Process for preparation of pyroxasulfone

Abstract

The present application relates to a process for the preparation of pyroxasulfone comprising reacting 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl) methylthio]-4, 5-dihydro-5, 5-dimethylisoxazole with hydrogen peroxide in the presence of a metal catalyst wherein the solvent comprises at least one carbonate and water.

Description

Technical Field

[0001] This invention relates to the field of organic compound synthesis, and more specifically to a method for preparing sulfonylpyrazine. Background Technology

[0002] US 2023012374 discloses the preparation of sulfonylpyrazol (3-[[5-(difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisooxazole) by oxidation of 3-[(5-difluoromethoxy-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfonyl]-5,5-dimethyl-4H-1,2-oxazole] in the presence of a metal catalyst and hydrogen peroxide. The yield of the reaction is generally reduced due to the incomplete oxidation of the thio group to the corresponding sulfoxide. Different organic solvents, such as butyl acetate, isopropyl acetate, ethyl acetate, methanol, butanol, ethanol, acetonitrile, DMF, or NMP, were tested in US 2023012374, and each solvent and solvent amount had different effects on the amount of sulfonylpyrazol formed and the amount of sulfoxide intermediate impurities obtained. According to the organic solvents tested in US 2023012374, the amount of organic solvent ranges from 0.4 liters to 1.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. Summary of the Invention

[0003] According to embodiments of the invention, oxidation in the presence of at least one carbonate as a solvent significantly reduces sulfoxide impurities. According to another embodiment of the invention, the amount of at least one carbonate solvent required for the reaction is significantly reduced compared to the amount required in US 2023012374. Furthermore, due to this reduction in solvent volume, a higher reactant loading can be achieved for the same volume, and therefore, a higher amount of sulfonylpyrazol product can be achieved in each production batch for any given equipment, relative to the amount obtained through US 2023012374.

[0004] Therefore, this application relates to a method for preparing sulfonylpyrazol (3-[[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylsulfonyl]-5,5-dimethyl-4H-1,2-oxazole), the method comprising reacting 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisooxazole with hydrogen peroxide in the presence of a metal catalyst, wherein the solvent comprises at least one C1-C 24 Carbonate and water.

[0005] The reaction can be summarized in the following equation:

[0006] Detailed Implementation

[0007] definition

[0008] Embodiments of the invention are discussed in detail below. Specific terminology is used in the description of the embodiments for clarity. However, the invention is not intended to limit the specific terminology chosen. While specific exemplary embodiments are discussed, it should be understood that this is merely for illustrative purposes. Although multiple embodiments and features are described herein, it should be understood that various features and aspects of the invention, even when described individually, can be combined unless mutually exclusive or contrary to the specific description. All references cited herein are incorporated by way of reference as if each reference were individually incorporated.

[0009] As used herein, the transitional terms “comprising” or “that comprises”, which are synonymous with “including” or “containing”, are inclusive or open-ended and do not exclude additional, unlisted elements or method steps. However, whenever “comprising” is used herein, as an alternative embodiment, the term is also intended to cover the phrases “substantially constitutes” and “consistent with”, wherein “consistent with” excludes any unspecified elements or steps, and “substantially constitutes” allows the inclusion of additional, unlisted elements or steps that do not materially affect the essential or essential and novel features of the composition or method under consideration.

[0010] Before detailing the subject matter of this invention, it may be helpful to provide definitions for certain terms used herein. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this subject matter pertains.

[0011] The term "C1-C" 12 "Alkyl" refers to a straight-chain or branched saturated hydrocarbon chain group that does not have multiple bonds and has one to twelve carbon atoms, and is attached to the rest of the molecule by single bonds. Suitable groups include, but are not limited to, alkyl groups such as methyl, ethyl, propyl (e.g., n-propyl or isopropyl), butyl (e.g., n-butyl, tert-butyl, sec-butyl), pentyl (e.g., 1-methylpentyl, 3-methylpentyl, n-pentyl), hexyl, octyl, or dodecyl.

[0012] The term "C2-C" 12"Alkenyl" refers to a straight-chain or branched hydrocarbon chain group having one or more carbon-carbon double bonds and two to twelve carbon atoms, and being attached to the rest of the molecule by single bonds. The double bonds in an alkenyl group can be non-conjugated or conjugated with another unsaturated group. Suitable alkenyl groups include, but are not limited to, vinyl, allyl, butenyl (e.g., 1-butenyl, 2-butenyl, 3-butenyl), pentenyl (e.g., 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl), and hexenyl (e.g., 1-hexenyl, 2-hexenyl, 3-hexenyl, ...). 4-Hexenyl, 5-Hexenyl), butadienyl, pentadienyl (e.g., 1,3-pentadienyl, 2,4-pentadienyl), hexadienyl (e.g., 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, 2,5-hexadienyl), 2-ethylhexenyl (e.g., 2-ethylhex-1-enyl, 2-ethylhex-2-enyl, 2-ethylhex-3-enyl, 2-ethylhex-4-enyl, 2-ethylhex-5-enyl), 2-propyl-2-butenyl, 4,6-dimethyl-oct-6-enyl.

[0013] The term "C2-C" 12 "Alynyl" refers to a straight-chain or branched hydrocarbon chain group having one or more carbon-carbon triple bonds and two to twelve carbon atoms, and being attached to the rest of the molecule by single bonds. The triple bond of the alkynyl group can be non-conjugated or conjugated with another unsaturated group. Suitable alkynyl groups include, but are not limited to, ethynyl, propynyl (e.g., 1-propynyl, 2-propynyl), butynyl (e.g., 1-butynyl, 2-butynyl, 3-butynyl), pentyynyl (e.g., 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl), hexynyl (e.g., 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl), methylpropynyl, 3-methyl-1-butynyl, 4-methyl-2-heptyynyl, and 4-ethyl-2-octyynyl.

[0014] “C6-C 15 "Aryl" refers to a hydrocarbon moiety having six to fifteen carbon atoms and at least one aromatic hydrocarbon structure, such as phenyl, naphthyl, or anthracene.

[0015] “C7-C 24 "Arylalkyl" refers to an aryl group that is attached to the rest of the molecule by an alkyl group, such as benzyl and phenethyl.

[0016] In each case, the group "C1-C" 12 Alkylene, C1-C 12 "alkenyl", "C1-C" 12 "Isynyne", "C6-C" 15 "Asaryl" and "C7-C" 15 "Arylalkylene" has the same properties as "C1-C12 Alkyl group, C1-C 12 "Alkenyl", "C1-C" 12 "Alkyne group", "C6-C" 15 "Aryl" and "C7-C" 24 "Arylalkyl" has the same meaning, but these groups are attached to the rest of the molecule by two single bonds. For example, where ethyl means "CH3-CH2-", ethylene means -CH2-CH2-, or where propyl means CH3-CH2-CH2-, propylene means -CH2-CH2-CH2- or -CH2-CH(CH3)-.

[0017] In this application, "C1-C" 24 "Carbonate" refers to a carbonate having formula (I), where C1-C2 is a carbonate with a carbonyl group of 1-364 ppm. 24 It refers to R attached to the acyl group 1 and R 2 Each of them, and its selection is from the following group: C1-C 12 Alkyl, C1-C 12 alkenyl, C1-C 12 alkynyl group, C6-C 15 Aryl and C7-C 24 arylalkyl; or R 1 and R 2 Together, they form a group selected from the following: C1-C 12 Alkylene, C1-C 12 alkenyl, C1-C 12 Ethyne group, C6-C 15 Aromatic and C7-C 15 Arylalkylene oxide.

[0018] Unless otherwise specified, the term "a / an" as used herein includes both the singular and the plural. Therefore, the terms "a / an" or "at least one" are used interchangeably in this application.

[0019] For the purpose of better understanding of this instruction and in no way limiting its scope, all numerical values ​​representing quantities, percentages, or proportions, as well as other numerical values ​​used in the specification and claims, unless otherwise specified, shall be understood to be modified by the term "about" in all cases. Therefore, unless indicated to the contrary, the numerical parameters listed in the following specification and appended claims are approximate values ​​that may vary depending on the desired characteristics sought to be obtained. At a minimum, each numerical parameter shall be interpreted according to the number of significant figures reported and by applying common rounding techniques. In this regard, the term "about" as used herein specifically includes ±10% of the indicated value within that range. Furthermore, the endpoints of all ranges relating to the same component or property herein include endpoints that are independently combinable and include all intermediate points and ranges. Similarly, the ranges and quantities of each element of the technology described herein may be used in conjunction with the ranges or quantities of any other element.

[0020] Methods for preparing sulfonylpyrazole

[0021] In a first aspect, this disclosure relates to a method for preparing sulfonylpyrazol, the method comprising reacting 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole with hydrogen peroxide in the presence of a metal catalyst, wherein the solvent comprises at least one C1-C 24 Carbonate and water.

[0022] This method provides an alternative to existing methods for preparing sulfonylpyrazine, and in particular, it provides a method in which the amount of organic solvent (i.e., carbonate) is lower than the amount of organic solvent when the solvent is an alcohol, nitrile, carboxylic acid ester or amide.

[0023] At least one C1-C 24 Carbonates can be compounds having formula (I).

[0024]

[0025] (I)

[0026] Where R 1 and R 2 Each of the choices is selected from the following groups: C1-C 12 Alkyl, C1-C 12 alkenyl, C1-C 12 alkynyl group, C6-C 15 Aryl and C7-C 24 arylalkyl; or

[0027] R 1 and R 2 Together, they form a group selected from the following: C1-C12 Alkylene, C1-C 12 alkenyl, C1-C 12 Ethyne group, C6-C 15 aryl and C7-C 15 Arylalkylene oxide.

[0028] At least one C1-C 24 Carbonates can be compounds having formula (I), wherein R 1 and R 2 Each of the choices is free from C1-C 12 A group composed of alkyl groups.

[0029] At least one C1-C 24 Carbonates can be compounds having formula (I), wherein R 1 and R 2 Each of the groups is selected from the group consisting of C1-C4 alkyl groups.

[0030] At least one C1-C 24 Carbonates can be compounds having formula (I), wherein R 1 and R 2 They are all methyl or ethyl.

[0031] At least one C1-C 24 Carbonates can be compounds having formula (I), wherein R 1 and R 2 Together they are -(CH2-CH2)- or -(CH(CH)3)CH2)-.

[0032] At least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, n-butyl propyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, or trimethylbenzene carbonate. At least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate. At least one C1-C 24Carbonates can be selected from the group consisting of: dimethyl carbonate, ethyl methyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate. When two or more C1-C... 24 When carbonates are combined, during the course of this method, two or more C1-C 24 The carbonate ratio can be any ratio.

[0033] At least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 Carbonate.

[0034] In one embodiment, at least one C1-C can be continuously distilled off during the reaction. 24 Carbonates, and can be added with fresh C1-C 24 Carbonate, provided that each mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole contains at least one C1-C 24 The amount of carbonate is kept within the range mentioned above.

[0035] At least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of the choices is free from C1-C 12 Compounds of formula (I) consisting of alkyl groups or wherein R 1 and R 2 Together is C1-C 12 Alkylene compounds having formula (I). At least one C1-C 24The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of the compounds selected from the group consisting of C1-C4 alkyl groups having formula (I) or wherein R 1 and R 2 Together they are C1-C4 alkylene compounds having formula (I). At least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of them is a compound of formula (I) having methyl or ethyl or wherein R 1 and R 2 Together they are compounds of formula (I) that are -(CH2-CH2)- or -(CH(CH)3)CH2)-.

[0036] At least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 carbonates, and at least one C1-C 24The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, methyl n-pentyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, ethyl pentyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, n-butyl propyl carbonate, dioctyl carbonate, diethylene carbonate, diallyl carbonate, allyl carbonate, allyl methyl carbonate, diphenyl carbonate, methyl phenyl carbonate, ethyl phenyl carbonate, phenyl propyl carbonate, tert-butyl phenyl carbonate, benzyl methyl carbonate, benzyl ethyl carbonate, benzyl vinyl carbonate, benzyl phenyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, trimethylolpropene carbonate, or vinylene carbonate. At least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, diallyl carbonate, allyl carbonate, diphenyl carbonate, methyl phenyl carbonate, ethyl phenyl carbonate, benzyl methyl carbonate, benzyl vinyl carbonate, benzyl phenyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, or vinylene carbonate. At least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate. At least one C1-C 24 The amount of carbonate can range from 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.24 carbonates, and at least one C1-C 24 Carbonates may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate.

[0037] The amount of water can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. The amount of water in the method of this invention includes water added as a solvent in the reaction vessel and water contained in the aqueous hydrogen peroxide solution.

[0038] The water volume can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and at least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 Carbonate. The water volume can range from 0.05 to 1, 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 Carbonate. The water volume can range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35 per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, or from 0.05 to 0.25 liters of C1-C 24 Carbonate.

[0039] The water volume can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of the choices is free from C1-C 12 Compounds of formula (I) consisting of alkyl groups or wherein R 1 and R 2 Together is C1-C 12 Alkylene compounds having formula (I). The water content can range from 0.05 to 1, 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of the compounds selected from the group consisting of C1-C4 alkyl groups having formula (I) or wherein R 1 and R 2 Together, they are C1-C4 alkylene compounds having formula (I). The water content can range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of them is a compound of formula (I) having methyl or ethyl or wherein R 1 and R 2 Together they are compounds of formula (I) that are -(CH2-CH2)- or -(CH(CH)3)CH2)-.

[0040] The water volume can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 carbonates, and at least one C1-C 24 Carbonates may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, methyl n-pentyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, ethyl pentyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, n-butyl propyl carbonate, dioctyl carbonate, diethylene carbonate, diallyl carbonate, allyl carbonate, allyl methyl carbonate, diphenyl carbonate, methyl phenyl carbonate, ethyl phenyl carbonate, phenyl propyl carbonate, tert-butyl phenyl carbonate, benzyl methyl carbonate, benzyl ethyl carbonate, benzyl vinyl carbonate, benzyl phenyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, trimethylolpropene carbonate, or vinylene carbonate. The water volume can range from 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24The carbonates may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, diallyl carbonate, allyl carbonate, diphenyl carbonate, methyl phenyl carbonate, ethyl phenyl carbonate, benzyl methyl carbonate, benzyl vinyl carbonate, benzyl phenyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, or vinylene carbonate. The water volume may range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate. The water volume may range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonates may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate.

[0041] At least one C1-C 24 The ratio of carbonate to water can range from 90:10 to 30:70, 80:20 to 50:50, and 75:25 to 60:40 by volume.

[0042] At least one C1-C 24 The ratio of carbonate to water can range from 90:10 to 30:70, 80:20 to 50:50, or 75:25 to 60:40 by volume, and the water volume can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and at least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 Carbonate. At least one C1-C 24 The ratio of carbonate to water can range from 80:20 to 50:50, or 75:25 to 60:40 by volume, and the water volume can range from 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 Carbonate. At least one C1-C 24 The ratio of carbonate to water can range from 75:25 to 60:40 by volume, and the amount of water can range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 Carbonate.

[0043] At least one C1-C 24The ratio of carbonate to water can range from 90:10 to 30:70, 80:20 to 50:50, or 75:25 to 60:40 by volume, and the water volume can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of the choices is free from C1-C 12 Compounds of formula (I) consisting of alkyl groups or wherein R 1 and R 2 Together is C1-C 12 Alkylene compounds having formula (I). At least one C1-C 24 The ratio of carbonate to water can range from 80:20 to 50:50 or 75:25 to 60:40 by volume, and the water volume can range from 0.05 to 1 or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of the compounds selected from the group consisting of C1-C4 alkyl groups having formula (I) or wherein R 1 and R 2 Together they are C1-C4 alkylene compounds having formula (I). At least one C1-C 24The ratio of carbonate to water can range from 75:25 to 60:40 by volume, and the amount of water can range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonate can be one of the R 1 and R 2 Each of them is a compound of formula (I) having methyl or ethyl or wherein R 1 and R 2 Together they are compounds of formula (I) that are -(CH2-CH2)- or -(CH(CH)3)CH2)-.

[0044] At least one C1-C 24 The ratio of carbonate to water can range from 90:10 to 30:70, 80:20 to 50:50, or 75:25 to 60:40 by volume, and the water volume can range from 0.01 to 1, 0.05 to 1, or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 1.25, 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole per mole of C1-C 24 carbonates, and at least one C1-C 24The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, methyl n-pentyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, ethyl pentyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, n-butyl propyl carbonate, dioctyl carbonate, diethylene carbonate, diallyl carbonate, allyl carbonate, allyl methyl carbonate, diphenyl carbonate, methyl phenyl carbonate, ethyl phenyl carbonate, phenyl propyl carbonate, tert-butyl phenyl carbonate, benzyl methyl carbonate, benzyl ethyl carbonate, benzyl vinyl carbonate, benzyl phenyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, trimethylolpropene carbonate, or vinylene carbonate. At least one C1-C 24 The ratio of carbonate to water can range from 80:20 to 50:50 or 75:25 to 60:40 by volume, and the water volume can range from 0.05 to 1 or 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.75, 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, tert-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, diallyl carbonate, allyl carbonate, diphenyl carbonate, methyl phenyl carbonate, ethyl phenyl carbonate, benzyl methyl carbonate, benzyl vinyl carbonate, benzyl phenyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, trans-2,3-butylene carbonate, or vinylene carbonate. At least one C1-C 24 The ratio of carbonate to water can range from 75:25 to 60:40 by volume, and the amount of water can range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24The amount of carbonate can range from 0.05 to 0.35, or 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 The carbonate may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate. At least one C1-C 24 The ratio of carbonate to water can range from 75:25 to 60:40 by volume, and the amount of water can range from 0.1 to 0.8 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, with at least one C1-C 24 The amount of carbonate can range from 0.05 to 0.25 liters of C1-C per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonates, and at least one C1-C 24 Carbonates may be selected from the group consisting of: dimethyl carbonate, methyl ethyl carbonate, methyl propyl carbonate, n-butyl methyl carbonate, diethyl carbonate, ethyl propyl carbonate, n-butyl ethyl carbonate, tert-butyl ethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dibutyl carbonate, ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, or trans-2,3-butylene carbonate.

[0045] The hydrogen peroxide in the method of the present invention can be an aqueous solution of 10 to 70 wt%, 20% to 65%, or 25% to 60%.

[0046] The amount of hydrogen peroxide can range from 2 to 8, 2 to 6, or 2 to 3 moles per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

[0047] The amount of hydrogen peroxide can range from 2 to 8, 2 to 6, or 2 to 3 moles of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the hydrogen peroxide can be 10 to 70 wt%, 20% to 65%, or 25% to 60% aqueous solution of hydrogen peroxide. The amount of hydrogen peroxide can range from 2 to 6, or 2 to 3 moles of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the hydrogen peroxide can be 20% to 65% or 25% to 60% aqueous solution of hydrogen peroxide. The amount of hydrogen peroxide can range from 2 to 3 moles per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the hydrogen peroxide can be a 25% to 60% aqueous solution of hydrogen peroxide.

[0048] The metal catalyst can be selected from Groups 5 to 10 and 5 to 6 of the periodic table, and is selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. Tungsten catalysts can be selected from the following group: tungstic acid, tungstates, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten bromide, tungsten sulfide, phosphotungstic acid or its salts, silicotungstic acid or its salts, or mixtures thereof. Tungsten catalysts can also be selected from the following group: tungstic acid, alkali metal or alkaline earth metal salts of tungstic acid, metallic tungsten, tungsten oxide, tungsten carbide, or mixtures thereof. Molybdenum catalysts can be selected from the following group: molybdic acid, molybdates, metallic molybdenum, molybdenum oxide, molybdenum carbide, molybdenum chloride, or mixtures thereof. Niobium catalysts can be selected from the following group: niobic acid, niobate, metallic niobium, niobium oxide, niobium carbide, niobium chloride, or mixtures thereof. The metal catalyst can be sodium tungstate dihydrate or ammonium molybdate tetrahydrate.

[0049] The amount of metal catalyst can range from 0.001 to 0.1, 0.01 to 0.1, or 0.03 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

[0050] The amount of metal catalyst can range from 0.001 to 0.1, 0.01 to 0.1, or 0.03 to 0.07 moles of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the metal catalyst can be selected from Groups 5 to 10 and 5 to 6 of the periodic table, and is selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. The amount of metal catalyst can range from 0.03 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the metal catalyst can be selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. The amount of metal catalyst can range from 0.03 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the metal catalyst can be a tungsten catalyst selected from the group consisting of tungstic acid, tungstates, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten bromide, tungsten sulfide, phosphotungstic acid or its salts, silicotungstic acid or its salts, or mixtures thereof. The amount of metal catalyst can range from 0.03 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the metal catalyst can be sodium tungstate dihydrate or ammonium molybdate tetrahydrate.

[0051] The reaction temperature range in the method of the present invention can be 30°C to 120°C, 40°C to 100°C, or 50°C to 95°C.

[0052] The reaction in the method of the present invention can be carried out within a time range of 1 hour to 24 hours, 2 hours to 16 hours, or 3 hours to 12 hours.

[0053] The reaction in the method of the present invention can be carried out over a period of 1 to 24 hours, 2 to 16 hours, or 3 to 12 hours, and the reaction temperature can be in the range of 30°C to 120°C, 40°C to 100°C, or 50°C to 95°C. The reaction in the method of the present invention can be carried out over a period of 2 to 16 hours, or 3 to 12 hours, and the reaction temperature can be in the range of 40°C to 100°C or 50°C to 95°C. The reaction in the method of the present invention can be carried out over a period of 3 to 12 hours, and the reaction temperature can be in the range of 50°C to 95°C.

[0054] The method of the present invention may further include a phase transfer catalyst. The method of the present invention may further include a phase transfer catalyst selected from the group consisting of: tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium bisulfate, tetraoctylammonium bromide, tetraoctylammonium bromide, methyltrialkylammonium chloride (Adogen 464), tetradecyltrimethylammonium bromide, methyltrioctylammonium chloride (Aliquat 336), dialcyldimethylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, octyltrimethylammonium chloride, octyltrimethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, tetrabutylphosphonium bromide, tetraoctylphosphonium bromide, or tetraphenylphosphonium bromide.

[0055] The amount of the additional phase transfer catalyst can range from 0 to 0.1, 0.001 to 0.1, or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

[0056] The method of the present invention may further include an acid catalyst. The method of the present invention may further include an acid catalyst selected from the group consisting of: hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, methyl phosphate, ethyl phosphate, or phenyl phosphate.

[0057] The amount of the additional acid catalyst can range from 0 to 0.1, 0.001 to 0.1, or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

[0058] The amount of the additional acid catalyst may range from 0 to 0.1, 0.001 to 0.1, or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the acid catalyst may be selected from the group consisting of: hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, methyl phosphate, ethyl phosphate, or phenyl phosphate. The amount of the additional acid catalyst may range from 0.001 to 0.1, or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the acid catalyst may be selected from the group consisting of: hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, or phosphoric acid. The amount of the additional acid catalyst may range from 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the acid catalyst may be selected from the group consisting of hydrochloric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, and phosphoric acid.

[0059] The metal catalyst may be selected from Groups 5 to 10 and 5 to 6 of the periodic table, and may be selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. The amount of the additional acid catalyst may be 0 to 0.1, 0.001 to 0.1, or 0.01 to 0.07 moles per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. The acid catalyst may be selected from the group consisting of hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, methyl phosphate, ethyl phosphate, or phenyl phosphate. The metal catalyst can be selected from Groups 5 and 6 of the periodic table, and can be selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. The amount of the additional acid catalyst can range from 0.001 to 0.1, or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. The acid catalyst can be selected from the group consisting of hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and phosphoric acid.

[0060] The amount of metal catalyst can range from 0.001 to 0.1, 0.01 to 0.1, or 0.03 to 0.07 moles of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. The metal catalyst can be selected from Groups 5 to 10 and 5 to 6 of the periodic table, and can be selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. Other acid catalysts are also acceptable. The amount of the agent can range from 0 to 0.1, 0.001 to 0.1, or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the acid catalyst can be selected from the group consisting of: hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, methyl phosphate, ethyl phosphate, or phenyl phosphate. The amount of metal catalyst can range from 0.01 to 0.1 or 0.03 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. The metal catalyst can be selected from Groups 5 and 6 of the periodic table, and can be selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. The amount of acid catalyst can also range from 0.001 to 0.1 or 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. The acid catalyst can be selected from the group consisting of hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and phosphoric acid. The amount of metal catalyst can range from 0.03 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the metal catalyst can be selected from tungsten catalysts, molybdenum catalysts, and niobium catalysts. The amount of acid catalyst can range from 0.01 to 0.07 mol per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, and the acid catalyst can be selected from the group consisting of hydrochloric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, and phosphoric acid. The method of the present invention can include the following steps: i) adding 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, at least one C1-C 24 ii) Adding an aqueous solution of hydrogen peroxide; iii) Adding an aqueous solution of hydrogen peroxide; iv) Separating and purifying the obtained sulfopyrazole from the reaction mixture, provided that a metal catalyst was added in at least one of steps i) or iii).

[0061] The metal catalyst may be added to the reaction vessel before and / or after the addition of the aqueous hydrogen peroxide solution. Water may be added to the reaction vessel as a solvent before and / or after the addition of the aqueous hydrogen peroxide solution, or it may not be added to the reaction vessel. An organic solvent may be added to the reaction vessel before and / or after the addition of the aqueous hydrogen peroxide solution, or it may not be added to the reaction vessel.

[0062] Metal catalysts can be added to the reaction vessel in solid form or pre-dissolved in water or organic solvents, either in portions, in twos or severals, or in a continuous manner.

[0063] Hydrogen peroxide solution can be added all at once, in several portions, or it can be added drop by drop.

[0064] Before separating and purifying the obtained sulfonylpyrazol from the reaction mixture, any possible unreacted hydrogen peroxide can be decomposed by treating the reaction mixture with any reducing agent known to those skilled in the art (such as, for example, but not limited to, sodium sulfite).

[0065] The separation and purification of sulfonylpyrazine can be carried out by any method known to those skilled in the art, such as, but not limited to, extraction, washing, or crystallization.

[0066] A second aspect of the invention is the use of sulfonylpyrazol obtained according to the method disclosed above in the preparation of agricultural chemical compositions. Example

[0067] Dimethyl carbonate (DMC)

[0068] 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole (100 gr, 78% purity) was added to a 1-liter reactor, followed by 200 ml of dimethyl carbonate (DMC) and stirring was initiated. The mixture was heated to 55°C. The catalyst solution was prepared as follows: sodium tungstate hydrate (0.02 equivalents, 1.42 gr) was dissolved in 10 ml of water. Half of the catalyst solution (5.7 gr) was added to the reactor. Then, hydrogen peroxide (28%–30%, 4.2 equivalents, 103.36 gr) was fed to the reaction over 2 hours. A slight exothermic reaction was observed at the start of the addition, and after its decline, the temperature was raised to 90°C. After the addition of hydrogen peroxide, the other half of the catalyst solution was added. After 4 hours of re-aging, the relative HPLC area percentage of the sulfoxide impurity 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methyl sulfoxide]-4,5-dihydro-5,5-dimethylisoxazole was 0.3% (230 nm). Then, 100 mL of MeOH was added, followed by 100 mL of water. The mixture was heated to 82°C–85°C for 1 hour. The mixture was then cooled to 15°C over 2 hours.

[0069] The mixture was filtered, and the resulting crystals were washed with cold MeOH (2 × 100 ml), NaHCO3 (5%, 100 ml) and water (2 × 100 ml), and dried overnight under vacuum at 50°C to obtain sulfonylpyrazol in a yield of 90.87%.

[0070] Diethyl carbonate (DEC)

[0071] 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole (100 gr, 78% purity) was added to a 1-liter reactor, followed by 100 ml of diethyl carbonate (DEC) and stirring was initiated. The mixture was heated to 55°C. The catalyst solution was prepared as follows: sodium tungstate hydrate (0.02 equivalents, 1.42 gr) was dissolved in 10 ml of water. Half of the catalyst solution (5.7 gr) was added to the reactor. Then, hydrogen peroxide (28%–30%, 4.2 equivalents, 103.36 gr) was fed to the reaction over 2 hours. A slight exothermic reaction was observed at the start of the addition, and after its decline, the temperature was raised to 90°C. After the addition of hydrogen peroxide, the other half of the catalyst solution was added. After 6 hours of re-aging, the relative HPLC area percentage of the sulfoxide impurity 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methyl sulfoxide]-4,5-dihydro-5,5-dimethylisoxazole was 0.31% (230 nm). Then, 100 mL of MeOH was added, followed by 100 mL of water. The mixture was heated to 82°C–85°C for 1 hour. The mixture was then cooled to 15°C over 2 hours.

[0072] The mixture was filtered, and the resulting crystals were washed with cold MeOH (2 × 100 ml), NaHCO3 (5%, 100 ml) and water (2 × 100 ml), and dried overnight under vacuum at 50°C to obtain sulfonylpyrazol in a yield of 87.49%.

[0073] Propylene carbonate (PC)

[0074] 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole (100 gr, approximately 78% purity) was added to a 1-liter reactor, followed by 100 ml of propylene carbonate (PC) and stirring was initiated. The mixture was heated to 55°C. The catalyst solution was prepared as follows: sodium tungstate hydrate (0.02 equivalents, 1.42 gr) was dissolved in 10 ml of water. Half of the catalyst solution (5.7 gr) was added to the reactor. Then, hydrogen peroxide (28%–30%, 4.2 equivalents, 103.36 gr) was fed to the reaction over 2 hours. A slight exothermic reaction was observed at the start of the addition, and after its decline, the temperature was raised to 90°C. After the addition of hydrogen peroxide, the other half of the catalyst solution was added. After 4 hours of re-aging, the relative HPLC area percentage of the sulfoxide impurity 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methyl sulfoxide]-4,5-dihydro-5,5-dimethylisoxazole was 0.05% (230 nm). Then, 100 mL of MeOH was added, followed by 100 mL of water. The mixture was heated to 82°C–85°C for 1 hour. The mixture was then cooled to 15°C over 2 hours.

[0075] The mixture was filtered, and the resulting crystals were washed with cold MeOH (2 × 100 ml), NaHCO3 (5%, 100 ml) and water (2 × 100 ml), and dried overnight under vacuum at 50°C to obtain sulfonylpyrazol in a yield of 88.48%.

[0076] Ethyl carbonate (EC)

[0077] 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole (100 gr, 78% purity) was added to a 1-liter reactor, followed by 100 ml of ethylene carbonate (EC) and stirring was initiated. The mixture was heated to 55°C. The catalyst solution was prepared as follows: sodium tungstate hydrate (0.02 equivalents, 1.42 gr) was dissolved in 10 ml of water. Half of the catalyst solution (5.7 gr) was added to the reactor. Then, hydrogen peroxide (28%–30%, 4.2 equivalents, 103.36 gr) was fed to the reaction over 2 hours. A slight exothermic reaction was observed at the start of the addition, and after its decline, the temperature was raised to 90°C. After the addition of hydrogen peroxide, the other half of the catalyst solution was added. After 2 hours of re-aging, the relative HPLC area percentage of the sulfoxide impurity 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methyl sulfoxide]-4,5-dihydro-5,5-dimethylisoxazole was 0.19% (230 nm). Then, 100 mL of MeOH was added, followed by 100 mL of water. The mixture was heated to 82°C–85°C for 1 hour. The mixture was then cooled to 15°C over 2 hours.

[0078] The mixture was filtered, and the resulting crystals were washed with cold MeOH (2 × 100 ml), NaHCO3 (5%, 100 ml) and water (2 × 100 ml), and dried overnight under vacuum at 50°C to obtain sulfopyrazole in 84% yield.

[0079] Dimethyl carbonate (DMC)

[0080] 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole (200 gr, 75% purity) was added to a 1-liter reactor, followed by 100 ml of dimethyl carbonate (DMC) and stirring was initiated. The mixture was heated to 80°C. The catalyst solution was prepared as follows: sodium tungstate hydrate (0.02 equivalents, 2.8 gr) was dissolved in 10 ml of water. The catalyst solution was added to the reactor, followed by sulfuric acid (0.02 equivalents, 0.83 gr, 98%). Hydrogen peroxide (28%–30%, 4.2 equivalents, 199 gr) was then fed into the reaction over a 2-hour period. A slight exothermic reaction was observed at the start of the addition, and after its decline, the temperature was raised to 80°C–90°C. Then, after an additional 6 hours of reaction, the relative HPLC area percentage of the sulfoxide impurity 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methyl sulfoxide]-4,5-dihydro-5,5-dimethylisoxazole was 0.08% (230 nm). Then, 100 mL of water was added to the reaction mixture. The mixture was heated to 80°C for 0.5 hours. Then, the mixture was cooled to 15°C for 2 hours. The mixture was filtered, and the resulting precipitate was washed with cold MeOH (100 mL twice), NaHCO3 (5%, 100 mL), and water (100 mL twice), and dried overnight under vacuum at 50°C to obtain sulfonylpyrazol in 90% yield.

[0081] Comparative example using methanol (MeOH)

[0082] Example 2-12 from prior art document US 2023012374 was repeated under the same temperature and reaction time conditions, but with the following amounts:

[0083]

[0084] M359 is the compound 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole

[0085] M375 is a sulfoxide impurity 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methyl sulfoxide]-4,5-dihydro-5,5-dimethylisoxazole

[0086] In these Comparative Examples 1 and 2, the average values ​​of sulfoxide impurities obtained were 48.04% and 82.75%, respectively. In both Comparative Examples 1 and 2, the amount of methanol was 0.3 liters per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

[0087] As can be seen, the methanol solvent from US 2023012374 does not work effectively in carbonates with high concentrations of starting material.

Claims

1. A process for the preparation of metaflumizone, comprising reacting 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole with hydrogen peroxide in the presence of a metal catalyst selected from Groups 5 to 6 of the Periodic Table, wherein the solvent comprises at least one C1-C4 aliphatic alcohol having the formula (I) ###0001### (I) and water. 24 carbonate and water (I) wherein R 1 and each of R 2 is selected from the group consisting of C1-C4 alkyl; or R 1 and R 2 together form a group selected from C1-C4alkylene, and wherein the at least one C1-C 24 The amount of carbonic acid ester ranges from 0.05 to 0.35 liter C1-C 24 carbonic acid ester per mole of 3-[(5-difluoromethoxy-1-methyl-3- trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

2. The method of claim 1, wherein, said at least one Ci-C 24 The carbonate is dimethyl carbonate.

3. The method of claim 1, wherein, said at least one Ci-C 24 The carbonate is diethyl carbonate.

4. The method of claim 1, wherein, R 1 and R 2 together are -(CH2-CH2)- or -(CH(CH)3)CH2)-.

5. The method of claim 1, wherein, said at least one Ci-C 24 The carbonate is selected from the group consisting of dimethyl carbonate, diethyl carbonate, ethylene carbonate or propylene carbonate.

6. The method according to any one of the preceding claims, wherein, said at least one C1-C4alkyl carbonate is present in an amount ranging from 0.05 to 0.25 mole of C1-C4alkyl carbonate per mole of 3-[(5-difluoromethoxy-1-methyl-3- trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonate is present in an amount ranging from 0.05 to 0.25 mole of C1-C4alkyl carbonate per mole of 3-[(5-difluoromethoxy-1-methyl-3- trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole. 24 carbonate is present in an amount ranging from 0.05 to 0.25 mole of C1-C4alkyl carbonate per mole of 3-[(5-difluoromethoxy- 7. The method according to any one of the preceding claims, wherein, the amount of water ranges from 0.01 to 1 liter per mole of 3-[(5-difluoromethoxy-1- methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

8. The method of any of the preceding claims, wherein, the hydrogen peroxide is a 10 to 70 wt% aqueous hydrogen peroxide solution.

9. The method according to any one of the preceding claims, wherein, the metal catalyst selected from Group 5 to 6 of the Periodic Table is selected from a tungsten catalyst, a molybdenum catalyst and a niobium catalyst.

10. The method of claim 9, wherein, the metal catalyst selected from Group 5 to 6 of the Periodic Table is a tungsten catalyst.

11. The method of claim 10, wherein, the metal catalyst selected from Group 5 to 6 of the Periodic Table is selected from the group consisting of tungstic acid, a tungstate salt, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten bromide, tungsten sulfide, phosphotungstic acid or a salt thereof, silicotungstic acid or a salt thereof, or a mixture thereof.

12. The method of claim 11, wherein, the metal catalyst selected from Group 5 to 6 of the Periodic Table is sodium tungstate.

13. The method of any of the preceding claims, wherein, the temperature of the reaction is between 30 °C and 120 °C.

14. The process for preparing metaflumizone according to claim 1, comprising reacting 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5- dihydro-5,5-dimethylisoxazole with hydrogen peroxide in the presence of a metal catalyst selected from Group 5 to 6 of the Periodic Table, wherein the solvent comprises dimethyl carbonate and water, wherein the amount of dimethyl carbonate ranges from 0.05 to 0.35 liter of dimethyl carbonate per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4- yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole, wherein the amount of water ranges from 0.01 to 0.8 liter per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5- dimethylisoxazole, and wherein the metal catalyst selected from Group 5 to 6 of the Periodic Table is selected from a tungsten catalyst, a molybdenum catalyst and a niobium catalyst.

15. The method of claim 14, wherein, the amount of dimethyl carbonate ranges from 0.05 to 0.25 liter of dimethyl carbonate per mole of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4- yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole.

Images