Synthesis of 5-acetoxymethylfurfural in the presence of reusable salt catalysts

Abstract

formula: [Formula 1] JPEG2025507914000016.jpg1637 1. A process for preparing an ester of 5-hydroxymethylfurfural of the formula: wherein R is a straight or branched alkyl or alkenyl, comprising: adding to a reaction vessel a C6 carbohydrate, an organic acid R-COOH, and a salt that is only slightly soluble in the organic acid to form a reaction mass; heating the reaction mass; allowing the reaction to proceed; separating the salt from the liquid phase; and recovering a reaction product comprising an ester of 5-hydroxymethylfurfural.

Description

[Background technology]

[0001] Carbohydrates are a renewable resource that can replace petroleum to produce chemicals, fuels and fuel additives. The carbohydrate-derived chemicals industry has grown significantly in recent years and is expected to continue to grow in the future.

[0002] Carbohydrates are subdivided into simple monosaccharides such as fructose, galactose or glucose, disaccharides formed from two monosaccharides, such as sucrose, lactose or maltose, carbohydrates formed from three to about ten monosaccharides are called oligosaccharides, such as raffinose, stachyose or dextrin, carbohydrates containing 11 or more monosaccharides are called polysaccharides, such as glycogen, starch or cellulose.

[0003] Another important way of classifying monosaccharides is the number of carbon atoms in the sugar molecule. According to the number of carbon atoms in the molecule, monosaccharides are subdivided into trioses (3 carbon atoms), tetroses (4 carbon atoms), pentoses (5 carbon atoms), hexoses (6 carbon atoms) or heptoses (7 carbon atoms). Hexoses based on a 5-membered furan ring are often called furanoses (or furanoids). Similarly, hexoses are classified as pyranoses (or pyranoids) when they are based on a 6-membered pyran ring. [ka]

[0004] It should also be noted that monosaccharides exist in equilibrium between open-chain and various non-open-chain forms. This equilibrium is called "ring-chain tautomerism." For example, the ring-chain tautomerism of D-fructose is: [ka] As shown in (See, for example, M. Bicker et al., ``Dehydration of d-fructose to hydroxymethylfurfural in sub- and supercritical fluids'', J. of Supercritical Fluids, 36, 2005, 118-126).

[0005] One of the important carbohydrate derivatives is 5-hydroxymethylfurfural (HMF), which has been classified as one of the most promising bio-based chemicals for the future (see JJ Bozell, GR Petersen, ``Technology development for the production of biobased products from biorefinery carbohydrates-the US Department of Energy's ''Top 10'' revisited'', Green Chem., 12, 2010, 539-554). [ka]

[0006] HMF can be used as a platform to produce diverse and highly valuable chemical products of great economic importance, such as fuels, monomers, resins, surfactants, solvents, etc.

[0007] HMF is a carbohydrate that is made up of monosaccharides such as fructose or glucose, or C-saccharides such as sucrose, starch, cellulose, etc. 6 HMF can be produced from disaccharides, oligosaccharides and polysaccharides containing sugar units. The production process of HMF proceeds by dehydration, but most of them may proceed with acid catalysts. Generally, this process is more efficient with fructose as starting material. The process starting from glucose requires an additional isomerization step, while the reaction starting from oligosaccharides or polysaccharides requires a depolymerization step, which results in low yields.

[0008] Conversion of carbohydrates to HMF in aqueous media results in poor yields due to the instability of HMF in aqueous media, especially in the presence of acidic catalysts, and due to the formation of by-products such as levulinic acid and formic acid from hydrolysis, and humic substances from polymerization and condensation.

[0009] Due to the tendency of by-products to form in aqueous solvents, other solvents for the preparation of HMF were investigated. Organic polar aprotic solvents such as DMSO, DMF, DMA, and NMP are more efficient than water as reaction solvents because they suppress the hydrolysis of HMF. For example, in U.S. Pat. No. 4,590,283, a yield of up to 97% of HMF was demonstrated from fructose using DMSO as the reaction solvent.

[0010] Even though higher yields of HMF and significantly reduced by-product formation can be achieved using high boiling polar aprotic solvents, especially with DMSO, recovery of HMF from such solvents remains a major challenge in large-scale production. In another approach, HMF preparation is carried out in a two-phase system consisting of an aqueous phase and an organic phase. In this methodology, HMF is extracted in situ from the aqueous phase by an organic solvent, which minimizes side reactions. For example, Dumesic et al. reported a two-phase system with an aqueous phase using MIBK as an organic solvent and hydrochloric acid or an acidic ion exchange resin as a catalyst for converting fructose to HMF. In this system, 80% HMF selectivity was achieved at 90% fructose conversion (Y. Roman-Leshkov, JN Chheda, JA Dumesic, ''Phase modifiers promote efficient production of hydroxymethylfurfural from fructose'', Science, 312, 2006, 1933-1937). However, the complexity of multi-solvent plant design makes this method economically less attractive.

[0011] High yields of HMF can be obtained in ionic liquid solvents. For example, the dehydration of fructose in methylimidazolium chloride gave a 92% yield of HMF (C.Moreau,A.Finiels and L.Vanoye,J.,``Dehydration of fructose and sucrose into 5-hydroxymethylfurfural in the presence of 1-H-3-methyl imidazolium chloride acting both as solvent and catalyst'',J.of Mol.Catal.A:Chem.,253,2006,165-169).

[0012] A different strategy to access valuable furan compounds is to convert carbohydrates to HMF derivatives, such as HMF esters, which are more stable and easier to work up and isolate than HMF.

[0013] For example, 5-acetoxymethyl furfural (AMF), an acetyl ester of HMF, is an environmentally friendly and potentially inexpensive ester of HMF. Being hydrophobic, AMF is easier to extract compared to HMF. Furthermore, its high stability allows it to be purified by vacuum distillation with minimal product loss, whereas distillation of thermally unstable HMF leads to substantial product loss due to its polymerization (German Patent No. 3309564). In addition, it should be noted that HMF exhibits weak toxicity and mutagenicity, whereas AMF has neither toxicity nor mutagenicity (RJ van Putten, JC van der Waal, E. de Jong, CB Rasrendra, HJ Heeres, JG de Vries, ''Hydroxymethylfurfural, a versatile platform chemical made from renewable resources'', Chem. Rev., 113, 3, 2013, 1499-1597). [ka]

[0014] Like HMF, AMF can be utilized as a starting material / intermediate for preparing various useful end products. For example, AMF can be used in the synthesis of biomonomers such as 2,5-furandicarboxylic acid (FDCA) (U.S. Pat. No. 8,558,018), 2,5-bis(hydroxymethyl)furan, and 5-hydroxymethyl-furan carboxylic acid (ES Kang et al., ``From lignocellulosic biomass to furans via 5-acetoxymethylfurfural as an alternative to 5-hydroxymethylfurfural'', ChemSusChem, 8, 2015, 1179-1188). In addition, AMF can be used as a starting material for various amines (ALNuzhdin et al., ``Reductive amination of 5-acetoxymethylfurfural over Pt / Al2O3 catalyst in a flow reactor'', Mol.Catal., 499, 2021, 111297).

[0015] AMF can be used in resin manufacture, as demonstrated for the condensation of AMF with urea in the preparation of resins that can be used as binders for mold making (U.S. Pat. No. 9,636,742).

[0016] In some applications, AMF can be used directly without any modification. For example, due to its high energy content of 8.7 kWh / L, compared to 8.8 kWh / L for gasoline and 6.1 kWh for ethanol, AMF can be utilized as a fuel candidate or as a fuel additive to replace MTBE (U.S. Patent No. 8,242,293).

[0017] WO 2013 / 121264 discloses AMF as a sweetness modulating agent capable of increasing the sweetness of low-calorie foods.

[0018] AMF has also been considered for use in therapy, for example to inhibit sickle cell disease, and exhibits a longer half-life and increased bioavailability when compared to HMF (US Pat. No. 10,875,834).

[0019] Due to the great economic and commercial potential and advantages of HMF esters, and especially AMF, over HMF, an industrially viable process for the production of AMF and other HMF esters from carbohydrates is highly desirable. However, compared to the conversion to HMF, there are relatively few reports on the conversion of sugars with six carbon atoms to AMF or other HMF esters.

[0020] A two-step method for synthesizing AMF from carbohydrates via halogenated furfural derivatives such as 5-chloromethyl furfural (CMF) was demonstrated by ESKang et al. (From lignocellulosic biomass to furans via 5-acetoxymethylfurfural as an alternative to 5-hydroxymethylfurfural'', ChemSusChem,8,2015,1179-1188). It was shown that CMF formed from carbohydrates could be converted to AMF in up to 94% yield by using alkylammonium acetate as catalyst and sodium acetate as acetate source in the acetylation reaction.

[0021] A two-step method for producing AMF from fructose has been disclosed by Huynh et al. (NTT Huynh, KW Lee, JK Cho, YJ Kim, SW Bae, JS Shin, S. Shin, ''Conversion of D-fructose to 5-acetoxymethyl-2-furfural using immobilized lipase and cation exchange resin'', Molecules, 24, 2019, 4623). In the first step, fructose was converted to 1,6-diacetylfructose using immobilized lipase enzyme catalyst and vinyl acetate as acyl donor. In the second step, the acetylated fructose was dehydrated to AMF using amberlyst-15, an acidic ion exchange resin, and 1,4-dioxane in DMSO.

[0022] Moreover, it is generally preferred to produce AMF directly from carbohydrates rather than through multi-step processes. Several patents and research publications have demonstrated direct routes to AMF from hexoses.

[0023] The preparation of AMF in subcritical acetic acid was described by Bicker et al. (M.Bicker et al., ''Dehydration of D-fructose to hydroxymethylfurfural in sub- and supercritical fluids'', J.of Supercritical Fluids, 36, 2005, 118-126). The reaction was carried out under a pressure of 20 MPa and a temperature of 180 °C. These conditions are not acceptable for an industrial-scale process. Moreover, the authors used sulfuric acid as a catalyst, but the recovery of the catalyst and solvent remained a challenge.

[0024] US Patent No. 8,314,260 discloses the production of HMF ethers and esters (including AMF) directly from carbohydrates in an ionic liquid system using a Lewis acid metal chloride catalyst and an organic acid as the ester forming agent, however, ionic liquids are expensive and difficult to purify and recover, especially from the water formed in the dehydration reaction.

[0025] The conversion of cellulose to AMF in a two-step process is described (L.Gavila,D.Esposito,Cellulose acetate as a convenient intermediate for the preparation of 5-acetoxymethylfurfural from biomass,Green Chem,19,2017,2496-2500). The first step involves the conversion of cellulose to cellulose acetate, mainly in triacetate form, using acetic anhydride and sulfuric acid as catalysts. In the second step, the acetylated cellulose was hydrolyzed to AMF in acetic acid as solvent in the presence of acetic anhydride and sulfuric acid catalysts. The procedure was tested in batch and continuous flow reactors. AMF was obtained from cellulose acetate with a maximum yield of 49% in the flow reactor at a residence time of 5 min. However, only low concentrations of cellulose acetate (5 g / L) proved to be effective in this procedure. In addition, the recovery of the catalyst and the acetic acid reactive solvent is the biggest challenge.

[0026] The use of chloride salts and acidic ion exchangers for the one-pot, two-step preparation of AMF from carbohydrates at temperatures ranging from 80 to 140 °C was shown in US Patent No. 8,642,790. The preferred catalyst, magnesium chloride hexahydrate, was stirred with the carboxylic acid solvent and carbohydrate reactant under heating. Acetylation was then carried out by adding acetic anhydride and pyridine derivatives as catalysts after removal of 80% of the acetic acid. After work-up, a 45% yield of AMF was demonstrated from fructose.

[0027] Direct conversion of mono- and disaccharides to AMF using tin-montmorillonite (Sn-Mont) as a heterogeneous catalyst was carried out using acetic acid and an acetylating agent as the reaction catalyst (S. Shinde, K. Deval, R. Chikate, C. Rode, ''Cascade synthesis of 5-(acetoxymethyl)furfural from carbohydrates over Sn-Mont catalyst'', ChemistrySelect, 3, 2018, 8770-8778).

[0028] Alkali halide catalysts were tested in carboxylic acid esters as reaction catalysts to convert carbohydrates in U.S. Patent No. 10,259,797. It was demonstrated that the formation of HMF and AMF mixtures followed by oxidation produced FDCA, a useful biomonomer. When methyl acetate is used as the reaction solvent, it is hydrolyzed by water to methanol and acetic acid during the dehydration of sugars, resulting in the formation of HMF and thus AMF. Summary of the Invention

[0029] The present inventors have found that in the presence of a salt that has low solubility in a carboxylic acid, a C6 carbohydrate is converted to the corresponding organic acid ester of 5-hydroxymethylfurfural in the carboxylic acid. The reaction has good selectivity for the formation of esters of 5-hydroxymethylfurfural.

[0030] That is, the reaction products consist of a mixture of 5-hydroxymethylfurfural and the corresponding ester, e.g., a mixture of AMF and HMF, with a ratio ranging from 2:3 to 100:1, and AMF is preferably the major component of the product mixture, e.g., 1:1 to 100:1, 1:1 to 10:1, 1:1 to 5:1, or even the only detectable product. Higher AMF selectivity is achieved by adjusting the temperature, type of catalyst and reaction time: [ka] can be obtained according to

[0031] The selection criterion for the salt used to catalyze the reaction is its solubility in the organic acid under consideration. For example, a salt that is only slightly soluble in the organic acid is used, and even better, a salt that is only slightly or practically not soluble in the organic acid is used. "Only slightly soluble" means that 10 parts or less, less than 5 parts or less than 3 parts of the salt are dissolved in 100 parts of the organic acid, and "slightly soluble" means that 1 part or less of the salt is dissolved in 100 parts of the organic acid at room temperature. With a fairly low solubility in the reaction solvent, the salt can be easily separated, for example, by filtration from the organic acid, and then reused for use in the batch.

[0032] Thus, the present invention relates primarily to a compound of the formula: [ka] wherein R is a straight or branched alkyl or alkenyl, the method comprising adding to a reaction vessel a C carbohydrate, a carboxylic acid R-COOH, and a salt that is only slightly soluble in an organic acid to form a reaction mass, heating the reaction mass, optionally under pressure, allowing the reaction to proceed, separating the salt from the liquid phase, and recovering a reaction product comprising an ester of 5-hydroxymethylfurfural.

[0033] The C6 carbohydrate starting material can be selected from monosaccharides (e.g. glucose, galactose, fructose, mannose), disaccharides (e.g. sucrose, lactose, maltose, cellobiose), oligosaccharides (e.g. α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin) or polysaccharides (e.g. starch, cellulose, inulin) or mixtures thereof, all of which are composed of sugar units of 6 carbon atoms. Monosaccharides such as glucose and fructose (especially the latter) and disaccharides such as sucrose are preferred starting materials for use in the present invention.

[0034] The organic acid serves a dual function as both the reaction solvent and reactant (e.g., acetylation reagent when acetic acid is used). Note that the reaction mass does not contain anhydrides or acyl halides, which are the most reactive carboxylic acid derivatives and are often used in organic synthesis for acetylation. However, in this case, neither acetic anhydride nor acetyl chloride need to be added to the reaction vessel to drive the conversion of C6 carbohydrates to AMF. In the most common form, the carboxylic acid is of the formula R-COOH, where R is a linear or branched C1-C20 alkyl (e.g., C1-C8, e.g., C1-C5), or a linear or branched C2-C20 alkenyl (e.g., C1-C8, e.g., C1-C5). The acids may include, for example, straight chain saturated or unsaturated carboxylic acids (such as acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, heptanoic acid, octanoic acid, acrylic acid, isocrotonic acid, etc.), or branched chain saturated or unsaturated carboxylic acids (such as isobutyric acid, methacrylic acid, etc.), or straight chain or branched saturated or unsaturated fatty acids (such as myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, etc.). The acids are fed to the reaction vessel in pure form, for example acetic acid (glacial acetic acid) used as acetic anhydride, although in some cases the presence of water (0-20 wt%) may have some advantage in promoting the reaction, especially for relatively stable starting materials such as glucose. It is preferred that the reaction vessel does not contain added alkyl esters of carboxylic acids such as methyl acetate. Although alkyl esters may form the corresponding acids in situ, the alcohol by-product is generally undesirable (i.e., methanol in the case of methyl acetate). If a mixture of HMF esters is required, a mixture of carboxylic acids may be used.

[0035] Turning now to the salts used to catalyze the reaction, data on the solubility of many salts in acetic anhydride at room temperature can be found in J. Am. Chem. Soc., 50, 7, 1928, 1890-1895 and J. Am. Chem. Soc., 60, 9, 1938, 2043-2046. The salts selected are alkali metal halides (e.g. chlorides, bromides, iodides such as sodium chloride, potassium chloride, sodium bromide, potassium bromide and potassium iodide), ammonium halides (ammonium chloride, ammonium bromide, ammonium iodide), metal hydrogen sulfates (such as alkali hydrogen sulfates), ammonium hydrogen sulfate, ammonium sulfate, and monovalent, divalent and trivalent metal sulfates and their hydrates (alkali metal sulfates such as aluminum sulfate and tin sulfate, including double salts consisting of a sulfate of a trivalent cation such as aluminum, alkaline earth metal sulfates, transition metal or post-transition metal sulfates), sulfates of monovalent cations such as potassium, sodium or ammonium with water of hydration, i.e. aluminum double salt compounds, in particular KAl(SO 4 ) 2 and N.H. 4 Al(SO 4 ) 2 , or a mixture of two or more of the above-mentioned salts. For example, a mixture of the individual salts listed above may be selected and proportioned to control the distribution of AMF and HMF. On the other hand, alkaline earth metal halides and (post)transition metal halides are usually readily soluble (i.e., more than 10 parts in 100 parts of acid) in glacial acetic acid (except for calcium fluoride (CaF2) which can be used in the present invention).

[0036] The salts can be used in either bulk or supported form. Commonly used solid forms include powders, pellets, flakes, etc. Supports include metal oxides (alumina, silica, titanium oxide, zirconium oxide, etc.), clays (montmorillonite K-10, kaolin, bentonite, etc.), zeolites, activated carbon, etc.

[0037] To carry out the reaction, the C6 carbohydrate, a salt (e.g., halide, hydrogen sulfate or sulfate) and a carboxylic acid (e.g., acetic acid) are placed in a reaction vessel. The concentrations of the C6 carbohydrate and salt in the organic acid range, for example, from 0.01 g / mL to 0.4 g / mL and from 0.005 g / mL to 0.2 g / mL, respectively.

[0038] The reaction is carried out under heating, for example at a temperature of 80° C. or higher (for example, above 100° C.). The reaction temperature depends on the concentration of the reagents (salt catalyst, carboxylic acid and C 6 For example, the temperature range for the reaction of fructose with acetic acid in the presence of an alkali halide salt as a catalyst is 120-200°C, preferably 140-200°C, more preferably 140-180°C. 4 The temperature range for the reaction of fructose with acetic acid in the presence of Cl) is 100 to 200°C, preferably 110 to 180°C, and more preferably 110 to 150°C.

[0039] The reaction can proceed under atmospheric pressure when relatively low temperatures are applied, e.g. under reflux or autogenous pressure, with heating in a closed reactor. The reaction vessel may also be pressurized with an inert gas up to 1-30 bar when the temperature is significantly higher than the reflux temperature of the carboxylic acid used, if it is desired to keep the solvent (organic acid) in the liquid state. The reaction vessel is therefore usually a high pressure reactor, batch (e.g. borosilicate ACE pressure tube, Hastelloy coated Parr batch reactor, etc.) or flow reactor, and hydrogenation units or steel autoclave type reactors can be used. However, reactions carried out under reflux in the presence of hydrogen sulfate salts, either as mere catalysts or in combination with other salts, have been shown to be very effective.

[0040] On a laboratory scale, the reaction lasts up to 5 hours (depending on the type of catalyst and the temperature). The progress of the reaction can be monitored by conventional analytical techniques (e.g., TLC, HPLC, etc.) to determine the conversion of the starting carbohydrate and the yield and ratio of the desired HMF and HMF esters.

[0041] The chloride salts (NaCl and NH) tested in the experimental section reported below to convert fructose 4 The reaction yielded a mixture of AMF:HMF products with a ratio of about 3:2 (yield, determined by HPLC), and the reaction time (3 h vs. 2 h) and temperature (150 °C vs. 130 °C) were significantly better with NH 4 Fructose conversion also proceeded efficiently using sulfates, such as aluminum double salts, in acetic acid at 150 °C to give a mixture of AMF:HMF products with a ratio of approximately 3:1 (yield, determined by HPLC).

[0042] The conversion of carbohydrates into acetic acid is achieved by the addition of alkali hydrogen sulfates (e.g., NaHSO 4 H 2 In the presence of 2,4-dimethylaminopropanediol (HO), it proceeds efficiently at reflux (the boiling point of acetic acid is 118° C.) to give AMF:HMF product mixtures in proportions of greater than 5:1, e.g., about 7:1 (yields, as determined by HPLC).

[0043] Thus, a specific embodiment of the present invention is a process comprising adding fructose, a catalyst selected from the group consisting of alkali halides, metal sulfates, metal and ammonium hydrogen sulfate, and acetic acid to a reactor (e.g., a pressure reactor), optionally sealing and pressurizing the reactor, heating the reaction mass to a temperature in the range of 100-200°C (e.g., 140-200°C), allowing the reaction to proceed, cooling the reaction mass, and working-up the reaction mass to obtain a mixture of AMF and HMF or a solution containing AMF alone. AMF is the major component of the mixture. For example, when a metal sulfate such as aluminum potassium sulfate was used, the ratio of AMF:HMF was greater than 2.5:1.

[0044] Another specific embodiment of the present invention is a process comprising adding fructose, an ammonium halide (e.g., chloride or bromide) and acetic acid to a reactor (e.g., a pressure reactor), optionally sealing and pressurizing the reactor, heating the reaction mass to a temperature in the range of 100-200° C. (e.g., 100-140° C.), allowing the reaction to proceed, cooling the reaction mass, and working-up the reaction mass to obtain a solution comprising a mixture of AMF and HMF, AMF being the major component of the mixture.

[0045] The present inventors have investigated the oxidation of alkali halides (e.g., sodium chloride, potassium chloride, and potassium bromide), alkali hydrogen sulfates (e.g., potassium hydrogen sulfate), ammonium hydrogen sulfate, and aluminum sulfate, i.e., Al, over a temperature range of 80 to 200° C., e.g., 100 to 200° C., e.g., 120 to 180° C. 2 (SO 4 ) 3 18H 2 O, and in addition, aluminum double salts (e.g., NH 4 Al(SO 4 ) 2 12H 2They have tested the conversion of sucrose in acetic acid (optionally containing up to 20% v / v water) in the presence of 2O and found that AMF was obtained as the major reaction product over HMF.

[0046] Thus, another aspect of the invention is a process comprising adding sucrose, a catalyst selected from the group consisting of an alkali halide, a metal sulfate, an alkali metal hydrogen sulfate or ammonium hydrogen sulfate, and acetic acid to a reactor (e.g., a pressure reactor), optionally sealing and pressurizing the reactor, heating the reaction mass to a temperature in the range of 100-200°C (e.g., 120-180°C), allowing the reaction to proceed, cooling the reaction mass, and working-up the reaction mass to obtain a mixture of AMF and HMF (AMF being the major component of the mixture) or a solution containing AMF alone. For example, when ammonium hydrogen sulfate was used, only sucrose was converted to AMF.

[0047] Experimental work presented below shows that hydrogen sulfates such as alkali hydrogen sulfates are also effective when the reaction is carried out at atmospheric pressure. Another specific embodiment of the present invention is a process that includes mixing a carbohydrate (such as fructose), a hydrogen sulfate (such as alkali hydrogen sulfate) and acetic acid in a reaction vessel, heating the reaction mass at a temperature ranging from 80 to reflux (e.g., 118° C.) and allowing the reaction to proceed (reaction times are quite reasonable), cooling the reaction mass, and working-up the reaction mass to obtain a mixture of AMF and HMF (AMF being the major component of the mixture) or a solution containing AMF alone.

[0048] To complete the reaction, the reaction vessel is cooled to room temperature (and pressure is released when an autoclave or the like is used) and the reaction mass is worked up. As pointed out above, due to its low solubility in organic acids, the salt catalyst can be separated at the end of the reaction and reused by conventional solid-liquid separation techniques such as filtration, decantation, etc. For example, after filtration the salt is washed with acetic acid and, if further washing is required, with acetone. The acidic filtrate may be treated with a poor solvent, for example an ether such as methyl tertbutyl ether, to precipitate the humic substances, which are removed by filtration, yielding a more pure solution of the product HMF esters and HMF in the organic acid.

[0049] For some applications, the product mixture may be used without separating the HMF esters from HMF, but if desired, the HMF esters (e.g., AMF) can be separated by extraction or vacuum distillation (e.g., ESKang et al., ``From lignocellulosic biomass to furans via 5-acetoxymethylfurfural as an alternative to 5-hydroxymethylfurfural'', ChemSusChem, 8, 2015, 1179-1188). At the end of the reaction, the carboxylic acid, such as acetic acid, can be separated and reused by evaporation. Fractional distillation is optional, for example, if recovery of pure acetic acid is desired. Thus, the present invention allows the recovery of the carboxylic acid and the salt catalyst used in the process. As pointed out above, AMF, in addition to being a useful product in itself, is an important chemical intermediate that can be used in the synthesis of several valuable end products. Non-limiting examples of useful chemicals that can be synthesized from AMF include: [ka] As shown in.

[0050] 2,5-Furandimethanol (FDM) can be obtained by reducing AMF using, for example, sodium borohydride, hydrogen atoms, or other reducing agents. For example, sodium borohydride is added to a solution of AMF in methanol at room temperature. The reaction mixture is stirred and then concentrated. The crude product is dissolved in water and neutralized to pH 6-7. The solution is then extracted with an organic solvent, dried and concentrated under reduced pressure. FDM can be recovered from the crude by column chromatography.

[0051] Tertiary amine derivatives of furfuryl alcohol (i.e., the group -CH 2 -N(Alk) 2 is attached to the 5-position of the ring, e.g., 5-(diethylaminomethyl)furfuryl alcohol, 5-(dimethylaminomethyl)furfuryl alcohol and their acid addition salts, where Alk is independently C1-C3 alkyl, is prepared by reductive amination. That is, AMF is reacted with a dialkylamine, such as diethylamine or dimethylamine. For example, anhydrous sodium sulfate is added to a solution of AMF in methanol, followed by diethylamine. The reaction mixture is stirred for several hours (e.g., 2 hours), sodium borohydride is added at room temperature, and stirred for an additional 18 hours. The resulting solution is then filtered, washed with methanol, and evaporated to give a viscous residue. The residue is partitioned between chloroform and 30% aqueous sodium hydroxide. The organic phase is dried over anhydrous magnesium sulfate and evaporated to give the tertiary amine product.

[0052] Because AMF can be more efficiently separated from the reaction mixture when compared to HMF, it is also advantageous to utilize the present invention to produce easily separable AMF as the main reaction product, separate the AMF, and then hydrolyze the AMF to HMF. AMF can be separated by base catalyzed hydrolysis (e.g., NaOH, K 2 CO 3or strong basic ion exchange resins such as Amberlite IRN78 hydroxide resin, Amberlyst A-26 OH, etc.) to selectively convert AMF to HMF with high yield and purity. For example, the reaction of a methanolic solution of AMF in the presence of potassium carbonate is carried out at room temperature for 15 hours. The reaction mixture is filtered and evaporated. The crude is diluted with ethyl acetate, washed with brine, dried and evaporated to obtain crude HMF (S. Shinde, K. Deval, R. Chikate, C. Rode, ''Cascade synthesis of 5-(acetoxymethyl) furfural from carbohydrates over Sn-Mont catalyst'', ChemistrySelect, 3, 2018, 8770-8778).

[0053] Thus, the present invention provides a process for isolating AMF from a solution of AMF and HMF, and optionally purifying the AMF, Oxidation of AMF to 2,5-furandicarboxylic acid, reduction of AMF to 2,5-furandimethanol, It further includes a further step such as reductive amination of AMF in the presence of a dialkylamine to form a tertiary amine derivative of furfuryl alcohol, or hydrolysis of AMF to HMF.

[0054] Thereby, the HMF obtained from AMF can be converted into useful products by one or more successive reaction steps. Non-limiting examples are as follows: [ka] Expressed as.

[0055] The selective oxidation of HMF to 2,5-diformylfuran (DFF) can be carried out in the presence of many kinds of catalysts, such as manganese oxide-based catalysts, GO-related catalysts, supported Ru catalysts, and vanadium-based catalysts (e.g., vanadium phosphate oxide (VPO)). For example, a DMSO solution of HMF in the presence of vanadium phosphate catalyst was heated and stirred at 120°C for 10 hours under air atmosphere to obtain several materials, including DFF as the main product (J. Lai et al., ``Selective oxidation of 5-hydroxymethylfurfural into 2,5-diformylfuran over VPO catalysts under atmospheric pressure'', RSC Adv., 9, 2019, 14242-14246).

[0056] Resinification of HMF is carried out using amines (e.g., urea, melamine, etc.) or phenolic compounds (e.g., phenol, cresol, hydroquinone, etc.). Resin formation is achieved using alkaline catalysts (e.g., NaOH, KOH, K 2 CO 3 etc.), acid catalysts (e.g., H 2 SO 4 The reaction can be catalyzed with phenols (such as HCl, oxalic acid, acetic acid, etc.) or by a combination of both. For example, a mixture of phenol, HMF and 50% sodium hydroxide solution catalyst is heated to 110° C. and stirred for an appropriate period of time until completion (analytical monitoring). The reaction mixture is cooled to 80° C. and evaporated under vacuum to remove water and unreacted phenol. Anti-solvent precipitation by addition of methanol / water followed by filtration and washing of the solid product with deionized water yields the HMF-phenolic resin (U.S. Pat. No. 9,725,552).

[0057] The other reactions starting from HMF in the scheme depicted above are carried out in a similar manner to those already described for AMF.

[0058] One important chemical prepared directly from either AMF or HMF derived from AMF is 2,5-Furandicarboxylic acid (FDCA), a monomer required to make the polymer polyethylene furanoate (PEF), which is recognized as an important bioplastic: FDCA, prepared as described above, is combined with ethylene glycol to form PEF.

[0059] example HPLC method conditions: Chromatographic analysis was performed using an Agilent HPLC1200 series. Column: Eclipse XDB C18 (4.6×150 mm); Injection volume: 5 μL; Column temperature: 35° C.; Mobile phase A: 0.1% formic acid in water; Mobile phase B: methanol; Mobile phase consisting of A:B (80:20) mixture; Flow rate: 0.8mL / min; detection at 280nm; injection volume: 1 μL; Run time: 17 min.

[0060] Example 1 AMF preparation from fructose in the presence of NaCl [ka] A pressure tube equipped with a magnetic stirrer was charged with fructose (1.06 g) and sodium chloride (0.75 g) followed by glacial acetic acid (10 ml). The pressure tube was sealed and heated (oil bath) to 150° C. with stirring for 3 h. The reaction flask was then cooled to room temperature and the reaction mixture was filtered to remove salts, which were washed with acetic acid. MTBE (60 ml) was added to the acidic filtrate with stirring. The resulting solution was filtered, washed with MTBE and distilled under vacuum (to remove MTBE). The AMF and HMF yields were determined to be 29.48% and 21.87%, respectively, by HPLC.

[0061] Example 2 NH 4AMF preparation from fructose in the presence of Cl [ka] A pressure tube equipped with a magnetic stirrer was charged with fructose (1.00 g) and ammonium chloride (0.50 g) followed by glacial acetic acid (10 ml). The pressure tube was sealed and heated (oil bath) to 130° C. with stirring for 2 h. The reaction flask was then cooled to room temperature and the reaction mixture was filtered to remove salts, which were washed with acetic acid. MTBE (60 ml) was added to the acidic filtrate with stirring. The resulting solution was filtered, washed with MTBE and distilled under vacuum (to remove MTBE). The AMF and HMF yields were determined to be 24.26% and 10.99%, respectively, by HPLC.

[0062] Example 3 Preparation of AMF from fructose in the presence of potassium aluminum sulfate dodecahydrate. [ka] A pressure tube equipped with a magnetic stirrer was charged with fructose (1.00 g) and potassium aluminum sulfate dodecahydrate (0.50 g) followed by glacial acetic acid (10 ml). The pressure tube was sealed and heated (oil bath) to 150° C. and stirred for 2 h. The reaction flask was then cooled to room temperature and the reaction mixture was filtered to remove salts, which were washed with acetic acid. MTBE (60 ml) was added to the acidic filtrate with stirring. The resulting solution was filtered, washed with MTBE and distilled under vacuum (to remove MTBE). The AMF and HMF yields were determined to be 31.46% and 11.18%, respectively, by HPLC.

[0063] Example 4 Preparation of AMF from fructose in the presence of sodium hydrogen sulfate monohydrate A round bottom flask equipped with a magnetic stirrer and connected to a condenser was charged with fructose (1.00 g) and sodium hydrogen sulfate monohydrate (0.75 g), followed by glacial acetic acid (10 ml). The flask was heated to reflux (oil bath) and stirred for 1 hour. The reaction flask was then cooled to room temperature and the reaction mixture was filtered to remove salts, which were washed with acetic acid. MTBE (60 ml) was added to the acidic filtrate with stirring. The resulting solution was filtered, washed with MTBE, and distilled under vacuum (to remove MTBE). The AMF and HMF yields were determined to be 29.18% and 3.81%, respectively, by HPLC.

[0064] Examples 5-11 Preparation of AMF from sucrose The procedure of Example 3 was carried out with sucrose (1.0 g) at 150° C. The reaction conditions (salt catalyst, solvent, reaction time) and the yields of AMF and HMF are shown in Table 1.

[0065] [Table 1]

Claims

1. formula: 【Chemistry 1】 1. A process for preparing an ester of 5-hydroxymethylfurfural comprising the steps of: wherein R is a linear or branched alkyl or alkenyl; In a reaction vessel, ６ adding a carbohydrate, an organic acid R-COOH and a salt that is only slightly soluble in said organic acid to form a reaction mass; heating the reaction mass; Allowing the reaction to proceed; and Separating the salt from the liquid phase; and recovering a reaction product comprising an ester of 5-hydroxymethylfurfural; and A method comprising:

2. The organic acid added is acetic acid, such that the ester formed has the formula: 【Chemistry 2】 The method according to claim 1, wherein the 5-acetoxymethylfurfural is of the formula:

3. Said C ６ 3. The method of claim 1 or 2, wherein the carbohydrate is a monosaccharide or a disaccharide.

4. The method of claim 3 , wherein the monosaccharide is fructose.

5. The method of claim 3 , wherein the disaccharide is sucrose.

6. The salt is Alkali metal halides; Ammonium halides; Metal hydrogen sulfates; Ammonium hydrogen sulfate; Ammonium sulfate, and Monovalent, divalent and trivalent metal sulfates and their hydrates, including sulfates of trivalent cations, double salts consisting of water of hydration and sulfates of monovalent cations; and Mixtures of two or more of the above salts The method according to any one of claims 1 to 5, wherein the compound is selected from the group consisting of:

7. the alkali metal halide is selected from sodium chloride, potassium chloride, sodium bromide, potassium bromide and potassium iodide; the ammonium halide is ammonium chloride; the metal hydrogen sulfate is an alkali hydrogen sulfate, the monovalent, divalent and trivalent metal sulfates and their hydrates are selected from alkali metal sulfates, alkaline earth metal sulfates and aluminum sulfate, including sulfate of aluminum, double salts consisting of water of hydration and sulfate of a monovalent cation such as potassium, sodium or ammonium; the mixture consists of two or more of said salts; The method according to claim 6.

8. 8. The method of claim 6 or 7, wherein the salt is selected from the group consisting of sodium chloride, potassium chloride, potassium bromide, ammonium chloride, potassium aluminum sulfate dodecahydrate, ammonium aluminum sulfate dodecahydrate, aluminum sulfate octahydrate, potassium hydrogen sulfate, sodium hydrogen sulfate and ammonium hydrogen sulfate.

9. 8. The method according to claim 6 or 7, wherein the salt is selected from alkali hydrogen sulfates, ammonium hydrogen sulfate and metal sulfates.

10. 10. The process according to any one of claims 1 to 9, wherein the reaction product is recovered by cooling the reaction mass, preferably to room temperature at the end of the reaction, and separating the salt from the liquid phase to obtain a mixture of the ester of 5-hydroxymethylfurfural and 5-hydroxymethylfurfural or a solution containing the ester alone.

11. adding to a reactor: fructose; a catalyst selected from the group consisting of an alkali halide, a metal sulfate, a metal hydrogen sulfate, and ammonium hydrogen sulfate; and acetic acid; Optionally sealing and pressurizing the reactor; heating the reaction mass to a temperature in the range of 140-200°C; Allowing the reaction to proceed; and cooling the reaction mass; and working up the reaction mass to obtain a mixture of AMF and HMF, with AMF being the main component, or a solution containing AMF alone; The method according to any one of claims 1 to 10, comprising:

12. adding fructose, ammonium halide and acetic acid to a reactor; Optionally sealing and pressurizing the reactor; heating the reaction mass to a temperature in the range of 100-140°C; Allowing the reaction to proceed; and cooling the reaction mass; and working up the reaction mass to obtain a mixture of AMF and HMF, with AMF being the main component, or a solution containing AMF alone; Including, The method according to any one of claims 1 to 10.

13. adding to the reactor sucrose; a catalyst selected from the group consisting of alkali halides, metal sulfates, alkali metal hydrogen sulfates, and ammonium hydrogen sulfate; and acetic acid; Optionally sealing and pressurizing the reactor; heating the reaction mass to a temperature in the range of 100 to 200° C.; Allowing the reaction to proceed; and cooling the reaction mass; and working up the reaction mass to obtain a mixture of AMF and HMF, with AMF being the main component, or a solution containing AMF alone; The method according to any one of claims 1 to 10, comprising:

14. combining a carbohydrate, hydrogen sulfate, and acetic acid in a reaction vessel; heating the reaction mass to a temperature ranging from 80 to reflux; Allowing the reaction to proceed; and cooling the reaction mass; and working up the reaction mass to obtain a mixture of AMF and HMF or a solution containing AMF alone; The method according to any one of claims 1 to 10, comprising:

15. 15. The method of claim 14, wherein the hydrogen sulfate is an alkali hydrogen sulfate.

16. The method according to any one of claims 2 to 15, further comprising a step of isolating AMF from the solution of AMF and HMF, and optionally purifying the AMF.

17. The following steps: Oxidation of AMF to 2,5-furandicarboxylic acid, reduction of AMF to 2,5-furandiethanol, reductive amination of AMF in the presence of dialkylamines to form tertiary amine derivatives of furfuryl alcohol, or hydrolysis of AMF to HMF The method of claim 16 further comprising:

18. AMF is hydrolyzed to HMF, the process comprising the steps of: Oxidation of the HMF formed as above to 2,5-furandicarboxylic acid, oxidation of the HMF formed as above to 2,5-diformylfuran, reduction of the HMF formed as above to 2,5-furandimethanol, reductive amination of the HMF formed as above, or resinification of HMF with amines or aromatic compounds. The method of claim 16 further comprising:

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