Preparation of 5-methylfurfural from starch in one step by iodide mediated metal-free hydrogenolysis

Article abstract of DOI:10.1039/c9gc01645g

Starch is available in large quantities and at cheap price, especially that from stale rice, root and tuber crops, etc., which makes it desirable for conversion to value-added products. A metal-free approach to convert starch to 5-methylfurfural (5-MF) using hydrochloric acid, sodium iodide and hydrogen in a biphasic solvent system has been developed. 5-MF is an important fine chemical, widely used in food, medicine, pesticides, cosmetics and other industries, and is also considered to be an important bio-gasoline precursor. I^- has superior nucleophilic substitution properties and high reactivity towards C-O bond cleavage, which is crucial for this transformation. Under optimal reaction conditions, 38.0% of 5-MF and 45.6% of total organic products can be obtained from starch with 22.5% levulinic acid as the main side product. Besides, 80.8% 5-MF can be directly obtained from 5-hydroxymethylfurfural (HMF) through the same process. To the best of our knowledge, this is the first reported example of a metal-free process to convert starch and HMF directly to 5-MF. The reaction mechanism was well studied. The catalyst system was proved to be stable and was recycled five times without loss of activity.

Full text of DOI:10.1039/c9gc01645g

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DOI: 10.1039/C9GC01645G
ARTICLE
Preparation of 5-Methylfurfural from Starch in One Step by
Iodide Mediated Metal-Free Hydrogenolysis
Yang Peng, Xianghua Li, Tian Gao, Teng Li, Weiran Yang *
Received 00th January 20xx,
Accepted 00th January 20xx
Starch is available in large quantities and in cheap price, especially those from stale rice, root and tube crop etc., which is
desirable to be converted to value-added products. A metal-free approach to convert starch to 5-methylfurfural (5-MF) using
hydrochloric acid, sodium iodide and hydrogen in a biphasic solvent system has been developed. 5-MF is an important fine
chemical, widely used in food, medicine, pesticides, cosmetics and other industries, and is also considered to be an important
DOI: 10.1039/x0xx00000x
-
bio-gasoline precursor. I has superior nucleophilic substitution properties and high reactivity towards C-O bond cleavage,
which is crucial for this transformation. Under optimal reaction condition, 38.0% of 5-MF and 45.6% of total organic products
can be obtained from starch with 22.5% levulinic acid as the main side product. Besides, 80.8% 5-MF can be directly obtained
from 5-hydroxymethylfurfural (HMF) through the same process. To the best of our knowledge, this is the first reported
example of metal-free process to convert starch and HMF directly to 5-MF. The reaction mechanism was well studied. The
catalyst system was proved to be stable, and was recycled for five times without loss in activity.
several functional groups including a furan ring, a carbonyl
group and double bonds, it is a good platform molecule to
produce other value-added products. At present, more than 70
Introduction
Biomass is the only sustainable source of organic carbon on earth，
kinds of compounds can be synthesized from 5-MF, some of
which are summarized in Fig. 1. Currently, the industrial
synthesis of 5-MF is by 2-methylfuran reacting with phosgene
and N, N-dimethylformamide (route 1 in Scheme 1).[4] Due to
the high production cost, wide application of 5-MF has been
limited.
which is an ideal petroleum alternative for fuels, chemicals and
materials.[1] Starch is a polymeric carbohydrate composed of a
large number of glucose units linked by glucosidic bonds. It
exists in potato, wheat, corn, rice, cassava, etc., and also is the
most common bio-based material in human diet. With the
increase of the agriculture production efficiency, starch is
available in large quantities, thus has been used in many areas
other than food. Besides, certain kinds of starch are not suitable
for food, such as those from stale rice，root and tube crop etc.
Thus, transformation of starch to value-added products is an
important research area. Consequently, starch is widely used
industrially in the production of dextrin, maltose, glucose, sugar
alcohol, ethanol, modified starch, etc., and in the manufacture of
various adhesives or glue, book binding, textile sizing, drug
tablets, and the like.[2]
5
-methylfurfural (5-MF) is an important fine chemical and
widely used in medicine, pesticide, cosmetics and other
industries. It is also an important edible flavors and is even
considered as an important anticancer drug.[3] Since 5-MF has
a. Key Laboratory of Poyang lake Environment and Resource Utilization (Nanchang
University), Ministry of Education, No. 999 Xuefu Avenue, Jiangxi 330031, R.P.
China. E-mail: wyang16@ncu.edu.cn
b. School of Resource Environmental and Chemical Engineering, Nanchang
University, No. 999 Xuefu Avenue, Jiangxi 330031, R.P. China.
Fig. 1 Valorization of 5-MF to various value-added products[5]
.
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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ARTICLE
Journal Name
With the development of biomass chemistry, 5-MF can also be MF by hydrogen with the synergistic catalysis of sVoiedwiuAmrticlieoOdnildinee
obtained from biomass-derived feedstock. And it is considered and hydrochloric acid. At the optimum reDacOtIi:o1n0.1c0o3n9d/Cit9ioGnC,0516-M45GF
as an important precursor for biofuels due to its low oxygen can be obtained with 80.8% yield from HMF, 38.0% yield from
content, high energy density, low volatility, and good solubility starch, and 24.0% yield from cellulose. To the best of our
in hydrocarbons (Fig. 2). Corma et al. reported that 5-MF can be knowledge, it is the first time that this metal-free method has
used as an important intermediate to produce high quality been reported to produce 5-MF directly from biomass feedstocks.
diesel.[6] Mascal et al. also reported that 5-MF can be used to
produce renewable fuel 2,5-dimethylfuran (DMF).[7]
Scheme 1 Synthetic routes for the production of 5-MF.
Fig. 2 Advantages of direct conversion of biomass into 5-MF in comparison to
HMF for fuels development.
Results and Discussion
With biomass as feedstock, 5-MF is now usually produced
from hydroxymethylfurfural (HMF) and its derivatives, the most
Development of the metal-free system
promising bio-based platform molecules. In 2014, Huang et al.
2
used W C/AC catalyst to convert HMF by hydrogen in THF
In the previous study, we developed a method to directly
convert fructose to 5-MF with RhCl /HI/H in a biphasic
system (200°C, 3 h) to obtain 87.1% yield of 5-MF.[8] In 2017,
Li et al. Developed a method to use heterogeneous iron as
catalyst for HMF hydrogenolysis by hydrogen in THF with 22.1%
3
2
system.[11] It was proved that HI is the reducing reagent to
convert fructose to 5-MF, and Rh catalyzed hydrogenation is
used to regenerate HI in-situ. To extend this system for starch
conversion, the reaction condition was optimized and different
metal catalysts such as Rh, Pd, Pt, Ru, Ni and Cu supported on
activated carbon were screened. The results are shown in Table
5
-MF yield.[9] In 2019, Sun et al. reported a method for
converting HMF to 5-MF in THF using Pd-PVP/C and formic
acid with 80% yield (route 2).[10] Mascal et al. converted
microcrystalline cellulose with LiCl and HCl to 5-
chloromethylfurfural, which was further hydrogenolyzed with
palladium chloride under hydrogen to obtain 5-MF with 62.5%
yield (route 3).[7] However ， due to the energy-intensive
separation and purification step of HMF, it is more desirable to
directly convert biomass to 5-MF, which is easier to be separated
due to its lower solubility in water and higher stability (Fig. 2).
Thus，several methods have been developed to directly convert
1. Under identical conditions, the total chemicals yield in the
organic phase seemly depends on the hydrogenation activity of
the metal catalyst with the order as Rh/C > Pd/C > Pt/C > Blank
>
Ru/C = WC > Ni/C = Cu/C. The most important observation
here is that even with no metal catalyst, the reactivity is still as
good as most of the metal catalysts with H present (Table 1,
entry 4). Besides, no I was produced as indicated by the starch
2
2
biomass resources to 5-MF. Yang et al. has used RhCl
to convert fructose into 5-MF under hydrogen atmosphere with
8% yield (route 4).[11] In addition, Ji et al. reported to use
3
and HI
potassium iodide test (Details was shown in Fig. S1). Thus,
under this reaction condition, the reaction mechanism is totally
different as the fructose to 5-MF system developed before.[11] HI
6
carbonized wood-loaded polyaniline with microwave to catalyze
the conversion of fructose to 5-methylfurfural with 70% yield.[12]
All the methods referenced above require precious metal
catalyst for the hydrogenolysis reaction to obtain 5-MF from
HMF and its derivatives or directly from sugars, which leads to
high production cost. Herein, we developed a metal-free method
that can directly convert HMF, starch and even cellulose to 5-
is not the reducing reagent here. However, without H
of the 5-MF was obtained, and I was detected at the end of the
reaction (Table 1, entry 9). Apparently, H is the reducing
reagent during the reaction and it has a good enough reactivity
even without any metal catalyst. Besides, metal-free system has
a better selectivity for 5-MF despite a slightly lower reactivity as
compared to Rh/C, which has a poorer selectivity due to the
2
, only 3.8%
2
2
2
| J. Name., 2012, 00, 1-3
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excessive hydrogenation of 5-MF to form 2-methylfuran (2- converted to 5-MF by H
MF), 2,5-dimethylfuran (2,5-DMF),
2
(Scheme 2).[11] On the other hand,
DOI: 10.1039/C9GC01645G
2,5- HMF can also be hydrolyzed to form levulinic acid and formic
View Article Online
dimethyltetrahydrofuran (DMTHF), and 2,5-hexanedione (2,5- acid in water by acid.[15] Thus, there is a competition reaction
HDO) (Table 1, compare entry 4 with entry 1). Among the between substitution reaction and hydrolysis of HMF. Iodide is
studied metals, Pd/C provided the highest yield of 5-MF (37.0 required due to its superior nucleophilic substitution properties
%) but still comparable with the yield of the metal free system and high reactivity towards C-O bond cleavage, which will be
(32.1%). Interestingly, 27.6% of 2,5-hexanedione (2,5-HDO) discussed in details in the mechanism study section.
was obtained with Pt/C. With Ni/C and Cu/C added, the total
organics yields are lower than the blank, which is probably due
to consumption of protons by Ni and Cu. Thus, it can be seen
2
from the result that metal-free system with HCl/NaI/H is a better
choice to convert starch to 5-MF than those with metal catalysts.
Under typical conditions (Table 1, entry 4), the starch conversion
was determined to be 99.7% (experimental details shown in SI).
And the major side product observed is levulinic acid in the
aqueous phase.
Table 1 Catalytic conversion of starch to produce 5-MF
Scheme 2 Possible reaction pathway for starch conversion to 5-MF.
Yield (%)
Entry Conditions
2
,5-
2,5-
HDO
To further prove that it is a metal-free system, the reaction
system was nitrated and analyzed by ICP-AES after the reaction.
The result showed that only Sn concentration was greater than
2
-MF Furfural
DMTHF 5-MF
Total
DMF
1
2
3
4
5
6
7
8
9
Rh/C
Pd/C
Pt/C
4.8
6.2
2.9
3.6
5.4
5.6
4.2
5.3
0.9
1.2
2.1
1.5
1.2
1.5
2.4
1.5
2.3
9.0
28.1
37.0
0.6
8.8
0.7
53.9
47.8
42.7
1ppm (1.23 ppm) with all the other metal contents less than 1ppm
2.7
N. D.
1.8
(
Table S1). Then, SnCl (3.5% equivalent) was added to the
2
7.7
27.6
reaction to test its catalytic activity, and it did not promote 5-MF
formation (Table S2). To exclude the effect of ppm levels of
homogeneous catalyst, 1.8% eq RhCl ·3H O and 2.0% eq PdCl
3 2 2
were added to the reaction system respectively, and there was no
obvious promotion effect as shown in Table S9 entries 2&3. In
addition, to eliminate the influence from unexpected factors, the
experiment was repeated with a brand new reactor, a new stirrer,
a new liner, ultrapure water, distilled MTHF and a new bottle of
starch.[16] Similar results (Table S9, entry 1) were obtained.
Thus, our system is indeed a metal-free process.
/
N. D.
1.4
N. D.
N. D.
N. D.
N. D.
N. D.
N. D.
32.1 N. D. 37.2
25.3 3.5 36.8
Ru/C
WC
N. D.
N. D.
N. D.
29.1 N. D. 36.2
21.2 N. D. 27.8
20.6 N. D. 27.4
Ni/C
Cu/C
300 psi N
2
N. D. N. D. N. D.
3.8 N. D.
3.8
0
1
0
1
2
No HCl N. D. N. D. N. D.
No water N. D. N. D. N. D.
N. D. N. D. N. D.
N. D. N. D. N. D.
N. D. N. D. N. D.
1
1
0
Optimization of reaction parameters
No NaI
1.0
1.1
N. D.
2.1
Effect of reagents amount
Reaction Condition:100 mg starch, 2 mmol NaI, 0.18 mmol HCl, 1% mol eq.
catalyst, 2 mL H O, 3 mL MTHF, 500 r/min, 4 h, 300 psi H , 160℃. 5.0 wt.%
Rh/C, Pd/C, Pt/C, Ru/C, Ni/C, Cu/C. Catalyst amount is based on the molar
content of glucose monomer in the starch.
2
2
The reaction condition was optimized to achieve a more
efficient process. First, the acidity of the reaction was screened
in the range of 0 ~ 0.36 mol/L H , and the result is shown in Fig.
+
3
a. The 5-MF yield first increased and then decreased with the
increase of acidity, and the best yield is achieved at H+
concentration of 0.09 mol/L. Low acidity leads to slower
hydrolysis rate, dehydration rate and the rate of iodide
substitution reaction. High acidity leads to formation of humins
from monosaccharides and HMF. In addition, different acids
were also screened on starch conversion (Fig. 3b). Compared
HCl, H
2
O and NaI are all proved to be necessary for this
O are
transformation (Table 1, entries 10-12). HCl and H
2
necessary for the hydrolysis of starch. Without NaI, the major
products detected are levulinic acid, HMF and glucose in the
aqueous phase with only a small amount of furfural. Based on
the literature study, the most possible reaction pathway for this
one step conversion of starch to 5-MF is that starch is first
hydrolyzed to form glucose;[13] glucose is isomerized to fructose,
with weak acids, such as CF
3 3 3 4
COOH, CH COOH, and H PO ,
strong acids (HCl, H SO , HI, CF SO H, HBr) have better effect
2
4
3
3
[14]
on 5-MF formation. KI and LiI was also used instead of NaI
(Table S3), and the experimental results were almost identical.
which is dehydrated to HMF under acidic condition; HMF is
-
then substituted by I under acidic condition to form 5-
iodomethylfurfural, which is not stable and can be quickly
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Thus, cations in the iodides has minimum effect on the suitable solubility. MTHF is more polar than toluVeienweAratinclde Otnhliunes
DOI: 10.1039/C9GC01645G
can extract intermediates and the product more effectively. THF
experiment.
NaI amount was also screened from 0 to 6 mmol (Fig. 3c). It and 1,4-dioxane are more soluble in water, so they do not
was found that 5-MF yield increased with the increase of NaI perform well.
-
amount. High concentration of I is necessary for the fast
substitution reaction to compete with HMF hydrolysis. HMF is
more readily hydrolyzed to levulinic acid when the concentration
of sodium iodide is low. On the other hand, excessive NaI
soluble in water can prevent aggregation of HMF and sugars, and
thus prevent humins formation.[17]
Hydrogen pressure also has a great influence on the
2
experiment. The 5-MF yield increased linearly with H pressure
when lower than 100 psi and then remained constant at pressure
higher than 200 psi as shown in Fig. 3d.
Fig. 4 Effect of solvent (a) and solvent ratio (b) on starch conversion. Reaction
Condition: 100 mg starch, 2 mmol NaI, 0.18 mmol HCl, 2 mL H O, organic
solvent, 500 r/min, 2 h, 300 psi H , 160℃.
2
2
With MTHF as organic solvent, we further optimized the
MTHF to water ratio. As the volume ratio of MTHF to water
increased from1 to 3, the 5-MF yield increased from 19.9% to
3
4
8.0%, and the total organics yield increased from 26.4% to
5.6% (Fig. 4b). The increase of the organic solvent enhanced
the extraction ability of the intermediates to promote the
formation of more organics.
Effect of temperature and time
Reactions were performed in the temperature range of 120℃
to 180℃ (Fig. 5a). The highest 5-MF yield (32.1%) is obtained
at 160℃ in 2h. Higher temperature leads to the formation of
humins, resulting in a decrease in yield. Then the product
compositions were examined at different reaction times. At 2 h,
the 5-MF yield reached the maximum value of 37.2% and then
started to decrease with longer reaction time (Fig. 5b). The 5-MF
recovery experiment showed that 5-MF is not stable and can be
further converted to 2-MF and decomposed to other side
products (details shown in Table S4). Thus, controlling the
reaction time is crucial for this transformation. Therefore, the
optimal conditions for starch (100 mg) conversion to 5-MF is
Fig. 3 Effect of acidity in water (a), sodium iodide (b), acid (c) and H
2
pressure
(d) on starch conversion. Reaction condition is as follows if not stated
otherwise: 100 mg starch, 2 mmol NaI, 0.18 mmol HCl, 2 mL H
2
O, 3 mL
2
MTHF, 500 r/min, 2 h, 300 psi H , 160℃.
Effect of organic solvent
Biphasic system (water and water-immiscible organic solvent)
is proved to be much better than the single phase system for
biomass conversion.[18] One important reason is that the unstable
2
with 0.09mol/L HCl, 6mmol NaI, 300psi H , and MTHF to water
ratio as 3 at 160°C for 2h, to achieve the 5-MF yield as 38.0%.
The major side product is levulinic acid with 22.5% yield (shown
in Table S5).
intermediates can be extracted into organic phase to be protected
against further degradation by acid.[19] During this reaction, the
side reaction of HMF hydrolysis to levulinic acid is competitive
with HMF hydrogenolysis to form 5-MF. The former reaction is
prone to occur in the aqueous phase and the latter reaction is
more stable in the organic phase. The organic solvent added here
is to extract and protect the intermediates and the final product.
Here, several common organic solvents were tested, including
1
,4-dioxane (dioxane), methyl isobutyl ketone (MIBK),
tetrahydrofuran (THF), 2-methyltetrahydrofuran (MTHF) and
toluene (Fig. 4a). Among them MTHF is more preferably with
3
2.1% 5-MF yield and 37.2% total organics yield. We believe
that the main reason for the good performance of MTHF is its
4
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Fig. 5 Effect of temperature (a) and time (b) on starch conversion. Reaction
Condition: 100 mg starch, 2 mmol NaI, 0.18 mmol HCl, 2 mL H O, 3 mL
leads to higher 5-MF yield. When the water amVioewunArtticfleuOrtnhliener
DOI: 10.1039/C9GC01645G
decreased to 0.5ml or 0ml, both 5-MF and 2,5-diformylfuran
2
2
MTHF, 500 r/min, 2 h, 300 psi H , 160℃.
(DFF) were formed(Table 3; entry 1 & 2). The less the water
added, the more the DFF formed, which probably goes through
an intramolecular-oxidation-reduction mechanism, and will not
be elaborated here. This is the first time reported metal-free
process to convert HMF to 5-MF with high selectivity.
Mechanistic study
During starch conversion to 5-MF process, intermediates such
as HMF, fructose, glucose and levulinic acid were detected in the
aqueous phase (shown in Table S6). Therefore, glucose, fructose
and HMF were used as starting materials respectively to look
into the reaction mechanism. As shown in table 2, the yields of
Table 3 Metal-free selective hydrogenolysis of HMF
Yield (%)
Entry
Conditions Conversion (%)
5
-MF produced by starch, glucose, fructose and HMF under the
5
-MF
DFF
26.3
9.4
same conditions were almost the same ， which implies that
starch hydrolysis, glucose isomeriszation or fructose dehydration
are not the rate-determining step. Moreover, the side products
1
2
3
4
5
6
7
8
9
without H O
2
100.0
100.0
100.0
100.0
100.0
100.0
100.0
0
58.0
74.6
80.8
74.4
65.5
31.2
N. D.
N. D.
56.3
31.7
0.5 mL H
0.7 mL H
0.8 mL H
1.0 mL H
2.0 mL H
2
2
2
2
2
O
O
O
O
O
(levulinic acid and humins) increased with the starting materials
used in the order of starch, glucose, fructose and HMF. It
suggests that HMF is not stable and easily undergoes aggregation
and hydrolysis in water, which is consistent with reports from
others.[20] Therefore, the hydrogenolysis of HMF to form 5-MF
is the rate-determining step of the starch conversion process.
Cellulose is a more abundant biomass resurces, and its
conversion to 5-MF is more attractive. Thus cellulose was also
used as substrate for the transformation. It also provided 5-MF
as the major product in the organic phase but with a lower yield
as compared to starch. This may be because starch is more
susceptible to hydrolysis than cellulose. However, it indeed show
that our system can also be used for cellulose conversion to 5-
MF.
6.4
3.9
2.1
0.9
without NaI
without acid
N. D.
N. D.
9.4
300 psi N
2
100.0
100.0
1
0C
Starch
N. D.
Table 2 Experiments with different intermediates as substrates
Yield (%)
Reaction Condition: 1 mmol HMF, 4 mmol NaI, 0.36 mmol H
2
SO
4
, 6 mL
Entry
Substrate
a
MTHF, 500 rpm, 4 h, 300 psi H
2
, 180℃. 186.2 mg starch (1.0 mmol glucose).
2
-MF
3.6
2.4
3.1
2.5
2.0
5-MF
32.1
30.1
30.2
32.1
24.0
Levulinic acid Humins (wt.)
1
2
3
4
5
Starch
Glucose
Fructose
HMF
20.2
23.3
22.5
25.4.
23.7
13.9
12.8
19.8
29.6
14.5
No product was detected with no NaI or acid (Table 3; entries
and 8). It was found that under N atmosphere, 56.3% 5-MF
7
2
was produced, and I is detected after the reaction (Table 3，
2
entry 9), which is consistent with the reaction of starch. We
speculated that under the acidic environment, HMF was first
-
substituted by I to form 5-iodomethylfurfural (IMF). Then,
without H
-MF with I
reagent thus with no I
Reaction Condition:0.5 mmol substrate, 2 mmol NaI, 0.18 mmol HCl, 2 mL substance which can not be detected under the normal reaction
2
, HI functions as the reducing reagent to convert it to
formed; while with H present, H is the reducing
formation. IMF is an extremely unstable
5
2
2
2
Cellulose
2
H
2
O, 3 mL MTHF, 500 r/min, 2 h, 300 psi H
2
, 160℃.
condition. By adjusting the reaction condition to anhydrous,
room temperature and nitrogen atmosphere, IMF was detected
with HMF as the substrate in the presence of acid and NaI in
2 5
Then, HMF as starting material for 5-MF formation was MTHF (Metaphosphoric acid was formed by P O absorbing
studied in details as shown in Table 3. Water amount was found water) (Scheme 3).
to have a dramatic effect on 5-MF yield. The best result was
obtained with 0.7 ml water to achieve 80.8% 5-MF (Table 3;
entry 3). Adding more water leads to decreased yield (compare
entries 4, 5&6 with entry 3). Since water present hinders the
Scheme 3 Detection of 5-iodomethylfuran-2-carbaldehyde (IMF).
iodide substitution reaction of hydroxyl group and HMF
conversion to 5-MF does not require hydrolysis, less water is
needed for HMF conversion as compared with starch, which
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To confirm that IMF can be reduced by H
Journal Name
2
to 5-MF without
View Article Online
DOI: 10.1039/C9GC01645G
any metal catalyst, 2-iodomethylfuran, which has a similar
structure with IMF and is more stable than IMF, was prepared to
use as a model molecule for the reduction study. The preparation
method of 2-iodomethylfuran was shown in the supporting
materials (Table S7).[21] It was shown that 2-iodomethylfuran
can be directly converted to 2-methylfuran with 85.3% yield
2 2
under H at 100℃ in 30min (Scheme 4, Reaction 1). In N
atmosphere, no 2-methylfuran was obtained (Scheme 4,
Reaction 2). Thus, 2-iodomethylfuran can be directly reduced by
H
2
without any metal catalyst with a reasonable reaction rate.[22]
Scheme 5 Intermediate capture. a Reaction Condition: 0.5 mmol HMF, 2.0
mmol NaI, 2.0 mmol TEMPO, 0.18 mmol HCl, 3 mL MTHF 500 r/min, 2h,
b
3
2 2
00 psi H , 160℃. 100 mg starch, 2 mL H O.
Based on the above experimental results, we proposed that the
metal-free hydrogenolysis of HMF with NaI/HCl/H is as
2
follows (Scheme 6). First, in the acidic environment, HMF is
-
substituted with I to form IMF and one molecule of water is
generated. Then, IMF dissociates into iodine radical and 5-MF
radical (a) by heat. The iodine radical reacts with hydrogen to
obtain HI and a hydrogen radical, which combines with 5-MF
free radical (a) to form 5-MF.
Scheme 4 Reduction of 2-iodomethylfuran and free radical trapping. (2-
iodomethylfuran : TEMPO = 1 : 5 molar ratio)
Since no metal catalyst is involved in the hydrogenolysis of
HMF, we inferred that it is most probably a heat induced radical
reaction. To confirm this, TEMPO was added to the reaction with
HMF as substrate, and no 5-MF was formed (Scheme 5). The
reaction solution was then analyzed by HPLC-QTOF, and
3
TEMPO captured 5-MF radical C15H23NO was detected (details
shown in Fig. S4). In addition, EPR spectrum also detected the
presence of free radicals as shown in Fig. S5. Thus, the 5-MF
radical must be generated during the reaction process most
probably from IMF. To confirm this, TEMPO was added to the
2
-iodomethylfuran hydrogenation process as shown in Scheme 4,
Reaction 3. 2-Methylfuran radical was captured after adding
TEMPO, and 2-MF was not found. Thus, the radical is indeed
generated by the iodo-substituted intermediate.
TEMPO was also added to the starch conversion experiment,
which also produced no 5-MF and with 5-MF radical captured.
Scheme 6 HMF hydrogenolysis mechanism diagram through radical reaction.
This mechanism is totally different with that of the previous
2
This proves that hydrogenolysis of HMF by NaI/HCl/H is a
RhCl
in which HI was the reducing reagent to convert IMF to form 5-
MF and I2. Then I was converted back to HI by RhCl catalyzed
hydrogenation. We figured the main reasons for this difference
are: 1) Lower temperature was used in the RhCl /HI/H system
as compared to the metal free NaI/HCl/H system (90 C vs
60 C) so that the radicals are difficult to be generated; 2) Higher
concentration of HI was applied in the RhCl /HI/H system as
compared to the metal free NaI/HCl/H system (1.5mmol/mL vs
.09mmol/mL) so that HI has a higher reducing reactivity.
3 2
/HI/H system we developed to convert fructose to 5-MF,
radical process with the 5-MF radical produced by IMF, which
is also an intermediate for the starch conversion.
2
3
During the process of testing different organic solvents (such as
MTHF as received and freshly distillated MTHF), we discovered that
BHT present in the organic solvent can slow down the initial reaction
rate, which further proves that the reaction is a radical process (as
shown in Table S10）.
3
2
o
2
o
1
3
2
2
0
Recycling experiment
6
| J. Name., 2012, 00, 1-3
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The catalyst was also recycled for the starch conversion reaction.
In the biphasic system, the product 5-MF is extracted into the organic
phase while HCl and NaI remain in the aqueous phase. To recycle the
Experimental
View Article Online
DOI: 10.1039/C9GC01645G
catalyst, organic phase was separated after the completion of the Materials
reaction. Then fresh organic solvent and starch were replenished and
The high pressure stainless steel reactor, temperature
controller and IKA magnetic stirring apparatus was supplied by
Anhui Kemi Company. Rh/C, Pt/C, phosphoric acid (H PO ), 2-
3 4
the experiment continued. The aqueous phase was reused without
further adding HCl or NaI for five times. The 5-MF yield and total
organics yield did not decrease for five cycles as shown in Fig. 6. After
methyltetrahydrofuran (MTHF), tetrahydrofuran (THF), furfuryl
alcohol were purchased from MΛCKLIN; Pd/C, Ru/C, WC,
fifth cycle, the starch potassium iodide reagent was added to the
-
reaction solution, and no I
2
was detected. Thus, no I was consumed
trifluoro sulfonic acid (CF
3 3
SO H), trifluoroacetic acid
during the reaction. The aqueous phase with acid and iodide can be
recycled, so that our process has limited pollution to the environment.
(
CF COOH), 1,4-epoxycyclohexane (Dioxane), methyl isobutyl
3
ketone (MIBK), 57.0 wt.% hydroiodic acid (HI), hydrobromic
acid (HBr) 5-hydroxymethylfurfural (HMF) and 2,5-
furandicarbaldehyde (DFF) were purchased from aladdin; Starch
potassium iodide reagent, microcrystalline cellulose, glucose,
fructose and sodium iodide (NaI) was purchased from Chinese
Medicine Group Chemical Reagent Co. Ltd.; Soluble starch,
2 4 2 5
sulfuric acid (H SO ), phosphorus pentoxide (P O ), and acetic
acid (CH COOH) were purchased from Tianjin Damao
3
Chemical Reagent Factory; Toluene and 37.0 wt.% hydrochloric
acid (HCl) were purchased from Xilong Chemical. 5% wt. Ni/C
and Cu/C are self-produced.[23] All reagents were used without
further purification and solvents are not distilled unless
specified.
Metal-free reaction procedures
Fig. 6 Recycling experiment. Reaction Condition: 100 mg starch, 2 mmol NaI,
In a typical reaction, 100 mg starch, 2 mmol NaI, 0.18 mmol
0
2 2
.18 mmol HCl, 2 mL H O, 3 mL Toluene, 500 r/min, 2 h, 300 psi H , 160℃.
HCl (0.015 mL), 2 mL H
placed into a 50 mL glass vial. Then the vial was placed into a
0 mL stainless steel autoclave. And the stainless steel autoclave
was put on an IKA magnetic stirring apparatus. The autoclave
In summary, we have developed a novel metal-free method to was purged by three cycles of pressurization/venting with H
convert starch to 5-MF by using HCl, NaI and H
in a biphasic system. (300 psi) before pressurized with H (300 psi). The mixture was
2
O and 3 mL MTHF are sequentially
5
Conclusions
2
2
2
Under optimal reaction condition, 38.0% 5-MF and 45.6% total stirred at a given temperature for the desired time. When the
organics yield can be obtained from starch. Besides, 80.8% of 5-MF reaction was stopped, the reactor was cooled with a water bath.
can be produced from HMF by this metal-free method, which is also Then the upper organic phase of the reaction liquid is collected
reported for the first time. The reaction pathway of starch conversion for analysis and fractionated to obtain 5-MF. Majority of the
to 5-MF was proposed based on the previous literature reports. The iodide and acid remain in the water phase can be reused directly.
independent reactions with possible intermediates were carried out,
which suggested that HMF hydrogenolysis is the rate-determining
step. The I substituted molecule IMF was proposed as one of the
-
Analytical procedures
critical intermediate during the reaction process, which can be directly
hydrogenated to 5-MF by H without any metal catalyst. This was
2
The product was quantitatively analyzed using an Agilent
820A gas chromatography (GC) manufactured by Agilent,
7
confirmed by intermediate capture and independent reaction with a
similar compound 2-iodomethylfuran. This metal-free hydrogenation
process was confirmed to go through the heat induced radical reaction
and the detailed mechanism was provided. Moreover, the aqueous
catalyst system can be recycled for five times without any decrease in
the reactivity. Thus, this catalytic method not only needs no metal
catalyst but also generates negligible waste water, which fits well with
green and sustainable chemistry. This work provides a promising
approach for the one-pot preparation of 5-MF by metal-free selective
hydrogenolysis of starch.
USA. The GC analysis method is as follows: chromatographic
column HP-5 capillary column(30m * 320μm * 0.25μm);
Hydrogen flame ionization detector (FID); initial oven
temperature is 40℃ , first increases with 3℃/min to 100℃, then
increases with 10℃/min to 200℃, finally keeps for 5 min;
Injection port temperature 280℃; detector temperature 280℃;
High purity nitrogen as carrier gas, flows with 1.5 mL/min; Split
ratio 20:1; The injection volume is 1 μL.
The product was qualitatively analyzed by thermo scientific
TRACE 1310 GCMS. GCMS analysis method is as follows:
chromatographic column HP-5 capillary column (30m * 320μm
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*
0.25μm); initial oven temperature is 40℃, keeps for 5min, and
Acknowledgments
This work was funded by the National Key Research and
Development Program of China (Grant No. 2017YFD0800900)
View Article Online
DOI: 10.1039/C9GC01645G
first increases with 5℃/min to 100℃, then increases with
1
2
0℃/min to 150℃, followed by increasing with 20℃/min to
80℃, finally keeps for 5min. Ion source temperature 290℃, the “Thousand Young Talents” Program of China, and “Thousand
filament opens at 0-2.1min and 3.5-35min, and closes at 2.1- Talents” Program of Jiangxi Province.
3
.5min; High purity helium was used as carrier gas, with a flow
rate of 1.0ml /min. Split ratio 20:1; The injection volume is 0.2
μL.
Notes and references
The aqueous phase product was qualitatively analyzed by
Water ACQUITY UPLC HClass. HPLC analysis method is as
follows: sugar column (300mm * 6.5mm); equipped with a
RefractoMax 520 refractive index detector; 0.5g/L sulfuric acid
as mobile phase with flow rate of 0.6mL/min, 60℃ column
temperature, and with 10μL injection volume.
For identification of unknown products, an HPLC equipped
with a mass spectrometer (HPLC-X500RQTOF) and a
ACQUITY UPLC@BEH C18 1.7μm (2.1mm × 50mm) column
was used. Solutions were prepared in the same way as described
above, with 1% formic acid was chosen as the mobile phase due
to compatibility with the mass spectrometer.
The concentration of metal ions in solution was measured by
inductively coupled plasma atomic emission spectrum (ICP-
AES, VAROEL). Before measurement, 2mL of aqueous phase
was diluted to 10ml with pure water and 100μL of 37% HCl was
added. Then samples were digested at 100℃ in 4h.
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