Hydrothermal conversion of N-acetyl-D-glucosamine to 5-hydroxymethylfurfural using ionic liquid as a recycled catalyst in a water-dimethyl sulfoxide mixture

Article abstract of DOI:10.1016/j.carres.2017.02.002

Here, N-acetyl-D-glucosamine (GlcNAc), the monomer composing the second most abundant biopolymer, chitin, was efficiently converted into 5-hydroxymethylfurfural (5-HMF) using ionic liquid (IL) catalysts in a water/dimethyl sulfoxide (DMSO) mixture solvent. Various reaction parameters, including reaction temperature and time, DMSO/water mass ratios and catalyst dosage were optimized. A series of ILs with different structures were analyzed to explore their impact on GlcNAc conversion. The substrate scope was expanded from GlcNAc to D-glucosamine, chitin, chitosan and monosaccharides, although 5-HMF yields obtained from polymers and other monosaccharides were generally lower than those from GlcNAc. Moreover, the IL N-methylimidazolium hydrogen sulfate ([Hmim][HSO₄]) exhibited the best catalyst performance (64.6% yield) when GlcNAc was dehydrated in a DMSO/water mixture at 180?°C for 6?h without the addition of extra catalysts. To summarize, these results could provide knowledge essential to the production of valuable chemicals that are derived from renewable marine resources and benefit biofuel-related applications.

Full text of DOI:10.1016/j.carres.2017.02.002

Accepted Manuscript
Hydrothermal conversion of N-acetyl-D-glucosamine to 5-hydroxymethylfurfural using
ionic liquid as a recycled catalyst in a water-dimethyl sulfoxide mixture
Hongjun Zang, Songbai Yu, Pengfei Yu, Hongying Ding, Yannan Du, Yuchan Yang,
Yiwen Zhang
PII:
S0008-6215(16)30406-2
10.1016/j.carres.2017.02.002
CAR 7321
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 20 September 2016
Revised Date: 23 January 2017
Accepted Date: 10 February 2017
Please cite this article as: H. Zang, S. Yu, P. Yu, H. Ding, Y. Du, Y. Yang, Y. Zhang, Hydrothermal
conversion of N-acetyl-D-glucosamine to 5-hydroxymethylfurfural using ionic liquid as a recycled catalyst
in a water-dimethyl sulfoxide mixture, Carbohydrate Research (2017), doi: 10.1016/j.carres.2017.02.002.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Hydrothermal Conversion of N-acetyl-D-glucosamine to 5-Hydroxymethylfurfural
Using Ionic Liquid as a Recycled Catalyst in a Water-Dimethyl Sulfoxide Mixture
∗
Hongjun Zang, Songbai Yu, Pengfei Yu, Hongying Ding, Yannan Du, Yuchan Yang,
Yiwen Zhang
State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Department
of Environmental and Chemistry Engineering, Tianjin Polytechnic University, 300387
Tianjin, China.
ABSTRACT
Here, N-acetyl-
abundant biopolymer, chitin, was efficiently converted into 5-hydroxymethylfurfural
5-HMF) using ionic liquid (IL) catalysts in a water/dimethyl sulfoxide (DMSO)
D-glucosamine (GlcNAc), the monomer composing the second most
(
mixture solvent. Various reaction parameters, including reaction temperature and time,
DMSO/water mass ratios and catalyst dosage were optimized. A series of ILs with
different structures were analyzed to explore their impact on GlcNAc conversion. The
substrate scope was expanded from GlcNAc to
D-glucosamine, chitin, chitosan and
monosaccharides, although 5-HMF yields obtained from polymers and other
monosaccharides were generally lower than those from GlcNAc. Moreover, the IL
N-methylimidazolium hydrogen sulfate ([Hmim][HSO ]) exhibited the best catalyst
4
performance (64.6% yield) when GlcNAc was dehydrated in a DMSO/water mixture at
∗
E-mail addresses: zanghongjun@tjpu.edu.cn (H. J. Zang) chemhong@126.com ( H. J.
Zang)
Corresponding author. Tel.: +86 22 2401 9762; fax: +86 22 2452 8055.
1

ACCEPTED MANUSCRIPT
◦
1
80 C for 6 h without the addition of extra catalysts. To summarize, these results could
provide knowledge essential to the production of valuable chemicals that are derived
from renewable marine resources and benefit biofuel-related applications.
Key words: 5-Hydroxymethylfurfural, N-Acetyl-D-glucosamine, Ionic liquid,
Dehydration, Hydrothermal Conversion
1
. Introduction
The decrease in fossil resources has caused serious energy issues. As the most
abundant, green, and renewable resource in the world, biomass can be considered a
suitable alternative to fossil fuels and can be used for the production of fuels and
1
various chemicals. The biomass relates mainly to cellulose, hemicellulose, lignin and
chitin, the catalytic conversion of cellulose and glucose has been comprehensively
2
studied. Treating cellulose and glucose over acid catalysts yields a series of
dehydration products, such as 5-hydroxymethylfurfural (5-HMF) and levulinic acid
3
-5
(
LeA). 5-HMF has been recognized as important versatile platform compound for the
synthesis of a broad range of new products as well as for the replacement of fossil
resources-derived
fuels
and
chemicals,
including
acid,
2,5-diformylfuran,
and importantly,
2
2
,5-furandicarbaldehyde,
2,5-furandicarboxylic
6
,7
,5-dimethylfuran.
Aside from cellulose and glucose, chitin biomass (in the text, this refers to chitin,
chitosan, and their corresponding monomers and derivatives) is also a suitable starting
2

ACCEPTED MANUSCRIPT
material for furan derivatives such as 5-HMF. However, there are few reports on the
8
conversion of chitin biomass into furan derivatives. Recently, Yan and Chen proposed
the concept of shell refinery, whereby crustacean shells are separated into different
fractions, and each fraction is upgraded or transformed into value-added products.
Chitin is the second most plentiful biopolymer on earth, which is generated at a rate of
9
about 100 billion tons every year. Therefore, efficient methods to convert chitin
biomass into valuable compounds are of great importance. Recently, SnCl ·5H O was
4
2
found to effectively catalyze the chitosan conversion into 5-HMF 10.0 wt.% yield in
1
0
water under microwave irradiation. A limitation was that the 5-HMF yield was very
low, whereas no 5-HMF was obtained from chitin. An alternative transformation
strategy was proposed by Hou and co-workers who utilized concentrated ZnCl solution
2
11
as the reaction solvent. After optimization, 5-HMF could be obtained from chitin
biomass (GlcNH2 21.9%, GlcNAc 2.8%, Chitin 9.0%, Chitosan-1K 12.8%,
Chitosan-5K 12.2%, Chitosan-50K 8.0%, Chitosan-100K 8.6%, and Chitosan–COOH
2+
9
.2%) using a concentrated ZnCl aqueous solution, and this result indicating Zn
2
promoted 5-HMF formation occurred by interaction with the amino group on the
substrate. Under hydrothermal conditions, chitosan was converted into 5-HMF in
7
o
diluted H SO , obtaining a 12.1 wt% yield at 174 C in 2.2 wt% H SO solution after
2
4
2
4
1
2
3
7 min. Chen et al. reported that GlcNAc, as chitin monomer, can be converted into
3
-acetamido-5-acetylfuran through pyrolysis at high temperatures and microwave
1
3
irradiation, obtaining 2% and 62% yields, respectively. Wang et al. reported that
3

ACCEPTED MANUSCRIPT
GlcNAc and
D-glucosamine can be degraded to 5-HMF in subcritical water. These
studies showed that chitin biomass has the potential to be a renewable feedstock for
-HMF. However, the catalysts used in these studies were poisonous and the 5-HMF
5
yield was very low. Therefore, efforts should be applied to investigate efficient ways to
transform chitin biomass into 5-HMF.
Very recently, our team screened nine acidic ILs with different cations and anions;
the acidity, hydrogen-bonding capacity and steric hindrance of ILs exhibited combined
influences on the reaction. N-Methyl imidazolium hydrogen sulfate ([Mim]HSO4)
afforded the highest 5-HMF yield of 29.5% from chitosan and 19.3% from chitin at 180
o
14
C after 5 h. The 5-HMF yield was the highest from chitin and chitosan among
literatures reported to date. The IL [Hmim][HSO ], used as both a green solvent and
4
catalyst, exhibited good solubility and catalytic performance for the conversion of
chitosan and chitin. These studies demonstrated the feasibility of converting chitin and
chitin derivatives into 5-HMF. However, the highest 5-HMF yield directly from chitin
was 19.3% is still low. Continued research is hence required in order to develop an
efficient and economically feasible 5-HMF production process from chitin biomass.
Dehydration of hexoses in an aqueous solution leads to excessive solids
1
5,16
15
formation.
It is believed that the solids are in the literature known as ‘humins’. The
solids behave and look like tar, a black oily mass that adheres to surfaces, and avoiding
precipitation and formation of these is crucial for industrialization. Solvents such as
DMSO can reduce humin formation drastically by protecting the hexose from
4

ACCEPTED MANUSCRIPT
degradation. Thus, DMSO, which has been previously added to reaction systems to
suppress undesired side reactions, can be used as both a dehydrating agent and as a
1
7
solvent. Román-Leshkov et al. showed that DMSO both suppressed the formation of
condensation by-products and hampered 5-HMF rehydration by lowering the overall
water concentration. However, the presence of water in this reaction system is also
1
8
essential. Cao et al. reported that an enzyme mimicking an ammonium polymer could
be used as a single catalyst in the dehydration reaction of glucose to 5-HMF. Their study
showed that the presence of water in the system can block the pathway for anhydrosugar
formation and push the reaction toward 5-HMF formation. Moreover, the presence of
water in the system also suppressed the side reaction, resulting in the formation of
2
,5-diformylfuran (DFF) and FA. In a DMSO/water solvent mixture, the dipolar aprotic
solvent dramatically broke hydrogen bonds—results that pointed to a promising binary
1
9
mixture solvent.
Based on the aforementioned results, mixtures of DMSO and water are used as
reaction solvent. We investigated whether similar transformations would be able to
produce 5-HMF from chitin/chitosan monomers. We explored the correlation between
monomer and copolymer degradation during Hydrothermal conversion (HTC) processes
7
as a helpful tool for screening appropriate catalysts for chitin biomass degradation.
GlcNAc was chosen for the study of this conversion process because it is the monomer
composing chitin. Efficient conversion of chitin/chitosan monomers to 5-HMF is a key
step for using chitin/chitosan to produce liquid fuels and value-added chemicals.
5

ACCEPTED MANUSCRIPT
Accordingly, this contribution presents a full account of our study towards the above
central objective.
2
. Materials and Methods
2
.1. Materials
GlcNAc and N-methylimidazole were purchased from Nanjing Xiezun Chemical
Co., LTD (Nanjin, China). 5-HMF (purity > 97%) was purchased from Heowns
Biochem Technologies LLC (Tianjin, China). Methanol (HPLC grade) and ethyl acetate
(AR grade) were purchased from Tianjin Kermel Chemical Reagent Co., Ltd. Vitriolic
acid, phosphoric acid, hydrochloric acid, and nitric acid were purchased from Tianjin
chemical reagent No. 5 plant (Tianjin, China). All other chemicals were supplied by
local suppliers and used without further purification.
2
.2. Synthesis of ILs
Brønsted acidic [Hmim][HSO ], [Hmim][H PO ], [Hmim][NO ], and [Hmim][Cl]
4
2
4
3
were synthesized in our laboratory via a neutralization reaction and developed on the
20-22
basis of a previous report.
Sulfuric acid (50% w/w) was added in a 1:1 molar ratio
with 1-methylimidazole over a period of 30 min with stirring and cooling to maintain
◦
the temperature at 0 C. The reaction mixture was stirred for an additional period of 2 h.
Then, water was removed under reduced pressure to yield the colorless liquid
[
Hmim][HSO ]. The crude product was washed several times with diethyl ether to
4
◦
remove non-ionic residue and then vacuum dried for 24 h under 80 C. [Hmim][H PO ],
2
4
[
Hmim][NO ], and [Hmim][Cl] were synthesized using similar procedures. Additionally,
3
6

ACCEPTED MANUSCRIPT
4
,5-dimethylthiazole hydrosulfate ([TM][HSO ]) and 2-isobutylthiazole hydrosulfate
4
(
[TB][HSO ]) were prepared by neutralization reactions. Then 4,5-dimethylthiazole (or
4
2
-isobutylthiazole) was combined with sulfuric acid (50% w/w) in a 1:1 molar ratio and
SO3H
refluxed for 12 h.
[TB] HSO was synthesized in our laboratory and developed on
4
2
3
the basis of a previous report. These ILs are air-stable, hydrophilic, and their
physicochemical properties have been studied.
2
.3. Classical procedure for the catalytic conversion of GlcNAc into 5-HMF
GlcNAc (100 mg, 0.452 mmol) was added into a mixed solvent composed of
DMSO (8 g) and deionized water (12 g) in a 50 mL stainless steel vessel with a Teflon
lining and sealed by a screw cap. Different amounts of ILs with different structures,
used as catalysts, were loaded into the reactor. Then, the reactor was then immersed into
a preheated oil bath, and the reaction mixture stirred for a given time. Time zero was
recorded when the reactor was immersed into the preheated oil bath. The clear solution
darkened gradually over time. After the scheduled time, the reactor was taken out from
the oil bath and immediately submerged in an ice-water bath to quench the reaction.
Then, the reaction mixture was taken out and filtered with filter paper to remove
insoluble humin polymer. Afterwards, 1 mL of this reaction mixture was diluted with 5
mL of methanol in a volumetric flask. This diluted solution was then taken out, filtered
through a 0.22 µm PTFE filter, and injected into a glass tube. The 5-HMF yield was
determined by high performance liquid chromatography (HPLC) of these aqueous
solutions, using a standard curve (Fig.S1, Supplementary material) in order to quantify
7

ACCEPTED MANUSCRIPT
the amount. 5-HMF yields were calculated as shown below:
5
-HMF yield [%] = Mole amount of 5-HMF/Mole amount of starting GlcNAc × 100
All experiments were performed at least in triplicates; the range of experimental
errors for the HPLC analysis was ±1%.
2
.4. Analysis of the products
Quantitative and qualitative analyses of 5-HMF were performed by HPLC and gas
chromatography and mass spectrometry (GC-MS). The concentration of 5-HMF was
analyzed using HPLC instruments (LC3000, Beijing Chuangxin Tongheng Science and
Technology Co., Ltd.), equipped with a reversed phase C18 column (250 mm × 4.6 mm)
and an ultraviolet detector at 284 nm. The mobile phase consisted of methanol and
water (23:77 v/v) with a flow rate of 0.5 mL/min. Column temperature was maintained
at 30 °C with an injection of 2 µL. Additionally, we used GC-MS to determine the
structure of the product. The GC–MS analysis was performed using the Bruker
SCIONSQ/436-GC system equipped with a 30 m × 0.25 mm × 0.25 µm HP-5 MS
capillary column. Helium was used as the carrier gas at a linear velocity of 1.0 mL/min.
◦
The injector temperature was maintained at 220 C, and the oven temperature was
◦
◦
programmed to start at 50 C (2 min), increasing in intervals of 15 C/min until a
◦
temperature of 230 C was obtained. This temperature was then maintained for 6 min.
Mass spectrometric measurements were performed using electron impact ionization at
7
0 eV and a scan range of m/z 50-500, at a rate of 1 scan/s. GC-MS analysis result is
shown in Fig.1.
8

ACCEPTED MANUSCRIPT
5
-HMF was separated by silica gel column chromatography with eluent of
1
13
petroleum ether and ethyl acetate with proportion of 1:1. H and C NMR spectra of the
1
13
isolated 5-HMF was identified. The H and C NMR spectra of the isolated 5-HMF are
given in Supplementary material.
3
. Results and discussion
3
.1 The characterization of Ionic liquids
1
The H NMR spectra and HPLC-MS spectra images of ionic liquids are given in
Supplementary material.
-methylimidazolium hydrosulfate, [Hmim][HSO ], H NMR (400 MHz, D O,
1
1
4
2
ppm) δ8.55 (s, 1H, CH), δ 7.33 (s, 2H, CH), δ 3.82 (s, 3H, CH ). Anal. Calcd. for
3
C H O N S: C 26.66; H 4.48; N 15.55; S 17.80; Found: C 26.63; H 4.50; N 15.51; S
4
8
4
2
1
7.84.
1
1
-methylimidazolium dihydric phosphate, [Hmim][H PO ], H NMR (400 MHz,
2
4
D O, ppm) δ8.56 (s, 1H, CH), δ 7.36 (s, 2H, CH), δ 3.84 (s, 3H, CH ). Anal. Calcd. for
2
3
C H O N P: C 26.68; H 5.04; N 15.55; Found: C 26.71; H 5.02; N 15.54.
4
9
4
2
1
1
-methylimidazolium nitrate, [Hmim][NO ], H NMR (400 MHz, D O, ppm)
3 2
δ8.60 (s, 1H, CH), δ 7.39 (s, 2H, CH), δ 3.88 (s, 3H, CH ). Anal. Calcd. for C H O N :
3
4
7
3
3
C 33.11; H 4.86; N 28.96; Found: C 33.14; H 4.85; N 28.92.
1
1
-methylimidazolium hydrochloride, [Hmim][Cl], H NMR (400 MHz, D O, ppm)
2
δ8.59 (s, 1H, CH), δ 7.37 (s, 2H, CH), δ 3.85 (s, 3H, CH ). Anal. Calcd. for C H N Cl:
3
4
7
2
C 40.52; H 5.95; N 23.63. Found: C 40.53; H 5.97; N 23.61.
9

ACCEPTED MANUSCRIPT
1
4
,5-dimethylthiazolium hydrosulfate, [TM] HSO , H NMR (400 MHz, D O, ppm)
4
2
δ9.47 (s, 1H, CH), δ2.35 (s, 3H, CH ), δ2.33 (s, 3H, CH ). Anal. Calcd. for C H O NS :
3
3
5
9
4
2
C 28.43; H 4.29; N 6.63; S 30.36; Found: C 28.41; H 4.27; N 6.70; S 30.31. MS (ESI,
+
-
m/z):114.0385 [M - HSO ]
4
1
2
-isobutylthiazolium hydrosulfate,[TB] HSO , H NMR (400 MHz, D O, ppm)
4 2
δ7.92 (d, J = 4 Hz, 1H, CH), δ7.79 (d, J = 4 Hz, 1H, CH), δ3.05 (d, J = 4 Hz, 2H, CH2),
δ3.05 (d, J = 4 Hz, 2H, CH ), δ1.94-2.04 (m, 1H, CH), δ0.823 (d, J = 6.8 Hz, 6H, CH ).
2
3
Anal. Calcd. for C H O NS : C 35.13; H 5.48; N 5.85; S 26.80; Found: C 35.10; H
7
13
4
2
+
-
5
.49; N 5.83; S 26.82. MS (ESI, m/z):142.0708 [M - HSO ]
4
SO3H
4
,5- dimethyl-3-(4-sulfonic acid butyl)thiazolium hydrosulfate ,
[TB] HSO4,
1
H NMR (400 MHz, D O, ppm) δ9.51 (s, 1H, CH), δ4.33 (t, J=7.2Hz,2H,CH ), δ2.83 (t,
2
2
J = 7.6 Hz, 2H, CH ), δ2.34 (s, 3H, CH ), δ2.33 (s, 3H, CH ), δ1.89-1.97 (m, 2H, CH ),
2
3
3
2
δ1.63-1.71 (m, 2H, CH ). Anal. Calcd. for C H O NS : C 31.11; H 4.93; N 4.03; S
2
9
17
7
3
2
7.69; Found: C 31.12, H 4.90, N 4.03, S 27.66.
3
.2 Catalytic conversion of GlcNAc into 5-HMF by various ILs
In the present study, we studied the effects of different ILs, including
imidazolium-type and thizolium-type ILs on GlcNAc conversion. Seven different ILs
were used in combination with various cations and anions, that is, [Hmim][HSO4],
[
Hmim][H PO ], [Hmim][NO ], [Hmim][Cl], [TM][HSO ], [TB][HSO ], and
2 4 3 4 4
SO3H
[
TB][HSO ]. The control experiment was carried out in DMSO/water without a
4
catalyst, where a 10.1% 5-HMF yield was observed (Table 1, entry 1). When sulfuric
1
0

ACCEPTED MANUSCRIPT
acid (equal molar amounts of GlcNAc) was used as a catalyst, a 23.7% yield of 5-HMF
was obtained. As shown in Table 1, ILs showed remarkable effects on the conversion of
GlcNAc into 5-HMF. Different types of ILs have a significant influence on the 5-HMF
yield (Table 1, entries 4-10). [Hmim][HSO ] was found to have the best catalytic
4
performance on the conversion of GlcNAc with 5-HMF (45.2% yield) (Table 1, entry 4).
Compared to the findings for sulfuric acid, it was observed that the [Hmim] cation
promotes the conversion of GlcNAc into 5-HMF.
The anions in the IL were also found to have a profound effect on reactivity. The
incorporation of an HSO counter ion (within the IL) proved to be necessary in order to
4
obtain significant quantities of 5-HMF. Low yields of 5-HMF were obtained when
phosphate, nitrate, or chloride ILs were used as counter ions (Table 1, entries 5-7).
SO3H
When the reaction was catalyzed by using excess sulfuric acid and
[TB][HSO ] as
4
catalysts, there was no formation of 5-HMF (Table 1, entries 3,10). Additionally, results
show that the acidity of the reaction system may also have a remarkable effect on the
yield of 5-HMF. Addition of acid facilitates formation of 5-HMF and increases
selectivity, the ratio between product and by-products is improved due to higher yield of
product; However, 5-HMF rapidly degrades as the acidity of the solution increases, the
yield is decreased due to decomposition of 5-HMF. For this reason, the ionic liquid
[
Hmim][HSO ] was employed for subsequent experiments.
4
3
.3 Catalytic conversion of GlcNAc into 5-HMF under various reaction conditions
Various reaction parameters such as reaction temperature and time, DMSO/water
1
1

ACCEPTED MANUSCRIPT
mass ratio, and catalyst dosage showed a remarkable effect on the dehydration of
GlcNAc to 5-HMF.
3
.3.1 Effect of the different mass ratio of the DMSO/water on the conversion of GlcNAc
into 5-HMF
As shown in Fig. 2, we found that differences in DMSO/water mass ratio had a
significant influence on 5-HMF yields. In the absence of DMSO, 5-HMF yields in water
were found to be 35.8%. However, when 40 wt.% of DMSO was used, 5-HMF yields
increased from 35.8% to 52.4%. When the reaction was carried out only in DMSO,
5
-HMF yields dropped to 8.9%. This suggests that the mixture of DMSO/water plays a
key role in the process of conversion of GlcNAc into 5-HMF. Our results were
consistent with previous results, where it was also found that appropriate water content
2
4
in the system had a remarkable effect on 5-HMF yields. It would be helpful to
elucidate the mechanism underlying the positive effects of water and DMSO on the
transformation of GlcNAc into 5-HMF. On one hand, the presence of water in this
system blocks dehydration of GlcNAc and pushes the reaction toward 5-HMF formation
1
8
in the deamination of GlcNAc. On the other hand, the existence of DMSO in the
reaction system can also inhibit undesired side reactions. Similar studies have indicated
that DMSO favorably shifts the equilibrium of the rate-determining step of 5-HMF
production and inhibits acyclic reaction sequences that may lead to undesirable
1
7
intermediates. Interestingly, it was observed that 5-HMF yields can decrease on
increase in the DMSO content in water (Fig.2). Previous research had revealed that
1
2

ACCEPTED MANUSCRIPT
DMSO exhibits its maximum association with water molecules when its content in
2
5
solution is 66-70%. However, our results showed the best DMSO/water mass ratio
was 8:12 for an effective conversion of GlcNAc into 5-HMF.
3
.3.2 Effect of the reaction temperature on the conversion of GlcNAc into 5-HMF
The effects of reaction temperature on substrate conversion and 5-HMF yields
were evaluated. The conversion reaction of GlcNAc to 5-HMF was more effective at
◦
◦
◦
◦
◦
◦
1
80 C than at 150 C, 160 C, 170 C, 190 C, and 200 C (Fig. 3). 5-HMF yields increased
◦
gradually before 180 C and then slowly decreased. There is evidence suggesting that the
activation energy for the formation of 5-HMF is higher than the activation energy for
1
5
5
-HMF disappearance; therefore, it is expected that 5-HMF concentration would
increase with increase in temperature. On the other hand, temperature increases will
◦
generate more by-products and insoluble humins. The results showed that 180 C was the
most appropriate temperature for the conversion of GlcNAc to 5-HMF. Based on these
◦
results, the reaction temperature was maintained at 180 C in order to further optimize
the reaction conditions.
3
.3.3 Effect of the reaction time on the conversion of GlcNAc into 5-HMF
We studied the relationship between reaction time and 5-HMF yields, which are
presented in Fig.4. Experiments were carried out at 3, 4, 5, 6, 7, and 8 h. As shown in
Fig.4, reaction times showed remarkable effects on the conversion of GlcNAc into
5
-HMF. 5-HMF yields increased gradually before 6 h and then slowly decreased.
Maximum 5-HMF yields (52.4%) were obtained at 6 h; the percentage slightly
1
3

ACCEPTED MANUSCRIPT
decreased to 48% after 8 h. 5-HMF yields decreased from 6 h to 8 h, indicating that
◦
5
6
3
-HMF was not stable at 180 C for prolonged periods of time. In this catalytic system,
h appears to be the most appropriate reaction time to obtain significant 5-HMF yields.
.3.4 Effect of amount of ionic liquid and hydrothermal conditions on the conversion of
GlcNAc into 5-HMF
Under the same reaction temperature and times, the effect of IL dosage on the
conversion of GlcNAc into 5-HMF was investigated. Fig. 5 shows that variations in the
concentration of [Hmim][HSO ] affect the conversion of GlcNAc into 5-HMF. IL
4
dosage also showed a significant effect on 5-HMF yields. 5-HMF yields increased with
increases in [Hmim][HSO ]/GlcNAc molar ratios, varying from 5 to 30. A 32.6% yield
4
◦
was obtained within 6 h at 180 C when the [Hmim][HSO ]/GlcNAc molar ratio was 5.
4
Furthermore, 5-HMF yields increased to 52.2%, 56.7%, and 64.6% when using 10, 15,
and 20 of [Hmim][HSO ]/GlcNAc molar ratios, respectively. This increase in 5-HMF
4
yields with increasing catalyst dosages (at the same reaction time points) can be
attributed to increases in the availability and number of catalytically active sites.
However, 5-HMF yields decreased with increasing amounts of [Hmim][HSO ], ranging
4
from 20 to 30 [Hmim][HSO ]/GlcNAc molar ratios. One possibility is that high catalyst
4
loading not only accelerates the conversion of GlcNAc into 5-HMF but also promotes
other side reactions such as the rehydration of 5-HMF into LA and cross-polymerization
1
5
reactions, which result in lower 5-HMF yields. In the present investigation, LA was
not observed.
1
4

ACCEPTED MANUSCRIPT
In addition, the effect of hydrothermal conditions was studied. Under the same
reaction parameters (reaction time and temperature, catalyst loading, and solvent), the
reaction was refluxed in a preheated oil bath without hydrothermal conditions (Table 2,
entry 1). During refluxing at atmospheric pressure, we put a thermometer into boiling
flask-3-neck and the thermometer was placed below the liquid surface, under these
conditions, a low yield of 3% was obtained. However, when the reaction was carried out
in a 50 mL stainless steel vessel with a Teflon lining and sealed by a screw cap, a 44%
yield was obtained (Table 2, entry 2). This result shows that reaction pressure is also a
critical factor in the conversion of GlcNAc into 5-HMF.
3
.4 [Hmim][HSO ] catalyzed the conversion of other carbohydrates into 5-HMF
4
Other chitin biomass substrates such as glucosamine hydrochloride (GlcNH ·HCl),
2
chitin, and chitosan, in addition to several carbohydrates, were also tested in this ionic
catalytic system to determine 5-HMF conversion yields (Table 3). The direct
preparation of 5-HMF from these less-expensive and easily available biopolymers is
essential for expanding the substrate scope. Under the same conditions, GlcNH ·HCl
2
conversion to 5-HMF produced a 54.9% yield. It stands to reason that monomers
(
GlcNAc and GlcNH ) are easier to convert into 5-HMF than copolymers (chitosan and
2
chitin). This may be due to strong intra- and intermolecular hydrogen bonds between
OH, –NH , and –NHAc groups found within chitin and chitosan, thereby hindering
–
2
chitin and chitosan dissolution and subsequent conversion into 5-HMF. The IL
Hmim][HSO ] is not an effective catalyst for the dissolution of the glycosidic bonds
[
4
1
5

ACCEPTED MANUSCRIPT
found within chitin and chitosan. As a result, 5-HMF yields roughly decreased as the
molecular weight of substrates increased. Table 3 compares the results of 5-HMF
production from chitosan, chitin, GlcNH , and GlcNAc. This study was able to achieve
2
high 5-HMF yields derived from chitin biomass under optimal conditions.
Other carbohydrates (glucose, D-fructose, rhamnose, lactose, D-galactose,
D-mannose) were also tested (Fig. 6). D-fructose produced a 57.7% yield of 5-HMF.
Comparing the results for glucose and fructose showed that the decreases in 5-HMF
yields were presumably due to slower glucose conversion as compared with fructose
2
6
conversion.
3
.5 A possible reaction pathways for GlcNAc dehydration in binary systems
Reaction pathways for the dehydration of GlcNAc into 5-HMF using
[
Hmim][HSO ] IL as catalyst in DMSO/water mixture systems attracted our attention.
4
To obtain a better understanding of GlcNAc dehydration pathways, HPLC-MS spectra
were used to monitor this process. As shown in Fig.S4, Supplementary material. At t = 1
h, a -NHAc group was removed from the cyclic form of GlcNAc, forming an
+
enol-intermediate (M = 162.05). At 3 h, 5-HMF (M = 126.03, 127.04 - H ) was
observed. When the reaction proceeded for 5 h, the HPLC-MS spectrum showed the
complete disappearance of the enol-intermediate (M = 162.05) peak. A very small
amount
of
GlcNAc
was
still
exist,
major
4
-hydroxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde was
the
by-product in reaction. In addition, the compounds with high molecular weight were not
1
6

ACCEPTED MANUSCRIPT
observed in aqueous solution. During this time, the 5-HMF peaks became increasingly
stronger.
2
7
In previous studies, Khokhlova et al. developed an efficient NMR approach with
characterizing molecular transformations of the conversion of carbohydrates to
5
-hydroxymethylfurfural in IL systems. A detailed study of the key sugar units involved
in the biomass conversion process has shown that the simple dissolution of fructose in
the ionic liquid 1-butyl-3-methylimidazolium chloride significantly changes the
anomeric composition and favors the formation of the open fructoketose form. Their
results reveal previously inaccessible mechanistic details of native-state IL systems at
the molecular level. It is likely that the mechanism for this reaction (Fig. 7) has much in
common with previously studied fructose and glucose dehydration processes. As the
first step, dissolution of GlcNAc in this catalyst system leads to a disruption of
hydrogen bonds between sugar molecules, and new hydrogen bonds are formed though
+
-
the coordination of H in HSO and imidazolium cations of IL with –OH groups. Then,
4
+
H and electron-rich aromatic imidazolium cations facilitate the ring-opening reaction to
form the open chain aldose. In the second step, the enol-intermediate is formed by
isomerization. Next, the formation of a five-membered ring and cyclic compounds,
which are key intermediates in the conversion process, are obtained. The third step is
the removal of a -NHAc group from the cyclic compounds, forming the
enol-intermediate (M = 162.05) once again. Finally, 5-HMF is formed through the
acidic hydrolysis from 4-hydroxy-5-hydroxymethyl-4,5-dihydrofuran-2-carbaldehyde.
1
7

ACCEPTED MANUSCRIPT
The usual byproducts observed in this biomass conversion, i.e. LeA and FA, were not
detected by HPLC-MS. The HPLC-MS provided evidence to sustain the proposed
mechanism.
3
.6 Recycling experiments
Catalyst recycling is an important goal in terms of green and sustainable chemistry.
Thus, the reusability of the catalyst [Hmim][HSO ] was studied (Fig. 8). The conversion
4
of GlcNAc into 5-HMF was used as the model reaction; experiments were carried out at
◦
1
80 C for 6 h in a DMSO/water mixture and using [Hmim][HSO ] as the catalyst. After
4
the reaction, most of the 5-HMF in the aqueous solution was removed by ethyl acetate
extraction until no 5-HMF was detected in the ethyl acetate. The water found in the
aqueous phase was completely removed through vacuum evaporation. The remaining
[
Hmim][HSO ] and DMSO were used directly in the next run by adding a fresh
4
GlcNAc sample and water under the same reaction conditions. This processes was
repeated 5 times, obtaining 5-HMF yields of 63.6%, 58.8%, 57.4%, 54.5%, and 51.8%,
respectively. The loss of catalytic activity was possibly due to mass loss during the
recycling procedure. Therefore, it can be concluded that the catalyst was stable in this
system, and has potential applications for large-scale industrial synthesis.
4
. Conclusion
For the first time, direct conversion (producing high yields) of GlcNAc into
-HMF was achieved via hydrothermal synthesis in an acidic IL aqueous solution. The
5
conversion method depends on a DMSO/water mixture catalyzed by [Hmim][HSO4].
1
8

ACCEPTED MANUSCRIPT
GC-MS and HPLC analyses showed 5-HMF as the main product, with undetectable
levels of byproducts such as LeA (except humins), highlighting high yields and
selective reaction. This is a proof-of-principle study that GlcNAc can be hydrolyzed to
obtain useful chemical building blocks. The catalytic system was effectively recycled
five times. This system has great potential for large-scale 5-HMF production. The
method described herein should be valuable to facilitate cost-effective conversion of
renewable marine resources into biofuels and bio-based products.
Acknowledgements
The authors would like to acknowledge the financial support from National Natural
Science Foundation of China (No.21406166) and the Municipal Natural Science
Foundation of Tianjin (No. 15JCQNJC13900).
References
1
. Osatiashtiani, A.; Lee, A. F.; Brown, D.R.; Melero, J. A.; Morales, G.; Wilson, K.
Catal. Sci. Technol., 2014, 4, 333-342.
2
1
3
4
5
. Bobbink, F. D.; Zhang, J.; Pierson, Y.; Chen, X.; Yan, N. Green Chem., 2015, 17,
024-1031.
. Song, J.; Fan, H.; Ma, J.; Han, B. Green Chem., 2013, 15, 2619-2635.
. Deng, W.; Zhang, Q.; Wang, Y. Catal. Today., 2014, 234, 31-41.
. Wu, L.; Song, J.; Zhang, B.; Zhou, B.; Zhou, H.; Fan, H.; Yang, Y.; Han, B. Green
Chem., 2014, 16, 3935-3941.
. Dashtban, M.; Gilbert, A.; Fatehi, P. RSC Adv., 2014, 4, 2037-2050.
6
1
9

ACCEPTED MANUSCRIPT
7
8
9
1
. Lee, S. B.; Jeong, G. T. Appl. Biochem. Biotechnol., 2015, 176, 1151-1161.
. Yan, N.; Chen, X. Nature., 2015, 524, 155-157.
. Chen, X.; Yang, H.; Yan, N. Chem. Eur. J., 2016, 22, 1-21.
0. Omari, K. W.; Besaw, J. E.; Kerton, F. M. Green Chem., 2012, 14, 1480-1487.
11. Wang, Y.; Pedersen, C. M.; Deng, T.; Qiao, Y.; Hou, X. Bioresour Technol., 2013,
1
1
1
1
2
1
1
1
1
2
1
2
2
2
2
1
43, 384-390.
2. Chen, X.; Liu, Y.; Kerton, F. M.; Yan, N. RSC Adv., 2015, 5, 20073-20080.
3. Wang, R.; Kobayashi, T.; Adachi, S. Food Sci. Technol. Res., 2011, 17, 273–278.
4. Li, M.; Zang, H.; Feng, J.; Yan, Q.; Yu, N.; Shi, X.; Cheng, B. Polym. Degrad. Stab.,
015, 121, 331-339.
5. Kuster, B. F. M. Starch-Stärke., 1990, 42, 314-321.
6. Kuster, B. F. M. Dehydration of D-Fructose, Eindhoven. 1975.
7. Román-Leshkov, Y.; Chheda, J. N.; Dumesic, J. A. Science., 2006, 312, 1933-1937.
8. Cao, X.; Teong, S. P.; Wu, D.; Yi, G.; Su, H.; Zhang, Y. Green Chem., 2015, 17,
348-2352.
9. Kimura, H.; Hirayama, M.; Yoshida, K.; Uosaki, Y.; Nakahara, M. J Phys Chem A.,
014, 118, 1309-1319.
0. Liu, S. W.; Yu, S. T.; Liu, F. S.; Xie, C. X.; Li, L.; Ji, K. H. J. Mol. Catal. A: Chem.,
008, 279, 177-181.
1. Mirjafari, A.; Mobarrez, N.; O’Brien, R. A.; Jr, J. H. D; Noei, J. C. R. Chimie., 2011,
4, 1065-1070.
2
0

ACCEPTED MANUSCRIPT
2
2
2. Ohno, H.; Yoshizawa, M. Solid State Ionics., 2002, 154, 303-309.
3. Yan, Q.; Zang, H.; Wu, C.; Feng, J.; Li, M.; Zhang, M.; Wang, L.; Cheng, B. J. Mol.
Liq., 2015, 204, 156-161.
2
1
2
2
2
2
4. Kimura, H., Yoshida, K., Uosaki, Y., Nakahara, M. J Phys Chem A., 2013, 117,
0987-10996.
5. Musau, R. M.; Munavu, R. M. Biomass., 1987, 13, 67-74.
6. Qi, L.; Mui, Y. F.; Lo, S. W.; Lui, M. Y.; Akien, G. R.; Horváth, I. T. ACS Catalysis.,
014, 4, 1470-1477.
7. Khokhlova, E. A.; Kachala, V. V. ChemSusChem., 2012, 5,783-789.
2
1

ACCEPTED MANUSCRIPT
Table 1
Effect of sulfuric acid and different ionic liquids on the conversion of the GlcNAc into
a
5
-HMF under hydrothermal conditions
Entry
catalyst
structure
5-HMF yield [%]
10.1±0.9
23.7±1.3
1
2
No catalyst
H SO (44.31mg)
2
4
O
HO S OH
O
3
4
H SO (443.02mg)
O
HO S OH
O
trace
2
4
[Hmim][HSO4]
45.2±2.9
H
N
HSO4
N
5
6
7
8
9
[Hmim][H PO ]
19.6±2.2
15.1±3.3
5.5±1.3
2
4
H
N
H PO
2
4
N
[Hmim][NO3]
H
N
NO3
N
[Hmim][Cl]
[TM][HSO4]
[TB][HSO4]
H
N
Cl
N
19.2±2.2
28.7±1.2
H
N
HSO4
S
H
N
HSO4
S
2
2

ACCEPTED MANUSCRIPT
SO3H
1
0
[TB] HSO4
SO H
trace
3
N
HSO4
S
a
The reaction conditions: GlcNAc (100 mg), the ILs with GlcNAc in a 10:1 molar ratio,
distilled water, 12g; DMSO, 8g; reaction temperature, 180 °C; reaction time, 5 h.
2
3

ACCEPTED MANUSCRIPT
Table 2
a
The effect of reaction pressure on the conversion of GlcNAc into 5-HMF
◦
Entry Solvent
Temperature( C) Time(h)
RCatalyst
10
5-HMF yield [%]
3.0±1.3
b
1
2
Water 16g DMSO 4g
Water 16g DMSO 4g
180
180
6
6
10
44.0±4.4
a
Reaction conditions: GlcNAc, 100 mg; [Hmim][HSO ], 813mg ; reaction temperature,
4
1
80 °C, reaction time, 6 h. Rcatalyst= the molar ratio of [Hmim][HSO ] / GlcNAc
4
b
◦
It was immersed in a preheated oil bath heated at 180 C and carried out atmospheric
pressure reflux for 6h.
2
4

ACCEPTED MANUSCRIPT
Table 3
Comparison of 5-HMF production from other chitin biomass substrates such as chitin,
chitosan D-fructose and GlcNAc
Y5
-HMF
Materials
Reaction conditions
a
Reference
This work
1
0
microwave irradiation , 100 mg
Chitin
ND
25.7mol%
34.7 mol%
chitosan in 15 mL water, 0.12 mmol
1
0
Chitosan
10.0 wt%
21.9 mol%
2.8 mol%
◦
SnCl ·5H O ,200 C, 30 min
4
2
1
1
GlcNH ·HCl
54.9 mol%
64.6 mol%
2
1
g substrate in 30 g 67 wt.% ZnCl2
◦
solution, 120 C, 90 min
1
1
GlcNAc
ND not detected
a
Reaction conditions: carbohydrate (100 mg),the [Hmim][HSO ] with carbohydrate in a
4
°
2
0:1 molar ratio, distilled water, 12g; DMSO, 8g; reaction temperature, 180 C; reaction
time, 6 h.
2
5

ACCEPTED MANUSCRIPT
Fig.1. Experiment GC-MS of the 5-HMF
2
6

ACCEPTED MANUSCRIPT
60
50
40
30
20
10
0
0.0
0.2
0.4
0.6
0.8
1.0
The percentage of DMSO in solvent
Fig.2. Effect of the different mass ratio of the DMSO/water on the conversion of
GlcNAc into 5-HMF under hydrothermal conditions. Reaction conditions: GlcNAc, 100
mg; [Hmim][HSO ], 4.516mmol ; reaction temperature, 180 °C.
4
2
7

ACCEPTED MANUSCRIPT
70
60
50
40
30
20
10
0
1
50
160
170
180
190
200
Temperature/ ℃
Fig.3. Effect of reaction temperature on 5-HMF production under hydrothermal
conditions. Reaction conditions: GlcNAc, 100 mg; distilled water, 12g; DMSO, 8g;
[
Hmim][HSO ], 9.040mmol; reaction time, 6 h.
4
2
8