Eco-friendly synthesis of 5-hydroxymethylfurfural (HMF) and its application to the Ferrier-rearrangement reaction

Article abstract of DOI:10.1080/07328303.2018.1428990

5-Hydroxymethylfurfural was conveniently synthesized by dehydration of D-fructose in a good yield. To further build bioactive derivatives from 5-hydroxymethylfurfural, 2,3-unsaturated glycosides were directly obtained through the Ferrier-rearrange-ment reaction of various glycals. Noticeably, a solid acid catalyst was successfully applied in the preparation of 5-hydroxyme-thylfurfural and then recycled to promote the Ferrier-rearrang-ement reaction, making it possible to achieve two steps of reaction in an eco-friendly manner through the simple process.

Full text of DOI:10.1080/07328303.2018.1428990

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Eco-friendly synthesis of 5-hydroxymethylfurfural
(HMF) and its application to the Ferrier-
rearrangement reaction
Zekun Ding, Xiaosheng Luo, Yibin Ma, Heshan Chen, Saifeng Qiu, Guosheng
Sun, Wan Zhang, Chao Yu, Zhenliang Wu & Jianbo Zhang
To cite this article: Zekun Ding, Xiaosheng Luo, Yibin Ma, Heshan Chen, Saifeng Qiu, Guosheng
Sun, Wan Zhang, Chao Yu, Zhenliang Wu & Jianbo Zhang (2018): Eco-friendly synthesis of 5-
hydroxymethylfurfural (HMF) and its application to the Ferrier-rearrangement reaction, Journal of
Carbohydrate Chemistry, DOI: 10.1080/07328303.2018.1428990
To link to this article: https://doi.org/10.1080/07328303.2018.1428990
Published online: 08 Feb 2018.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lcar20

JOURNAL OF CARBOHYDRATE CHEMISTRY
, VOL. , NO. , –

https://doi.org/./..
Eco-friendly synthesis of -hydroxymethylfurfural (HMF)
and its application to the Ferrier-rearrangement reaction
Zekun Ding, Xiaosheng Luo, Yibin Ma, Heshan Chen, Saifeng Qiu, Guosheng Sun,
Wan Zhang, Chao Yu, Zhenliang Wu, and Jianbo Zhang
School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China
ABSTRACT
ARTICLE HISTORY
5
-Hydroxymethylfurfural was conveniently synthesized by
Received  November 
Accepted  January 
dehydration of D-fructose in a good yield. To further build bioac-
tive derivatives from 5-hydroxymethylfurfural, 2,3-unsaturated
glycosides were directly obtained through the Ferrier-rearrange-
ment reaction of various glycals. Noticeably, a solid acid catalyst
was successfully applied in the preparation of 5-hydroxyme-
thylfurfural and then recycled to promote the Ferrier-rearrang-
ement reaction, making it possible to achieve two steps of
reaction in an eco-friendly manner through the simple process.
KEYWORDS
Ferrier-rearrangement
reaction; glycal; recyclable;
solid acid catalyst;
,-unsaturated glycoside;
-hydroxymethylfurfural
GRAPHICAL ABSTRACT
Introduction
5
-Hydroxymethylfurfural (HMF) as a significant platform compound and valuable
molecule can be obtained from carbohydrates such as fructose, sucrose, cellulose
or from biomass materials.
[
1–14]
For example, HMF shows its value not only as a
material for the production of dimethylfuran (DMF) and other important molecules
such as levulinic acid, 2,5-furandicarboxylic acid (FDA), and 2,5-diformylfuran
[
3–5,13–15]
(DFF),
but also as an abundant constituent widely distributed in tradi-
tional Chinese medicine such as processed steamed Rehmanniae Radix, a Chinese
medicine used to treat several diseases, including anemia and diabetes. In recent
studies, HMF also showed good antibacterial properties.[
16]
CONTACT Jianbo Zhang
China Normal University, Shanghai , China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lcar.
 Taylor & Francis Group, LLC
jbzhang@chem.ecnu.edu.cn
School of Chemistry and Molecular Engineering, East
©

2
Z. DING ET AL.
Scheme . Preparation of ,-unsaturated glycosides with recyclable catalyst.
Additionally, 2,3-unsaturated sugars that can be obtained through Ferrier reac-
tion are significant intermediates in the synthesis of natural products and bioactive
[
17–22]
molecules.
Based on the admirable reactivity of HMF, which can be expected
to react in the presence of glycals to obtain a series of pharmaceutical products, we
attempt to achieve HMF and its glycosylation reaction with the same recyclable cat-
alyst (Sch. 1), inspired by our previous work in the area.[
20,23–27]
Results and discussion
Although HMF is commercially available and various preparation methods have
been developed in the past few decades, we were dedicated to develop a greener
and more efficient synthetic method toward HMF. There is still room for further
improvement of previously reported solid acid catalyst applied in synthesizing HMF,
e.g., to avoid toxicity, high price, and complicated preparation. In order to find out
an efficient and available catalyst and circumvent the aforementioned problems,
we test various low or non-toxic acid catalysts, including inorganic Brønsted acid
[
2,10–11,14,28]
such as HCl, H BO , NaH PO , H MoO , and so on,
organic Brønsted
3
3
2
4
2
4
acid such as propyl sulfonic acid, propionic acid, acrylic acid, benzoic acid, ala-
[
29–31]
nine, etc.,
and Lewis acid such as ZnCl , FeCl , FeCl ·6H O, and CrCl .
2
3
3
2
3
Their efficiencies to catalyze the transformation of D-fructose to HMF are shown in
[
32,33]
Figure 1.
Thereafter, different catalytic systems and immobilization ratios of solid acid
catalysts were tested, based on previous exploration.[20,25–27] Along with solid
super acids, a strongly acidic cation exchange resin, p-TsOHꢀH O, FeCl , and
2
3
FeCl ꢀ6H O, which also showed high catalytic activities, was selected for further
3
2
immobilization experiments as well. As shown in Table 1, H SO and p-TsOHꢀH O
2
4
2
loaded onto SiO failed to provide satisfactory catalytic performance (entry 1–4),
2
and solid super acid (entry 5) was hardly applied to this reaction. Although acti-
vation with strong-acid cation exchange resin (entry 6) afforded HMF in a 72%
yield, the adsorption on the surface of resin by polymeric by-products was observed,
which led to the catalyst poisoning and seriously impeded the catalyst recycling. The
3+
results also indicated that FeCl ꢀ6H O was superior to FeCl as a Fe source (entry
3
2
3
7
–14). Obviously, FeCl ꢀ6H O/C (2 g:3 g) (entry 12) had the highest efficiency to
3 2
catalyze the dehydration reaction of D-fructose in dimethyl sulfoxide (DMSO).
To improve the result of the catalysts further, different solvents were exam-
ined, with optimal condition observed employing 0.1 equivalent of FeCl ꢀ6H O/C
3
2

JOURNAL OF CARBOHYDRATE CHEMISTRY
3
Figure . The efficiencies of various acid catalysts applied to D-fructose dehydration.
(2 g:3 g) at 90°C. Clearly, the results (Table 2) indicated that DMSO (entry 1) was the
best solvent, whereas polyethylene glycol 400 (PEG 400) (entry 1) was comparable.
Besides, experiments were also carried out to explore the recyclability of solid
acid catalyst (Sch. 2). It was clearly demonstrated in Table 3 that the yields remained
steady (77%) in the first three recycles but declined slowly thereafter. Delightfully,
this catalyst still gave an acceptable yield (62%) in the fifth recycle, suggesting that it
Table . Efficiencies of different solid acids to catalyze D-fructose dehydration in DMSO.
Entry
Catalyst
Yield (%)

HSO/SiO ( mL: g)
HSO/SiO ( mL: g)
TsOH/SiO ( g: g)













TsOH/SiO ( g: g)

−
SO /ZrO (:)
Cation exchange resin FPCNa
FeCl/C ( g: g)


FeCl/C ( g: g)
FeCl/C( g: g)
FeClꢀHO/C (. g: g)
FeClꢀHO/C ( g: g)
FeClꢀHO/C ( g: g)
FeClꢀHO/C ( g: g)
FeClꢀHO/C ( g: g)


















4
Z. DING ET AL.
Table . The catalytic performance of FeClꢀHO/C in different solvents.
Entry
Solvent
Yield (%)

DMSO
PEG 
,-dioxane
Cyclohexanol
-Butanol
n-Butanol
Acetonitrile













Scheme . Use of recyclable catalyst in the preparation of HMF.
can meet the requirements of green chemistry and be further developed for indus-
trial mass production.
Considering that most metal Lewis acid catalysts used in the Ferrier-
rearrangement reaction usually present similar problems such as high price and
toxicity, not being environmentally friendly, etc.,[
34–42]
our group has explored
previously FeCl and FeCl ꢀ6H O as glycosylation promoters, especially in
3
3
2
[
20,24,43,44]
Ferrier-rearrangement reactions, to attain satisfactory results.
Further,
immobilization of homogeneous catalysts can also solve operational and moisture-
[
20,26,27]
absorption problems.
Inspired by these studies and the reactivity of the OH
group in HMF, the same catalyst used to generate HMF under optimal conditions
was explored for Ferrier-type glycosylation to directly build 2,3-unsaturated gly-
[
45–48]
cosides (Table 4).
did not give satisfactory results and were also difficult to achieve one-pot method
entries 1 and 2). Persistently, we focused on using the same recyclable catalyst in
Initially, DMSO and PEG 400 were used as solvents, which
(
other solvents to simplify operational process. Thus, different common solvents,
such as CH CN, dichloromethane (DCM) and dichloroethane (DCE) applied into
3
[
23,26,27]
the Ferrier reaction were explored (entries 3–5),
and it was found that using
Table . Efficiencies of recycled catalyst in preparation of HMF.
Run





a
Yields (%)





aReaction time was  h.

JOURNAL OF CARBOHYDRATE CHEMISTRY
5
Table . Optimization of Ferrier-type glycosylation of acceptor 2 with donor 1a.
Entry
Solvent
DMSO
PEG 
CHCN
DCM
DCE
DCE
DCE
DCE
DCE
Eq. (D:A)
Eq. (cat.)
T (°C)
Time (h)
Yield (%)

:
:
:
:
:
:
:
:.
:.
:.
:.
:.
:.
:.








rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt




Trace
nd

















.
.
.
.
.
.
.
.
.



.
.
.
.
.
.










DCE
DCE
DCE
DCE
DCE
.

DCE as solvent led to a higher yield in a short reaction time at room temperature
entry 5). Then, a screen of various equivalent ratios of donor 1a and acceptor 2
(
revealed that an acceptor/donor equivalent ratio of 1.2/1 was optimal (entry 8)
and that a decrease of equivalent ratio was detrimental for the yield of 3a (entry
7
). We postulated that excess acceptor (entry 6) might bring about complexation
[
44]
with catalyst, thus reducing the yield of product.
Modifying the equivalent
of catalyst ranging from 1 to 0.05 equivalent was shown to retain the same yield
85%, entries 8–12), until it was decreased to 0.02 equivalent, which afforded an
unsatisfactory result (30%, entry 13). In view of the fact that the previous step
Fig. 1) also employed 0.1 equivalent of catalyst and the catalyst was recyclable, we
chose 0.1 equivalent of FeCl ꢀ6H O/C as the optimal amount of catalyst for this
(
(
3
2
reaction (entry 12). Besides, an elevation of the impact of temperature revealed that
increased temperature, 40°C vs room temperature, had a hindering effect (entry 14).
Having established the optimal reaction conditions, we decided to expand the gly-
cosylation method for different glycals (Table 5).[ We were eager to see whether
the high yield observed for product 3a could be translated to other types of 2,3-
unsaturated glycosides to provide more derivatives from HMF and further expand
its pharmaceutical value. Thus, a diverse range of glycals including glucal, galactal,
rhamnal, xylal, maltal, and arabinal with different protecting groups such as acetyl,
benzyl, and benzoyl groups were explored to afford the desired glycosylated prod-
ucts in good to excellent yields (67–92%) and the anomeric ratio (α:β) ranged from
49]
5:1 to only α. The glycosylations were also fairly quick (7 min to 4 h), especially the
reaction time of compound 1a could be shortened from 24 h to 10 min, compared
[
45,47]
with the reported data (Table 5, entry 1).
These results demonstrated that the
catalyst and the optimal reaction condition are broadly applicable to different gly-
cal donors and have thus built the foundation for the synthesis of natural bioactive
molecules and their analogs through the Ferrier-rearrangement reaction.

6
Z. DING ET AL.
Table . The scope of FeClꢀHO/C-catalyzed Ferrier-type glycosylation using different glycals.
a
Entry
Donors
Time (h)
Yield (%), α:β

.
%, :



%, :
%, :
.


.
%, :
%, :
.


%, :

.

%, >.

%, :
a

The anomeric ratio was determined by H NMR spectra.
Besides, a recent study showed that the derivatives of HMF possess different
kinds of biological activity and some of them are even more active than HMF.[50,51]
Based on this consideration, we preliminarily studied the antitumor activity (in vitro
[
20,52]
against the K562 cell line)
of the 2,3-unsaturated glycosdies derived from HMF
and evaluated their structure–activity relationship. We found that isomerization at
the C-4 position, glucal 3a vs galactal 3b (the former was more potent), glycosyl
substitution at C-4, 3a vs 3f (substitution had an inhibitory effect), and difference

JOURNAL OF CARBOHYDRATE CHEMISTRY
7
a
Table . In vitro antitumor activities of glycosidic HMF derivatives against the K cell line.
Entry
Compound
Concentration (µg/mL)
Inhibition rate (%)

Cisplatin
3a

.
.
− .
− .
.
.













3b
3c
3d
3f
3g
.
.

3h
aDMSO was used as solvent.
in protecting groups, 3a vs 3d (OBn was better than OAc) and 3c vs 3h (OBz was
better than OAc) could all influence the antitumor activity. Form these results, we
concluded that compounds 3g and 3h derived from acetyl-arabinal and benzoyl-
rhamnal, respectively, showed promising antitumor activities (Table 6, entries 7 and
8
). Further orthogonal research on the antitumor activities of different types of gly-
cals and protecting groups is undergoing.
Conclusion
In summary, we have developed a novel method to achieve HMF from D-fructose
and its Ferrier-type glycosylation by using the same recyclable catalyst through
a simple operational process. This method boasts several remarkable features,
most significantly employing a recyclable, low-toxic and easily accessible solid acid
catalyst FeCl ꢀ6H O/C for both steps, which can greatly simplify experimental
3
2
procedure and meet the concept of green chemistry. Besides, this Ferrier-type
glycosylation offers a new method for rapid and efficient synthesis of various
2
, 3-unsaturated glycosides in good to excellent yields, which possess potential
bioactivity and pharmaceutical values.
Experimental
1
13
General methods: H and C NMR spectra were recorded using a 500 MHz spec-
trometer with tetramethylsilane (TMS) as internal standard. Mass spectra were
detected using an Agilent 5973N EI mass spectrometer. All the reactions were
monitored using thin layer chromatography (TLC) on silica gel HF254 [10–40 µm,
Yantai, China (0.2 mm)]. Reaction products were purified by flash chromatography
using silica gel 60 (300–400 mesh or 200–300 mesh, Yantai, China).
Procedure for the preparation of 5-hydroxymethylfurfural (HMF: D-Fructose
(
0.18 g, 1 mmoL) and FeCl ꢀ6H O/C (67.5 mg, 0.1 mmoL) were dissolved in 2 mL
3 2
of DMSO and stirred for 5 h with an oil bath heated at 90°C. Then, the mixture
was filter out through to remove the catalyst, which can be employed in the next
step. The solution was extracted with ethyl acetate (6 × 30 mL), and the solvent was
evaporated. The product could be employed in the next reaction directly for one-pot
synthesis. Also, the residue was purified by column chromatography (4:1 petroleum

8
Z. DING ET AL.
1
ether/ EtOAc) to obtain HMF as brownish yellow syrupy (97 mg, 77%). H NMR
(
500 MHz, CDCl ): δ 9.55 (s, 1 H), 7.20 (d, J = 3.5 Hz, 1 H), 6.50 (d, J = 3.5 Hz, 1
3
+
H), 4.69 (s, 2 H), and 3.08 (s, 1 H). High resolution mass spectrum (HRMS) (ESI ):
m/z calcd. for C H O Na [M+Na] 149.0209, found 149.0205.
+
6
6
3
General procedure for the preparation of unsaturated sugar glycosides 3a–h: To
a mixture of 3,4,6-tri-O-acetyl-D-glucal (1 mmoL) and HMF (1.2 mmol) in DCE
(
10 mL) was added the catalyst, which was followed by stirring at rt. The reac-
tion was monitored by TLC (PE/EA 1.0/1.0 v/v). After the reaction is finished, it
was filtered on a Celite pad. The solution was concentration and the raw prod-
uct was purified on a silica gel column (CH Cl ) to give a mixture of α and β
2
2
anomers.
1
3
a: H NMR (500 MHz, CDCl ): δ 9.62 (s, 1 H), 7.21 (d, J = 3.5 Hz, 1 H), 6.55
3
(
5
(
d, J = 3.5 Hz, 1 H), 6.03 (dd, J = 11.7, 3.8 Hz, 1 H), 5.92 (d, J = 10.2 Hz, 1 H),
.87–5.79 (m, 1 H), 5.34 (dd, J = 9.7, 1.4 Hz, 1 H), 5.24 (s, 1 H), 5.15 (s, 1 H), 4.84
d, J = 13.3 Hz, 1 H), 4.78 (d, J = 13.3 Hz, 1 H), 4.66 (t, J = 12.6 Hz, 1 H), 4.25 (dd,
J = 12.2, 5.1 Hz, 1 H), 4.17 (dd, J = 12.2, 2.4 Hz, 1 H), 4.14–4.07 (m, 1H), 2.10 (s,
+
3
H), 2.08 (s, 4 H). Low resolution mass spectrum (LRMS) (ESI ): m/z calcd. for
+
C H O Na [M+Na] 361.09, found 361.08.
1
6
18
1
8
3
b: H NMR (500 MHz, CDCl ): δ 9.62 (d, J = 1.3 Hz, 1 H), 7.21 (d, J = 3.5 Hz, 1
3
H), 6.55 (d, J = 3.5 Hz, 1 H), 6.16 (dd, J = 10.0, 5.5 Hz, 1 H), 6.03 (dd, J = 10.0, 3.0 Hz,
1
1
H), 5.18 (d, J = 2.9 Hz, 1 H), 5.04 (dd, J = 5.4, 2.1 Hz, 1 H), 4.78 (d, J = 13.3 Hz,
H), 4.66 (d, J = 13.3 Hz, 1 H), 4.40–4.33 (m, 1 H), 4.26 – 4.21 (m, 2 H), 2.08 (d,
13
J = 1.4 Hz, 6 H). C NMR (125 MHz, CDCl ): δ 177.73, 170.60, 170.30, 157.42,
3
1
2
0
52.87, 129.82, 125.88, 121.71, 111.69, 93.38, 67.11, 62.63, 62.54, 61.54, 20.80,
+
+
0.79. HRMS (ESI ): m/z calcd. for C H O Na [M+Na] 361.0899, found 361.
16
18
8
894.
3
1
c: H NMR (500 MHz, CDCl ): δ 9.62 (d, J = 4.0 Hz, 1 H), 7.20 (t, J = 3.4 Hz,
3
1
1
1
1
(
9
H), 6.54 (d, J = 3.5 Hz, 1 H), 5.88 (d, J = 10.3 Hz, 1 H), 5.80 (dt, J = 10.3, 2.2 Hz,
H), 5.24 (d, J = 1.6 Hz, 1 H), 5.06 (dd, J = 12.2, 1.8 Hz, 2 H), 4.82 (d, J = 13.3 Hz,
H), 4.76 (d, J = 13.4 Hz, 1 H), 4.66 (t, J = 12.0 Hz, 1 H), 3.95 (tt, J = 17.9, 6.2 Hz,
13
H), 2.08 (s, 3 H), 1.33 (d, J = 6.6 Hz, 1 H), 1.20 (d, J = 6.3 Hz, 3 H). C NMR
125 MHz, CDCl ): δ 177.76, 170.53, 158.07, 152.84, 130.46, 126.99, 121.91, 111.45,
3
+
4.22, 70.70, 65.23, 62.03, 21.05, 17.91. HRMS (ESI ): m/z calcd. for C H O Na
14
16
6
+
[
M+Na] 303.0845, found 303.0836.
1
3
d: H NMR (500 MHz, CDCl ): δ 9.62–9.57 (m, 1 H), 7.35–7.27 (m, 10 H), 7.25
3
(
1
d, J = 6.7 Hz, 2 H), 7.16 (d, J = 3.5 Hz, 1 H), 6.50 (d, J = 3.3 Hz, 1 H), 6.10 (t, J =
0.3 Hz, 1 H), 5.86 (dd, J = 10.3, 1.4 Hz, 1 H), 5.80–5.74 (m, 1 H), 5.24 (s, 1 H), 5.14
(
s, 1 H), 4.83 (d, J = 13.4 Hz, 1 H), 4.79 (d, J = 13.4 Hz, 1 H), 4.69 (s, 1 H), 4.66 (d,
J = 3.1 Hz, 1 H), 4.62 (d, J = 7.7 Hz, 1 H), 4.60–4.55 (m, 1 H), 4.52 (d, J = 12.1 Hz, 1
H), 4.45 (d, J = 11.5 Hz, 1 H), 4.19 (d, J = 9.4 Hz, 1 H), 4.00–3.93 (m, 1 H), 3.74 (dd,
13
J = 10.7, 4.1 Hz, 1 H), 3.70–3.66 (m, 1 H). C NMR (125 MHz, CDCl ): δ 177.90,
3
1
58.26, 152.81, 138.21, 138.05, 131.56, 128.53, 128.50, 127.98, 127.94, 127.81,

JOURNAL OF CARBOHYDRATE CHEMISTRY
9
1
27.11, 125.89, 121.84, 111.56, 94.48, 73.56, 71.30, 70.32, 69.69, 68.84, 62.04. HRMS
+
+
(ESI ): m/z calcd. for C H O Na [M+Na] 457.1627, found 457.1624.
2
6
26
6
1
3
e: H NMR (500 MHz, CDCl ): δ 9.63 (s, 1 H), 7.21 (d, J = 3.2 Hz, 1 H), 6.54 (d,
3
J = 3.1 Hz, 1 H), 6.12 (dd, J = 9.7, 5.2 Hz, 1 H), 6.04 (dd, J = 10.0, 2.6 Hz, 1 H), 5.12
(
s, 1 H), 4.96 (s, 1 H), 4.77 (d, J = 13.3 Hz, 1 H), 4.65 (d, J = 13.3 Hz, 1 H), 4.16 (dd,
13
J = 12.9, 2.0 Hz, 1 H), 3.86 (d, J = 13.0 Hz, 1 H), 2.10 (s, 3 H). C NMR (125 MHz,
CDCl ): δ 177.91, 170.82, 157.74, 152.98, 130.22, 125.77, 111.83, 92.78, 63.18, 61.85,
3
+
+
6
1.63, 21.22. HRMS (ESI ): m/z calcd. for C H O Na [M+Na] 289.0688, found
13
14
6
289.0681.
1
3
f: H NMR (500 MHz, CDCl ): δ 9.64 (s, 1 H), 7.22 (d, J = 3.4 Hz, 1 H), 6.57
3
(
d, J = 3.3 Hz, 1 H), 5.89 (d, J = 10.4 Hz, 1 H), 5.83 (d, J = 10.3 Hz, 1 H), 5.41
t, J = 10.0 Hz, 1 H), 5.31 (d, J = 3.7 Hz, 1 H), 5.10 (d, J = 11.7 Hz, 1 H), 5.06 (d,
(
J = 9.6 Hz, 1 H), 4.83 (dd, J = 10.1, 3.5 Hz, 1 H), 4.78 (d, J = 13.3 Hz, 1 H), 4.65
(
d, J = 13.2 Hz, 1 H), 4.34 (dd, J = 6.6, 3.5 Hz, 2 H), 4.28 (d, J = 3.2 Hz, 1 H), 4.25
(d, J = 4.2 Hz, 1 H), 4.08 (s, 1 H), 4.06 (s, 2 H), 2.13 (s, 3 H), 2.10 (s, 4 H), 2.06 (s,
13
4
1
9
2
6
H), 2.03 (s, 4 H), 2.01 (s, 3 H). C NMR (125 MHz, CDCl ): δ 177.89, 170.75,
3
70.73, 170.42, 170.14, 169.70, 157.59, 152.97, 129.31, 127.20, 121.95, 111.83, 94.18,
3.99, 70.88, 69.89, 69.63, 68.35, 68.27, 67.81, 63.25, 62.14, 61.78, 20.97, 20.81, 20.79,
+
+
0.78, 20.73. HRMS (ESI ): m/z calcd. for C H O Na [M+Na] 649.1745, found
28
34 16
49.1742.
1
3
g: H NMR (500 MHz, CDCl ): δ 9.63 (s, 1 H), 7.21 (d, J = 3.4 Hz, 1
3
H), 6.54 (d, J = 3.4 Hz, 1 H), 6.12 (dd, J = 9.9, 5.2 Hz, 1 H), 6.04 (dd, J =
1
0.1, 2.9 Hz, 1 H), 5.12 (d, J = 2.7 Hz, 1 H), 4.98–4.94 (m, 1 H), 4.77 (d, J =
3.3 Hz, 1 H), 4.65 (d, J = 13.3 Hz, 1 H), 4.16 (dd, J = 13.0, 2.6 Hz, 1 H), 3.86
1
13
(
d, J = 13.0 Hz, 1 H), 2.09 (s, 3 H). C NMR (125 MHz, CDCl ): δ 177.91,
3
1
2
0
70.72, 157.74, 152.98, 130.22, 125.77, 121.88, 111.84, 92.78, 63.18, 61.85, 61.63,
+
+
1.22. HRMS (ESI ): m/z calcd. for C H O Na [M+Na] 289.0688, found 289.
13
14
6
683.
1
3
h: H NMR (500 MHz, CDCl ): δ 9.64 (s, 1 H), 8.03 (d, J = 8.0 Hz, 2 H), 7.58 (t,
3
J = 7.4 Hz, 1 H), 7.45 (t, J = 7.7 Hz, 2 H), 7.22 (d, J = 3.4 Hz, 1 H), 6.57 (d, J = 2.8 Hz,
1
H), 6.10 (d, J = 10.3 Hz, 1 H), 6.02 (d, J = 10.2 Hz, 1 H), 5.96 (d, J = 10.3 Hz, 1
H), 5.87 (d, J = 10.2 Hz, 1 H), 5.34 (d, J = 9.3 Hz, 1 H), 5.14 (s, 1 H), 4.86 (d, J =
1
3.4 Hz, 1 H), 4.81 (d, J = 13.3 Hz, 1 H), 4.69 (d, J = 13.3 Hz, 1 H), 4.16 (dt, J = 12.4,
13
6
.2 Hz, 1 H), 4.10–4.05 (m, 1 H), 1.27 (d, J = 6.3 Hz, 3 H). C NMR (125 MHz,
CDCl ): δ 177.91, 166.11, 158.09, 152.93, 137.97, 133.46, 130.69, 129.87, 129.85,
3
+
1
28.60, 127.22, 121.98, 111.67, 94.42, 71.24, 65.48, 62.24, 18.11. HRMS (ESI ): m/z
+
calcd. for C H O Na [M+Na] 365.1001, found 365.1002.
19
18
6
Acknowledgments
We sincerely thank the analytic center of East China Normal University for data measure-
ments.We also express our gratitude to Mr. Tianjun Tang for his suggestions of manuscript
modification.

1
0
Z. DING ET AL.
Funding
The project was supported by the Natural Science Foundation of Shanghai (11ZR1410400),
“
DAXIA” Science Research Foundation of East China Normal University (2012DX-138), large
instruments Open Foundation of East China Normal University (20151043 & 20162015),
and National Undergraduate Training Program for Innovation and Entrepreneurship
(
201710269030G).
References
[
1] Dou, Y.; Zhou, S.; Oldani, C.; Fang, W.; Cao, Q. 5-Hydroxymethylfurfural production from
dehydration of fructose catalyzed by Aquivion@silica solid acid. Fuel 2018, 214, 45–54.
1
0.1016/j.fuel.2017.10.124.
[
2] Xia, H.; Xu, S.; Yang, L. Efficient conversion of wheat straw into furan compounds, bio-oils,
and phosphate fertilizers by a combination of hydrolysis and catalytic pyrolysis. RSC Adv.
2
017, 7 (3), 1200–1205. 10.1039/C6RA27072G.
[
[
3] Du, X.; Zhang, J.; Wang, Y.; Qu, Y. Conversion of carbohydrates into platform chemicals
catalyzed by alkaline ionic liquids. Catalysts 2017, 7 (9), 245. 10.3390/catal7090245.
4] Yutthalekha, T.; Suttipat, D.; Salakhum, S.; Thivasasith, A.; Nokbin, S.; Limtrakul, J.; Wat-
tanakit, C. Aldol condensation of biomass-derived platform molecules over amine-grafted
hierarchical FAU-type zeolite nanosheets (Zeolean) featuring basic sites. Chem. Commun.,
2
017, 53, 12185–12188. 10.1039/c7cc06375j.
[
[
[
[
[
5] Kucherov, F. A.; Gordeev, E. G.; Kashin, A. S.; Ananikov, V. P., Three-dimensional printing
with biomass-derived PEF for carbon-neutral manufacturing. Angew. Chem. Int. Ed. 2017,
5
6, 1–6.
6] Qiu, G.; Wang, X.; Huang, C.; Li, Y.; Chen, B. Facile, One-Pot Two-step, strategy for the
production of potential bio-diesel candidates from fructose. Catalysts 2017, 7 (8), 237.
1
0.3390/catal7080237.
7] Xia, H.; Houghton, J. A.; Clark, J. H.; Matharu, A. S. Potential utilization of unavoidable
food supply chain wastes – Valorization of pea vine wastes. ACS Sustain. Chem. Eng. 2016,
4
8] Wang, Z.; Chen, Q. Conversion of 5-hydroxymethylfurfural into 5-ethoxymethylfurfural
(11), 6002–6009. 10.1021/acssuschemeng.6b01297.
and ethyl levulinate catalyzed by MOF-based heteropolyacid materials. Green Chem. 2016,
1
8, 5884–5889. 10.1039/C6GC01206J.
9] Wang, Y.; Yu, K.; Lei, D.; Si, W.; Feng, Y.; Lou, L.-L.; Liu, S. Basicity-tuned
hydrotalcite-supported Pd catalysts for aerobic oxidation of 5-hydroxymethyl-2-
furfural under mild conditions. ACS Sustain. Chem. Eng. 2016, 4 (9), 4752–4761.
1
0.1021/acssuschemeng.6b00965.
[
[
[
10] Song, Y.; Wang, X.; Qu, Y.; Huang, C.; Li, Y.; Chen, B. Efficient dehydration of fructose
to 5-hydroxy-methylfurfural catalyzed by heteropolyacid salts. Catalysts 2016, 6 (4), 49.
1
11] Roman-Leshkov, Y.; Chheda, J. N.; Dumesic, J. A. Phase modifiers promote efficient
production of hydroxymethylfurfural from fructose. Science 2006, 312, 1933–1937.
1
12] Shen, Y.; Zhang, Y.; Zhu, E.; Chen, Y.; Jin, P.; Liu, M.; Yan, Y.; Li, C. Facile synthesis
of hierarchical pore foam catalysts with Brønsted–Lewis acid sites for the one-pot con-
version of cellulose to 5-hydroxymethylfurfural. RSC Adv. 2016, 6 (84), 80368–80382.
0.3390/catal6040049.
0.1126/science.1126337.
1
0.1039/C6RA14615E.

JOURNAL OF CARBOHYDRATE CHEMISTRY
11
[
[
[
[
[
13] Rosatella, A. A.; Simeonov, S. P.; Frade, R. F. M.; Afonso, C. A. M. 5-Hydroxymethylfurfural
HMF) as a building block platform: Biological properties, synthesis and synthetic applica-
tions. Green Chem. 2011, 13 (4), 754. 10.1039/c0gc00401d.
14] Roman-Leshkov, Y.; Barrett, C. J.; Liu, Z. Y.; Dumesic, J. A. Production of dimethylfu-
ran for liquid fuels from biomass-derived carbohydrates. Nature 2007, 447 (7147), 982–5.
(
10.1038/nature05923.
15] Ly, N.; Al-Shamery, K.; Chan-Thaw, C. E.; Prati, L.; Carniti, P.; Gervasini, A. Impact of
support oxide acidity in Pt-catalyzed HMF hydrogenation in alcoholic medium. Catal. Lett.
2
016, 147, 345–359. 10.1007/s10562-016-1945-9.
16] Pacheco, J. J.; Davis, M. E. Synthesis of terephthalic acid via Diels–Alder reactions with
ethylene and oxidized variants of 5-hydroxymethylfurfural. Proc. Natl. Acad. Sci. USA 2014,
1
11 (23), 8363–8367. 10.1073/pnas.1408345111.
17] Moshapo, P. T.; Sokamisa, M.; Mmutlane, E. M.; Mampa, R. M.; Kinfe, H. H. A con-
venient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of
novel benzopyran-fused pyranoquinolines. Org. Biomol. Chem. 2016, 14 (24), 5627–5638.
1
0.1039/C5OB02536B.
[
18] Dantas, C. R.; de Freitas, J. J.; Barbosa, Q. P.; Militao, G. C.; Silva, T. D.; da Silva, T.
G.; Paulino, A. A.; Freitas, J. C.; Oliveira, R. A.; Menezes, P. H. Stereoselective synthesis
and antitumoral activity of Z-enyne pseudoglycosides. Org. Biomol. Chem. 2016, 14 (28),
6
786–6794. 10.1039/C6OB00945J.
[
19] Minbiole, E. C.; Minbiole, K. P. The Petasis-Ferrier rearrangement: developments and appli-
cations. J. Antibiot. (Tokyo) 2016, 69 (4), 213–219. 10.1038/ja.2015.136.
[
20] Zhou, J.; Chen, H.; Shan, J.; Li, J.; Yang, G.; Chen, X.; Xin, K.; Zhang, J.; Tang,
J. FeCl3·6H2O/C: an efficient and recyclable catalyst for the synthesis of 2,3-
unsaturated O- and S-glycosides. J. Carbohydr. Chem. 2014, 33 (6), 313–325.
1
0.1080/07328303.2014.941995.
[
[
21] Peh, G.; Floreancig, P. E. Convergent one-pot oxidative [n + 1] approaches to spiroacetal
synthesis. Org. Lett. 2015, 17 (15), 3750–3753. 10.1021/acs.orglett.5b01736.
22] Rusin, A.; Zawisza-Puchalka, J.; Kujawa, K.; Gogler-Piglowska, A.; Wietrzyk, J.; Switalska,
M.; Glowala-Kosinska, M.; Gruca, A.; Szeja, W.; Krawczyk, Z.; Grynkiewicz, G. Synthetic
conjugates of genistein affecting proliferation and mitosis of cancer cells. Bioorg. Med. Chem.
2
011, 19 (1), 295–305. 10.1016/j.bmc.2010.11.024.
[
[
[
[
[
[
23] Sun, G. S.; Qiu, S. F.; Ding, Z. K.; Chen, H. S.; Zhou, J. F.; Wang, Z. F.; Zhang, J. B. Magnetic
core-shell Fe3O4@C-SO3H as an efficient and renewable ‘Green Catalyst’ for the synthesis
of O-2,3-unsaturated glycopyranosides. Synlett 2017, 28 (3), 347–352.
24] Chen, H.; Luo, X.; Qiu, S.; Sun, W.; Zhang, J. TMSOTf mediated stereoselective synthesis
of alpha-C-glycosides from unactivated aryl acetylenes. Glycoconj. J. 2017, 34 (1), 13–20.
1
0.1007/s10719-016-9718-7.
25] Zhang, J.; Zhang, B.; Zhou, J.; Chen, H.; Li, J.; Yang, G.; Wang, Z.; Tang, J. A facile H2SO4-
SiO2–catalyzed Ferrier rearrangement of 3,4,6-tri-O-benzyl-d-glucal. J. Carbohydr. Chem.
2
013, 32 (5–6), 380–391. 10.1080/07328303.2013.809093.
26] Zhou, J.; Zhang, B.; Yang, G.; Chen, X.; Wang, Q.; Wang, Z.; Zhang, J.; Tang, J. A facile
˚
H2SO4/4 A molecular sieves catalyzed synthesis of 2,3-unsaturated O-glycosides via Ferrier-
type rearrangement. Synlett 2010, 2010 (06), 893–896. 10.1055/s-0029-1219539.
27] Zhou, J. F.; Chen, X.; Wang, Q. B.; Zhang, B.; Zhang, L. Y.; Yusulf, A.; Wang, Z. F.; Zhang, J. B.;
Tang, J. H2SO4-SiO2: Highly efficient and novel catalyst for the Ferrier-type glycosylation.
Chin. Chem. Lett. 2010, 21 (8), 922–926. 10.1016/j.cclet.2010.03.013.
28] Girka, Q.; Estrine, B.; Hoffmann, N.; Le Bras, J.; Marinkovi c´ , S.; Muzart, J. Simple efficient
one-pot synthesis of 5-hydroxymethylfurfural and 2,5-diformylfuran from carbohydrates.
React. Chem. Eng. 2016, 1 (2), 176–182. 10.1039/C5RE00004A.

1
2
Z. DING ET AL.
[
[
[
[
[
[
[
[
[
[
29] Kanzler, C.; Schestkowa, H.; Haase, P. T.; Kroh, L. W. Formation of reactive intermedi-
ates, color, and antioxidant activity in the maillard reaction of maltose in comparison to
d-glucose. J. Agric. Food Chem. 2017, 65 (40), 8957–8965. 10.1021/acs.jafc.7b04105.
30] Tucker, M. H.; Alamillo, R.; Crisci, A. J.; Gonzalez, G. M.; Scott, S. L.; Dumesic, J. A. Sus-
tainable solvent systems for use in tandem carbohydrate dehydration hydrogenation. ACS
Sustain. Chem. Eng. 2013, 1 (5), 554–560. 10.1021/sc400044d.
31] Crisci, A. J.; Tucker, M. H.; Lee, M.-Y.; Jang, S. G.; Dumesic, J. A.; Scott, S. L. Acid-
functionalized SBA-15-type silica catalysts for carbohydrate dehydration. ACS Catal. 2011,
1
(7), 719–728. 10.1021/cs2001237.
32] Xin, H.; Zhang, T.; Li, W.; Su, M.; Li, S.; Shao, Q.; Ma, L., Dehydration of glucose to 5-
hydroxymethylfurfural and 5-ethoxymethylfurfural by combining Lewis and Brønsted acid.
RSC Adv. 2017, 7 (66), 41546–41551. 10.1039/C7RA07684C.
33] Li, H.; Xu, W.; Huang, T.; Jia, S.; Xu, Z.; Yan, P.; Liu, X.; Zhang, Z. C. Distinctive aldose
isomerization characteristics and the coordination chemistry of metal chlorides in 1-Butyl-
3-methylimidazolium chloride. ACS Catal. 2014, 4 (12), 4446–4454. 10.1021/cs5012684.
34] Sau, A.; Williams, R.; Palo-Nieto, C.; Franconetti, A.; Medina, S.; Galan, M. C. Palladium-
catalyzed direct stereoselective synthesis of deoxyglycosides from glycals. Angew. Chem. Int.
Ed. 2017, 56 (13), 3640–3644. 10.1002/anie.201612071.
35] Chen, P.; Bi, B. Preparation of 2,3-unsaturated pseudoglycosides with Ferrier rearrange-
ment promoted by Tm(OTf)3 as a highly efficient catalyst. Tetrahedron Lett. 2015, 56 (34),
4
895–4899. 10.1016/j.tetlet.2015.06.077.
36] Chen, P.; Li, S. Y(OTf)3 as a highly efficient catalyst in Ferrier rearrangement for the
synthesis of O- and S-2,3-unsaturated glycopyranosides. Tetrahedron Lett. 2014, 55 (42),
5
813–5816. 10.1016/j.tetlet.2014.08.092.
37] Bound, D. J.; Bettadaiah, B. K.; Srinivas, P. ZnBr2-catalyzed and microwave-assisted synthe-
sis of 2,3-unsaturated glucosides of hindered phenols and alcohols. Synth. Commun. 2014,
4
4 (17), 2565–2576. 10.1080/00397911.2014.909490.
38] Roy, R.; Rajasekaran, P.; Mallick, A.; Vankar, Y. D. Gold(III) chloride and phenylacetylene:
A catalyst system for the Ferrier rearrangement, and O-glycosylation of 1-O-acetyl sugars
as glycosyl donors. Eur. J. Org. Chem. 2014, 2014 (25), 5564–5573. 10.1002/ejoc.201402606.
39] Gómez, A. M.; Lobo, F.; Uriel, C.; López, J. C. Recent developments in the Ferrier rearrange-
ment. Eur. J. Org. Chem. 2013, 2013 (32), 7221–7262. 10.1002/ejoc.201300798.
[
[
40] Tatina, M.; Kusunuru, A. K.; Yousuf, S. K.; Mukherjee, D. Tandem regio- and diastereo-
selective synthesis of halogenated C-vinyl glycosides from unactivated arylacetylenes.
Chem. Commun. 2013, 49 (97), 11409–11411. 10.1039/c3cc46914j.
[
[
[
[
[
41] Freitas, J. C. R.; Couto, T. R.; Paulino, A. A. S.; de Freitas Filho, J. R.; Malvestiti, I.; Oliveira,
R. A.; Menezes, P. H. Stereoselective synthesis of pseudoglycosides catalyzed by TeCl4 under
mild conditions. Tetrahedron 2012, 68 (51), 10611–10620. 10.1016/j.tet.2012.09.073.
42] Williams, D. B.; Simelane, S. B.; Kinfe, H. H. Aluminium triflate catalysed O-glycosidation:
Temperature-switched selective Ferrier rearrangement or direct addition with alcohols. Org.
Biomol. Chem. 2012, 10 (29), 5636–5642. 10.1039/c2ob25540e.
43] Qiu, S.; Sun, G.; Ding, Z.; Chen, H.; Zhang, J. Ferric chloride: An eco-friendly catalyst for
the stereoselective synthesis of 2-deoxy aryl-O-rhamnosides. Synlett 2017, 28, 2024–2029.
1
0.1055/s-0036-1588864.
44] Qiu, S.; Zhang, W.; Sun, G.; Wang, Z.; Zhang, J. A facile and direct glycosidation method for
the synthesis of 2-deoxy α-rhamnosides catalyzed by ferric chloride. ChemistrySelect 2016,
1
(15), 4840–4844. 10.1002/slct.201600802.
45] Yaya, S.; Sorhoa, S.; Cottier, L.; Descotes, G. Synthesis of 2,3-unsaturated furanic hex- and
pent-enopyranoside employing the Ferrier rearrangement. Bull. Chem. Soc. Ethiopia 2005,
1
9 (2), 233–241.

JOURNAL OF CARBOHYDRATE CHEMISTRY
13
[
[
[
[
[
46] Cottier, L. Synthesis of acetylated ranunculin diastereoisomers and δ-gluccsyl-γ -oxy-Oxo
esters from α or β glucosy I methyIfurfura I. J. Carbohydr. Chem. 2005, 24, 55–71.
1
0.1081/CAR-200049688.
47] Filho, J. R. d. F.; Srivastava, R. M.; Soro, Y.; Cottier, L.; Descotes, G. Synthesis of new 2,3-
unsaturated O-glycosides through Ferrier rearrangement. J. Carbohydr. Chem. 2001, 20,
5
61–567. 10.1081/CAR-100108274.
48] Lichtenthaler, F. W.; Martins, D.; Webera, T.; Schiweckb, H. 5-(a-D-Glucosyloxymethyl)
furfural: Preparation from isomaltulose and exploration of its ensuing chemistry. Liebigs
Ann. Chem. 1993, 967–974. 10.1002/jlac.1993199301154.
49] Chen, H.; Xian, T.; Zhang, W.; Si, W.; Luo, X.; Zhang, B.; Zhang, M.; Wang, Z.; Zhang, J.
An efficient method for the synthesis of pyranoid glycals. Carbohydr. Res. 2016, 431, 42–46.
1
0.1016/j.carres.2016.05.013.
50] Xu, G. G.; Pagare, P. P.; Ghatge, M. S.; Safo, R. P.; Gazi, A.; Chen, Q.; Safo, M. K.; Abdulmalik,
O. Design, synthesis, and biological evaluation of ester and ether derivatives of antisickling
agent 5-HMF for the treatment of sickle cell disease. Mol. Pharm. 2017, 14, 3499–3511.
1
0.1021/acs.molpharmaceut.7b00553.
[
51] Feng Z.; Zhan, Z.; Yang, Y.; Jiang, J.; Zhang, P. New heterocyclic compounds from Ranun-
culus ternatus Thunb. Bioorg. Chem. 2017, 74, 10–14. 10.1016/j.bioorg.2017.07.004.
52] Kuroda, M.; Mimaki, Y.; Sashida, Y.; Hirano, T.; Oka, K.; Dobashi, A.; Li, H.; Harada, N.
Novel cholestane glycosides from the bulbs of Ornithogalum saundersiae and their cyto-
static activity on leukemia HL-60 and MOLT-4 cells. Tetrahedron 1997, 53, 11549–11562.
[
1
0.1016/S0040-4020(97)00750-3.