optimal amounts of the 4-acetamido-TEMPO and

4-OCH3-TEMPO catalysts were 0.04 mmol and 0.05 mmol, respectively.

Fig. 2 shows the effect of different reaction conditions on the oxidation of 5-HMF.

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As shown in Fig. 2a, in the absence of Fe(NO3)3, 13% of the 5-HMF reacted but

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without any conversion to 2,5-DFF. As the amount of Fe(NO3)3 increased to 0.025

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mmol, the 5-HMF conversion rate rapidly increased to 100%, and the yield of

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2,5-DFF increased to 89%. A further increase in the amount of Fe(NO3)3 slightly

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reduced the yield of 2,5-DFF because the 2,5-DFF product was further oxidized to
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5-formyl-2-furan-carboxylic acid (FFCA) (Fig. S1).
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Fig. 2b shows the temperature dependence of the 5-HMF conversion and 2,5-DFF
M

yield. When the reaction was conducted at 25 C, the catalytic performance was poor,
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and as the temperature increased to 30 C or 35 C, both the 5-HMF conversion and

2,5-DFF yield improved. At 40 C for 2 h, the 5-HMF conversion and 2,5-DFF yield
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were 100% and 89%, respectively. However, as the reaction temperature increased
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from 40 C to 50 C, the 2,5-DFF yield decreased slightly due to the as-formed
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2,5-DFF undergoing some side reactions at the higher temperature.

The effect of the O2 flow rate on the 5-HMF conversion and 2,5-DFF yield is
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shown in Fig. 2c. Without supplying oxygen, 5-HMF could still be oxidized to afford

2,5-DFF due to the dissolved oxygen in the air. However, the reaction rate was slower.

When the oxygen flow rate was varied in the range of 5-20 mL/min, the 2,5-DFF

12
yield first increased and then decreased. However, in general, there was little change.

The effect of an increased substrate concentration on the conversion of 5-HMF and

the yield/selectivity of 2,5-DFF was investigated, and the results are shown in Fig. 2d.

As the substrate concentration increased from 0.125 mol/L to 0.25 mol/L, the 5-HMF

was completely converted. However, the yield of 2,5-DFF decreased slightly to 87%.

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As the concentration of 5-HMF was further increased to 0.5 mol/L and 1 mol/L, the

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yield of 2,5-DFF decreased to 78% and 52%, respectively, which is most likely due to

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the mass transfer of the entire system being restricted by the increase in the substrate

SC
concentration. Therefore, the selectivity for 2,5-DFF decreased.

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Under the previously mentioned optimal conditions, the reaction process for the
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4-acetamido-TEMPO catalyzed oxidation of 5-HMF to form 2,5-DFF was
A

investigated. As shown in Fig. 3, the 5-HMF conversion and 2,5-DFF yield rapidly
M

increased to 81% and 64%, respectively, during the first 40 min of the reaction. As the
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reaction time elapsed, nearly all the 5-HMF participated in the reaction in 90 min but

the yield of 2,5-DFF peaked at 89% in 120 min. When the reaction time was extended
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to 180 min, the yield of 2,5-DFF decreased slightly to 85%. It is important to note that
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in the first 40 min of the reaction, the selectivity significantly increased, indicating
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that an undetected intermediate was produced. This result is consistent with the report

by Hansen et al. in which TEMPO and CuCl were used to oxidize 5-HMF [35].
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3.4 Catalyst recycling

Next, we studied the performance of recycled 4-acetamido-TEMPO. As shown in

Fig. 4, at a reaction temperature of 40 C for 2 h, the first three recycled uses of the

13
catalyst achieved complete conversion, and the yield of 2,5-DFF only slightly

decreased from 89% to 86%. However, the HMF conversion rate with the 4th recycled

use of the catalyst decreased to 93%, and the 2,5-DFF yield decreased to 78%, which

is most likely due to various operations, such as centrifugation and transfer during the

recycling process, which led to the loss of 4-acetamido-TEMPO and a decrease in the

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2,5-DFF yield. To avoid the contribution of catalyst dose, the recycling of catalyst

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was carried out with a 75% of 5-HMF conversion at 30 min. As shown in Fig. S2, the

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5-HMF conversion decreased from 75% to 70% after being recycled three times, and

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the 2,5-DFF yield decreased from 51% to 45%. These results indicate that catalyst

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recycling of the current catalyst system can be achieved via simple centrifugation. In
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previous studies involving the use of an N-oxyl catalyst for the conversion of 5-HMF
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to DFF, except for immobilized catalysts, catalyst recycling was difficult, as shown in
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the comparison in Table S1.

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3.5 Proposed reaction mechanism

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Based on the catalytic mechanism of TEMPO/FeCl3 /NaNO2 on alcohols [43], we

propose a possible mechanism for the 4-acetamido-TEMPO catalytic conversion of

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5-HMF to 2,5-DFF (Fig. 5). Briefly, in Step 1, 4-acetamido-TEMPO captures a H

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from 5-HMF to form 4-acetamido-TEMPOH, and Fe3+ combines with the

A

dehydrogenated 5-HMF to form intermediate I. In Step 2, another

4-acetamido-TEMPO captures a H from intermediate I, giving rise to 2,5-DFF as well

as 4-acetamido-TEMPOH and Fe(II). In Step 3, the 4-acetamido-TEMPOH that

obtained a H can be oxidized by O2 or NO2 to regenerate 4-acetamido-TEMPO,

14
achieving the recycling of the 4-acetamido-TEMPO catalyst. In Step 4, the generated

Fe(II) is reoxidized to Fe(III) by NO2, recycling the iron. In addition, as Fe(III) is

reduced to Fe(II), a protonic acid is produced and reacts with NaNO3 to produce NO2.

In summary, after Steps 1 and 2, two Hs are captured from 5-HMF by

4-acetamido-TEMPO to generate 2,5-DFF. After Steps 3 and 4,4-acetamido-TEMPO

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(catalyst) and Fe(NO3)3 (cocatalyst) are regenerated and return to their initial states,

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catalyzing the conversion of 5-HMF to 2,5-DFF.

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4. Conclusions
In summary, we report a green synthesis process for 2,5-DFF that uses ethyl acetate

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as a low-boiling-point solvent, 4-acetamido-TEMPO as a catalyst and Fe(NO3)3 and
N
A
NaCl as cocatalysts to highly selectively synthesize 2,5-DFF via the oxidation of
M

5-HMF at room temperature and atmospheric pressure with a product yield as high as

89%. More importantly, because 4-acetamido-TEMPO has a low solubility in ethyl

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acetate, this catalyst can be recovered by simple centrifugation and reused as a

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catalyst with a 2,5-DFF yield of 86% after three recycling uses. In comparison to a

conventional immobilized TEMPO catalyst system, the process developed in this

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study is green and simple with a recyclable catalyst, and this process has the potential
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for use in the large-scale production of 2,5-DFF.

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Acknowledgments

This work was supported by the Natural Science Foundation of Tianjin, China (No.

16JCYBJC19600), the National Key R&D Program of China (No. 2017YFB0306502)

15
and the Natural Science Foundation of China (No. 21621004).

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, at

http://dx.doi.org/10.1016/j.cattod.

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References

[1] D. Esposito, M. Antonietti, Chem. Soc. Rev., 44 (2015) 5821-5835.

[2] I.K.M. Yu, D.C.W. Tsang, Bioresour. Technol., 238 (2017) 716-732.
[3] L. Hu, L. Lin, Z. Wu, S. Zhou, S. Liu, Renew. Sust. Energ. Rev., 74 (2017)
230-257.
[4] N. Jiang, W. Qi, Z. Wu, R. Su, Z. He, Catal. Today, (2017)

T
doi.org/10.1016/j.cattod.2017.1005.1081.

IP
[5] Z. Yang, W. Qi, R. Huang, J. Fang, R. Su, Z. He, Chem. Eng. J., 296 (2016)

R
209-216.

SC
[6] R. Huang, W. Qi, R. Su, Z. He, Chem. Commun., 46 (2010) 1115-1117.
[7] A.A. Rosatella, S.P. Simeonov, R.F.M. Frade, C.A.M. Afonso, Green. Chem., 13
(2011) 754-793.
U
N
[8] Y. Román-Leshkov, J.N. Chheda, J.A. Dumesic, Science, 312 (2006) 1933.
[9] S. Nishimura, N. Ikeda, K. Ebitani, Catal. Today, 232 (2014) 89-98.
A

[10] A.B. Gawade, A.V. Nakhate, G.D. Yadav, Catal. Today, (2017).
M

[11] L. Özcan, P. Yalçın, O. Alagöz, S. Yurdakal, Catal. Today, 281 (2017) 205-213.
[12] J. Ma, Z. Du, J. Xu, Q. Chu, Y. Pang, ChemSusChem, 4 (2011) 51–54.
ED

[13] N.T. Le, P. Lakshmanan, K. Cho, Y. Han, H. Kim, Appl. Catal. A-Gen., s 464–465
(2013) 305-312.
PT

[14] J. Artz, S. Mallmann, R. Palkovits, ChemSusChem, 8 (2015) 672-679.

[15] F. Neaţu, N. Petrea, R. Petre, V. Somoghi, M. Florea, V.I. Parvulescu, Catal.
E

Today, 278 (2016) 66-73.

CC

[16] P.M. Del, W.A. Schell, C.C. Dykstra, S. Jones, R.R. Tidwell, A. Czarny, M. Bajic,
A. Kumar, D. Boykin, J.R. Perfect, Antimicrob. Agents Chemother., 42 (1998)
A

2495-2502.
[17] V.P. Grigor'Ev, A.N. Didenko, Russ. Phys. J., 21 (1978) 27-40.
[18] F.W. Lichtenthaler, Acc. Chem. Res., 35 (2002) 728-737.
[19] Z. Yang, W. Qi, R. Su, Z. He, ACS Sustainable Chem. Eng., 5 (2017) 4179-4187.
[20] Z. Yang, W. Qi, R. Su, Z. He, Energy Fuels, 31 (2016) 533-541.

17
[21] C. Moreau, R. Durand, C. Pourcheron, D. Tichit, Stud. Surf. Sci. Catal., 108
(1997) 399-406.
[22] M. Cui, R. Huang, W. Qi, R. Su, Z. He, RSC Adv., 7 (2017) 7560-7566.
[23] W. Zhang, W. Hou, T. Meng, W. Zhuang, J. Xie, Y. Zhou, J. Wang, Catal. Sci.
Technol., 7 (2017) 6050-6058.
[24] Z.Z. Yang, J. Deng, T. Pan, Q.X. Guo, Y. Fu, Green. Chem., 14 (2012)
2986-2989.

T
[25] J. Nie, H. Liu, J. Catal., 316 (2014) 57-66.

IP
[26] G.D. Yadav, R.V. Sharma, Appl. Catal. B-Environ., 147 (2014) 293-301.

R
[27] S. Biswas, B. Dutta, A. Mannodi-Kanakkithodi, R. Clarke, W. Song, R.

SC
Ramprasad, S.L. Suib, Chem. Commun., 53 (2017) 11751-11754.
[28] K. Ghosh, R.A. Molla, M.A. Iqubal, S.S. Islam, S.M. Islam, Appl. Catal. A-Gen.,
520 (2016) 44-52.
U
N
[29] C.A. Antonyraj, J. Jeong, B. Kim, S. Shin, S. Kim, K.Y. Lee, K.C. Jin, J. Ind. Eng.
A
Chem., 19 (2013) 1056-1059.
[30] Y. Zhu, M. Shen, Y. Xia, M. Lu, Catal. Commun., 64 (2015) 37-43.
M

[31] T. Cao, M. Wu, V.V. Ordomsky, X. Xin, H. Wang, P. Métivier, M. Pera-Titus,

ED

ChemSusChem, 10 (2017) 4851-4854.

[32] L. Ning, S. Liao, Y. Sun, L. Yu, X. Tong, Waste Biomass Valor., 9 (2018) 95-101.
[33] C. Aellig, D. Scholz, S. Conrad, I. Hermans, Green. Chem., 15 (2013) 1975-1980.
PT

[34] C.X. Miao, L.N. He, J.Q. Wang, J.L. Wang, Adv. Synth. Catal., 351 (2009) 2209–
2216.
E

[35] T.S. Hansen, I. Sádaba, E.J. García-Suárez, A. Riisager, Appl. Catal. A-Gen., 456
CC

(2013) 44-50.
[36] J. Li, G. Lv, B. Lu, Y. Wang, T. Deng, X. Hou, Y. Yang, Energy Technol., 5 (2017)
A

1429-1434.
[37] B. Karimi, H.M. Mirzaei, E. Farhangi, ChemCatChem, 6 (2014) 758-762.
[38] N. Mittal, G.M. Nisola, J.G. Seo, S.P. Lee, W.J. Chung, J. Mol. Catal. A-Chem.,
404-405 (2015) 106-114.
[39] V.P. Kashparova, V.A. Klushin, D.V. Leontyeva, N.V. Smirnova, V.M.
18
 Chernyshev, V.P. Ananikov, Chem. -Asian J., 11 (2016) 2578-2585.
[40] N. Mittal, G.M. Nisola, L.B. Malihan, Korean J. Chem. Eng., 31 (2014)
1362-1367.
[41] L. Cottier, G. Descotes, J. Lewkowski, R. Skowronski, E. Viollet, J. Heterocycl.
Chem., 32 (1995) 927-930.
[42] M.B. Lauber, S.S. Stahl, ACS Catal., 3 (2013) 2612–2616.
[43] Y. Peng, D. Fu, R. Liu, F. Zhang, X. Liang, Chemosphere, 71 (2008) 990-997.

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Figure Captions

Scheme 1. Synthesis of 2,5-DFF via the oxidation of 5-HMF in ethyl acetate using

4-acetamido-TEMPO as a catalyst.

Fig. 1. Effect of different solvents on 5-HMF conversion and 2,5-DFF yield. Reaction

conditions: HMF (63 mg, 0.5 mmol), 4-acetamido-TEMPO (8.5 mg, 0.04 mmol),

T
Fe(NO3)3  9H2O (10.1 mg, 0.025 mmol), NaCl (1.5 mg, 0.025 mmol), solvent (4 mL),

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O2 (10 mL/min), 40 C, 2 h.

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Fig. 2. Effect of reaction conditions on the conversion of 5-HMF to 2,5-DFF. a)

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cocatalyst dose; b) temperature; c) oxygen flow rate; d) 5-HMF concentration. If not

U
specified, the default reaction conditions were as follows: HMF (63 mg, 0.5 mmol),
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4-acetamido-TEMPO (8.5 mg, 0.04 mmol), Fe(NO3)3 (10.1 mg, 0.025 mmol), NaCl
A
(1.5 mg, 0.025 mmol), EtOAC (4 mL), O2 (10 mL/min), 40 °C, 2 h.
M

Fig. 3. Time course of the oxidation of 5-HMF to 2,5-DFF. The default reaction
ED

conditions were as follows: HMF (63 mg, 0.5 mmol), 4-acetamido-TEMPO (8.5 mg,

0.04 mmol), Fe(NO3)3 (10.1 mg, 0.025 mmol), NaCl (1.5 mg, 0.025 mmol), EtOAC
PT

(4 mL), O2 (10 mL/min), 40 C.

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Fig. 4. Recycling results for the 4-acetamido-TEMPO-catalyzed aerobic oxidation of

CC

5-HMF. Reaction conditions: 5-HMF (63 mg, 0.5 mmol), EtOAC (4 mL), O2 (10

mL/min), 40 C, 2 h.
A

Fig. 5. Mechanism for the 4-NH-Ac-TEMPO-catalyzed aerobic oxidation of 5-HMF

to 2,5-DFF.

20
 A
CC
EPT
ED

21
M
A
N
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SC
RIP
T
 100 100
Conversion / Yield (%)
80 80

Selectivity (%)
60 60

40 40

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20 20

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0 0
100
EtOAC MeCN
110 MIBK
120 130
DMF DMSO
140 MeOH
150

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Solvent

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A
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E PT
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A

22
 a) b)
100 100 100 100
Conversion / Yield (%)

Conversion / Yield (%)

80 80 80 80

Selectivity (%)

Selectivity (%)
60 60 60 60

40 40 40 40

20 20 20 20

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0 0
0 0
90
0 100
0.01 110
0.025 120
0.04 130
0.05 100
25 110
30 120
35 130
40 140
50

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o
Cocatalyst dose (mmol) Temperature ( C)

c) d)

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100 100 100 100
Conversion / Yield (%)

Conversion / Yield (%)

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80 80 80 80

Selectivity (%)
Selectivity (%)

60 60 60 60

40 40 40 40

20 20 20
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0 0
0 0
100
0 110
5 120
10 130
20 100
0.125 110
0.25 120
0.5 130
1
Oxygen flow rate (mL/min) 5-HMF concentration (mol/L)
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 100 100
Conversion / Yield (%)

80 80

Selectivity (%)
60 60

40 40

Conversion
20 20

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Yield
Selectivity

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0 0
0 30 60 90 120 150 180

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Time (min)

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24
 A
Conversion / Yield (%)

0
20
40
60
80
100
CC
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1
100
PT
2
110
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Run (No.)
3
120

25
M
A
4
130

N
0
20
40
60
80

U
100

Selectivity (%)
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 A
CC
EPT
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M
A
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RIP
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Table 1. Effect of different catalysts on 5-HMF conversion and 2,5-DFF yield

5-HMF conversion 2,5-DFF yield Selectivity

No. Catalyst
(%) (%) (%)

1 4-Acetamido-TEMPO 100 89 89

2 4-OCH3 -TEMPO 99 84 85

3 TEMPO 100 85 85

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4 4-OH-TEMPO 95 83 87

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5 4-NCS-TEMPO 84 73 87

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6 4-O-TEMPO 31 16 52

Reaction conditions: 5-HMF (63 mg, 0.5 mmol), catalyst (0.04 mmol), Fe(NO3)3 (10.1 mg, 0.025

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mmol), NaCl (1.5 mg, 0.025 mmol), EtOAC (4 mL), O 2 (10 mL/min), 40 C, 2 h.
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A
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A

27
Table 2. Effect of different cocatalysts on 5-HMF conversion and 2,5-DFF yield

HMF conversion 2,5-DFF yield Selectivity

No. Cocatalyst
(%) (%) (%)

1 - 10.2 0 0

2 Fe(NO3)3 100 85 85

3 Fe(NO3)3 + NaCl 100 88 88

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4 FeCl3  6H2O + NaCl 0 0 0

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5 Fe2(SO4)3 + NaCl 15 0 0

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6 Cu(NO3)2  3H2O + NaCl 73 56 77

7 Mg(NO3)2 + NaCl 10 6 60

8 Co(NO3)2  6H2O + NaCl 26 U 10 38

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9 NaNO3 + NaCl 8 5 62
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Reaction conditions: 5-HMF (63 mg, 0.5 mmol), 4-OCH3-TEMPO (9.4 mg, 0.05 mmol),

cocatalyst (0.025 mmol), NaCl (1.5 mg, 0.025 mmol), EtOAC (4 mL), O2 (10 mL/min), 40 C, 2
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h.
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A

28
Table 3. Effect of catalyst dose on 5-HMF conversion and 2,5-DFF yield

Catalyst dose HMF 2,5-DFF Selectivity

No. Catalyst
(mmol) conversion (%) yield (%) (%)

1 4-Acetamido-TEMPO - 15 - -

2 4-Acetamido-TEMPO 0.01 86 70 81

3 4-Acetamido-TEMPO 0.02 99 81 82

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4 4-Acetamido-TEMPO 0.03 100 85 85

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5 4-Acetamido-TEMPO 0.04 100 89 89

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6 4-Acetamido-TEMPO 0.05 100 89 89

7 4-OCH3-TEMPO 0.01 84 65 77

8 4-OCH3-TEMPO 0.025 96 U 82 85
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9 4-OCH3-TEMPO 0.04 99 84 85
A
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10 4-OCH3-TEMPO 0.05 100 88 88

11 4-OCH3-TEMPO 0.08 100 87 87

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Reaction conditions: 5-HMF (63 mg, 0.5 mmol), Fe(NO3)3 (10.1 mg, 0.025 mmol), NaCl (1.5 mg,
PT

0.025 mmol), EtOAC (4 mL), O2 (10 mL/min), 40 C, 2 h.

E
CC
A

29