Process for preparing at least partially acetal-protected sugars

Abstract

The present invention relates to a process for preparing an at least partially acetal-protected sugar, comprising the step of reacting a sugar or sugar derivative selected from the group consisting of aldopentoses, aldohexoses, aldopentosides and aldohexosides with an aldehyde or aldehyde source in the presence of a heterogeneous acidic catalyst to form an at least partially acetal-protected sugar selected from the group consisting of compounds of formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) and (XII): In the formula, R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 12 and R and R′, R and R′, R and R′, and R 12 and R 12 are identical or different from one another; and Y is hydrogen or a straight, branched, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms; Z is a linear, branched, or cyclic hydrocarbon moiety having 0 to 12 carbon atoms, optionally substituted with 1 to 4 C1-C4 alkyl groups, or 1 to 4 halogen atoms, or a benzyl group; and E is -COOH, -CH(COOH)2, -COOR 19 , -CH(COOR 20 )(COOR 21 ), -CHO, -CH(CHO)2, -C2H3, -CH(C2H3)2, -CHCHR 22 , -CHCR 23 R 24 , -C2H, -C2R 25 , -N3, -NH2, -CH(NH2)2, -NHR 26 , -CH(NHR 27 )(NHR 28 ), -NR 29 R 30 , -CH(NR 31 R 32 )(NR 33 R 34 ), -OH, -OR35 , or -CH(R 36 OH)(R 37 OH); and R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 and R 35 are C1 to C 20 is alkyl; and R 20 and R 21 , R 23 and R 24 , R 27 and R 28 , R 29 and R 30 , R 31 and R 32 , and R 33 and R 34 are identical to or different from one another; and R 36 and R 37 are, independently of one another, absent or straight-chain or branched C1-C 12 is a hydrocarbon chain; and R 13 , R 14 , R 15 , R 16 , R 17 and R 18 are each independently hydrogen or a straight-chain, branched-chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms. JPEG2025536078000039.jpg83102

Description

[Technical Field]

[0001] The present invention relates to a method for preparing at least partially acetal-protected sugars. [Background technology]

[0002] In recent years, the gradual depletion of fossil fuel resources, the increase in global energy consumption, and environmental concerns have driven the development of new materials and technologies that utilize renewable biological resources such as biomass and food waste. One of the cutting-edge topics in this field is the development of bio-based chemicals, which are considered as more environmentally friendly alternatives to petroleum-derived chemicals. Essentially, bio-based chemicals often do not result in a net increase in carbon dioxide in the atmosphere at the end of their useful life, thus ensuring less environmental damage.

[0003] WO 2022 / 223480 discloses acetal-protected xylose, i.e., diformylxylose (DFX), and its derivatives as environmentally friendly polar aprotic solvents. Example 1 demonstrates a synthetic route from commercially available D-xylose and paraformaldehyde using a homogeneous acidic catalyst (HSO) that must be added dropwise to avoid sugar degradation.

[0004] WO 2021 / 074211 discloses a method for producing polymerizable monomers from renewable resources such as biomass. It demonstrates that xylose protected with glyoxylic acid can be produced in the presence of a homogeneous acid catalyst. This glyoxylic acid-protected xylose can be used in polymer synthesis.

[0005] Y.M. Questell-Santiago, R. Zambrano-Varela, M. Talebi Amiri and J.S. Luterbacher, Nat. Chem. 2018, 10, 1222-1228, disclose that DFX can be synthesized directly from D-xylose in the presence of a 37 wt.% aqueous solution of formaldehyde and a 37 wt.% aqueous solution of HCl, using 1,4-dioxane as the solvent and n-hexane as the extraction solvent.

[0006] All methods require constant addition and neutralization of homogeneous acid, which is undesirable in large scale processing due to the added cost and waste management. Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention was to provide a simpler method for preparing acetal-protected sugars in high yields using a scalable method. [Means for solving the problem]

[0008] This problem is solved by a method according to claim 1. Further preferred embodiments are the subject matter of dependent claims 2-15.

[0009] It has now been found that an at least partially acetal-protected sugar can be prepared by a process comprising the step of reacting a sugar or sugar derivative selected from the group consisting of aldopentoses, aldohexoses, aldopentosides and aldohexosides with an aldehyde or aldehyde source in the presence of a heterogeneous acidic catalyst to form an at least partially acetal-protected sugar selected from the group consisting of compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI and XII:

[0010] [ka] [ka] [ka]

[0011] In the formula, R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 12 R′ is Y or ZE, and R and R′, R and R′, R and R′, and R 12 and R 12 ' are the same or different from each other, Y is hydrogen or a linear, branched, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms; Z is a linear, branched, or cyclic hydrocarbon moiety having 0 to 12 carbon atoms, optionally substituted with 1 to 4 C1-C4 alkyl groups, or 1 to 4 halogen atoms, or benzyl groups; and E is -COOH, -CH(COOH)2, -COOR 19 , -CH(COOR 20 )(COOR 21 ), -CHO, -CH(CHO)2, -C2H3, -CH(C2H3)2, -CHCHR 22 , -CHCR 23 R 24 , -C2H, -C2R 25 , -N3, -NH2, -CH(NH2)2, -NHR 26 , -CH(NHR 27 )(NHR 28 ), -NR 29 R 30 , -CH(NR 31 R 32 )(NR 33 R 34 ), -OH, -OR 35 , or -CH(R 36 OH)(R 37 OH), and R 19 , R 20 , R 21 , R22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 and R 35 are C1 to C 20 alkyl, and R 20 and R 21 , R 23 and R 24 , R 27 and R 28 , R 29 and R 30 , R 31 and R 32 , and R 33 and R 34 are the same or different from each other, and R 36 and R 37 are, independently of one another, absent or straight-chain or branched C1-C 12 a hydrocarbon chain, and R 13 , R 14 , R 15 , R 16 , R 17 and R 18 are each independently hydrogen or a straight-chain, branched-chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms.

[0012] The use of heterogeneous acidic catalysts reduces the need for constant addition and neutralization of homogeneous acids.The catalysts can be easily recycled, for example, by filtration, which is advantageous from the economic and environmental perspectives.Furthermore, the catalysts can be used as packing materials in continuous flow reactors for large-scale production.In addition, the yield and selectivity of acetal-protected sugars can be improved compared to traditional homogeneous catalyst systems such as HCl or H2SO4.

[0013] Furthermore, despite the high reactivity of aldehydes toward undesired aldol condensation, oxidation, self-polymerization, and formation of geminal diols during the reaction, it is possible to obtain compounds of formulae I-XII in the presence of heterogeneous catalysts. Furthermore, the inherent hydrate formation of aldehydes allows for the control of the rate and selectivity of sugar protection by adjusting the water content in the reaction system.

[0014] The selectivity of the acetal-protected sugar can be further enhanced by the heterogeneous catalyst's varying pore size and affinity for reactants and products. Selectivity for small products can be enhanced by small pore heterogeneous catalysts, e.g., increasing the selective formation of compounds of formulas IV-XI over compounds of formulas I, II, III, and XII, or by bulkier R groups (R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 12 R groups (R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R') are smaller than the R groups (R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 12 The selective formation of compounds of Formulas I-XII having a hydroxyl group selected from the group consisting of hydroxyl groups (a group selected from the group consisting of hydroxyl groups) can be enhanced. Conversely, selectivity for larger products can be enhanced by a large-pore heterogeneous catalyst, e.g., enhancing the selective formation of compounds of Formulas I, II, III, and XII over compounds of Formulas IV-XI, or enhancing the selective formation of compounds of Formulas I-XII having bulkier R groups over smaller R groups. Similarly, selectivity can be tuned by the affinity between the aldehyde and the heterogeneous catalyst. High affinity between the aldehyde and the heterogeneous catalyst results in higher selectivity for the formation of compounds of Formulas I, II, III, and XII over compounds of Formulas IV-XI. Low affinity between the aldehyde and the heterogeneous catalyst results in higher selectivity for the formation of compounds of Formulas IV-XI over compounds of Formulas I, II, III, and XII.

[0015] Some of the compounds produced by the method of the present invention can be used as environmentally friendly polar aprotic solvents. Some of these compounds that can be used as these types of solvents have performance comparable to or better than their traditional fossil-based counterparts. Furthermore, they have many other applications. For example, these compounds can be used as the base molecules for the production of many other bio-based products, and therefore, efficient production of these compounds is important. For example, DFX can be a starting compound for producing the food additive xylitol. Partially acetal-protected sugars with long-chain hydrocarbon aldehydes, such as alkyl or alkenyl aldehydes, can also be used as bio-based surfactants. Fully protected sugars with ester, carboxyl, or hydroxyl groups in their corresponding R groups can be used as building blocks for polymer production.

[0016] Within the scope of the present invention, the term "aldopentose" refers to a pentose having an aldehyde function as its most terminal carbon atom, preferably selected from the group consisting of D-ribose, L-ribose, D-arabinose, L-arabinose, D-xylose, L-xylose, D-lyxose and L-lyxose. Due to tautomerization of the sugar, this aldopentose can be used in the linear pyranose or furanose conformation or in mixtures thereof.

[0017] Within the scope of the present invention, the term "aldohexose" refers to a hexose having an aldehyde function as the most terminal carbon atom, preferably selected from the group consisting of D-allose, L-allose, D-altrose, L-altrose, D-glucose, L-glucose, D-mannose, L-mannose, D-gulose, L-gulose, D-idose, L-idose, D-galactose, L-galactose, D-talose, and L-talose. Due to tautomerization of the sugar, this aldohexose can be used in the linear pyranose or furanose conformation or in mixtures thereof.

[0018] Within the scope of the present invention, the term "aldopentoside" refers to a pentose, as defined above, having attached to the oxygen atom at position 1 of the aldopentose via a glycosidic bond a functional group selected from the group consisting of a linear, branched, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms, preferably a C1-C4 alkyl group, and therefore refers to a 1-O-alkyl aldopentose, preferably selected from the group consisting of 1-O-alkyl-D-ribose, 1-O-alkyl-L-ribose, 1-O-alkyl-D-arabinose, 1-O-alkyl-L-arabinose, 1-O-alkyl-D-xylose, 1-O-alkyl-L-xylose, 1-O-alkyl-D-lyxose, and 1-O-alkyl-L-lyxose, where the alkyl group is preferably selected from the group consisting of methyl, ethyl, propyl, and butyl, most preferably methyl. Most preferably, the aldopentoside is 1-O-methyl-D-xylose. Due to tautomerization of the sugar, the alkyl aldopentose can be used in a linear pyranose or furanose conformation, or a mixture thereof. Due to the additional protection of the hydroxyl group at the 1-position of the sugar, this starting material can lead to easier production of one-sided acetal monomers containing a free hydroxyl group. This can lead to bifunctional monomers (such as hydroxy acids when glyoxylic acid is used).

[0019] Within the scope of the present invention, the term "aldohexoside" means a hexose as defined above in which a functional group selected from the group consisting of a linear, branched or cyclic hydrocarbon moiety having 1 to 20 carbon atoms, preferably a C1 to C4 alkyl group, is attached via a glycosidic bond to the oxygen atom at position 1 of the aldohexose, and therefore means a 1-O-alkylaldohexose. It is preferably selected from the group consisting of 1-O-alkyl-D-allose, 1-O-alkyl-L-allose, 1-O-alkyl-D-altrose, 1-O-alkyl-L-altrose, 1-O-alkyl-D-glucose, 1-O-alkyl-L-glucose, 1-O-alkyl-D-mannose, 1-O-alkyl-L-mannose, 1-O-alkyl-D-gulose, 1-O-alkyl-L-gulose, 1-O-alkyl-D-idose, 1-O-alkyl-L-idose, 1-O-alkyl-D-galactose, 1-O-alkyl-L-galactose, 1-O-alkyl-D-talose and 1-O-alkyl-L-talose, and the alkyl group is preferably selected from the group consisting of methyl, ethyl, propyl and butyl, most preferably methyl. Most preferably, the aldohexoside is 1-O-methyl-D-glucose. Due to tautomerization of the sugar, the alkyl aldohexose can be used in the linear pyranose or furanose conformation, or a mixture thereof. Due to the additional protection of the hydroxyl group at the 1-position of the sugar, this starting material leads to a more stable product without a free -OH group, which can be useful for generating linear polymers.

[0020] The term "at least partially acetal-protected sugar" means a sugar or sugar derivative selected from the group consisting of aldopentose, aldohexose, aldopentoside, and aldohexoside, where the aldopentose, aldohexose, aldopentoside, or aldohexoside is either partially protected with an aldehyde, i.e., only two hydroxyl groups together with one aldehyde form one cyclic acetal (thus forming a compound of formula IV, V, VI, VII, VIII, IX, X, or XI), or where the aldopentose, aldohexose, aldopentoside, or aldohexoside is fully protected, i.e., four hydroxyl groups together with two aldehydes form two corresponding cyclic acetals (thus forming a compound of formula I, II, III, or XII).

[0021] An aldehyde is an organic compound containing the group -CHO, and an aldehyde source is a polymeric or oligomeric compound capable of producing an aldehyde under reaction conditions. The term aldehyde also encompasses the geminal diols of the corresponding aldehyde, i.e., aldehyde hydrates. DETAILED DESCRIPTION OF THE INVENTION

[0022] One embodiment of the present invention relates to the preparation of a fully protected compound selected from the group consisting of compounds of formula I, II, III and VII:

[0023] [ka]

[0024] In one embodiment of the present invention, R 13 , R 14 , R 15 , R 16 and R 17 is hydrogen, resulting in an at least partially protected compound selected from the group consisting of compounds of formula IVa, VIa, VIIIa, Xa and XIa:

[0025] [ka]

[0026] In one embodiment of the present invention, R 13 , R 14 , R 15 , R 16 and R 17 is a straight chain, branched chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms, preferably 1 to 6 carbon atoms, most preferably methyl, ethyl, propyl, and butyl, and ideally methyl, resulting in an at least partially protected compound selected from the group consisting of formula IVb, VIb, VIIIb, VIIb, Xb, XIb, and XII:

[0027] [ka] [ka]

[0028] In one embodiment of the present invention, R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 12 ' is Y and Y is hydrogen.

[0029] In a further embodiment of the present invention, R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 12 ' is Y and is a linear or branched C1-C 20 Alkyl, straight or branched chain C2-C 20 Alkenyl, cycloaliphatic or aromatic systems, preferably C6-C 20alkyl, and combinations thereof.

[0030] Straight or branched chain C1 to C 20 The term "alkyl" refers to a straight or branched chain hydrocarbon group containing from 1 to 20 carbon atoms. Examples of "alkyl" as used herein include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl and eicosyl.

[0031] Straight or branched chain C2 to C 20 The term "alkenyl" refers to a straight-chain or branched-chain hydrocarbon group containing 2 to 20 carbon atoms and having at least one carbon-carbon double bond. Examples of "alkenyl" as used herein include vinyl (ethenyl), propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and isobutenyl.

[0032] The term "cycloaliphatic ring or aromatic system" refers to an aliphatic or aromatic ring system having 3 to 10, preferably 5 to 8, carbon atoms.

[0033] In one embodiment of the present invention, R1, R1', R2, R2', R3, R3', R4, R5, R6, R7, R8, R9, R in compounds of formula I, II, III, IV (IVa and IVb), V, VI (VIa and VIb), VII, VIII (VIIIa and VIIIb), IX, X (Xa and Xb), XI (XIa and XIb) and XII 10 , R 11 , R 12 and R 12 ' is ZE, where Z is a linear, branched, or cyclic hydrocarbon moiety having 0 to 12 carbon atoms, optionally substituted with 1 to 4 C1-C4 alkyl groups, or 1 to 4 halogen atoms, or benzyl groups; and E is -COOH, -CH(COOH)2, -COOR 19 , -CH(COOR 20 )(COOR 21 ), -CHO, -CH(CHO)2, -C2H3, -CH(C2H3)2, -CHCHR 22 , -CHCR 23 R 24 , -C2H, -C2R 25 , -N3, -NH2, -CH(NH2)2, -NHR 26 , -CH(NHR 27 )(NHR 28 ), -NR 29 R 30 , -CH(NR 31 R 32 )(NR 33 R 34 ), -OH, -OR 35 , or -CH(R 36 OH)(R 37 OH), and R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 and R 35 are C1 to C 20 alkyl, and R 20 and R 21 , R 23 and R 24 , R 27 and R 28 , R 29 and R 30 , R 31 and R 32 , and R 33 and R 34 are the same or different from each other, and R 36 and R 37are, independently of one another, absent or straight-chain or branched C1-C 12 a hydrocarbon chain, and R 13 , R 14 , R 15 , R 16 , R 17 and R 18 are each independently hydrogen or a straight-chain, branched-chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms.

[0034] According to an embodiment of the present invention, in compounds of formula I, II, III, IV (IVa and IVb), V, VI (VIa and VIb), VII, VIII (VIIIa and VIIIb), IX, X (Xa and Xb), XI (XIa and XIb), and XII, ZE is preferably -(CH2) m COOH; -C6H4COOH, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 COOH, wherein the aliphatic ring may be substituted with 1 to 10 C1 to C4 alkyl groups; -(CH2) m CH(COOH)2; -(CH2) m COOR 19 ;-C6H4COOR 19 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 COOR 19 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) m (COOR 20 )(COOR 21 );-C6H4CH(COOR 20 )(COOR 21 ) wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 CH(COOR20 )(COOR 21 ), wherein the aliphatic ring is optionally substituted with 1 to 10 C1 to C4 alkyl groups; -(CH2) m CHO; -C6H4CHO, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 CHO, wherein the aliphatic ring may be substituted with 1 to 10 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -(CH2) m CH(CHO)2; -(CH2) m C2H3; -C6H4C2H3, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 C2H3, wherein the aliphatic ring is optionally substituted with 1 to 10 C1 to C4 alkyl groups; -(CH2) m CH(C2H3)2; -(CH2) m CHCHR 22 ;-C6H4CHCHR 22 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 CHCHR 22 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) m CHCR 23 R 24 ;-C6H4CHCR 23 R 24 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 CHCR 23 R 24 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) mC2H; -C6H4C2H, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 C2H, wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) m C2R 25 ;-C6H4C2R 25 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 C2R 25 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups;

[0035] -(CH2) m N3; -C6H4N3, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 N3, wherein the aliphatic ring is optionally substituted with 1 to 10 C1 to C4 alkyl groups; -(CH2) m NH2; -C6H4NH2, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 NH2, wherein the aliphatic ring may be substituted with 1 to 10 C1 to C4 alkyl groups; -(CH2) m CH(NH2)2; -(CH2) m NHR 26 ;-C6H4NHR 26 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 NHR 26 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) m NR 29 R 30 ;-C6H4NR29 R 30 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 NR 29 R 30 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) m CH(NR 31 R 32 )(NR 33 R 34 );-C6H4CH(NR 31 R 32 )(NR 33 R 34 ) wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 CH(NR 31 R 32 )(NR 33 R 34 ), wherein the aliphatic ring is optionally substituted with 1 to 4 C1-C4 alkyl groups; -(CH2) m OH; -C6H4OH, wherein the aromatic ring may be substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; -C6H 10 OH, wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -(CH2) m OR 35 ;-C6H4OR 35 wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; 10 OR 35 wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; -CH(R 36 OH)(R 37 OH);-C6H4CH(R 36 OH)(R 37OH), wherein the aromatic ring is optionally substituted with 1 to 4 C1 to C4 alkyl groups or 1 to 4 halogen atoms; or —CH 10 CH(R 36 OH)(R 37 OH), wherein the aliphatic ring is optionally substituted with 1 to 10 C1-C4 alkyl groups; R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 and R 35 are C1 to C 20 alkyl, and R 20 and R 21 , R 23 and R 24 , R 27 and R 28 , R 29 and R 30 , R 31 and R 32 , and R 33 and R 34 are the same or different and are preferably methyl, ethyl, propyl and butyl; and R 36 and R 37 are, independently of one another, absent (e.g., —CH(OH) or —CH(OH)CHOH) or linear or branched C1-C 12 The hydrocarbon chain is preferably methylene, ethylene, propylene or butylene.

[0036] m is an integer from 0 to 12, in particular from 0 to 4.

[0037] Within the scope of the present invention, the term "heterogeneous acidic catalyst" means that the acidic catalyst is in the solid phase and the reactants are in the liquid phase. Preferably, the acidic catalyst is a Brønsted acidic catalyst, more preferably an anhydrous Brønsted acidic catalyst. More specifically, it may be a heterogeneous acidic material and / or optionally a Brønsted acidic catalyst that can be incorporated into, incorporated onto, or covalently bonded to a solid support, such as resin beads, membranes, porous carbon particles, zeolite materials, and other solid supports. The solid support may be, for example, a material comprising carbon, silicon dioxide, titanium dioxide, zirconium oxide, aluminum oxide, or any combination of these oxides.

[0038] Bronsted acids are capable of donating protons and are known to those skilled in the art. Bronsted acids may be, for example, bridging hydroxyl groups of zeolites or resins functionalized with Bronsted acid sites. Examples of such Bronsted acids that can be used to functionalize resins are preferably selected from the group consisting of sulfuric acid, phosphoric acid, and methanesulfonic acid, or mixtures thereof.

[0039] Preferably, the Bronsted acidic catalyst is selected from the group consisting of: a. acidic zeolite, b. Acid-doped zeolite; c. a resin functionalized with acid moieties; d. oxides functionalized with acid moieties; e. acid oxides, f. Heteropolyacids and their derivatives.

[0040] As used herein, the term "acid moiety-functionalized resin" refers to a resin or polymer synthesized from an organic polymer substrate that acts as a medium for ion exchange. The organic polymer substrate may be, for example, sulfonated polystyrene divinylbenzene or sulfonated tetrafluoroethylene-based fluoropolymer-copolymer, resulting in a strongly acidic cation exchange resin or polymer. Non-limiting examples include Amberlyst®-15, Amberlyst®-36, Amberlyst®-XNIOIO, Amberlite® (e.g., Amberlite® IRC120), Dowex® D 2030, Nafion® NR50, and Nafion® SAC13.

[0041] The term "oxide functionalized with acid sites" refers to, for example, sulfated or sulfonated materials resulting from functionalization of oxides such as zirconia, alumina, or silica. Such solid acidic metal oxides may optionally be supported on a support material.

[0042] The term "acidic oxide" means a metal oxide having Bronsted acidity, such as niobia or alumina.

[0043] As used herein, the term "zeolite" refers to both natural and synthetic microporous, crystalline silicate materials (including aluminosilicates, borosilicates, and aluminoborosilicates) with a well-defined crystal structure as determined by X-ray diffraction. Zeolites contain a system of channels that may be interconnected with other channel systems or cavities, such as side pockets or cages. This channel system may be three-dimensional, two-dimensional, or one-dimensional. Zeolites contain SiO4 and XO4 tetrahedra, where X can be Al (aluminum) or B (boron). Zeolites can contain a combination of AlO4 and BO4 tetrahedra. In one embodiment, X is Al, and the zeolite does not contain BO4 tetrahedra. The SiO4 and XO4 tetrahedra are connected at their corners through common oxygen atoms. The "Atlas of Zeolite Framework Types" (C. Baerlocher, L.B. McCusker, D.H. Olson, 6th ed., Elsevier, Amsterdam, 2007), together with a web-based version (http: / / www.iza-structure.org / databases / ), is a summary of topological and structural details regarding zeolite frameworks, including the types of ring structures present in zeolites and the dimensions of the channels defined by each ring type. Proven methods and good laboratory practices for the synthesis of zeolites can be found in "Verified synthesis of zeolitic materials," 2nd ed., 2001. Various proven methods for the synthesis of BO tetrahedra are available. For example, the synthesis and characterization of boron-based zeolites with the MFI topology have been described by Cichocki and Parasiewicz-Kaczmarska (Zeolites, 1990, 10, 577-582).

[0044] Zeolites suitable for use in the process according to the invention may include: - a zeolite comprising at least two, preferably two or three, non-interconnected parallel channel systems, at least one of which is composed of channels with eight or more ring members; and having a framework Si / X2 ratio, as determined by NMR, of at least 4; or - a zeolite comprising at least two, preferably two or three, interconnected non-parallel channel systems, at least one of which is composed of channels with 10 or more ring members; and having a framework Si / X2 ratio, as determined by NMR, of at least 4; or - a zeolite comprising three interconnected non-parallel channel systems, at least two of which are composed of channels with 10 or more ring members; and having a framework Si / X2 ratio of at least 4, as determined by NMR; where each X is Al or B.

[0045] As used herein, the term "channel system" refers to a system of parallel or non-parallel and crystallographically equivalent channels, where the channels are 8-ring channels or larger, e.g., the channels are 10-ring channels or 12-ring channels. Thus, as used herein, the term "channel" refers to an 8-ring or larger channel that is part of a system of parallel or non-parallel and crystallographically equivalent channels.

[0046] Zeolites suitable for use in the method of the present invention contain channels with 10 or more ring members, for example, 12-ring channels (12MR) or larger. The ring sizes of each of the known zeolite framework types are provided in the "Atlas of Zeolite Framework Types" (C Baerlocher, LB McCusker, DH Olson, 6th ed., Elsevier, Amsterdam, 2007), the contents of which are incorporated herein by reference.

[0047] As used herein, the term "8-membered ring channel" or "8MR" refers to a channel containing an uninterrupted 8-membered ring, where the 8-membered ring defines the smallest diameter of the channel. The 8-membered ring contains 8 T atoms and 8 alternate oxygen atoms (forming a ring), where each T is Si, Al, or B. As used herein, the term "10-membered ring channel" or "10MR" refers to a channel containing an uninterrupted 10-membered ring, where the 10-membered ring defines the smallest diameter of the channel. The 10-membered ring contains 10 T atoms and 10 alternate oxygen atoms (forming a ring), where each T is Si, Al, or B. As used herein, the term "12-membered ring" or "12MR" refers to a channel containing an uninterrupted 12-membered ring, where the 12-membered ring defines the smallest diameter of the channel. A 12-membered ring contains 12 T atoms and 12 alternate oxygen atoms (forming the ring), where each T is Si, Al, or B. As used herein, the term "10- or greater-membered ring channel" refers to a 10-membered ring channel or larger, and thus includes, for example, both 10-membered ring channels and 12-membered ring channels.

[0048] The framework Si / X2 ratio can be determined by nuclear magnetic resonance (NMR) measurements, more specifically, 29 Si-NMR and 27The Si / B2 ratio can be determined by Al-NMR. In a preferred embodiment, framework B is absent, and the Si / X2 ratio is equal to the Si / Al2 ratio. The Si / Al2 ratio can be determined by NMR as described by Klinowski (Ann. Rev. Mater. Sci. 1988, 18, 189-218); or as described by G. Engelhardt and D. Michel ("High-Resolution Solid-State NMR of Silicates and Zeolites", John Wiley & Sons, Chichester 1987, 14, 485). The Si / B2 ratio can be determined by NMR as discussed by D. Trong On et al. ("Studies in Surface Science and Catalysis", 1995, 97, 535-541; Journal of Catalysis, November 1995, Volume 157, Issue 1, pp. 235-243).

[0049] Zeolites are thermostable catalysts and therefore can be regenerated by calcination, in contrast to classical thermolabile ion exchange resins such as Amberlyst®-15.

[0050] The term "heteropolyacid," as used herein, refers to a compound that includes: a metal selected from the group consisting of tungsten, molybdenum and vanadium, - elements from the p-block of the periodic table, such as silicon, phosphorus or arsenic, - oxygen, and - Hydrogen.

[0051] Preferably, the heteropolyacid is selected from the group consisting of phosphotungstic acid, silicotungstic acid, arsenetungstic acid, phosphomolybdic acid, silicomolybdic acid, arsenemolybdic acid, phosphovanadic acid, silicovanadic acid, and arsenovanadic acid. In another preferred embodiment, heteropolyacid derivatives are prepared by common derivatization techniques to render them solidified / immobilized, particularly including their salts and immobilized forms on solid supports or resin beads.

[0052] In one embodiment of the present invention, the method comprises contacting an aldopentose or aldohexose and an aldehyde or aldehyde source with an acidic zeolite, wherein the zeolite comprises: - a zeolite comprising at least two, preferably two or three, non-interconnected parallel channel systems, at least one of which is composed of channels with eight or more ring members; and having a framework Si / X2 ratio, as determined by NMR, of at least 4; or - a zeolite comprising at least two, preferably two or three, interconnected non-parallel channel systems, at least one of which is composed of channels with 10 or more ring members; and having a framework Si / X2 ratio, as determined by NMR, of at least 4; or - a zeolite comprising three interconnected non-parallel channel systems, at least two of which are composed of channels with 10 or more ring members; and having a framework Si / X2 ratio of at least 4, as determined by NMR; where each X is Al or B.

[0053] Zeolites containing three interconnected non-parallel channel systems, at least two of which are composed of channels with 10 or more ring members, and having a framework Si / X2 ratio of at least 4, as determined by NMR, give excellent results.

[0054] The term "channel system" preferably refers to a system of parallel, crystallographically equivalent channels, where the channels are eight-membered ring channels or larger.

[0055] Good results have been obtained using zeolites that contain at least two interconnected non-parallel channel systems (2D or 3D micropore structures). Thus, the zeolites used in the methods described herein contain a 2D or 3D micropore structure, more particularly an interconnected 2D or 3D micropore structure.

[0056] Good results have also been obtained with zeolites containing at least one channel of 10 or more ring members.

[0057] Thus, in certain embodiments, zeolites for use in the methods described herein can include those having a framework Si / X2 ratio of at least 4, e.g., a framework Si / Al2 ratio of at least 4, where the zeolite further comprises at least two, preferably two or three, non-interconnected parallel channel systems, at least one of which comprises channels with eight or more ring members. Examples of such zeolites include, but are not limited to, zeolites having the mordenite (MOR) topology.

[0058] In certain embodiments, zeolites for use in the methods described herein can include those having a framework Si / X2 ratio of at least 4, e.g., those having a framework Si / Al2 ratio of at least 4; wherein the zeolite further comprises at least two interconnected non-parallel channel systems, at least one of which comprises channels with 10 or more ring members, i.e., at least one of the channel systems comprises channels with 10 or more ring members, and at least one other channel system comprises channels with 8 or more ring members.

[0059] In certain embodiments, zeolites for use in the methods described herein can include those having a framework Si / X2 ratio of at least 4, e.g., a framework Si / Al2 ratio of at least 4; wherein the zeolite further comprises three interconnected non-parallel channel systems, at least two of which comprise channels with 10 or more ring members, i.e., at least two of which comprise channels with 10 or more ring members, and the other channel system comprises channels with 8 or more ring members. Examples of such zeolites include, but are not limited to, zeolites comprising a topology selected from the group including BEA, FAU, and MEL.

[0060] In certain embodiments, the zeolites comprise at least two non-interconnected parallel channel systems, at least one of which comprises channels with eight or more ring members; wherein the zeolites further comprise those having a framework Si / X2 ratio of at least 4, more particularly at least 4, such as a ratio of at least 15, for example a ratio of at least 20, for example a ratio of at least 25, for example a ratio of at least 30, for example a ratio of at least 35, for example a ratio of at least 40, for example a ratio of at least 50, for example a ratio of at least 50 This includes ratios of at least 50, such as at least 60, such as at least 70, such as at least 80, such as at least 90, or such as at least 100, or such as at least 110, or such as at least 120, or such as at least 130, or such as at least 140, or such as at least 150, or such as at least 160, or such as at least 170, or such as at least 180, or such as at least 190, or such as at least 200.

[0061] In certain embodiments, the zeolites comprise at least two, preferably two or three, interconnected non-parallel channel systems, at least one of which comprises channels with 10 or more ring members; wherein the zeolites further include those having a framework Si / X2 ratio of at least 4, more particularly at least 8, such as a ratio of at least 10, for example a ratio of at least 15, for example a ratio of at least 20, such as a ratio of at least 25, for example a ratio of at least 30, for example a ratio of at least 35, for example a ratio of at least including a ratio of 40, such as a ratio of at least 50, such as a ratio of at least 60, such as a ratio of at least 70, such as a ratio of at least 80, such as a ratio of at least 90, or such as a ratio of at least 100, or such as a ratio of at least 110, or such as a ratio of at least 120, or such as a ratio of at least 130, or such as a ratio of at least 140, or such as a ratio of at least 150, or such as a ratio of at least 160, or such as a ratio of at least 170, or such as a ratio of at least 180, or such as a ratio of at least 190, or such as a ratio of at least 200.

[0062] In certain embodiments, the zeolites comprise three interconnected non-parallel channel systems, at least two of which comprise channels with 10 or more ring members; wherein the zeolites further comprise those having a framework Si / X2 ratio of at least 4, more particularly at least 8, such as a ratio of at least 10, for example a ratio of at least 15, for example a ratio of at least 20, for example a ratio of at least 25, for example a ratio of at least 30, for example a ratio of at least 35, for example a ratio of at least 40, for example a ratio of at least 50, for example a ratio of at least 60, for example a ratio of at least 70 This includes a ratio of at least 50, such as a ratio of at least 60, such as a ratio of at least 70, such as a ratio of at least 80, or such as a ratio of at least 90, or such as a ratio of at least 100, or such as a ratio of at least 110, or such as a ratio of at least 120, or such as a ratio of at least 130, or such as a ratio of at least 140, or such as a ratio of at least 150, or such as a ratio of at least 160, or such as a ratio of at least 170, or such as a ratio of at least 180, or such as a ratio of at least 190, or such as a ratio of at least 200.

[0063] In most embodiments, the conversion of the protected sugar to a fully acetal-protected product increases with increasing Si / X2 ratio, preferably with increasing Si / X2 ratio. In some embodiments, it is recognized that at high Si / X2 ratios, the yield of partially protected sugar may decrease as the Si / X2 ratio is further increased. Without wishing to be bound by theory, this is believed to be related to the small number of acidic sites in zeolites with high Si / X2 ratios, yet higher Bronsted acid strength. Thus, in certain embodiments, the zeolite has a framework Si / X2 ratio of less than 280. In further embodiments, the zeolite has a framework Si / X2 ratio of less than 150. Preferably, the zeolite has a framework Si / X2 ratio of less than 280. In further embodiments, the zeolite has a framework Si / X2 ratio of less than 200.

[0064] The zeolites used in the methods described herein can include AlO4 tetrahedra, BO4 tetrahedra, or both. Thus, in some embodiments, X2 is (Al2 + B2). Thus, for a given zeolite, the Si / X2 framework ratio remains the same when framework Al is replaced with B, or vice versa. However, in certain embodiments, it is contemplated that the zeolite will contain no BO4 tetrahedra or only a small amount (e.g., an Al / B ratio of 100 or greater). Thus, in certain embodiments, X2 can be Al2.

[0065] The Si / X2 ratios referred to herein are molar ratios determined by NMR unless otherwise specified. Those skilled in the art will understand that the Si / X2 ratios referred to herein are equivalent to the SiO2 / X2O3 molar ratio, where X2O3 is (Al2O3 and / or B2O3). Furthermore, those skilled in the art will understand that dividing the Si / X2 ratio by 2 will give the Si / X molar ratio, where X is (Al and / or B).

[0066] Preferably, the channels defined by the zeolite topology are large enough to allow access by the sugars to be protected, yet small enough to prevent significant formation and / or diffusion of by-products. Thus, in certain embodiments, the zeolite comprises only channels with ring sizes of at most 18, preferably at most 14, e.g., at most 12.

[0067] In preferred embodiments, zeolites suitable for use in the methods described herein comprise a topology selected from the group consisting of BEA, FAU, and MEL. These zeolites provide high yields of end-product. In certain embodiments, the one or more zeolites comprise a topology selected from the group consisting of MOR. In certain embodiments, the one or more zeolites comprise zeolites with FAU or BEA topology, which provide superior results.

[0068] In certain embodiments, the zeolite comprises channels having an average (equivalent) diameter of at least 5 Å. More particularly, the zeolite may comprise five or more non-parallel channels having an average diameter of at least 5 Å. Channel diameters can be determined theoretically via zeolite framework information or via X-ray diffraction (XRD) measurements, as known to those skilled in the art. Preferably, the zeolite comprises two or more non-parallel, interconnected channels having an average (equivalent) diameter of 5 to 13.0 Å, more preferably 5 to 11 Å. Preferably, diameters for suitable topologies are obtained from the International Standard Book: Atlas of Zeolite Structures or the corresponding online database found at http: / / www.iza-structure.org / databases / , referenced above. The (equivalent) diameter of the channels can also be measured experimentally via N adsorption, as discussed for example by Groen et al. (Microporous and Mesoporous Materials 2003, 60, 1-17), Storck et al. (Applied Catalysis A: General 1998, 174, 137-146), and Rouquerol et al. (Rouquerol F, Rouquerol J and Sing K, Adsorption by powders and porous solids: principles, methodology and applications, Academic Press, London, 1999).

[0069] In some embodiments, the zeolite may further comprise mesopores. The presence of mesopores may increase the accessibility of the sugar to be protected to both pores (micropores and mesopores), thus further increasing the reaction rate. However, it is also contemplated that the zeolite may not comprise mesopores.

[0070] As used herein, the term "mesopore" refers to pores in zeolite crystals having an average diameter between 2.0 nm and 50 nm. For pore shapes that deviate from cylindrical, the above diameter range of mesopores refers to equivalent cylindrical pores. The average diameter of mesopores can be determined by gas adsorption techniques such as N2 adsorption.

[0071] The zeolite(s) can be used as is, for example, as a powder. In certain embodiments, the zeolite(s) can be formulated into a catalyst by combining them with other substances that provide additional shape, hardness, or catalytic activity to form a finished catalyst product. Materials that can be blended with the zeolite can be various inert or catalytically active substances, or various binder materials. These materials include compositions such as kaolin and other clays, phosphates, alumina or alumina sols, titania, metal oxides such as zirconia, quartz, silica or silica sols, metal silicates, and mixtures thereof. These components are effective in densifying the catalyst and increasing the strength of the formulated catalyst.

[0072] The catalyst can be formulated into pellets, spheres, extruded into other shapes, or formed into spray-dried particles.

[0073] In some embodiments, one or more zeolites for use in the methods described herein can be subjected to (post-synthesis) treatment to increase the Si / Al2 framework ratio. Methods for increasing the Si / Al2 ratio of zeolites are known in the art and include framework dealumination by (hydro)thermal treatment, framework aluminum extraction with acid, and framework aluminum replacement with silicon by reaction with silicon halides or hexafluorosilicates. An exemplary method of dealumination is described by Remy et al. (J. Phys. Chem. 1996, 100, 12440-12447). Zeolites for use in the methods described herein are preferably Brønsted acidic zeolites, i.e., zeolites that have proton-donating sites within their pores. When all Al T-sites are balanced with acidic protons (as opposed to cations), the Brønsted acid density can be derived directly from the Si / Al2 ratio, as known to those skilled in the art.

[0074] The zeolites for use in the processes described herein can be obtained in the acidic form (acidic H-type zeolites or acidic H-form zeolites) or (partially) H + In some embodiments, acidic H-form zeolites can be used as is. In some other embodiments, zeolites for use in the processes described herein can be subjected to (post-synthesis) treatments to increase the Bronsted acid density. Bronsted acid sites in zeolites can be readily generated by aqueous ion exchange with ammonium salts, followed by thermal decomposition of the ammonium ions within the zeolite. Alternatively, acid sites can be generated by the addition of polyvalent metal cations (Mg 2+ , Ca 2+ , La 3+ , or mixed rare earth cations) followed by thermal dehydration (J. Weitkamp, ​​Solid State Ionics 2000, 131, 175-188).

[0075] The zeolite catalysts described herein may be regenerated and reused in this process. Accordingly, certain embodiments of the processes described herein may include a step of regenerating the zeolite catalyst. The regeneration of the zeolite catalyst may be achieved via washing or calcination. Preferably, the regeneration of the zeolite catalyst is achieved via calcination, for example, at a temperature of at least 150°C. In certain embodiments, the calcination temperature is at least 200°C, for example, at least 300°C, for example, at least 400°C, for example, at least 450°C, for example, about 550°C.

[0076] The above-mentioned zeolites can include various dopants, such as, but not limited to, gallium, tin, or rare earth metals, which can provide better catalyst stability or can provide higher conversion of sugars to desired fully or partially protected products.

[0077] Exemplary commercially available zeolites suitable for use in the processes described herein include, but are not limited to, beta polymorph type A (BEA topology), Y-type zeolite (FAU topology), and mordenite.

[0078] [Table 1-1]

[0079] Preferably, the acidic zeolite catalyst is selected from the group consisting of zeolite Y (SiO2:Al2O3=5.2:1), zeolite Y (SiO2:Al2O3=12:1), zeolite Y (SiO2:Al2O3=30:1), zeolite Y (SiO2:Al2O3=60:1), zeolite Y (SiO2:Al2O3=80:1), zeolite beta (SiO2:Al2O3=25:1), zeolite beta (SiO2:Al2O3=38:1), zeolite beta (SiO2:Al2O3=150:1), and mordenite (SiO2:Al2O3=19:1).

[0080] Preferably, the aldehydes used in the process according to the invention are formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, isovaleraldehyde, hexanal, heptanal, octanal, nonanal, decanal, dodecanal, tetradecanal, hexadecanal, octadecanal, crotonaldehyde, glyoxal, malonic dialdehyde, succinic dialdehyde, glutaraldehyde, adipic dialdehyde, 2-hydroxyadipic dialdehyde, pimelic dialdehyde, The aldehyde may be selected from the group consisting of suberic dialdehyde, azelaic dialdehyde, sebacic dialdehyde, maleic aldehyde, fumaric aldehyde, phthalaldehyde, isophthalaldehyde, terephthalaldehyde, and 1,4-diformylcyclohexane, glyoxylic acid, glyoxylic acid monohydrate, formylacetic acid, terephthalaldehyde, and succinic semialdehyde, and preferably from the group consisting of formaldehyde, acetaldehyde, dodecanal, glyoxylic acid, glyoxylic acid monohydrate, and glutaraldehyde.

[0081] Alternatively, the aldehyde source is selected from the group consisting of paraformaldehyde, 1,3,5-trioxane, polyoxymethylene, and metaldehyde, which polymeric or oligomeric compounds form the corresponding aldehydes under reaction conditions.

[0082] Thus, the aldehyde may be a gas, liquid or solid, and may exist as a solution or as a pure compound, e.g., in the case of formaldehyde, it may be provided as a gas, as a formaldehyde solution (e.g., formalin), as paraformaldehyde, or as 1,3,5-trioxane, polyoxymethylene (POM).

[0083] In one embodiment of the present invention, R and R′, R and R′, R and R′, and R 12 and R 12These compounds can be obtained using the same aldehyde, resulting in a simple synthetic procedure.

[0084] In another embodiment of the present invention, R and R′, R and R′, R and R′, and R 12 and R 12 are different from each other. For example, in a first step, the sugar to be protected is reacted with a first aldehyde (i.e., dodecanal) in the presence of a heterogeneous acidic catalyst to protect one side of the sugar. Then, in a second step, this partially protected sugar is reacted with a different aldehyde (e.g., glyoxylic acid) in the presence of a heterogeneous acidic catalyst to obtain the fully protected sugar.

[0085] In one embodiment according to the present invention, the protected sugar is an aldopentose resulting in compounds of formula I, IV, V, IX, X and XI: [ka] In the formula, R1, R1', R4, R5, R9, R 10 and R 11 has the same definition as above.

[0086] An exemplary reaction to obtain a compound of formula I, IV, V, IX, X, or XI in the presence of a heterogeneous acidic catalyst is shown below:

[0087] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0088] The aldopentose may be selected from the group consisting of D-ribose, L-ribose, D-arabinose, L-arabinose, D-xylose, L-xylose, D-lyxose and L-lyxose, most preferably D-arabinose and D-xylose, and ideally D-xylose. The stereochemistry of aldopentoses is known to those skilled in the art.

[0089] In one embodiment according to the invention, the protected sugar is an aldopentoside resulting in a partially protected sugar selected from compounds of formula IVb, Xb or XIb: [ka] In the formula, R4, R 10 and R 11 has the same definition as above, and R 13 , R 16 and R 17 are each independently hydrogen or a straight-chain, branched-chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms, preferably methyl, ethyl, propyl, or butyl.

[0090] An exemplary reaction to obtain compounds of formula IVb, Xb or XIb in the presence of a heterogeneous acidic catalyst is shown below:

[0091] [Table 1-7] [Table 1-8] [Table 1-9]

[0092] In another embodiment according to the invention, the protected sugar is an aldohexose resulting in compounds of formula II, III, VIa, VII and VIIIa: [ka] In the formula, R2, R2', R3, R3', R6, R7 and R8 have the same definitions as above.

[0093] The aldohexose is preferably selected from the group consisting of D-allose, L-allose, D-altrose, L-altrose, D-glucose, L-glucose, D-mannose, L-mannose, D-gulose, L-gulose, D-idose, L-idose, D-galactose, L-galactose, D-talose, and L-talose, and is most preferably selected from D-glucose. The stereochemistry of aldohexoses is known to those skilled in the art.

[0094] Exemplary reactions to obtain compounds of formula II, III, VIa, VII, and VIIIa in the presence of a heterogeneous acidic catalyst are shown below:

[0095] [Table 1-10] [Table 1-11] [Table 1-12] [Table 1-13]

[0096] In one embodiment according to the invention, the protected sugar is an aldohexoside resulting in an at least partially protected sugar selected from compounds of formulae VIb, VIIIb, and XII: [ka] In the formula, R6, R8, R 12 and R 12 ' has the same definition as above, and R 14 , R 15 and R 18are each independently hydrogen or a straight-chain, branched-chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms, preferably methyl, ethyl, or propyl.

[0097] An exemplary reaction to obtain compounds of formula VIb, VIIIb and VII in the presence of a heterogeneous acidic catalyst is shown below:

[0098] [Table 1-14] [Table 1-15] [Table 1-16]

[0099] Preferably, the catalyst has a pore structure as described for the zeolite detailed above. The pore shape selectivity of the heterogeneous catalyst allows for tailoring of product selectivity and avoids a common problem in homogeneous catalytic systems: sugar molecules and their ring systems with many OH groups tend to form many by-products, making it difficult to obtain high selectivity for one desired product.

[0100] For compounds of formula I, II, III, or XII, there is no limitation on the pore size, as long as the pore size allows the reactants to reach the Bronsted acid site and allows the fully acetal-protected sugar to diffuse. Also, the pore size should be large enough to allow the product to leave the catalyst after the reaction. If high selectivity for partially protected sugars is desired, the pore size should be larger than the size of the desired partially protected sugar, but smaller than the size of the fully protected alternative product. The exact pore size depends on the type of sugar and aldehyde used in the reaction. Those skilled in the art can predict the range of pore sizes to be used in these cases. Due to steric reasons alone, unprotected or partially protected aldopentoses, aldopentosides, aldohexoses, and aldohexosides can reach the catalytically active center through the pores and then leave the pores. Therefore, such catalysts can produce compounds of formulas IV (IVa and IVb), V, VI (VIa and VIb), VII, VIII (VIIa and VIIb), IX, X (Xa and Xb), and XI (XIa and XIb). However, to obtain higher yields, pore diameters of 0.7 nm or greater are preferred for protecting aldohexoses and aldohexosides, and pore diameters of 0.5 nm or greater are preferred for protecting aldopentoses and aldopentosides. Catalysts containing mesopores with an average diameter of 2 nm to 50 nm are preferred.

[0101] In one embodiment according to the present invention, the reaction is carried out in an organic solvent. Thus, a sugar selected from the group consisting of aldopentoses, aldohexoses, aldopentosides, and aldohexosides can be reacted with an aldehyde or an aldehyde source in the presence of the heterogeneous Brønsted acidic catalyst and an organic solvent, either in a batch reactor or a continuous reactor, preferably a flow reactor. The heterogeneous Brønsted acidic catalyst used is preferably essentially insoluble in the organic solvent. After the reaction, unless the catalyst is already confined inside the reactor, for example, in a basket or column packing, the catalyst can be removed, for example, by filtration, recycled, and returned to the reactor. The remaining reaction mixture can be concentrated by evaporating the solvent. The final product can be obtained from the concentrate by crystallization. Preferably, the organic solvent is selected from the group consisting of dimethyl isosorbide, cyclic ethers, in particular 1,4-dioxane, 2-methyltetrahydrofuran, sulfolane, sulfolene, aliphatic acids, in particular acetic acid, alkylpyrrolidones, cyclic carbonates, cyclic esters, in particular γ-valerolactone, γ-butyrolactone, acetonitrile, dialkyl ethers, in particular CPME (cyclopentyl methyl ether) and diethyl ether, cyclic ethers, and glycol mono- and diethers.

[0102] The solvent can be removed while at the same time allowing for high conversion of the protected sugar. This solvent system is particularly preferred for aldehydes with long chains (e.g., decanal).

[0103] In another embodiment, the reaction is carried out in an aqueous solution. Thus, a sugar selected from the group consisting of aldopentoses, aldohexoses, aldopentosides, and aldohexosides can be reacted with an aldehyde or an aldehyde source in the presence of the heterogeneous Brønsted acidic catalyst and water, either in a batch reactor or a continuous reactor, preferably a flow reactor. The heterogeneous Brønsted acidic catalyst used is essentially water-insoluble. After the reaction, unless the catalyst is already confined inside the reactor, for example, in a basket or column packing, the catalyst can be separated and recycled, for example, by filtration and / or centrifugation. The remaining liquid can be extracted with a solvent (e.g., hexane, DCM (dichloromethane), diethyl ether, ethyl acetate, or CPME (cyclopentyl methyl ether)) to remove the product. The extraction solvent can then be removed by evaporation to separate the product. Alternatively, the product-containing extract layer can be concentrated, and the product can be gradually crystallized in the concentrate. The extracted aqueous phase contains unreacted reactants, i.e., sugars, aldehydes, and intermediates. This extracted aqueous phase can be concentrated and recycled to the reactor to improve the overall yield. For environmental reasons, aqueous solutions are particularly preferred as solvent systems.

[0104] In one embodiment of the present invention, the reaction is carried out in a two-phase solvent system, thereby achieving in situ separation of the product from the reaction mixture and improving product yield by shifting the reaction equilibrium. Specifically, an extractant phase is added to a batch reactor together with the reaction mixture and the heterogeneous acidic catalyst. In a continuous-flow reactor, the extractant can be added in either a cocurrent, crosscurrent, or countercurrent manner. Preferably, the two-phase solvent system is selected from the group consisting of dialkyl ether / water (e.g., CPME / water, dialkyl ether / water), anisole / water, dialkyl ketone / water (e.g., methyl isobutyl ketone / water), and toluene / water, preferably CPME / water and toluene / water, and most preferably CPME / water. The reaction occurs in the aqueous phase, and the product is extracted into the organic phase during the reaction. For stability reasons, a two-phase solvent system selected from the group consisting of dialkyl ether / water and dialkyl ketone / water is more suitable for aldehydes with no or short side chains, such as formaldehyde and acetaldehyde. The extractant phase containing the product is concentrated to crystallize the product. The remaining product in the aqueous phase can be removed by further extraction with a solvent (e.g., ethyl acetate or CPME), and the product can also be crystallized after evaporating the extractant. The extracted aqueous phase can be concentrated and reused as described above.

[0105] Preferably, the reaction is carried out at a temperature of 50-160° C., most preferably 80-140° C. In organic solvents, the reaction temperature is typically 80-130° C., in biphasic solvent systems 120-140° C., and in aqueous solutions preferably 120-150° C. The reaction time is determined by the degree of conversion reached.

[0106] The amount of heterogeneous acidic catalyst used is based on the amount of sugar to be protected. For the alternative, and preferred, continuous mode of operation, the relative amount of catalyst is adjusted for the reactor size and aldopentose or aldohexose flow. In this case, it will be understood that the determination of appropriate relative amounts based on values ​​for a batch mode of operation is within the ordinary skill of a manufacturing chemist or chemical engineer.

[0107] The process according to the invention is conveniently carried out in normal ambient conditions, but can also be carried out under an inert gas atmosphere, preferably gaseous nitrogen, helium or argon. [Example]

[0108] Examples 1-5 below are based on the use of formaldehyde to produce DFX (diformylxylose). The same principles can be applied to other aldehydes to produce different types of fully or partially protected xylose, including dipropylxylose, di-n-butylxylose, diisobutylxylose, and didodecylxylose, among others.

[0109] Example 1 : D-xylose (2 g, 13.3 mmol, 1.0 equiv.), paraformaldehyde (2 g, 66.7 mmol formaldehyde, 5.0 equiv.), and H-form Y-type zeolite (SiO2:Al2O3 = 80:1, 2 g) were added to 2-Me-THF (32 mL) in a 50 mL round-bottom flask. The mixture was then heated at 120 °C for 6 h with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C), filtered through a nylon membrane filter, and concentrated in vacuo using a rotary evaporator with a bath temperature of 45 °C. HPLC analysis indicated a DFX yield of 82.3% from D-xylose. The concentrated residue crystallized at 4-5 °C.

[0110] Other catalysts can also be used using this same method. Table 1 shows the various DFX yields using various catalysts. These reactions were performed using 0.25 g of D-xylose, and all other chemicals were scaled down relatively from the above examples. The reactions were performed in a 10 mL glass reactor.

[0111] [Table 1-17]

[0112] Example 2 : D-xylose (0.1 g, 0.67 mmol, 1.0 equiv.), paraformaldehyde (0.1 g, 3.34 mmol, 5 equiv.) and ZrO2 / SO4 2- DFX (self-synthesized, 50 mg) was added to 2-Me-THF (2 mL) in a 10 mL glass reactor. The mixture was then heated at 110 °C for 9 hours with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C), filtered through a nylon membrane filter, and diluted 10-fold with distilled water. HPLC analysis indicated a 79% DFX yield from D-xylose.

[0113] Using this same method, other groups of acidic catalysts (e.g., Amberlite®, sulfated ZrO2, heteropolyacids, niobia oxides) can also be used (Table 2).

[0114] [Table 2]

[0115] Example 3 : D-xylose (0.1 g, 0.67 mmol, 1.0 equiv.), 37% aqueous formalin (0.5 mL, 10.3 equiv.), and β-type zeolite (SiO2:Al2O3 = 25:1, 0.1 g) were added to GVL (γ-valerolactone, 5 mL) in a 10 mL glass reactor. The mixture was then heated to 140 °C for 2 h with stirring. The resulting solution was cooled to room temperature (approximately 23–25 °C), filtered through a nylon membrane filter, and distilled under reduced pressure (10 mbar) at 80 °C to remove GVL. HPLC analysis indicated a 76% DFX yield from D-xylose. The concentrated residue crystallized at 4–5 °C.

[0116] Other catalysts and solvents can also be used using this same method. Table 3 shows various DFX yields using other catalysts.

[0117] [Table 3]

[0118] Example 4 : D-xylose (8 g, 53.3 mmol, 1.0 equivalent), 37% aqueous formalin solution (40 mL, 10.3 equivalents), and Y-type zeolite (SiO2:Al2O3 = 80:1, 1.6 g) were mixed in a 60 mL glass reactor. The mixture was then heated with stirring at 140°C for 6 hours. HPLC analysis indicated a 57.6% DFX yield from D-xylose. The resulting solution was cooled to room temperature (approximately 23-25°C) and filtered through a nylon membrane filter. The filtrate was extracted four times with 10 mL of ethyl acetate or cyclopentyl methyl ether in a separatory funnel. The resulting organic phase was concentrated under reduced pressure (0.02 mbar) at 45°C to obtain a DFX-rich solution. The DFX in the solution was then crystallized at 4-5°C or at room temperature.

[0119] Other catalysts can also be used using this same method. Table 4 shows the various DFX yields using other catalysts.

[0120] [Table 4]

[0121] Example 5 : D-xylose (0.3 g, 2 mmol, 1.0 equiv.), 37 wt.% aqueous formalin solution (1.5 mL, 10.3 equiv.), and Y-type zeolite (SiO2:Al2O3 = 80:1, 0.2 g) were mixed in a 10 mL glass reactor. Cyclopentyl methyl ether (CPME; 4.5 mL, 3 volume equiv.) was added to the aqueous phase. The mixture was then heated at 140 °C with stirring for 4 h. HPLC analysis indicated a DFX yield of 50.4% in the organic cyclopentyl methyl ether phase and 18.4% in the aqueous phase. The solution was cooled to room temperature (approximately 23–25 °C). The aqueous and organic phases were separated and filtered through a nylon membrane filter. The organic phase was distilled under reduced pressure (0.02 mbar) at 45 °C to obtain a concentrate. The aqueous filtrate was extracted three times with 1.5 mL of ethyl acetate or cyclopentyl methyl ether in a separatory funnel. The extractant phase was distilled under reduced pressure (0.02 mbar) at 45°C to obtain a concentrate. The two concentrates were combined and then crystallized at 4-5°C to obtain DFX as white crystals.

[0122] Other extraction solvents such as anisole, methyl isobutyl ketone (MIBK), dibutyl ether, and toluene can be used in the same manner at various dosages (Table 5).

[0123] [Table 5]

[0124] Example 6 : D-xylose (0.25 g, 1.67 mmol, 1.0 equiv.), dodecanal (0.75 mL, 2 equiv.), and Y-type zeolite (SiO2:Al2O3 = 30:1, 0.1 g) were added to dioxane (5 mL) in a 10 mL glass reactor. The mixture was then heated at 65 °C for 5 h with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C), filtered through a nylon membrane filter, and the dioxane was removed by rotary evaporation in a 45 °C water bath. GC-FID analysis showed a 66.2% yield of MDX (3,5-O-dodecylidene-xylose), a 7.2% yield of MDX (1,2-O-dodecylidene-xylose), and a 3.9% yield of DDX (didodecylidene-xylose) from D-xylose. Similar reactions using other heterogeneous catalysts are summarized in the table below (MDX and DDX yields and xylose conversion using various heterogeneous catalysts in Example 6).

[0125] [Table 6]

[0126] Example 7 : Glyoxylic acid monohydrate (0.29 g, 2 equivalents) was added to 1,4-dioxane (5 mL). This mixture was pre-dried with 0.6 g of 4A molecular sieves to remove water. In a 10 mL glass reactor, this dried mixture was combined with Amberlyst® 15 (0.125 g) and MDX (0.5 g, 1.6 mmol, 1 equivalent, isolated from Example 6) was added. The mixture was then heated at 80°C with stirring for 4 hours. The resulting solution was cooled to room temperature (approximately 23-25°C), filtered through a nylon membrane filter, and the dioxane was removed by rotary evaporation in a 45°C water bath. GC-FID analysis indicated a GMAX (1,2-O-glyoxylic acid-3,5-O-dodecylidene-xylose) yield of 59.4%.

[0127] Example 8 : D-xylose (5.0 g, 33 mmol, 1.0 equiv.), glyoxylic acid monohydrate (7.66 g, 2.5 equiv.), and sulfonated resin (Dowex® r 50wx8, hydrogen form, 200-400 mesh, 1.5 g) were added to sulfolane (20 mL) in a 100 mL round-bottom flask. The mixture was heated at 90°C under reduced pressure (40 mbar) for 5 h while stirring by flask rotation. The resulting solution was cooled to room temperature (approximately 23-25°C) and filtered through a nylon membrane filter to remove the Dowex® catalyst. The yield of xylose diglyoxylate (DGAX) was 77% based on xylose loading, as determined by HPLC.

[0128] Example 9 : D-xylose (0.25 g, 1.67 mmol, 1.0 equiv.), various aldehydes (2 equiv.), and Y-type zeolite (SiO2:Al2O3 = 80:1, 0.25 g) were added to 1,4-dioxane (5 mL) in a 10 mL glass reactor. The mixture was then heated at 65 °C for 5 h with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C) and filtered through a nylon membrane filter. The dioxane was removed by rotary evaporation in a 45 °C water bath.

[0129] For comparison, D-xylose (0.25 g, 1.67 mmol, 1.0 equiv.), various aldehydes (2 equiv.), and H2SO4 (5.3 μL) were added to dioxane (5 mL) in a 10 mL glass reactor. The mixture was then heated at 65 °C for 5 h with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C), filtered through a nylon membrane filter, and the dioxane was removed by rotary evaporation in a 45 °C water bath.

[0130] For each aldehyde type, the yields of various products measured by GC-FID from the heterogeneous and homogeneous reactions are compared pairwise in the table below (yields of products IVa, Va, Xa, XIa and I using various aldehydes and xylose conversion in Example 9).

[0131] [Table 7]

[0132] Example 10 : L-arabinose (0.25 g, 1.67 mmol, 1.0 equiv.), dodecanal (0.75 mL, 2 equiv.), and Y-type zeolite (SiO2:Al2O3 = 30:1, 0.25 g) were added to 1,4-dioxane (5 mL) in a 10 mL glass reactor. The mixture was then heated at 65 °C for 5 h with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C) and filtered through a nylon membrane filter. The 1,4-dioxane was removed by rotary evaporation in a 45 °C water bath. GC-FID analysis indicated 77.3% partially protected arabinose and 12.7% fully protected arabinose.

[0133] Example 11 : D-glucose (0.3 g, 1.67 mmol, 1.0 equiv.), dodecanal (1.85 mL, 5 equiv.), and Y-type zeolite (SiO2:Al2O3 = 30:1, 0.25 g) were added to 1,4-dioxane (5 mL) in a 10 mL glass reactor. The mixture was then heated at 80 °C for 5 h with stirring. The resulting solution was cooled to room temperature (approximately 23-25 ​​°C), filtered through a nylon membrane filter, and the 1,4-dioxane was removed by rotary evaporation in a 45 °C water bath. GC-FID analysis indicated a 58.0% yield of partially protected glucose and a 34.3% yield of fully protected glucose.

Claims

1. 1. A method for preparing an at least partially acetal-protected sugar, comprising reacting a sugar or sugar derivative selected from the group consisting of aldopentose, aldohexose, aldopentoside, and aldohexoside with an aldehyde or aldehyde source in the presence of a heterogeneous acidic catalyst to form an at least partially acetal-protected sugar selected from the group consisting of compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, and XII: 【Chemistry 1-1】 【Chemistry 1-2】 [Chemistry 1-3] In the formula, R １ , R １ ', R ２ , R ２ ', R ３ , R ３ ', R ４ , R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １２ ' is Y or ZE, and R １ and R １ ', R ２ and R ２ ', R ３ and R ３ ', and R １２ and R １２ ' are the same or different from each other, Y is hydrogen or a linear, branched, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms; Z is a straight, branched, or cyclic hydrocarbon moiety having 0 to 12 carbon atoms, and １ ~C ４ may be substituted with an alkyl group, or 1 to 4 halogen atoms, or a benzyl group; and E is -COOH, -CH(COOH) ２ , -COOR １９ , -CH(COOR ２０ ) (COOR ２１ ), -CHO, -CH(CHO) ２ , -C ２ H ３ , —CH(C ２ H ３ ) ２ , -CHCHR ２２ , -CHCR ２３ R ２４ , -C ２ H, -C ２ R ２５ , -N ３ , -NH ２ , —CH(NH ２ ) ２ , -NHR ２６ , —CH(NHR ２７ ) (NHR ２８ ), -NR ２９ R ３０ , —CH(NR ３１ R ３２ ) (NR ３３ R ３４ ), —OH, —OR ３５ , or —CH(R ３６ OH) (R ３７ OH), and R １９ , R ２０ , R ２１ , R ２２ , R ２３ , R ２４ , R ２５ , R ２６ , R ２７ , R ２８ , R ２９ , R ３０ , R ３１ , R ３２ , R ３３ , R ３４ and R ３５ are independently C １ ~C ２０ alkyl, and R ２０ and R ２１ , R ２３ and R ２４ , R ２７ and R ２８ , R ２９ and R ３０ , R ３１ and R ３２ , and R ３３ and R ３４ are the same or different from each other, and R ３６ and R ３７ are, independently of one another, absent or linear or branched C １ ~C １２ a hydrocarbon chain, and R １３ , R １４ , R １５ , R １６ , R １７ and R １８ are, independently of each other, hydrogen or a straight-chain, branched-chain, or cyclic hydrocarbon moiety having 1 to 20 carbon atoms.

2. 2. The method of claim 1, wherein the heterogeneous acidic catalyst is a Bronsted acidic catalyst, preferably selected from the group consisting of: a. acidic zeolite; b. Acid-doped zeolites; c. a resin functionalized with acid moieties; d. oxides functionalized with acid moieties; e. acidic oxides; f. Heteropolyacids and their derivatives.

3. 3. The method of claim 2, wherein the heterogeneous Bronsted acidic catalyst is an acidic zeolite, preferably comprising: - at least two, preferably two or three, non-interconnected parallel channel systems, at least one of which is composed of channels with eight or more ring members; and - as determined by NMR, the framework Si / X ２ a zeolite having a ratio of at least 4; or - at least two, preferably two or three, interconnected non-parallel channel systems, at least one of which is composed of channels with 10 or more ring members; and - as determined by NMR, the framework Si / X ２ a zeolite having a ratio of at least 4; or - three interconnected non-parallel channel systems, at least two of which are composed of channels with 10 or more ring members; and - the framework Si / X ２ a zeolite having a ratio of at least 4; where each X is Al or B.

4. The aldehyde may be formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, isovaleraldehyde, hexanal, heptanal, octanal, nonanal, decanal, dodecanal, tetradecanal, hexadecanal, octadecanal, crotonaldehyde, glyoxal, malonic dialdehyde, succinic dialdehyde, glutaraldehyde, adipic dialdehyde, 2-hydroxyadipic dialdehyde, pimelic dialdehyde, 4. The method according to any one of claims 1 to 3, wherein the aldehyde is selected from the group consisting of acetaldehyde, glutaraldehyde, isophthalaldehyde, terephthalaldehyde, 1,4-diformylcyclohexane, glyoxylic acid, glyoxylic acid monohydrate, formylacetic acid, and succinic semialdehyde, preferably formaldehyde, acetaldehyde, dodecanal, glyoxylic acid, glyoxylic acid monohydrate, and glutaraldehyde.

5. The method of any one of claims 1 to 3, wherein the aldehyde source is selected from the group consisting of paraformaldehyde, 1,3,5-trioxane, polyoxymethylene, and metaldehyde.

6. R １３ , R １４ , R １５ , R １６ , R １７ and R １８ The process according to any one of claims 1 to 5, wherein is hydrogen, methyl or ethyl, preferably hydrogen.

7. The method of any one of claims 1 to 6, wherein the sugar is an aldopentose.

8. The method according to any one of claims 1 to 7, wherein the sugar is arabinose or xylose, preferably D-xylose.

9. The method according to any one of claims 1 to 6, wherein the sugar is glucose, preferably D-glucose.

10. The method according to any one of claims 1 to 9, wherein the catalyst has a microporous structure.

11. The process according to any one of claims 1 to 10, wherein the reaction is carried out in an organic solvent, preferably an organic solvent selected from the group consisting of dimethyl isosorbide, cyclic ethers, in particular 1,4-dioxane, 2-methyltetrahydrofuran, tetrahydrofuran, sulfolane, sulfolene, aliphatic acids, in particular acetic acid, alkylpyrrolidones, cyclic carbonates, cyclic esters, in particular γ-valerolactone, γ-butyrolactone, acetonitrile, dialkyl ethers, in particular diethyl ether, cyclic ethers, in particular CPME and diethyl ether, cyclic ethers, and glycol mono- and diethers.

12. The method according to any one of claims 1 to 10, wherein the reaction is carried out in an aqueous solution.

13. 11. The process according to any one of claims 1 to 10, wherein the reaction is carried out in a biphasic solvent system, preferably selected from the group consisting of CPME / water, anisole / water, dialkyl ether / water, dialkyl ketone / water, and toluene / water, preferably selected from the group consisting of CPME / water and toluene / water, most preferably CPME / water.

14. A process according to any one of claims 1 to 13, wherein the reaction is carried out at a temperature of from 50 to 160°C, preferably from 80 to 140°C.

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