JP2013203666A - Method of producing 5-hydroxymethylfurfural oxide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of easily and economically producing a highly pure 5-hydroxymethylfurfural oxide from sugar raw material.SOLUTION: A method of producing a 5-hydroxymethylfurfural oxide includes following processes a-d. In the process a: sugar raw material is subjected to a dehydration reaction in the presence of a reaction solvent to produce 5-hydroxymethylfurfural (HMF) in the reaction solvent, and the reaction solvent including HMF is obtained. In the process a: sugar raw material is subjected to a dehydration reaction in the presence of a reaction solvent to produce 5-hydroxymethylfurfural in the reaction solvent, and the reaction solvent including HMF is obtained. In the process b: HMF is extracted into a hydrophobic solvent from the reaction solvent including HMF obtained in the process a, and the hydrophobic solvent including HMF is obtained. In the process c: HMF is extracted into water from the hydrophobic solvent including HMF obtained in the process b, and an aqueous solution including HMF is obtained. In the process d: HMF obtained in the process c is oxidized.

Description

  The present invention relates to a method for producing 5-hydroxymethylfurfural oxide.

  2,5-furandicarboxylic acid (hereinafter also referred to as “FDCA”), 2,5-diformylfuran (hereinafter referred to as “DFF”), which is an oxide of 5-hydroxymethylfurfural (hereinafter also referred to as “HMF”). ), 2-carboxy-5-formylfuran (hereinafter also referred to as “CFF”), 5-hydroxymethyl-2-furancarboxylic acid (hereinafter also referred to as “HMFA”), 5-acetoxymethyl-2- Furan carboxylic acid (hereinafter also referred to as “AcMFA”) is a useful compound as an intermediate for fine chemicals, pharmaceuticals, and agricultural chemicals. Among these, FDCA has a high utility value as an intermediate in various fields such as monomers for resins and toner binders, pharmaceuticals, agricultural chemicals, insecticides, antibacterial agents, perfumes, and the like. DFF is attracting attention as a polymer monomer, a crosslinking agent, and the like. Similar applications are also expected for HMF oxides other than FDCA and DFF.

  As a method for producing these 5-hydroxymethylfurfural oxides, HMF is generated by dehydration reaction of a saccharide containing a hexose sugar skeleton, and then HMF is oxidized using permanganate in an alkaline environment. (See Patent Document 1). As a method using oxygen as an oxidizing agent, a method of oxidizing HMF in the presence of a platinum group metal catalyst (see Patent Document 2), a method of oxidizing HMF in the presence of bromine and a metal catalyst (see Patent Document 3), A method of oxidizing HMF in an acetic acid solvent in the presence of a metal bromide catalyst (see Patent Document 4 and Non-Patent Document 1) and the like are known.

JP 2007-261990 A JP-A-2-88569 JP 2011-84540 A Special table 2003-528868 gazette

Adv. Synth. Catal., 343, 102-111 (2001)

However, in the method using the permanganate of Patent Document 1, the oxidation reaction can be performed without purifying the raw material HMF synthesized from the sugar raw material, but the permanganate is a homogeneous catalyst and is difficult to recycle. For this reason, there is a problem that separation operation and catalyst disposal become complicated, and productivity and economy are poor.
In addition, the methods of Patent Documents 2 to 4 and Non-Patent Document 1 can obtain 5-hydroxymethylfurfural oxide with a good yield, and the catalyst can be reused. Since the by-products generated during the production of the catalyst cause reaction inhibition and reduced catalyst activity, complicated purification steps of HMF by high vacuum distillation, column chromatography, etc. are necessary, and there are problems in production equipment and economy. is there.
Therefore, the present invention provides a method for easily and economically producing 5-hydroxymethylfurfural oxide from a sugar raw material.

That is, this invention provides the manufacturing method of 5-hydroxymethyl furfural oxide which has the following process ad.
Step a: Step of obtaining a reaction solvent containing 5-hydroxymethylfurfural by dehydrating a sugar raw material in the presence of the reaction solvent to produce 5-hydroxymethylfurfural in the reaction solvent Step b: Obtained in Step a Step of extracting 5-hydroxymethylfurfural into a hydrophobic solvent from the obtained reaction solvent containing 5-hydroxymethylfurfural to obtain a hydrophobic solvent containing 5-hydroxymethylfurfural obtained in step c: step b Step of extracting 5-hydroxymethylfurfural into water from a hydrophobic solvent containing 5-hydroxymethylfurfural to obtain an aqueous solution containing 5-hydroxymethylfurfural Step d: 5-hydroxymethylfurfural obtained in Step c Oxidation process

  According to the present invention, 5-hydroxymethylfurfural oxide can be efficiently and efficiently produced from a sugar raw material by a simple extraction operation and an oxidation reaction.

The method for producing 5-hydroxymethylfurfural oxide (hereinafter also referred to as “HMF oxide”) of the present invention includes the following steps a to d.
Step a: Step of obtaining a reaction solvent containing 5-hydroxymethylfurfural by dehydrating a sugar raw material in the presence of the reaction solvent to produce 5-hydroxymethylfurfural in the reaction solvent Step b: Obtained in Step a Step of extracting 5-hydroxymethylfurfural into a hydrophobic solvent from the obtained reaction solvent containing 5-hydroxymethylfurfural to obtain a hydrophobic solvent containing 5-hydroxymethylfurfural obtained in step c: step b Step of extracting 5-hydroxymethylfurfural into water from a hydrophobic solvent containing 5-hydroxymethylfurfural to obtain an aqueous solution containing 5-hydroxymethylfurfural Step d: 5-hydroxymethylfurfural obtained in Step c Oxidation step With the production method of the present invention, the HMF oxide is efficiently and productive. The reason why it can be produced is not clear, but it is assumed that an intermediate raw material obtained by efficiently separating HMF and impurities can be obtained through steps a to c, so that an oxidation reaction with a good yield can be performed. Is done.

<Step a>
Step a in the production method of the present invention is a step of obtaining a reaction solvent containing HMF by dehydrating a sugar raw material in the presence of the reaction solvent to produce HMF in the reaction solvent.

(Reaction form)
The reaction form of step a is not particularly limited, and may be a batch type, a semi-batch type, a continuous type, or a combination of these. From the viewpoint of improving productivity, semi-batch reaction and continuous reaction are preferable, and from the viewpoint of easy operation, batch reaction is preferable.

(Sugar raw material)
The sugar raw material used in step a may be naturally derived, artificially synthesized, or a mixture of two or more of them. Specific examples of the sugar raw material include saccharides such as monosaccharides, disaccharides, oligosaccharides, and polysaccharides.
Examples of the monosaccharide include fructose, glucose, galactose, mannose, sorbose and the like. Examples of the disaccharide include sucrose, maltose, cellobiose, and lactose. Examples of the oligosaccharide include a combination of arbitrary monosaccharides, and examples of the polysaccharide include a combination of arbitrary monosaccharides, starch, cellulose, and inulin.
In addition, as sugar raw materials, sugar solutions derived from starch, sugarcane, sugar beet, soybean, etc., which are mixtures containing the above sugars, and purified intermediates and purified by-products thereof such as high fructose corn syrup, purified sugar, and crude sugar Waste molasses, invert sugar, isomerized sugar and the like can be used.

  The sugar raw material used in step a is preferably a sugar raw material containing fructose from the viewpoint of economically and efficiently producing HMF oxide. As a sugar raw material containing fructose, preferably, for example, fructose, a disaccharide combining fructose and any monosaccharide, an oligosaccharide combining fructose and any monosaccharide, a polysaccharide combining fructose and any monosaccharide, High fructose corn syrup, and refined intermediates and byproducts thereof, soybean sugar solution, sugar solution derived from sugarcane and sugar beet and purified sugar obtained from the sugar solution, crude sugar, molasses, invert sugar, inulin, etc. It is done. Among these, from the viewpoint of producing HMF oxide economically and efficiently, a mixture of glucose and fructose, purified sugar, crude sugar, molasses, fructose, sucrose, or inulin is more preferable.

  When a sugar raw material that does not contain fructose or has a low fructose content is used, pretreatment may be performed in advance to increase the fructose content. Specific examples of the pretreatment include isomerization treatment, hydrolysis treatment, acid treatment, base treatment and the like with enzymes and chemical substances. Among these, from the viewpoint of productivity and economy, pretreatment using an enzyme is preferred, and pretreatment including isomerase treatment is preferred.

  In the step a, the concentration of the sugar raw material in the reaction solvent is preferably 0.1 to 80% by mass, more preferably 0.5 to 70% by mass from the viewpoint of achieving both improvement in reaction rate and improvement in HMF yield. %, More preferably, it is 1-60 mass%, More preferably, it is 3-50 mass%.

(Dehydration reaction)
The synthesis reaction of HMF from the sugar raw material in step a is a three-molecule dehydration reaction from hexose, mainly fructose. This dehydration reaction is preferably performed using a reaction solvent and a catalyst from the viewpoint of improving the productivity of HMF and improving the purity of the obtained HMF.

(Reaction solvent)
The reaction solvent used in step a is preferably a polar solvent from the viewpoint of improving the productivity of HMF oxide and improving the purity of the obtained HMF. Preferred polar solvents include one or more selected from the group consisting of water, highly polar aprotic organic solvents, and ionic liquids.
Examples of the highly polar aprotic organic solvent include dimethyl sulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylmorpholine, N-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazo. Examples include lysinone, hexamethylphosphoric triamide, tetramethylurea, acetonitrile, ethylene glycol dimethyl ether, tetrahydrofuran and acetone.
Examples of the ionic liquid include imidazolium salts such as 1-ethyl-3-methylimidazolium chloride; pyrrolidinium salts such as 1-butyl-1-methylpyrrolidinium bromide; 1-butyl-1-methylpiperidi Piperidinium salts such as nitrotriflate; pyridinium salts such as 1-butylpyridinium tetrafluoroborate; ammonium salts such as tetrabutylammonium chloride; phosphonium salts such as tetrabutylammonium bromide; sulfonium salts such as triethylsulfonium bis (trifluoromethanesulfonyl) imide Etc.
Of these, water, dimethyl sulfoxide, dimethylacetamide, N, N-dimethylformamide, N-methyl-2-pyrrolidinone, imidazolium from the viewpoint of improving the productivity of HMF oxide, improving the purity of HMF, operability and economy One or more selected from the group consisting of salts and pyridinium salts are more preferable, and one or more selected from the group consisting of water, dimethyl sulfoxide, N-methyl-2-pyrrolidinone, and imidazolium salts Are more preferable, and one or more selected from the group consisting of water, dimethyl sulfoxide, and imidazolium salts are more preferable.

(Hydrophobic solvent)
In the present invention, from the viewpoint of improving the productivity of HMF oxide, suppressing the formation of by-products, and improving the purity of HMF, when water is used as the reaction solvent, the step a and the step b described later are performed simultaneously. Is preferred. Specifically, by performing the dehydration reaction in step a in the presence of water and a hydrophobic solvent, while generating HMF in water, at least a part of the generated HMF is transferred into the hydrophobic solvent, It is preferable to obtain water containing HMF and a hydrophobic solvent containing HMF.

The hydrophobic solvent used when performing step a and step b simultaneously is low in miscibility with water from the viewpoint of improving the productivity of HMF oxide, suppressing the formation of by-products, and improving the purity of HMF. It is preferable that the aqueous phase and the hydrophobic solvent phase are phase-separated. Specifically, the water-octanol partition coefficient (Log P value) is preferably 0.4 or more, more preferably 0.5 or more, still more preferably in the range of 0.5 to 10, and still more preferably. It is in the range of 0.5 to 7, more preferably in the range of 0.5 to 5.
Furthermore, methyl isobutyl ketone (hereinafter also referred to as “MIBK”), cyclohexanone, from the viewpoints of improving the productivity of HMF oxide, suppressing the formation of by-products, improving the purity of HMF, and stability to reaction temperature and catalyst. N-butanol, 2-butanol, tetrahydrofuran, n-amyl alcohol, dichloromethane, trichloromethane, toluene, isophorone, ethyl acetate, propyl acetate, and butyl acetate, and more preferably Is one or more selected from the group consisting of methyl isobutyl ketone, cyclohexanone, n-butanol, 2-butanol, toluene and isophorone, more preferably from the group consisting of methyl isobutyl ketone, isophorone and toluene. One or more selected It is.

  The amount of the hydrophobic solvent used when the step a and the step b are simultaneously performed is 0 with respect to the water used as the reaction solvent from the viewpoints of economy, suppression of HMF by-product formation, and reduction of equipment load. 0.01-100000 mass% is preferable, More preferably, it is 0.1-50000 mass%, More preferably, it is 0.2-25000 mass%, More preferably, it is 1-10000 mass%, More preferably, it is 5-5000 mass%, More preferably, it is 10-2500 mass%.

(Reaction temperature)
The reaction temperature in step a is preferably 50 to 300 ° C., more preferably 60 to 280 ° C. from the viewpoint of improving the reaction rate and suppressing the production of byproducts, although it depends on the type of catalyst used, the reaction solvent and the reaction type. More preferably, it is 70-270 degreeC, More preferably, it is 80-260 degreeC, More preferably, it is 90-250 degreeC, More preferably, it is 100-240 degreeC.

(Reaction pressure)
The reaction pressure in step a depends on the type of catalyst used, the reaction solvent and the reaction type, but is preferably 0.01 to 40 MPa from the viewpoint of improving the reaction rate, reducing the amount of by-products generated, and reducing the equipment load. Preferably it is 0.05-20MPa, More preferably, it is 0.1-15MPa.

(catalyst)
In step a, the dehydration reaction is preferably carried out in the presence of a catalyst from the viewpoint of improving the productivity of HMF and improving the selectivity of HMF. As the catalyst, either a homogeneous catalyst or a heterogeneous catalyst can be used, and an acid catalyst is preferred.
For example, as homogeneous catalysts, inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, boric acid; sulfonic acids such as p-toluenesulfonic acid, xylenesulfonic acid; acetic acid, levulinic acid, oxalic acid, fumaric acid, maleic acid And carboxylic acids such as citric acid; and neutralized salts thereof.
Examples of the heterogeneous catalyst include strongly acidic cation exchange resins represented by amberlist, amberlite, diamond ion, etc .; zeolite, alumina, silica-alumina, silica-magnesia, silica-titania, titania, tin- Metal oxides such as titania and niobia, clays, sulfuric acid immobilization catalysts represented by sulfated zirconia; phosphoric acid immobilization catalysts represented by phosphorylated titania; heteropoly acids, Lewis acids such as aluminum chloride and chromium chloride Metal salts having an action; and mixtures thereof.

  Among these, as the catalyst used in step a, inorganic acids, carboxylic acids, strongly acidic cation exchange resins, sulfuric acid-immobilized catalyst, and phosphoric acid-immobilized from the viewpoint of improving the yield of HMF oxide and economy. One or more selected from the group consisting of catalysts is preferred, more preferably one or more selected from the group consisting of inorganic acids, carboxylic acids, and strongly acidic cation exchange resins, more preferably hydrochloric acid, sulfuric acid, phosphoric acid, One or more selected from the group consisting of nitric acid, boric acid, acetic acid, levulinic acid, oxalic acid, fumaric acid, maleic acid, citric acid, and neutralized salts thereof, more preferably sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid, One or more selected from the group consisting of levulinic acid, oxalic acid, boric acid and neutralized salts thereof, more preferably one selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid and neutralized salts thereof It is a top.

(Amount of catalyst used)
In the case of using a homogeneous catalyst, the amount of the catalyst used in the step a is from the viewpoint of improving the pH in the reaction system and the productivity of HMF oxide, suppressing the production of by-products, and economical efficiency. The content is preferably 0.001 to 50% by mass, more preferably 0.005 to 30% by mass, still more preferably 0.01 to 20% by mass, still more preferably 0.025 to 15% by mass, and still more preferably 0. .05 to 10% by mass. This is not the case when a homogeneous catalyst is used, for example, when a continuous reaction using a fixed catalyst bed is performed.

(Neutralization process)
When an acid catalyst is used in step a, or when the reaction system is in an acidic state, from the viewpoint of improving the productivity of HMF oxide and improving the purity of HMF, It is preferable to neutralize after completion, and more preferably neutralize after completion of the reaction.
Preferred neutralizing agents include basic substances such as anion exchange resins, basic zeolites, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, organic amines. , Calcium oxide, magnesium oxide, and ammonium salts. Of these, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates and organic amines are preferred from the viewpoints of productivity improvement and economic efficiency of HMF oxides. More preferred are hydroxides and alkaline earth metal hydroxides.

  When performing neutralization, from the viewpoint of improving the HMF yield and improving the purity of HMF, the pH of the solution after neutralization is preferably 4 to 10, more preferably 5 to 9, and still more preferably 6 to 8.

(Removal of insoluble matter)
In step a, insoluble matter may be generated during the reaction depending on the reaction conditions, catalyst type, catalyst amount, sugar raw material, and concentration thereof. This insoluble matter is an anhydrous sugar or sugar condensate due to intramolecular and intermolecular dehydration of sugar in the sugar raw material, HMF polymer, HMF, sugar raw material, reaction intermediate, and HMF overreaction product due to condensation polymerization between HMFs. Presumed to be humic substances produced from This insoluble matter is preferably removed by filtration or centrifugation as necessary. The removal step may be performed after step b or step c described later.

<Process b>
Step b in the method of the present invention is a step of obtaining a hydrophobic solvent containing HMF by extracting HMF into a hydrophobic solvent from the reaction solvent containing HMF obtained in the step a.
As specific examples of the extraction method, a reaction solvent containing HMF and a hydrophobic solvent are mixed, and HMF is extracted into the hydrophobic solvent, or the solvent is once distilled off from the reaction solvent containing HMF and concentrated. And a solvent that can be used as the reaction solvent and a hydrophobic solvent are added to the concentrate, and HMF is extracted into the hydrophobic solvent.
When step a and step b are performed simultaneously, after step a and step b are performed at the same time, the step b of extracting HMF into a hydrophobic solvent from the water containing HMF obtained in step a is further performed. Preferably it is done.

  From the viewpoint of economy, reduction of equipment load, and improvement of HMF extraction efficiency, the reaction solvent containing HMF obtained in step a may be appropriately concentrated before performing step b. In this case, examples of the concentration method include concentration under reduced pressure, a method using an osmotic membrane, transpiration, lyophilization, and the like. In the case of concentration under reduced pressure, from the viewpoint of the thermal stability of HMF, it is preferably performed at 150 ° C. or lower, more preferably 120 ° C. or lower, more preferably 100 ° C. under sufficient reduced pressure conditions that can distill off the reaction solvent. ° C or lower, more preferably 80 ° C or lower.

  When the reaction solvent containing HMF obtained in step a is concentrated before carrying out step b, it is added to the hydrophobic solvent used in step b from the viewpoint of improving the amount of solution and operability and improving the HMF purity. Water may be added. The water used is preferably distilled water, ion-exchanged water or pure water from the viewpoints of economic efficiency and HMF purity improvement.

(Hydrophobic solvent)
The hydrophobic solvent used in step b is low in miscibility with water from the viewpoint of improving the productivity of HMF oxide, suppressing the formation of by-products, and improving the purity of HMF. It is preferable that they are phase-separated. Further, from the same viewpoint, the hydrophobic solvent preferably has a water-octanol partition coefficient (Log P value) of 0.3 or more, more preferably 0.4 or more, still more preferably 0.5 or more, and still more. Preferably it is the range of 0.5-10.
Preferred hydrophobic solvents used in step b include aliphatic ketones, aliphatic ethers, aliphatic alcohols, aliphatic esters, lactones, aromatic hydrocarbons having a water-octanol partition coefficient of 0.4 or more. , Aliphatic hydrocarbons, halogenated hydrocarbons, hydrophobic ionic liquids and the like. Of these, 3-methyl-2-butanone, methylisobutylketone, diisobutylketone, 5-methyl-3-heptanone, cyclopentanone, cyclohexanone from the viewpoints of HMF extraction efficiency and suppression of the amount of hydrophobic solvent dissolved in water , Cycloheptanone, cyclooctanone, isophorone, tetrahydrofuran, furfural, furfuryl alcohol, n-butanol, 2-butanol, n-amyl alcohol, isopentyl alcohol, hexyl alcohol, chloromethane, dichloromethane, trichloromethane, trichloroethane, diethyl Ether, methyl-tert-butyl ether, diisopropyl ether, toluene, xylene, decane, decene, dodecane, dodecene, hexane, pentane, petroleum ether, ethyl acetate, propyl acetate, and acetic acid One or more selected from the group consisting of chill are preferred, more preferably methyl isobutyl ketone, cyclohexanone, n-butanol, 2-butanol, n-amyl alcohol, dichloromethane, trichloromethane, ethyl acetate, diethyl ether, One or more selected from the group consisting of methyl tert-butyl ether, diisopropyl ether, toluene, hexane, propyl acetate, and butyl acetate, more preferably methyl isobutyl ketone, cyclohexanone, 2-butanol, dichloromethane, trichloromethane , Diethyl ether, diisopropyl ether, ethyl acetate, butyl acetate, toluene, and one or more selected from the group consisting of hexane.

Extraction can be performed by, for example, batch extraction or countercurrent extraction. The temperature at the time of extraction is preferably 5 to 120 ° C, more preferably 10 to 100 ° C, and further preferably 15 to 80 ° C, from the viewpoint of the thermal stability of HMF.
The amount of the hydrophobic solvent used per extraction process is not particularly limited. From the viewpoint of improving the extraction efficiency of HMF, for example, when performing a batch extraction method, the mass ratio of the reaction solvent or water (reaction solvent) Or water: hydrophobic solvent), preferably 1: 0.1 to 1: 100, more preferably 1: 0.2 to 1:50, and still more preferably 1: 0.5 to 1:20.

(Removal of insoluble matter)
In step b, insoluble matter may be generated depending on the type of sugar raw material, solvent, catalyst, and the like used. This is presumed to be humic substances produced from anhydrous sugar, sugar condensate, HMF polymer by condensation polymerization of HMF, and HMF, sugar raw material, reaction intermediate and HMF overreaction product. This insoluble matter is preferably removed by filtration, centrifugation or the like, if necessary. The removal step may be performed after step b or after step c described later.

<Process c>
Step c in the method of the present invention is a step of obtaining an aqueous solution containing HMF by extracting HMF into water from the hydrophobic solvent containing HMF obtained in the aforementioned step b.
Specific examples of the extraction method include a method in which a hydrophobic solvent containing HMF and water are mixed to extract HMF into water, or after the hydrophobic solvent is once distilled off from the hydrophobic solvent containing HMF, Examples include a method of adding HMF and water to extract HMF in water.

From the viewpoint of reducing equipment load and improving the extraction efficiency of HMF, the hydrophobic solvent used for extraction may be distilled off after step b and before step c to concentrate HMF.
Examples of the method for concentrating HMF include vacuum concentration, a method using an osmotic membrane, and transpiration. In the case of concentration under reduced pressure, from the viewpoint of the thermal stability of HMF, it is preferably performed at 150 ° C. or lower, more preferably 120 ° C. or lower, and more preferably 120 ° C. or lower, under a sufficient reduced pressure condition that can distill off the hydrophobic solvent. 100 ° C. or lower, more preferably 80 ° C. or lower.

  When performing the extraction operation after concentrating the HMF extract obtained in step b, in addition to water, a hydrophobic solvent that can be used in step b is added as appropriate from the viewpoint of improving the amount of solution, operability, and HMF purity. May be.

  The water used in step c is preferably distilled water, ion-exchanged water, or pure water from the viewpoints of economic efficiency, HMF purity improvement, and HMF oxide productivity. In step c, one or more organic solvents may be further mixed with water from the viewpoint of improving extraction efficiency and operability during extraction, and shortening the work process. Preferred organic solvents include methanol, ethanol, propanols, butanols, acetonitrile, tetrahydrofuran, dioxanes, acetone, methyl ethyl ketone, and the like. Among these, from the viewpoint of improving the purity of HMF, methanol, ethanol or isopropanol is preferable, more preferably methanol or isopropanol, and still more preferably isopropanol.

  The mixing ratio (mass ratio) of water and the hydrophobic solvent containing HMF in step c is not particularly limited. From the viewpoint of improving the extraction efficiency of HMF, for example, when performing a batch type extraction method, per extraction process The ratio is preferably from 1: 0.01 to 1: 100, more preferably from 1: 0.05 to 1:50, still more preferably from 1: 0.1 to 1:20.

  After completion of step c, the aqueous solution used for extraction may be distilled off and concentrated. Examples of the concentration method include concentration under reduced pressure, a method using an osmotic membrane, transpiration, lyophilization, and the like. In the case of concentration under reduced pressure, from the viewpoint of the thermal stability of HMF, it is preferably performed at 150 ° C. or lower, more preferably 120 ° C. or lower, more preferably 100 ° C. under a sufficient reduced pressure condition that water can be distilled off. Below, it is 80 degrees C or less more preferably. At this time, it is preferable to distill off a gas such as nitrogen from the viewpoint of the obtained HMF purity. Or it is also preferable from the viewpoint of HMF purity improvement to add and distill off the solvent which forms an azeotrope with water, for example, methanol, ethanol, isopropanol, or acetone.

<Step (c-2)>
The production method of the present invention preferably includes a step (c-2) (hereinafter sometimes referred to as “step c-2”) for further purifying HMF from the aqueous solution containing HMF obtained in step c. Preferable purification methods include, for example, dehydration, crystallization and recrystallization, solvent extraction, adsorption treatment, column chromatography, and distillation.
In the case of dehydration, for example, drying under reduced pressure or using a dehydrating agent such as sodium sulfate or molecular sieves is performed.
In the case of recrystallization, for example, it is performed by cooling to a temperature at which HMF is recrystallized.
In the case of solvent extraction, the solvent to be used is preferably one that has low miscibility with water used in step c and phase separation of the aqueous phase and the hydrophobic solvent phase.
As the preferable solvent used in the solvent extraction in step c-2, the above-mentioned hydrophobic solvent is preferable. The hydrophobic solvent preferably has a water-octanol partition coefficient (Log P value) of 0.5 or more, more preferably 1.0 or more, and still more preferably 1.3 to 5, such as toluene. , Xylene, hexane and the like. Of these, toluene is preferable from the viewpoint of improving the HMF purity.
In the case of adsorption treatment, depending on the impurities in the solution after step c and its concentration, for example, silica, activated carbon, white clay, adsorption treatment resin, ion exchange resin, or the like can be used.
Among these, from the viewpoint of the purity of the obtained HMF, one or more selected from the group consisting of dehydration, recrystallization, solvent extraction, and adsorption treatment are preferable, and recrystallization is more preferable.

<Process d>
Step d in the method of the present invention is a step of oxidizing the HMF obtained in step c or step c-2.
The method for oxidizing HMF is not particularly limited, but preferred methods include (1) a method of oxidizing HMF by contacting it with an oxidizing gas in an organic acid solvent in the presence of a metal catalyst and a halogen compound (hereinafter referred to as “the HMF”). (Also referred to as “oxidation method 1”), and (2) a method in which an oxidizing gas and HMF are brought into contact with each other in the presence of a catalyst containing at least one metal element selected from Groups 8 to 11 of the periodic table. (Hereinafter also referred to as “oxidation method 2”).

(Oxidation method 1)
The oxidation method 1 is a method of oxidizing HMF in contact with an oxidizing gas in an organic acid solvent in the presence of a metal catalyst and a halogen compound.

(Reaction format)
The reaction of the oxidation method 1 may be carried out by any of batch, semi-continuous and continuous methods.
The batch method is a method in which the raw material HMF and the whole amount of the catalyst are charged in a reactor in advance, an oxidizing gas is passed through the reaction solution to perform an oxidation reaction, and the reaction solution is recovered at a time after the reaction is completed.
The semi-continuous method is, for example, a method in which the entire amount of the catalyst is charged into the reactor, the oxidation reaction is performed while continuously supplying the raw material HMF and the oxidizing gas to the reactor, and the reaction liquid is recovered at once after the reaction is completed. It is.
The continuous method is a method in which the reaction solution is continuously recovered by performing an oxidation reaction while continuously supplying all of the raw material HMF, the catalyst, and the oxidizing gas to the reactor.
In industrial implementation, the continuous type or semi-continuous type is preferable from the viewpoint of operation efficiency.

(Organic acid solvent)
The organic acid solvent used in the oxidation method 1 is preferably acetic acid, propionic acid, or a mixed solvent of acetic acid / acetic anhydride, more preferably acetic acid, from the viewpoint of reaction yield and solvent recovery.
Although the usage-amount of an organic acid solvent is not specifically limited, 1.0-30 are preferable by weight ratio of [organic acid solvent / HMF] from a viewpoint of productivity, 3-20 are more preferable, and 5-15 are still more preferable. .

(catalyst)
The metal catalyst used in the oxidation method 1 is preferably one or more selected from a cobalt-based catalyst and a manganese-based catalyst. The cobalt-based catalyst and the manganese-based catalyst are not particularly limited as long as they can be dissolved in the reaction solvent at the reaction temperature.
Examples of the cobalt-based catalyst include one or more selected from an inorganic acid salt of cobalt (for example, bromide, carbonate, etc.) and an organic acid salt (for example, acetate, propionate, etc.). Among these, from the viewpoints of availability and economy, preferably cobalt acetate, cobalt bromide, cobalt sulfate, cobalt nitrate, cobalt carbonate, cobalt chloride, and cobalt, and more preferably cobalt acetate and cobalt bromide. In addition, cobalt acetate is preferable, and a hydrate thereof may be used.
Examples of the manganese-based catalyst include one or more selected from inorganic salts of manganese (for example, bromide, carbonate, etc.) and organic acid salts (for example, acetate, propionate, etc.). Among these, manganese acetate, manganese bromide, manganese sulfate, manganese nitrate, manganese carbonate, manganese chloride, and manganese are preferable from the viewpoint of availability and economy, and more preferably manganese acetate and manganese bromide. Further, manganese acetate is preferable, and a hydrate thereof may be used.

The halogen compound used in oxidation method 1 may be any halogen compound that can be dissolved in a reaction solvent at the reaction temperature to supply halogen ions. Bromine, chlorine, fluorine, iodine, hydrides of these halogens, alkali metal salts, cobalt Examples include salts, manganese salts, ammonium salts, and organic halides.
Among these, bromine, sodium bromide, potassium bromide, cobalt bromide, and manganese bromide are preferable from the viewpoint of reactivity.
Cobalt bromide and manganese bromide can serve as both the cobalt catalyst and the halogen compound.

(Oxidation catalyst amount)
The amount of the metal catalyst and halogen compound used in oxidation method 1 is cobalt based on HMF from the viewpoint of reactivity to the raw material HMF obtained by the method including steps a to c and the yield of HMF oxide. It is preferable that the catalyst is 0.1 to 30.0 mol%, the manganese-based catalyst is 0.1 to 30 mol%, the halogen compound is 0.01 to 20.0 mol%, and the cobalt-based catalyst is 0.5 to 20.0 mol%, manganese-based catalyst is 0.5 to 20.0 mol%, and halogen compound is 0.00. 1 to 15.0 mol% is more preferable, the cobalt catalyst is 1.0 to 15.0 mol%, the manganese catalyst is 1.0 to 20.0 mol%, and the halogen compound is 0.1 to 10 mol%. More preferably, it is 0.0 mol%.

(Oxidizing gas supply method, pressure, flow rate)
The oxidizing gas used in the oxidation method 1 may be oxygen, air, and a mixed gas of two or more selected from oxygen, air, and an inert gas for dilution (nitrogen, argon, etc.).
The method for supplying the oxidizing gas is not particularly limited as long as it can be supplied to the reactor at a predetermined pressure and flow rate. The oxidizing gas may be circulated in the gas phase space or may be blown from the liquid.

A typical supply method of the oxidizing gas is a mixture of air and an inert gas for dilution (nitrogen, argon, etc.) by a known mixer, and a predetermined pressure and / or a predetermined flow rate as a mixed gas in which the oxygen concentration is controlled. This is a method of supplying to the reactor.
The higher the pressure of the oxidizing gas, the higher the reactivity, as long as the reaction solvent can maintain a liquid phase at the reaction temperature. However, if the pressure is too high, the capital investment for securing confidentiality increases, and the preparation time before and after the reaction often increases, which increases the possibility of reducing productivity. From these viewpoints, the pressure of the oxidizing gas is preferably 0.01 MPa to 10 MPa, more preferably 0.1 MPa to 8 MPa, and still more preferably 0.1 MPa to 5 MPa.
As the flow rate of the oxidizing gas increases, the reactivity increases. However, if the flow rate is too large, the equipment investment for supply increases and the amount of exhaust gas increases, resulting in a decrease in economic efficiency. Therefore, the flow rate of the oxidizing gas is preferably 1 to 20 L / min, more preferably 2 to 10 L / min per 1.0 mol of charged HMF.

(Reaction temperature)
The reaction temperature of the oxidation reaction 1 is preferably 50 to 250 ° C, more preferably 60 to 240 ° C, still more preferably 80 to 230 ° C, still more preferably 90 to 220 ° C, and more preferably 100 to 200 ° C from the viewpoint of reactivity. Further preferred.

(Purification)
From the viewpoint of improving the purity, the HMF oxide may be purified after completion of the oxidation reaction, and can be purified by a known method such as JP-A-2001-288139.
For example, when the HMF oxide is FDCA, a liquid containing water is added to the HMF oxide obtained by filtration after completion of the oxidation reaction to form a slurry, which is heated and dissolved in the presence of the hydrogenation catalyst. It can refine | purify by performing a hydrogenation process and subjecting the obtained reaction material to crystallization and solid-liquid separation. It is preferable to dry the solid obtained by solid-liquid separation after the purification step as it is to obtain a product. Furthermore, after adding water and washing | cleaning newly, the solid substance isolate | separated into solid and liquid may be dried and it may be set as a product.

(Oxidation method 2)
The oxidation method 2 is a method in which an oxidizing gas and HMF are brought into contact with each other and oxidized in the presence of a catalyst containing at least one metal element selected from Groups 8 to 11 of the periodic table.

(Oxidation catalyst)
The catalyst used in the oxidation method 2 is a catalyst containing at least one metal element selected from Groups 8 to 11 of the periodic table (hereinafter also referred to as “noble metal catalyst”).
The noble metal catalyst contains one or more elements selected from ruthenium, rhodium, palladium, osmium, iridium, platinum, gold, and cobalt (hereinafter also referred to as “platinum group elements”) from the viewpoint of catalytic activity. It is more preferable to contain one or more elements selected from palladium, gold, ruthenium and platinum, and it is more preferable to contain one or more elements selected from palladium and platinum.

Further, when the noble metal catalyst contains one or more elements selected from platinum group elements (hereinafter, also referred to as “catalyst first component”), as a catalyst component, tin, bismuth, selenium, zinc, lead, It is preferable to contain one or more elements selected from tellurium and antimony (hereinafter also referred to as “catalyst second component”).
Further, when the noble metal catalyst contains the first catalyst component and the second catalyst component, the catalyst component further contains one or more elements selected from rare earth elements (hereinafter also referred to as “catalyst third component”) as the catalyst component. can do.
The ratio of the catalyst first component to the catalyst second component is preferably 0.001 to 10, more preferably 0.005 to 7 in terms of the atomic ratio of [catalyst second component / catalyst first component] from the viewpoint of catalyst activity. 0.01 to 6 is more preferable. Further, the ratio of the catalyst first component to the catalyst third component is preferably 0.01 to 5 in terms of the [catalyst third component / catalyst first component] atomic ratio.

The noble metal catalyst used in the oxidation method 2 is preferably used as a supported catalyst supported on a carrier. The carrier is preferably an inorganic carrier such as activated carbon, alumina, silica gel, activated clay, diatomaceous earth, clay, zeolite, silica, silica-alumina, silica-magnesia, silica-titania, titania, tin-titania, niobium, zirconia, and ceria. Of these, alumina, silica, titania, ceria, and activated carbon are more preferable.
The total supported amount of the first catalyst component is preferably 0.1 to 20% by mass, more preferably 1 to 15% by mass, and still more preferably 2.0 to 13% by mass, based on the total amount of the supported catalyst. The total supported amount of the second catalyst component is preferably 0.001 to 20% by mass, more preferably 0.01 to 15% by mass, and still more preferably 0.05 to 10% by mass of the total amount of the supported catalyst. The total supported amount of the third catalyst component is preferably 0.01 to 20% by mass, more preferably 0.05 to 15% by mass, and still more preferably 0.1 to 5% by mass, based on the total amount of the supported catalyst.

The noble metal catalyst used in the oxidation method 2 can be produced by a known method such as JP-A-62-269746. For example, an aqueous solution of a compound containing an element of the first catalyst component (palladium chloride, chloroplatinic acid, etc.), an aqueous solution of a compound containing the element of the second catalyst component (bismuth chloride, antimony pentachloride, etc.), It can be produced by a method in which an aqueous solution of a compound containing three elements (cerium chloride, lanthanum chloride, etc.) is adsorbed on a carrier such as activated carbon in water in a lump or divided and then the catalyst component is reduced.
From the viewpoint of catalytic activity, the total amount of the first catalyst component in the noble metal catalyst is preferably 0.0001 to 2.0 mass%, more preferably 0.001 to 1.5 mass%, based on HMF. More preferably, it is used so that it may become 0.01-1.0 mass%.
Further, when the noble metal catalyst includes the first catalyst component and the second catalyst component, the total of the first catalyst component and the second catalyst component is preferably 0.0001 to 4.0% by mass with respect to HMF. Preferably it is 0.001-3.0 mass%.
When the noble metal catalyst includes a catalyst first component, a catalyst second component, and a catalyst third component, the total of the catalyst first component and the catalyst second component is preferably 0.001 to 6.0 mass with respect to HMF. %, More preferably 0.01 to 4.0% by mass.

(solvent)
In the oxidation method 2, it is preferable to use a solvent. As the solvent, water is preferable from the viewpoints of availability, economy, and safety. Moreover, an organic solvent can also be used as needed. From the viewpoint of improving the productivity of the HMF oxide, the concentration of water in the liquid phase at the time of preparation is usually 0 to 99% by mass, preferably 5 to 95% by mass, and more preferably 5 to 80% by mass.

(Oxidizing gas)
The oxidizing gas used in the oxidation method 2 is the same as the oxidizing gas used in the oxidation method 1 described above.
In the oxidation reaction of oxidation method 2, the amount of dissolved oxygen in the liquid phase is preferably 1 ppm or less, more preferably 0 to 0.8 ppm, still more preferably 0 to 0.5 ppm, and then an oxidizing gas such as oxygen is supplied. It is preferable to start. In this way, the reaction proceeds promptly even in the initial reaction.
Before starting the supply of oxidizing gas, the amount of dissolved oxygen in the liquid phase is 1 ppm or less. (1) In the liquid phase, helium, argon, nitrogen, carbon dioxide, etc., methane, ethane, propane, etc. (2) Add methanol, ethanol, propanol, formaldehyde, acetaldehyde, propionaldehyde, hydrogen, etc. that react with oxidizing gas to the reaction solution. Although the method etc. are mentioned, the method of (1) is preferable from a viewpoint of operativity and safety | security.
In the case of using an oxygen-containing mixed gas, the oxygen concentration in the gas to be blown is preferably 10% by volume or more, more preferably 20% by volume or more, but particularly preferably oxygen alone is blown.

(Reaction temperature)
The reaction temperature in the oxidation reaction by the oxidation method 2 is preferably 30 to 200 ° C., more preferably 35 to 180 ° C., and further preferably 40 to 150 ° C. from the viewpoints of oxygen solubility and low energy. Alternatively, the reaction temperature may be controlled in multiple stages such that several hours after the start of the reaction is kept at 50 ° C. or lower and then raised to 50 ° C. or higher.

(Reaction pressure)
The reaction pressure may be normal pressure, but is usually 0.01 to 3.0 MPa, preferably 0.01 to 2.0 MPa, more preferably 0.01 to 1.5 MPa.

(Alkaline substance)
The oxidation of HMF by the oxidation method 2 is preferably performed in a liquid phase containing an alkaline substance. Examples of alkaline substances include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, alkali metal carbonates, and alkaline earth metal carbonates. Is mentioned. Of these, alkali metal hydroxides are preferred from the viewpoints of reactivity and economy.
From the viewpoint of reaction rate and suppression of side reaction of HMF, it is preferable to use an alkali substance in such an amount that the pH of the liquid phase is preferably 7.5 or more, more preferably pH 8-13. Since the pH of the reaction system decreases with the progress of the oxidation reaction, it is preferable to charge the alkali all at once or continuously or intermittently so as to be in the above pH range to advance the oxidation reaction.

When the oxidation of HMF by oxidation method 2 is carried out in a liquid phase containing an alkaline substance, HMF, FDCA, and carboxylic acids are included in the liquid phase after completion of the reaction and after removal of the catalyst by a method such as filtration or centrifugation. Is dissolved in the form of a salt with an alkaline substance. If necessary, it can be acidified with a mineral acid such as hydrochloric acid to obtain an oxide of HMF.
From the viewpoint of simplifying the acidification step and improving productivity, it is preferable to oxidize HMF in water or an organic solvent without using an alkaline substance.

(5-hydroxymethylfurfural oxide)
Examples of the 5-hydroxymethylfurfural oxide of the present invention include 2,5-furandicarboxylic acid (FDCA), diformylfuran (DFF), 2-carboxy-5-formylfuran (CFF), 5-hydroxymethyl-2- Examples include furancarboxylic acid (HMFA) and 5-acetoxymethyl-2-furancarboxylic acid (AcMFA). The desired product is produced by performing an oxidation reaction by appropriately selecting the reaction conditions in step d. be able to. Among these, 2,5-furandicarboxylic acid (FDCA) is preferable from the viewpoint of usefulness as a chemical raw material.

  Examples and the like specifically showing the present invention will be described below. In the following examples and comparative examples, “%” means “mass%” unless otherwise specified.

<Sugar conversion and hexose content>
Measurement was performed by high performance liquid chromatography. The sugar content in the biomass raw material was also calculated by the following method.
・ Detector: CAD
Column: Asahipak NH2P-50
・ Temperature: 25 ℃
・ Eluent: a) Acetonitrile b) Water containing 30% methanol ・ Flow rate: 1.0 mL / min

<HMF, organic acid content>
Measurement was performed by high performance liquid chromatography.
・ Detector: RI
Column: ICSep COREGEL-87H
・ Temperature: 80 ℃
・ Eluent: Water containing 0.1% trifluoroacetic acid ・ Flow rate: 0.6 mL / min

<HMF purity>
Measurement was performed by gas chromatography.
-GC equipment: 6850, manufactured by Gilent Technology
・ Column: DB-WAX (30 m × 0.25 mm × 0.25 μm) manufactured by Agilent Technologies
・ Detector: FID
Carrier: Helium gas, 24.5 mL / min Temperature rising condition: 40 ° C. held for 10 minutes, heated from 40 ° C. to 230 ° C. at 10 ° C./min. Thereafter, maintained at 230 ° C. for 8 minutes.

<HMF oxidation composition>
Measurement was performed by high performance liquid chromatography.
・ Detector: UV
Column: L-column2 ODS
・ Temperature: 40 ℃
-Eluent: 0.1% trifluoroacetic acid-containing water, 0.1% trifluoroacetic acid-containing methanol-Flow rate: 1.0 mL / min

<Water-octanol partition coefficient of solvent (Log P value)>
The water-octanol partition coefficient of the hydrophobic solvent used in the examples is as shown in Table 1.
The “Log P value” in this specification means the logarithmic value of the 1-octanol / water partition coefficient of the solvent, and is calculated by the fragment approach according to SRC's LOGKOW / KOWWIN Program of KowWin (Syracuse Research Corporation, USA). The KowWin Program methodology is described in the following journal article: Meylan, WM and PH Howard. 1995. Atom / fragment contribution method for using octanol-water partition coefficients. J. Pharm. Sci. 84: 83- 92.).
The fragment approach is based on the chemical structure of the compound and takes into account the number of atoms and the type of chemical bond. The LogP value is a numerical value generally used for relative evaluation of the hydrophilicity / hydrophobicity of an organic compound.

Production Example 1 (Production of HMF from fructose)
(Process a)
1 L glass solenoid valve autoclave (made by pressure-resistant glass industry), 40 g of D-fructose (made by Wako Pure Chemical Industries) as a sugar raw material, 80 g of ion exchange water as a reaction solvent, MIBK (Wako Pure Chemical Industries, Ltd.) as a hydrophobic solvent 320 g manufactured by Kogyo Co., Ltd., LogP value: 1.31), and 4.0 g phosphoric acid (purity 85%, manufactured by Sigma-Aldrich Japan Co., Ltd.) were charged as a catalyst. After sealing the container, the internal space was sufficiently replaced with nitrogen. Thereafter, the contents were heated to 140 ° C. with sufficient stirring, and then the reaction was carried out for 3 hours while maintaining the temperature and stirring. The gauge pressure during the reaction was 0.4 MPa.
After completion of the reaction, the contents were cooled until the temperature of the contents became 30 ° C. or lower while maintaining stirring. After cooling, the content was filtered, and then the filtrate was stirred and neutralized by adding 50% aqueous sodium hydroxide solution to adjust the pH of the content to 7. After neutralization, the contents were filtered to remove insoluble matters.
After removing the insoluble matter, samples were taken from each of the aqueous solution layer and MIBK solution layer, diluted with pure water, and the peak areas of D-fructose and HMF were measured by high performance liquid chromatography. From the peak areas of D-fructose and 5-hydroxymethylfurfural in the obtained chromatogram, a D-fructose and 5-hydroxymethylfurfural concentration-area relational expression prepared in advance was used to determine D- in the sample. When the fructose and HMF concentrations were calculated, the conversion rate of D-fructose was 93%, and it was confirmed that 73% (20.4 g) of HMF was produced based on the molar amount of D-fructose charged.

(Process b)
After completion of the reaction obtained in step a, each of the filtrate aqueous solution layer and MIBK solution layer was separated. The obtained aqueous solution phase was transferred to a separatory funnel, and 0.5 times mass of MIBK was added to the aqueous solution phase to separate and extract HMF in the aqueous solution layer. This extraction operation was performed three times, and the MIBK solution layer obtained by the extraction operation and the MIBK solution layer after completion of the reaction separated as described above were mixed, and MIBK was distilled off with a rotary evaporator (50 ° C. warm bath). HMF was concentrated. When measured by high performance liquid chromatography in the same manner as in step a, the mass of HMF in the concentrate was 20.1 g, and the extraction recovery rate of HMF was 98.6%. Further, the concentrated solution and tetradecane (internal standard substance) were mixed and diluted with acetone (manufactured by Wako Pure Chemical Industries, Ltd.), and the peak areas of HMF and tetradecane were measured by gas chromatography. From the peak area ratio of 5-hydroxymethylfurfural and tetradecane and the sample preparation mass ratio in the obtained chromatogram, the relational expression of the area ratio-mass ratio of 5-hydroxymethylfurfural and tetradecane prepared in advance was used. The HMF purity in the sample was calculated, and the HMF purity was 82.2% by mass.
The same operation was performed to obtain 11.0 g of HMF concentrate (purity 79.7%).
Further, the same operation was performed to obtain 4.1 g of HMF concentrate (purity 80.3%).

(Process c)
1.0 g of the HMF concentrate obtained in step b is weighed, transferred to a separatory funnel, 5.0 g of MIBK is added, the HMF concentrate is diluted, 7.5 g of ion-exchanged water is added, and organic Separation extraction operation of HMF in the solvent layer was performed. This extraction operation was performed three times, and the aqueous solution obtained by the extraction operation was concentrated with a rotary evaporator (50 ° C. warm bath) to obtain an HMF concentrate. The extraction recovery rate of HMF and the HMF purity in the HMF concentrate were measured in the same manner as in Step b of Example 1. The HMF extraction rate into the aqueous layer was 88.5%, and the HMF purity in the HMF concentrate was 83. It was 0 mass%. The residual amount of MIBK in the concentrate was below the detection limit as measured by gas chromatography.

Production Example 2 (Production of HMF from fructose)
(Process c: Water extraction purification)
5.5 g of the HMF concentrate obtained in Step b of Production Example 1 was weighed and transferred to a separatory funnel, and 40.0 g of dichloromethane (Wako Pure Chemical Industries, Ltd., Log P value: 1.25) was added. After diluting the HMF concentrate, 1.0 g of isopropyl alcohol (manufactured by Kanto Chemical Co., Inc.) and 20.0 g of ion-exchanged water were added, and a liquid separation extraction operation of HMF in the organic solvent layer was performed. This extraction operation was performed 5 times, and the aqueous solution obtained by the extraction operation was concentrated with a rotary evaporator (50 ° C. warm bath) to obtain an HMF concentrate. The HMF extraction rate into the aqueous layer was 92%, and the HMF purity in the HMF concentrate was 97.0%.

Production Example 3 (Production of HMF from fructose)
(Process c: Water extraction purification)
5.0 g of the HMF concentrate obtained by the same operation as in Step b of Production Example 1 was weighed, transferred to a separatory funnel, 40.0 g of cyclohexanone (Sigma Aldrich Japan) was added, and the HMF concentrate was added. After dilution, 20.0 g of ion-exchanged water was added, and a separation extraction operation of HMF in the organic solvent layer was performed. This extraction operation was performed 5 times, and the aqueous solution obtained by the extraction operation was concentrated with a rotary evaporator (50 ° C. warm bath) to obtain an HMF concentrate. The HMF extraction rate into the aqueous layer was 51.0%, and the HMF purity in the HMF concentrate was 95.9%.

Production Example 4 (Production of HMF from fructose)
(Step c-2: Solvent extraction purification)
1.5 g of the HMF concentrate obtained in Step c of Production Example 1 was dissolved in 1.5 ml of ethyl acetate (Wako Pure Chemical Industries, Ltd., Log P value: 0.73). The obtained ethyl acetate solution was slowly added dropwise while stirring 50 ml of toluene (manufactured by Wako Pure Chemical Industries, Ltd.) in a glass beaker in advance. After completion of dropping, the solution was allowed to stand and the organic solvent layer was separated. The residue was again dissolved in 1.5 ml of ethyl acetate and collected. The collected ethyl acetate solution was again subjected to the above step, and the organic solvent layer was separated. The obtained organic solvent layers were mixed and concentrated with a rotary evaporator (50 ° C. warm bath) to obtain 1.2 g of orange HMF concentrate. The HMF purity in the concentrate was 98.2%.

Production Example 5 (Production of HMF from fructose)
(Step c-2: Recrystallization purification)
1.2 g of the HMF concentrate obtained in Production Example 4 was dissolved in 100 g of toluene and allowed to cool and stand at −30 ° C. to precipitate pale yellow needle-like crystals. The toluene solution was collected and concentrated with a rotary evaporator (50 ° C. warm bath), and the same operation was repeated twice. The obtained crystals were washed with sufficiently cooled toluene and dried under reduced pressure. 0.9 g of pale yellow needle crystals were obtained.
The same operation was repeated to obtain 4.5 g of pale yellow needle crystals. The HMF purity in the concentrate was 96.7%.

Production Example 6 (Production of HMF from fructose)
(Step c-2: Adsorption treatment purification)
Purified by column chromatogram using 6.37 g of HMF concentrate (HMF content: 3.96 g, HMF purity: 62.2%) obtained in step b of production example 1 (step c was not carried out) . 200 g of silica (Silica Gel 60N, 40-50 μm, manufactured by Kanto Chemical Co., Inc.) and a developing solvent were mixed in a glass column container. The developing solvent used was prepared by mixing acetone (manufactured by Wako Pure Chemical Industries) and hexane (manufactured by Wako Pure Chemical Industries) at 1: 1 (volume ratio). The HMF concentrate was fractionated into a test tube by a certain amount by a column, and the solvent was distilled off to obtain 4.1 g of HMF concentrate. The HMF recovery rate was 99.7% and the HMF purity in the concentrate was 94.7%.

Example 1 (Production of 2,5-furandicarboxylic acid (FDCA) by oxidation method 1)
HMF (purity 97.0%) 3.97 g obtained in Production Example 2 in a 500 mL titanium solenoid valve autoclave (manufactured by Nitto High Pressure Co., Ltd.), 44.89 g of acetic acid (manufactured by Wako Pure Chemical Industries, Ltd.), 0.26 g Of cobalt acetate (manufactured by Wako Pure Chemical Industries, Ltd.), 0.47 g of manganese acetate (manufactured by Sigma-Aldrich Japan), and 0.10 g of sodium bromide (manufactured by Wako Pure Chemical Industries, Ltd.) were charged. After sealing the container, the internal space was sufficiently replaced with oxygen. Thereafter, the contents were heated to 150 ° C. with sufficient stirring, and maintained at 0.3 MPa while supplying oxygen to the internal space. Thereafter, the reaction was carried out for 3 hours while maintaining the temperature and stirring. After completion of the reaction, the contents were cooled until the temperature of the contents became 30 ° C. or lower while maintaining stirring. After cooling, the contents were filtered to separate the solid and the filtrate, and the solid and the filtrate were diluted with a mixed solution of pure water and methanol and measured by liquid chromatography.
HMF measured the peak area of HMF in the chromatogram obtained by the UV detection method (absorption wavelength: 254 nm), and calculated the concentration in the sample using the HMF concentration-area relational expression prepared in advance. . As a result, the conversion of HMF was 100% based on the amount of HMF charged, and the yield of HMF oxide was 80.9% (3.78 g). Among them, the yield of FDCA was 73.8% (3.52 g), and the yield of DFF was 7.1% (0.27 g).

Example 2 (Production of FDCA and formylfuran (DFF) by oxidation method 1)
4.53 g of HMF (purity 96.7%) obtained in Production Example 5, 41.93 g of acetic acid (manufactured by Wako Pure Chemical Industries, Ltd.), 0.26 g of cobalt acetate, 0.52 g of manganese acetate, 0.14 g The reaction was carried out under the same conditions as in Example 1 except that sodium bromide was charged, and measurement was performed by liquid chromatography.
As a result, the conversion of HMF was 99.9% based on the amount of HMF charged, and the yield of HMF oxide was 84.2% (4.42 g). Among them, the yield of FDCA was 71.0% (3.85 g), and the yield of DFF was 13.1% (0.57 g).

Comparative Example 1
10.0 g of HMF (purity 79.7%) obtained by the step b of production example 1 (step c is not carried out), 48.85 g of acetic acid, 0.31 g of cobalt acetate, 0.59 g of manganese acetate, The reaction was performed under the same conditions as in Example 1 except that 0.14 g of sodium bromide was charged, and the measurement was performed by liquid chromatography.
As a result, the conversion of HMF was 99.9% based on the amount of HMF charged, and FDCA was confirmed as a HMF oxide in a yield of 1.3% (0.12 g).

Comparative Example 2
Other than charging 3.92 g of HMF (purity 94.7%) obtained in Production Example 6, 46.05 g acetic acid, 0.07 g cobalt acetate, 0.15 g manganese acetate, 0.06 g sodium bromide Were reacted under the same conditions as in Example 1 and measured by liquid chromatography.
As a result, the conversion of HMF was 94.1% on the basis of the amount of HMF charged, and the yield of HMF oxide was 0.5% (0.018 g). Among them, the yield of FDCA was 0.3% (0.012 g), the yield of DFF was 0.1% (0.003 g), and the yield of CFF was 0.1% (0.003 g).

Example 3 (Production of 2,5-furandicarboxylic acid (FDCA) by oxidation method 2)
A catalyst (Evonik Deguss, Inc.) in which a 50 ml glass three-necked flask was loaded with 1.71 g of HMF (purity 95.9%) obtained in Production Example 3, 4% palladium, 1% platinum, 5% bismuth on activated carbon. Manufactured, water content 53.7%) 0.19 g and ion-exchanged water 12.92 g were added. Next, a stirring blade (crescent moon type), an oxygen gas introduction pipe, a discharge pipe and a thermometer were attached to the flask. The liquid phase was stirred at 400 rpm, and the temperature of the reaction liquid (liquid phase) was increased to 60 ° C. in 16 minutes while flowing nitrogen at 50 ml / min. Next, an oxidation reaction was carried out for 24 hours while 2.15 g of a 48% aqueous sodium hydroxide solution (25.80 mmol as sodium hydroxide) and oxygen were blown at a rate of 100 mol% / hour (to the HMF charge ratio).
After completion of the reaction, the catalyst was filtered off from the reaction solution to obtain an aqueous solution of HMF. The aqueous phase was collected, diluted with a mixture of pure water and methanol, and measured by liquid chromatography. As a result, the conversion of HMF was 99.6% based on the amount of HMF charged, and FDCA (sodium salt type) was confirmed as the HMF oxide in a yield of 37.3% (0.97 g).

Example 4 (Production of FDCA by oxidation method 2)
HMF obtained by Production Example 4 (purity 96.7%) 1.21 g, catalyst having 4% palladium, 1% platinum, 5% bismuth supported on activated carbon (manufactured by Evonik Degussa, water content 53.7%) 0.18 g and 9.07 g of ion-exchanged water were respectively added, and the temperature of the reaction solution (liquid phase) was raised to reach 60 ° C. in 23 minutes, and 1.79 g of 48% sodium hydroxide aqueous solution (sodium hydroxide) 21.48 mmol) was added and the reaction was carried out for 27 hours.
As a result, the conversion of HMF was 100% based on the amount of HMF charged, and FDCA (sodium salt type) was confirmed as the HMF oxide in a yield of 56.0% (1.03 g).

Comparative Example 3 (Production of FDCA and CFF by oxidation method 2)
Catalyst obtained by supporting 3.57 g of HMF (purity 80.3%) obtained by Step b of Production Example 1 (Step c is not performed), 4% palladium, 1% platinum, 5% bismuth on activated carbon (Evonik Degussa Co., Ltd. (water content 53.7%) was charged with 0.38 g and ion-exchanged water 27.76 g. The temperature of the reaction solution (liquid phase) reached 60 ° C. in 15 minutes, and 48% The same operation as in Example 3 was performed except that 4.01 g of sodium hydroxide aqueous solution (48.12 mmol as sodium hydroxide) was added and the reaction was performed for 30 hours.
As a result, the conversion of HMF was 100% based on the amount of HMF charged, and the yield of HMF oxide was 26.9% (1.08 g). Among them, the yield of FDCA (sodium salt type) was 25.9% (1.04 g), and the yield of CFF was 1.0% (0.04 g).

According to the above embodiment, high-purity 5-hydroxymethylfurfural is produced by producing high-purity 5-hydroxymethylfurfural by a simple extraction operation using a hydrophobic solvent and water, and simply oxidizing it. It can be seen that the oxide can be produced efficiently and economically.
On the other hand, in Comparative Examples 1 to 3 in which the step c according to the method of the present invention is not performed, it can be seen that even if the step d is performed, the oxidation is inhibited and the 5-hydroxymethylfurfural oxide cannot be obtained in a high yield.

Claims (11)

The manufacturing method of 5-hydroxymethyl furfural oxide which has the following process ad.
Step a: Step of obtaining a reaction solvent containing 5-hydroxymethylfurfural by dehydrating a sugar raw material in the presence of the reaction solvent to produce 5-hydroxymethylfurfural in the reaction solvent Step b: Obtained in Step a Step of extracting 5-hydroxymethylfurfural into a hydrophobic solvent from the obtained reaction solvent containing 5-hydroxymethylfurfural to obtain a hydrophobic solvent containing 5-hydroxymethylfurfural obtained in step c: step b Step of extracting 5-hydroxymethylfurfural into water from a hydrophobic solvent containing 5-hydroxymethylfurfural to obtain an aqueous solution containing 5-hydroxymethylfurfural Step d: 5-hydroxymethylfurfural obtained in Step c Oxidation process   The method for producing 5-hydroxymethylfurfural oxide according to claim 1, wherein the reaction solvent used in step a is one or more selected from water, a highly polar aprotic organic solvent, and an ionic liquid.   The method for producing 5-hydroxymethylfurfural oxide according to claim 1 or 2, wherein the hydrophobic solvent used in step b has a water-octanol partition coefficient of 0.3 or more.   The hydrophobic solvent used in step b is one or more selected from methyl isobutyl ketone, cyclohexanone, 2-butanol, dichloromethane, trichloromethane, diethyl ether, diisopropyl ether, ethyl acetate, butyl acetate, toluene, and hexane. The manufacturing method of the 5-hydroxymethyl furfural oxide in any one of Claims 1-3 which is.   The reaction solvent used in step a is water, and in step a, a sugar raw material is subjected to a dehydration reaction in the presence of water and a hydrophobic solvent, and water containing 5-hydroxymethylfurfural and 5-hydroxymethylfurfural are contained. The method for producing 5-hydroxymethylfurfural oxide according to any one of claims 1 to 4, wherein Step a and Step b are simultaneously performed by obtaining a hydrophobic solvent. Furthermore, the manufacturing method of the 5-hydroxymethyl furfural oxide in any one of Claims 1-5 which has the following process c-2.
Step c-2: A step of purifying 5-hydroxymethylfurfural from one or more selected from recrystallization, solvent extraction, and adsorption treatment from the aqueous solution containing 5-hydroxymethylfurfural obtained in Step c.   The 5-hydroxymethylfurfural in step d is oxidized in contact with an oxidizing gas in an organic acid solvent in the presence of a metal catalyst and a halogen compound. A method for producing methylfurfural oxide.   The method for producing 5-hydroxymethylfurfural oxide according to claim 7, wherein the metal catalyst is one or more selected from a cobalt catalyst and a manganese catalyst.   The oxidation of 5-hydroxymethylfurfural in step d is carried out in contact with an oxidizing gas in the presence of a catalyst containing at least one metal element selected from Groups 8 to 11 of the periodic table. 9. The method for producing 5-hydroxymethylfurfural oxide according to any one of 8 above.   The catalyst contains at least one metal element selected from Groups 8 to 11 of the periodic table, and contains one or more elements selected from tin, bismuth, selenium, tellurium and antimony as the second metal. 10. A method for producing an oxide of 5-hydroxymethylfurfural according to 9.   5-hydroxymethylfurfural oxide is 2,5-furandicarboxylic acid, diformylfuran, 2-carboxy-5-formylfuran, 5-hydroxymethyl-2-furancarboxylic acid, or 5-acetoxymethyl-2-furan The method for producing 5-hydroxymethylfurfural oxide according to claim 1, which is a carboxylic acid.