Method for producing sulfone derivatives as herbicides

Abstract

The present invention provides an industrially preferred method for producing a sulfone derivative that is useful as an herbicide.　This method is for producing a compound of formula (2). In the method, a compound of formula (1) is reacted with an oxidizer in the presence of a metal catalyst and the presence of a carboxylic acid to produce the compound of formula (2).

Description

Technical Field

[0001] The present invention relates to a method for producing a sulfone derivative useful as a herbicide, that is, a compound of the following formula (2).

[0002]

Chemical formula

[0003] (In the formula, R

[0007] , , , , , , , , R 2 , R 3 , R 4 and R 5 are as described in this specification.)

Background Art

[0004] As disclosed in WO2002 / 062770A1 (Patent Document 1), the sulfone derivative of the above formula (2) is known to have herbicidal activity. Among them, pyroxasulfone is well known as an excellent herbicide.

[0005] As a method for producing the compound of formula (2), a method by oxidizing a sulfide derivative, that is, the compound of formula (1), is known, and this is shown below.

[0006]

Chemical formula

[0007] As shown in the figure below, in Reference Example 3 of WO2004 / 013106A1 (Patent Document 2), 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline (1-a) (ISFP) was oxidized with m-chloroperbenzoic acid (mCPBA) to produce 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazoline (2-a) (Pyroxasulfone).

[0008]

Chemical formula

[0009] In the method for producing the compound of formula (2) from the compound of formula (1), m-chloroperbenzoic acid (mCPBA) described in WO2004 / 013106A1 (Patent Document 2) is expensive for industrial use and has problems in handling and waste. Therefore, the production method described in WO2004 / 013106A1 (Patent Document 2) is not practical for production on an industrial scale.

[0010] Also, in the method for producing the compound of formula (2) (sulfone derivative: SO2 derivative) from the compound of formula (1) (sulfide derivative: S derivative), the sulfoxide derivative (SO derivative), which is an intermediate of the oxidation reaction, that is, the following formula (3):

[0011]

Chemical formula

[0012] (where R 1 , R 2 , R 3 , R 4 and R 5 are as described in this specification.) The reaction may be stopped by the presence of the compound (1). Therefore, the compound of formula (3) may remain in the product as a by-product. If the compound of formula (3) is mixed into products such as herbicides, it may lead to a decrease in quality and phytotoxicity to crops. However, since the physical and chemical properties of the compound of formula (3) are very similar to those of the compound of formula (2), it is difficult to separate the compound of formula (3) and purify the compound of formula (2). Therefore, in a method for producing the compound of formula (2) from the compound of formula (1), a method is needed in which the oxidation reaction proceeds sufficiently and the compound of formula (3) does not substantially remain in the product.

[0013] Patent Document 3 (JP2013-512201) (JP2013-512201A), Example 9C, describes a method for producing pyroxasulfone using acetic acid. However, the method described in JP2013-512201, Example 9C, has the drawback of leaving a large amount of the intermediate of formula (3) (sulfoxide derivative: SO derivative). See Reference Example 1 in this specification.

[0014] Patent document 3 (JP2013-512201) (JP2013-512201A) corresponds to patent document 4 (US2012 / 264947A1).

[0015] CN111574511A (Patent Document 5), Example 5, describes a method for producing pyroxasulfone using acetic acid. However, the method described in CN111574511A, Example 5, is not reproducible and has the disadvantage of leaving a large amount of the intermediate of formula (3) (sulfoxide derivative: SO derivative). See Reference Example 2 in this specification.

[0016] WO2021 / 002484A2 (Patent Document 6) describes a method for producing pyroxasulfone. This method is excellent as it solves the above-mentioned problems. However, the method described in WO2021 / 002484A2 still has room for improvement, such as being carried out at relatively high temperatures in general.

[0017] Furthermore, since these prior art methods sometimes involved relatively slow reaction rates, there is still room for improvement. [Prior art documents] [Patent Documents]

[0018] [Patent Document 1] International Publication No. 2002 / 062770 [Patent Document 2] International Publication No. 2004 / 013106 [Patent Document 3] Special Publication No. 2013-512201 [Patent Document 4] U.S. Patent Application Publication No. 2012 / 264947 [Patent Document 5] Chinese Patent Application Publication No. 111574511 Specification [Patent Document 6] International Publication No. 2021 / 002484 [Overview of the project] [Problems that the invention aims to solve]

[0019] The object of the present invention is to provide a method for producing a compound of formula (2) from a compound of formula (1), wherein the proportion of the compound of formula (3) in the product is sufficiently low, the yield is excellent, and the method is industrially preferable. [Means for solving the problem]

[0020] In light of the above circumstances, the inventors diligently researched methods for producing the compound of formula (2). As a result, they unexpectedly discovered that the above-mentioned problems could be solved by providing the following method for producing the compound of formula (2). Based on this finding, the inventors have completed the present invention. That is, in one aspect, the present invention is as follows.

[0021] [A-1] A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid;

[0022] [ka] (Here, R 1 , R 2 and R 3 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R 4 and R 5 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R 4 and R 5 These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents. [A-2] A method according to [A-1], wherein the reaction is carried out at 35°C or higher.

[0023] [A-3] The method according to [A-1], wherein the reaction is carried out at a temperature above 35°C.

[0024] [A-4] A method according to [A-1], wherein the reaction is carried out at a temperature of 40°C or higher.

[0025] [A-5] A method according to [A-1], wherein the reaction is carried out at 45°C or higher.

[0026] [A-6] A method according to [A-1], wherein the reaction is carried out at a temperature of 50°C or higher.

[0027] [A-7] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at 60°C or below.

[0028] [A-8] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at a temperature below 60°C.

[0029] [A-9] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at 55°C or below.

[0030] [A-10] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at a temperature below 55°C.

[0031] [A-11] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at 50°C or below.

[0032] [A-12] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at a temperature below 50°C.

[0033] [A-13] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at 45°C or below.

[0034] [A-14] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at 40°C or below.

[0035] [A-15] A method according to any one of items [A-1] to [A-6], wherein the reaction is carried out at 35°C or below.

[0036] [A-16] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 0.05 moles or more (preferably 0.1 moles or more) per mole of the compound of formula (1).

[0037] [A-17] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 0.5 moles or more (1 mole or more, 2 moles or more, or 3 moles or more) per mole of the compound of formula (1).

[0038] [A-18] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 5 moles or more per mole of the compound of formula (1).

[0039] [A-19] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 8 moles or more (or 9 moles or more) per mole of the compound of formula (1).

[0040] [A-20] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 10 moles or more (or 12 moles or more) per mole of the compound of formula (1).

[0041] [A-21] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 15 moles or more per mole of the compound of formula (1).

[0042] [A-22] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 18 moles or more (or 20 moles or more) per mole of the compound of formula (1).

[0043] [A-23] A method according to any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 26 moles or more (preferably 28 moles or more, more preferably 30 moles or more) per mole of the compound of formula (1).

[0044] [A-24] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 32 moles or more per mole of the compound of formula (1).

[0045] [A-25] A method according to any one of items [A-1] to [A-15], wherein the amount of carboxylic acid is 35 moles or more per mole of the compound of formula (1).

[0046] [A-26] A method according to any one of items [A-1] to [A-25], wherein the amount of carboxylic acid is 90 moles or less (preferably 70 moles or less) per mole of the compound of formula (1).

[0047] [A-27] A method according to any one of items [A-1] to [A-25], wherein the amount of carboxylic acid is 55 moles or less per mole of the compound of formula (1).

[0048] [A-28] A method according to any one of items [A-1] to [A-25], wherein the amount of carboxylic acid is 10 moles or less (or 9 moles or less) per mole of the compound of formula (1).

[0049] [A-29] A method according to any one of items [A-1] to [A-25], wherein the amount of carboxylic acid is 5 moles or less per mole of the compound of formula (1).

[0050] [A-30] A method according to any one of items [A-1] to [A-29], wherein the amount of carboxylic acid is 0.3 liters or more (preferably 0.5 liters or more) per mole of the compound of formula (1).

[0051] [A-31] A method according to any one of items [A-1] to [A-29], wherein the amount of carboxylic acid is 0.8 liters or more (preferably 1.0 liter or more) per mole of the compound of formula (1).

[0052] [A-32] A method according to any one of items [A-1] to [A-29], wherein the amount of carboxylic acid is 1.2 liters or more (preferably 1.5 liters or more) per mole of the compound of formula (1).

[0053] [A-33] A method according to any one of items [A-1] to [A-29], wherein the amount of carboxylic acid is 1.8 liters or more (preferably 2.0 liters or more) per mole of the compound of formula (1).

[0054] [A-34] A method according to any one of items [A-1] to [A-33], wherein the amount of carboxylic acid is 5 liters or less (preferably 3 liters or less) per mole of the compound of formula (1).

[0055] [A-35] A method according to any one of items [A-1] to [A-33], wherein the amount of carboxylic acid is 2.0 liters or less (preferably 1.0 liter or less) per mole of the compound of formula (1).

[0056] [A-36] A method according to any one of items [A-1] to [A-33], wherein the amount of carboxylic acid is 0.9 liters or less (preferably 0.8 liters or less) per mole of the compound of formula (1). [A-37] A method according to any one of items [A-1] to [A-33], wherein the amount of carboxylic acid is 0.5 liters or less (0.3 liters or less, or 0.2 liters or less) per mole of the compound of formula (1).

[0057] [A-38] A method according to any one of items [A-1] to [A-37], wherein the reaction is carried out in the absence of an organic solvent.

[0058] [A-39] A method according to any one of items [A-1] to [A-37], wherein the reaction is carried out in the presence or absence of an organic solvent.

[0059] [A-40] A method according to any one of items [A-1] to [A-37], wherein the reaction is carried out in the presence of an organic solvent.

[0060] [A-41] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent having 5 to 45 acceptors.

[0061] [A-42] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent having 7 to 42 acceptors.

[0062] [A-43] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent having a relative permittivity of 1 to 45.

[0063] [A-44] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent having a relative permittivity of 4 to 40.

[0064] [A-45] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent having a Rohrschneider polarity parameter of 1 to 7 (preferably 3 to 6).

[0065] [A-46] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent other than a carboxylic acid.

[0066] [A-47] A method according to [A-39] or [A-40], wherein the organic solvent is an organic solvent other than the carboxylic acid of formula (a);

[0067] [ka] (Here, A is as described herein.)

[0068] [A-48] A method according to [A-39] or [A-40], wherein the organic solvent is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, and sulfones.

[0069] [A-49] A method according to [A-39] or [A-40], wherein the organic solvent is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and amides.

[0070] [A-50] A method according to [A-39] or [A-40], wherein the organic solvent is selected from benzene which may be substituted with 1 to 3 (preferably 1 or 2) substituents selected from (C1-C4) alkyl and chlorine atoms, (C1-C4) alkanes which may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms), (C1-C6) alcohols, (C2-C5) alkanenitriles, (C1-C4) alkyl(C2-C6) carboxylates, and N,N-di((C1-C4)alkyl)(C1-C4) alkaneamides.

[0071] [A-51] A method according to [A-39] or [A-40], wherein the organic solvent is selected from toluene, xylene, chlorobenzene, dichlorolonzene, dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol and its isomers, cyclohexanol, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers, hexyl acetate and its isomers, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and N,N-diethylacetamide.

[0072] [A-52] A method according to [A-39] or [A-40], wherein the organic solvent is selected from toluene, xylene, chlorobenzene, dichlorolonzene, dichloromethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, sec-amyl alcohol, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and N,N-diethylacetamide.

[0073] [A-53] A method according to [A-39] or [A-40], wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and amides.

[0074] [A-54] A method according to [A-39] or [A-40], wherein the organic solvent is selected from (C1-C4)alkanes, (C1-C6)alcohols, (C2-C5)alkanenitriles, (C1-C4)alkyl(C2-C6)carboxylates, and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, which may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms).

[0075] [A-55] The method according to [A-39] or [A-40], wherein the organic solvent is dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol and its isomers, cyclohexanol, acetonitrile, A method selected from methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and N,N-diethylacetamide.

[0076] [A-56] A method according to [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, sec-amyl alcohol, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and N,N-diethylacetamide.

[0077] [A-57] A method according to [A-39] or [A-40], wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, and nitriles.

[0078] [A-58] A method according to [A-39] or [A-40], wherein the organic solvent is selected from (C1-C4) alkanes, (C1-C6) alcohols, and (C2-C5) alkanenitriles, which may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms).

[0079] [A-59] A method according to [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, 1,2-dichloroethane, chloroform, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol and its isomers, cyclohexanol, and acetonitrile.

[0080] [A-60] A method according to [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, sec-amyl alcohol, and acetonitrile.

[0081] [A-61] A method according to [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, methanol, and acetonitrile.

[0082] [A-62] A method according to [A-39] or [A-40], wherein the organic solvent is dichloromethane. [A-63] A method according to either item [A-39] or [A-40], wherein the organic solvent is a (C1-C6) alcohol.

[0083] [A-64] A method according to [A-39] or [A-40], wherein the organic solvent is selected from methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, and tert-amyl alcohol.

[0084] [A-65] A method according to [A-39] or [A-40], wherein the organic solvent is methanol.

[0085] [A-66] A method according to [A-39] or [A-40], wherein the organic solvent is acetonitrile. [A-67] A method according to any one of [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, and the solvent comprises a carboxylic acid. [A-68] A method according to any one of items [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, and a carboxylic acid is used as the solvent.

[0086] [A-69] A method according to any one of items [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, and the solvent is a mixed solvent of a carboxylic acid and an organic solvent other than a carboxylic acid. [A-70] A method according to any one of the items [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, and the solvent used is a mixed solvent of a carboxylic acid and an organic solvent other than a carboxylic acid.

[0087] [A-71] A method according to any one of items [A-1] to [A-70], wherein the amount of organic solvent is 0.1 liters or more (preferably 0.2 liters or more) per mole of the compound of formula (1).

[0088] [A-72] A method according to any one of items [A-1] to [A-70], wherein the amount of organic solvent is 0.3 liters or more per mole of the compound of formula (1).

[0089] [A-73] A method according to any one of items [A-1] to [A-70], wherein the amount of organic solvent is 0.5 liters or more per mole of the compound of formula (1).

[0090] [A-74] A method according to any one of items [A-1] to [A-70], wherein the amount of organic solvent is 0.8 liters or more per mole of the compound of formula (1).

[0091] [A-75] A method according to any one of items [A-1] to [A-74], wherein the amount of organic solvent is 3 liters or less per mole of the compound of formula (1).

[0092] [A-76] A method according to any one of items [A-1] to [A-74], wherein the amount of organic solvent is 2 liters or less per mole of the compound of formula (1).

[0093] [A-77] A method according to any one of items [A-1] to [A-74], wherein the amount of organic solvent is 1 liter or less per mole of the compound of formula (1).

[0094] [A-78] A method according to any one of items [A-1] to [A-37], wherein the reaction is carried out in the presence of a solvent, and the solvent is a carboxylic acid.

[0095] [A-79] A method according to any one of items [A-1] to [A-78], wherein the reaction is carried out in the presence of a solvent, and the solvent includes water.

[0096] [A-80] A method according to any one of items [A-1] to [A-78], wherein the reaction is carried out in the presence of an aqueous solvent. [A-81] A method according to either item [A-79] or [A-80], wherein the amount of aqueous solvent is greater than 0 liters per mole of the compound of formula (1). [A-82] A method according to either item [A-79] or [A-80], wherein the amount of aqueous solvent is 0.1 liters or more per mole of the compound of formula (1). [A-83] A method according to either item [A-79] or [A-80], wherein the amount of aqueous solvent is 0.18 liters or more per mole of the compound of formula (1). [A-84] A method according to either item [A-79] or [A-80], wherein the amount of aqueous solvent is 0.5 liters or less per mole of the compound of formula (1). [A-85] A method according to either item [A-79] or [A-80], wherein the amount of aqueous solvent is 0.3 liters or less per mole of the compound of formula (1). [A-86] A method according to either item [A-79] or [A-80], wherein the amount of aqueous solvent is 0.25 liters or less per mole of the compound of formula (1).

[0097] [A-87] A method according to any one of [A-1] to [A-86], wherein the carboxylic acid is the carboxylic acid of formula (a);

[0098] [ka] (Here, A is hydrogen, an optionally substituted (C1-C6) alkyl group; an optionally substituted (C3-C6) cycloalkyl group; an optionally substituted (C2-C6) alkenyl group; or an optionally substituted (C2-C6) alkynyl group.) [A-88] A method according to [A-87], wherein A is an alkyl (C1-C4) which may be substituted with one or more substituents. [A-89] A method according to [A-87], wherein A is an alkyl (C1-C4) which may be substituted with 1 to 9 halogen atoms. [A-90] A method according to [A-87], wherein A is an alkyl group which may be substituted with 1 to 9 fluorine atoms or chlorine atoms (C1-C4). [A-91] A method according to [A-87], wherein A is an alkyl group which may be substituted with 1 to 9 fluorine atoms. [A-92] A method according to [A-87], wherein A is an alkyl (C1-C4) which may be substituted with 1 to 9 chlorine atoms. A method according to [A-93] [A-87], wherein A is (C1-C4)alkyl.

[0099] [A-94] A method according to any one of [A-1] to [A-86], wherein the carboxylic acid is selected from acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid.

[0100] [A-95] A method according to any one of [A-1] to [A-86], wherein the carboxylic acid is selected from difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid.

[0101] [A-96] A method according to any one of [A-1] to [A-86], wherein the carboxylic acid is selected from acetic acid, dichloroacetic acid, and trichloroacetic acid.

[0102] [A-97] A method according to any one of items [A-1] to [A-86], wherein the carboxylic acid is acetic acid.

[0103] [A-98] A method according to any one of [A-1] to [A-86], wherein the carboxylic acid is selected from dichloroacetic acid and trichloroacetic acid.

[0104] [A-99] A method according to any one of items [A-1] to [A-86], wherein the carboxylic acid is dichloroacetic acid.

[0105] [A-100] A method according to any one of items [A-1] to [A-86], wherein the carboxylic acid is trichloroacetic acid.

[0106] [A-101] A method according to any one of items [A-1] to [A-100], wherein the metal of the metal catalyst is a transition metal.

[0107] [A-102] A method according to any one of [A-1] to [A-100], wherein the metal of the metal catalyst is selected from Group 5 and Group 6 of the periodic table.

[0108] [A-103] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is selected from a tungsten catalyst and a molybdenum catalyst.

[0109] [A-104] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is a tungsten catalyst.

[0110] [A-105] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is a molybdenum catalyst.

[0111] [A-106] A method according to any one of [A-1] to [A-100], wherein the metal catalyst is selected from tungstic acid, tungstate, molybdic acid, and molybdate.

[0112] [A-107] A method according to any one of [A-1] to [A-100], wherein the metal catalyst is selected from tungstic acid, alkali metal tungstate salts, ammonium tungstate salts, molybdic acid, alkali metal molybdate salts, and ammonium molybdate salts.

[0113] [A-108] A method according to any one of [A-1] to [A-100], wherein the metal catalyst is selected from sodium tungstate and ammonium molybdate.

[0114] [A-109] A method according to any one of [A-1] to [A-100], wherein the metal catalyst is an alkali metal tungstate (preferably sodium tungstate).

[0115] [A-110] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is ammonium molybdate.

[0116] [A-111] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is selected from sodium tungstate dihydrate and ammonium molybdate tetrahydrate salt.

[0117] [A-112] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is sodium tungstate dihydrate.

[0118] [A-113] A method according to any one of items [A-1] to [A-100], wherein the metal catalyst is ammonium molybdate tetrahydrate salt.

[0119] [A-114] A method according to any one of items [A-1] to [A-113], wherein the oxidizing agent is hydrogen peroxide.

[0120] [A-115] A method according to any one of items [A-1] to [A-113], wherein the hydrogen peroxide is a 10-70 wt% aqueous solution of hydrogen peroxide.

[0121] [A-116] A method according to any one of items [A-1] to [A-113], wherein the method is an aqueous solution of 20 to 65 wt% hydrogen peroxide.

[0122] [A-117] A method according to any one of items [A-1] to [A-113], wherein the solution is a 25-65 wt% aqueous solution of hydrogen peroxide.

[0123] [A-118] A method according to any one of items [A-1] to [A-117], wherein the reaction is carried out in the presence or absence of an acid catalyst.

[0124] [A-119] A method according to any one of items [A-1] to [A-118], wherein the reaction is carried out in the presence of an acid catalyst, and the acid catalyst is sulfuric acid.

[0125] [A-120] The method described in any one of the items [A-1] to [A-119], R 1 is (C1-C4) alkyl, R 2 is a (C1-C4) perfluoroalkyl group, R 3(C1-C4) alkyl which may be substituted with 1 to 9 fluorine atoms, R 4 and R 5 However, each is independently a (C1-C4) alkyl group.

[0126] [A-121] The method described in any one of items [A-1] to [A-119], R 1 It is methyl, R 2 It is trifluoromethyl, R 3 It is difluoromethyl, R 4 and R 5 A method in which it is methyl.

[0127] In another embodiment, the present invention is as follows:

[0128] [B-1] A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid, Here, the reaction is carried out at temperatures above 35°C;

[0129] [ka] (Here, R 1 , R 2 and R 3 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R 4 and R 5Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R 4 and R 5 These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

[0130] [B-2] A method according to [B-1], wherein the reaction is carried out at a temperature of 40°C or higher.

[0131] [B-3] A method according to [B-1], wherein the reaction is carried out at 45°C or higher.

[0132] [B-4] A method according to any one of items [B-1] to [B-3], wherein the reaction is carried out at a temperature of 60°C or lower.

[0133] [B-5] A method according to any one of the items [B-1] to [B-3], wherein the reaction is carried out at a temperature of 55°C or lower.

[0134] [B-6] A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid, A method in which the amount of carboxylic acid is 18 moles or more per mole of the compound of formula (1);

[0135] [ka] (Here, R 1 , R 2 and R 3Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R 4 and R 5 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R 4 and R 5 These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

[0136] [B-7] A method according to [B-6], wherein the amount of carboxylic acid is 30 moles or more per mole of the compound of formula (1).

[0137] [B-8] A method according to [B-6], wherein the amount of carboxylic acid is 35 moles or more per mole of the compound of formula (1).

[0138] [B-9] A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid, Here, the reaction is carried out in the presence of an organic solvent other than the carboxylic acid;

[0139] [ka] (Here, R 1 , R 2 and R 3 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R 4 and R 5 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R 4 and R 5 These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

[0140] [B-10] A method according to [B-9], wherein the organic solvent is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and amides.

[0141] [B-11] A method according to [B-9], wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, and nitriles.

[0142] [B-12] A method according to [B-9], wherein the organic solvent is selected from (C1-C4) alkanes, (C1-C6) alcohols, and (C2-C5) alkanenitriles, which may be substituted with 1 to 10 halogen atoms.

[0143] [B-13] The method according to [B-9], wherein the organic solvent is selected from dichloromethane, methanol, and acetonitrile.

[0144] [B-14] A method according to any one of [B-1] to [B-13], wherein the carboxylic acid is the carboxylic acid of formula (a);

[0145] [ka] (Here, A is hydrogen, an optionally substituted (C1-C6) alkyl group; an optionally substituted (C3-C6) cycloalkyl group; an optionally substituted (C2-C6) alkenyl group; or an optionally substituted (C2-C6) alkynyl group.)

[0146] [B-15] A method according to any one of items [B-1] to [B-13], wherein the carboxylic acid is acetic acid.

[0147] [B-16] A method according to any one of items [B-1] to [B-13], wherein the carboxylic acid is dichloroacetic acid.

[0148] [B-17] A method according to any one of items [B-1] to [B-13], wherein the carboxylic acid is trichloroacetic acid.

[0149] [B-18] A method according to any one of items [B-1] to [B-17], wherein the metal catalyst is selected from a tungsten catalyst and a molybdenum catalyst.

[0150] [B-19] A method according to any one of items [B-1] to [B-17], wherein the metal catalyst is a tungsten catalyst.

[0151] [B-20] A method according to any one of items [B-1] to [B-17], wherein the metal catalyst is a molybdenum catalyst.

[0152] [B-21] A method according to any one of items [B-1] to [B-20], wherein the oxidizing agent is hydrogen peroxide.

[0153] [B-22] The method described in any one of the items [B-1] to [B-21], R 1 is (C1-C4) alkyl, R 2 is a (C1-C4) perfluoroalkyl group, R 3 (C1-C4) alkyl which may be substituted with 1 to 9 fluorine atoms, R 4 and R 5 However, each is independently a (C1-C4) alkyl group.

[0154] [B-23] The method described in any one of the items [B-1] to [B-21], R 1 It is methyl, R 2 It is trifluoromethyl, R 3 It is difluoromethyl, R 4 and R 5 A method in which it is methyl.

[0155] In yet another embodiment, the present invention is as follows:

[0156] [C-1] A method for producing the compound of formula (2), wherein the compound of formula (1) is reacted with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid to produce the compound of formula (2);

[0157] [ka] (Here, R 1 , R2 and R 3 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R 4 and R 5 Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R 4 and R 5 These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

[0158] [C-2] A method according to [C-1], wherein the reaction is carried out at a temperature above 35°C.

[0159] [C-3] A method according to [C-1], wherein the reaction is carried out at a temperature of 40°C or higher.

[0160] [C-4] A method according to [C-1], wherein the reaction is carried out at 45°C or higher.

[0161] [C-5] A method according to any one of items [C-1] to [C-4], wherein the amount of carboxylic acid used is more than 26 moles per mole of the compound of formula (1).

[0162] [C-6] A method according to any one of items [C-1] to [C-4], wherein the amount of carboxylic acid used is 30 moles or more per mole of the compound of formula (1).

[0163] [C-7] A method according to any one of items [C-1] to [C-4], wherein the amount of carboxylic acid used is 35 moles or more per mole of the compound of formula (1).

[0164] [C-8] A method according to any one of [C-1] to [C-7], wherein the carboxylic acid is the carboxylic acid of formula (a);

[0165] [ka] (Here, A is hydrogen, an optionally substituted (C1-C6) alkyl; an optionally substituted (C3-C6) cycloalkyl; an optionally substituted (C2-C6) alkenyl; or an optionally substituted (C2-C6) alkynyl.)

[0166] A method according to [C-9] and [C-8], wherein A is an optionally substituted (C1-C4) alkyl.

[0167] [C-10] A method according to any one of items [C-1] to [C-7], wherein the carboxylic acid is acetic acid.

[0168] [C-11] A method according to any one of items [C-1] to [C-10], wherein the metal catalyst is a tungsten catalyst or a molybdenum catalyst.

[0169] [C-12] A method according to any one of items [C-1] to [C-10], wherein the metal catalyst is a tungsten catalyst.

[0170] [C-13] A method according to any one of items [C-1] to [C-10], wherein the metal catalyst is a molybdenum catalyst.

[0171] [C-14] A method according to any one of items [C-1] to [C-13], wherein the oxidizing agent is hydrogen peroxide.

[0172] [C-15] A method described in any one of the items [C-1] to [C-14], R 1 is (C1-C4) alkyl, R 2 is a (C1-C4) perfluoroalkyl group, R 3 (C1-C4) alkyl which may be substituted with 1 to 9 fluorine atoms, R 4 and R 5 However, each is independently a (C1-C4) alkyl group.

[0173] [C-16] A method described in any one of the items [C-1] to [C-14], R 1 It is methyl, R 2 It is trifluoromethyl, R 3 It is difluoromethyl, R 4 and R 5 A method in which it is methyl. [Effects of the Invention]

[0174] The present invention provides a method for producing a compound of formula (2) (sulfone derivative: SO2 derivative) from a compound of formula (1) (sulfide derivative: S derivative), wherein the proportion of compound of formula (3) (sulfoxide derivative: SO derivative) in the product is sufficiently low, and the industrially preferred production method is provided.

[0175] The compound of formula (2) produced by the method of the present invention is substantially free of the compound of formula (3), which may cause a decrease in herbicide quality and phytotoxicity to crops, and is therefore useful as a herbicide. [Modes for carrying out the invention]

[0176] The present invention will be described in detail below.

[0177] This section explains the symbols and terms used in this specification.

[0178] In this specification, the following abbreviations and prefixes may be used, and their meanings are as follows: Me: Methyl Et: Ethyl Pr, n-Pr, and Pr-n:propyl (i.e., n-propyl) i-Pr and Pr-i: Isopropyl Bu, n-Bu, and Bu-n:butyl (i.e., n-butyl) s-Bu and Bu-s:sec-butyl (i.e., secondary butyl) i-Bu and Bu-i: Isobutyl t-Bu and But-t:tert-butyl (i.e., tertiary butyl) Ph: Phenyl n-: normal s- and sec-: Secondary i- and iso-: iso t- and tert-: tertiary c- and cyc-: cyclo o-: Ortho m-: meta p-:para

[0179] The term "nitro" refers to the substituent "-NO2". The terms "cyano" or "nitrile" refer to the substituent "-CN". The term "hydroxy" refers to the substituent "-OH". The term "amino" refers to the substituent "-NH2".

[0180] (Ca-Cb) means that the number of carbon atoms is between a and b. For example, in "(C1-C4)alkyl," "(C1-C4)" means that the alkyl group has 1 to 4 carbon atoms.

[0181] In this specification, general terms such as “alkyl” are interpreted to include both straight-chain and branched-chain compounds such as butyl and tert-butyl. On the other hand, the specific term “butyl” refers to straight-chain “n-butyl” and not branched-chain “tert-butyl.” Branched-chain isomers such as “tert-butyl” are specifically referred to where intended.

[0182] Examples of halogen atoms include fluorine, chlorine, bromine, and iodine atoms.

[0183] (C1-C6) alkyl refers to a linear or branched alkyl group having 1 to 6 carbon atoms. Examples of (C1-C6) alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, and hexyl.

[0184] (C1-C4) alkyl refers to a linear or branched alkyl group having 1 to 4 carbon atoms. Examples of (C1-C4) alkyl include appropriate examples from the (C1-C6) alkyl examples above.

[0185] (C3-C6) cycloalkyl refers to a cycloalkyl group having 3 to 6 carbon atoms. Examples of (C3-C6) cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0186] (C2-C6) alkenyls refer to straight-chain or branched-chain alkenyls having 2 to 6 carbon atoms. Examples of (C2-C6) alkenyls include, but are not limited to, vinyl, 1-propenyl, isopropenyl, 2-propenyl, 1-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl, 1-pentenyl, and 1-hexenyl.

[0187] (C2-C6) alkynyl refers to a linear or branched alkynyl having 2 to 6 carbon atoms. Examples of (C2-C6) alkynyl include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, 1-pentynyl, and 1-hexynyl.

[0188] Examples of (C6-C10)aryl compounds are phenyl, 1-naphthyl, and 2-naphthyl.

[0189] (C1-C6) haloalkyl refers to a linear or branched alkyl group with 1 to 6 carbon atoms, substituted with 1 to 13 identical or different halogen atoms (where halogen atoms have the same meaning as defined above). Examples of (C1-C6) haloalkyls include fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, chlorodifluoromethyl, bromodifluoromethyl, 2-fluoroethyl, 1-chloroethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 3-chloropropyl, 2-chloro-1-methylethyl, 2,2,3,3,3-pentafluoropropyl, and 2,2,2-trifluoro-1 This includes, but is not limited to, trifluoromethylethyl, heptafluoropropyl, 1,2,2,2-tetrafluoro-1-trifluoromethylethyl, 4-fluorobutyl, 4-chlorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, nonafluorobutyl, 1,1,2,3,3,3-hexafluoro-2-trifluoromethylpropyl, 2,2,2-trifluoro-1,1-di(trifluoromethyl)ethyl, undecafluoropentyl, tridecafluorohexyl, etc.

[0190] (C1-C4) perfluoroalkyl refers to a linear or branched alkyl group having 1 to 4 carbon atoms, in which all hydrogen atoms are replaced by fluorine atoms. Examples of (C1-C4) perfluoroalkyls include trifluoromethyl (i.e., -CF3), pentafluoroethyl (i.e., -CF2CF3), heptafluoropropyl (i.e., -CF2CF2CF3), 1,2,2,2-tetrafluoro-1-trifluoromethylethyl (i.e., -CF(CF3)2), nonafluorobutyl (i.e., -CF2CF2CF2CF3), 1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl (i.e., -CF(CF3)CF2CF3), 1,1,2,3,3,3-hexafluoro-2-trifluoromethylpropyl (i.e., -CF2CF(CF3)2), and 2,2,2-trifluoro-1,1-di(trifluoromethyl)ethyl (i.e., -C(CF3)3).

[0191] Examples of (C1-C4) alkyl groups that may be substituted with 1 to 9 fluorine atoms include, but are not limited to, fluoromethyl (i.e., -CH2F), difluoromethyl (i.e., -CHF2), trifluoromethyl (i.e., -CF3), 2-fluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 2,2,3,3,3-pentafluoropropyl, 2,2,2-trifluoro-1-trifluoromethylethyl, heptafluoropropyl, 1,2,2,2-tetrafluoro-1-trifluoromethylethyl, 4-fluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, nonafluorobutyl, 1,1,2,3,3,3-hexafluoro-2-trifluoromethylpropyl, and 2,2,2-trifluoro-1,1-di(trifluoromethyl)ethyl.

[0192] (C1-C6)alkoxy means (C1-C6)alkyl-O- (where the (C1-C6)alkyl portion has the same meaning as defined above). Examples of (C1-C6)alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, etc.

[0193] A cyclic hydrocarbon group refers to a monocyclic or polycyclic cyclic group in which all atoms constituting the ring are carbon atoms. In one embodiment, examples of cyclic hydrocarbon groups include, but are not limited to, aromatic or non-aromatic, monocyclic, bicyclic, or tricyclic cyclic hydrocarbon groups with 3 to 14 members (preferably 5 to 14 members, more preferably 5 to 10 members). In another embodiment, examples of cyclic hydrocarbon groups include, but are not limited to, aromatic or non-aromatic, monocyclic or bicyclic (preferably monocyclic) cyclic hydrocarbon groups with 4 to 8 members (preferably 5 to 6 members). Examples of cyclic hydrocarbon groups include, but are not limited to, cycloalkyl and aryl groups. Examples of cycloalkyl include the (C3-C6) cycloalkyl examples above. Aryl is an aromatic cyclic group among the cyclic hydrocarbon groups as defined above. Examples of aryl include the (C6-C10) aryl examples above. The cyclic hydrocarbon groups defined or exemplified above may, if possible, include non-condensed cyclic (e.g., monocyclic or spirocyclic) and condensed cyclic groups. The cyclic hydrocarbon groups defined or exemplified above may, if possible, be unsaturated, partially saturated, or saturated. The cyclic hydrocarbon groups defined or exemplified above are also called carbocyclic groups. A carbocyclic ring is a ring corresponding to the cyclic hydrocarbon group defined or exemplified above. Examples of carbocyclic rings include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cyclopentene, and cyclohexene. Examples of 3- to 12-membered carbocyclic rings are as described above.

[0194] In this specification, the term "substituents" in "may be substituted" is not particularly limited, as long as they are chemically acceptable and exhibit the effects of the present invention.

[0195] In this specification, examples of “substituents” with respect to the term “may be substituted” include, but are not limited to, one or more substituents (preferably 1 to 4 substituents) independently selected from substituent group (I).

[0196] The substituent group (I) consists of halogen atoms; nitro groups; cyano groups; hydroxyl groups; amino groups; (C1-C6) alkyl; (C1-C6) haloalkyl; (C3-C6) cycloalkyl; (C2-C6) alkenyl; (C2-C6) alkynyl; (C1-C6) alkoxy; phenyl; and phenoxy, preferably consisting of halogen atoms; nitro groups; cyano groups; hydroxyl groups; amino groups; and (C1-C4) alkyl, and more preferably consisting of halogen atoms; hydroxyl groups; and (C1-C4) alkyl. Even more preferably consisting of halogen atoms and (C1-C4) alkyl.

[0197] In this specification, the terms “as described herein” and similar terms are incorporated by reference to all applicable definitions and, if any, all applicable examples, preferred examples, more preferred examples, even more preferred examples, and particularly preferred examples.

[0198] In this specification, compounds having isomers include all isomers and any mixtures thereof in any proportion. For example, xylene includes o-xylene, m-xylene, p-xylene and any mixtures thereof in any proportion. For example, dichlorobenzene includes o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene and any mixtures thereof in any proportion.

[0199] In this specification, the terms "amount of..." and "amount of..." have the same meaning and can be used interchangeably, as long as they illustrate the effects of the present invention.

[0200] In this specification, the terms "except..." and "other than..." are interchangeable.

[0201] In this specification, the non-restrictive term "comprise(s) / comprising" may be optionally replaced with the restrictive term "consist(s) of / consisting of".

[0202] Unless otherwise explicitly stated, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which this disclosure belongs.

[0203] Unless otherwise indicated, figures representing characteristics such as quantities, sizes, concentrations, and reaction conditions used herein are understood to be modified by the term “approximately.” In some embodiments, disclosed figures are interpreted with respect to the reported number of significant figures and the application of common rounding techniques. In some embodiments, disclosed figures are interpreted to include errors that inevitably arise from the standard deviation observed in each test measurement method.

[0204] (Ingredients: Compound of formula (1)) The compound of formula (1) is used as a raw material. The compound of formula (1) is a known compound, or can be produced from a known compound by a known method. Particularly preferred specific examples of the compound of formula (1) are as follows:

[0205] [ka]

[0206] (Product: Compound of formula (2)) The product is the compound of formula (2) corresponding to the compound of formula (1) used as a starting material. Particularly preferred specific examples of the compound of formula (2) are as follows:

[0207] [ka]

[0208] The intermediate in the oxidation reaction is the compound of formula (3) corresponding to the compound of formula (1) used as a starting material. Specific examples of the compound of formula (3) are as follows:

[0209] [ka]

[0210] As mentioned above, in the method for producing the compound of formula (2) (SO2 derivative) from the compound of formula (1) (S derivative), it is desirable that the oxidation reaction proceeds sufficiently and that the proportion of the compound of formula (3) (SO derivative) in the product is sufficiently low. For example, the proportion of the compound of formula (3) (SO derivative) in the reaction mixture after the reaction is preferably 10% or less, more preferably 5% or less, even more preferably 4% or less, even more preferably 3% or less, even more preferably 2% or less, and even more preferably 1% or less.

[0211] After oxidizing equation (1) to obtain equation (3), it is also possible to oxidize it to equation (2).

[0212] (Oxidizing agent: hydrogen peroxide) Examples of oxidizing agents include, but are not limited to, peroxides, hypochlorites (e.g., sodium hypochlorite, potassium hypochlorite), manganates, manganese dioxide, etc. Examples of peroxides include, but are not limited to, hydrogen peroxide, peracids and their salts (e.g., peracetic acid), persulfates and their salts (e.g., potassium peroxymonosulfate (Oxon®), sodium peroxodisulfate), etc. From the viewpoint of safety, economic efficiency, etc., a preferred example of an oxidizing agent is hydrogen peroxide.

[0213] Any form of hydrogen peroxide may be used, as long as the reaction proceeds. The form of hydrogen peroxide can be appropriately selected by those skilled in the art. However, considering safety, hazards, and economic efficiency, preferred forms of hydrogen peroxide include 10-70 wt% aqueous hydrogen peroxide solution, more preferably 20-65 wt% aqueous hydrogen peroxide solution, even more preferably 25-65 wt% aqueous hydrogen peroxide solution, even more preferably 30-65 wt% aqueous hydrogen peroxide solution, and particularly preferably 30-60 wt% aqueous hydrogen peroxide solution. Specific examples of hydrogen peroxide forms include, but are not limited to, 30 wt% aqueous hydrogen peroxide solution, 35 wt% aqueous hydrogen peroxide solution, 50 wt% aqueous hydrogen peroxide solution, 60 wt% aqueous hydrogen peroxide solution, etc. The range of hydrogen peroxide concentration also includes, for example, any combination of the lower and upper limits of those ranges described herein.

[0214] The amount of oxidizing agent (preferably hydrogen peroxide) used can be any amount as long as the reaction proceeds. The amount used can be adjusted as appropriate by those skilled in the art. However, from the viewpoint of yield, suppression of by-products, economic efficiency, safety, and hazards, the amount used should be, for example, 2 moles or more, preferably 2 to 8 moles, more preferably 2 to 6 moles, even more preferably 2 to 5 moles, and still more preferably 2 to 4 moles per mole of compound (raw material) of formula (1).

[0215] (Metal catalyst) Any metal catalyst may be used, as long as the reaction proceeds. Examples of metal catalysts include, but are not limited to, the following: Tungsten catalysts (e.g., tungstic acid, tungstates (e.g., sodium tungstate (including sodium tungstate dihydrate and sodium tungstate decahydrate), potassium tungstate, calcium tungstate, ammonium tungstate), metallic tungsten, tungsten oxides (e.g., tungsten(VI) oxide, tungsten(VI) oxide is also called tungsten trioxide), tungsten carbide, tungsten chlorides (e.g., tungsten(VI) chloride, tungsten(VI) chloride is also called tungsten hexachloride), tungsten bromides (e.g., tungsten(V) bromide), tungsten sulfides (e.g., tungsten(IV) sulfide, tungsten(IV) sulfide is also called tungsten disulfide), phosphotungstic acid and its salts (e.g., phosphotungstic acid, sodium phosphotungstate, ammonium phosphotungstate, etc.), silicotungstic acid and its salts (e.g., silicotungstic acid, sodium silicotungstate, etc.), etc., and mixtures thereof), Molybdenum catalysts (e.g., molybdic acid, molybdates (e.g., sodium molybdate (including sodium molybdate dihydrate), potassium molybdate, ammonium molybdate (including ammonium molybdate tetrahydrate)), metallic molybdenum, molybdenum oxides (e.g., molybdenum(VI) oxide, molybdenum(VI) oxide is also called molybdenum trioxide), molybdenum chlorides (molybdenum(V) chloride, molybdenum(V) chloride is also called molybdenum pentachloride), molybdenum sulfides (e.g., molybdenum(IV) sulfide, molybdenum(IV) sulfide is also called molybdenum disulfide), phosphomolybdic acid and its salts (e.g., phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, etc.), silicomolybdic acid and its salts (e.g., silicomolybdic acid, sodium silicomolybdate, etc.), bis(2,4-pentanedionato)molybdenum(VI) dioxide, etc., and mixtures thereof), Iron catalysts (e.g., iron(I) acetylacetonate, iron(I) chloride, iron(I) nitrate, etc., and mixtures thereof), Manganese catalysts (e.g., potassium permanganate, manganese(II) oxide, manganese(II) chloride, etc., and mixtures thereof), Vanadium catalysts (e.g., vanadyl acetylacetonate, vanadium(V) oxide, vanadium(V) oxytrichloride, vanadium(V) oxytriethoxide, vanadium(V) oxytriisopropoxide, etc., and mixtures thereof), Niobium catalysts (e.g., niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and mixtures thereof), Tantalum catalysts (e.g., tantalum carbide (TaC), tantalum(V) chloride (TaCl5), tantalum(V) pentaethoxide (Ta(OEt)5), etc., and mixtures thereof), Titanium catalysts (e.g., titanium tetrachloride, titanium trichloride, titanium(IV) tetraisopropoxide, etc., and mixtures thereof), Zirconium catalysts (e.g., zirconium dioxide, zirconium(I) chloride, zirconium(IV) chloride, zirconium chloride oxide, etc., and mixtures thereof), Copper catalysts (e.g., copper(I) acetate, copper(II) acetate, copper(I) bromide, copper(I) iodide, etc., and mixtures thereof), Thallium catalysts (e.g., thallium(I) nitrate, thallium(I) acetate, thallium(I) trifluoroacetate, etc., and mixtures thereof).

[0216] In the present specification, acids and their salts that can be in the form of hydrates may be in the form of hydrates, and any form is within the scope of the present invention. Therefore, for example, "sodium tungstate" includes "sodium tungstate dihydrate" and "sodium tungstate decahydrate". In the present specification, acids and their salts that can be in the form of polyacids (e.g., tungstic acid and its salts, etc.) may be in the form of polyacids, and any form is within the scope of the present invention.

[0217] The metal used in the metal catalyst is preferably a transition metal. Specifically, this includes group 3 elements (Sc, Y, etc.), group 4 elements (Ti, Zr, Hf), group 5 elements (V, Nb, Ta), group 6 elements (Cr, Mo, W), group 7 elements (Mn, Tc, Re), group 8 elements (Fe, Ru, Os), group 9 elements (Co, Rh, Ir), group 10 elements (Ni, Pd, Pt), and group 11 elements (Cu, Ag, Au).

[0218] The transition metal of the metal catalyst is preferably a metal from Group 4, Group 5, and Group 6 of the periodic table, more preferably from Group 5 and Group 6, and even more preferably from Group 5.

[0219] Preferred examples of metal catalysts include tungsten catalysts and molybdenum catalysts.

[0220] In one embodiment, a preferred example of a metal catalyst is a tungsten catalyst.

[0221] In another embodiment, a preferred example of a metal catalyst is a molybdenum catalyst.

[0222] In one embodiment, preferred examples of tungsten catalysts from the viewpoint of yield, suppression of by-products, and economic efficiency include the following: Tungstic acid, tungstates, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten sulfide, phosphotungstic acid, silicatungstic acid and its salts, and mixtures thereof. More comfortable tungstic acid, tungstates, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride and its salts, and mixtures thereof. More preferably, tungstic acid, tungstate salts, metallic tungsten, tungsten oxide, tungsten carbide, and mixtures thereof. More preferably, tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metallic tungsten, tungsten(VI) oxide, tungsten carbide, and mixtures thereof. More preferably, tungstic acid, sodium tungstate, metallic tungsten, tungsten carbide, and mixtures thereof. More preferably tungstic acid and sodium tungstate, particularly preferably sodium tungstate.

[0223] From the viewpoint of yield, suppression of by-products, and economic efficiency, preferred examples of molybdenum catalysts include the following: Molybdic acid, molybdate salts, metallic molybdenum, molybdenum oxide, molybdenum carbide, molybdenum chloride, molybdenum sulfide, molybdenum bromide, phosphomolybdic acid, silicic molybdic acid and its salts, and mixtures thereof. More preferably, molybdic acid, molybdate salts, metallic molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride and mixtures thereof, More preferably, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicic acid, sodium silicic acid, and mixtures thereof. More preferably, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum(V) chloride, and mixtures thereof. More preferably, sodium molybdate, potassium molybdate, ammonium molybdate, Particularly preferred is ammonium molybdate.

[0224] From the viewpoint of yield, suppression of by-products, and economic efficiency, more preferred examples of metal catalysts include: Tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metallic tungsten, tungsten oxide, tungsten carbide, Sodium molybdate, potassium molybdate, ammonium molybdate.

[0225] More preferred examples of the metal catalyst include the following: Tungstic acid, sodium tungstate, Sodium molybdate, potassium molybdate, ammonium molybdate.

[0226] More preferred examples of the metal catalyst include the following: Sodium tungstate, ammonium molybdate.

[0227] In another aspect, the preferred metal catalyst is as described in [A-101] to [A-113] herein.

[0228] The metal catalyst may be used alone or in combination of two or more in any ratio. The form of the metal catalyst may be in any form as long as the reaction proceeds. The form can be appropriately selected by those skilled in the art. The amount of the metal catalyst used may be in any amount as long as the reaction proceeds. The amount used can be appropriately adjusted by those skilled in the art. However, from the viewpoints of yield, by-product suppression, economic efficiency, etc., the amount used is, for example, 0.001 to 0.1 mol, preferably 0.01 to 0.1 mol, more preferably 0.01 to 0.05 mol, still more preferably 0.03 to 0.05 mol, per 1 mol of the compound (raw material) of formula (1).

[0229] In one aspect, examples of the carboxylic acid include, but are not limited to, the following. The carboxylic acid of formula (a);

[0230]

Chemical formula

[0231] From the viewpoint of yield, suppression of by-products, and economic efficiency, in one embodiment, a preferred example of A includes (C1-C4) alkyl which may be substituted with one or more substituents, more preferably (C1-C4) alkyl which may be substituted with 1 to 9 halogen atoms, even more preferably (C1-C4) alkyl which may be substituted with 1 to 9 substituents selected from fluorine atoms and chlorine atoms (in other words, (C1-C4) alkyl which may be substituted with 1 to 9 fluorine atoms or chlorine atoms), and even more preferably (C1-C4) alkyl which may be substituted with chlorine atoms.

[0232] From a similar viewpoint, in yet another embodiment, specific examples of preferred A include methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, and trichloromethyl. Specific examples of more preferred A include methyl, ethyl, trifluoromethyl, and trichloromethyl. Even more preferred examples of A include methyl, trifluoromethyl, and trichloromethyl. Even more preferred examples of A include methyl, trifluoromethyl. From a similar viewpoint, in yet another embodiment, specific examples of preferred A include methyl, ethyl, difluoromethyl, trifluoromethyl, dichloromethyl, and trichloromethyl. Specific examples of more preferred A include methyl, difluoromethyl, trifluoromethyl, dichloromethyl, and trichloromethyl. Even more preferred examples of A include methyl, dichloromethyl, and trichloromethyl. In yet another embodiment, A is trifluoromethyl. In yet another embodiment, A is trichloromethyl. In yet another embodiment, A is dichloromethyl. In yet another embodiment, A is methyl.

[0233] In yet another embodiment, examples of carboxylic acids include, but are not limited to, substituted or otherwise saturated or unsaturated aliphatic monocarboxylic acids (e.g., formic acid, acetic acid, propionic acid, butyric acid, monofluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, lactic acid), substituted or otherwise saturated or unsaturated aliphatic dicarboxylic acids (e.g., oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, malic acid, tartaric acid), and substituted or otherwise saturated or unsaturated aliphatic tricarboxylic acids (e.g., citric acid). In this specification, formic acid is understood to be a type of aliphatic monocarboxylic acid. Preferred specific examples of carboxylic acids include, but are not limited to, acetic acid, trifluoroacetic acid, trichloroacetic acid, more preferably acetic acid. In yet another embodiment, preferred specific examples of carboxylic acids include acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid. More preferred specific examples of carboxylic acids include acetic acid, dichloroacetic acid, and trichloroacetic acid. More preferred specific examples of carboxylic acids include acetic acid and dichloroacetic acid.

[0234] As long as the effects of the present invention are demonstrated, the amount of carboxylic acid used is not particularly limited. However, from the viewpoint of yield, suppression of by-products, and economic efficiency, in one embodiment, the lower limit of the amount of carboxylic acid used is, for example, more than 0 moles, preferably 0.01 moles or more, more preferably 0.05 moles or more, even more preferably 0.1 moles or more, 0.3 moles or more, 0.5 moles or more, 1 mole or more, 2 moles or more, 3 moles or more, or 5 moles or more, per mole of compound (raw material) of formula (1). In another embodiment, the lower limit of the amount of carboxylic acid used is, for example, preferably 8 moles or more, 10 moles or more, 12 moles or more, 15 moles or more, 18 moles or more, or 20 moles or more, per mole of compound (raw material) of formula (1). In yet another embodiment, the lower limit of the amount of carboxylic acid used is, for example, 26 moles or more, preferably more than 26 moles, more preferably 27 moles or more, 28 moles or more, even more preferably 30 moles or more, 32 moles or more, and even more preferably 35 moles or more, per mole of compound (raw material) of formula (1). From the same viewpoint as above, in one embodiment, the upper limit of the amount of carboxylic acid used is, for example, 90 moles or less, 70 moles or less, and 55 moles or less per mole of compound (raw material) of formula (1). In another embodiment, the upper limit of the amount of carboxylic acid used is, for example, 30 moles or less, 20 moles or less, 10 moles or less, and 9 moles or less per mole of compound (raw material) of formula (1). In yet another embodiment, the upper limit of the amount of carboxylic acid used is, for example, 5 moles or less and 0.3 moles or less per mole of compound (raw material) of formula (1). The range of the amount of carboxylic acid used is, for example, any appropriate and arbitrary combination of the lower and upper limits above. For example, the combinations of upper and lower limits are as follows, but are not limited to these: From the same viewpoint as above, in one embodiment, the amount of carboxylic acid used is, for example, more than 0 moles and 70 moles or less, more than 0 moles and 55 moles or less, more than 0 moles and 30 moles or less, preferably 0.01 moles or more and 70 moles or less, 0.01 moles or more and 55 moles or less, 0.01 moles or more and 30 moles or less, more preferably 0.05 moles or more and 70 moles or less, 0.05 moles or more and 55 moles or less, 0.05 moles or more and 30 moles or less, even more preferably 0.1 moles or more and 70 moles or less, 0.1 moles or more and 55 moles or less, 0.1 moles or more and 30 moles or less.In another embodiment, the amount of carboxylic acid used is, for example, more than 26 moles and 70 moles or less, more than 26 moles and 55 moles or less, preferably 30 moles and 70 moles or less, 30 moles and 55 moles or less, more preferably 35 moles and 70 moles or less, or 35 moles and 55 moles or less, per mole of compound (starting material) of formula (1). Depending on the purpose and circumstances, the above amounts of carboxylic acid may be used as a solvent.

[0235] Insofar as the effects of the present invention are demonstrated, some or all of the carboxylic acids may be salts and / or acid anhydrides.

[0236] (Acid catalyst) The oxidation reaction of the present invention may be carried out in the presence or absence of an acid catalyst. Whether or not to use an acid catalyst can be appropriately determined by those skilled in the art. The acid of the acid catalyst is an acid other than a carboxylic acid. Examples of acid catalysts include, but are not limited to, the following: mineral acids such as hydrochloric acid, sulfuric acid, and nitric acid; sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; phosphoric acids such as phosphoric acid, methyl phosphate, ethyl phosphate, and phenyl phosphate; preferably sulfuric acid, phosphoric acid, and phenyl phosphate; more preferably sulfuric acid and phenyl phosphate; and even more preferably sulfuric acid. The acid catalyst may also be a salt thereof.

[0237] The acid catalyst may be used alone or in any combination of two or more in any proportion. The form of the acid catalyst may be any form as long as the reaction proceeds. For example, examples of sulfuric acid include, but are not limited to, 50%-98% sulfuric acid, 50%-100% sulfuric acid, preferably 90%-98% sulfuric acid, and 90%-100% sulfuric acid (concentrated sulfuric acid). The form of the acid catalyst can be appropriately selected by those skilled in the art. The amount of acid catalyst used may be any amount as long as the reaction proceeds. The amount of acid catalyst used can be appropriately adjusted by those skilled in the art. However, from the viewpoint of yield, suppression of by-products, and economic efficiency, in one embodiment, the amount of acid catalyst used is, for example, 0 to 0.5 moles, greater than 0 and less than or equal to 0.5 moles, 0.005 to 0.5 moles, 0.01 to 0.5 moles, 0.05 to 0.5 moles, preferably 0 to 0.2 moles, greater than 0 and less than or equal to 0.2 moles, 0.005 to 0.2 moles, 0.01 to 0.2 moles, and 0.05 to 0.2 moles per mole of compound (raw material) of formula (1).

[0238] (phase transfer catalyst) The oxidation reaction of the present invention may be carried out in the presence or absence of a phase transfer catalyst. Whether or not to use a phase transfer catalyst can be appropriately determined by those skilled in the art. Examples of phase transfer catalysts include, but are not limited to, the following: quaternary ammonium salts (e.g., tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium bisulfate, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, octyltrimethylammonium chloride, octyltrimethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, benzyl lauryldimethylammonium chloride (benzyldodecyldimethylammonium chloride), benzyl lauryldimethylammonium bromide (benzyldodecyldimethylammonium bromide) Examples of phase transfer catalysts include ammonium bromide, myristyltrimethylammonium chloride (tetradecyltrimethylammonium chloride), myristyltrimethylammonium bromide (tetradecyltrimethylammonium bromide), benzyldimethylstearylammonium chloride (benzyloctadecyldimethylammonium chloride), benzyldimethylstearylammonium bromide (benzyloctadecyldimethylammonium bromide), etc., quaternary phosphonium salts (tetrabutylphosphonium bromide, tetraoctylphosphonium bromide, tetraphenylphosphonium bromide, etc.), crown ethers (e.g., 12-crown-4, 15-crown-5, 18-crown-6, etc.). From the viewpoint of yield, suppression of by-products, and economic efficiency, preferred examples of phase transfer catalysts include tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium bisulfate, and more preferably tetrabutylammonium bisulfate. Tetrabutylammonium bisulfate may be abbreviated as TBAHS.

[0239] The phase transfer catalyst may be used alone or in any combination of two or more types in any proportion. The form of the phase transfer catalyst may be any form as long as the reaction proceeds. The form of the phase transfer catalyst can be appropriately selected by a person skilled in the art. The amount of phase transfer catalyst used may be any amount as long as the reaction proceeds. The amount of phase transfer catalyst used can be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the amount of phase transfer catalyst used is, for example, 0 to 0.5 moles, greater than 0 to 0.5 moles or less, 0.005 to 0.5 moles, 0.01 to 0.5 moles, 0.05 to 0.5 moles, preferably 0 to 0.2 moles, greater than 0 to 0.2 moles or less, 0.005 to 0.2 moles, 0.01 to 0.2 moles, or 0.05 to 0.2 moles per mole of compound (raw material) of formula (4).

[0240] (reaction solvent) From the viewpoint of ensuring the smooth progress of the reaction, the oxidation reaction of the present invention is preferably carried out in the presence of a solvent. Any solvent may be used as the reaction solvent, as long as the reaction proceeds. The reaction solvent may be a carboxylic acid or an organic solvent other than a carboxylic acid. In either case, the reaction may be carried out in the presence of water.

[0241] In one embodiment, examples of reaction solvents include, but are not limited to, the following: aromatic hydrocarbon derivatives (e.g., benzene which may be substituted with 1 to 3 (preferably 1 or 2) substituents selected from (C1-C4) alkyl (preferably (C1-C3) alkyl, more preferably (C1-C2) alkyl) and chlorine atoms, specifically, for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene; specific examples of aromatic hydrocarbon derivatives may also include nitrobenzene), halogenated aliphatic hydrocarbons (e.g., (C1-C4) alkanes which may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms), preferably (C1-C2) alkanes which may be substituted with 1 to 6 chlorine atoms, specifically, for example, dichloromethane, 1,2-dichloroethane (EDC), chloroform), alcohols (e.g., (C1-C6) alcohols, specifically For example, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol. The alcohols are preferably (C1-C5) alcohols, more preferably (C1-C4) alcohols, and specific examples thereof include appropriate examples from the above examples. Examples of alcohols may also include cyclohexanol.) Nitriles (for example, (C2-C5) alkanenitriles, preferably (C2-C3) alkanenitriles, specifically, for example, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, succinonitrile, preferably acetonitrile. In this specification, C2 alkanenitrile is acetonitrile. Examples of nitriles may also include benzonitrile.), carboxylic acids (acetic acid, propionic acid, trifluoroacetic acid, dichloroacetic acid, trichloroacetic acid), carboxylic acid esters (for example, (C1-C4)alkyl(C2-C6) carboxylates, preferably (C1-C4)alkyl(C2-C3) carboxylates, specifically, for example, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers (in the present invention, "isomer of butyl acetate" is an equivalent of "butyl acetate," and "isomer of pentyl acetate" is an equivalent of "pentyl acetate")), ethers (for example, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether) , cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme), ketones (e.g., acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK)), amides (e.g., N,N-di((C1-C4)alkyl)(C1-C4) alkanamides, specifically, for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC). Examples of amides may include N-methylpyrrolidone (NMP)), ureas (e.g., N,N'-dimethylimidazolidinone (DMI), tetramethylurea), sulfones (e.g., sulfolanes), water, and any combination thereof in any proportion. 2-Propanol is also called isopropyl alcohol or isopropanol. Tert-butanol is also known as tert-butyl alcohol.

[0242] From the viewpoint of yield, suppression of by-products, and economic efficiency, preferred examples of reaction solvents include alcohols, nitriles, carboxylic acids, carboxylic acid esters, amides, water, and any combination thereof in any proportion.

[0243] More preferred examples of reaction solvents include alcohols, nitriles, carboxylic acids, amides, water, and any combination thereof in any proportion.

[0244] Further preferred examples of reaction solvents include alcohols, nitriles, carboxylic acids, water, and any combination thereof in any proportion.

[0245] From the same viewpoint as above, preferred specific examples of reaction solvents include methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers, acetic acid, propionic acid, trifluoroacetic acid, dichloroacetic acid, trichloroacetic acid, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), water, and any combination thereof in any proportion.

[0246] More preferred specific examples of reaction solvents include methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, acetonitrile, acetic acid, dichloroacetic acid, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), water, and any combination thereof in any proportion.

[0247] More preferred specific examples of reaction solvents include methanol, ethanol, propanol, 2-propanol, butanol, acetonitrile, acetic acid, dichloroacetic acid, N,N-dimethylformamide (DMF), water, and any combination thereof in any proportion.

[0248] More preferred specific examples of reaction solvents include methanol, acetonitrile, acetic acid, dichloroacetic acid, N,N-dimethylformamide (DMF), water, and any combination thereof in any proportion.

[0249] More preferred specific examples of reaction solvents include methanol, acetonitrile, acetic acid, dichloroacetic acid, water, and any combination thereof in any proportion.

[0250] In another embodiment, preferred reaction solvents are as described herein. For example, preferred reaction solvents are as described in sections [A-40] to [A-70] and [A-78] herein. Examples and specific examples thereof are as described herein. In all the methods described herein, for example, in sections [A-40] to [A-70] and [A-78], the reaction may occur "in the presence of an aqueous solvent".

[0251] Examples of preferred organic solvents include organic solvents as defined herein by the following parameters:

[0252] (Number of acceptors) In this specification, for the purpose of determining the acceptor number, for example, one can refer to the following document: Christian Reichardt, "Solvents and Solvent Effects in Organic Chemistry", 3rd, updated and enlarged edition, WILEY-VCH, 2003, pp. 25-26. The definition of the acceptor number using 31P-NMR chemical shift values ​​is described in the aforementioned document and is incorporated herein by reference. Examples of solvents having specified values ​​are described in the aforementioned document and are incorporated herein by reference.

[0253] (Relative permittivity) In this specification, with respect to relative permittivity (also commonly known as "dielectric constant"), for example, the following references can be consulted: The Chemical Society of Japan, ed., "Chemical Handbook (Basic Edition)", Maruzen Co., Ltd., 5th revised edition, 2004, pp. I-770-777. A. Maryott and Edgar R. Smith, National Bureau of Standards Circular 514, Table of Dielectric Constants of Pure Liquids, United States Department of Commerce, National Bureau of Standards, August 10, 1951. These are incorporated into the present invention by reference. Examples of solvents having the specified values ​​are described in the aforementioned references and are incorporated into the present invention by reference.

[0254] (Rohrschneider polarity parameter) For Rohrschneider's polarity parameters, see, for example, the following website: https: / / www.shodex.com / ja / dc / 06 / 0117.html. These are incorporated by reference into the present invention. Examples of solvents having the specified values ​​are described in the aforementioned document and are incorporated by reference into the present invention.

[0255] Examples of organic solvents excluding carboxylic acids are as described herein. When using organic solvents excluding carboxylic acids, examples of the amount are as follows, from the viewpoint of yield, suppression of by-products, and economic efficiency: In one embodiment, the lower limit of the amount of organic solvent excluding carboxylic acids used is more than 0 liters, 0.1 liters or more, preferably 0.2 liters or more, more preferably 0.3 liters or more, 0.4 liters or more, even more preferably 0.5 liters or more, and 0.8 liters or more, per mole of compound (1). In one embodiment, the upper limit of the amount of organic solvent excluding carboxylic acids used is 5 liters or less, preferably 3 liters or less, more preferably 2 liters or less, and even more preferably 1 liter or less, per mole of compound (1). The range of the amount of organic solvent excluding carboxylic acids used is, for example, any appropriate and arbitrary combination of the lower and upper limits above. For example, combinations of upper and lower limits are as follows, but are not limited to these: From the same viewpoint as above, in one embodiment, the amount of organic solvent excluding carboxylic acids used is, for example, 0.3 liters or more and 3 liters or less, preferably 0.5 liters or more and 2 liters or less, per mole of compound (starting material) of formula (1).

[0256] In either case, as long as the reaction proceeds, the solvent may be a single layer or separated into two layers. On the other hand, when the present invention was considered after its completion, it was found that when a carboxylic acid and a specific organic solvent were used, favorable conditions (reaction system) were obtained in the present invention from the viewpoint of solubility and affinity between the organic solvent and the aqueous solvent.

[0257] Furthermore, it has been found that by using carboxylic acids in this invention, appropriate conditions can be selected depending on the purpose and circumstances of industrial implementation. This is an advantageous effect of the present invention.

[0258] The "reaction solvent" includes all "organic solvents other than carboxylic acids" used in the reaction, "carboxylic acids used as solvents," and "water solvent." The "reaction solvent" does not include organic solvents and water solvents used for post-reaction workup (e.g., isolation, purification, etc.). The "organic solvents" used in the reaction include organic solvents in the starting material solution and the reactant solution. The "water solvent" used in the reaction includes water in the starting material solution and the reactant solution (e.g., water in the hydrogen peroxide aqueous solution).

[0259] The amount of reaction solvent used is not particularly limited as long as the reaction system can be sufficiently stirred. However, from the viewpoint of yield, suppression of by-products, and economic efficiency, in one embodiment, the amount of reaction solvent used is, for example, 0 to 10 L, 0 to 5 L, greater than 0 and 10 L or less, greater than 0 and 5 L or less, preferably 0.2 to 10 L, 0.2 to 5 L, 0.2 to 3 L, 0.2 to 2 L, more preferably 0.3 to 10 L, 0.3 to 5 L, 0.3 to 3 L, 0.3 to 2 L, and even more preferably 0.4 to 10 L, 0.4 to 5 L, 0.4 to 3 L, or 0.4 to 2 L per mole of compound (starting material) of formula (1). When using a combination of two or more solvents, the proportions of the two or more solvents may be any proportion as long as the reaction proceeds.

[0260] (Reaction temperature) The reaction temperature is not particularly limited as long as the effects of the present invention are demonstrated. However, from the viewpoint of yield, suppression of by-products, and economic efficiency, in one embodiment, the lower limit of the reaction temperature is, for example, 10°C or higher, preferably 20°C or higher, 25°C or higher, 35°C or higher, greater than 35°C, 40°C or higher, 45°C or higher, or 50°C or higher. The upper limit of the reaction temperature is, for example, 200°C or lower, 150°C or lower, 100°C or lower, preferably 80°C or lower, more preferably 75°C or lower, less than 75°C, 70°C or lower, less than 70°C, 65°C or lower, 60°C or lower, and even more preferably 55°C or lower, less than 55°C, 50°C or lower, less than 50°C, 45°C or lower, 40°C or lower, or 35°C or lower. The range of the reaction temperature is, for example, any appropriate and arbitrary combination of the lower and upper limits above. For example, combinations of upper and lower limits are as follows, but are not limited to these. From the same viewpoint as above, in another embodiment, the reaction temperature is, for example, 10°C to 100°C, preferably 20°C to 100°C, more preferably more than 35°C to 100°C, even more preferably 40°C to 100°C, even more preferably 45°C to 100°C, and even more preferably 50°C to 100°C. From the same viewpoint as above, in yet another embodiment, the reaction temperature is, for example, 10°C to 80°C, preferably 20°C to 80°C, more preferably more than 35°C to 80°C, even more preferably 40°C to 80°C, even more preferably 45°C to 80°C, and even more preferably 50°C to 80°C. From the same viewpoint as above, in yet another embodiment, the reaction temperature is, for example, 10°C to 60°C, preferably 20°C to 60°C, more preferably more than 35°C to 60°C, even more preferably 40°C to 60°C, even more preferably 45°C to 60°C, and even more preferably 50°C to 60°C. The reaction temperature is preferable from a safety standpoint, and closer to room temperature (ambient temperature), the more environmentally friendly it is and the more it contributes to sustainability, but it is not limited by these factors.

[0261] (Reaction time) The reaction time is not particularly limited as long as the effects of the present invention are demonstrated. However, from the viewpoint of yield, suppression of by-products, and economic efficiency, in one embodiment, the lower limit of the reaction time is, for example, 1 hour or more, 1 hour 30 minutes or more, or 2 hours or more, but is not limited to these. In one embodiment, the upper limit of the reaction time is, for example, 48 hours or less, 36 hours or less, preferably 24 hours or less, 16 hours or less, or 12 hours or less, but is not limited to these. In another embodiment, the upper limit of the reaction time is, for example, 8 hours or less, 6 hours or less, 5 hours or less, or 4 hours or less, but is not limited to these. The range of the reaction time is, for example, any appropriate and arbitrary combination of the lower and upper limits above. For example, 1 hour to 48 hours, 1 hour to 36 hours, more preferably 1 hour to 24 hours, but is not limited to these. However, the reaction time can be appropriately adjusted by those skilled in the art depending on the purpose and circumstances.

[0262] The present invention will be described in more detail below with reference to examples, but the present invention is not limited in any way by these examples.

[0263] In this specification, the following equipment and conditions were used to measure the physical properties and yields of the examples, comparative examples, and reference examples. In addition, the products obtained in this invention are known compounds and were identified by conventional methods known to those skilled in the art.

[0264] (HPLC analysis: High-performance liquid chromatography analysis) (HPLC analysis conditions) Equipment: Shimadzu Corporation LC2010 series or equivalent. Column: YMC-Pack, ODS-A, A-312 (150mm x 6.0mm ID, S-5μm, 120A) Eluent:

[0265] [Table 1]

[0266] Flow rate: 1.0 ml / min Detection: UV 230nm Column temperature: 40℃ Injection volume: 5 μL

[0267] For HPLC analysis methods, please refer to the following literature as needed. Reference (a): The Chemical Society of Japan (ed.), "New Experimental Chemistry Course 9: Analytical Chemistry II", pp. 86-112 (1977), published by Shingo Iizumi, Maruzen Co., Ltd. Reference (b): The Chemical Society of Japan (ed.), "Experimental Chemistry Course 20-1 Analytical Chemistry," 5th edition, pp. 130-151 (2007), Publisher: Seishiro Murata, Maruzen Co., Ltd.

[0268] ( 1 H-NMR: 1 (H nuclear magnetic resonance spectrum) Equipment: JEOL JMN-ECS-300 or JEOL JMN-Lambda-400 (manufactured by JEOL RESONANCE) Solvent: CDCl3 and / or DMSO-d6 Internal reference substances: Tetramethylsilane (TMS) and others known to those skilled in the art.

[0269] (Yield and purity) Unless otherwise specified, the yield in this invention can be calculated from the number of moles of the target compound obtained relative to the number of moles of the raw material compound (starting compound). In other words, the term "yield" means "molar yield." Therefore, the yield is expressed by the following formula: Yield (%) = (moles of target compound obtained) / (moles of starting compound) × 100

[0270] However, for example, in evaluating the reaction yield of the target substance, the yield of impurities, and the purity of the product, HPLC area percentage analysis or GC area percentage analysis may be used.

[0271] In this specification, room temperature and ambient temperature are defined as temperatures between 10°C and 35°C.

[0272] In this specification, the term "overnight" means between 8 and 16 hours.

[0273] In this specification, the operation of “age / aged / aging” includes stirring the mixture by a conventional method known to those skilled in the art.

[0274] In the examples herein, unless otherwise specified, “sulfuric acid” means concentrated sulfuric acid. Examples of concentrated sulfuric acid include, but are not limited to, 98% sulfuric acid. [Examples]

[0275] [Example 1] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0276] [ka]

[0277] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), 10.0 g (1.5 L / mol) of acetonitrile, 1.53 g (25.5 mmol, 300 mol%) of acetic acid, and 0.084 g (0.26 mmol, 3 mol%) of sodium tungstate dihydrate were added to a reaction flask. A 35% aqueous hydrogen peroxide solution (2.48 g (25.5 mmol, 300 mol%) containing 1.6 g (0.2 L / mol) of water) was added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred for 6 hours at an internal temperature of 50°C to 55°C. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 2.51% (HPLC area percentage; 230 nm) at this point. The mixture was homogeneous. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 95.6% for the target product (2-a). 1 H-NMR value (CDCl3 / TMS δ(ppm)): 6.83(1H,t,J=71.9Hz), 4.60(2H,s), 3.88(3H,s), 3.11(2H,s), 1.52(6H,s)

[0278] [Example 2] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0279] [ka]

[0280] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), 10.0 g (1.5 L / mol) of acetonitrile, 0.26 g (4.25 mmol, 50 mol%) of acetic acid, and 0.084 g (0.26 mmol, 3 mol%) of sodium tungstate dihydrate were added to a reaction flask. A 35% aqueous hydrogen peroxide solution (2.48 g, 25.5 mmol, 300 mol%, containing 1.6 g (0.2 L / mol) of water) was added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 12 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 1.90% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 97.4% for the target product (2-a).

[0281] [Example 3] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0282] [ka]

[0283] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), 10.0 g (1.5 L / mol) of acetonitrile, 0.051 g (0.85 mmol, 10 mol%) of acetic acid, and 0.084 g (0.26 mmol, 3 mol%) of sodium tungstate dihydrate were added to a reaction flask. A 35% aqueous hydrogen peroxide solution (2.48 g (25.5 mmol, 300 mol%) containing 1.6 g (0.2 L / mol) of water) was added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 12 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 2.87% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 96.4% for the target product (2-a).

[0284] [Reference example 1] Reproduction experiment of Example 9C in Patent Publication No. 2013-512201 (JP2013-512201A) (Patent Document 3) Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0285] [ka]

[0286] Under a nitrogen atmosphere, 2.8 g (100 mol%) of compound (1-a), 8.4 g (1.0 L / mol) of acetic acid, and 80 mg (3 mol%) of sodium tungstate dihydrate were added to a reaction flask. 2.2 g (250 mol%) of 30% hydrogen peroxide was added dropwise to the mixture over 20 minutes at an internal temperature of 26°C to 35°C, and the mixture was aged for 16 hours while maintaining the internal temperature at 26°C to 35°C. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 5.0% after 16 hours of aging (HPLC area percentage). 4g of water was added to the reaction mixture, and after aging at 10°C for 1 hour, the precipitated crystals were filtered off. The obtained crystals were sequentially washed with 20 ml of petroleum ether and 20 ml of water. When the obtained crystals were analyzed by HPLC (area percentage; 230 nm), the reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was found to have an HPLC area percentage of 5.5%.

[0287] Reference Example 1 is a reproduction experiment of Example 9C of JP2013-512201 (JP2013-512201A) (Patent Document 3). In the manufacturing method described in JP2013-512201 (JP2013-512201A) (Patent Document 3), 5.0% of the reaction intermediate compound (3-a) remained even after 16 hours of maturation. Furthermore, the proportion of compound (3-a) did not decrease even after purification. This reaffirmed the difficulty of purifying the compound of formula (2) by separating the compound of formula (2) from the compound of formula (3).

[0288] [Reference example 2] Reproduction experiment of Example 5 in Chinese Patent Publication No. 111574511 (CN111574511A) (Patent Document 5) Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0289] [ka]

[0290] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetic acid (13.4 g, 223 mmol, 2600 mol%, 1.5 L / mol), sulfuric acid (0.078 g, 0.765 mmol, 9 mol%), and sodium tungstate dihydrate (0.056 g, 0.170 mmol, 2 mol%) were added to a reaction flask. A 30% aqueous hydrogen peroxide solution (2.75 g, 24.2 mmol, 285 mol%, containing 1.9 g of water (0.23 L / mol)) was added dropwise over 1 hour at room temperature (internal temperature 25°C-30°C). The mixture was stirred at room temperature (internal temperature 25°C-30°C) for 6 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 12.74% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 79.9% for the target product (2-a).

[0291] Reference Example 2 is a reproduction experiment of Example 5 of Chinese Patent Publication No. 111574511 (CN111574511A) (Patent Document 5). In the manufacturing method described in Chinese Patent Publication No. 111574511 (CN111574511A) (Patent Document 5), compound (3-a) of the reaction intermediate remained despite the use of a large amount of carboxylic acid (acetic acid).

[0292] [Example 4] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0293] [ka]

[0294] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetic acid (13.4 g, 223 mmol, 2600 mol%, 1.5 L / mol), sulfuric acid (0.078 g, 0.765 mmol, 9 mol%), and sodium tungstate dihydrate (0.056 g, 0.170 mmol, 2 mol%) were added to a reaction flask. A 30% aqueous hydrogen peroxide solution (2.75 g, 24.2 mmol, 285 mol%, containing 1.9 g of water (0.23 L / mol)) was added dropwise over 1 hour at an internal temperature of 71°C. The mixture was stirred at 71°C for 6 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 6-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 88.0% for the target product (2-a).

[0295] [Example 5] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0296] [ka]

[0297] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetic acid (3.90 g, 65.0 mmol, 2600 mol%, 1.5 L / mol), sodium tungstate dihydrate (0.0165 g, 0.050 mmol, 2 mol%), sulfuric acid (0.025 g, 0.25 mmol, 10 mol%), and 35% hydrogen peroxide aqueous solution (0.69 g, 7.13 mmol, 285 mol%, containing 0.45 g of water (0.18 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 2 hours. After precipitation, crystals formed, and the mixture became a suspension. The mixture was then aged for another 2 hours at an internal temperature of 50°C to 55°C. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0.4% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 89.6% for the target product (2-a).

[0298] [Example 6] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0299] [ka]

[0300] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetic acid (2.69 g, 44.8 mmol, 1790 mol%, 1.0 L / mol), and sodium tungstate dihydrate (0.025 g, 0.075 mmol, 3 mol%) were added to a reaction flask. A 30% aqueous hydrogen peroxide solution (0.71 g, 6.25 mmol, 250 mol%, containing 0.50 g of water (0.2 L / mol)) was then added dropwise over 20 minutes at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 2 hours, after which crystals precipitated and the mixture became a suspension. The mixture was then aged for another 2 hours at an internal temperature of 50°C to 55°C. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 1.1% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 90.0% for the target product (2-a).

[0301] [Example 7] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0302] [ka]

[0303] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), methanol (10.1 g, 1.5 L / mol), acetic acid (1.53 g, 25.5 mmol, 300 mol%), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask, and the mixture was heated to an internal temperature of 50°C to 55°C. A 35% aqueous hydrogen peroxide solution (2.48 g, 25.5 mmol, 300 mol%, containing 1.6 g of water (0.2 L / mol)) was added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 9 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 2.15% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 94.1% for the target product (2-a).

[0304] [Example 8] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0305] [ka]

[0306] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetonitrile 6.7 g (1.0 L / mol), acetic acid (4.44 g, 74.0 mmol, 870 mol%, 0.5 L / mol), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask, and the mixture was heated to an internal temperature of 50°C to 55°C. A 35% aqueous solution of hydrogen peroxide (2.48 g, 25.5 mmol, 300 mol%, containing 1.6 g of water (0.2 L / mol)) was added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 5 hours. The mixture was homogeneous. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0.22% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 91.3% for the target product (2-a).

[0307] [Example 9] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0308] [ka]

[0309] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), 6.7 g of acetonitrile (1.0 L / mol), acetic acid (4.44 g, 74.0 mmol, 870 mol%, 0.5 L / mol), sulfuric acid (0.085 g, 0.85 mmol, 10 mol%), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask, and the mixture was heated to an internal temperature of 50°C to 55°C. A 35% aqueous solution of hydrogen peroxide (2.48 g, 25.5 mmol, 300 mol%, containing 1.6 g of water (0.2 L / mol)) was then added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 3 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 95.5% for the target product (2-a).

[0310] [Example 10] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0311] [ka]

[0312] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), methanol 6.75 g (1.0 L / mol), acetic acid (4.44 g, 74.0 mmol, 870 mol%, 0.5 L / mol), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask, and the mixture was heated to an internal temperature of 50°C to 55°C. A 35% aqueous hydrogen peroxide solution (2.48 g, 25.5 mmol, 300 mol%, containing 1.6 g of water (0.2 L / mol)) was added dropwise over 1 hour at an internal temperature of 50°C to 55°C. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 5 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 1.98% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 96.2% for the target product (2-a).

[0313] [Example 11] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0314] [ka]

[0315] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetic acid (17.7 g, 295 mmol, 3470 mol%, 2 L / mol), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask. A 35% aqueous hydrogen peroxide solution (2.48 g, 25.5 mmol, 300 mol%, containing 1.6 g of water (0.2 L / mol)) was then added dropwise over 1 hour at an internal temperature of 25°C to 30°C. The mixture was stirred at an internal temperature of 25°C to 30°C and aged for 24 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 1.88% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 93.0% for the target product (2-a).

[0316] [Example 12] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0317] [ka]

[0318] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetic acid (3.90 g, 65.0 mmol, 2600 mol%, 1.5 L / mol), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), sulfuric acid (0.025 g, 0.25 mmol, 10 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 3 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0.61% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 94.3% for the target product (2-a).

[0319] [Example 13] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0320] [ka]

[0321] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetic acid (3.90 g, 65.0 mmol, 2600 mol%, 1.5 L / mol), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 3 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0.95% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 91.0% for the target product (2-a).

[0322] [Example 14] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0323] [ka]

[0324] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetic acid (2.61 g, 43.5 mmol, 1740 mol%, 1.0 L / mol), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 4 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 1.71% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 95.6% for the target product (2-a).

[0325] [Example 15] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0326] [ka]

[0327] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetic acid (0.075 g, 1.25 mmol, 50 mol%), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 3 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method showed a yield of 97.8% for the target product (2-a).

[0328] [Example 16] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0329] [ka]

[0330] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetonitrile (1.5 L / mol), acetic acid (0.45 g, 7.5 mmol, 300 mol%), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 6 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0.45% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method showed a yield of 97.5% for the target product (2-a).

[0331] [Example 17] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0332] [ka]

[0333] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetonitrile (1.0 L / mol), acetic acid (1.31 g, 21.7 mmol, 870 mol%, 0.5 L / mol), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), and 35% hydrogen peroxide aqueous solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 6 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0.16% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 98.1% for the target product (2-a).

[0334] [Example 18] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0335] [ka]

[0336] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), methanol (1.0 L / mol), acetic acid (1.31 g, 21.7 mmol, 870 mol%, 0.5 L / mol), ammonium molybdate tetrahydrate (0.031 g, 0.025 mmol, 1 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 8 hours. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 2.87% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 93.3% for the target product (2-a).

[0337] [Example 19] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0338] [ka]

[0339] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetonitrile (3.75 ml, 1.5 L / mol), trichloroacetic acid (1.23 g, 7.5 mmol, 300 mol%), sodium tungstate dihydrate (0.025 g, 0.075 mmol, 3 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 4 hours. The mixture remained a homogeneous solution from the start to the end of the reaction. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 89.9% for the target product (2-a).

[0340] [Example 20] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0341] [ka]

[0342] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), dichloroacetic acid (5.85 g, 45.4 mmol, 1815 mol%, 1.5 L / mol), sodium tungstate dihydrate (0.025 g, 0.075 mmol, 3 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 2 hours. The mixture remained a homogeneous solution from the start to the end of the reaction. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method showed a yield of 91.7% for the target product (2-a).

[0343] [Example 21] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0344] [ka]

[0345] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), dichloroacetic acid (5.85 g, 45.4 mmol, 1815 mol%, 1.5 L / mol), sodium tungstate dihydrate (0.025 g, 0.075 mmol, 3 mol%), sulfuric acid (0.025 g, 0.25 mmol, 10 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 2 hours. The mixture remained a homogeneous solution from the start to the end of the reaction. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 91.3% for the target product (2-a).

[0346] [Example 22] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0347] [ka]

[0348] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), acetonitrile (2.5 ml, 1.0 L / mol), dichloroacetic acid (1.95 g, 15.1 mmol, 605 mol%, 0.5 L / mol), sodium tungstate dihydrate (0.025 g, 0.075 mmol, 3 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 3.5 hours. The mixture remained a homogeneous solution from the start to the end of the reaction. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method showed a yield of 91.7% for the target product (2-a).

[0349] [Example 23] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0350] [ka]

[0351] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), dichloromethane (2.5 ml, 1.0 L / mol), dichloroacetic acid (1.95 g, 15.1 mmol, 605 mol%, 0.5 L / mol), sodium tungstate dihydrate (0.025 g, 0.075 mmol, 3 mol%), and 35% aqueous hydrogen peroxide solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred under reflux at an internal temperature of 41°C and aged for 5.5 hours. The mixture remained an emulsion from the start to the end of the reaction. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture to create a homogeneous solution. Analysis by HPLC external standard method revealed a yield of 86.5% for the target product (2-a).

[0352] [Example 24] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0353] [ka]

[0354] Under a nitrogen atmosphere, compound (1-a) (0.90 g, purity: 100%, 2.5 mmol, 100 mol%), dichloroacetic acid (5.85 g, 45.4 mmol, 1815 mol%, 1.5 L / mol), ammonium molybdate tetrahydrate (0.029 g, 0.025 mmol, 1 mol%), and 35% hydrogen peroxide aqueous solution (0.73 g, 7.50 mmol, 300 mol%, containing 0.47 g of water (0.2 L / mol)) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and aged for 2 hours. The mixture remained a homogeneous solution from the start to the end of the reaction. The reaction intermediate, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazole-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), was present at 0% (HPLC area percentage; 230 nm) at this point. Acetonitrile was added to the reaction mixture. Analysis by HPLC external standard method revealed a yield of 89.3% for the target product (2-a).

[0355] All publications, patents, and patent applications described herein are incorporated herein in their entirety by reference for the purpose of describing and disclosing the methods described herein, which may be used in connection with the description herein. All publications, patents, and patent applications described herein are expressly incorporated herein by reference to the extent necessary to understand or complete the disclosure of the present invention, to the same extent as if each were incorporated individually. All publications, patents, and patent applications discussed above and throughout this specification are provided solely for disclosure prior to the filing date of this application.

[0356] All methods described herein may be combined in any way unless they are clearly contradictory in content; however, any combination of methods described herein that contradicts their content is excluded.

[0357] Any method or reagent similar to or equivalent to those described herein may be used in the methods and practices of the present invention. Therefore, the present invention is not limited by the foregoing description, but is intended to be defined by the claims and their equivalents. These equivalents fall within the scope of the present invention as defined by the appended claims.

Claims

1. A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and a carboxylic acid selected from dichloroacetic acid and trichloroacetic acid, Here, the reaction is carried out at temperatures above 35°C; 【Chemistry 1】 (Here, R １ , R ２ and R ３ Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R ４ and R ５ Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R ４ and R ５ These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

2. A method according to claim 1, wherein the reaction is carried out at 40°C or higher.

3. The method according to claim 1, wherein the reaction is carried out at a temperature of 45°C or higher.

4. A method according to any one of claims 1 to 3, wherein the reaction is carried out at a temperature of 60°C or lower.

5. A method according to any one of claims 1 to 3, wherein the reaction is carried out at a temperature of 55°C or lower.

6. A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and a carboxylic acid selected from dichloroacetic acid and trichloroacetic acid, A method in which the amount of carboxylic acid is 18 moles or more per mole of the compound of formula (1); 【Chemistry 2】 (Here, R １ , R ２ and R ３ are each independently (C1-C6) alkyl optionally substituted with one or more substituents; (C3-C6) cycloalkyl optionally substituted with one or more substituents; (C2-C6) alkenyl optionally substituted with one or more substituents; (C2-C6) alkynyl optionally substituted with one or more substituents; or (C6-C10) aryl optionally substituted with one or more substituents, R ４ and R ５ Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R ４ and R ５ These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

7. A method for producing the compound of formula (2), comprising reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and a carboxylic acid selected from dichloroacetic acid and trichloroacetic acid, Here, the reaction is carried out in the presence of an organic solvent other than the carboxylic acid; 【Transformation 3】 (Here, R １ , R ２ and R ３ Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents. R ４ and R ５ Each of these is independently a (C1-C6) alkyl which may be substituted with one or more substituents; a (C3-C6) cycloalkyl which may be substituted with one or more substituents; a (C2-C6) alkenyl which may be substituted with one or more substituents; a (C2-C6) alkynyl which may be substituted with one or more substituents; a (C1-C6) alkoxy which may be substituted with one or more substituents; or a (C6-C10) aryl which may be substituted with one or more substituents; or R ４ and R ５ These atoms, together with the carbon atoms to which they are bonded, form a 3- to 12-membered carbon ring, and the ring formed therein may be substituted with one or more substituents.

8. A method according to claim 7, wherein the organic solvent is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and amides.

9. A method according to claim 7, wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, and nitriles.

10. A method according to claim 7, wherein the organic solvent is selected from (C1-C4) alkanes, (C1-C6) alcohols, and (C2-C5) alkanenitriles, which may be substituted with 1 to 10 halogen atoms.

11. The method according to claim 7, wherein the organic solvent is selected from dichloromethane, methanol, and acetonitrile.

12. A method according to any one of claims 1 to 11, wherein the carboxylic acid is dichloroacetic acid.

13. A method according to any one of claims 1 to 11, wherein the carboxylic acid is trichloroacetic acid.

14. A method according to any one of claims 1 to 13, wherein the metal catalyst is selected from a tungsten catalyst and a molybdenum catalyst.

15. A method according to any one of claims 1 to 13, wherein the metal catalyst is a tungsten catalyst.

16. A method according to any one of claims 1 to 13, wherein the metal catalyst is a molybdenum catalyst.

17. A method according to any one of claims 1 to 16, wherein the oxidizing agent is hydrogen peroxide.

18. A method according to any one of claims 1 to 17, R １ is (C1-C4) alkyl, R ２ is a (C1-C4) perfluoroalkyl group, R ３ (C1-C4) alkyl which may be substituted with 1 to 9 fluorine atoms, R ４ and R ５ However, each is independently a (C1-C4) alkyl group.

19. A method according to any one of claims 1 to 17, R １ It is methyl, R ２ It is trifluoromethyl, R ３ It is difluoromethyl, R ４ and R ５ A method in which it is methyl.

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