PRODUCTION OF HYDROXYMETHYLFURFURAL

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° 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.

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Description
TECHNICAL FIELD

The present invention relates to a method of producing hydroxymethylfurfural.

BACKGROUND OF THE INVENTION

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.

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.

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.

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.

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.

Recent reports illustrate the use of 1-H-3-methyl imidazolium chloride (HMIM+Cl−) 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 CrCl2) and glucose (a record high of 68% with CrCl2) (H. Zhao, J. E. Holladay, H. Brown, Z. C. Zhang, Science 2007, 316, 1597).

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

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

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.

The following options may be used in conjunction with the first aspect, either individually or in any suitable combination.

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.

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.

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.

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.

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.

The process may additionally comprise isolating the hydroxymethyl furfural.

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%.

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.

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.

In another embodiment there is provided a process for making hydroxymethylfurfural comprising:

    • generating a chromium complex of an N-heterocyclic carbene; and
    • exposing fructose, glucose or a mixture of these to the chromium complex of the N-heterocyclic carbene in an ionic liquid.

In another embodiment there is provided a process for making hydroxymethylfurfural comprising:

    • 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
    • exposing fructose, glucose or a mixture of these to the chromium complex of the N-heterocyclic carbene in an ionic liquid.

The invention also provides hydroxymethyl furfural when made by the process of the first aspect.

In a second aspect of the invention there is provided use of a metal complex of an N-heterocyclic carbene for making hydroxymethyl furfural.

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.

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.

In a fifth aspect of the invention there is provided 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° C. or below.

The following options may be used in conjunction with the fifth aspect, either individually or in any suitable combination.

The saccharide may comprise a monosaccharide. The monosaccharide may comprise fructose, glucose or a mixture of these.

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.

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.

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.

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.

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.

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.

The process may be conducted as a continuous reaction. It may be conducted as a continuous batch reaction.

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.

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.

In an embodiment, there is provided a process for making hydroxymethylfurfural comprising:

    • (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
    • (ii) allowing the saccharide to react in the reaction mixture to form hydroxymethylfurfural,
      wherein steps (i) and (ii) are conducted at about 70° 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.

In another embodiment, there is provided a process for making hydroxymethylfurfural comprising:

    • (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;
    • (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
    • (iii) allowing the saccharide to react in the reaction mixture to form hydroxymethylfurfural,
      wherein steps (ii) and (iii) are conducted at about 70° C. or below.

In another embodiment there is provided a process for making hydroxymethylfurfural comprising:

    • (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
    • (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° 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° C.

In another embodiment, there is provided a process for making hydroxymethylfurfural comprising:

    • (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;
    • (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
    • (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° C. or below.

In another embodiment, there is provided a process for making hydroxymethylfurfural comprising:

    • (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;
    • (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
    • (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° C.

In a sixth aspect of the invention there is provided 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° C. or below.

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

A preferred embodiment of the present invention will now be described, by way of an example only, with reference to the accompanying drawings wherein:

FIG. 1 is a graph showing the effect of reaction temperature on HMF yield from (▪) fructose and (♦) glucose over 9 mol % of 6-CrCl2 (substrate/BMIM weight ratio=0.2, 6 h);

FIG. 2 is a graph showing the effect of reaction time on HMF yield from (▪) fructose and (♦) glucose over 9 mol % of 6-CrCl2 (substrate/BMIM weight ratio=0.2, 100° C.);

FIG. 3 is a graph showing the effect of 6-CrCl2 loading on HMF yield from (▪) fructose and (♦) glucose (substrate/BMIM weight ratio=0.2, 6 h, 100° C.);

FIG. 4 is a graph showing the effect of substrate loading on HMF yield from (▪) fructose and (♦) glucose over 9 mol % of 6-CrCl2 (6 h, 100° C.);

FIG. 5 is an XPS spectrum of the reaction intermediate of 6-CrCl2;

FIG. 6 shows a graph of: (▪) 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-WCl6, 500 mg of BMIMCl, 100 mg of fructose, 50° C.;

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

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-WCl6, 500 mg of BMIMCl, 10 ml of THF (refreshed 3 times), 50° C., 6 h; 100 mg of fructose were added directly after 6 h for the subsequent batches.

 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

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.

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.

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 α,α′-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.

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%.

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)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° 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° C, e.g. about 20, 30, 40, 50, 60, 70, 80, 90 or 100° 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.

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° C., or about 80 to 100, 80 to 90, 90 to 120, 100 to 120 or 90 to 100° C., e.g. about 80, 85, 90, 95, 100, 105, 110, 115 or 120° 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.

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.

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.

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° C. or less. The heating may be at a temperature of about 80 to about 150° C., or about 80 to 120, 80 to 100, 100 to 150, 120 to 150, 100 to 120 or 90 to 110° C., e.g. about 80, 90, 100, 110, 120, 130, 140 or 150° 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.

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.

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.

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, KOtBu 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° 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.

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 1 Conversion of sugars to HMF by NHC-Cr catalysts.a Yield from glucose Yield from fructose (%)[b] (%)[b] entry catalyst BMIM DMSO BMIM DMSO  1 1-CrCl2 65 28 66 25  2 2-CrCl2 68 32 65 25  3 3-CrCl2 76 39 62 26  4 4-CrCl2 89 52 90 31  5 5-CrCl2 76 — 50 —  6 6-CrCl2 96 41 81 32  7 7-CrCl2 93 — 70 26  8 8-(CrCl2)2 — — 81 —  9 8-CrCl2 74 — 14 — 10 4-CrCl3 90 40 78 30 11 5-CrCl3 77 — 72 — 12 6-CrCl3 96 40 78 32 13 7-CrCl3 83 — 81 — 14[c] 6-CrCl3 82 — 65 — 15[d] 6-CrCl3 — — 76 — 16[e] 6-CrCl3 96 — 76 — 17[f] 6-CrCl3 98 — 76 — [a]Reaction conditions: 500 mg of solvent, 50 mg of sugar, 9 mol % of catalyst, 100° C., 6 h, in air, unless otherwise stated. [b]Yield was determined by gas chromatography (GC) with internal standard and isolated pure product. [c]Reaction was conducted under argon. [d]9 mol % of bipyridine was added to the reaction system. [e]Recycled reaction system from entry 12. [f]Recycled reaction system from entry 16.

Structures of carbenes used in the reactions summarised in Table 1 are shown below.

Remarkably, catalyst activity was found to be closely related to the stereo property of the NHC ligands. 1-CrCl2 catalyzed the dehydration fructose and glucose with HMF yields of 65% and 66%, respectively (Table 1). Catalyst with the isopropyl-substituted NHC ligand, 2-CrCl2, showed similar efficiency as 1-CrCl2. In contrast, the HMF yields from sugars were significantly increased using chromium catalysts with the more bulky NHC ligands, such as 3-7. 6-CrCl2 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)2 gave a good HMF yield (81%) from glucose, while 8-(Cr)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 ° C. and 100° 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).

Kinetics studies of this reaction over 6-CrCl2 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.

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.

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.

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° C. After the ether extraction, the reaction medium was pre-heated at 100° 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.

The present results clearly suggested that NHC—CrClx 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)1. In contrast, no inhibition effect was observed with the addition of bipyridine ligand in the case of 6-CrCl3 (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 2p3/2 and 2p1/2 peaks for the reaction intermediate of 6-CrCl2. The shoulder of Cr 2p3/2 and Cr 2p1/2 peaks at 577 eV and 587 eV, respectively, indicated the presence of oxidized Cr species (see FIG. 5).

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.

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° C.) and the commonly used extraction method using diethyl ether, a low boiling point solvent.

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° C. or below. It may be conducted at or below about 65, 60, 55, 50, 45, 40, 35, 30, 25 or 20° C, or at about 20 to about 70° 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° 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° 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.

The reaction mixture may be a two phase reaction mixture. This has several potential advantages including:

    • it facilitates continuous or semi-continuous operation; and/or
    • it facilitates reuse/recycling of the metal complex; and/or
    • it facilitates separation of the product; and/or
    • higher yield of HMF.

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.

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%.

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)

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° C. The metal may be complexed to the carbene portion of the NHC.

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.

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.

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.

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° C.). It may be fitted with a warmer to maintain the HMF line above the melting point of HMF.

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.

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.

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.

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.

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 ≦50° 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 (≦50° 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.

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.

An ionic liquid-tungsten salt catalyst system has been developed that can effectively convert fructose to HMF at a much lower temperature (≦50° 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 <80° 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.

In a typical reaction protocol, 100 mg fructose was mixed with 500 mg butyl-methyl imidazolium chloride (BMIMCl) and 5 mol % of WCl6 catalyst. The reaction mixture was kept at 50° 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.

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-WCl6 catalyst. The Ipr/WCl6 ratio and the type of base used in the synthesis of Ipr-WCl6 catalyst did not substantially affect the HMF yield: the HMF yields using Ipr-WCl6, (Ipr)2-WCl6 and Ipr*-WCl6 (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° C. At 30° 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 50° C. Tungsten(IV) salts could also catalyze this reaction at 50° 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 2 Conversion of fructose to HMF by metal catalysts in BMIMCl.a Entry Catalyst Yield from fructose [%][b] 1 WCl6 58 2 Ipr-WCl6 65 3 Ipr*-WCl6[c] 63 4 (Ipr)2-WCl6 65 5 Ipr-WCl6/H—Y zeolite 69 6 WCl4 61 7 Ipr-WCl4 62 8 (Ipr)2-WCl4 65 9 Ipr-WCl4/H—Y zeolite 59 10 CrCl3 3 11 CrCl2 2 12 TiCl4 43 13 ZrCl2 47 14 RuCl3 42 aReaction conditions: 500 mg of BMIMCl, 100 mg of fructose, 5 mol % of catalyst, 50° C., 6 h. [b]Yield was determined by the NMR spectrum of the extracted product with an external standard. [c]Catalyst prepared using NaH.

The optimized Ipr-WCl6 catalyst loading for this reaction at 50° 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.

Kinetic studies of this reaction using Ipr-WCl6 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.

The reaction can be described as follows, with fructose concentration=[F], intermediate concentration=[Int], HMF concentration=[HMF], and by-product concentration=[BP].

It appears that the reaction rate is controlled by Equation (2) (k1>k2). The existence of a large amount of intermediate will result in more by-product ([BP]∝ k3.[Int]n>1). It is assumed that lower [Int], [HMF] and [H2O] 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).

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° 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-WCl6 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.

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-WCl6 catalyst-ionic liquid system retained a high catalytic activity over multiple batch runs, may be the major reason for the long system lifetime.

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 ≦50° 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

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). 1H and 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-WCl6 Catalysts

1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (467 mg, 1.1 mmol) was mixed with KOtBu (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 WCl6 (397 mg, 1 mmol) was added to the mixture, which was then heated to 80° 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

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° 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.

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° 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.

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° 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

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-d6, CDCl3, CD3OD and acetone-d6). The HMF yield was obtained from 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).

Claims

1. A process for making hydroxymethylfurfural comprising: wherein steps (i) and (ii) are conducted at about 70° C. or below.

(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;

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: wherein steps (i) and (ii) are conducted at about 70° C. or below.

(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;

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.

Patent History
Publication number: 20090313889
Type: Application
Filed: Apr 8, 2009
Publication Date: Dec 24, 2009
Applicant: Agency for Science, Technology and Research (Singapore)
Inventors: Yugen ZHANG (Singapore), Jin Y.G. Chan (Singapore)
Application Number: 12/420,757
Classifications
Current U.S. Class: The Hetero Ring Contains Five Members Including Carbon And Chalcogen (44/350); Additional Chalcogen Attached Indirectly To The Hetero Ring By Nonionic Bonding (549/488)
International Classification: C10L 1/18 (20060101); C07D 307/48 (20060101);