U.S. patent application number 12/420757 was filed with the patent office on 2009-12-24 for production of hydroxymethylfurfural.
This patent application is currently assigned to Agency for Science, Technology and Research. Invention is credited to Jin Y.G. Chan, Yugen ZHANG.
Application Number | 20090313889 12/420757 |
Document ID | / |
Family ID | 41429804 |
Filed Date | 2009-12-24 |
United States Patent
Application |
20090313889 |
Kind Code |
A1 |
ZHANG; Yugen ; et
al. |
December 24, 2009 |
PRODUCTION OF HYDROXYMETHYLFURFURAL
Abstract
The invention provides a process for making
hydroxymethylfurfural. A reaction mixture comprising a saccharide
and a metal complex of an N-heterocyclic carbene is initially
provided. The saccharide is then allowed to react at about
70.degree. C. or below to form hydroxymethylfurfural. The
saccharide may be a hexose or a mixture of hexoses, or a dimer,
oligomer or polymer or copolymer of a hexose or a mixture
thereof.
Inventors: |
ZHANG; Yugen; (Singapore,
SG) ; Chan; Jin Y.G.; (Singapore, SG) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER, EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Assignee: |
Agency for Science, Technology and
Research
Singapore
SG
|
Family ID: |
41429804 |
Appl. No.: |
12/420757 |
Filed: |
April 8, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
PCT/SG2008/000215 |
Jun 18, 2008 |
|
|
|
12420757 |
|
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Current U.S.
Class: |
44/350 ;
549/488 |
Current CPC
Class: |
B01J 2231/70 20130101;
Y02P 30/20 20151101; Y02P 20/582 20151101; C10G 2300/1014 20130101;
B01J 2531/62 20130101; C10G 2300/44 20130101; B01J 31/2269
20130101; B01J 31/2273 20130101; C10G 2300/1011 20130101; C07D
307/50 20130101 |
Class at
Publication: |
44/350 ;
549/488 |
International
Class: |
C10L 1/18 20060101
C10L001/18; C07D 307/48 20060101 C07D307/48 |
Claims
1. A process for making hydroxymethylfurfural comprising: (i)
providing a reaction mixture comprising a saccharide and a metal
complex of an N-heterocyclic carbene wherein said saccharide is a
hexose or a mixture of hexoses, or a dimer, oligomer or polymer or
copolymer of a hexose or a mixture thereof; and (ii) allowing the
saccharide to react in the reaction mixture to form
hydroxymethylfurfural; wherein steps (i) and (ii) are conducted at
about 70.degree. C. or below.
2. The process of claim 1 wherein the saccharide comprises a
monosaccharide.
3. The process of claim 2 wherein the monosaccharide comprises
fructose, glucose or a mixture of these.
4. The process of claim 1 wherein the reaction mixture additionally
comprises an ionic liquid.
5. The process of claim 4 wherein during step (ii) the reaction
mixture is continuously or intermittently contacted with a solvent
for hydroxymethylfurfural, said solvent being immiscible with the
ionic liquid, so as to extract the hydroxymethylfurfural into the
solvent.
6. The process of claim 4 wherein the reaction mixture is contacted
with a solvent for hydroxymethylfurfural after step (ii), said
solvent being immiscible with the ionic liquid, so as to extract
the hydroxymethylfurfural into the solvent.
7. The process of claim 1 wherein the metal complex of the
N-heterocyclic carbene is a metal complex of a monomeric
N-heterocyclic carbene.
8. The process of claim 7 wherein the metal complex of the
N-heterocyclic carbene is a metal complex of an imidazol-2-ylidene
or of an imidazolin-2-ylidine.
9. The process of claim 1 wherein the metal complex is selected
from the group consisting of a tungsten complex, a titanium
complex, a zirconium complex, a ruthenium complex and a mixture of
any two or more of these types of complex.
10. The process of claim 9 wherein the metal complex is a tungsten
complex of an imidazol-2-ylidene or of an imidazolin-2-ylidine.
11. The process of claim 1 comprising the step of generating the
metal complex of the N-heterocyclic carbene.
12. The process of claim 11 wherein the step of generating the
metal complex of the N-heterocyclic carbene comprises reacting a
nitrogen heterocycle salt with a base in the presence of a salt of
the metal.
13. The process of claim 12 wherein the base is potassium
t-butoxide.
14. The process of claim 11 comprising removing a solvent in which
said step of generating is conducted, said removing being conducted
after said generating.
15. The process of claim 1, said process being a continuous
reaction.
16. The process of claim 1 wherein the metal complex of the
N-heterocyclic carbene is recycled following removal of the
hydroxymethylfurfural from the reaction mixture.
17. The process of claim 4 wherein the ionic liquid is reused
following removal of the hydroxymethylfurfural from the reaction
mixture.
18. A process for making a fuel comprising: (i) providing a
reaction mixture comprising a saccharide and a metal complex of an
N-heterocyclic carbene wherein said saccharide is a hexose or a
mixture of hexoses, or a dimer, oligomer or polymer or copolymer of
a hexose or a mixture thereof; (ii) allowing the saccharide to
react in the reaction mixture to form hydroxymethylfurfural; and
(iii) converting the hydroxymethylfurfural to the fuel; wherein
steps (i) and (ii) are conducted at about 70.degree. C. or
below.
19. The process of claim 18 comprising the step of separating the
hydroxymethylfurfural from the reaction mixture prior to step
(iii).
20. The process of claims 18 wherein the metal complex of the
N-heterocyclic carbene is a tungsten complex of an
imidazol-2-ylidene or of an imidazolin-2-ylidine.
Description
TECHNICAL FIELD
[0001] The present invention relates to a method of producing
hydroxymethylfurfural.
BACKGROUND OF THE INVENTION
[0002] The present consumption of fossil fuels has led to
significant levels of environmental pollution and rapidly
diminishing petrochemical reserves. The diminishing fossil fuel
reserves and the globe warming effects have become major concerns.
The search for sustainable, alternative energy is of critical
importance.
[0003] Biofuels are highly attractive as the only sustainable
source of liquid fuels currently. However, the replacement of
petroleum feedstock by biomass is limited by the lack of highly
efficient methods to selectively convert carbohydrates to chemical
compounds for the biofuel production. A practical catalytic process
that can transform the abundant biomass into versatile chemicals
would also provide the chemical industry with renewable feedstocks.
Biomass-derived carbohydrates represent a promising carbon-based
alternative as an energy source and a sustainable chemical
feedstock. However, more efficient processes need to be developed
for the selective conversion of carbohydrates into useful organic
intermediates.
[0004] Substantial efforts have been recently devoted towards
converting biomass to 5-hydroxymethylfurfural (HMF), a versatile
and key intermediate in biofuel chemistry and petrochemical
industry. HMF production from sugars has been successfully
conducted in water, aprotic solvents (e.g. dimethylsulfoxide
(DMSO)), and biphasic systems using acid catalysts such as mineral
acids and solid acids. Ionic liquids have been used as solvents for
this conversion using metal salts and other catalysts. However, the
large-scale production of HMF is still impeded by the lack of
cost-effective synthesis methods. The water-methyl isobutyl ketone
(MIBK) biphasic system developed by Dumesic et al. has a great
potential for industrial applications [(a) Y. Roman-Leshkov, J. N.
Chheda, J. A. Dumesic, Science 2006, 312, 1933; (b) J. N. Chheda,
Y. Roman-Leshkov, J. A. Dumesic, Green Chem. 2007, 9, 342; (c) G.
W. Huber, J. N. Chheda, C. J. Barrett, J. A. Dumesic, Science 2005,
308, 1446; (d) R. M. West, Z. Y. Liu, M. Peter, C. A. Gartner, J.
A. Dumesic, J. Mol. Catal. A Chem. 2008, 296, 18]. However, the
strongly acidic conditions and the high reaction temperature result
in significant material replacement costs and energy
consumption.
[0005] It has been demonstrated that transition metals are good
catalysts for the transformation of sugars to HMF in ionic liquids.
However, the product extraction and system recovery processes still
suffer from low efficiencies.
[0006] Recently, much effort has been devoted towards converting
biomass to 5-hydroxymethylfurfural (HMF), a versatile and key
intermediate in biofuel chemistry and petroleum industry. HMF and
its 2,5-disubstituted furan derivatives can replace key
petroleum-based building blocks. There are currently a number of
catalysts that are active towards the dehydration of sugars to form
HMF. However, most of them promote side-reactions that form
undesired by-products and further rehydration of HMF to form
levulinic acid and formic acid. They are also often limited to
simple sugar feedstock, such as fructose.
[0007] Recent reports illustrate the use of 1-H-3-methyl
imidazolium chloride (HMIM.sup.+Cl.sup.-) as a solvent and an acid
catalyst to efficiently convert fructose to HMF with about 90%
yield. However, such system has not be shown to convert glucose,
which is a more stable and abundant sugar source. Dumesic's group
has developed a two-phase system (aqueous/organic phases) for the
separation and stabilization of HMF product((a) Y. Roman-Leshkov,
J. N. Chheda, J. A. Dumesic, Science 2006, 312, 1933; (b) J. N.
Chheda, Y. Roman-Leshkov, J. A. Dumesic, Green Chem. 2007, 9, 342).
Zhang's group has reported a metal chloride/ionic liquid system
that gives moderate to good HMF yields for both fructose (83% with
Pt or Rh chloride, 65% with CrCl.sub.2) and glucose (a record high
of 68% with CrCl.sub.2) (H. Zhao, J. E. Holladay, H. Brown, Z. C.
Zhang, Science 2007, 316, 1597).
[0008] There is a need for an improved method for converting both
fructose and glucose to HMF in good to excellent yields, for
example over about 80%. There is also a need for an improved method
for converting other saccharides to HMF. There is also a need for a
method for converting readily available saccharides into HMF at
moderate temperatures, preferably at temperatures below the normal
boiling point of suitable extraction solvents.
OBJECT OF THE INVENTION
[0009] It is an object of the present invention to substantially
overcome or at least ameliorate one or more of the above
disadvantages. It is a further object to at least partially satisfy
at least one of the above needs.
SUMMARY OF THE INVENTION
[0010] In a first aspect of the invention there is provided a
process for making hydroxymethylfurfural comprising exposing a
saccharide to a metal complex of an N-heterocyclic carbene.
[0011] The following options may be used in conjunction with the
first aspect, either individually or in any suitable
combination.
[0012] The saccharide may comprise a monosaccharide. It may
comprise a disaccharide. It may comprise an oligosaccharide. It may
comprise a polysaccharide. It may comprise (or may be) a mixture of
any two or more of these. The monosaccharide may comprise fructose,
glucose or a mixture of these. The disaccharide may be sucrose.
[0013] The exposing may be conducted in a dipolar aprotic solvent.
The solvent may be, or may comprise, an ionic liquid. The ionic
liquid may be, or may comprise, an imidazolium salt (e.g. halide,
for example chloride). It may be, or may comprise,
1-butyl-3-methylimidazolium chloride.
[0014] The metal complex may be a transition metal complex. It may
be a chromium complex or a titanium complex or a tungsten complex
or a molybdenum complex or a nickel complex or a palladium complex
or a ruthenium complex or an aluminium complex, or it may be a
mixture of any two or more of these. It may be a CrII complex or a
CrIII complex.
[0015] The N-heterocyclic carbene may be monomeric. It may be
dimeric. It may be oligomeric. It may be polymeric. The metal
complex of the N-heterocyclic carbene may be a metal complex of an
N-imidazole carbene for example a metal complex of a monomeric
N-imidazole carbene or of a polymeric N-imidazole carbene.
[0016] The process may also comprise the step of generating the
metal complex of the N-heterocyclic carbene. The step of generating
the metal complex of the N-heterocyclic carbene may comprise
reacting a nitrogen heterocycle salt with a base in the presence of
a salt of the metal. The base may be potassium t-butoxide.
[0017] The process may additionally comprise isolating the
hydroxymethyl furfural.
[0018] The monosaccharide may be fructose and the yield of
hydroxymethyl furfural may be greater than about 80%. The
monosaccharide may be glucose and the yield of hydroxymethyl
furfural may be greater than about 70%.
[0019] The metal complex of an N-heterocyclic carbene may be
recycled following removal of the hydroxymethylfurfural from the
reaction mixture. In the event that the exposing is conducted in an
ionic liquid, said ionic liquid may be recycled following removal
of the hydroxymethylfurfural from the reaction mixture. The
recycling may comprise heating the reaction mixture following
removal of the hydroxymethylfurfural therefrom for sufficient time
to remove volatile substances therefrom.
[0020] In one embodiment there is provided a process for making
hydroxymethylfurfural comprising exposing fructose, glucose or a
mixture of these to a chromium complex of an N-heterocyclic carbene
in an ionic liquid.
[0021] In another embodiment there is provided a process for making
hydroxymethylfurfural comprising: [0022] generating a chromium
complex of an N-heterocyclic carbene; and [0023] exposing fructose,
glucose or a mixture of these to the chromium complex of the
N-heterocyclic carbene in an ionic liquid.
[0024] In another embodiment there is provided a process for making
hydroxymethylfurfural comprising: [0025] reacting a nitrogen
heterocycle with a base in the presence of a chromium salt so as to
generate a chromium complex of an N-heterocyclic carbene; and
[0026] exposing fructose, glucose or a mixture of these to the
chromium complex of the N-heterocyclic carbene in an ionic
liquid.
[0027] The invention also provides hydroxymethyl furfural when made
by the process of the first aspect.
[0028] In a second aspect of the invention there is provided use of
a metal complex of an N-heterocyclic carbene for making
hydroxymethyl furfural.
[0029] In a third aspect of the invention there is provided use of
hydroxymethylfurfural made by the process of the first aspect for
producing a fuel, e.g. a biofuel.
[0030] In a fourth aspect of the invention there is provided a
biofuel made using hydroxymethylfurfural which has been made by the
process of the first aspect.
[0031] In a fifth aspect of the invention there is provided a
process for making hydroxymethylfurfural comprising: [0032] (i)
providing a reaction mixture comprising a saccharide and a metal
complex of an N-heterocyclic carbene wherein said saccharide is a
hexose or a mixture of hexoses, or a dimer, oligomer or polymer or
copolymer of a hexose or a mixture thereof, and
[0033] (ii) allowing the saccharide to react in the reaction
mixture to form hydroxymethylfurfural
wherein steps (i) and (ii) are conducted at about 70.degree. C. or
below.
[0034] The following options may be used in conjunction with the
fifth aspect, either individually or in any suitable
combination.
[0035] The saccharide may comprise a monosaccharide. The
monosaccharide may comprise fructose, glucose or a mixture of
these.
[0036] The reaction mixture may additionally comprise an ionic
liquid. The ionic liquid may be a solvent for the saccharide or for
the metal complex or for both. The saccharide may be in solution in
the ionic liquid. The metal complex may be in solution in the ionic
liquid.
[0037] The process may be conducted as a two-phase process. The
process may be conducted such that, during step (ii), the reaction
mixture is continuously contacted with a solvent for
hydroxymethylfurfural, or such that, during step (ii), the reaction
mixture is intermittently contacted with a solvent for
hydroxymethylfurfural. Commonly the solvent is immiscible, or
substantially immiscible, with the ionic liquid. This may therefore
serve to extract the hydroxymethylfurfural into the solvent.
[0038] The reaction mixture may be contacted with a solvent for
hydroxymethylfurfural after step (ii). In this case also the
solvent may be immiscible, or substantially immiscible, with the
ionic liquid. Thus this may also serve to extract the
hydroxymethylfurfural into the solvent.
[0039] The metal complex of the N-heterocyclic carbene may be a
metal complex of a monomeric N-heterocyclic carbene. It may be a
metal complex of an imidazol-2-ylidene or of an
imidazolin-2-ylidine.
[0040] The metal complex may be a tungsten complex, a titanium
complex, a zirconium complex, a ruthenium complex or a mixture of
any two or more of these types of complex. It may be for example a
tungsten complex of an imidazol-2-ylidene or of an
imidazolin-2-ylidine.
[0041] The process may comprise the step of generating the metal
complex of the N-heterocyclic carbene. This step may comprise
reacting a nitrogen heterocycle salt with a base in the presence of
a salt of the metal. The base may be for example potassium
t-butoxide. The process may comprise removing a solvent in which
said step of generating is conducted, said removing being conducted
after said generating. In this case the reaction mixture may be
made using the resulting dried metal complex of the N-heterocyclic
carbene. Alternatively the solvent may not be removed, and the
reaction mixture may be made using a solution of the metal complex
of the N-heterocyclic carbene in the solvent.
[0042] The process may be conducted as a continuous reaction. It
may be conducted as a continuous batch reaction.
[0043] The metal complex of the N-heterocyclic carbene may be
recycled following removal of the hydroxymethylfurfural from the
reaction mixture. The ionic liquid (if present) may be reused
following removal of the hydroxymethylfurfural from the reaction
mixture.
[0044] The process may be conducted under non-acidic conditions. It
may be conducted at approximately neutral pH. It may be conducted
under basic conditions. It may be conducted under substantially
non-aqueous conditions. In this context "non-aqueous" should be
taken to indicate simply that water is not intentionally added as a
solvent. It will be recognised that small amounts of water may
nevertheless be present in a process as described herein.
[0045] In an embodiment, there is provided a process for making
hydroxymethylfurfural comprising: [0046] (i) providing a reaction
mixture comprising a saccharide and a metal complex of a
1,3-disubstituted imidazol-2-ylidine in an ionic liquid, wherein
said saccharide is fructose, glucose or a mixture of these; and
[0047] (ii) allowing the saccharide to react in the reaction
mixture to form hydroxymethylfurfural, wherein steps (i) and (ii)
are conducted at about 70.degree. C. or below and wherein the metal
complex is selected from the group consisting of a tungsten
complex, a titanium complex, a zirconium complex, a ruthenium
complex and a mixture of any two or more of these types of
complex.
[0048] In another embodiment, there is provided a process for
making hydroxymethylfurfural comprising: [0049] (i) reacting an
N,N'-disubstituted imidazolium salt with a base in the presence of
a salt of a metal, said metal being selected from the group
consisting of tungsten, titanium, zirconium, ruthenium and a
mixture of any two or more of these, so as to produce a complex of
the metal with a 1,3-disubstituted imidazol-2-ylidine derived from
said N,N'-disubstituted imidazolium salt; [0050] (ii) providing a
reaction mixture comprising a saccharide and the metal complex of
the 1,3-disubstituted imidazol-2-ylidine in an ionic liquid,
wherein said saccharide is fructose, glucose or a mixture of these;
and [0051] (iii) allowing the saccharide to react in the reaction
mixture to form hydroxymethylfurfural, wherein steps (ii) and (iii)
are conducted at about 70.degree. C. or below.
[0052] In another embodiment there is provided a process for making
hydroxymethylfurfural comprising: [0053] (i) providing a reaction
mixture comprising a saccharide and a metal complex of an
N-heterocyclic carbene in an ionic liquid, wherein said saccharide
is a hexose or a mixture of hexoses, or a dimer, oligomer or
polymer or copolymer of a hexose or a mixture thereof and wherein
said first and second solvents are sufficiently immiscible that the
reaction mixture is a two phase reaction mixture; and [0054] (ii)
allowing the saccharide to react in the reaction mixture to form
hydroxymethylfurfural while continuously or intermittently
contacting the reaction mixture with a solvent for
hydroxymethylfurfural, said solvent being immiscible with the ionic
liquid; wherein steps (i) and (ii) are conducted at about
70.degree. C. or below. In this embodiment, the metal may be
selected from the group consisting of tungsten, titanium,
zirconium, ruthenium and a mixture of any two or more of these. It
may be for example tungsten, in which case steps (i) and (ii) may
be conducted at about 50.degree. C.
[0055] In another embodiment, there is provided a process for
making hydroxymethylfurfural comprising: [0056] (i) reacting an
N,N'-disubstituted imidazolium salt with a base in the presence of
a salt of a metal, said metal being selected from the group
consisting of tungsten, titanium, zirconium, ruthenium and a
mixture of any two or more of these, so as to produce a complex of
the metal with a 1,3-disubstituted imidazol-2-ylidine derived from
said N,N'-disubstituted imidazolium salt; [0057] (ii) providing a
reaction mixture comprising a saccharide and the metal complex of
the 1,3-disubstituted imidazol-2-ylidine in an ionic liquid,
wherein said saccharide is fructose, glucose or a mixture of these;
and [0058] (iii) allowing the saccharide to react in the reaction
mixture to form hydroxymethylfurfural while continuously or
intermittently contacting the reaction mixture with a solvent for
hydroxymethylfurfural, said solvent being immiscible with the ionic
liquid, wherein steps (ii) and (iii) are conducted at about
70.degree. C. or below.
[0059] In another embodiment, there is provided a process for
making hydroxymethylfurfural comprising: [0060] (i) reacting an
N,N'-disubstituted imidazolium salt with a base in the presence of
a tungsten salt so as to produce a tungsten complex of a
1,3-disubstituted imidazol-2-ylidine derived from said
N,N'-disubstituted imidazolium salt; [0061] (ii) providing a
reaction mixture comprising a saccharide and the tungsten complex
of the 1,3-disubstituted imidazol-2-ylidine in an ionic liquid,
wherein said saccharide is fructose, glucose or a mixture of these;
and [0062] (iii) allowing the saccharide to react in the reaction
mixture to form hydroxymethylfurfural while continuously or
intermittently contacting the reaction mixture with a solvent for
hydroxymethylfurfural, said solvent being immiscible with the ionic
liquid, wherein steps (ii) and (iii) are conducted at about
50.degree. C.
[0063] In a sixth aspect of the invention there is provided a
process for making a fuel comprising: [0064] (i) providing a
reaction mixture comprising a saccharide and a metal complex of an
N-heterocyclic carbene wherein said saccharide is a hexose or a
mixture of hexoses, or a dimer, oligomer or polymer or copolymer of
a hexose or a mixture thereof, [0065] (ii) allowing the saccharide
to react in the reaction mixture to form hydroxymethylfurfural; and
[0066] (iii) converting the hydroxymethylfurfural to the fuel;
wherein steps (i) and (ii) are conducted at about 70.degree. C. or
below.
[0067] The process may comprise the step of separating the
hydroxymethylfurfural from the reaction mixture prior to step
(iii). The metal complex of an N-heterocyclic carbene may be for
example a tungsten complex of an imidazol-2-ylidene or of an
imidazolin-2-ylidine.
BRIEF DESCRIPTION OF THE DRAWINGS
[0068] A preferred embodiment of the present invention will now be
described, by way of an example only, with reference to the
accompanying drawings wherein:
[0069] FIG. 1 is a graph showing the effect of reaction temperature
on HMF yield from (.box-solid.) fructose and (.diamond-solid.)
glucose over 9 mol % of 6-CrCl.sub.2 (substrate/BMIM weight
ratio=0.2, 6 h);
[0070] FIG. 2 is a graph showing the effect of reaction time on HMF
yield from (.box-solid.) fructose and (.diamond-solid.) glucose
over 9 mol % of 6-CrCl.sub.2 (substrate/BMIM weight ratio=0.2,
100.degree. C.);
[0071] FIG. 3 is a graph showing the effect of 6-CrCl.sub.2 loading
on HMF yield from (.box-solid.) fructose and (.diamond-solid.)
glucose (substrate/BMIM weight ratio=0.2, 6 h, 100.degree. C.);
[0072] FIG. 4 is a graph showing the effect of substrate loading on
HMF yield from (.box-solid.) fructose and (.diamond-solid.) glucose
over 9 mol % of 6-CrCl.sub.2 (6 h, 100.degree. C.);
[0073] FIG. 5 is an XPS spectrum of the reaction intermediate of
6-CrCl.sub.2;
[0074] FIG. 6 shows a graph of: (.box-solid.) Fructose conversion,
( ) HMF yield, and () sum of fructose and HMF masses as a function
of time for fructose dehydration (dashed curve)--reaction
conditions: 0.05 mmol of Ipr-WCl.sub.6, 500 mg of BMIMCl, 100 mg of
fructose, 50.degree. C.;
[0075] FIG. 7 shows a schematic of (A) batch process, and (B)
continuous batch process, for fructose conversion to HMF in the
THF-BMIMCl biphasic system; and
[0076] FIG. 8 is a graph showing HMF yield from the continuous
batch process using the THF-BMIMCl biphasic system--reaction
conditions for the first batch: 100 mg of fructose, 5 mol % of
Ipr-WCl.sub.6, 500 mg of BMIMCl, 10 ml of THF (refreshed 3 times),
50.degree. C., 6 h; 100 mg of fructose were added directly after 6
h for the subsequent batches.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0077] The inventors have found that N-heterocyclic carbene-metal
complexes are capable of catalysing the conversion of saccharides
such as glucose or fructose to hydroxymethylfurfural
(5-(hydroxymethyl)-2-furaldehyde; HMF). The reaction proceeds in
relatively high yield, particularly when an ionic liquid solvent is
employed. Mixtures of suitable saccharides may also be used. The
reaction may be used with monosaccharides (e.g. glucose, fructose),
disaccharides (e.g. sucrose), oligosaccharides or polysaccharides
(e.g. starch, cellulose). The saccharide may be a hexose or a
mixture of hexoses, or a dimer, oligomer or polymer or copolymer of
a hexose or a mixture thereof. The reaction described herein has
the advantage that it uses relatively inexpensive and/or readily
available substrates, which, in some cases, represent waste
materials. For example, 30% HMF yield was achieved by conversion of
cellulose according to the process of the invention. Polymeric NHC
based catalysts were found to provide slightly lower HMF yields
from fructose and glucose than their monomeric counterparts,
however the polymeric NHC based catalysts have the advantage of
better recyclability than the monomeric counterparts. The
N-heterocyclic carbene-metal complex may be used in conjunction
with an acid catalyst. The acid catalyst may be a heterogeneous
acid catalyst. It may be a solid heterogeneous acid catalyst. It
may for example be a zeolite. This may be particularly beneficial
in cases where the saccharide is a disaccharide, oligosaccharide or
polysaccharide. The process may comprise hydrolysis of the
disaccharide, oligosaccharide or polysaccharide. The hydrolysis may
be an in situ hydrolysis. It may be catalysed by the acid
catalyst.
[0078] Suitable solvents for the process are dipolar aprotic
solvents. The solvent may comprise, or may be, an ionic liquid. A
suitable ionic liquid is 1-butyl-3-methylimidazolium chloride.
Other imidazolium salts are also suitable. The counterion of the
imidazolium salt may be a halide, for example chloride. The solvent
may be a mixture of solvents, for example a mixture of dipolar
aprotic solvents. The solvent may comprise an ionic liquid together
with a different dipolar aprotic solvent (such as
dimethylformamide, dimethylsulfoxide, hexamethylphosphoramide etc.)
The solvent may primarily consist of the ionic liquid, e.g. greater
than about 50%, or greater than about 60, 70, 80 or 90% by weight
or volume.
[0079] The metal complex of the N-heterocyclic carbene may be a
metal complex of an N-imidazole carbene. It may be a chromium II or
chromium III complex of an N-heterocyclic carbene. The
N-heterocyclic carbene (NHC) may be derived from imidazolium salt,
or from a substituted imidazoliuim salt, in particular an
N,N'-disubstituted imidazolium salt. The imidazolium salt may be a
bisimidazolium salt, e.g. a pyridine bisimidazolium salt. The NHC
may be derived from an imidazolinium salt, or from a substituted
imidazolinium salt in particular an N,N'-disubstituted
imidazolinium salt. The imidazolinium salt may be a imidazolinium
salt, e.g. a pyridine imidazolinium salt. The NHC may be an
.alpha.,.alpha.'-dinitrogen carbon. Each of the a-nitrogen atoms
may be substituted. They may each, independently, be substituted
with a bulky group. They may both substituted with a bulky group
(optionally with the same bulky group). Suitable bulky groups are
t-butyl, neopentyl, 2,6-dimethylphenyl, 2,4,6-trimethylphenyl,
2,6-diisopropylphenyl, 2,4,6-triisopropylphenyl etc. The
substituents on the nitrogen atoms may be, independently, alkyl
groups or aryl groups or heteroaryl groups. Thus the NHC may be an
imidazol-2-ylidene. It may be an N,N'-disubstituted
imidazol-2-ylidine, i.e. a 1,3-disubstituted imidazol-2-ylidine. It
may be an imidazolin-2-ylidine. It may be an N,N'-disubstituted
imidazolin-2-ylidine, i.e. a 1,3-disubstituted
imidazolin-2-ylidine.
[0080] The metal complex of the N-heterocyclic carbene may be
soluble in the solvent (or in the reaction mixture) or it may be
insoluble therein. It may be used as a homogeneous catalyst or as a
heterogeneous catalyst. Particularly in the case of a polymeric
complex, it may be used as a heterogeneous catalyst. If the complex
is used as a heterogeneous catalyst, it may, optionally,
subsequently be removed from the reaction mixture by precipitation,
filtration, centrifugation or some combination of these. It may
then be reused in a subsequent reaction if desired. It may be
reused with a loss of catalytic activity of less than about 10%, or
less than about 5, 2 or 1%.
[0081] The metal complex of the N-heterocyclic carbene may be
generated from the corresponding nitrogen heterocycle salt by
reaction with a base in the presence of a salt of the metal. The
base may be potassium t-butoxide or some other strong base, for
example sodium hydride, potassium hydride, NaN(TMS).sub.2 etc. The
base may be a sufficiently strong base to be capable of converting
the nitrogen heterocycle salt to the corresponding N-heterocyclic
carbene. Thus for example to generate a metal complex of a
1,3-disubstituted imidazol-2-ylidine, the corresponding
1,3-disubstituted imidazolium salt may be treated with a strong
base in the presence of a salt of the metal. The nitrogen
heterocycle salt may be a halide, e.g. chloride, bromide or iodide,
or may have some other counterion. The salt of the metal may be a
halide, e.g. chloride, bromide or iodide, or may have some other
counterion. The counterion of the salt of the metal may be the same
as or different to the counterion of the nitrogen heterocycle salt.
The metal may be a transition metal. The metal may be chromium,
titanium, tungsten, molybdenum, nickel, palladium, ruthenium or
aluminium, or may be a mixture of any two or more of these. The
reaction may be conducted in a solvent. The solvent may be a
dipolar aprotic solvent. It may be a solvent that is not base
sensitive. It may be for example DMF, DMSO, HMPT, HMPA or some
other suitable solvent. It may be a solvent for the heterocycle
salt. It may be a solvent for the base. It may be a solvent for the
metal salt. It may be a solvent for the metal complex of the NHC.
It may be desirable to heat the reaction mixture in order to form
the metal complex of the NHC. In some cases heating may not be
used. Suitable temperatures are between about 20 and about
100.degree. C., or about 30 to 100, 50 to 100, 20 to 80, 20 to 50,
30 to 70, 50 to 80, 70 to 100 or 70 to 90.degree. C, e.g. about 20,
30, 40, 50, 60, 70, 80, 90 or 100.degree. C. The reaction may be
conducted for sufficient time for substantially complete
conversion. It may be conducted for about 1 to about 6 hours, or
about 1 to 3, 3 to 6 or 2 to 5 hours, e.g. about 1, 2, 3, 4, 5 or 6
hours. The temperature and time should be sufficient to form the
metal complex of the NHC.
[0082] In the process of the invention, the sugar (fructose and/or
sucrose) may be mixed with the solvent (e.g. ionic liquid). A
suitable ratio of sugar to solvent is about 20% w/w, or about 5 to
about 30%, or about 5 to 25, 5 to 20, 5 to 10, 10 to 30, 20 to 30,
10 to 25 or 15 to 25%, e.g. about 5, 10, 15, 20, 25 or 30%. In the
case of glucose as substrate, this may be as high as 50, 60, 70,
80, 90 or even 100% (e.g. may also be about 40, 50, 60, 70, 80, 90
or 100% w/w). The catalyst (metal-carbene complex) may then be
added. A suitable addition ratio may be about 1 to about 15 mol %
relative to the sugar, or about 1 to 10, 1 to 5, 5 to 15, 10 to 15,
5 to 10, 1 to3, 2 to 5 or 2 to 4%, e.g. about 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14 or 15 mol %. The addition ratio should be
sufficient to obtain an acceptable, optionally an optimal, yield of
product. The reaction may be conducted at a temperature of about 80
to about 120.degree. C., or about 80 to 100, 80 to 90, 90 to 120,
100 to 120 or 90 to 100.degree. C., e.g. about 80, 85, 90, 95, 100,
105, 110, 115 or 120.degree. C., or at some other suitable
temperature. The temperature may be selected so as to provide an
optimum yield or to obtain an acceptable yield. It may be selected
to provide a trade-off between poor yield and excessive by-product
formation. It may be selected to provide an acceptably low yield of
by-product. The reaction may be conducted for between about 2 and
about 10 hours, or about 2 to 8, 2 to 6, 4 to 10, 6 to 10, 4 to 8
or 5 to 7 hours, or about 2, 3, 4, 5, 6, 7, 8, 9 or 10 hours. The
time may depend on the temperature. The reaction may be conducted
under an inert atmosphere, e.g. nitrogen, carbon dioxide, helium,
neon, argon or a mixture of any two or more of these, or it may be
conducted in air or some other oxygen containing gas mixture. In
some cases it may be conducted under reduced pressure, e.g. an
absolute pressure of about 0.2 atmospheres or less, or about 0.1,
0.05, 0.02 or 0.01 atmospheres or less. In such cases at least some
byproducts may be removed as they are formed. This may enable
recycling of the metal complex of the N-heterocyclic carbene and/or
of the solvent without a separate step of removing the
volatiles.
[0083] The hydroxymethylfurfural product may be isolated from the
reaction mixture by known methods. These include solvent extraction
(e.g. diethyl ether extraction), water washing, column
chromatography, gas chromatography, hplc or a combination of any
two or more of these.
[0084] The reaction may be conducted using fructose as a substrate,
or glucose, or with a mixture of the two. If suitable conditions
are used (as described above), a yield of hydroxymethyl furfural
may be at least about 70%, or at least about 75, 80, 85 or 90%.
Commonly the yield from glucose and from glucose will be
different.
[0085] The metal complex of an N-heterocyclic carbene may be
recycled following removal of the hydroxymethylfurfural from the
reaction mixture. In particular, it may be reused in a subsequent
reaction, said subsequent reaction being the process for making
hydroxymethylfurfural described herein. This provides cost savings
in the process and can be achieved with little or no loss of yield
of hydroxymethyl furfural (e.g. less than about 5%, loss of yield,
or less than about 4, 3 or 2% loss of yield). In the event that the
exposing is conducted in an ionic liquid, the ionic liquid may also
be recycled. Commonly, the product hydroxymethylfurfural is removed
from the reaction mixture by solvent extraction (optionally
repeated solvent extraction). The reaction mixture (with the
hydroxymethyl furfural removed) may then be treated so as to remove
volatile materials (e.g. substantially all volatile materials, or
at least about 80, 85, 90, 95 or 98% of volatile materials) by
heating and/or applying a vacuum thereto. Alternatively or
additionally, removal of volatiles may be conducted prior to
removal of the hydroxymethylfurfural. In this context, "volatile"
materials are considered to have a boiling point of about
100.degree. C. or less. The heating may be at a temperature of
about 80 to about 150.degree. C., or about 80 to 120, 80 to 100,
100 to 150, 120 to 150, 100 to 120 or 90 to 110.degree. C., e.g.
about 80, 90, 100, 110, 120, 130, 140 or 150.degree. C. The vacuum
may have an absolute pressure of about 0.2 atmospheres or less, or
about 0.1, 0.05, 0.02 or 0.01 atmospheres or less. The time for
said treating may be sufficient under the treatment conditions to
remove the desired proportions of volatile materials. It may be
about 1 to about 5 hours, or about 1 to 3, 2 to 5 or 1.5 to 2.5
hours, e.g. about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5 hours. The
heating/vacuum may be applied in a suitable apparatus, e.g. a
vacuum chamber, a cyclone evaporator or some other suitable
apparatus. In some cases no vacuum is applied.
[0086] The production of hydroxymethylfurfural according to the
present invention may be conducted as a continuous process. In an
example, saccharide(s) and catalyst are continuously added to an
addition zone of a reaction cycle, the resulting mixture is then
held at a suitable temperature for a suitable time (as described
earlier) for reaction to form hydroxymethylfurfural in a reaction
zone of the reaction cycle, volatiles and hydroxymethylfurfural are
continuously separated in a separation zone and the solvent and
catalyst recycled to the addition zone for reuse. The reaction zone
may have vacuum applied to it, so that volatiles are removed during
the reaction, and hydroxymethylfurfural is removed subsequently in
the separation zone.
[0087] Thus in many embodiments the present invention presents a
new Cr--N-heterocyclic carbene (NHC)/ionic liquid system that
selectively produces hydroxylmethylfurfural (HMF) from glucose and
fructose. This novel catalyst achieved the highest efficiency known
from both fructose and glucose feedstocks. The HMF yields were as
high as 96% and 82% from fructose and glucose respectively. The new
system provided high selectivity towards HMF, and tolerance towards
high substrate loading. It also allowed for ease of recycling of
catalyst and ionic liquid.
[0088] The inventors have investigated N-heterocyclic carbene
(NHC)-metal complexes as catalysts for the sugar dehydration
reaction. These ligands offered a great deal of flexibility towards
modifying the catalytic activity by varying the stereo and
electronic properties of NHCs. The conversions of fructose and
glucose were tested over 1-butyl-3-methylimidazolium chloride
(BMIM) with different catalysts (Scheme 1). The NHC-metal complexes
were pre-generated by mixing imidazolium salts, KO.sup.tBu and
metal chlorides in N,N-dimethylformamide (DMF) under heating for
several hours before adding to the reaction system. In a typical
reaction protocol, 100 mg of sugar was mixed with 500 mg of BMIM
and 2 mol % pre-prepared Cr--NHC catalyst. The reaction mixture was
kept at 100.degree. C. for 6 h. HMF was extracted by ether (three
times). All experiments were repeated, and the HMF yield was
confirmed by both GC and NMR of the isolated product.
##STR00001##
[0089] Several metals were selected for the screening studies, but
only Cr(II) and Cr(III) gave promising results. Unlike the
previously reported metal chloride/ionic liquid system, herein
Cr(II) and Cr(III) showed similar activities toward converting
fructose or glucose to HMF (Table 1).
TABLE-US-00001 TABLE 1 Conversion of sugars to HMF by NHC-Cr
catalysts..sup.a Yield from glucose Yield from fructose (%).sup.[b]
(%).sup.[b] entry catalyst BMIM DMSO BMIM DMSO 1 1-CrCl.sub.2 65 28
66 25 2 2-CrCl.sub.2 68 32 65 25 3 3-CrCl.sub.2 76 39 62 26 4
4-CrCl.sub.2 89 52 90 31 5 5-CrCl.sub.2 76 -- 50 -- 6 6-CrCl.sub.2
96 41 81 32 7 7-CrCl.sub.2 93 -- 70 26 8 8-(CrCl.sub.2).sub.2 -- --
81 -- 9 8-CrCl.sub.2 74 -- 14 -- 10 4-CrCl.sub.3 90 40 78 30 11
5-CrCl.sub.3 77 -- 72 -- 12 6-CrCl.sub.3 96 40 78 32 13
7-CrCl.sub.3 83 -- 81 -- 14.sup.[c] 6-CrCl.sub.3 82 -- 65 --
15.sup.[d] 6-CrCl.sub.3 -- -- 76 -- 16.sup.[e] 6-CrCl.sub.3 96 --
76 -- 17.sup.[f] 6-CrCl.sub.3 98 -- 76 -- .sup.[a]Reaction
conditions: 500 mg of solvent, 50 mg of sugar, 9 mol % of catalyst,
100.degree. C., 6 h, in air, unless otherwise stated. .sup.[b]Yield
was determined by gas chromatography (GC) with internal standard
and isolated pure product. .sup.[c]Reaction was conducted under
argon. .sup.[d]9 mol % of bipyridine was added to the reaction
system. .sup.[e]Recycled reaction system from entry 12.
.sup.[f]Recycled reaction system from entry 16.
[0090] Structures of carbenes used in the reactions summarised in
Table 1 are shown below.
##STR00002##
[0091] Remarkably, catalyst activity was found to be closely
related to the stereo property of the NHC ligands. 1-CrCl.sub.2
catalyzed the dehydration fructose and glucose with HMF yields of
65% and 66%, respectively (Table 1). Catalyst with the
isopropyl-substituted NHC ligand, 2-CrCl.sub.2, showed similar
efficiency as 1-CrCl.sub.2. In contrast, the HMF yields from sugars
were significantly increased using chromium catalysts with the more
bulky NHC ligands, such as 3-7. 6-CrCl.sub.2 system provided a HMF
yield as high as 96% from fructose. It also gave a HMF yield of 81%
from glucose, which was a record high efficiency for glucose
feedstock. There was no difference in yield for the metal catalysts
with saturated vs. unsaturated NHC ligands. The catalysts with the
most bulky NHC ligand,
1,3-bis(2,6-diisopropylphenyl)imidazolylidene 6 and
1,3-bis(2,6-diisopropyl)phenylimidazolinylidene 7 provided the
highest yields. To better understand the details of this reaction,
bidentate ligand 8 was examined. Interestingly, catalyst
8-(Cr).sub.2 gave a good HMF yield (81%) from glucose, while
8-(Cr).sub.1 showed a poor HMF yield (14%). These results suggested
that an over-crowded complex would have a lower activity in binding
with substrates and initiating the reaction. Control reaction
without catalyst showed a very low HMF yield (less than 40% and 1%
from fructose and glucose, respectively). The reaction temperature
was investigated between 80 .degree. C. and 100.degree. C. for both
fructose and glucose. Lower temperature led to a lower HMF yield:
higher temperature gave rise to byproducts, mainly diformylfuran
(DFF) (see FIG. 1).
[0092] Kinetics studies of this reaction over 6-CrCl.sub.2 showed
that the HMF yield peaked at our standard reaction condition of 6 h
for both fructose and glucose (see FIG. 2). The HMF yield gradually
decreased at reaction periods beyond 6 h. This could be due to the
slow decomposition of HMF in the reaction system. HMF yield for
fructose and glucose after 6 h began to decrease as the NHC--Cr
catalyst loading was reduced to less than 1 mol % (see FIG. 3).
Generally, lower catalyst loading would require a longer reaction
time to achieve a high conversion. However, in this system, the
product could decompose under the reaction condition, so longer
reaction time would lead to lower yield of the desired product.
Thus, if a low catalyst loading of 1 mol % is to be employed, other
reaction conditions have to be optimized to maximize the HMF
yield.
[0093] The substrate/solvent weight ratio was also found to be
important for the overall efficiency of the reaction system (see
FIG. 4). When the fructose/BMIM weight ratio was increased from
0.05 to 0.2, the HMF yield changed slightly from 95% to 94%. As the
fructose/ionic liquid weight ratio increased from 0.2 to 0.5, the
HMF yield decreased substantially to 70%. Further increase in the
fructose/ionic liquid weight ratio did not lead to significant
variation in HMF yield. Remarkably, the HMF yields remained rather
unaffected (81-77%) as the glucose/BMIM weight ratio was varied
from 0.05 to 0.67. The HMF yield was only slightly decreased (to
73%) when the glucose/BMIM weight ratio was increased to 1.0. In
this case, BMIM acted more like an assisting reagent than a
solvent.
[0094] The different behavior of fructose and glucose in FIG. 4
suggested different possible reaction mechanisms for the two
feedstocks. In the latter, glucose might be first converted to
fructose and subsequently to HMF over the NHC--Cr catalyst (see
Scheme 2). In this case, fructose concentration would be relatively
low even when the glucose substrate loading was high since
fructorse was merely an intermediate in the conversion of glucose
to HMF. Interestingly, HMF yields of about 15% lower were obtained
for the reaction conducted in argon vs. in air (Table 1, entry 14
vs. entry 12). The NHC--Cr catalysts were also tested in
dimethylsulfoxide (DMSO). Much lower HMF yields were obtained from
fructose (28-52%) and glucose (25-32%) in this solvent (see Table
1). Again, catalysts with bulky NHC ligands showed higher
efficiency in the DMSO system.
##STR00003##
[0095] The high efficiency of the catalyst and the high substrate
loading render the process of the invention very attractive for
industrial scale-up. This reaction process would also allow for the
continuous extraction of product, and the recycling of catalyst
NHC--Cr and ionic liquid. HMF would be the sole product in ether
extraction when the conversion of glucose and fructose was
conducted at temperatures below 100.degree. C. After the ether
extraction, the reaction medium was pre-heated at 100.degree. C.
for 2 h to remove the low boiling point components, such as ether
and water, and then directly used in the next run by adding the
sugar substrate. The recycled reaction system retained high
activity in the conversion of glucose and fructose to HMF (Table 1,
entries 16 and 17). The high substrate loading and the ease of
catalyst and ionic liquid recycling make this system attractive for
industrial applications.
[0096] The present results clearly suggested that NHC--CrCl.sub.x
complexes play a key role in glucose dehydration in BMIM. Bulky NHC
ligand prevented chromium from forming multiple NHC coordination in
BMIM, reducing the catalytic activity as in the case of
8-(Cr).sub.1. In contrast, no inhibition effect was observed with
the addition of bipyridine ligand in the case of 6-CrCl.sub.3 (HMF
yield of 76% from glucose) (Table 1, entry 15). Glucose is proposed
to be converted to fructose or HMF by NHC--Cr complex via redox
processes (see Scheme 2). This may explain why chromium, which has
versatile oxidation states, is suitable for this reaction. X-ray
photoelectron spectroscopy (XPS) indicated split peaks for Cr
2p.sub.3/2 and 2p.sub.1/2 peaks for the reaction intermediate of
6-CrCl2. The shoulder of Cr 2p.sub.3/2 and Cr 2p.sub.1/2 peaks at
577 eV and 587 eV, respectively, indicated the presence of oxidized
Cr species (see FIG. 5).
[0097] In summary, a new NHC--Cr/ionic liquid system has been
developed for the selective conversion of sugars to HMF. This new
system achieved excellent efficiency and the highest HMF yields
reported thus far for both fructose and glucose feedstocks. The HMF
yields were as high as 96% and 82% for fructose and glucose,
respectively. The new system also allowed for ease of catalyst and
ionic liquid recycling, provided sole HMF product by simple
extraction, and was tolerant towards high substrate loading.
[0098] The ionic liquid-metal catalyst system described above has
excellent stability and selectivity in HMF conversion from
carbohydrates. However, the process described above is limited to
batch reaction protocols due to the incompatibility of the high
reaction temperature (80-120.degree. C.) and the commonly used
extraction method using diethyl ether, a low boiling point
solvent.
[0099] In an adaptation of the above process for making
hydroxymethylfurfural, a reaction mixture comprising a saccharide
and a metal complex of an N-heterocyclic carbene is prepared. As
described earlier, the saccharide may be a hexose or a mixture of
hexoses, or it may be a dimer, oligomer or polymer or copolymer of
a hexose or a mixture thereof. Details of suitable saccharides have
been described earlier in this specification. The saccharide is
then allowed to react in the presence of the metal complex in the
reaction mixture so as to form hydroxymethylfurfural. By use of
suitable reaction conditions and metal complex, this reaction may
be conducted at about 70.degree. C. or below. It may be conducted
at or below about 65, 60, 55, 50, 45, 40, 35, 30, 25 or 20.degree.
C, or at about 20 to about 70.degree. C, or about 20 to 50, 20 to
40, 20 to 30, 30 to 50, 40 to 50, 50 to 70, 40 to 60 or 30 to
40.degree. C. The time required reaction will depend in part on
factors such as the temperature, the nature of the catalyst, the
catalyst concentration, the desired degree of conversion, the
nature of the saccharide etc. In general the time taken will be
comparable to that described earlier (i.e. about 1 to about 6
hours) although in some cases it may be longer than this, e.g. up
to about 12 hours. Unless separately described, the conditions used
for this adaptation (i.e. at or below 70.degree. C.) are the same
as those for the process described earlier in this specification.
The adapted process may be capable of producing HMF at relatively
low temperature (as described above) with a yield from fructose of
at least about 40%, or at least about 45, 50, 55 or 60%. The
process may be adapted to operate continuously so as to
continuously produce HMF.
[0100] The reaction mixture may be a two phase reaction mixture.
This has several potential advantages including: [0101] it
facilitates continuous or semi-continuous operation; and/or [0102]
it facilitates reuse/recycling of the metal complex; and/or [0103]
it facilitates separation of the product; and/or [0104] higher
yield of HMF.
[0105] The two phase reaction mixture commonly comprises a reaction
mixture phase and an extraction solvent phase. The reaction is
commonly conducted below the normal boiling point of the extraction
solvent. Commonly the reaction mixture phase comprises an ionic
liquid, which may function as a solvent for the reaction. Thus the
saccharide and/or the metal complex may be dissolved in the ionic
liquid in the reaction mixture phase. Suitable solvents are
described earlier in the specification as solvents for the process.
The second phase of the two phase reaction mixture is an extraction
solvent phase, i.e. it comprises an extraction solvent. The
extraction solvent preferably is capable of dissolving the HMF
produced in the reaction. Preferably the saccharide and/or the
metal complex has low solubility (or is insoluble) in the
extraction solvent. Thus the extraction solvent may be capable of
extracting the HMF from the reaction mixture phase without
substantially extracting saccharide and/or metal complex. The
extraction solvent may be substantially incapable of extracting an
intermediate formed from the saccharide, said intermediate being
convertible under the conditions of the process into HMF. The
extraction solvent may be such that the solubility of HMF in the
extraction solvent is greater than its solubility in the reaction
mixture (e.g. in the ionic liquid). The extraction solvent may be a
dipolar aprotic solvent. It may be an ether, e.g. a cyclic ether.
It may be for example THF. It may have a boiling point below that
of the reaction temperature.
[0106] In the above discussion it will be understood that the two
phases may have a finite but low miscibility. The miscibility may
be sufficiently low that the reaction mixture forms a two phase
reaction mixture at the temperature used in the reaction. The
miscibility of the reaction mixture phase in the extraction solvent
phase, or, independently, of the extraction solvent phase in the
reaction mixture phase, may be less than about 10% at the
temperature used in the reaction, or less than about 5, 2 or 1%. It
may be about 0.1 to about 10%, or about 0.1 to 5, 0.1 to 1, 0.1 to
0.5, 0.5 to 10, 1 to 10, 5 to 10, 1 to 5 or 0.5 to 2%, e.g. about
0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7,
8, 9 or 10%.
[0107] The N-heterocyclic carbene may be a monomeric N-heterocyclic
carbene. Suitable N-heterocyclic carbenes have been discussed
earlier in this specification. In some embodiments a co-catalyst is
used. The cocatalyst may be an acidic cocatalyst. It may be a
heterogeneous cocatalyst. It may for example be a zeolite, e.g.
zeolite H--Y (CBV720)
[0108] The metal complex may be a tungsten complex or a titanium
complex or a zirconium complex or a ruthenium complex or a mixture
of any two or more of these types of complex. The metal complex of
the N-heterocyclic carbene may be a metal complex of an N-imidazole
carbene. It may be complex with a metal such that said complex is
capable of catalysing the process at less than about 70.degree. C.
The metal may be complexed to the carbene portion of the NHC.
[0109] The process may comprise the step of generating the metal
complex of the N-heterocyclic carbene. This process has been
described earlier. The NHC may be used as a solution in the solvent
in which it is generated, or the solution in which it is generated
may be dried and the dried NHC metal complex may be used in the
process (i.e. to form the reaction mixture). The metal complex may
be made from a salt of the metal. In the event that the metal is
tungsten, it may be made from a W(IV) salt or it may be made from a
W(VI) salt, or it may be made from a mixture of the two.
[0110] The process may additionally comprise isolating the
hydroxymethylfurfural. As discussed earlier, an advantage of the
lower reaction temperature is that it allows for extraction of the
hydroxymethyl furfural during the course of the reaction. In one
option the reaction mixture is extracted with a solvent after
completion of the reaction as before, optionally after cooling the
reaction mixture below the reaction temperature used (although in
some embodiments the reaction mixture is not cooled, as the
extraction solvent has a boiling point at or above the reaction
temperature). In another option, however, HMF is removed from the
reaction mixture as the reaction is proceeding. This is termed
herein a two phase system. Removal of HMF from the reaction mixture
may serve to drive the reaction forwards so as to improve the yield
of HMF. In some embodiments the reaction mixture is continuously
extracted by the extraction solvent. This may be achieved for
example by use of a continuous countercurrent extractor. It may be
achieved by conducting the reaction in a two phase system in which
the extraction solvent in contact with the reaction mixture phase
is continuously removed and fresh extraction solvent added. In some
embodiments, the removed extraction solvent (containing HMF) is
treated (e.g. evaporated) so as to regenerate fresh extraction
solvent which may then recycled to contact with the reaction
mixture phase. This may also serve to isolate the crude HMF
product. In other embodiments the extraction is not continuous. For
example, at regular intervals (i.e. intermittently) the extraction
solvent phase may be removed (either partially or substantially
completely) from the reaction mixture phase and replaced with a
fresh aliquot of extraction solvent. As described above for the
continuous option, in the intermittent option the extraction
solvent may be recycled into the two phase system. The two phase
reaction system may be agitated (stirred, shaken, sonicated or
similar) in order to promote reaction of saccharide or extraction
of HMF or both. Alternatively the system may be substantially
unagitated, so as to promote separation of the phases.
[0111] In some embodiments the saccharide is fed continuously or
intermittently to the reaction mixture. This embodiment may be used
in conjunction with either the continuous extraction or the
intermittent extraction described above. Thus the reaction may be
conducted as a continuous reaction. In an example of a fully
continuous system therefore, a two phase mixture comprises a
reaction mixture phase, comprising the NHC-metal complex and an
ionic liquid solvent, and an extraction liquid phase (e.g. THF)
which is immiscible with the reaction mixture phase. The saccharide
(optionally in a solvent) is then fed continuously into the
reaction mixture phase, where it reacts with the NHC-metal complex
to form HMF, which is continuously extracted into the extraction
solvent. The extraction solvent is continuously removed and
replaced at the same rate with a fresh extraction solvent. The
removed extraction solvent is evaporated to generate the fresh
extraction solvent, which is, as mentioned above, fed continuously
to the two phase mixture with any top-up extraction solvent that is
required. The evaporation also continuously generates HMF product
which is then removed and stored or used as required.
[0112] An apparatus for conducting the process of the invention
batchwise may comprise a reactor vessel and a separator. The
reactor vessel is adapted to contain the reaction mixture and the
extraction liquid. It may comprise an agitator, for example a
stirrer, a shaker, a sonicator or similar, or may not comprise an
agitator. A take-off line leads from the reactor vessel to the
separator and is positioned so as to be capable, in operation, of
removing extraction liquid from the reactor vessel without removing
reaction mixture therefrom. In the event that the extraction liquid
has lower specific gravity than the reaction mixture, the take-off
line may be located above the interface between the extraction
liquid and the reaction mixture. The separator may be any device
capable of separating the extraction liquid from the HMF product.
It may for example be an evaporator or distillation apparatus. The
separator has a return line for returning the extraction liquid to
the reactor vessel after separation of the HMF. The return line may
be disposed so as to return the extraction liquid into the reaction
mixture, so that the extraction liquid passes through the reaction
mixture as it separates therefrom, thereby extracting HMF from the
reaction mixture. Alternatively, the return line may be disposed so
that the extraction liquid is not returned into the reaction
mixture. It may for example be returned into extraction liquid that
remains in the reactor vessel. In that event, HMF is extracted into
the extraction liquid through the normal interface between the
extraction liquid and the reaction liquid. The take-off line, the
separator or the return line may be fitted with a pump (or more
than one pump) so as to promote flow of the extraction liquid to
and from the separator. They may be fitted with one or more valves
in order to ensure flow in the desired direction and prevent
backflow. In some embodiments no pumps or valves are present. In
such embodiments, correct liquid flow may be promoted by situating
the evaporator so that gravity causes the desired liquid flows to
occur. The separator may also be fitted with an HMF line for
removing HMF from the separator. The HMF line may be maintained at
a temperature above the melting point of HMF (about 30-34.degree.
C.). It may be fitted with a warmer to maintain the HMF line above
the melting point of HMF.
[0113] The batchwise apparatus described above may be adapted to
form a continuous apparatus by providing a saccharide feed vessel
coupled to the reactor vessel by a feed line. The feed line may be
disposed so that the saccharide is fed directly into the reaction
mixture in the reactor vessel in use. In the event that the
extraction liquid has lower specific gravity than the reaction
mixture, the feed line may feed into the reactor vessel below the
interface between the extraction liquid and the reaction mixture.
The feed line and/or the feed vessel may be fitted with a pump
and/or a valve in order to promote desired flow of saccharide into
the reactor vessel. In some instances one or other of these may not
be required, for example a pump may not be required if
gravitational flow is enabled by suitable location of the feed
vessel, and a valve may not be required if the pump performs both
the function of a valve and of a pump.
[0114] The metal complex of the N-heterocyclic carbene may be
recycled following removal of the hydroxymethylfurfural from the
reaction mixture. This may comprise reusing a solution of the metal
complex in a subsequent reaction. It may comprise isolating the
metal complex from the reaction mixture, for example by solvent
precipitation and filtering/decanting, or by evaporation of the
reaction mixture. The metal complex so isolated may be used as is,
or may be purified, e.g. by washing with a suitable solvent, by
reprecipitation or recrystallisation or by some other suitable
method. In the event that a two phase process is used (as described
above), the recycling may be achieved by adding further saccharide
to the reaction mixture and contacting fresh extraction liquid with
the reaction mixture.
[0115] In the event that the reaction mixture comprises an ionic
liquid, the ionic liquid may be recycled following removal of the
hydroxymethylfurfural from the reaction mixture. This may for
example comprise distillation of the ionic liquid or it may
comprise solvent extraction of the ionic liquid, or it may comprise
some other recycling process. As described above for the metal
complex, the ionic liquid need not be separated in order to recycle
it. Thus the reaction mixture, comprising the ionic liquid and the
metal complex, may be simply reused by addition of further
saccharide. As also described earlier, this may be converted to a
continuous system by continuously feeding saccharide to the
reaction mixture and continuously removing the HMF product from the
reaction mixture by continuous extraction with an extraction
liquid.
[0116] The HMF produced by the process described herein may be
converted into a fuel. Thus using the process of the invention as
described herein, a fuel, in particular a biofuel, may be made by
converting a saccharide to HMF, and then the HMF may be used to
make the fuel by known methods.
[0117] A particular embodiment of the invention provides a novel
tetrahydrofuran (THF)-butyl-methyl imidazolium chloride (BMIMCl)
biphasic system with tungsten salt catalyst for fructose conversion
to HMF under mild reaction conditions. The novel tungsten salt
catalyst enables HMF to be efficiently synthesized at
.ltoreq.50.degree. C. in the ionic liquid system. The biphasic
system has been successfully applied to a continuous batch reaction
process, and may be suitable for large-scale synthesis of HMF from
fructose. This is the first organic solvent-ionic liquid biphasic
system that enables the conversion of sugars to HMF at low
temperatures (.ltoreq.50.degree. C.) using a novel tungsten salt
catalyst. Compared to other systems, this approach is attractive
for its mild reaction conditions. The new system may be applied in
making biofuel and in the fine chemical industries.
[0118] The inventors have also developed a new protocol so that an
organic solvent-ionic liquid biphasic system could be used for
product separation in establishing a scalable continuous process.
After screening different metal salts, it was found that tungsten
salts were the most promising in catalyzing fructose conversion to
HMF at low temperatures.
[0119] An ionic liquid-tungsten salt catalyst system has been
developed that can effectively convert fructose to HMF at a much
lower temperature (.ltoreq.50.degree. C.) than previously used.
Disclosed herein is an ionic liquid-tetrahydrofuran (THF) biphasic
system using the tungsten salt catalyst or similar. This system
offers a feasible large-scale continuous HMF production protocol
under moderate temperatures and ambient pressure. It represents the
first efficient catalytic system that converts sugars to HMF at a
reaction temperature of <8.sup.0.degree. C. This is a notable
achievement and advantageous system for many reasons. Firstly, the
lower reaction temperature produces less by-products that cause
system contamination. Secondly, it allows lower boiling point
solvents to be used as the mobile phase in the biphasic system,
facilitating HMF product recovery by solvent distillation. Thirdly,
the mild conditions lower the energy consumption and give rise to a
longer system lifetime, which are important towards developing a
sustainable biofuel system.
[0120] In a typical reaction protocol, 100 mg fructose was mixed
with 500 mg butyl-methyl imidazolium chloride (BMIMCl) and 5 mol %
of WCl.sub.6 catalyst. The reaction mixture was kept at 50.degree.
C. for 3-6 h. HMF was extracted by ether (three times) with 58%
yield. The HMF yield was confirmed by nuclear magnetic resonance
(NMR) spectrum of the extracted product with an added external
standard, and the results were confirmed by repeated
experiments.
[0121] When N-heterocyclic carbene,
1,3-bis(2,6-diisopropylphenyl)imidazolylidene (Ipr), was used as
the ligand, a slight higher HMF yield (65%) was achieved with the
resulting Ipr-WCl.sub.6 catalyst. The Ipr/WCl.sub.6 ratio and the
type of base used in the synthesis of Ipr-WCl.sub.6 catalyst did
not substantially affect the HMF yield: the HMF yields using
Ipr-WCl.sub.6, (Ipr).sub.2-WCl.sub.6 and Ipr*-WCl.sub.6 (Ipr
carbene generated by NaH) catalysts were similar. When solid acid
zeolite H--Y (CBV720) was used as a co-catalyst, a slightly higher
HMF yield (69%) was obtained. Remarkably, the tungsten salt
catalyst functioned well at temperatures below 50.degree. C. At
30.degree. C., although the BMIMCl and fructose mixture behaved as
a paste and was difficult to stir, a HMF yield of 53% was achieved
after 4 h of reaction time. The temperature effect was inhibitory
above 5.sup.0.degree. C. Tungsten(IV) salts could also catalyze
this reaction at 50.degree. C. with slightly lower activities, as
compared to tungsten(VI) salts (see Table 2). Other salts such as
titanium chloride, zirconium chloride and ruthenium chloride could
also catalyze fructose conversion to HMF with yields of 43%, 47%
and 42%, respectively (entries 12-14, Table 1).
TABLE-US-00002 TABLE 2 Conversion of fructose to HMF by metal
catalysts in BMIMCl..sup.a Entry Catalyst Yield from fructose
[%].sup.[b] 1 WCl.sub.6 58 2 Ipr-WCl.sub.6 65 3
Ipr*-WCl.sub.6.sup.[c] 63 4 (Ipr).sub.2-WCl.sub.6 65 5
Ipr-WCl.sub.6/H--Y zeolite 69 6 WCl.sub.4 61 7 Ipr-WCl.sub.4 62 8
(Ipr).sub.2-WCl.sub.4 65 9 Ipr-WCl.sub.4/H--Y zeolite 59 10
CrCl.sub.3 3 11 CrCl.sub.2 2 12 TiCl.sub.4 43 13 ZrCl.sub.2 47 14
RuCl.sub.3 42 .sup.aReaction conditions: 500 mg of BMIMCl, 100 mg
of fructose, 5 mol % of catalyst, 50.degree. C., 6 h. .sup.[b]Yield
was determined by the NMR spectrum of the extracted product with an
external standard. .sup.[c]Catalyst prepared using NaH.
[0122] The optimized Ipr-WCl.sub.6 catalyst loading for this
reaction at 50.degree. C. was 5 mol %. Lower catalyst loading would
require a longer reaction time to achieve a high conversion, while
higher catalyst loading only marginally increased the
conversion.
[0123] Kinetic studies of this reaction using Ipr-WCl.sub.6 showed
that HMF yield quickly reached 55% in 3 h, and slowly increased to
the maximum yield 65% in 6 h (see FIG. 6). On the other hand, the
fructose amount remaining in the mixture sharply dropped to 12% in
90 min, and then slowly decreased to about 2% in 6 h (see FIG. 1
(red curve)). The dashed curve in FIG. 6 represents the sum of
fructose and HMF masses in the reaction mixture. It demonstrated a
clear minimum 40 mg at 90 min, and then increased to 65 mg at 180
min. This suggested that fructose quickly formed an
intermediate(s), and subsequently formed HMF and by-products. The
intermediate(s) existed in significant quantities in the reaction
mixture early in the reaction.
[0124] The reaction can be described as follows, with fructose
concentration=[F], intermediate concentration=[Int], HMF
concentration=[HMF], and by-product concentration=[BP].
##STR00004##
It appears that the reaction rate is controlled by Equation (2)
(k.sub.1>k2). The existence of a large amount of intermediate
will result in more by-product ([BP].varies.
k.sub.3.[Int].sup.n>1). It is assumed that lower [Int], [HMF]
and [H.sub.2O] in the reaction mixture will lead to a higher HMF
yield. This can be achieved by using a biphasic continuous reaction
system. In a biphasic continuous system, fructose can be
continuously added in small portion so that the intermediate
concentration can be controlled. HMF (and water) can be extracted
out of the ionic liquid and into THF in situ to push the reaction
forward in Equation (2).
[0125] The ionic liquid-tungsten salt catalyst system allowed for
the extraction of HMF from the ionic liquid phase at lower
temperatures. This provided more options in selecting suitable
organic solvents for the biphasic system. The ideal solvent must
form a separate phase from the ionic liquid, and have a boiling
point above 50.degree. C. The solvent should also be easily
separated from the extracted HMF through evaporation. Of the
solvents that were screened, THF showed the greatest potential. By
using a batch biphasic reactor (FIG. 7(A)), 72% HMF yield was
attained with the THF/BMIMCl system, which was higher than that
obtained with the monophase ionic liquid system. Furthermore, THF
was able to remove trace water produced during the dehydration of
fructose, keeping the reaction clean. Toluene suppressed the
reaction under the same conditions, giving only 25% HMF yield,
whereas EtOAc led to 59% HMF yield. In FIG. 7A, ionic liquid
(white) contains BMIMCl, Ipr-WCl.sub.6 and fructose, while the
organic phase (gray) contains THF. HMF is extracted into the THF
phase and separated through an evaporation step; THF can be reused
upon evaporation-condensation. By contrast, in the continuous batch
process described below fructose is added continuously or batch by
batch.
[0126] After modifications to the batch reactor system, a
continuous batch reaction process was tested (FIG. 7(B)). A
constant amount of fructose was added to the reactor system every 6
hours, and the THF phase was collected and refreshed every 90
minutes. The reaction system was kept active without interruption
between different batch runs. Through collection of the THF phase,
the HMF yield of every 6 hour batch was quantified. Fructose
concentration was also monitored at these 6 hour intervals. It was
found that the HMF yield actually increased steadily from 70%
(first batch run) to 82% (third batch run) (see FIG. 8). This might
be due to the accumulation of small amounts of unreacted fructose
or intermediates from the previous batch(es). In fact, the
remaining fructose at the end of each batch run was very low (2-3
mg). The average HMF yield at the end of each batch run stabilized
at about 80%. Remarkably, the Ipr-WCl.sub.6 catalyst-ionic liquid
system retained a high catalytic activity over multiple batch runs,
may be the major reason for the long system lifetime.
[0127] In conclusion, a novel THF-BMIMCl biphasic system with
tungsten salt catalyst for fructose conversion to HMF under mild
reaction conditions has been developed. With the tungsten salt
catalyst, HMF was efficiently synthesized at .ltoreq.50.degree. C.
in the ionic liquid. The biphasic system was successfully applied
to a continuous batch reaction process, and might be suitable for
the large-scale synthesis of HMF from fructose.
EXAMPLES
General Information
[0128] All solvents and chemicals were used as obtained from
commercial suppliers, unless otherwise indicated. Centrifugation
was performed on Eppendorf Centrifuge 5810R (4000 rpm, 10 min).
.sup.1H and .sup.13C NMR spectra were recorded on Bruker AV-400
spectrometer (400 MHz). Fructose was quantified using SU-300 Sugar
Analyzer (TOA-DKK Corp.).
Preparation of Ipr-WCl.sub.6 Catalysts
[0129] 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (467 mg,
1.1 mmol) was mixed with KO.sup.tBu (123 mg, 1.1 mmol) in 20 ml of
anhydrous N,N-dimethylformamide (DMF). The reaction mixture was
allowed to stir for 1 h at room temperature before WCl.sub.6 (397
mg, 1 mmol) was added to the mixture, which was then heated to
80.degree. C. and stirred for another 6 h. The reaction mixture was
cooled to room temperature and filtered. The green DMF solution was
directly used as the catalyst stock solution. Alternatively, the
catalyst solution was dried. The resulting green powder was washed
with ether and THF, and dried under vacuum.
Conversion of Sugars to HMF
[0130] Batch Reaction: In a typical reaction, 0.556 mmol of
fructose (100 mg) was dissolved in BMIMCl (500 mg), and the
tungsten salt catalyst (5 mol %) was added. The reaction mixture
was then heated to 50.degree. C. for 3-6 h. It was allowed to cool
to room temperature before 1 ml of water was added. HMF was
extracted 3 times with 15 ml of ether.
[0131] Biphasic Batch Reaction: In a typical reaction, 0.556 mmol
of fructose (100 mg) was dissolved in BMIMCl (500 mg), and the
tungsten salt catalyst (5 mol %) and THF (10 ml) were added. The
reaction mixture was then heated to 50.degree. C. for 3-6 h. The
THF phase was refreshed 3 times during the reaction, and all three
THF portions were combined for HMF quantification.
[0132] Continuous Biphasic Batch Reaction: In a typical reaction,
0.556 mmol of fructose (100 mg) was dissolved in BMIMCl (500 mg),
and the tungsten salt catalyst (5 mol %) and THF (10 ml) were
added. The reaction mixture was then heated to 50.degree. C. for
3-6 h. The THF phase was refreshed 3 times during the reaction, and
all three THF portions were combined for HMF quantification. After
6 h, a new batch of 100 mg of fructose was added directly to the
reaction mixture to start the second batch run. The HMF yield and
the fructose remaining were monitored at the end of each batch
run.
Quantification of HMF Yield
[0133] The combined ether (or THF) extracts were concentrated under
vacuum at room temperature. A known amount of the external
standard, mesitylene, was added to the product container with
deuterium solvent (e.g. DMSO-d.sub.6, CDCl.sub.3, CD.sub.3OD and
acetone-d.sub.6). The HMF yield was obtained from .sup.1H NMR
spectrum using mesitylene as the external standard. It was
calculated by the integration of proton peaks of HMF (6.589 ppm)
and mesitylene (6.745 ppm).
* * * * *