MANUFACTURING OF 2,3,5-TRIMETHYLHYDROQUINONE FROM A MIXTURE OF MESITOL AND 2,3,6-TRIMETHYLPHENOL

Abstract

The present invention relates to a process of manufacturing 2,3,5-tri- methylhydroquinone from a mixture of mesitol and 2,3,6-trimethylphenol (=2,3,6- TMP). This process offers a highly interesting and commercial interesting way of producing α-tocopherol.

Description

1 / 33 MANUFACTURING OF 2,3,5-TRIMETHYLHYDROQUINONE FROM A MIXTURE OF MESITOL AND 2,3,6-TRIMETHYLPHENOL TECHNICAL FIELD

[001] The present invention relates to the field of manufacturing 2,3,5-trimethylhydroquinone and α-tocopherols. BACKGROUND OF THE INVENTION

[002] 2,3,5-Trimethylhydroquinone (TMHQ) is a key substance in the synthesis of α-tocopherols. The compound is typically produced from m-cresol, followed by methylation to produce 2,3,6-trimethylphenol and oxidized to trimethylquinone (TMQ) and reduced to produce TMHQ, as reported, for example, by W. Bonrath et al. Angew. Chem. Int. Ed. 2012, 51, 1298212985 or Bonrath, W. et al. (2021). Vitamins, 4. Vitamin E (Tocopherols, Tocotrienols). In Ullmann's Encyclopedia of Industrial Chemistry. https: / / doi.org / 10.1002 / 14356007.o27 o07.pub2.

[003] Traditionally, cresols can be extracted from coal tar. However, this leads to a mixture of the o-cresol, m-cresol, and p-cresol isomers. From this mixture, o-cresol is easily separated; however, m-cresol is very difficult to isolate from the residual mixture of m-cresol and p-cresol. Therefore, in the current industrial production of TMHQ, o-cresol is obtained through other synthetic routes that specifically lead to the m-isomer. However, these processes are very complex and expensive, which has a high impact on the price of m-cresol suitable for this process.

[004] In view of the increased awareness of the sustainability of chemical processes, interest in using raw materials from natural resources has increased significantly.

[005] Document WO 2015 / 110654 A1 or WO 2015 / 110655 A1 revealed that 2,5-dimethylphenol or 2,3,6-trimethylphenol, respectively, can be obtained from 2,5-dimethylfuran. Petition 870250074938, dated 08 / 25 / 2025, p. 17 / 60 2 / 33 and ethyne or propyne, respectively, in the presence of Au(I) complexes. However, these procedures result in isomeric mixtures of phenols. It is known that, particularly in the case of ethyne, considerable amounts of 2,4-dimethylphenol are produced as a byproduct in the synthesis of the desired 2,5-dimethylphenol.

[006] New oxidation methods leading to TMHQ have recently been discovered. Document WO 2021 / 234077 A1 revealed that 2,3,5-trimethylphenol can be photooxidized to 2,3,5-trimethylbenzoquinone.

[007] Document WO 2022 / 128852 A1 disclosed that 2,4,6-trimethylphenol can be photooxidized to 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one, which can be transformed into 2,3,5-trimethylhydroquinone.

[008] All these prior art documents have in common the fact that their respective syntheses start from specific isomers of dimethylphenol or trimethylphenols.

[009] Document CH 576 928 discloses a TMHQ process that starts from a mixture of 2,3,6- and 2,4,6-trimethylphenol using sulfonation and separation of the desired isomer from the undesired isomer. This process, however, is very disadvantageous, since only one trimethylphenol isomer (2,3,6) from an isomeric mixture is used for the synthesis of the desired 2,3,5-trimethylhydroquinone, while the other isomer (2,4,6-TMP) present in significant quantities (24%) is wasted. SUMMARY OF THE INVENTION

[010] It has been surprisingly discovered that 2,3,5-trimethylhydroquinone can be formed from a mixture of 2,4,6-trimethylphenol and 2,3,6-trimethylphenol using a process according to claim 1.

[011] This has offered new avenues for the use of raw materials that are isomeric mixtures of phenols. There is no need to separate the aforementioned isomers by techniques of Petition 870250074938, dated 08 / 25 / 2025, page 18 / 60 3 / 33 separation methods are very expensive or use complex and costly synthetic pathways that result specifically in only one isomer for the starting material. It has been found that a mixture of p-cresol can be used to produce TMHQ with high yield and selectivity. Furthermore, this invention increases the attractiveness of using 2,5-dimethylfuran as a sustainable starting material for the synthesis of TMHQ.

[012] This process is very advantageous, since both the 2,4,6-trimethylphenol and 2,3,6-trimethylphenol isomers can be converted into the desired 2,3,5-trimethylhydroquinone.

[013] Other aspects of the invention are the subject of other independent claims. Particularly preferred embodiments are the subject of dependent claims. DETAILED DESCRIPTION OF THE INVENTION

[014] In a first aspect, the present invention relates to a process for manufacturing 2,3,5-trimethylhydroquinone (TMHQ) of formula (I) from a mixture of mesitol (=2,4,6-trimethylphenol=2,4,6-TMP) of formula (IIa) and 2,3,6-trimethylphenol (=2,3,6-TMP) of formula (IIb). (IIb)

[015] This process comprises the consecutive steps of Petition 870250074938, dated 08 / 25 / 2025, p. 19 / 60 4 / 33 a) provide a mixture of the compound with formula (IIa) and the compound with formula (IIb) (IIa) (IIb) b) oxidize the mixture of formula (IIa) and the compound of formula (IIb) to form a mixture of the compound of formula (IIIa) and the compound of formula (IIIb), (IIIa) (IIIb) c) reduce the mixture of compound (IIIa) and compound (IIIb) by means of a reducing agent to produce a mixture of compound (IV) and compound (I), (IV) (I) d) rearrange the compound of formula (IV) into a mixture of the compound of formula (IV) and the compound of formula (I) by treating said mixture with a basic substance at a Petition 870250074938, dated 08 / 25 / 2025, p. 20 / 60 5 / 33 temperature > 200°C, preferably > 240°C, to obtain the compound of formula (I)

[016] In this document, a Cx-y-alkyl group is an alkyl group composed of xay carbon atoms, i.e., for example, a C1-3-alkyl group is an alkyl group composed of 1 to 3 carbon atoms. The alkyl group can be linear or branched. For example, —CH(CH3)—CH2—CH3 is considered a C4-alkyl group.

[017] Similarly, a Cx-y alkanol, respectively a Cx-y alkylenediol, is an alcohol that has one, respectively two, OH groups, where the alcohol has an alkyl group, respectively an alkylene group comprising xay carbon atoms.

[018] The term independently of each other in this document means, in the context of substituents, fractions or groups, that identically designated substituents, fractions or groups may occur simultaneously with a different meaning in the same molecule.

[019] If identical identifiers for symbols or groups are present in several formulas in this document, the definition of said group or symbol made in the context of a specific formula also applies to other formulas that include the same identifier mentioned.

[020] The term inert, as used in this document to describe a material, means that, under the reaction conditions, the material in question does not undergo any chemical reaction. Petition 870250074938, dated 08 / 25 / 2025, p. 21 / 60 6 / 33

[021] The peak wavelength is the wavelength at which the spectrum reaches its highest intensity. Provide a mixture of mesitol (formula (IIa)) and 2,3,6TMP ​​(formula (IIb)) (step a))

[022] In step a) a mixture of the compound of formula (IIa) (mesitol (=2,4,6-trimethylphenol=2,4,6-TMP)) and the compound of formula (IIb) (of 2,3,6-trimethylphenol (=2,3,6-TMP)) is provided. (IIa) OH

[023] In a first preferred embodiment, said mixture is provided by a methylation step a'') of a mixture of m-cresol and p-cresol into a mixture of mesitol and 2,3,6-TMP.

[024] Therefore, it is preferable that the mixture of compound (IIa) and compound of formula (IIb) be obtained by the reaction step a'') a”) methylation of a mixture of p-cresol of formula (0p) and m-cresol of formula (0m) (0p) (0m) . mixture of the compound of formula (IIa) and of formula (IIb).

[025] Methylation at step a') can be performed by several methods.

[026] Preferably, the p-cresol mixture in cresol is methylated, for example, in an autoclave with methanol in Petition 870250074938, dated 08 / 25 / 2025, p. 22 / 60 7 / 33 presence of lithium hydroxide monohydrate at elevated temperatures, as disclosed in document EP 1 108 705 A1, particularly by example 3, resulting in a mixture of mesitol and 2,4,6-TMP, the full disclosure of which is incorporated herein by reference.

[027] Even more preferably, the methylation of the p-cresol and m-cresol mixture is achieved by gas-phase methylation, particularly by subjecting the p-cresol mixture in cresol to a mixture of methanol and, optionally, water in the presence of an oxide catalyst in an inert atmosphere at a temperature between 300 and 500°C, to produce a mixture of mesitol and 2,4,6-TMP. This process produces less residual material, allows for a continuous process and is therefore highly advantageous from an economic and ecological point of view.

[028] In a second embodiment, the mixture of mesitol and 2,3,6-TMP is provided by a methylation step a') of a mixture of 2,4-dimethylphenol (=2,4-DMP, Formula (IIa-1H)) and 2,5-dimethylphenol (=2,5-DMP, Formula (IIb-H)). (IIa-1H) (IIb-1H) OH OH

[029] Methylation at step a') can be performed by several methods.

[030] Preferably, the mixture of 2,4-DMP and 2,5-DMP is methylated, for example, in an autoclave with methanol in the presence of lithium hydroxide monohydrate at elevated temperatures, as disclosed in document EP 1 108 705 A1, particularly by example 3, resulting in a mixture of mesitol and 2,4,6-TMP, the full disclosure of which is incorporated herein by reference. Petition 870250074938, dated 08 / 25 / 2025, p. 23 / 60 8 / 33

[031] Even more preferably, the methylation of the 2,4-DMP and 2,5-DMP mixture is achieved by gas-phase methylation, particularly by subjecting the 2,4-DMP and 2,5-DMP mixture to a mixture of methanol and, optionally, water in the presence of an oxide catalyst in an inert atmosphere at a temperature between 300 and 500°C, to produce a mixture of mesitol and 2,4,6TMP.

[032] The main advantages of the gas-phase methylation process are its high selectivity, which results in reduced waste formation, and its continuous nature. The use of this process results in particularly high economic and ecological advantages.

[033] The mixture of 2,4-DMP (Formula (IIa-1H)) and 2,5-DMP (Formula (IIb-H)) can be obtained from the reaction of the compound of formula (V) and ethyne in the presence of a Pt or Au catalyst, which is in the form of a salt or a complex. L.'>(v)0

[034] In a third preferred embodiment, the mixture of mesitol and 2,3,6-TMP is obtained from the reaction of the compound of formula (V) and propyne in the presence of a Pt or Au catalyst, which is in the form of a salt or a complex.

[035] Therefore, in a more preferred embodiment, the mixture of compound (IIa) and compound of formula (IIb) is obtained by a reaction step a0) a0) reacting compound of formula (V) with compound of formula (VI) L.'>(v)0 HC=C--R (VI) where R represents H or CH3, preferably CH3; Petition 870250074938, dated 08 / 25 / 2025, p. 24 / 60 9 / 33 in the presence of a Pt or Au catalyst, which is in the form of forming a mixture of the compound, a salt, or a complex to form a salt or complex. and the compound of formula (IIb-1H) is subjected to a reaction step of (IIa-1H) OH (IIa-1H) (IIb-1H) a' ) methylation of the mixture of formula (IIa-1H) and formula (IIb-1H) to produce the mixture of compound of formula (IIa) of formula (IIb)

[036] 2,5-dimethylfuran (IIa) (IIb). (R=CH3) or acetylene (R=H). Both propyne and acetylene are gases.

[037] If R represents CH3, propyne can also be mixed with propadiene. A particular mixture comprising propyne and propadiene is known as MAF gas (MAF = methylacetylene-alene fraction) by those skilled in the art. MAF gas is a Petition 870250074938, dated 08 / 25 / 2025, page 25 / 60 10 / 33 process gas is inexpensive and commercially available from various suppliers.

[038] In one embodiment, step a0) is carried out in the presence of a gold catalyst.

[039] This is described in detail in document WO 2015 / 110655 A1 (using ethino) or WO 2015 / 110654 A1 (using propino), full disclosure of which is incorporated herein by reference.

[040] In another embodiment, step a0) is carried out in the presence of a platinum catalyst.

[041] The aforementioned platinum catalyst is preferably in the form of a platinum salt or platinum complex.

[042] In one embodiment, the said platinum catalyst is preferably a Pt(II) salt, particularly PtCl2.

[043] In another embodiment, the said platinum catalyst is preferably a Pt(II) complex, particularly a Pt(II) complex having at least one organic ligand comprising at least one phosphorus atom, particularly a ligand selected from the group consisting of phosphites, phosphates, phosphonates and phosphines.

[044] The PtCl2 catalyst is particularly preferred in the presence of an organic ligand comprising at least one phosphorus atom, particularly a ligand selected from the group consisting of phosphites, phosphates, phosphonates and phosphines.

[045] The said organic ligand is preferably selected from the group consisting of triphenylphosphite (P(OPh)a), diphenylphosphate ((PhO)2P=O(OH)), triphenylphosphate ((PhO)sP=O), triethylphosphate ((EtO)sP=O), dibenzylphosphite ((PhCH2O)2P=disodium (yldiphenylphosphite ((MeO)P(OPh))), triphenylphosphine (P(Ph)a), P(Ph5F)3, bis-(2,2,2-trifluoroethyl)phosphite ((CF3CH2O)2P=O(H)), triethyl 2-fluoro-2-phosphonoacetate ((CHFCOOEt)(EtO)2P=O), tris(2-tolyl)phosphite, ethyl 3-(diethoxyphosphoryl)propanoate (=triethyl 3-phosphonopropionate) Petition 870250074938, dated 08 / 25 / 2025, page 26 / 60 11 / 33 ((CH2CH2COOEt) (EtO)2P=O), 2-(diphenylphosphino)benzoic acid (P(Ph)2C6H4COOH), 3,9-Bis(2,4-di-tert—butylphenoxy)-2,4,8,10tetraoxa-3,9-diphosfaspiro[5.5]undecane (Ultranox 626), P(Oisooctyl)a), P(O-isopropyl)a), P(O i-PrFa)a, P(O n-Bu)a, bis(2,4di-tert-butylphenoxy)-X2-phosphane, CHaP(EtO)2, 1,1'-binaphthyl-2,2' diyl hydrogen phosphate ( = 4-hydroxydinaphtho[2,1-d :1',2'f] [1,3,2]dioxaphosphepine 4-oxide), hydrogen phosphate VAPOL (= 18hydroxy-8,9-diphenyldiphenanthro[4,3-d:3',4'f][1,3,2]dioxaphosphepine 18-oxide), methyltriphenoxyphosphonium iodide ([CH3P(OPh)3]+I-, 4-ethyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane ((CH2CH2COOEt)(EtO)2P=O, trimethylolpropane phosphite), triphenylphosphine trisodium trisulfonate (= TPPTS), triphenylphosphine disodium disulfonate (= TPPDS) and triphenylphosphine disodium monosulfonate (= TPPMS); where Ph represents phenyl, Ph5F represents pentafluorophenyl, Et represents ethyl, and Me represents methyl.

[046] The organic ligand is most preferably selected from the group consisting of triphenylphosphite (P(OPh)s), diphenylphosphate ((PhO)2P=O(OH)), dibenzylphosphite ((PhCH2O)2P=O(H)), triphenylphosphate ((PhO)3P=O), methyldiphenylphosphite ((MeO)P(OPh)2), trisodium triphenylphosphine trisulfonate (=TPPTS), P(Ph5F)3, bis-(2,2,2-trifluoroethyl)phosphite ((CF3CH2O)2P=O(H)), tris(2-tolyl)phosphite, ethyl 3-(diethoxyphosphoryl)propanoate (=triethyl 3-phosphonopropionate) ((CH2CH2COOEt)(EtO)2P=O), acid 2-(diphenylphosphino)benzoic acid (P(Ph)2C6H4COOH) and 9-Bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphospyro[5,5]undecane (Ultranox 626); wherein Ph represents phenyl, Ph5F represents pentafluorophenyl, Et represents ethyl, and Me represents methyl.

[047] It is preferable that the said reaction between 2,5-dimethylfuran and propyne or acetylene be carried out in the presence of an ether or a ketone, particularly a cyclic ether, of Petition 870250074938, dated 08 / 25 / 2025, page 27 / 60 12 / 33 preferably tetrahydrofuran, or acetone or methyl ethyl ketone or diethyl ketone, preferably acetone.

[048] It is even preferable that the amount of Pt catalyst be present in an amount in the range of 0.1 - 25 mol%, particularly 6 - 12 mol%, relative to the compound of formula (V).

[049] It is further preferred that the molar ratio of the organic ligand mentioned above comprising at least one phosphorus atom to Pt be in the range of 1 - 2, preferably 0.5 - 1.5, and more preferably 0.4 - 1.2.

[050] It is preferable that the molar ratio of the compound of formula (V) to the compound of formula (VI) be in the range of 1:1 to 1:8, particularly 1:1 to 1:8, preferably 1:1 to 1:3.

[051] It is even preferable that the reaction be carried out at a temperature between 0°C and 80°C, particularly between 10°C and 60°C, preferably between 20°C and 30°C.

[052] At temperatures above the boiling point of the solvent, the reaction is preferably carried out under pressure.

[053] The above process produces a mixture of the compound of formula (IIa) and formula (IIb) or of formula (IIa-1H) and formula (IIb-1H), respectively.

[054] If R is H, the formation of 2,4-DMP (IIa-1H) is predominantly carried out. Typically, the molar ratio of 2,4-DMP : 2,5-DMP is greater than 50:50.

[055] As in the current process, 2,4-DMP, containing a methyl group in the para position relative to the phenolic OH group in 2,4-DMP, can be used to produce the desired 2,3,5 TMHQ, the formation of a high content of 2,5-DMP is not a disadvantage.

[056] It was observed that the molar ratio of the compound with formula (IIa-1H) (=2,4-dimethylphenol = 2,4-DMP): compound with formula (IIb-1H) (=2,5-dimethylphenol = 2,5-DMP) is typically < 70:30, particularly < 60:40, preferably < 50:50. Petition 870250074938, dated 08 / 25 / 2025, p. 28 / 60 13 / 33

[057] In the case of R being CH3, the molar ratio of the compound of formula (IIa): compound of formula (IIb) is id 50:50, particularly < 10:90, more particularly < 5:95, preferably < 3:97, more preferably < 2:98. Oxidation (step b))

[058] In step b), the mixture of mesitol compound (formula (IIa)) and 2,3,6-TMP (formula (IIb)) is oxidized to form a mixture of the compound of formula (IIIa) and the compound of formula (IIIb) provided. OH (IIa) OOH (IIIa) (IIb) (IlIb)

[059] In one embodiment, the oxidation in step b) is a classic chemical oxidation and can be carried out by methods primarily known to those skilled in the art.

[060] In particular, it can be carried out by molecular oxygen, especially in the presence of a cobalt complex and / or in the presence of a base, in particular an alkali metal salt, the details of which are disclosed in document DE 2 314 600 or DE 2 747 497.

[061] Furthermore, the oxidation in step b) can be carried out by chlorine in a suitable solvent, preferably in the absence of a base, followed by hydrolysis with water, as Petition 870250074938, dated 08 / 25 / 2025, page 29 / 60 14 / 33 described in US document 4,612,401, the full disclosure of which is incorporated herein by reference.

[062] Furthermore, the oxidation in step b) can be carried out by hypohalous acid or salt in aqueous medium or a mixture of water and an organic solvent; whose details are disclosed in document EP 0 084 158 A1, the full disclosure of which is incorporated herein by reference.

[063] In another, more preferred embodiment, the oxidation in step b) is a photochemical oxidation.

[064] It is particularly preferable that the oxidation step b) be a photo-oxidation using oxygen and a photosensitizer of formula (X) (X) wherein R8, R8', R8'' and R8''' independently represent an H or C1-4 alkyl group; or where R8 and R8' and / or R8'' and R8''' form, together with N, a ring of five or six members; provided that at least one of the residues R8, R8', R8'' and R8''' is different from H; and X represents an anion; in a solvent mixture of water and at least one C1-8 alkanol or at least one C2-4 alkylenediol; and using light with a peak wavelength (λmax) in its spectrum in the range between 580 and 780 nm.

[065] Further details of preferential photo-oxidation can be found in document WO 2022 / 128852 A1, the full disclosure of which is incorporated here by reference. Petition 870250074938, dated 08 / 25 / 2025, page 30 / 60 15 / 33

[066] In one embodiment, R8e R8' and / or R8'' and R8''' together form -(CH2)5- or — (CH2)2-NH-(CH2)2— or -(CH2)2-N(C1-4 alkyl)(CH2)2- or -(CH2)2-S-(CH2)2- or -(CH2)2-O—(CH2) 2-.

[067] It is even preferable that R8= R8'' and / or R8' = R8'''. More preferable is that R8=R8'=R8''=R8'''.

[068] More preferably, the substituent R8, R8', R8'' and R8''' represent a C1-4 alkyl group, even more preferably R8, R8', R8'' and R8''' = methyl or ethyl.

[069] Primarily R8=R8'=R8''=R8'''= CH3.

[070] In formula (X), X- represents an anion. The role of the anion is to counterbalance the charge of the cation, which is represented in the formula above by the part inside the parentheses ([) (]). Therefore, in principle, any anion can be used.

[071] Preferably, X- represents a halide, primarily a chloride.

[072] Preferably, the compound of formula (X) is methylene blue. More preferably still is the compound of formula (X) in the form of a double salt with zinc chloride, particularly a double salt of methylene blue with zinc chloride or in the form of a hydrate, preferably methylene blue hydrate (CAS:122965-43-9).

[073] It is essential that, for the above photo-oxidation, light is used that has a peak wavelength (Àmax) in its spectrum in the range between 580 and 780 nm.

[074] In a preferred embodiment, light is used that has a peak wavelength (Àmax) in its spectrum in the range between 585 and 625 nm. This corresponds to light that is perceived as orange.

[075] In another, more preferred embodiment, light is used that has a peak wavelength (λmax) in its spectrum in the range between 625 and 740 nm. This corresponds to light that is perceived as red. Petition 870250074938, dated 08 / 25 / 2025, p. 31 / 60 16 / 33

[076] This light belongs primarily to the high wavelength range of the visible spectrum.

[077] In another preferred embodiment, a light is used characterized in such a way that more than 80% of the light has a wavelength between 525 and 780 nm, preferably more than 80% of the light has a wavelength between 525 and 700 nm, more preferably more than 65% of the emitted light has a wavelength between 550 and 650 nm.

[078] In a further preferred embodiment, light is used characterized in such a way that more than 80% of the light has a wavelength between 550 and 780 nm, preferably more than 80% of the light has a wavelength between 600 and 760 nm, more preferably more than 65% of the emitted light has a wavelength between 625 and 700 nm, and more primarily more than 85% of the emitted light has a wavelength between 625 and 700 nm. [07 9] Therefore, it is important that the light used does not have a significant amount of light with wavelengths below 580 nm in its spectrum. It is essential that light of the colors green, blue and violet, or colors that contain significant amounts of green, blue and violet in their spectrum, have been considered unsuitable for the aforementioned photo-oxidation.

[080] In one embodiment, the light used for photo-oxidation can be obtained by filtering out unwanted wavelengths of light from a light source. For example, a light source with multichromatic or white emission can be filtered by a filter that blocks the unwanted wavelength.

[081] There are different possibilities of such filters known and commercially available, such as absorption, dichroic, monochromatic, bandpass, shortpass or wedge filters, using different physical methods for filtering light. Petition 870250074938, dated 08 / 25 / 2025, page 32 / 60 17 / 33

[082] Absorption or cut-off filters are particularly useful.

[083] It is particularly preferable that the light source be a white LED lamp in combination with a filter that blocks wavelengths below 500 nm, more particularly below 625 nm.

[084] In a further embodiment, the light used for photo-oxidation can be produced by a respective light source emitting light at the desired wavelengths. The light source is preferably an orange or red light, more preferably an orange or red LED to provide light that utilizes light with a peak wavelength (λmax) in its spectrum in the range between 580 and 780 nm.

[085] Specific examples of light sources in this embodiment are red LEDs or red or orange lasers, preferably red or orange LED lamps. Red and orange LED lamps are widely available commercially. Red and orange LEDs can generate high intensities of red or orange light. In some embodiments, a flexible strip has a plurality of individual LEDs incorporated in said strip. This makes it possible to ensure the radial orientation of the LED around a curved surface, such as a transparent tube, for example, simply by wrapping said strip around the tube, preferably in a helical manner.

[086] A red LED lamp is the most preferred light source for lighting.

[087] Photo-oxidation is carried out in a solvent mixture of water and at least one C1-8 alkanol or at least one C2-4 alkylenediol.

[088] The C1-8 alkanol is preferably selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, Petition 870250074938, dated 08 / 25 / 2025, page 33 / 60 18 / 33 heptanol and hexanol, being more preferably selected from the group consisting of methanol, ethanol and isopropanol.

[089] The C2-4 alkylenediol is preferably selected from the group consisting of ethane-1,2-diol, propane-1,2-diol, propane-1,3-diol, butane-1,3-diol, butane-1,4-diol, butane-1,2-diol and butane-2,3-diol, preferably selected from the group consisting of ethane-1,2-diol, propane-1,2-diol and propane-1,3-diol.

[090] It is preferable that the solvent mixture be a mixture of water and at least one C1-8 alkanol or at least one C2-4 alkylenediol to form a homogeneous phase.

[091] It is preferable that the solvent mixture be a mixture of water and at least one C1-8 alkanol or at least one C2-4 alkylenediol. The most preferred solvent mixture is a mixture of water and C1-8 alkanol.

[092] The most preferred solvent mixture is a mixture of water and C1-6 alkanol.

[093] More preferably, the solvent mixture is a mixture of water and methanol and / or ethanol and / or isopropanol. Primarily, the solvent mixture is a mixture of water and methanol and / or ethanol.

[094] It is preferable that the volume ratio of water to the sum of C1-8 alkanol and C2-4 alkylenediol be in the range between 1:10 and 1:1, particularly between 1:5 and 1:2.

[095] In a more preferred embodiment, the solvent mixture is a mixture of water and methanol, preferably in a water to methanol volume ratio in the range of 1:20 to 1:2, preferably 1:10 and 1:2, more preferably 1:6 and 1:3, and most preferably 1:4.

[096] A key advantage is that photooxidation is carried out in a solvent mixture consisting of water and at least one C1-8 alkanol or at least one C2-4 alkylenediol, which are ecologically and ecotoxicologically very favorable and also economically advantageous solvents. Therefore, it is very favorable Petition 870250074938, dated 08 / 25 / 2025, page 34 / 60 19 / 33 that the aforementioned process be carried out in the absence of any chlorinated solvent.

[097] It is preferable that the concentration of the mixture of compounds of formulas (IIa) and (IIb) be in the range of 0.002 to 2.0 mol / L, preferably 0.01 to 0.2 mol / L at the beginning of photo-oxidation.

[098] Even more preferable is that the proportion of the compound of formula (X) to the compounds of formulas (IIa) and (IIb) be in the range between 0.005 and 20 mol%, preferably between 0.05 and 20 mol%, more preferably between 0.2 and 10 mol%.

[099] By means of the photoreaction, a mixture of the compound of formula (IIIa) and (IIIb) is produced by photochemical reaction from the mixture of compound (IIa) and (IIb) and oxygen, particularly in a gaseous mixture comprising at least 15% by volume of oxygen.

[100] In one embodiment, oxygen is used in the form of a mixture comprising oxygen and an inert gas. It is preferable that the amount of oxygen in such a mixture comprising oxygen and an inert gas be at least 15% by volume, especially at least 20% by volume. Such a mixture may, for example, be a binary mixture, such as an oxygen / nitrogen or oxygen / argon mixture, or the like. Such a mixture may consist of or comprise two or more inert gases. It is particularly preferable to use air as such a mixture comprising oxygen and an inert gas.

[101] In a preferred embodiment, oxygen is used in a substantially pure form, that is, the amount of oxygen in the gas is 90% - 100%, more preferably 95% - 100%, even more preferably 99% - 100%.

[102] Photo-oxidation can occur at ambient pressure or under pressure. It is preferable that oxidation occurs under pressure, especially under a pressure of more than 2 bar, preferably Petition 870250074938, dated 08 / 25 / 2025, page 35 / 60 20 / 33 more than 3 bar, even more preferably under a pressure between 2 and 20 bar.

[103] Photo-oxidation is carried out in a suitable photoreactor. A preferred photoreactor is a flow reactor, particularly a spiral flow reactor.

[104] The individual components can be introduced separately or as a mixture into the photoreactor. Preferably, the reaction mixture is prepared before entering the photoreactor.

[105] The reaction is preferably carried out in such a way that the oxygen pressure is controlled by suitable valves and a mass flow controller. Such process control equipment and methods for photoreactions using liquids and gases are known to those skilled in the art.

[106] It is preferable that photo-oxidation be carried out in a reactor that allows a continuous process, as it is preferable that the said process be a continuous process.

[107] It was observed that the mixture of the compound of formula (IIIa) (4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one) and the compound of formula (IIIb) can be obtained with a very high yield, preferably greater than 95%, even more preferably greater than 98%, and with a very high selectivity by means of this photo-oxidation process (step b). Reduction (step c)

[108] In step c), the mixture of compound (IIIa) and compound (IIIb) is reduced by means of a reducing agent to produce a mixture of compound (IV) and compound (I),

[109] For the reduction in step c), several reducing agents can be used.

[110] Thiosulfates, tertiary phosphine, hydrogen, dithionates may be suitable as reducing agents, Petition 870250074938, dated 08 / 25 / 2025, page 36 / 60 21 / 33 dithionites, sulfites, trialkylphosphites, iodides, metals or dialkylsulfides.

[111] The reducing agent is preferably selected from the group consisting of Na2S2Oa (sodium thiosulfate), PPha (triphenylphosphine), H2 / PdC, Na2S2O4 (sodium dithionite), Na2SOa (sodium sulfite), P(OEt)a (triethyl phosphite), NaI (sodium iodide), Zn (and / or other metals) and DMS (dimethyl sulfide).

[112] Thiosulfate, particularly sodium thiosulfate, is preferred as a reducing agent.

[113] It is preferable that the reducing agent be used in a significant molecular excess, preferably in an amount between 2 and 10 equivalents relative to the compound of formula (I). It is also preferable that the reduction be carried out in an aqueous alcohol, especially at room temperature.

[114] The reduction can be carried out on a quantitative scale and with very high yields.

[115] The reduction in step c) can be carried out in a batch process or in a continuous process.

[116] It is preferable that step c) be carried out continuously. Rearrangement (step d))

[117] In step d), the compound of formula (IV), in the mixture of compound of formula (IV) and compound of formula (I) is rearranged by treating said mixture with a basic substance at a temperature of > 200°C, preferably > 240°C, to obtain compound of formula (I)

[118] Among the basic substances that can be used, the alkali metals, such as sodium, potassium, lithium, rubidium, and cesium, stand out; as do the alkaline earth metals, such as calcium, magnesium, barium, and strontium; as well as basic compounds containing at least one of these metals in their molecular structure. The following compounds are mentioned as examples of such basic substances: Petition 870250074938, dated 08 / 25 / 2025, p. 37 / 60 22 / 33 A. Alkali metal or alkaline earth metal hydroxides, such as, for example, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, and barium hydroxide; and B. Carbonates and bicarbonates of alkali metals or alkaline earth metals, such as, for example, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, barium carbonate, and magnesium carbonate; and C. Oxides of alkaline earth metals, such as, for example, calcium oxide, magnesium oxide, and barium oxide; and D. Compounds containing alkali metals or alkaline earth metals that have hitherto been used as buffers, such as, for example, a suitable mixture of an alkali dihydrogen phosphate, such as monopotassium dihydrogen phosphate, and an alkali dihydrogen phosphate, such as dipotassium monohydrogen phosphate, or alkali metal salts of organic carboxylic acids, such as boric acid, citric acid, lactic acid, tartaric acid, and acetic acid; and E. Metallic oxides, particularly iron oxides.

[119] It is preferable that step d) be carried out in the presence of water. And it is even more preferable that, in addition to water, at least one water-soluble alcohol, preferably methanol and / or ethanol and / or isopropanol, be present in step c).

[120] Step d) is preferably carried out in the presence of the basic substance so that the pH is not lower than 6.5 and preferably not lower than 7. The priority pH range of the reaction mixture is 7 to 14.

[121] It is preferable that step d) be carried out under reducing conditions or in an inert atmosphere, especially under nitrogen or argon.

[122] Preferably, the basic reaction mixture is neutralized at the end of the reaction by means of an acid. Petition 870250074938, dated 08 / 25 / 2025, page 38 / 60 23 / 33

[123] Preferably, the rearrangement step d) is carried out as disclosed in US document 3,957,887, especially as described in its example 12, or in document FR 2 200 225 or DE 2 345 062, the full disclosure of which is incorporated herein by reference.

[124] The reaction in step d) can be carried out in a batch process or in a continuous process.

[125] It is preferable that step d) be carried out continuously. Reduction / rearrangement (step c / d)

[126] In a preferred embodiment, the reduction step c) and the rearrangement step d) are performed as a single combined step c / d).

[127] c / d reduce / rearrange by treating the mixture of formula (IIIa) and the compound of formula (IIIb) with a basic substance and the presence of a reducing agent at a temperature of > 200°C, preferably > 240°C, to obtain the compound of formula (I).

[128] The details of the reduction and rearrangement have already been described previously for step c) or step d), respectively.

[129] The present invention shows that 2,3,5-trimethylhydroquinone can be obtained with high yield and selectivity from a mixture of 2,4,6-TMP and 2,3,6-TMP, which can particularly be obtained from 2,5-dimethylfuran obtained from renewable sources or from mixtures of m- and p-cresol, which, as a mixture, is readily and economically available in large industrial volumes from commercial suppliers. It is particularly surprising that both components of the respective mixtures can undergo the reaction under the same conditions and without disturbance to each other in each of the respective reaction steps.

[130] As already mentioned, 2,3,5-trimethylhydroquinone is a key ingredient in the synthesis of α-tocopherol. Petition 870250074938, dated 08 / 25 / 2025, pp. 39 / 60 24 / 33

[131] Thus, the present invention also relates to the process for manufacturing α-tocopherol comprising the steps of i) providing 2,3,5-trimethylhydroquinone manufactured from a mixture of mesitol (formula (IIa)) and 2,3,6-TMP (formula (IIb)) by a process as discussed above in greater detail; ii) condense 2,3,5-trimethylhydroquinone from step i) with a compound of formula (VII-A) or formula (VII-B) to produce α-tocopherol of formula (VIII) (VII-A) (VII-B) (VIII) where Q is a substituent selected from the group consisting of OH, halide, acyloxy, especially acetoxy or benzoyloxy, methanesulfonyloxy (=mesiloxy), ethanesulfonyloxy, benzenesulfonyloxy and toluenesulfonyloxy (=tosiloxy); where any wavy line represents a carbon-carbon bond that, when attached to the carbon-carbon double bond, is in the Z or E configuration.

[132] In the case where Q represents a halide, Q preferably represents Cl.

[133] In the case where Q represents an acyloxy, the acyloxy is preferably a group of the formula Petition 870250074938, dated 08 / 25 / 2025, pp. 40 / 60 25 / 33 where R10 represents a C1-6-alkyl group or an aryl group, which is optionally replaced, especially by at least one C1-6-alkyl group.

[134] Preferably, R10 represents a C1-6-alkyl or a phenyl group.

[135] More preferably, R10 represents a methyl or phenyl group, preferably a methyl group.

[136] Specific examples for compounds of formula (VII-A) include isophytol, isophytil chloride, isophytil bromide, isophytil iodide, isophytil acetate, isophytil methanesulfonate, isophytil ethanesulfonate, isophytil benzenesulfonate and isophytil toluenesulfonate.

[137] Specific examples of compounds of formula (VII-B) include phytol, phytyl chloride, phytyl bromide, phytyl iodide, phytyl acetate, phytyl methanesulfonate, phytyl ethanesulfonate, phytyl benzenesulfonate and phytyl toluenesulfonate.

[138] The compound of formula (VII-B) can be used as an E / Z mixture, as well as in pure E or pure Z form. It is preferable to use these as E / Z mixtures.

[139] Q preferably stands for OH or Cl.

[140] Therefore, the preferred compounds of formula (VIIA) or (VII-B) are phytol, isophytol, phytyl chloride or isophytol chloride, phytol or isophytol being more preferred. Isophytol is the most preferred.

[141] The use of compounds of formula (VII-A) is preferable to compounds of formula (VII-B).

[142] The condensation step ii) is shown schematically in figure 3.

[143] It has been found that the condensation reaction of step ii) can be carried out as described, for example, in W. Bonrath et al. Angew. Chem. Int. Ed. 2012, 51, 12982-12985 or Bonrath, W. et al. (2021). Vitamins, 4. Vitamin E (Tocopherols, Petition 870250074938, dated 08 / 25 / 2025, page 41 / 60 26 / 33 Tocotrienols). In Ullmann's Encyclopedia of Industrial Chemistry. https: / / doi.org / 10.1002 / 14356007.o27 o07.pub2 .

[144] This condensation reaction (step ii) is preferably carried out using a Lewis or Brønsted acid.

[145] The Lewis or Brønsted acids mentioned are particularly those mentioned in document EP 0949255 A1 and in Bonrath et al., Adv. Synth. Catal. 2002, 344, 37-39.

[146] Figure 1 schematically shows the different preferred synthetic routes of the manufacturing process of 2,3,5-trimethylhydroquinone of formula (I) from a mixture of mesitol (formula IIa) and 2,3,6-TMP (formula IIb), as discussed in greater detail above.

[147] Figure 2 schematically shows the different preferred synthetic pathways for producing a mixture of mesitol (formula IIa) and 2,3,6-TMP (formula IIb), as discussed in greater detail above.

[148] Figure 3 schematically shows the manufacture of alpha-tocopherol (formula (VIII)) from 2,3,5-trimethylhydroquinone of formula (I). EXAMPLES

[149] The present invention is further illustrated by the following experiments. First experimental series (examples 1-26): Reaction of 2,5-dimethylfuran with acetylene: step a0)

[150] 2,5-Dimethylfuran was reacted with acetylene (2% by weight) in an organic solvent and a platinum catalyst, as indicated in Table 1.

[151] For this purpose, platinum chloride (6 mol%), 2,5-dimethylfuran (1.0 equivalent) and acetylene (1.0 equivalent) dissolved (2% by weight) in the respective organic solvent were added to a 10 mL flask with a magnetic stirring bar under an argon atmosphere. The flask was then sealed. Petition 870250074938, dated 08 / 25 / 2025, page 42 / 60 27 / 33 with a lid and the mixture was stirred in an aluminum block at 23°C for a time as indicated in Table 1. The reaction mixture was then filtered to remove the catalyst and the ligand. All volatiles (including unreacted 2,5-dimethylfuran) were removed under vacuum at 50°C / <30 mbar to obtain an oily residue. The amounts of 2,4- and 2,5-dimethylphenol were determined by GC (gas chromatography). The ratio, as well as the yield, are indicated in Table 1.

[152] The results in Table 1 show that, in particular, ligands possessing an aromatic substituent are suitable as part of the platinum catalyst. The ligand P(Ph5F)3 (tris(pentafluorophenyl)phosphine) is one of the most suitable ligands. Furthermore, Table 1 shows that acetone and 3-pentanone are particularly suitable as organic solvents.

[153] All examples in Table 1 result in a mixture of 2.4 DMP and 2.5 DMP. TABLE 1 Reaction of 2,5-dimethylfuran with acetylene in different solvents and with different catalysts Ex. Acetylene1 Ligand Ligand [mol%]2 Time [h] Yield [% by weight]3 2.4: 2.54 1 acetone P(OPh)3 6 120 25 65:35 2 acetone P(OPh)3 12 148 32 65:35 3 THF P(OPh)3 12 148 5 68 : 32 4 acetone (PhO)2P=O(OH) 6 148 12 68 : 32 5 acetone (PhCH2O) 2P=O (H) 6 148 22 61:39 6 acetone (PhCH2O) 2P=O (H) 6 148 21 59:41 7 THF (PhCH2O) 2P=O (H) 6 148 6 66:34 8 acetone (PhO)3P=O 6 148 11 43:57 9 acetone (MeO)P(OPh)2 6 148 27 60:40 10 acetone (MeO)P(OPh)2 12 148 36 62 : 38 11 THF (MeO)P(OPh)2 6 148 7 68 : 32 12 acetone TPPTS 6 148 13 57 : 43 13 THF TPPTS 6 148 8 56:44 14 acetone P ( Ph5F ) 3 6 148 45 66:34 Petition 870250074938, dated 08 / 25 / 2025, p. 43 / 60 28 / 33 Ex. Acetylene1 Ligand Ligand [mol%]2 Time [h] Yield [% by weight]3 2.4: 2.54 15 acetone (CF3CH2O) 2P=O (H) 6 148 10 56:44 16 acetone (CHFCOOEt)(EtO)2 P=O 6 148 13 52 : 48 17 acetone tris(2tolyl)phosphite 6 148 14 58 : 42 18 acetone (CH2CH2COOEt) (Et O) 2P=O 6 148 6 48 : 52 19 acetone P(Ph)2C6H4COOH 6 148 6 61:39 20 acetone Ultranox 626 6 148 3 50:50 21 3pentanone4 P(OPh)3 6 148 28 nd7 22 3pentanone6 P(OPh)3 6 148 21 nd7 23 3pentanone6 P ( Ph5F ) 3 6 148 16 nd7 24 3pentanone5 P ( Ph5F ) 3 6 148 48 nd7 25 3pentanone6 P ( Ph5F ) 3 6 148 33 nd7 26 3pentanone6 P ( Ph5F ) 3 6 148 28 nd7 1 acetylene at 2% in mentioned organic solvent2 in relation to 2,5-dimethylfuran3 combined yield of 2,4-DMP and 2,5-DMP4 2.4:2.5: ratio 2,4-DMP : 2.5-DMP % of area)5 molar ratio acetylene : 2,5-DMP = 2:16 molar ratio acetylene : 2,5-DMP = 3:16 molar ratio acetylene : 2,5-DMP = 5:17 n.d.: not determined Second experimental series (examples 27-37): Reaction of 2,5-dimethylfuran with propyne: step a0)

[154] 2,5-Dimethylfuran was reacted with propyne (2 wt%) in an organic solvent and a platinum catalyst, as indicated in Table 2. Petition 870250074938, dated 08 / 25 / 2025, pp. 44 / 60 29 / 33

[155] For this purpose, platinum chloride (6 mol%), 2,5-dimethylfuran (1.0 equivalent) and propyne (1.0 equivalent) dissolved (2% by weight) in the respective organic solvent were added to a 10 mL flask with a magnetic stirring bar under an argon atmosphere. The flask was then sealed with a cap and the mixture was stirred on an aluminum block at 23°C for a time as indicated in Table 2. The reaction mixture was then filtered to remove the catalyst and ligand. All volatiles (including unreacted 2,5-dimethylfuran) were removed under vacuum at 50°C / <30 mbar to obtain an oily residue. The amounts of 2,4,6-TMP and 2,3,6-TMP were determined by GC (gas chromatography). The ratio, as well as the yield, are indicated in Table 2. TABLE 2 Reaction of 2,5-dimethylfuran with propyne in different solvents and with different catalysts Ex. Propyne1 Ligand Ligand [mol%]2 Time [h] Yield [% by weight]3 2,4,6: 2,3,64 27 acetone (PhO)2P=O(OH) 6 148 3 3:97 28 acetone P ( Ph5F ) 3 6 120 34 8 : 92 29 acetone P ( Ph5F ) 3 6 148 33 5:95 30 3-pentanone P ( Ph5F ) 3 6 240 29 7 : 93 31 3-pentanone P ( Ph5F ) 3 6 240 24 7 : 93 32 3-pentanone (MeO)P(OPh)2 6 148 3 3:97 33 3-pentanone (PhO)2P=O(OH) 6 148 15 2 : 98 34 3-pentanone P(OPh)3 6 148 6 2 : 98 35 3-pentanone P ( Ph5F ) 3 6 148 39 4:96 36 3-pentanone P ( Ph5F ) 3 6 240 34 6:94 1propyne at 2% in mentioned organic solvent2in relation to 2,5-dimethylfuran3combined yield of 2,4,6-TMP and 2,3,6-TMP42,4,6:2,3,6: ratio 2,4,6-TMP and 2,3,6-TMP % area)) Third experimental series (examples 37-43): Reaction of 2,5-dimethylfuran with MAF Petition 870250074938, dated 08 / 25 / 2025, pages 45 / 60 30 / 33

[156] 2,5-Dimethylfuran was reacted with MAF gas (2 wt%) in an organic solvent and a platinum catalyst, as indicated in Table 2.

[157] For this purpose, platinum chloride (6 mol%), 2,5-dimethylfuran (1.0 equivalent) and MAF gas (1.0 equivalent) dissolved (2% by weight) in the respective organic solvent were added to a 10 mL flask with a magnetic stirring bar under an argon atmosphere. The flask was then sealed with a cap and the mixture was stirred on an aluminum block at 23°C for a time as indicated in Table 3. The reaction mixture was then filtered to remove the catalyst and ligand. All volatiles (including unreacted 2,5-dimethylfuran) were removed under vacuum at 50°C / <30 mbar to obtain an oily residue. The amounts of 2,4,6-TMP and 2,3,6-TMP were determined by GC (gas chromatography). The ratio, as well as the yield, are indicated in Table 2. TABLE 3 Reaction of 2,5-dimethylfuran with propyne / propadiene (MAF) in different solvents and with different catalysts Ex. MAF1 Ligand Ligand [mol%]2 Time [h] Yield [% by weight]3 2,4,6:2, 3, 64 37 3-pentanone P(OPh)3 6 148 4 1:99 38 3-pentanone P(OPh)3 12 148 8 1:99 39 3-pentanone (MeO)P(OPh)2 6 148 6 2 : 98 40 3-pentanone (PhO)2P=O(OH) 6 148 13 1:99 41 3-pentanone (PhO)2P=O(OH) 12 148 23 2 : 99 42 acetone P ( Ph5F ) 3 6 148 5 4:96 43 3-pentanone P ( Ph5F ) 3 6 148 27 4:96 1MAF at 2% in the mentioned organic solvent2in relation to 2,5-dimethylfuran3combined yield of 2,4,6-TMP and 2,3,6-TMP42,4,6:2,3,6: ratio 2,4,6-TMP and 2,3,6-TMP % area) Example 44: Methylation: step a')

[158] A gas-phase flow reactor was filled with an iron oxide-based catalyst (13 g). The reactor was closed and heated under nitrogen at 350°C in the reactor. A Petition 870250074938, dated 08 / 25 / 2025, pages 46 / 60 31 / 33 The feed consisted of a mixture of 2,5-dimethylphenol and 2,4-dimethylphenol (example 2) and methanol and water in a molar ratio of 0.35:0.65:30:1.7. The mixture was pumped at 0.39 mL / min from top to bottom in the gas-phase reactor. After the hot zone, the reaction mixture was cooled to room temperature and collected in a flask. The flask was emptied and analyzed every 24 h for five days.

[159] The average conversion and selectivity over the five days were: Conversion of 2,5-dimethylphenol: 16% Conversion of 2,4-dimethylphenol: 32% Selectivity for 2,3,6-trimethylphenol: 95% Selectivity for 2,4,6-trimethylphenol: 89% Example 45: Photo-oxidation of the mixture of 2,4,6-TMP and 2,3,6-TMP: Step b)

[160] A solution of the mixture of 2,4,6-TMP (3.3 mmol) and 2,3,6TMP ​​(1.7 mmol)) and methylene blue hydrate ([CAS: 122965-439]), 14.4 mg, 0.900 mol%) in methanol and water (4:1, v / v, 250 mL) was prepared to obtain a homogeneous blue solution. The solution was pumped through a high-pressure liquid chromatography pump to the photoreactor (piping system: 0.75 mm internal diameter, 1.58 mm external diameter, PFA coil) (liquid flow rate: 0.250 - 0.023 mL / min, piston pump set for HPLC) at a constant pressure of 10 bar.

[161] Before entering the photoreactor, the solution was enriched with air (air flow rate: 1.350 - 0.125 mL / min, mass flow controller). Inside the photoreactor, the reaction mixture was exposed to a hyperred LED light source for a residence time of 40 min. Complete conversion was confirmed by thin-layer chromatography and QNMR. The photoreactor was maintained at room temperature (20 °C). The volume of the reaction mixture (25 mL) was collected after two residence times using a round bottom. Added Petition 870250074938, dated 08 / 25 / 2025, pp. 47 / 60 32 / 33 water (50 mL) and the solution was extracted with pentane (2 x 50 mL) and diethyl ether (2 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and the organic solvent was removed under reduced pressure (15 mbar) to obtain a mixture of 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one) (formula (IIIa)) (conversion: >99%, yield: 99%) and 2,3,5-trimethylbenzoquinone (=2,3,5trimethylcyclohexa-2,5-diene-1,4-dione, TMQ) (formula (IIIb)) (conversion: >99%, yield: 71%). Example 46: Reduction of the mixture of 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one) and 2,3,5-trimethylbenzoquinone: step c)

[162] Platinum on charcoal (1.0 mol%) was charged into a flame-dried flask and methanol was carefully added to obtain a dark heterogeneous solution. A solution of the mixture of 4-hydroperoxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one (formula (IIIa)) and 2,3,5-trimethylbenzoquinone (=2,3,5-trimethylcyclohexa-2,5-diene-1,4-dione, TMQ) (formula (IIIb)) (0.25 mmol) in methanol and water (4:1, v / v) is prepared to obtain a homogeneous yellow solution which was added to the catalyst solution. The flask was evacuated, and then hydrogen was introduced. The reaction mixture was stirred for more than 1 hour at room temperature (20 °C) until complete conversion. Water (10 mL) was added, and the solution was extracted with diethyl ether (3 x 5 mL).The combined organic layers were washed over Na2SO4, filtered, and the organic solvent was removed under reduced pressure (15 mbar) to obtain a mixture of 2,3,5-trimethylhydroquinone (formula (I)) (conversion: >99%, yield: 74%) and 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one (formula (IV)) (conversion: >99%, yield: 51%). Example 47: Rearrangement of 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one to 2,3,5-trimethylhydroquinone: step d) Petition 870250074938, dated 08 / 25 / 2025, pages 48 / 60 33 / 33

[163] A mixture of 2,3,5-trimethylhydroquinone (formula (I)) and 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dien-1-one (formula (IV)) in an aqueous solution of NaOH and methanol and sodium sulfite (6.3 mol%, relative to formula (IV), was pumped through a flow reactor (diameter 1.5 mm, length: 2000 mm) at 10 mL / min at 250 °C. The solution was neutralized at the end of the flow reactor with sulfuric acid. The reaction mixture was extracted with ethyl acetate, dried over MgSO4 and concentrated under vacuum. Petition 870250074938, dated 08 / 25 / 2025, pp. 49 / 60

Claims

1 / 8 CLAIMS 1. Process for manufacturing 2,3,5-trimethylhydroquinone of formula (I) characterized in that it comprises the consecutive steps of a) providing a mixture of the compound of formula (IIa) and the compound of formula (IIb) (IIa) (IIb) b) oxidizing the mixture of formula (IIa) and the compound of formula (IIb) to form a mixture of the compound of formula (IIIa) and the compound of formula (IIIb), and the compound of formula (IIIb) by means of a reducing agent to produce a mixture of the compound of formula (IV) and the compound of formula (I), treating said mixture with a basic substance at a temperature of > 200°C, preferably > 240°C, to obtain the compound of formula (I) 2. Process according to claim 1, characterized in that the mixture of compound (IIa) and compound of formula (IIb) is obtained by a reaction step a0) a0) reacting the compound of formula (V) with the compound of formula (VI) (V) HC=C--R (VI) wherein R represents H or CH3 preferably CH3; in the presence of a Pt or Au catalyst, which is in the form of a salt or a complex to form a mixture of the compound of formula (IIa-1) and of formula (II-b) Petition 870250074938, dated 08 / 25 / 2025, p. 51 / 60 3 / 8 (IIa-1) (IIb-1) with the condition that, in the case of R representing H, the mixture of the compound of formula (IIa-1H) and of formula (IIb-1H) is subjected to a reaction step a') (IIa-1H) (IIb-1H) a' ) methylation of the mixture of formula (IIa-1H) and formula (IIb-1H) to produce the mixture of the compound of formula (IIa) and formula (IIb) (IIa) (IIb).

3. Process according to claim 2, characterized in that the mixing of step a0) is carried out in the presence of a Pt catalyst, which is in the form of a Pt salt or a Pt complex.

4. Process according to claim 2 or 3, characterized in that, if R represents CH3, propyne is used in this reaction in combination with propadiene. Petition 870250074938, dated 08 / 25 / 2025, pp. 52 / 60 4 / 8 5. Process according to any one of the preceding claims 2 to 4, characterized in that the Pt catalyst is a Pt(II) salt, particularly PtCl2.

6. Process according to any one of the preceding claims 2 to 5, characterized in that the Pt catalyst is a Pt(II) complex having at least one organic ligand comprising at least one phosphorus atom, particularly a ligand selected from the group consisting of phosphites, phosphates, phosphonates and phosphines.

7. Process, according to any one of the preceding claims 2 to 6, characterized in that the Pt catalyst is PtCl2 in the presence of an organic ligand comprising at least one phosphorus atom, particularly a ligand selected from the group consisting of phosphites, phosphates, phosphonates and phosphines.

8. Process according to claim 6 or 7, characterized in that the organic ligand is selected from the group consisting of triphenylphosphite (P(OPh)a), diphenylphosphate ((PhO)2P=O(OH)), triphenylphosphate ((PhO)3P=O), triethylphosphate ((EtO)sP=O), dibenzylphosphite ((PhCH2O)2P=disodium (yldiphenylphosphite ((MeO)P(OPh)2), triphenylphosphine (P(Ph)a), P(Ph5F)3, bis-(2,2,2-trifluoroethyl)phosphite ((CF3CH2O)2P=O(H)), triethyl 2-fluoro-2-phosphonoacetate ((CHFCOOEt)(EtO)2P=O), tris(2-tolyl)phosphite, ethyl 3(diethoxyphosphoryl)propanoate (=triethyl 3-phosphonopropionate) ((CH2CH2COOEt)(EtO)2P=O), 2-(diphenylphosphino)benzoic acid (P(Ph) 2C6H4COOH), 3,9-Bis(2,4-di-tert-butylphenoxy)-2,4,8,10tetraoxa-3,9-diphosfaspiro[5.5]undecane, P(O-isooctyl)3), P(Oisopropyl)3), P(O i-PrF6)3, P(O n-Bu)3, bis(2,4-di-tertbutylphenoxy)-X2-phosphane, CH3P(EtO)2, 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate ( = 4-hydroxydinaphtho[2,1-d: 1',2'f][1,3,2]dioxaphosphepine 4-oxide), VAPOL hydrogen phosphate (=18hydroxy-8,9-diphenyldiphenanthro[4,3-d:3',4'- Petition 870250074938, of 08 / 25 / 2025, p. 53 / 60 5 / 8 f] [1,3,2]dioxaphosphepine 18-oxide), iodide methyltriphenoxyphosphonium ([CH3P(OPh)3]+I-, 4-ethyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane ((CH2CH2COOEt)(EtO)2P=O, trimethylolpropane phosphite), trisodium triphenylphosphine trisulfonate (= TPPTS), disodium triphenylphosphine disulfonate (= TPPDS) and disodium triphenylphosphine monosulfonate (= TPPMS); wherein Ph represents phenyl, Ph5F represents pentafluorophenyl, Et represents ethyl and Me represents methyl.

9. Process according to claim 1, characterized in that the mixture of compound (IIa) and compound of formula (IIb) is obtained by a methylation reaction step of a mixture of p-cresol of formula (0p) and m-cresol of formula (0m) OH (0p) (0m) to produce the mixture of compound of formula (IIa) and formula (IIb).

10. Process, according to any of the preceding claims, characterized in that the oxidation step b) is a photo-oxidation that uses oxygen and a photosensitizer of formula (X) (X) Petition 870250074938, dated 08 / 25 / 2025, page 54 / 60 6 / 8 where R8, R8', R8'' and R8''' independently represent an H or C1-4 alkyl group; or where R8 and R8' and / or R8'' and R8''' form, together with N, a five- or six-membered ring; provided that at least one of the residues R8, R8', R8'' and R8''' is different from H; and X- represents an anion; in a solvent mixture of water and at least one C1-8 alkanol or at least one C2-4 alkylenediol; and using light with a peak wavelength (λmax) in its spectrum in the range between 580 and 780 nm.

11. Process, according to claim 10, characterized in that the light used has a peak wavelength (λmax) in its spectrum in the range between 625 and 740 nm.

12. Process, according to claims 10 or 11, characterized in that the light source for the light is a white LED lamp in combination with a filter that blocks wavelengths below 500 nm, particularly below 625 nm.

13. A process, according to any one of the preceding claims 10 to 11, characterized in that the light source for the light is a red LED lamp.

14. Process, according to any one of the preceding claims 10 to 13, characterized in that the solvent mixture is a mixture of water and methanol and / or ethanol and / or isopropanol.

15. Process, according to any one of the preceding claims 10 to 14, characterized in that r8=r8'=r8''=r8'''= ch3 and preferably X- represents a halide, particularly chloride. Petition 870250074938, dated 08 / 25 / 2025, pp. 55 / 60 7 / 8 16. Process, according to any of the preceding claims, characterized in that the reduction step c) is carried out in the presence of a reducing agent selected from the group consisting of thiosulfates, tertiary phosphine, hydrogen, dithionates, dithionites, sulfites, trialkylphosphites, iodides, metals and dialkylsulfides.

17. A manufacturing process for α-tocopherol characterized in that it comprises the steps of i) providing 2,3,5-trimethylhydroquinone manufactured from a mixture of mesitol (formula (IIa)) and 2,3,6-TMP (formula (IIb)) by a process defined in any one of the preceding claims 1 to 16; (IIa) (IIb) ii) condense 2,3,5-trimethylhydroquinone from step i) with a compound of formula (VII-A) or formula (VII-B) to produce α-tocopherol of formula (VIII) (VII-A) (VII-B) (VIII) where Q is a substituent selected from the group consisting of OH, halide, acyloxy, especially acetoxy or benzoyloxy, Petition 870250074938, 25 / 08 / 2025, p. 56 / 60 8 / 8 methanesulfonyloxy (=mesiloxy), ethanesulfonyloxy, benzenesulfonyloxy and toluenesulfonyloxy (=tosiloxy); and where any wavy line represents a carbon-carbon bond which, when connected to the carbon-carbon double bond, is in the Z or E configuration. Petition 870250074938, dated 08 / 25 / 2025, pp. 57 / 60