Improved process for the synthesis and purification of hmf

Abstract

The present invention relates to a process for the production of 5-hydroxymethylfurfural (HMF) from saccharides in the presence of quaternary ammonium salts and its purification. The process of the present invention comprises the steps a) of dehydrating at least one saccharide resulting in a reaction mixture comprising the quaternary ammonium salt, HMF, by-products and any intermediates, catalyst and unreacted saccharide; b) separating water- insoluble by-products from the reaction mixture, resulting in an aqueous solution; c) adding an organic solvent or mixture of organic solvents, resulting in the quaternary ammonium salt in the aqueous phase and HMF together with the organic solvent or mixture of organic solvents in the organic phase; d) separating said aqueous phase obtained in step c) and optionally removing water from it, obtaining quaternary ammonium salt and any intermediates and unreacted saccharide; and e) obtaining the organic phase separated in step d) comprising the dissolved HMF and optionally removing at least part of the solvent from the organic phase, resulting in purified HMF.

Description

[0001] IMPROVED PROCESS FOR THE SYNTHESIS AND PURIFICATION OF HMF

[0002] The present invention relates to a process for the production of 5-hydroxymethylfurfural (HMF) from saccharides in the presence of quaternary ammonium salts and its purification. In particular it relates to an efficient process for producing and separating 5- hydroxymethylfurfural (HMF) in high yields and high purity from saccharides, and for easily reusing the quaternary ammonium salt in the dehydration step.

[0003] HMF is a very important product for obtaining a number of useful intermediates such as 2,5- furandicarboxylic acid, 2, 5 -dimethylfuran and 2,5-(dihydroxymethyl)furan from renewable sources.

[0004] The most direct synthesis route for obtaining HMF is the acid-catalysed dehydration of 6- carbon-atom monosaccharides such as fructose and glucose, or of disaccharides and polysaccharides derived from them, such as sucrose and inulin, to yield HMF by the elimination of 3 water molecules per monosaccharide unit:

[0005] C6HI2O6 HMF + 3H2O

[0006] The conversion can be performed in various types of solvents: water, dipolar aprotic solvents (for example dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide), two-phase systems consisting of water and organic solvents (for example 2-butanol, 4-methyl-2-pentanone), ionic liquids (for example N-methyl-2- pyrrolidonium methyl sulfonate, l-ethyl-3-methylimidazolium chloride, l-butyl-3- methylimidazolium chloride, l-butyl-3-methylimidazolium tetrafluorob orate).

[0007] Hitherto various catalyst systems have been used to achieve the conversion, such as acid catalysts of the mineral acid type, acid ion exchange resins, zeolites, supported heteropolyacids, and metal chlorides (for example FeCh, CrCh, SnCh).

[0008] However, the acidity of the catalysts may also favour the rehydration of HMF and its subsequent fragmentation to give levulinic and formic acids, or its oligomerisation or polymerisation to give further by-products that contribute to lowering the overall reaction yield.

[0009] Alkyl ammonium salts have also been proposed as catalysts or solvents for this type of reaction (patent application CN 101906088; patent application CN 101811066; “Tetrahedron Letters”, 53, 2012, p. 983-985; “Carbohydrate Research”, 346, 2011, p. 2019-2023), with HMF yields varying from 45% to 70% depending on the starting saccharide used.

[0010] Although good conversions to HMF can be achieved with combinations of some of these solvents and catalysts, particularly from fructose, in every case it is still difficult to separate it from the medium and reaction by-products and to obtain it as a high-purity isolated product because of HMF’s high solubility in water, low melting point (30°C-34°C) and relative thermal instability. In fact the HMF yields reported in the literature are generally calculated by analysing reaction mixtures (for example by HPLC) and are not determined on the basis of the amount of product actually isolated and purified.

[0011] Some processes in the known art describe the preparation of HMF from saccharides using quaternary ammonium salts in the presence of water. For example, the process in patent EP 2994458 Bl involves dehydrating the saccharide in the presence of water and a specific heterogeneous catalyst, which is removed as a solid phase together with the alkyl ammonium salt after an organic solvent has been added. However the process requires complex operations for the recovery of HMF, salt, catalyst and for recycling the solvents used; in particular re-use of the ammonium salt and / or catalyst requires laborious purification treatments to remove by-products and in particular oligomers and polymers deriving from the degradation and / or condensation of the components of the reaction mixture (known as humins), which accumulate and prevent recycling many successive times.

[0012] In the process described in EP 3 820855 Al, HMF is prepared in the presence of a quaternary ammonium salt and water, and the HMF is obtained without solvent treatment by separation with specific membranes. However the recovery of HMF requires considerable volumes of water (more than 10 times the volume of the dehydration product); furthermore, the quaternary ammonium salt is included in the retentate together with by-products such as humins and any unreacted saccharides, which again hinder its re-use. The process therefore also has the problem that the quaternary ammonium salt has to be further purified from the humins, in addition to the high running cost of separation operations using nanofiltration or electrodialysis membranes, which require considerable volumes of water and are subject to fouling problems, mainly caused by the presence of high molecular weight compounds.

[0013] In the process in WO 2017 / 1845 Al (ADM / Rennovia), the saccharide is dehydrated in the presence of water, quaternary ammonium salt (TEAB) and under controlled conditions aimed at containing the formation of humins. This process involves a complex series of operations in the presence of several solvents; moreover, the recovery of HMF from the fraction containing humins still requires specific membrane separation operations. It therefore has the same disadvantages as listed above.

[0014] Ultimately, the methods in the literature described so far still have many drawbacks, both from a practical and economic point of view, and are not suitable for the production of large quantities of HMF on an industrial scale.

[0015] The applicant has now identified a process through which it is possible to both efficiently produce and purify HMF and at the same time also obtain the quaternary ammonium salt in a form suitable for its re-use in the dehydration step, without any special purification operations being necessary; advantageously, the quaternary ammonium salt can be reused after simple concentration from an aqueous solution. In addition the process according to the invention makes it possible to considerably reduce the volume of water used during the dehydration step and also during purification, because of the introduction of a step for the separation of humins before the HMF is separated from the quaternary ammonium salt, by extraction in an organic solvent.

[0016] In particular, the object of the present invention is a process for the production and separation of 5-hydroxymethylfurfural (HMF) comprising the steps of a) dehydrating at least one saccharide selected from the group consisting of 6-carbon- atom monosaccharides and disaccharides, oligosaccharides and polysaccharides formed from 6-carbon-atom units and mixtures thereof, in the presence of at least one quaternary ammonium salt (and optionally a homogeneous catalyst) at a temperature of 80-140°C, resulting in a reaction mixture comprising the quaternary ammonium salt, HMF, by-products and any intermediates, catalyst and unreacted saccharide; b) separating, after the optional addition of water, the water-insoluble by-products from the reaction mixture, resulting in an aqueous solution; c) adding to said aqueous solution an organic solvent or mixture of organic solvents in which the quaternary ammonium salt and the catalyst are insoluble or slightly soluble, whereas 5-hydroxymethylfurfural is soluble at a temperature between 15°C and the boiling point of the organic solvent or mixture of organic solvents, and obtaining the quaternary ammonium salt, any intermediates and unreacted saccharide in the aqueous phase, and 5- hydroxymethylfurfural together with the organic solvent or mixture of organic solvents in the organic phase; d) separating said aqueous phase obtained in step c) and optionally removing the water from it, obtaining the quaternary ammonium salt and any intermediates and unreacted saccharide; and e) obtaining the organic phase separated in step d) comprising the dissolved HMF and optionally removing at least part of the solvent from the organic phase, resulting in purified HMF.

[0017] Step a) of the process according to the present invention comprises the step of dehydrating at least one saccharide selected from the group consisting of 6-carbon atom monosaccharides, disaccharides formed from 6-carbon atom units, oligosaccharides formed from 6-carbon atom units, polysaccharides formed from 6-carbon atom units and mixtures thereof, in the presence of at least one quaternary ammonium salt and in the absence of a catalyst or in the presence of a a homogeneous catalyst, i.e. of a catalyst soluble at the conditions of process steps a) and b). Step a) yields a reaction mixture comprising the quaternary ammonium salt, HMF and by-products and, optionally, intermediates, catalyst and unreacted saccharide.

[0018] According to a preferred aspect, dehydration step a) is carried out without adding water, thus facilitating the dehydration reaction and at the same time allowing the reaction volumes to be kept small at an early stage in the process.

[0019] Instead, water is preferably fed (depending on the amount present following the dehydration reaction) at the time of the solid / liquid separation in step b) or shortly before, in sufficient quantities to bring the HMF and the quaternary ammonium salt into solution, together with catalyst, unreacted saccharide and any intermediates present. The separation in step b) therefore enables the water-insoluble by-products, such as humins, to be separated from the aqueous phase comprising HMF before the organic solvent is added.

[0020] In step c), HMF is then extracted in organic solvent or organic solvent mixture by liquid / liquid (L / L) separation from the aqueous phase obtained in step b).Thus, the quaternary ammonium salt and any catalyst remain in the aqueous phase, together with any unreacted saccharide and intermediates, which can be easily re-used by feeding them back to the dehydration step.

[0021] In step d), an aqueous phase comprising the quaternary ammonium salt is obtained, and from this, according to a preferred aspect, at least some of the water is removed in order to recover the quaternary ammonium salt.

[0022] According to another preferred aspect, the aqueous phase obtained in step d) is recycled, preferably following suitable concentration, by feeding it to dehydration step a). This recycling is particularly advantageous, as it allows the dehydration reaction to be carried out even at low conversions, thus further limiting the formation of high molecular weight byproducts and maximising the yield of HMF.

[0023] Finally, in step e), the HMF product is obtained as the organic phase containing the dissolved HMF separated in step c), from which optionally at least some of the solvent may be removed.

[0024] According to another embodiment of the process, the HMF product separated in step d) is used in organic solvent. Alternatively, it may be transferred to a different solvent (e.g. water).

[0025] The HMF product obtained according to the process according to the present invention can advantageously be used without further purification treatment for subsequent transformation into useful intermediates, for example for oxidation to 2, 5 -furandi carb oxy lie acid (FDCA). According to this embodiment, it is particularly useful to use furandicarboxylic acid as the catalyst in step a), no separation operation from the HMF product being required.

[0026] This subsequent oxidation of HMF to FDCA can advantageously be carried out, either in the aqueous phase or in the organic phase, for example with the ruthenium-based heterogeneous catalyst described in patent application WO 2021 / 123240 Al.

[0027] The process will be described in more detail below, with reference to the diagram in Figure 1.

[0028] Examples of saccharides that can be dehydrated in step a) to obtain HMF according to this process are monosaccharides such as fructose, glucose, galactose, mannose, disaccharides such as sucrose, maltose, lactose, cellobiose, oligosaccharides such as oligofructose containing 3 to 10 fructose units and polysaccharides such as fructans (for example inulin), starch, cellulose.

[0029] Specific examples of oligofructose are those with the formula GFn, where G represents the glucose unit, F the fructose unit, n the number of fructose units and is between 3 and 10.

[0030] Preferred polysaccharides are polysaccharides that are soluble in water at process temperatures (i.e. 80°C-130°C), such as inulin. Oligosaccharides and polysaccharides that are poorly soluble or insoluble in water may still be used, preferably after prior hydrolysis treatment, for example after acid or enzyme hydrolysis.

[0031] The saccharides preferably used in the process according to the present invention are selected from the group consisting of fructose, glucose, sucrose, inulin and mixtures thereof. A particularly preferred saccharide is fructose. Among the mixtures, mixtures of saccharides that are different from each other, such as those resulting from the hydrolysis of inulin, and particularly mixtures of glucose and fructose, are preferred.

[0032] According to a preferred embodiment, fructose is used as saccharide in step a) of the process.

[0033] With regard to the quaternary ammonium salt according to the present invention, quaternary ammonium salts of formula RsR'N+X- are preferred, in which:

[0034] R, which is the same or different, represents a substituted or unsubstituted Ci-Ce alkyl group;

[0035] R' belongs to the group consisting of: hydrogen, substituted or unsubstituted Ci-Ce alkyl groups, substituted or unsubstituted monocyclic aryl groups;

[0036] X- represents an anion selected from chloride, bromide, iodide, fluoride, hydroxide, BF4-, PF6-.

[0037] The R group is preferably selected from the C1-C4 alkyl groups, which are the same or different; methyl, ethyl, propyl, isopropyl, butyl, isobutyl groups are preferred.

[0038] R' is preferably selected from hydrogen (H) and substituted or unsubstituted, linear or branched C1-C16 alkyl groups; methyl, ethyl, propyl isopropyl, butyl, isobutyl, sec-butyl, terbutyl, benzyl, phenyl, hexyl, octyl, dodecyl, pentadecyl groups are preferred.

[0039] Possible substituents of R and R' alkyl groups are preferably chosen from halogens, carbonyl groups, carboxyl groups, hydroxyl groups, ester groups, and R2R'N+groups.

[0040] X~ preferably represents a halide or hydroxide anion.

[0041] Preferably used quaternary ammonium salts are selected from the group consisting of: tetraalkyl ammonium salts with fluorinated and non-fluorinated chains, ammonium salts with aliphatic and non-aliphatic asymmetric groups, bis-quatemary ammonium salts, and trialkyl ammonium salts. Of these, tetraalkyl ammonium salts are particularly preferred.

[0042] The tetraalkyl ammonium salts which may conveniently be used in the process according to the present invention are tetraalkyl ammonium halides or hydroxides, preferably having Ci- C15, more preferably C1-C4, alkyl groups, optionally substituted with hydroxyl groups. Preferred tetraalkyl ammonium salts are chlorides and bromides, such as tetramethyl ammonium chloride, (2-hydroxyethyl)trimethyl ammonium chloride (choline chloride), tetraethyl ammonium chloride, tetrapropyl ammonium chloride, tetrabutyl ammonium chloride, tetramethyl ammonium bromide, tetraethyl ammonium bromide, tetrapropyl ammonium bromide and tetrabutyl ammonium bromide. Bromides are particularly preferred.

[0043] Tetraethyl ammonium bromide, tetrapropyl ammonium bromide and tetrabutyl ammonium bromide are particularly preferred.

[0044] According to one aspect of the invention, the preferred tetraalkyl ammonium salt is tetraethyl ammonium bromide.

[0045] The saccharide and the quaternary ammonium salt for use in the process according to the present invention are preferably used in equimolar quantities.

[0046] The saccharide and quaternary ammonium salt can be fed to dehydration step a) in any order and at the same or different temperatures, optionally in the presence of water and / or a catalyst. For example, the saccharide and quaternary ammonium salt may be placed in contact with each other and pre-mixed, to yield a premix, before being fed to the dehydration step.

[0047] According to one preferred aspect of the process according to the present invention, said premixing, resulting in a premix, is carried out at temperatures below the dehydration temperature, preferably at a temperature in the range from room temperature (20° C and a pressure of 1 atmosphere) to 90° C, more preferably in the range from 60° C to 90° C, even more preferably from 70° C to 90° C and even more preferably from 80° C to 90°C, until a homogeneous liquid mixture is obtained. According to a preferred aspect, this pre-mixing is carried out in the absence of water.

[0048] According to another aspect, said pre-mixing is carried out after bringing the saccharide and / or ammonium salt to the same temperature as the reaction temperature or higher, preferably in the range of 80° C to 100° C.

[0049] Advantageously, pre-mixing is carried out after the salt has been brought to a temperature of 90° C or higher. In such circumstances it is preferable to heat the ammonium salt to temperatures in the range of 90° C to 100° C, advantageously in the presence of 1% to 50% water, preferably 1.5% to 40%, more preferably 2% to 30%, even more preferably 2% to 20% by weight, with respect to the salt used, and then add the saccharide (optionally premixed with sufficient water to keep it in solution).

[0050] Alternatively, the quaternary ammonium salt and saccharide may be fed separately to the dehydration step. In this case, each is advantageously fed at a temperature equal to the reaction temperature; alternatively, one of the two (preferably the salt) is preheated to a temperature above the reaction temperature, while the other is added at a lower temperature.

[0051] Either in the case where the quaternary ammonium salt and the saccharide are fed to the dehydration step separately, or in the case where the quaternary ammonium salt and the saccharide are previously pre-mixed with each other, according to a preferred aspect of the present invention at least one of the saccharide and the salt is pre-mixed with water before being fed to the dehydration step.

[0052] It is preferable that the water content in the reaction mixture during the dehydration step is not such as to favour HMF rehydration phenomena, with consequent degradation to levulinic and formic acids.

[0053] Those skilled in the art can easily determine the amount of water required on the basis of the saccharide and salt used. For example, according to a preferred aspect of the invention in which fructose and tetrabutyl ammonium bromide (TBAB) are used, at the start of step a) water is present in amounts equal to or less than 10% by weight of the sum of quaternary ammonium salt and said fructose.

[0054] This amount of water is advantageously added to the salt and / or saccharide before they are heated.

[0055] In accordance with this application, we refer to step a) as the “dehydration step”.

[0056] Advantageously, dehydration step a) is carried out in the absence of organic solvents.

[0057] According to one aspect, dehydration step a) is carried out without the addition of water, which can be fed later in order to perform the separation in step b). In spite of the high melting points of the quaternary ammonium salts and saccharide, under the operating conditions of the present process the reaction mixture is not in fact solid, even in the absence of water, but is in fluid form due to the formation of a eutectic point lower than the melting temperature of the two when said quaternary ammonium salts and said saccharide are present in the appropriate weight ratios. This also facilitates transfer of the mixture from a possible preheating area and feeding to the dehydration step. If the process is operated continuously, the saccharide and salt are in fact advantageously pre-mixed and pre-heated in a reactor separate from the one in which the dehydration step is carried out; the pre-heated fluid mixture can then conveniently be fed to the step a) reactor(s) by means of a common pumping system.

[0058] If the process is carried out in batch mode, this preheating and the dehydration step are advantageously performed in the same reactor.

[0059] According to another aspect, an aqueous solution containing quaternary ammonium salt is fed to step a), optionally together with catalyst and / or any unreacted saccharides and / or any intermediates resulting from the separation carried out in step d) of the process (known as quaternary ammonium salt recycling).

[0060] During dehydration step a) the reaction mixture is kept stirred at a temperature preferably in the range 80°C to 140°C, for a reaction time typically ranging from 1 minute to 240 minutes. The dehydration step is also preferably carried out in an inert environment, for example under nitrogen.

[0061] Advantageously, the dehydration step is carried out at a temperature of 85°C to 110°C to shorten reaction times and avoid the formation of decomposition products related to high temperature. When operating in the absence of added catalysts, the temperature is instead held at 95°C to 140°C, more advantageously at 100°C to 130°C.

[0062] The timing of the dehydration step varies depending on the mode of operation. If the dehydration step is carried out in batch mode, the reaction time is more preferably between 10 minutes and 120 minutes. If it is carried out in continuous mode, the retention time in the dehydration reactor(s) is preferably from 1 minute to 120 minutes and more preferably from 2 minutes to 90 minutes.

[0063] The reaction is advantageously carried out at atmospheric pressure (1 bar) or slightly higher pressures, preferably up to 5 bar, for example 2 or 3 bar. In another embodiment the pressure is maintained at values below 1 bar (0.1 MPa), for example between 400-900 millibars (0.04- 0.09 MPa), by removing some of the water from the reaction environment.

[0064] According to a preferred embodiment, before dehydration step a) the process according to the present invention comprises a step of pre-mixing saccharide and water at a temperature advantageously in the range 40°C to 70°C, more preferably at a temperature of 55°C to 65°C. This pre-mixing operation, taking advantage of the increased solubility of saccharides at such temperatures, allows for the raw materials to be fed continuously to the dehydration step and the amount ofwater used to be reduced. According to this continuous embodiment, the premixing of poorly soluble or insoluble polysaccharides with water is advantageously preceded by a preliminary hydrolysis operation, for example using acids or enzymes.

[0065] When step a) is performed at high temperatures (for example 105°C to 110°C), it is possible to achieve good conversion of saccharide to HMF, for example above 90%, even in the absence of a catalyst. By operating in the presence of a suitable acid catalyst, temperatures and reaction times are significantly reduced, further limiting the possibility of HMF degradation. Said catalyst can be fed during the dehydration step or pre-mixed with the quaternary ammonium salt and / or saccharide before the dehydration step. According to a preferred aspect, it is pre-mixed with water before being fed to the dehydration step.

[0066] Acid catalysts which can in principle be used in the process according to the present invention include both Bronsted and Lewis acids. Thus it is possible to use mineral acids (for example hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid), organic acids (for example oxalic acid, levulinic acid, maleic acid, p-toluenesulfonic acid, methanesulfonic acid, furandicarboxylic acid), heteropolyacids (for example phosphotungstic acid), metal oxides (for example titanium (IV) oxide, zirconium oxide), metal halides (for example zinc chloride, aluminium trichloride, ferric chloride, chromium chlorides, boron trifluoride), metal phosphates (for example zirconium phosphate, titanium phosphate), or doped zirconium hydroxides (for example sulfated or tungstated).

[0067] Homogeneous catalysts such as mineral acids (for example hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid), organic acids (for example oxalic acid, levulinic acid, maleic acid, p-toluenesulfonic acid, methanesulfonic acid, furandicarboxylic acid) are preferred, which can be at least in part recovered in the aqueous solution obtained in step b) by separation and purification treatments using known techniques. These acids are not subject to deactivation problems and can advantageously be re-used by feeding them to the initial dehydration stage of the process, together with the quaternary ammonium salt, with considerable savings in terms of cost and process time. Among the mineral acids, nitric acid and sulfuric acid are particularly preferred. Mixtures of catalysts may be used.

[0068] If catalysts of the heterogeneous type, i.e. not soluble in the reaction environment, are used, these catalysts are separated from HMF during separation step d) as a solid phase. Their reuse is preferably preceded by one or more separation and / or purification and / or reactivation treatments.

[0069] The amount of acid catalyst to be used is preferably 0.1% to 20% by weight of the saccharide, preferably 0.2% to 10%, more preferably 0.5% to 2%.

[0070] The reaction in the dehydration step is preferably conducted in one or more items of equipment, fitted with appropriate stirring and heating means, suitable for effective mixing and providing adequate heat exchange surfaces.

[0071] The dehydration step may be carried out in one or more reactors, which are either the same or different, which may be placed in series.

[0072] At the end of step a), the reaction mixture comprises HMF, the quaternary ammonium salt, by-products and, optionally, intermediates, catalyst and unreacted saccharide.

[0073] This reaction mixture is then suitably diluted with water, so that in step b) the waterinsoluble by-products can be separated by means of one or more solid / liquid (S / L) separation operations.

[0074] The amount of water added varies depending on the amount and type of reaction by-products present, as well as the amount of water already present at the end of step a).

[0075] Dilution is conveniently effected in such a way as to achieve a ratio of dry weight of the reaction mixture obtained at the end of step 1 to water of preferably between 1 : 1 and 1 :8 by weight, more preferably between 1:2 and 1 :6 by weight and even more preferably around 1 :4, i.e. adding 4 parts water to 1 part by weight of reaction mixture.

[0076] Such a water content keeps HMF and quaternary ammonium salt, together with any intermediates and unreacted saccharide, in aqueous solution during step b), thus facilitating the separation of insoluble by-products, including humins, from the mixture obtained at the end of step a).

[0077] Separation step b) of the process comprises one or more S / L separation operations, commonly known to those skilled in the art, performed in series or in parallel, to separate insoluble compounds, such as humins, from the aqueous phase. These operations are performed in one or more stages; they may be repeated several times, adding new water to the retentate and optionally employing different techniques to maximise the separation of insoluble compounds.

[0078] Preferred S / L separation operations are chosen from filtration, centrifuging, decanting, and chromatography. For example, a filter press may conveniently be used; filtration may be performed using microfiltration, ultrafiltration membranes or combinations thereof, for example ceramic membranes. Examples of membranes typically used for ultrafiltration operations in this process are membranes based on polyethylene, PTFE, polypropylene, PAN, cellulose acetate, PES, PVDF. Depending on the characteristics of the mixture subjected to the separation operations in step b) of the process, those skilled in the art will be able to select the separation operation to be used, the optimal operating conditions (for example, pH and pressure) during each separation operation, and to assess the advisability of performing one or more dilution or diafiltration steps (i.e. dilution of the retentate by addition of water and repetition of the separation operation).

[0079] Separation by filtration according to the invention may be carried out in batch or continuous mode; depending on the case, a normal (perpendicular) or tangential flow filtration method is preferably used respectively.

[0080] During the separation operation(s) in step b) the mixture is preferably kept at a temperature ranging from room temperature (20°C - 25°C) to 35°C, 45°C or 50°C.

[0081] Said aqueous solution obtained in step b) is preferably fed to step c) after concentration and / or purification.

[0082] According to a preferred aspect of the process, the S / L separation operations in phase b) are optionally followed by one or more further operations of purifying the resulting aqueous phase. For example, one or more treatments with filtering elements with high adsorptive power, such as activated carbon, are conveniently carried out in batch or continuous mode, with the effect of decolourising the aqueous solution and making it more stable over time while avoiding the subsequent precipitation of insoluble by-products.

[0083] The aqueous solution obtained at the end of step b) comprises mainly HMF and quaternary ammonium salt, the catalyst in step a) - if a homogeneous, water-soluble catalyst is used -, any unreacted saccharide and any intermediates.

[0084] According to a preferred aspect, the obtained aqueous solution is concentrated before step c), i.e. at least some of the water present is removed from the aqueous solution by known techniques, for example by one or more operations selected from evaporation, distillation, reverse osmosis, and combinations thereof. Techniques that do not involve conditions that degrade the reusable components in the process such as quaternary ammonium salt, catalyst, any unreacted saccharide and any intermediates, (for example high temperature and pressure, extended time) are preferred.

[0085] In step c), the aqueous solution obtained in step b) is brought into contact with an organic solvent or a mixture of organic solvents in which the quaternary ammonium salt and the catalyst are insoluble or poorly soluble (generally with a solubility of less than 20 g / 1 at 20 °C) and the 5-hydroxymethylfurfural is soluble (generally with a solubility of more than 100 g / 1 at 20 °C).

[0086] Solvents stable to process conditions having low or no miscibility in water are suitable, selected for example from esters and ketones.

[0087] Preferably said organic solvent is selected from: ethyl acetate, butyl acetate, isopropyl acetate, 4-methyl-2-pentanone (MIBK), 2-butanone (methyl ethyl ketone), 2-pentanone (methyl n-propyl ketone), cyclopentanone and mixtures thereof. According to one aspect, cyclopentanone is preferably used in a mixture with one or more organic solvents, advantageously chosen from those listed above.

[0088] Those skilled in the art will be able to determine the amount of solvent to be used depending on the extraction method employed and the equipment available. For example, an amount of organic solvent may be added at a ratio of 3 : 1 or less by weight to the weight of the aqueous phase, more preferably at a ratio of 2: 1 or less, advantageously also at a ratio of 1 :1 or less by weight to the weight of the aqueous phase.

[0089] This organic solvent (or mixture of organic solvents) is brought into contact with the aqueous solution at a temperature of between 15°C and the boiling point of the organic solvent or mixture of organic solvents.

[0090] Thus, for example, step c) is performed within the temperature range 15°C to 77°C when ethyl acetate (having a boiling point of 77°C) is used as the organic solvent, or between 15°C and 79.6°C when 2-butanone (having a boiling point of 79.6°C) is used as the organic solvent.

[0091] Preferably, step c) is carried out while maintaining a temperature range of 20°C to 80°C.

[0092] The operation is carried out in one or more items of equipment suitable for performing L / L extraction, for example capable of promoting contact between the aqueous and organic phases. For example, equipment with a suitable mechanical stirring system or countercurrent extraction columns are suitable.

[0093] Those skilled in the art will be able to identify the right conditions depending on the equipment and the type of solvent used. For example, by carrying out the operation in a counterflow extraction column it is possible to use a volume of solvent as small as the volume of water present. The operation may be repeated several times, possibly even using a continuous extraction system.

[0094] HMF remains dissolved in the organic phase, from which it can be easily recovered, for example by distillation of the solvent or solvent mixture, preferably under reduced pressure at the end of the process (step e).

[0095] Since the aqueous phase contains the quaternary ammonium salt, any catalyst (if water- soluble), soluble saccharides and any intermediates present after this L / L extraction, this aqueous phase is preferably recycled by feeding it to dehydration step a), with or without purification and / or intermediate concentration steps.

[0096] According to a preferred aspect, before recycling or in order to recover the quaternary ammonium salt, at least some of the water present is removed from the aqueous phase by known techniques, for example by one or more operations selected from evaporation, distillation, reverse osmosis, and combinations thereof. Techniques that do not involve conditions that degrade the reusable components in the process (for example temperature, pressure, extended time) are preferred.

[0097] According to a preferred aspect of the process, therefore, said quaternary ammonium salt separated (together with catalyst, residual saccharide and optionally present intermediates) and concentrated in step d) is re-used by feeding it back to dehydration step a) together with fresh saccharide and optionally together with another salt. This re-use is preferably carried out in the aqueous phase. Also according to this aspect of the process, the amount of water during step a) is preferably kept below 15%, preferably below 10% by weight.

[0098] Concentration is preferably, but not necessarily, preceded by one or more purification treatments, for example using filter elements with high adsorptive power, such as activated carbon. Such treatments have the advantage of removing any molecules present, for example those formed as by-products, which would make HMF unstable during the dehydration reaction in the event of re-use or recycling.

[0099] According to a particularly preferred embodiment, before concentrating the aqueous solution with quaternary ammonium salt, an equimolar amount of fructose is added so that a mixture is obtained in the liquid, not solid, phase after concentration.

[0100] Finally, in step e), the HMF product is obtained as a solution of HMF in the organic phase separated in step c). Optionally, the solvent may be partially removed to increase the concentration, or fully removed to isolate the purified HMF.

[0101] This removal is effected by known techniques, for example by one or more operations selected from evaporation, distillation, reverse osmosis, and combinations thereof. Techniques that do not involve conditions that degrade HMF (for example temperature, pressure, extended time) are preferred.

[0102] According to one aspect of the process, the organic solvent thus separated is advantageously re-used by feeding it to step c).

[0103] According to one aspect, the HMF product is removed from the solvent in step e) by contacting the organic phase separated in step c) with water or another solvent through L / L extraction, or distillation and / or evaporation with solvent exchange.

[0104] This operation is advantageously preceded by appropriate concentration of the solvent.

[0105] In the preferred case where water is subsequently added, HMF is therefore again brought into aqueous solution and used, even without the need for further purification treatments, for subsequent transformation into useful intermediates, for example for oxidation to 2,5- furandicarboxylic acid (FDCA).

[0106] According to another process embodiment that does not involve the partial or total removal of the organic solvent during step e), the HMF product dissolved in an organic solvent separated in step d) is used directly and advantageously without the need to undergo further purification, for subsequent transformation into chemical intermediates, for example for oxidation to 2,5-furandicarboxylic acid (FDCA).

[0107] Such oxidation of HMF to FDCA may advantageously be carried out in both the aqueous phase and the organic phase, using an oxidizing agent such as molecular oxygen (e.g., in the form of air) together with an oxidation catalyst. For example, using the ruthenium -based heterogeneous catalyst described in patent application WO 2021 / 123240 Al.

[0108] A further object of the invention is therefore a process for the production and separation of HMF and further production of FDCA therefrom, comprising the steps of: a) dehydrating at least one saccharide selected from the group consisting of 6-carbon- atom monosaccharides and disaccharides, oligosaccharides and polysaccharides formed from 6-carbon-atom units and mixtures thereof, in the presence of at least one quaternary ammonium salt and optionally of a homogeneous catalyst, at a temperature of 80 -140°C, resulting in a reaction mixture comprising the quaternary ammonium salt, HMF, by-products and any intermediates, catalyst and unreacted saccharide; b) separating water-insoluble by-products from the reaction mixture, resulting in an aqueous solution; c) adding an organic solvent or mixture of organic solvents in which the quaternary ammonium salt and the catalyst are insoluble or slightly soluble, and the 5- hydroxymethylfurfural is soluble at a temperature between 15°C and the boiling point of the organic solvent or mixture of organic solvents, to said aqueous solution, resulting in the quaternary ammonium salt in the aqueous phase and 5-hydroxymethylfurfural together with the organic solvent or mixture of organic solvents in the organic phase; d) separating said aqueous phase obtained in step c) and optionally removing water from it, obtaining quaternary ammonium salt and any intermediates and unreacted saccharide; e) obtaining the organic phase separated in step d) comprising the dissolved HMF and optionally removing at least part of the solvent from the organic phase separated in step d); and f) oxidizing the obtained HMF to FDCA.

[0109] The HMF obtained at the end of the process generally has a high degree of purity, for example above 85%, preferably 90% or more, and more preferably 95% or more, and is suitable for further chemical transformation, such as oxidation to 2,5- furandicarboxylic acid. Alternatively, it may be subjected to further purification processes (for example by crystallisation) if a higher degree of purity is required.

[0110] The process for the synthesis of 5 -hydroxy -methylfurfural according to the invention may be carried out either in batch or continuous or semi-continuous mode.

[0111] The present invention also relates to the product obtained by the process described and claimed.

[0112] The process according to the invention will now be described according to non-limiting examples.

[0113] EXAMPLES

[0114] Example 1 Step a) (dehydration)

[0115] 97.2 g of a solid mixture obtained from 44.9 g fructose and 52.3 g tetraethyl ammonium bromide (TEAB) was placed in a 3 -neck flask fitted with a mechanical stirrer, reflux condenser and thermometer.

[0116] The flask was immersed in a bath of ethylene glycol placed on a heating plate. The mixture was heated with stirring until completely melted and 0.85 g of 40% w / w nitric acid was added when the internal temperature reached 95°C.

[0117] The reaction mixture was held at that temperature and stirred at atmospheric pressure for a reaction time of 30 minutes.

[0118] Step b) (S / L separation)

[0119] The yield of HMF in the mixture obtained at the end of the reaction, determined by HPLC analysis with external calibration, was 80% in moles compared to the theoretical obtainable from the starting fructose.

[0120] The analysis was carried out by means of HPLC fitted with a Cl 8 reversed-phase column (for example Phenomenex Gemini 5 pm NX-C18 110 A 150 x 3 mm) and a UV detector (wavelengths: 265, 275, 285, 310 nm); the weighed samples were dissolved in a suitable solvent (for example water) and the analytical determination was carried out under the following conditions:

[0121] • oven temperature: 35°C;

[0122] • flow: 0.5 ml / min;

[0123] • eluents: A: methanol + 1% formic acid; B: water + 1% formic acid; fed according to the gradient:

[0124] The product from step a) ( basically comprising HMF, TEAB, catalyst, unreacted fructose, intermediates, water and by-products) at the end of the dehydration reaction was diluted in water in a ratio of 1 :4 by weight (1 part reaction product to 4 parts water). A suspension was obtained, and this was filtered through a Buchner filter fitted with filter paper to separate water-insoluble by-products from the resulting aqueous solution.

[0125] Steps c and d) (L / L extraction and separation of the organic phase from the aqueous phase)

[0126] This aqueous solution was then subjected to 3 cross-current extractions with methyl isobutyl ketone (MIBK) using a solvent / water solution weight ratio of 2 for each extraction.

[0127] These extractions were performed in a stirred reactor with a volume of 2 litres equipped with a bottom outlet, setting the extract aside after each extraction and reloading the aqueous phase together with fresh solvent.

[0128] At the end of the 3 cross-current extractions, 437 g of aqueous phase with a residual HMF content of 1.55 g / L and 2839 g of organic phase (sum of the 3 extracts) having an HMF content of 6.92 g / L were obtained.

[0129] Fructose was added to the aqueous phase in order to restore the equimolar ratio with the quaternary ammonium salt and then the water was removed by means of a rotary evaporator at 60°C and reduced pressure.

[0130] At the end of this concentration phase, a liquid, homogeneous product with a water content of around 6 per cent by weight was obtained, which was suitable to be fed to step a) of the process.

[0131] Step e) (removal of organic solvent)

[0132] MIBK was recovered by evaporating it in the presence of water and then removing it as an azeotrope.

[0133] 2700 g of organic phase (total extract) and 864 g of distilled water were placed in a 5-litre flask fitted with a mechanical stirrer, a distillation fitting with coolant and condensate collection flask.

[0134] The flask was immersed in a bath of ethylene glycol heated to 50°C and connected to a vacuum pump set at 130 mbar.

[0135] With continuous stirring, the heterogeneous MIBK / water azeotrope was evaporated.

[0136] At the end of this step, 271 g of an aqueous solution with a HMF content of 83 g / L and 3178 g of condensate consisting of MIBK and water were obtained, from which 2629 g of solvent was separated and could be recycled to step c).

[0137] Example 2

[0138] Example 1 was repeated using the liquid homogeneous product with a water content of around 6% by weight and including quaternary ammonium salt, obtained in step a) of Example 1.

[0139] Specifically, 75 g of said liquid product was placed into a 3 -neck flask fitted with mechanical stirrer, reflux condenser and thermometer. No further catalyst was added.

[0140] The flask was immersed in a bath of ethylene glycol placed on a heating plate. The mixture was heated with stirring to an internal temperature of 110°C and was held at that temperature with stirring at atmospheric pressure for a reaction time of 20 minutes.

[0141] The yield of HMF in the mixture obtained at the end of the reaction, determined by HPLC analysis with external calibration, was 83% in moles in comparison with the theoretical obtainable from the starting fructose.

[0142] Example 3

[0143] Step a) (dehydration)

[0144] A solid mixture obtained from fructose and tetraethyl ammonium bromide (TEAB) in an equimolar ratio was placed in a jacketed reactor with a volume of 5 litres.

[0145] The solid mixture was heated until melting was complete and then fed continuously, via a peristaltic pump, to 2 glass-jacketed reactors placed in series (with a volume of 150 and 43 ml and fitted with a mechanical stirrer and a magnetic stirrer respectively) at a flow rate of 620 g / h. An aqueous solution of 40% nitric acid was fed into the inlet of the first reactor at a flow rate of 0.073 ml / min.

[0146] The reaction mixture was kept stirred at atmospheric pressure and heated to a temperature of 111-113 °C in the first reactor and 90-93 °C in the second reactor.

[0147] At the outlet from the second reactor the reaction product was continuously withdrawn via a peristaltic pump at the same flow rate as the feed and sent to step b).

[0148] The yield of HMF in the mixture obtained at the outlet from the second reactor, determined by HPLC analysis with external calibration, averaged 81% in moles compared to the theoretical obtainable from the starting fructose.

[0149] Step b) (S / L separation)

[0150] At the outlet from the second reactor, the product from step a) (comprising basically HMF, TEAB, catalyst, unreacted fructose, intermediates, water and by-products) was sent continuously into a 1 -litre tank and then diluted in water (1 part reaction product to 4 parts water). The resulting suspension was filtered through paper to separate water-insoluble byproducts. Steps c and d) (L / L extraction and separation of the organic phase from the aqueous phase) The resulting aqueous solution was continuously fed to a 1 -litre tank where, with stirring, it was mixed with an aqueous suspension of activated carbon at 8% w / w. The resulting suspension was continuously fed to the vacuum filtration system to separate the aqueous solution from the spent activated carbon. The decolourised aqueous solution was fed to the liquid / liquid extraction column where it was counter-currently contacted with methyl isobutyl ketone (MIBK) using a solvent to aqueous solution flow rate ratio of 3 (1.5 kg / h for the aqueous solution and 4.5 kg / h for the solvent).

[0151] The organic phase was continuously collected at the head of the extraction column and an aqueous phase with an average residual HMF content of 6 g / L was continuously collected from the bottom. On average, the HMF content of the organic phase was 10.4 g / L.

[0152] Fructose was added to the aqueous phase in order to restore the equimolar ratio with the quaternary ammonium salt; the water was then removed by means of a thin-film evaporator (with a flow rate of 600 g / h), at a constant temperature of 85°C (by means of glycol in a jacket) and a pressure of 35 mbar.

[0153] At the end of this concentration, a liquid homogeneous product with a water content of around 5% by weight was obtained, and this may be fed to step a).

[0154] Step e) (removal of organic solvent)

[0155] 16 kg of organic phase and 5.7 kg of distilled water were placed in a rotary evaporator and the water / MIBK azeotrope was evaporated at 50°C and 125-135 mbar.

[0156] 2.8 kg of an aqueous solution with an HMF content of 74.5 g / L and 18.9 kg of condensate consisting of MIBK and water were obtained, from which 15.8 kg of solvent was separated and which could be recycled to step c).

[0157] Comparative Example 4

[0158] Step a) dehydration

[0159] 97.4 g of a solid mixture obtained from 45 g of fructose and 52.4 g of tetraethylammonium bromide (TEAB) were loaded into a 3 -neck flask equipped with a mechanical stirrer, reflux condenser and thermometer.

[0160] The flask was immersed in an ethylene glycol bath placed on a hot plate. The mixture was heated under stirring until completely melted and when the internal temperature reached 95°C, 0.85 g of 40% nitric acid by weight were added.

[0161] The reaction mixture was maintained at temperature and stirred at atmospheric pressure for a reaction time of 30 minutes.

[0162] The yield of HMF in the mixture obtained at the end of the reaction, determined by HPLC analysis with external calibration, was 81.4% by moles compared to the theoretical obtainable from the starting fructose. The analysis was performed as described in Example 1. The mixture further comprised TEAB, catalyst, unreacted fructose, intermediates, water and by-products.

[0163] 44.7 g of the mixture thus obtained as reaction product of step a) were transferred to a beaker and diluted with 179 g of water (1 part of reaction product and 4 parts of water).

[0164] An aqueous suspension was obtained which was subjected to three cross-current extraction stages with methyl isobutyl ketone (MIBK) using a solvent / aqueous suspension weight ratio of 2 for each extraction. The separation of the aqueous phase from the organic phase was performed in a separating funnel by setting aside the organic phase (extract) after each extraction and recharging the aqueous phase together with fresh solvent.

[0165] After 3 cross-current extraction stages, 208 g of aqueous phase and 1344 g of organic phase (as the sum of the 3 extracts, including most of the water-insoluble by-products) were obtained. The HMF content of the organic phase was 6.45 g / L.

[0166] Fructose was added to the aqueous phase to restore the equimolar ratio with the quaternary ammonium salt and then the water was removed via a rotary evaporator at 60°C and reduced pressure. A liquid and homogeneous product was obtained with a water content of around 6% by weight, which has been recycled to step a) of the process.

[0167] In particular, 47.5 g of said liquid product were loaded into a 3 -neck flask equipped with a mechanical stirrer, reflux condenser and thermometer. No further catalyst was added. The flask was immersed in an ethylene glycol bath placed on a hot plate. The mixture was heated under stirring to an internal temperature of 110 °C and then maintained at this temperature under stirring at atmospheric pressure for 20 minutes.

[0168] The yield of HMF in the mixture obtained at the end of the reaction, determined by HPLC analysis with external calibration, was 71% in moles with respect to the theoretical obtainable from the starting fructose, i.e. a yield more than 12% lower than that obtained starting from the fresh mixture. Example 5

[0169] 25.2 g of the mixture obtained as reaction product of step a) in comparative Example 4 were transferred to a beaker and diluted with 101 g of water (1 part of reaction product and 4 parts of water).

[0170] An aqueous suspension was obtained that was filtered through a Buchner filter equipped with filter paper to separate the water-insoluble by-products from the resulting aqueous solution (Step b) . An amount of solid equal to approximately 0.5% by weight of the reaction product was separated.

[0171] The aqueous solution was subjected to three cross-current extraction stages with methyl isobutyl ketone (MIBK) using for each extraction a weight ratio of solvent / aqueous solution of 2 (Step c). The separation of the aqueous phase from the organic phase was performed in a separating funnel by setting aside the organic phase (extract) after each extraction and recharging the aqueous phase together with fresh solvent. After 3 cross-current extraction stages, 116 g of aqueous phase and 730 g of organic phase (as sum of the 3 extracts) were obtained (Step d). The HMF content of the organic phase was 6.18 g / L.

[0172] Fructose was added to the aqueous phase separated in step d) to restore the equimolar ratio with the quaternary ammonium salt and then the water was removed via a rotary evaporator at 60°C and reduced pressure. A liquid and homogeneous product was obtained with a water content of around 6% by weight, which has been recycled to step a) of the process.

[0173] 20.9 g of said liquid product were loaded into a 3-neck flask equipped with a mechanical stirrer, reflux condenser and thermometer. No further catalyst was added. The flask was immersed in an ethylene glycol bath placed on a hot plate. The mixture was heated under stirring to an internal temperature of 110 °C and was maintained at this temperature and stirring at atmospheric pressure for 20 minutes. The yield of HMF in the mixture obtained at the end of the reaction, determined by HPLC analysis with external calibration, was 80.6% in moles with respect to the theoretical obtainable from the starting fructose, i.e. substantially the same yield obtained starting from the fresh mixture.

Claims

CLAIMS1. Process for the production and separation of 5-hydroxymethylfurfural (HMF) comprising the steps of a) dehydrating at least one saccharide selected from the group consisting of 6-carbon- atom monosaccharides and di saccharides, oligosaccharides and polysaccharides formed from 6-carbon-atom units and mixtures thereof, in the presence of at least one quaternary ammonium salt and optionally of a homogeneous catalyst, at a temperature of 80 -140°C, resulting in a reaction mixture comprising the quaternary ammonium salt, HMF, by-products and any intermediates, catalyst and unreacted saccharide; b) separating water-insoluble by-products from the reaction mixture, resulting in an aqueous solution; c) adding an organic solvent or mixture of organic solvents in which the quaternary ammonium salt and the catalyst are insoluble or slightly soluble, and the 5- hydroxymethylfurfural is soluble at a temperature between 15°C and the boiling point of the organic solvent or mixture of organic solvents, to said aqueous solution, resulting in the quaternary ammonium salt in the aqueous phase and 5- hydroxymethylfurfural together with the organic solvent or mixture of organic solvents in the organic phase; d) separating said aqueous phase obtained in step c) and optionally removing water from it, obtaining quaternary ammonium salt and any intermediates and unreacted saccharide; and e) obtaining the organic phase separated in step d) comprising the dissolved HMF and optionally removing at least part of the solvent from the organic phase, resulting in purified HMF.

2. Process according to claim 1 in which said step a) is carried out in the absence of organic solvents and in the presence of an amount of water preferably not exceeding 15% by weight.

3. Process according to any one of claims 1 to 2 in which said saccharide fed in step a) is selected from the group consisting of: fructose, glucose, galactose, mannose, sucrose, maltose, lactose, cellobiose, oligofructose containing from 3 units to 10 units of fructose, inulin, starch, cellulose and mixtures thereof.

4. Process according to any one of claims 1-3 in which said quaternary ammonium salt isselected from tetraalkyl ammonium halides and hydroxides, preferably having C1-C15 alkyl groups.

5. Process according to each of claims 1-4 in which said homogeneous catalyst in step a) is selected from the group consisting of: mineral acids, organic acids, heteropolyacids, metal oxides, metal halides, metal phosphates, and doped zirconium hydroxides (for example sulfated or tungstated).

6. Process according to any one of claims 1 -5 in which said step b) is carried out after adding water to the dehydration product up to a ratio by weight of said reaction product to water of 1 : 1 to 1 :8.

7. Process according to any one of claims 1-6 in which said aqueous solution obtained in step b) is fed to step c) after concentration and / or purification.

8. Process according to any one of claims 1-7 in which said organic solvent in step c) is selected from the group consisting of: ethyl acetate, butyl acetate, isopropyl acetate, 4- methyl-2-pentanone (MIBK), 2-butanone (methyl ethyl ketone), 2-pentanone (methyl n- propyl ketone), cyclopentanone and mixtures thereof.

9. Process according to any one of claims 1-8 in which said organic solvent is added to the aqueous phase in step c) in an amount equal to or less than 3 : 1 by weight, preferably equal to or less than 2: 1, more preferably equal to or less than 1 : 1 by weight with respect to the weight of the aqueous phase.

10. Process according to any one of claims 1-9 in which said quaternary ammonium salt fed to step a) is obtained at least in part from step d) of the process.

11. Process according to claim 10 in which said quaternary ammonium salt obtained in step d) is fed to step a) after concentration and / or purification.

12. Process according to any one of claims 1-11 in which said solvent removed during step e) is fed to step c).

13. Process for the production and separation of HMF and further production of FDCA therefrom, comprising the steps of: a) dehydrating at least one saccharide selected from the group consisting of 6-carbon- atom monosaccharides and disaccharides, oligosaccharides and polysaccharidesformed from 6-carbon-atom units and mixtures thereof, in the presence of at least one quaternary ammonium salt and optionally of a homogeneous catalyst, at a temperature of 80 -140°C, resulting in a reaction mixture comprising the quaternary ammonium salt, HMF, by-products and any intermediates, catalyst and unreacted saccharide; b) separating water-insoluble by-products from the reaction mixture, resulting in an aqueous solution; c) adding an organic solvent or mixture of organic solvents in which the quaternary ammonium salt and the catalyst are insoluble or slightly soluble, and the 5- hydroxymethylfurfural is soluble at a temperature between 15°C and the boiling point of the organic solvent or mixture of organic solvents, to said aqueous solution, resulting in the quaternary ammonium salt in the aqueous phase and 5- hydroxymethylfurfural together with the organic solvent or mixture of organic solvents in the organic phase; d) separating said aqueous phase obtained in step c) and optionally removing water from it, obtaining quaternary ammonium salt and any intermediates and unreacted saccharide; e) obtaining the organic phase separated in step d) comprising the dissolved HMF and optionally removing at least part of the solvent from the organic phase separated in step d); and f) oxidizing the obtained HMF to FDCA.

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