Syntheses of substituted furans
Patent Information
- Application Number
- BR112021024039
- Authority / Receiving Office
- BR · BR
- Patent Type
- Patents
- Current Assignee / Owner
- Publication Date
- 2026-08-25
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Abstract
Description
1 / 21 SYNTHESES OF SUBSTITUTED FURANS
[001] The present invention relates to methods for synthesizing substituted furans, in particular, to methods for synthesizing furans from sugar-derived compounds. BASIS OF THE INVENTION
[002] Substituted furans are a class of compounds of significant interest, as they can be derived from renewable resources such as sugars and are useful in a wide range of applications. Substituted furans are useful in the preparation of polymers. 2,5-Furandicarboxylic acid (FDCA) is particularly useful as it represents a renewable monomer that can be used in polymers instead of terephthalic acid. Furthermore, polymers such as polyethylene 2,5-furandicarboxylate (PEF) containing FDCA can exhibit improved properties compared to the equivalent terephthalate-containing polymer.
[003] However, the production of substituted furans, such as FDCA, from renewable sources has been a challenge. In particular, many of the steps involved in converting sugars into substituted furans exhibit low selectivity and therefore low yield. Furthermore, some methods require the use of fructose as a starting material, instead of more readily available sugars such as glucose. Although some methods use glucose, it is usually processed into fructose, which can be inefficient.
[004] Recently, there have been several advances in the production of substituted furans. For example, a method is disclosed in US 2017 / 050944 in which gluconic acid derivatives are chemically dehydrated in the presence of a catalyst. Petition 870210110496, dated 11 / 29 / 2021, page 22 / 51 2 / 21 dehydration to provide FDCA. Another method is described in US 2018 / 057897 in which 5-hydroxymethylfuroic acid, a substituted furan, is prepared from 2-keto-3-deoxygluconate (KDG).
[005] Although recent developments are promising, the relatively high temperatures and high acid concentration required lead to relatively modest yields with significant amounts of byproduct. Furthermore, such methods can only provide higher yields when dehydration is carried out in a solvent system that is not entirely aqueous, for example, in an acetic acid or ethanol-based system, which increases the economic cost of the process. Where predominantly aqueous systems have been used, a low yield is obtained.
[006] Thus, there is a need for additional methods to prepare substituted furans that preferably address one or more of the disadvantages associated with existing preparation methods. SUMMARY OF THE INVENTION
[007] The present invention provides a method for preparing a compound of formula II: Formula II where: R1 and R2 are selected independently of -CH2OR', -CHO, -COOR' and -H, provided that R1 and R2 are not both -H; and R' is selected from -H and Ci-s groups. Petition 870210110496, dated 11 / 29 / 2021, p. 23 / 51 3 / 21 hydrocarbyl, from a compound of formula I: HO Formula I: Compounds of formulas I and II, optionally in the form of a salt. The method comprises dehydrating compound of formula I at a pH in the range of 0 to 6 or 8 to 11.5; and a temperature in the range of 10 to 80°C.
[008] It has been surprisingly discovered that compounds of formula I represent useful materials for the preparation of substituted furans. In particular, they can be used in methods where relatively mild conditions are employed, yet they can provide high levels of conversion and selectivity for substituted furans of formula II in a short time.
[009] A method for preparing a compound of formula III is also provided: where: R4 is selected from -OH and -R'; the compound of formula III optionally being in the form of a salt. The method comprises preparing a compound of formula II using a method as defined herein; and, provided that compounds of formula II and III do not have the same Petition 870210110496, dated 11 / 29 / 2021, p. 24 / 51 4 / 21 structure, convert the compound of formula II into a compound of formula III.
[010] The present invention further provides a method for preparing a polymer comprising a polymeric unit of formula IV:
[011] The method comprises preparing a compound of formula III or a salt thereof using a method as defined herein; and forming the polymer by carrying out a polymerization reaction using the compound of formula III.
[012] A compound of formula I is also provided: Formula I where: R1 and R2 are independently selected from -CH2OR', -CHO, -COOR' and -H, provided that R1 and R2 are not both -H; and R' is selected from -H and C1-6 hydrocarbyl groups, the compound of formula I optionally being in the form of a salt. BRIEF DESCRIPTION OF THE DRAWINGS
[013] Fig. 1 is a graph showing the yield obtained when a compound of formula I is dehydrated to Petition 870210110496, dated 11 / 29 / 2021, page 25 / 51 5 / 21 form a compound of formula II under mild conditions, but at various pH levels.
[014] Fig. 2 is a graph showing the yield obtained at different time points during the conversion of a compound of formula I into a compound of formula II under mild conditions.
[015] Fig. 3 is a graph showing the yield obtained when 2-keto-3-deoxygluconate, which is not a compound of formula I, is dehydrated under mild conditions but at varying pH levels to give a compound of formula II. DETAILED DESCRIPTION
[016] The present invention provides a method for preparing a compound of formula II from a compound of formula I. Thus, the method involves carrying out the following dehydration reaction: HO Formula I Formula II
[017] It will be appreciated that one molecule of water is lost from each molecule of compound of formula I as it converts into a compound of formula II. DEHYDRATION REACTION CONDITIONS
[018] The method of the present invention involves the dehydration of the compound of formula I under relatively mild conditions. Specifically, the dehydration reaction is carried out at a pH in the range of 0 to 6 or 8 to 11.5, and at a temperature in the range of 10 to 80°C.
[019] The dehydration reaction can be carried out at a Petition 870210110496, dated 11 / 29 / 2021, p. 26 / 51 6 / 21 temperature up to 70°C, preferably up to 55°C, and more preferably up to 50°C. The dehydration reaction can be carried out at a temperature of at least 15°C, preferably at least 20°C, and more preferably at least 25°C. Thus, the dehydration reaction can be carried out at a temperature of 15 to 70°C, preferably from 20 to 55°C, and more preferably from 25 to 50°C.
[020] In some cases, the dehydration reaction is carried out under acidic conditions. For example, the dehydration reaction can be carried out at a pH of up to 5, preferably up to 4, and more preferably up to 3.5. The dehydration reaction can be carried out at a pH of at least 1.5, preferably at least 1.75, and more preferably at least 2. Thus, the dehydration reaction can be carried out at a pH of 1.5 to 5, preferably 1.75 to 4, and more preferably 2 to 3.5.
[021] In other cases, the dehydration reaction is carried out under basic conditions. For example, the dehydration reaction can be carried out at a pH of at least 8.5, preferably at least 9, and more preferably at least 9.5. The dehydration reaction can be carried out at a pH of up to 11.5, preferably up to 11, and more preferably up to 10.5. Thus, the dehydration reaction can be carried out at a pH of 8.5 to 11.5, preferably 9 to 11, and more preferably 9.5 to 10.5.
[022] pH can be measured using conventional methods, for example, using a pH probe, under the reaction conditions.
[023] A suitable pH can be imparted to the reaction mixture by virtue of the R1 and R2 groups in the compound of formula Petition 870210110496, dated 11 / 29 / 2021, page 27 / 51 7 / 21 I, for example, if Ri and / or R2 are acidic groups, such as -COOH, or basic groups, such as -COO-, where the compound of formula I is present in the form of a salt.
[024] However, at least one of an acid, base, or buffer will typically be added to the reaction mixture to adjust the pH. A buffer should generally be used, optionally with an additional acid or base.
[025] The acid and base will typically catalyze the reaction, that is, they will not be consumed during the course of the reaction.
[026] A wide range of acids can be used. For example, the acid can be selected from organic acids, such as from C1- and carboxylic acids. The acid can be selected from inorganic acids, such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid and hydrobromic acid.
[027] In some embodiments, an acid can be used in the form of a solid. Thus, the reaction can be carried out using a heterogeneous catalyst and, preferably, a solid-phase catalyst.
[028] A wide range of bases can be used. For example, the base can be selected from nitrogen-containing bases such as ammonia, an amine (e.g., a primary, secondary or tertiary amine, and preferably tertiary) and nitrogen-containing heterocycles (e.g., pyridine, imidazole, piperidine or piperazine). The base can be selected from metal-containing bases such as metal hydroxides (e.g., alkali or alkaline earth metal hydroxides), metal oxides (e.g., transition metal oxides) or metal carbonates (e.g., alkali or alkaline metal carbonates). Petition 870210110496, dated 11 / 29 / 2021, page 28 / 51 8 / 21 earthy or hydrogen carbonates).
[029] As with acids, in some embodiments, a base can be used in the form of a solid.
[030] A wide variety of buffers can be used. For example, the buffer can be selected from a citrate buffer, a formate buffer, an acetate buffer, a carbonate buffer, a phosphate buffer, an N-cyclohexyl-2-aminoethanesulfonic acid (CHES) buffer, a borate buffer, a citrate-phosphate buffer, a 2[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES) buffer, a tris(hydroxymethyl)aminomethane (Tris) buffer, a 2-(N-morpholino)ethanesulfonic acid (MES) buffer, a sugar acid buffer, or an ammonia buffer.
[031] The pH will normally remain reasonably constant during the reaction, particularly when a buffer is used. However, it may be desirable to monitor and, when necessary, adjust the pH (e.g., so that it remains within a range of ± 0.8 and preferably ± 0.5 of the target pH) during the course of the dehydration reaction, for example, where the reaction is carried out in a continuous mode.
[032] The dehydration reaction can be carried out in the presence of a protic solvent, such as water. Preferably, the solvent system in which the reaction is carried out contains water in an amount of at least 50%, preferably at least 70%, and more preferably at least 90% by volume. In some cases, the solvent system consists substantially of water.
[033] The compound of formula I can be added to the reactor in an amount greater than 5 g / L, preferably greater than 10 g / L, and more preferably greater than 20 Petition 870210110496, dated 11 / 29 / 2021, p. 29 / 51 9 / 21 g / L of solvent. However, in some embodiments, for example where a single-vessel synthesis is carried out, in which the compound of formula I is prepared from a sugar acid in the same reactor as the compound of formula II (this is described in more detail below), the concentration of the compound of formula I may be low. In these cases, the compound of formula I may be present in the reactor in an amount greater than 0.1 g / L, preferably greater than 0.2 g / L, and more preferably greater than 0.5 g / L. When the compounds of formula I are present in the form of a salt, these values represent the amount of the corresponding free salt form (for example, if the compound of formula I contains the -COOLi group, then the corresponding free salt form would contain the -COOH group).
[034] The dehydration reaction will generally be conducted at ambient pressure, i.e., without the application or removal of pressure. Thus, the dehydration reaction can occur at a pressure of about 1 atm (101.3 kPa), for example, from 0.95 to 1.05 atm (96.3 to 106.4 kPa). However, higher pressures can also be used.
[035] The dehydration reaction will normally take place under agitation conditions, for example, under agitation.
[036] One advantage of the present invention is that the dehydration reaction occurs very quickly and with high yield.
[037] In some cases, the dehydration reaction can be carried out as a batch process. A batch process can be carried out for a period of up to 336 hours, preferably up to 168 hours, more preferably up to 72 hours. Once the dehydration reaction occurs Petition 870210110496, dated 11 / 29 / 2021, page 30 / 51 10 / 21 quickly, in some cases, and even on an industrial scale, the batch process can be carried out over a period of up to 24 hours or even less, for example, over a period of up to 12 hours. Batch processes will be carried out in a batch reactor system.
[038] However, the dehydration reaction will preferably be carried out as a continuous process. A continuous process can be carried out for at least 14 days, preferably at least 30 days, and more preferably at least 60 days. Continuous processes will be carried out in a continuous reactor system.
[039] Another advantage is that minimal byproducts are formed, even when a single-vessel synthesis is carried out in which the compound of formula I is prepared from a sugar acid in the same reactor as the compound of formula II (i.e., described in greater detail below).
[040] The dehydration reaction is preferably carried out on an industrial scale. Thus, the dehydration reaction can be carried out in a reactor with a volume greater than 100 L, preferably greater than 500 L, and most preferably greater than 1000 L.
[041] The compound of formula II can be produced in a quantity greater than 5 g / L, preferably greater than 10 g / L, and more preferably greater than 20 g / L of solvent.
[042] The compounds of formula II can be obtained with a yield of at least 60%, preferably at least 80%, preferably at least 90%, preferably at least 95%, preferably at least 99%, and most preferably at least 99.5% of formula I. Petition 870210110496, dated 11 / 29 / 2021, pp. 31 / 51 11 / 21 Compounds
[043] The compounds with formulas I and II are shown below: HO Formula 1 Formula II
[044] It will be appreciated that the groups present as R1 and R2 in compounds of formula I will not be modified during the course of the dehydration reaction, that is, R1 and R2 are equal in compounds of formula I and formula II.
[045] Ri and R2 are selected independently of -CH2OR', -CHO, -COOR' and -H. Ri and R2 are not both -H or, in other words, the compounds of formulas I and II must be substituted.
[046] R' is selected from H and C1-6 hydrocarbyl groups. Preferably, R' is selected from -H and C1-4 hydrocarbyl groups, more preferably from -H and C2-3 hydrocarbyl groups, and most preferably, it is H. The hydrocarbyl group is preferably an alkyl group, although other groups, such as alkenyl groups, may be present.
[047] Ri and R2 are preferably selected from -CH2OH, -CHO, -COOH and -H, and more preferably from -CH2OH, -CHO, -COOH.
[048] At least one of Ri and R2 can be selected from -COOH.
[049] At least one of Ri and R2 can be selected from -CH2OH. Petition 870210110496, dated 11 / 29 / 2021, pp. 32 / 51 12 / 21
[050] Preferably, one of Ri and R2 is selected from -CH2OH and the other is selected from -COOH, and more preferably, Ri is -CH2OH and R2 is -COOH. Thus, the compound of formula I preferably has the structure:
[051] This structure is particularly preferred, since it is derived from 2-keto-3-deoxygluconate which, in turn, can be derived from glucose. This preferred structure yields a compound of formula II which is 5-hydroxymethyl-2-furoic acid:
[052] In other embodiments, Ri and R2 are selected from -COOH. These embodiments advantageously allow the compound of formula II to be used directly in a polymerization reaction.
[053] The compounds of formulas I and II may be in the form of a salt. Preferred salts may be selected from alkali metal salts (e.g., lithium, sodium, or potassium salts) and alkaline earth metal salts (e.g., magnesium or calcium salts). Carboxyl groups (-COOH) are particularly suitable for salt formation. A compound of formula II may be in the same salt form as the compound of formula I. Petition 870210110496, dated 11 / 29 / 2021, pp. 33 / 51 13 / 21 Preparing compounds of formula I
[054] Compounds of formula I can be prepared from a precursor compound having the following formula: Precursor I
[055] It will be appreciated that precursor I can convert between other tautomeric forms in the reaction mixture, for example, it may be present in the form of a linear chain molecule or in the form of a 5- or 6-membered ring. The 5- or 6-membered ring forms may include, in addition to the form shown above, 5- or 6-membered lactones, where one of R1 or R2 is a COOH group, and 6-membered pyranose compounds, where one of R1 or R2 represents the CH2OH group.
[056] Thus, the method of the present invention may comprise providing the compound of formula I from precursor I, for example, by a dehydration reaction: Precursor I Formula I
[057] The dehydration reaction is preferably carried out in the presence of an enzyme, such as a dehydratase.
[058] The compound of formula II can be obtained with a yield of at least 50%, preferably at least 70%, and preferably at least 90% from precursor I.
[059] In some forms, a precursor I may be Petition 870210110496, dated 11 / 29 / 2021, pp. 34 / 51 14 / 21 is converted into a compound of formula I and, in the same reactor, the compound of formula I can be converted into a compound of formula II. Thus, the reactions can be advantageously carried out as a single-vessel synthesis, i.e., a synthesis in which no intermediate processing is involved.
[060] When a single-vessel synthesis is performed, although an enzyme may be present to promote the conversion of precursor I into a compound of formula I, the enzyme will normally not be able to convert compound of formula I into a compound of formula II under the reaction conditions of the present invention. In such embodiments, it is desirable to use a pH level that promotes the conversion of a compound of formula I into a compound of formula II, but that does not reduce the activity of the enzyme that is, in the same vessel, promoting the conversion of precursor I to a compound of formula II. As mentioned above, in such embodiments, the preferred acidic pH levels are 1.5 to 6, preferably 2 to 6, and more preferably 3.5 to 6. The preferred basic pH levels are 8 to 11.5, preferably 8 to 10.5, and more preferably 8 to 9.5.
[061] In other embodiments, the method of the present invention may comprise converting a precursor I into a compound of formula I, isolating the compound of formula I and subsequently converting a compound of formula I into a compound of formula II.
[062] Preferably, compounds of formula I are obtained from sugar acids. Sugar acids are well known in the art as monosaccharides that Petition 870210110496, dated 11 / 29 / 2021, pp. 35 / 51 15 / 21 comprise at least one carboxyl group (-COOH). Thus, compounds of formula I can be obtained from a precursor I, in which at least one of R1 and R2, and preferably R2, is -COOH.
[063] The method of the present invention may further comprise providing the acid sugar from an acid-free sugar. It will be appreciated that, in the context of the present invention, the term acid-free sugar is intended to denote monosaccharides that do not contain a -COOH group. In particular, the acid sugar may be derived from glucose, for example, according to the following route:
[064] The above pathway shows the oxidation of glucose, followed by dehydration. Alternatively, glucose can be dehydrated and then oxidized, although this is less preferred. Similarly, although the above pathway shows the preferred stereochemistry for glucose, any other stereochemistry may be present.
[065] The conversion of glucose into an acidic sugar is preferably carried out enzymatically, for example, with a Petition 870210110496, dated 11 / 29 / 2021, pp. 36 / 51 16 / 21 first enzyme for the oxidation step and a second enzyme for the dehydration step. Suitable methods for converting glucose to 2-keto-3-deoxygluconate are described in US 2018 / 057897, the contents of which are incorporated herein by reference.
[066] Alternatively, compounds of formula I can be prepared synthetically. A person skilled in the art would be able to determine suitable methods. Using compounds of formula II
[067] Compounds of formula II can be used in a method of preparing a compound of formula III:
[068] Thus, according to another aspect, the present invention provides a method for preparing a compound of formula III. The method comprises preparing a compound of formula II using a method as defined herein and, provided that compounds of formulas II and III do not have the same structure, converting the compound of formula II into a compound of formula III.
[069] Thus, the method involves carrying out the following reaction: HO Formula 1 Formula II Petition 870210110496, dated 11 / 29 / 2021, pp. 37 / 51 17 / 21 Formula III
[070] Ri and R2 are as described above.
[071] R4 is selected from -OH and -R', where R' is as described above. Preferably, R4 is OH.
[072] The compound of formula III may be in the form of a salt. Preferred salts may be selected from alkali metal salts (e.g., lithium, sodium, or potassium salts) and alkaline earth metal salts (e.g., magnesium or calcium salts). Carboxyl groups (COOH) are particularly suitable for salt formation. A compound of formula III may be in the same salt form as the compound of formula II.
[073] In preferred embodiments, at least one of Ri and R2 in formula II is selected from -CH2OH and -COR', and the method comprises oxidizing the compound of formula II to convert at least one -CH2OH and -COR' group to -COR4, where R4 is OH. Suitable oxidation conditions are known in the art.
[074] In some embodiments, a compound of formula I can be converted into a compound of formula II and, in the same reactor, a compound of formula II can be converted into a compound of formula III. Thus, the reactions can be advantageously carried out as a single-vessel synthesis, i.e., a synthesis in which no intermediate processing is involved.
[075] In alternative embodiments, a compound of formula I can be converted into a compound of formula II Petition 870210110496, dated 11 / 29 / 2021, pp. 38 / 51 18 / 21 in a first reactor, and then the compound of formula II can be converted into a compound of formula III in a second reactor. In these embodiments, the compound of formula II can be extracted and / or purified before being transferred to the second reactor.
[076] The compounds of formula III represent monomers useful in the preparation of polymers. Thus, in another aspect of the present invention, a method is provided for preparing a polymer comprising a polymeric unit of formula IV: Formula IV
[077] The method comprises preparing a compound of formula III, or a salt thereof, using a method as defined herein, and forming the polymer by carrying out a polymerization reaction using the compound of formula III.
[078] Normally, the compound of formula III will be isolated, and optionally purified, before being used to prepare a polymeric unit of formula IV.
[079] The present invention further provides compounds of formula II, compounds of formula III or polymers comprising a polymeric unit of formula IV which can be obtained using the methods described herein.
[080] The invention will now be described with reference to the accompanying non-limiting examples. EXAMPLES Example 1: Dehydration of a compound of formula I at various pH levels. Petition 870210110496, dated 11 / 29 / 2021, pp. 39 / 51 19 / 21
[081] Experiments were conducted to determine whether compounds of formula I can be dehydrated into compounds of formula II in high yield under mild conditions. The following compound of formula I was used: HO
[082] A 1 mM aqueous solution of the compound of formula I was diluted 20 times by volume using buffer, water, or 1% formic acid. Aqueous citric acid solutions (50 mM) were prepared and adjusted with sodium hydroxide to provide citrate acid buffers with pH levels of 3, 3.5, and 4. A sodium phosphate buffer (50 mM) was used to provide a pH of 7. Water was used to provide a pH of ~9.5-10. 1% formic acid was used to provide a pH of 2.2. Each reaction mixture was incubated in an oven at 55°C for 18 hours. A sample of each reaction mixture after the aforementioned 18 hours of incubation was analyzed by LC-MS / MS to determine the concentration of the compound of formula II, i.e., 5-hydroxymethyl-2-furoic acid (HMFA). Figure 1 shows the yield obtained in each reaction.
[083] It can be seen that a very high yield of the compound of formula II was obtained under acidic or basic conditions, while a low yield was obtained at or near neutral pH. Thus, this example demonstrates a viable method of producing the compound of formula II under relatively mild conditions. Example 2: Dehydration yield of a compound of Petition 870210110496, dated 11 / 29 / 2021, pages 40 / 51 20 / 21 Formula I with time
[084] Experiments were conducted to determine whether the dehydration of a compound of formula I under mild conditions occurs rapidly enough to be industrially viable. The compound of formula I that was used in Example 1 was also used in these experiments, thus providing HMFA as the compound of Formula II.
[085] A 10 mM solution of the compound of formula I was diluted with citrate buffer (50 mM) to provide a 2.5 mM solution of the compound of formula I with a pH of 3.5. The resulting reaction mixture was incubated at 35°C. A sample was taken approximately every 1.5 minutes and analyzed by LC-MS / MS. The results are shown in Figure 2.
[086] It can be seen that the compound of formula I dehydrates extremely rapidly under mild conditions, with conversion of approximately 50% observed in just 10 minutes. Example 3: Dehydration of other compounds of formula I under mild conditions.
[087] Experiments were conducted to determine whether other compounds of formula I can be dehydrated under mild conditions. The following compounds were used in the experiments: Petition 870210110496, dated 11 / 29 / 2021, pp. 41 / 51 21 / 21
[088] Both compounds were converted into the corresponding compounds of formula II under mild conditions. A temperature as low as 18°C was further used to quantitatively convert the second compound (i.e., where R1 is -CH2OH and R2 is H). Comparative Example: Dehydration of 2-keto-3-deoxygluconate under mild conditions
[089] Experiments were conducted to determine whether 2-keto-3-deoxygluconate (KDG) could be dehydrated under mild conditions to provide HMFA, i.e., a compound of formula II, in good yield.
[090] McIlvaine buffer was prepared using a combination of 200 mM disodium hydrogen phosphate and 100 mM citric acid for use in reaction mixtures with a pH of 3, 3.5, 4, or 4.5. 100 mM sodium phosphate buffer was prepared to serve as a neutral pH control. 1 mL of 2 mM KDG in its sodium salt form was combined with 1 mL of buffer and incubated at 55°C in an oven for 27 hours. A sample from each reaction was analyzed by LC-MS / MS to determine the HMFA concentration. The results are shown in Figure 3.
[091] Unlike compounds of formula I, the yield observed in the dehydration of KDG in HMFA under mild conditions was not greater than 1%, even after 27 hours. Petition 870210110496, dated 11 / 29 / 2021, pages 42 / 51
Claims
1 / 6 CLAIMS 1. Method for preparing a compound of formula II: Ri R2 Formula II where: R1 and R2 are selected independently from CH2OR', -CHO, -COOR' and -H, provided that R1 and R2 are not both -H; and R' is selected from -H and C1-6 hydrocarbyl groups, from a compound of formula I: Formula I the compounds of formulas I and II optionally being in the form of a salt, characterized in that the method comprises dehydrating the compound of formula I at: a pH in the range of 0 to 6 or 8 to 11.5; and a temperature in the range of 10 to 80°C.
2. Method according to claim 1, characterized in that the dehydration reaction is carried out at a temperature in the range of 15 to 70°C.
3. Method according to claim 2, characterized in that the dehydration reaction is carried out at a temperature in the range of 25 to 50°C.
4. Method according to claim 1 or 2, Petition 870260065263, dated 02 / 07 / 2026, page 11 / 24 2 / 6 characterized in that the dehydration reaction is carried out at a pH in the range of 1.5 to 5, in the presence of an acid selected from: organic acids, such as C1-6 carboxylic acids; and inorganic acids, such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid and hydrobromic acid.
5. Method according to claim 4, characterized in that the dehydration reaction is carried out at a pH in the range of 2 to 3.
5.
6. Method according to claim 1 or 2, characterized in that the dehydration reaction is carried out at a pH in the range of 8.5 to 11.5 in the presence of a base selected from: nitrogen-containing bases (for example, ammonia, an amine or a nitrogen-containing heterocycle); and metal-containing bases (for example, a metal hydroxide, a metal oxide or a metal carbonate).
7. Method, according to any one of claims 1 to 6, characterized in that the dehydration reaction is carried out in the presence of: a heterogeneous solid-phase catalyst; and / or a buffer selected from a citrate buffer, a formate buffer, an acetate buffer, a carbonate buffer, a phosphate buffer, an N-cyclohexyl-2-aminoethanesulfonic acid (CHES) buffer, a borate buffer, a citrate-phosphate buffer, a 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES) buffer, a tris(hydroxymethyl)aminomethane (Tris) buffer, a 2-(N-morpholino)ethanesulfonic acid (MES) buffer, a sugar acid buffer, or an ammonia buffer.
8. A method according to any one of claims 1 to 7, characterized in that the dehydration reaction is carried out in the presence of a protic solvent, such as water, and in that the dehydration reaction is carried out in a solvent system containing water in an amount of at least 50% by volume.
9. A method according to any one of claims 1 to 8, characterized in that the dehydration reaction is carried out as a batch process or as a continuous process.
10. A method according to any one of claims 1 to 9, characterized in that the final concentration of the compound of formula II in the reaction mixture is greater than 5 g / L of solvent.
11. Method according to claim 10, characterized in that the final concentration of the compound of formula II in the reaction mixture is greater than 20 g / L of solvent.
12. Method, according to any one of claims 1 to 11, characterized in that the compound of formula II is obtained in a yield of at least 60% of formula I.
13. Method, according to any one of claims 1 to 12, characterized in that the compounds of formulas I and II may be in the form of an alkali metal or alkaline earth metal salt.
14. Method, according to any one of claims 1 to 13, characterized in that the method comprises providing the compound of formula I to Petition 870260065263, dated 02 / 07 / 2026, page 13 / 24 4 / 6 of the following precursor I: Precursor I in which the conversion of precursor I into the compound of formula I is carried out in the presence of an enzyme.
15. Method according to claim 14, characterized in that precursor I is converted into a compound of formula I, and the compound of formula I is converted into a compound of formula II, in the same reactor, wherein the pH level in the reactor is selected from: acidic pH levels of 3.5 to 6; and basic pH levels of 8 to 9.
5.
16. A method according to any one of claims 1 to 15, characterized in that the method comprises providing the compound of formula I from a sugar acid, and the method further comprises providing the sugar acid from a sugar.
17. Method, according to any one of claims 1 to 16, characterized in that Ri and R2 are selected from -CH2OH, -CHO, -COOH and -H.
18. A method according to any one of claims 1 to 17, characterized in that at least one of R1 and R2 is selected from -COOH and -CH2OH.
19. Method, according to any one of claims 1 to 18, characterized in that both R1 and R2 are -COOH.
20. Method for preparing a compound of formula III: Petition 870260065263, dated 02 / 07 / 2026, p. 14 / 24 5 / 6 where: R4 is selected from -OH and R'; and R' is selected from -H and C1-6 hydrocarbyl groups; the compound of formula III being optionally in the form of a salt, wherein the method is characterized in that it comprises: preparing a compound of formula II using a method as defined in any one of claims 1 to 16; and provided that the compounds of formula II and III do not have the same structure, converting the compound of formula II into a compound of formula III.
21. Method according to claim 20, characterized in that at least one of Ri and R2 in formula II is selected from -CH2OH, the method comprises the oxidation of the compound of formula II.
22. Method for preparing a polymer, comprising a polymeric unit of formula IV: Formula IV characterized in that the method comprises: preparing a compound of formula III or a salt thereof using a method as defined in claim 20 or 21; and forming the polymer by carrying out a polymerization reaction using the compound of formula III.