Microwave heating for rapid conversion of sugars and polysaccharides to 5-chloromethyl furfural

Article abstract of DOI:10.1039/c2gc36290b

A range of carbohydrates has been rapidly and selectively converted to 5-chloromethyl furfural using microwave heating in a biphasic reaction system with a range of organic solvents. Fructose and inulin were especially effective for production of this valuable bio-platform molecule, with yields of >70% obtained in 15 minutes under microwave heating. Yields from cellulose were dramatically increased with ball mill pre-treatment, this being associated with a reduction in polysaccharide crystallinity.

Full text of DOI:10.1039/c2gc36290b

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Simple, rapid and selective synthesis of CMF is demonstrated from polysaccharides and sugars, in a bi-
phasic reaction, under microwave heating.
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ARTICLE TYPE
Microwave Heating for Rapid Conversion of Sugars and
Polysaccharides to 5-chloromethyl furfural
S W Breeden, a J H Clark, a T J Farmer, a D J Macquarrie,* a J S Meimoun,b Y Nonnec and J E S J Reid a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
avoiding heating of the organic layer and as such reducing side-
product formation. While recent research has demonstrated the
50 effective application of flow reactors for the production of CMF
from sugars, it is likely that use of non-food polysaccharides such
as cellulose and inulin would lead to viscosity issues with a
reactor of this kind.12 Herein we report a biphasic reaction
system, heated by microwave energy, which is capable of yields
55 of CMF over 70%, but in a shorter time and with reduced by-
product formation than those previously presented using
conventional heating. We also show applications of greener
solvents, replacing the currently favoured 1,2-dichloroethane.
A range of carbohydrates have been rapidly and selectively
converted to 5-chloromethyl furfural using microwave
heating in a biphasic reaction system with a range of organic
solvents. Fructose and inulin were especially effective for
10 production of this valuable bio-platform molecule, with yields
of >70% obtained in 15 minutes under microwave heating.
Yields from cellulose were dramatically increased with ball
mill pre-treatment, this being associated with a reduction in
polysaccharide crystallinity.
15 The need for the chemical and associated industries to move
away from unsustainable fossil derived building block molecules
to those sourced from biomass is well documented and
extensively discussed.1,2 A key step in this progression from
fossil to bio-derived chemicals and materials is the establishment
20 of a range of simple, yet functional, bio-platform molecules, from
which more complex compounds and materials can be produced.3
These bio-platform molecules must be sustainably and cheaply
produced from biomass, avoiding competition with food
production and ideally be sourced from the waste streams (e.g.
25 orange peel, waste paper and bagasse), while their production
must also incorporate green chemistry techniques.4 Both
pyrolysis and fermentations are currently utilised for the
production of chemicals from biomass, though both have
disadvantages. Pyrolysis is limited due to the complexity of the
30 chemical mixture produced, while fermentation requires biomass
pre-treatment, the addition of nutrients and difficult recovery of
the molecules from the broth.5 Recent research has demonstrated
the potential to selectively produce 5-chloromethyl furfural
(CMF) from a range of carbohydrate sources, opening the door to
35 a new multifunctional bio-platform molecule of great potential
value.6-8 CMF can be converted to numerous valuable furan
moieties by means of oxidation, reduction and aldol additions,
while synthesis of various levulinate esters has also been
demonstrated (Figure 1).9-11
60
65
70
Figure 1 5-chloromethyl furfural (CMF) as
75 molecule
a bio-platform
During the study we investigated the potential to utilise a range of
carbohydrate sources, both sugars and polysaccharides (Figure 2),
for production of CMF. When using fructose under the standard
80 reaction protocol (entry 1a, Table 1) a yield of 71% and a
selectivity of 98% was achieved in just 15 minutes microwave
heating. Doubling the loading of fructose (entry 1b) resulted in
only a slight reduction in yield (66%) while maintaining the
excellent selectivity of the reaction (98%). This yield was further
85 increased by lowering the reaction temperature and time (entry
1c), with a yield of 85% obtained in 10 minutes at 70 °C.
Conventional heating for the same loading (entry 1d) gave both a
drop in yield (75%) and selectivity (96%). When using glucose
(entry 2) under microwave activation the yield of CMF dropped,
90 in comparison to fructose under the same conditions (entry 1a, 15
minutes, 70 °C), to 37%, though the excellent selectivity
40
Typically, production of CMF utilises a conventionally heated
biphasic reaction medium, where concentrated HCl is used for
dissolution, hydrolysis, dehydration and halogenation of the
carbohydrate, yielding CMF. The CMF rapidly passes into the
45 organic layer of the biphasic system. Evident from this reaction
protocol described above is the desire to selectively heat the
concentrated acid layer where the reactions takes place, while
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remained. We believed this difference in yield was a result of the
6-membered ring pyranose configuration of the glucose requiring
conversion to the 5-membered furanose before dehydration to the 50 dissolution and resulting in a significant increase in the rate of
>90%. Evidently, decreasing crystallinity of the cellulose allowed
greater access into the polysaccharide structure, increasing
furan could occur, while the fructose, already in the furanose
form, could undergo rapid conversion to the furan.
conversion to CMF. During Mascal’s initial work using
conventional heating a comparable reaction set-up (65 °C, 5%wt
cellulose loading) produced a similar yield, 71%, to our ball mill
pre-treated microwave reaction, but with a reaction time of 30
55 hours (18 + 12 hours) compared to just 155 minutes for our
combined ball milling and microwave methodology.6 A later
iteration of Mascal’s conventional thermal heating method
produced CMF in an 84% yield from microcrystalline cellulose in
a reaction time of 3 hours, this approaching the time required for
60 methodology. 5-hydroxymethyl furfural (HMF) was also
investigated as a starting material, and was found to rapidly
convert to CMF (87%, entry 5), with only CMF isolated from the
organic layer.
5
10
15
Figure 2 Carbohydrates used for CMF production
65
70
75
Entry
1a
1b
1c
1d
2
Carbohydrate
Fructose
Fructose
Fructose
Fructose
Glucose
Inulin
Cellulose
Cellulose
Cellulose
HMF
% Isolated Yield
71%
% Selectivity
98%
66%
85%
75%
39%
70%
5%
12%
24%
98%
98%
96%
>99%
98%
>99%
98%
>99%
>99%
3
4a
4b
4c
5
87%
Figure 3 Effect of extended reaction duration on the recovered
%yield of CMF from microcrystalline cellulose. 250 mg
cellulose, 5 ml conc. HCl, 6x10 ml DCE, MW 80 °C, 6x15
80 minutes
Table 1 CMF synthesis from a range of carbohydrates. 250 mg
20 carbohydrate, 5 ml conc. HCl, 10 ml DCE, 80 °C, 15 minutes. 1b:
carbohydrate amount increased to 500 mg. 1c: 500 mg fructose,
70 °C, 10 minutes. 1d: same conditions as 1c but conventionally
heated, 4b: 80 °C, 45 minutes. 4c: 80 °C, 3x15 minutes, 3x10 ml
DCE.
Entry
Ball milling /
% Isolated Yield
% Selectivity
mins
0
20
50
110
25
6a
6b
6c
6d
24%
35%
43%
71%
>99%
91%
95%
93%
Mascal highlighted in his research the importance of utilising
non-food carbohydrates for the production of CMF, thus we
wished to demonstrate the use of polysaccharides in our
microwave assisted synthesis. When using the polyfructan inulin
30 (entry 3) a 70% yield, with 98% selectivity, was achieved under
standard reaction conditions, this being almost identical to that
achieved for fructose under the same conditions (71%). When
using microcrystalline cellulose, under the same conditions, the
yield dropped significantly to just 5%. Longer reaction times (45
35 minutes, 4b) and fresh DCE used at 15 minute intervals (4c)
increased isolated yields of CMF from cellulose, though only up
to 24%. Extending the number of washes further increased yields,
Table 2 Effect of ball milling of microcrystalline cellulose on
the yield and selectivity of CMF formation. 250 mg cellulose, 5
ml conc. HCl, 3x10 ml DCE, MW 80 °C, 3x15 minutes
85
The above reactions, and those discussed in the literature, all use
1,2-dichloroethane, a solvent with serious health and safety
concerns. As such we investigated the potential to use alternative
solvents for our microwave assisted methodology, with the
with a maximum of 58% achieved after 90 minutes (6x15 90 results for a range of solvents shown in Table 3. Using the lower
minutes, Figure 3).
boiling point halogentated solvents, chloroform and DCM, led to
a drop in yield, though the high selectivity remained. Cyclopentyl
methyl ether (CPME), toluene and cyclohexane (entries 10-12)
all gave good isolated yields, but in all cases residual solvent
40
It is known that the crystalline nature of cellulose can impact
greatly on its reactivity as high crystallinity limits penetration of
solvents and reactants, and that the level of crystallinity can be 95 lowered the final CMF purity. Of the alternative solvents
reduced by pre-treatment such as ball milling.13-16 Ball mill pre-
45 treatment of the microcrystalline cellulose prior to reaction in the
microwave significantly improved CMF yield, up to 71% with
110 minutes milling pre-treatment, while maintaining selectivities
investigated cyclohexane (entry 12a) showed the greatest promise
and is our current solvent of choice, and showed a significant
improvement in yield under microwave heating compared to
conventional heating (entry 12b, 42%). Para-cymene, α-pinene,
2
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tbutylacetate and 2,5-dimethylfuran were also investigated as
alternative solvents, though in all cases yields were low (<50%)
setting and a typical ramp time of 2 minutes. After microwave
heating the reaction mixture was passed into a separating funnel
with extensive by-product formation, typically from solvent 50 and the lower organic layer collected, filtered and the DCE
degradation.
removed in vacou yielding a light brown oil (143 mg, 71% yield,
98% purity by GC). H NMR (CDCl3, 400 MHz): 4.59 (s, 2 H,
1
5
CH2), 6.55 (d, J = 3.6 Hz, 1 H, Ar-H), 7.16 (d, J = 3.6 Hz, 1 H,
Ar-H), 9.58 (s, 1 H, CHO) ppm. 13C NMR (CDCl3, 100 MHz):
55 36.6 (CH2), 112.1, 121.9 (Ar), 152.9 (Ar), 156.1 (Ar), 177.8
(CHO) ppm. Spectroscopic data are in agreement with the
literature.17 Purity of the isolated product was determined by GC-
FID and peaks assigned using GC-MS. Ball mill pre-treatment
was performed in a Retsch PM-400. Conventional heating studies
60 were performed in 35 ml CEM microwave tubes, charged with
reagents, and placed into a pre-heated water-bath for the allotted
time. See supplementary information for further experimental
details.
Entry
Solvent
% Isolated Yield
85%
% Purity (GC)
98%
7
8
9
10
11
12a
12b
DCE
chloroform
DCM
CPME
toluene
58%
61%
70%
68%
75%
42%
98%
98%
88%
74%
91%
98%
cyclohexane
cyclohexane
Table 3 CMF synthesis in a range of solvents. 500 mg fructose,
5 ml conc. HCl, 10 ml solvent, 70 °C, 10 minutes. 12b:
conventional heating in pre-heated water bath.
Notes and references
10 The excellent selectivity observed throughout this investigation
was likely a result of the microwave energy selectivity heating
the acid layer of the biphasic layer based on the difference in
dissipation factors for this and the organic layer. In previous
investigations into formation of CMF using conventional heating
15 levulinic acid is formed as a by-product typically in 5-10%
yields, however we did not observe this in any cases during our
investigation of microwave heating.
65 a Green Chemistry Centre of Excellence, Department of Chemistry,
University of York, Heslington, York, United Kingdom, YO10 5DD. Fax:
+44 (0) 1904 322705; Tel: +44 (0) 1904 322568; E-mail:
duncan.macquarrie@york.ac.uk
b ENSICAEN, 6 boulevard Maréchal Juin, 14050 CAEN Cedex 04,
70 France
c ESCOM, 1 allée du réseau Jean-Marie Buckmaster, 60200 Compiegne,
France
† Electronic Supplementary Information (ESI) available: Further
information regarding experimental procedures including ball-mill
75 pretreatment, conventional heating and sample analysis. See
DOI: 10.1039/b000000x/
Conclusions
We have demonstrated the simple, rapid and selective synthesis
20 of CMF from a range of carbohydrates using a biphasic reaction
mixture and microwave heating. The excellent selectivity
observed in comparison to earlier syntheses of this molecule is
attributed to the selective microwave heating of the acidic
aqueous layer while avoiding excessive heating of the relatively
25 microwave transparent DCE layer. The impressive yield obtained
from inulin is a particular highlight as this demonstrates the
ability to use a non-food polysaccharide for formation of an
interesting and valuable bio-platform molecule in extremely high
yields and selectivities. Ball mill pre-treatment of
30 microcrystalline cellulose resulted in a three-fold increase of
CMF yield, demonstrating the detrimental effect high crystallinity
of cellulose can have for its application in CMF syntheses.
1
2
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Experimental Procedure
α-D-Glucose, α-D-fructose, microcrystalline cellulose and inulin
35 were purchased from Sigma-Aldrich. 1,2-dichloroethane was
purchased from Fluka Chemicals. Concentrated hydrochloric acid
(S.G. 1.19, ~37%) was purchased from Fisher Scientific. All
chemicals were used as supplied, with the exception of the
experiments using ball milling pre-treatment of the
40 microcrystalline cellulose. Typical experimental procedure for
microwave reaction: 250 mg of fructose was charged into a 35 ml
CEM microwave reactor vessel with a magnetic stirrer bar. To
this 10 ml of 1,2-dichloroethane and 5 ml concentrated HCl were
added. The reaction vessel was sealed with a rubber lid (CEM)
45 and placed in A CEM Discover SP Microwave Synthesiser. A
fixed temperature method protocol with 15 minute hold time at
80 °C and high stirring speed was used, with a 200 W max power
12 M. Brasholz, K. von Kanel, C. H. Hornung, S. Saubern, J.
Tsanaktsidis, Green Chem., 2011, 13, 1114.
95 13 G. Maier, P. Zipper, M. Stubicar, J. Schurz, Cellul. Chem. Technol.,
2005, 39, 167.
14 N. Mosier, C. Wyman, B. Dale, R. Elander, Y. Y. Lee, M.
Holtzapple, M. Ladisch, Bioresour. Technol., 2005, 96, 673.
15 P. Alvira, E. Tomas-Pejo, M. Ballesteros, M. J. Negro, Bioresour.
100
Technol., 2010, 101, 4851.
16 Z. D. Liao, Z. Q. Huang, H. Y. Hu, Y. J. Zhang, Y. F. Tan,
Bioresour. Technol., 2011, 102, 7953.
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