Method for manufacturing sulfone derivative as herbicide

Abstract

This invention provides an industrially preferred method for manufacturing a sulphur derivative for use as a herbicide. The invention also provides a method for manufacturing a compound of formula (2), comprising reacting a compound of formula (1) with an oxidant in the presence of a metal catalyst and a carboxylic acid to produce a compound of formula (2).

Description

Technical Field

[0001] The present invention relates to a method for manufacturing a herbicide derivative, namely a compound of formula (2) below.

[0002]

[0003]

[0004] (Where R1, R2, R3, R4, and R5 are as described in this specification.) Prior Technology

[0005] The herbicidal derivatives of formula (2) above, as disclosed in WO2002 / 062770A1 (Patent Document 1), are known to have herbicidal activity. Among them, Pyroxasulfone is known to be a superior herbicide.

[0006] The method for producing the compound of formula (2) is known to be by means of oxidation of a sulfide derivative, that is, the compound of formula (1), as shown below.

[0007]

[0008]

[0009] As shown in the figure below, WO2004 / 013106A1 (Patent Document 2) describes a method for producing 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline (1-a) (ISFP) by oxidizing 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline (2-a) (Pyroxasulfone) by m-chloroperoxybenzoic acid (mCPBA).

[0010]

[0011]

[0012] In the method for manufacturing compound of formula (2) from compound of formula (1), the meta-chloroperoxybenzoic acid (mCPBA) described in WO2004 / 013106A1 (Patent Document 2) is expensive for industrial use and has disposal and waste problems. Therefore, the manufacturing method described in WO2004 / 013106A1 (Patent Document 2) is not practical for industrial-scale manufacturing.

[0013] Furthermore, the method for preparing compound (2) (sulfide derivative: SO2 derivative) from compound (1) (sulfide derivative: S derivative) is based on sulfide derivative (SO derivative), which is an intermediate in oxidation reaction, i.e., compound (3) below:

[0014]

[0015]

[0016] (Where R1, R2, R3, R4, and R5 are as described in this specification.)

[0017] This could lead to the cessation of the reaction. Therefore, sometimes the compound of formula (3) may remain as a byproduct in the product. The presence of the compound of formula (3) in products such as herbicides can lead to a decrease in quality and may cause 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 and purify the compound of formula (2). Therefore, in the method of producing the compound of formula (2) from the compound of formula (1), a method is sought that allows the oxidation reaction to proceed sufficiently and leaves no residue of the compound of formula (3) in the product.

[0018] Patent Document 3 (Japanese Patent Application Publication No. 2013-512201) (JP2013-512201A) and Example 9C describe a method for manufacturing pyrazosulfan using acetic acid. However, the method described in Japanese Patent Application Publication No. 2013-512201 and Example 9C has the disadvantage of leaving a large amount of intermediates of formula (3) (sulfuron derivative: SO derivative). Refer to the specification of this patent application and Reference Example 1.

[0019] Patent document 3 (Japanese Patent Publication No. 2013-512201) (JP2013-512201A) corresponds to patent document 4 (US2012 / 264947A1).

[0020] CN111574511A (Patent Document 5) and Example 5 describe a method for manufacturing pyrazosulfan using acetic acid. However, the method described in CN111574511A and Example 5 has the disadvantage of being unreproducible and having a large amount of residual intermediates of formula (3) (sulfan derivatives: SO derivatives). Refer to this patent specification and Reference Example 2.

[0021] WO2021 / 002484A2 (Patent Document 6) discloses a method for manufacturing pyroclastic styrax. This method solves the aforementioned problems and is a superior method. However, the method described in WO2021 / 002484A2 is generally carried out at a relatively high temperature, and there is still room for improvement.

[0022] In addition, there is room for improvement in these previous methods due to their relatively slow response speed.

[0023] [Previous Technical Documents]

[0024] [Patent Literature]

[0025]

[0026] [Patent Document 1] International Publication No. 2002 / 062770

[0027] [Patent Document 2] International Publication No. 2004 / 013106

[0028] [Patent Document 3] Japanese Patent Publication No. 2013-512201

[0029] [Patent Document 4] U.S. Patent Application Publication No. 2012 / 264947

[0030] [Patent Document 5] Chinese Patent Application Publication No. 111574511 Specification

[0031] [Patent Document 6] International Publication No. 2021 / 002484 Summary of the Invention Problems to be Solved by the Invention

[0032] An object of the present invention is to provide a method for producing a compound of formula (2) from a compound of formula (1), in which the proportion of the compound of formula (3) in the product is very low, the yield is excellent, and it is an industrially preferable production method. Means for Solving the Problems

[0033] In view of the above situation, the present inventors have conducted in-depth research on the method for producing the compound of formula (2). As a result, unexpectedly, it has been found that by providing the following production method of the compound of formula (2), the above problems can be solved. Based on this insight, the present inventors have thus completed the present invention. That is, in one aspect, the present invention is as described below.

[0034] [A-1] A method for producing a compound of formula (2), which comprises reacting a compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid;

[0035]

[0036]

[0037] (wherein, R1, R2 and R3 are each independently a (C1-C6) alkyl group which may be substituted with one or more substituents; a (C3-C6) cycloalkyl group which may be substituted with one or more substituents; a (C2-C6) alkenyl group which may be substituted with one or more substituents; a (C2-C6) alkynyl group which may be substituted with one or more substituents; or a (C6-C10) aryl group which may be substituted with one or more substituents,

[0038] R4 and R5 are each independently a (C1-C6) alkyl group which may be substituted with one or more substituents; a (C3-C6) cycloalkyl group which may be substituted with one or more substituents; a (C2-C6) alkenyl group which may be substituted with one or more substituents; a (C2-C6) alkynyl group which may be substituted with one or more substituents; a (C1-C6) alkoxy group which may be substituted with one or more substituents; or a (C6-C10) aryl group which may be substituted with one or more substituents; or

[0039] R4 and R5 together with the carbon atom to which they are attached form a 3- to 12-membered carbocyclic ring, and the ring formed herein may be substituted with one or more substituents).

[0040] [A-2] is the method described in [A-1], wherein the reaction is carried out at a temperature above 35°C.

[0041] [A-3] is the method described in [A-1], wherein the reaction is carried out at a temperature above 35°C.

[0042] [A-4] is the method described in [A-1], wherein the reaction is carried out at a temperature above 40°C.

[0043] [A-5] is the method described in [A-1], wherein the reaction is carried out at a temperature above 45°C.

[0044] [A-6] is the method described in [A-1], wherein the reaction is carried out at a temperature above 50°C.

[0045] [A-7] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature below 60°C.

[0046] [A-8] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature not exceeding 60°C.

[0047] [A-9] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature below 55°C.

[0048] [A-10] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at less than 55°C.

[0049] [A-11] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature below 50°C.

[0050] [A-12] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at less than 50°C.

[0051] [A-13] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature below 45°C.

[0052] [A-14] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature below 40°C.

[0053] [A-15] is the method described in any one of [A-1] to [A-6], wherein the reaction is carried out at a temperature below 35°C.

[0054] [A-16] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 0.05 mol or more (preferably 0.1 mol or more) relative to 1 mol of the compound of formula (1).

[0055] [A-17] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 0.5 mol or more (1 mol or more, 2 mol or more, or 3 mol or more) relative to 1 mol of the compound of formula (1).

[0056] [A-18] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 5 moles or more relative to 1 mole of the compound of formula (1).

[0057] [A-19] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 8 mol or more (or 9 mol or more) relative to 1 mol of the compound of formula (1).

[0058] [A-20] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 10 mol or more (or 12 mol or more) relative to 1 mol of the compound of formula (1).

[0059] [A-21] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 15 moles or more relative to 1 mole of the compound of formula (1).

[0060] [A-22] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 18 mol or more (or 20 mol or more) relative to 1 mol of the compound of formula (1).

[0061] [A-23] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 26 mol or more (preferably 28 mol or more, more preferably 30 mol or more) relative to 1 mol of the compound of formula (1).

[0062] [A-24] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 32 mol or more relative to 1 mol of the compound of formula (1).

[0063] [A-25] is the method described in any one of [A-1] to [A-15], wherein the amount of carboxylic acid is 35 moles or more relative to 1 mole of the compound of formula (1).

[0064] [A-26] is the method described in any one of [A-1] to [A-25], wherein the amount of carboxylic acid is 90 moles or less (preferably 70 moles or less) relative to 1 mole of the compound of formula (1).

[0065] [A-27] is the method described in any one of [A-1] to [A-25], wherein the amount of carboxylic acid is 55 moles or less relative to 1 mole of the compound of formula (1).

[0066] [A-28] is the method described in any one of [A-1] to [A-25], wherein the amount of carboxylic acid is 10 moles or less (or 9 moles or less) relative to 1 mole of the compound of formula (1).

[0067] [A-29] is the method described in any one of [A-1] to [A-25], wherein the amount of carboxylic acid is less than 5 moles relative to 1 mole of the compound of formula (1).

[0068] [A-30] is the method described in any one of [A-1] to [A-29], wherein the amount of carboxylic acid is 0.3 liters or more (preferably 0.5 liters or more) relative to 1 mole of the compound of formula (1).

[0069] [A-31] is the method described in any one of [A-1] to [A-29], wherein the amount of carboxylic acid is 0.8 liters or more (preferably 1.0 liters or more) relative to 1 mole of the compound of formula (1).

[0070] [A-32] is the method described in any one of [A-1] to [A-29], wherein the amount of carboxylic acid is 1.2 liters or more (preferably 1.5 liters or more) relative to 1 mole of the compound of formula (1).

[0071] [A-33] is the method described in any one of [A-1] to [A-29], wherein the amount of carboxylic acid is 1.8 liters or more (preferably 2.0 liters or more) relative to 1 mole of the compound of formula (1).

[0072] [A-34] is the method described in any one of [A-1] to [A-33], wherein the amount of carboxylic acid is 5 liters or less (preferably 3 liters or less) relative to 1 mole of the compound of formula (1).

[0073] [A-35] is the method described in any one of [A-1] to [A-33], wherein the amount of carboxylic acid is 2.0 liters or less (preferably 1.0 liters or less) relative to 1 mole of the compound of formula (1).

[0074] [A-36] is the method described in any one of [A-1] to [A-33], wherein the amount of carboxylic acid is 0.9 liters or less (preferably 0.8 liters or less) relative to 1 mole of the compound of formula (1).

[0075] [A-37] is the method described in any one of [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) relative to 1 mole of the compound of formula (1).

[0076] [A-38] is the method described in any one of [A-1] to [A-37], wherein the reaction is carried out in the absence of an organic solvent.

[0077] [A-39] is the method described in any one of [A-1] to [A-37], wherein the reaction is carried out in the presence or absence of an organic solvent.

[0078] [A-40] is the method described in any one of [A-1] to [A-37], wherein the reaction is carried out in the presence of an organic solvent.

[0079] [A-41] is the method described in [A-39] or [A-40], wherein the organic solvent is an organic solvent having an acceptor number of 5 to 45.

[0080] [A-42] is the method described in [A-39] or [A-40], wherein the organic solvent is an organic solvent having a acceptor number of 7 to 42.

[0081] [A-43] is the method described in [A-39] or [A-40], wherein the organic solvent is an organic solvent having a relative capacitance of 1 to 45.

[0082] [A-44] is the method described in [A-39] or [A-40], wherein the organic solvent has an organic solvent having a relative capacitance of 4 to 40.

[0083] [A-45] is the method described in [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).

[0084] [A-46] is the method described in [A-39] or [A-40], wherein the organic solvent is an organic solvent other than a carboxylic acid.

[0085] [A-47] is the method described in [A-39] or [A-40], wherein the organic solvent of formula (a) is an organic solvent other than a carboxylic acid;

[0086]

[0087] A-COOH (a)

[0088] (where A is as described in this specification).

[0089] [A-48] is the method described in [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 sulfides.

[0090] [A-49] is the method described in [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.

[0091] [A-50] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from benzene that may be substituted with 1 to 3 (preferably 1 or 2) (C1-C4) alkyl groups and chlorine atoms, (C1-C4) alkanes that may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms), (C1-C6) alcohols, (C2-C5) alkanenitriles, (C1-C4) alkyl (C2-C6) carboxylic esters, and N,N-di((C1-C4)alkyl)(C1-C4)alkylamines.

[0092] [A-51] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, pentanol, dipentanol, 3-pentanol, 2-methyl-1-butanol, isopentanol, terpentanol, 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.

[0093] [A-52] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, dipentanol, 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.

[0094] [A-53] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and amides.

[0095] [A-54] is the method described in [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) carboxylic esters, and N,N-di((C1-C4)alkyl)(C1-C4)alkylamines that may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms).

[0096] [A-55] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, pentanol, dipentanol, 3-pentanol, 2-methyl-1-butanol, isopentanol, terpentanol, hexanol and its isomers, cyclohexanol, acetonitrile,

[0097] Methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N,N-diethylacetamide.

[0098] [A-56] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, dipentanol, 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.

[0099] [A-57] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, and nitriles.

[0100] [A-58] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from (C1-C4) alkanes, (C1-C6) alcohols, and (C2-C5) alkylnitriles that may be substituted with 1 to 10 halogen atoms (preferably chlorine atoms).

[0101] [A-59] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, 1,2-dichloroethane, chloroform, methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, pentanol, dipentanol, 3-pentanol, 2-methyl-1-butanol, isopentanol, terpentanol, hexanol and its isomers, cyclohexanol, and acetonitrile.

[0102] [A-60] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, methanol, ethanol, propanol, 2-propanol, butanol, second butanol, isobutanol, third butanol, second pentanol, and acetonitrile.

[0103] [A-61] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from dichloromethane, methanol, and acetonitrile.

[0104] [A-62] is the method described in [A-39] or [A-40], wherein the organic solvent is dichloromethane.

[0105] [A-63] is the method described in any one of [A-39] or [A-40], wherein the organic solvent is a (C1-C6) alcohol.

[0106] [A-64] is the method described in [A-39] or [A-40], wherein the organic solvent is selected from methanol, ethanol, propanol, 2-propanol, butanol, second butanol, isobutanol, third butanol, and third pentanol.

[0107] [A-65] is the method described in [A-39] or [A-40], wherein the organic solvent is methanol.

[0108] [A-66] is the method described in [A-39] or [A-40], wherein the organic solvent is acetonitrile.

[0109] [A-67] is the method described in any one of [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, the solvent being a carboxylic acid.

[0110] [A-68] is the method described in any one of [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, using a carboxylic acid as the solvent.

[0111] [A-69] is the method described in any one of [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, which is a mixture of a carboxylic acid and an organic solvent other than a carboxylic acid.

[0112] [A-70] is the method described in any one of [A-1] to [A-66], wherein the reaction is carried out in the presence of a solvent, and a mixture of a carboxylic acid and an organic solvent other than a carboxylic acid is used as the solvent.

[0113] [A-71] is the method described in any one of [A-1] to [A-70], wherein the amount of organic solvent is 0.1 liters or more (preferably 0.2 liters or more) relative to 1 mole of the compound of formula (1).

[0114] [A-72] is the method described in any one of [A-1] to [A-70], wherein the amount of organic solvent is 0.3 liters or more relative to 1 mole of the compound of formula (1).

[0115] [A-73] is the method described in any one of [A-1] to [A-70], wherein the amount of organic solvent is 0.5 liters or more relative to 1 mole of the compound of formula (1).

[0116] [A-74] is the method described in any one of [A-1] to [A-70], wherein the amount of organic solvent is 0.8 liters or more relative to 1 mole of the compound of formula (1).

[0117] [A-75] is the method described in any one of [A-1] to [A-74], wherein the amount of organic solvent is less than 3 liters relative to 1 mole of the compound of formula (1).

[0118] [A-76] is the method described in any one of [A-1] to [A-74], wherein the amount of organic solvent is less than 2 liters relative to 1 mole of the compound of formula (1).

[0119] [A-77] is the method described in any one of [A-1] to [A-74], wherein the amount of organic solvent is less than 1 liter relative to 1 mole of the compound of formula (1).

[0120] [A-78] is the method described in any one of [A-1] to [A-37], wherein the reaction is carried out in the presence of a solvent, the solvent being a carboxylic acid.

[0121] [A-79] is the method described in any one of [A-1] to [A-78], wherein the reaction is carried out in the presence of a solvent, the solvent being water.

[0122] [A-80] is the method described in any one of [A-1] to [A-78], wherein the reaction is carried out in the presence of an aqueous solvent.

[0123] [A-81] is the method described in any one of [A-79] or [A-80], wherein the amount of water solvent is more than 0 (zero) liters relative to 1 mole of the compound of formula (1).

[0124] [A-82] is the method described in any one of [A-79] or [A-80], wherein the amount of solvent is 0.1 liters or more relative to 1 mole of the compound of formula (1).

[0125] [A-83] is the method described in any one of [A-79] or [A-80], wherein the amount of water solvent is 0.18 liters or more relative to 1 mole of the compound of formula (1).

[0126] [A-84] is the method described in any one of [A-79] or [A-80], wherein the amount of water solvent is less than 0.5 liters relative to 1 mole of the compound of formula (1).

[0127] [A-85] is the method described in any one of [A-79] or [A-80], wherein the amount of water solvent is less than 0.3 liters relative to 1 mole of the compound of formula (1).

[0128] [A-86] is the method described in any one of [A-79] or [A-80], wherein the amount of water solvent is less than 0.25 liters relative to 1 mole of the compound of formula (1).

[0129] [A-87] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is the carboxylic acid of formula (a);

[0130]

[0131] A-COOH (a)

[0132] (Where A is hydrogen, (C1-C6) alkyl that can be substituted by one or more substituents; (C3-C6) cycloalkyl that can be substituted by one or more substituents; (C2-C6) alkenyl that can be substituted by one or more substituents; (C2-C6) ynyl that can be substituted by one or more substituents).

[0133] [A-88] is the method described in [A-87], wherein A is a (C1-C4) alkyl group that can be substituted by one or more substituents.

[0134] [A-89] is the method described in [A-87], wherein A is a (C1-C4) alkyl group that can be substituted with 1 to 9 halogen atoms.

[0135] [A-90] is the method described in [A-87], wherein A is a (C1-C4) alkyl group that may be substituted with 1 to 9 fluorine or chlorine atoms.

[0136] [A-91] is the method described in [A-87], wherein A is a (C1-C4) alkyl group that may be substituted with 1 to 9 fluorine atoms.

[0137] [A-92] is the method described in [A-87], wherein A is a (C1-C4) alkyl group that can be substituted with 1 to 9 chlorine atoms.

[0138] [A-93] is the method described in [A-87], wherein A is a (C1-C4) alkyl group.

[0139] [A-94] is the method described in 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.

[0140] [A-95] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is selected from difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid.

[0141] [A-96] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is selected from acetic acid, dichloroacetic acid, and trichloroacetic acid.

[0142] [A-97] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is acetic acid.

[0143] [A-98] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is selected from dichloroacetic acid and trichloroacetic acid.

[0144] [A-99] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is dichloroacetic acid.

[0145] [A-100] is the method described in any one of [A-1] to [A-86], wherein the carboxylic acid is trichloroacetic acid.

[0146] [A-101] is the method described in any one of [A-1] to [A-100], wherein the metal of the metal catalyst is a transition metal.

[0147] [A-102] is the method described in 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.

[0148] [A-103] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is selected from tungsten catalysts and molybdenum catalysts.

[0149] [A-104] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is a tungsten catalyst.

[0150] [A-105] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is a molybdenum catalyst.

[0151] [A-106] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is selected from tungstic acid, tungstate, molybdate, and molybdate.

[0152] [A-107] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is selected from tungstic acid, alkali metal salt of tungstate, ammonium tungstate, molybdic acid, alkali metal salt of molybdate, and ammonium molybdate.

[0153] [A-108] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is selected from sodium tungstate and ammonium molybdate.

[0154] [A-109] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is an alkali metal salt of tungstate (preferably sodium tungstate).

[0155] [A-110] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is ammonium molybdate.

[0156] [A-111] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is selected from sodium tungstate dihydrate and ammonium molybdate tetrahydrate salt.

[0157] [A-112] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is sodium tungstate dihydrate.

[0158] [A-113] is the method described in any one of [A-1] to [A-100], wherein the metal catalyst is an ammonium molybdate tetrahydrate salt.

[0159] [A-114] is the method described in any one of [A-1] to [A-113], wherein the oxidant is hydrogen peroxide.

[0160] [A-115] is the method described in any one of [A-1] to [A-113], wherein the hydrogen peroxide is a 10 to 70 wt% aqueous solution of hydrogen peroxide.

[0161] [A-116] is the method described in any one of [A-1] to [A-113], wherein the method comprises a 20 to 65 wt% aqueous solution of hydrogen peroxide.

[0162] [A-117] is the method described in any one of [A-1] to [A-113], wherein the method comprises a 25 to 65 wt% aqueous solution of hydrogen peroxide.

[0163] [A-118] is the method described in any one of [A-1] to [A-117], wherein the reaction is carried out in the presence or absence of an acid catalyst.

[0164] [A-119] is the method described in any one of [A-1] to [A-118], wherein the reaction is carried out in the presence of an acid catalyst, the acid catalyst being sulfuric acid.

[0165] [A-120] is the method described in any one of [A-1] to [A-119], wherein

[0166] R1 is a (C1-C4) alkyl group.

[0167] R2 is a (C1-C4) perfluoroalkyl group.

[0168] R3 is a (C1-C4) alkyl group that can be substituted with 1 to 9 fluorine atoms.

[0169] R4 and R5 are each independently (C1-C4) alkyl groups.

[0170] [A-121] is the method described in any one of [A-1] to [A-119], wherein

[0171] R1 is a methyl group.

[0172] R2 is trifluoromethyl.

[0173] R3 is difluoromethyl.

[0174] R4 and R5 are methyl groups.

[0175] In other respects, the present invention is as described below.

[0176] [B-1] is a method for manufacturing the compound of formula (2), which involves reacting the compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and a carboxylic acid.

[0177] The reaction is carried out at temperatures exceeding 35°C.

[0178]

[0179]

[0180] (Whereinafter, R1, R2, and R3 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents.)

[0181] R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C2-C6) alkynyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or

[0182] R4 and R5 together with the carbon atoms they are linked to form a 3 to 12-membered carbon ring, and the ring formed here may be substituted by more than one substituent.

[0183] [B-2] is the method described in [B-1], wherein the reaction is carried out at a temperature above 40°C.

[0184] [B-3] is the method described in [B-1], wherein the reaction is carried out at a temperature above 45°C.

[0185] [B-4] is the method described in any one of [B-1] to [B-3], wherein the reaction is carried out at a temperature below 60°C.

[0186] [B-5] is the method described in any one of [B-1] to [B-3], wherein the reaction is carried out at a temperature below 55°C.

[0187] [B-6] is a method for manufacturing the compound of formula (2), which includes reacting the compound of formula (1) with an oxidant in the presence of a metal catalyst and a carboxylic acid.

[0188] In this case, the amount of carboxylic acid is 18 mol or more relative to 1 mol of the compound of formula (1);

[0189]

[0190]

[0191] (Whereinafter, R1, R2, and R3 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents.)

[0192] R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C1-C6) alkoxy group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or

[0193] R4 and R5 together with the carbon atoms they are linked to form a 3 to 12-membered carbon ring, and the ring formed here may be substituted by more than one substituent.

[0194] [B-7] is the method described in [B-6], wherein the amount of carboxylic acid is 30 mol or more relative to 1 mol of the compound of formula (1).

[0195] [B-8] is the method described in [B-6], wherein the amount of carboxylic acid is 35 moles or more relative to 1 mole of the compound of formula (1).

[0196] [B-9] is a method for manufacturing the compound of formula (2), which includes a method for reacting the compound of formula (1) with an oxidant in the presence of a metal catalyst and a carboxylic acid.

[0197] The reaction is carried out in the presence of an organic solvent other than a carboxylic acid.

[0198]

[0199]

[0200] (Whereinafter, R1, R2, and R3 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents.)

[0201] R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C1-C6) alkoxy group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or

[0202] R4 and R5 together with the carbon atoms they are linked to form a 3 to 12-membered carbon ring, and the ring formed here may be substituted by more than one substituent.

[0203] [B-10] is the method described in [B-9], wherein the organic solvent is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and amides.

[0204] [B-11] is the method described in [B-9], wherein the organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, and nitriles.

[0205] [B-12] is the method described in [B-9], wherein the organic solvent is selected from (C1-C4) alkanes, (C1-C6) alcohols, and (C2-C5) alkyl nitriles that can be substituted with 1 to 10 halogen atoms.

[0206] [B-13] is the method described in [B-9], wherein the organic solvent is selected from dichloromethane, methanol, and acetonitrile.

[0207] [B-14] is the method described in any one of [B-1] to [B-13], wherein the carboxylic acid is the carboxylic acid of formula (a);

[0208]

[0209] A-COOH (a)

[0210] (Where A is hydrogen, (C1-C6) alkyl that can be substituted by one or more substituents; (C3-C6) cycloalkyl that can be substituted by one or more substituents; (C2-C6) alkenyl that can be substituted by one or more substituents; (C2-C6) ynyl that can be substituted by one or more substituents).

[0211] [B-15] is the method described in any one of [B-1] to [B-13], wherein the carboxylic acid is acetic acid.

[0212] [B-16] is the method described in any one of [B-1] to [B-13], wherein the carboxylic acid is dichloroacetic acid.

[0213] [B-17] is the method described in any one of [B-1] to [B-13], wherein the carboxylic acid is trichloroacetic acid.

[0214] [B-18] is the method described in any one of [B-1] to [B-17], wherein the metal catalyst is selected from tungsten catalysts and molybdenum catalysts.

[0215] [B-19] is the method described in any one of [B-1] to [B-17], wherein the metal catalyst is a tungsten catalyst.

[0216] [B-20] is the method described in any one of [B-1] to [B-17], wherein the metal catalyst is a molybdenum catalyst.

[0217] [B-21] is the method described in any one of [B-1] to [B-20], wherein the oxidant is hydrogen peroxide.

[0218] [B-22] is the method described in any one of [B-1] to [B-21], wherein

[0219] R1 is a (C1-C4) alkyl group.

[0220] R2 is a (C1-C4) perfluoroalkyl group.

[0221] R3 is a (C1-C4) alkyl group that can be substituted with 1 to 9 fluorine atoms.

[0222] R4 and R5 are each independently (C1-C4) alkyl groups.

[0223] [B-23] is the method described in any one of [B-1] to [B-21], wherein

[0224] R1 is a methyl group.

[0225] R2 is trifluoromethyl.

[0226] R3 is difluoromethyl.

[0227] R4 and R5 are methyl groups.

[0228] In other respects, the present invention is as described below.

[0229] [C-1] is a method for producing the compound of formula (2), wherein the compound of formula (1) is reacted with an oxidant in the presence of a metal catalyst and a carboxylic acid to produce the compound of formula (2);

[0230]

[0231]

[0232] (Whereinafter, R1, R2, and R3 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents.)

[0233] R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C2-C6) alkynyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or

[0234] R4 and R5 together with the carbon atoms they are linked to form a 3 to 12-membered carbon ring, and the ring formed here may be substituted by more than one substituent.

[0235] [C-2] is the method described in [C-1], wherein the reaction is carried out at a temperature exceeding 35°C.

[0236] [C-3] is the method described in [C-1], wherein the reaction is carried out at a temperature above 40°C.

[0237] [C-4] is the method described in [C-1], wherein the reaction is carried out at a temperature above 45°C.

[0238] [C-5] is the method described in any one of [C-1] to [C-4], wherein the amount of carboxylic acid used is more than 26 moles relative to 1 mole of the compound of formula (1).

[0239] [C-6] is the method described in any one of [C-1] to [C-4], wherein the amount of carboxylic acid used is 30 moles or more relative to 1 mole of the compound of formula (1).

[0240] [C-7] is the method described in any one of [C-1] to [C-4], wherein the amount of carboxylic acid used is 35 moles or more relative to 1 mole of the compound of formula (1).

[0241] [C-8] is the method described in any one of [C-1] to [C-7], wherein the carboxylic acid is the carboxylic acid of formula (a);

[0242]

[0243] A-COOH (a)

[0244] (Where, A is hydrogen, a substituted (C1-C6) alkyl group, a (C3-C6) cycloalkyl group that can be substituted by one or more substituents, a (C2-C6) alkenyl group that can be substituted by one or more substituents, or a (C2-C6) alkynyl group that can be substituted by one or more substituents).

[0245] [C-9] is the method described in [C-8], wherein A is a substituted (C1-C4) alkyl group.

[0246] [C-10] is the method described in any one of [C-1] to [C-7], wherein the carboxylic acid is acetic acid.

[0247] [C-11] is the method described in any one of [C-1] to [C-10], wherein the metal catalyst is a tungsten catalyst or a molybdenum catalyst.

[0248] [C-12] is the method described in any one of [C-1] to [C-10], wherein the metal catalyst is a tungsten catalyst.

[0249] [C-13] is the method described in any one of [C-1] to [C-10], wherein the metal catalyst is a molybdenum catalyst.

[0250] [C-14] is the method described in any one of [C-1] to [C-13], wherein the oxidizing agent is hydrogen peroxide.

[0251] [C-15] is the method described in any one of [C-1] to [C-14], wherein

[0252] R1 is a (C1-C4) alkyl group,

[0253] R2 is a (C1-C4) perfluoroalkyl group,

[0254] R3 is a (C1-C4) alkyl group which may be substituted with from 1 to 9 fluorine atoms,

[0255] R4 and R5 are each independently a (C1-C4) alkyl group.

[0256] [C-16] is the method described in any one of [C-1] to [C-14], wherein

[0257] R1 is methyl,

[0258] R2 is trifluoromethyl,

[0259] R3 is difluoromethyl,

[0260] R4 and R5 are methyl. Advantages of the Invention

[0261] The present invention can provide a method for producing a compound of formula (2) (sulfone derivative: SO2 derivative) from a compound of formula (1) (sulfide derivative: S derivative), and the proportion of the compound of formula (3) (sulfoxide derivative: SO derivative) in the product is very low, which is a preferable production method industrially.

[0262] The compound of formula (2) produced by the method of the present invention substantially does not contain the compound of formula (3) which may cause reduction in the quality of the herbicide and phytotoxicity to crops, and is useful as a herbicide. Embodiments

[0263] The present invention will now be described in detail.

[0264] The symbols and terms used in this instruction manual are explained.

[0265] The following abbreviations and prefixes are used in this manual and have the following meanings.

[0266] Me: Methyl

[0267] Et: Ethyl

[0268] Pr, n-Pr, and Pr-n:propyl (i.e., n-propyl)

[0269] i-Pr and Pr-i: Isopropyl

[0270] Bu, n-Bu, and Bu-n: Butyl (i.e., n-butyl)

[0271] s-Bu and Bu-s:sec-butyl (i.e., second butyl)

[0272] i-Bu and Bu-i: Isobutyl

[0273] t-Bu and Bu-t:tert-butyl (i.e., tert-butyl)

[0274] Ph:Phenyl

[0275] n-: positive

[0276] s- and sec-: second

[0277] i- and iso-: different

[0278] t- and tert-: third

[0279] c- and cyc-: rings

[0280] o-:neighbor

[0281] m-: space

[0282] p-: to

[0283] The term "nitro" refers to the substituent "-NO2".

[0284] The terms "cyano" or "nitrile" refer to the substituent "-CN".

[0285] The term "hydroxyl group" refers to the substituent "-OH".

[0286] The term "amine" refers to the substituent "-NH2".

[0287] (Ca-Cb) refers to alkyl groups with a to b carbon atoms. For example, "(C1-C4)" in "(C1-C4)alkyl" refers to alkyl groups with 1 to 4 carbon atoms.

[0288] In this specification, the term "alkyl" is generally interpreted to include both straight-chain and branched chains, such as butyl and tributyl. On the other hand, the specific term "butyl" refers to the straight-chain "n-butyl" and not the branched chain "tributyl". Therefore, branched isomers such as "tributyl" will be specifically mentioned where intended.

[0289] Examples of halogen atoms include fluorine, chlorine, bromine, and iodine atoms.

[0290] (C1-C6) alkyl refers to a straight-chain or branched alkyl group having 1 to 6 carbon atoms. Examples of (C1-C6) alkyl include methyl, ethyl, propyl, isopropyl, butyl, dibutyl, isobutyl, terbutyl, pentyl, hexyl, etc., but are not limited to these.

[0291] (C1-C4) alkyl refers to a straight-chain or branched alkyl group having 1 to 4 carbon atoms. Examples of (C1-C4) alkyl include suitable examples of the (C1-C6) alkyl groups described above.

[0292] (C3-C6) cycloalkyl refers to cycloalkyl groups having 3 to 6 carbon atoms. Examples of (C3-C6) cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0293] (C2-C6) alkenyl refers to a straight-chain or branched alkenyl group having 2 to 6 carbon atoms. Examples of (C2-C6) alkenyl include 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, 1-hexenyl, etc., but are not limited to these.

[0294] (C2-C6) ynyl refers to a straight-chain or branched ynyl group having 2 to 6 carbon atoms. Examples of (C2-C6) ynyl groups include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 1-hexynyl, etc., but are not limited to these.

[0295] Examples of (C6-C10) aryl groups are phenyl, 1-naphthyl, and 2-naphthyl.

[0296] (C1-C6) Halogenated alkyl groups refer to straight-chain or branched alkyl groups with 1 to 6 carbon atoms, substituted with 1 to 13 identical or different halogen atoms (wherein, the halogen atom has the same meaning as defined above). Examples of (C1-C6) halogenated alkyl groups 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, 2,2,2-trifluoro- 1-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, undecylfluoropentyl, tridecafluorohexyl, etc., but not limited to these.

[0297] (C1-C4) Perfluoroalkyl refers to straight-chain or branched alkyl groups having 1 to 4 carbon atoms, in which all hydrogen atoms are replaced by fluorine atoms. Examples of (C1-C4) perfluoroalkyl groups are 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).

[0298] Examples of (C1-C4) alkyl groups that can be substituted with 1 to 9 fluorine atoms include 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, 2,2,2-trifluoro-1,1-di(trifluoromethyl)ethyl, but are not limited to these.

[0299] (C1-C6)alkoxy refers to (C1-C6)alkyl-O- (wherein the (C1-C6)alkyl part has the same meaning as defined above). Examples of (C1-C6)alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, dibutoxy, isobutoxy, terbutoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, etc., but are not limited to these.

[0300] Cyclic hydrocarbon groups refer to monocyclic or polycyclic cyclic groups in which all the atoms constituting the ring are carbon atoms. In one embodiment, examples of cyclic hydrocarbon groups include aromatic or non-aromatic monocyclic, bicyclic, or tricyclic cyclic hydrocarbon groups of 3 to 14 members (preferably 5 to 14 members, more preferably 5 to 10 members), but are not limited to these. In other embodiments, examples of cyclic hydrocarbon groups include aromatic or non-aromatic monocyclic or bicyclic (preferably monocyclic) cyclic hydrocarbon groups of 4 to 8 members (preferably 5 to 6 members), but are not limited to these. Examples of cyclic hydrocarbon groups include cycloalkyl, aryl, etc., but are not limited to these. Examples of cycloalkyl include the (C3-C6) cycloalkyl examples described above. If an aryl group is among the cyclic hydrocarbon groups defined above, it is an aromatic cyclic group. Examples of aryl groups include the (C6-C10) aryl groups described above. Cyclic hydrocarbon groups as defined or illustrated above may, if possible, include non-fused-ring (e.g., monocyclic or spirocyclic) and fused-ring cyclic groups. Cyclic hydrocarbon groups as defined or illustrated above may, if possible, be unsaturated, partially saturated, or saturated. Cyclic hydrocarbon groups as defined or illustrated above are also called carbocyclic groups. A carbocyclic ring corresponds to the ring of a cyclic hydrocarbon group as defined or illustrated 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.

[0301] In this specification, the use of the term "substituent" in the phrase "substituentable" is not particularly limited in terms of its effect on the invention, provided that such substituents are chemically permissible.

[0302] In this specification, examples of "substituent" in relation to the term "substitutable" include one or more substituents (preferably one to four substituents) selected independently from the substituent group (I), but are not limited to these.

[0303] The substituent group (I) is a group consisting of halogen atoms; nitro; cyano; hydroxyl; amino; (C1-C6) alkyl; (C1-C6) haloalkyl; (C3-C6) cycloalkyl; (C2-C6) alkenyl; (C2-C6) alkynyl; (C1-C6) alkoxy; phenyl; phenoxy, preferably a group consisting of halogen atoms; nitro; cyano; hydroxyl; amino; (C1-C4) alkyl, more preferably a group consisting of halogen atoms; hydroxyl; (C1-C4) alkyl. Even more preferably a group consisting of halogen atoms; (C1-C4) alkyl.

[0304] In this specification, the terms "as described in this specification" and similar terms are incorporated by reference to all applicable definitions and, if any, all applicable examples, preferred examples, more preferred examples, further preferred examples and exceptionally preferred examples.

[0305] The compounds having isomers in this specification include all isomers and any mixtures of these in any proportion. For example, xylene includes o-xylene, m-xylene, p-xylene, and any mixtures of these in any proportion. For example, dichlorobenzene includes o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, and any mixtures of these in any proportion.

[0306] In this specification, any expression indicating the effect of the invention has the same meaning as the terms "the amount of… used" and "the amount of…" and may be used interchangeably.

[0307] The terms "except for..." and "other than..." used in this instruction manual are interchangeable.

[0308] In this specification, the non-restrictive term "comprise(s) / comprising" can be arbitrarily replaced with the restrictive phrase "consist(s) of / consisting of".

[0309] Unless otherwise expressly stated, all technical and scientific terms used in this specification have the same meaning as commonly understood by the practitioner to whom this disclosure pertains.

[0310] Unless otherwise stated, figures indicating the amount, size, concentration, reaction conditions, etc., used in this specification are to be understood as being modified by the term "approximately". For various samples, the disclosed values ​​are interpreted using the number of significant figures reported and the usual rounding methods. For various samples, the disclosed values ​​are interpreted as the error that necessarily arises from the standard deviation observed in each experimental method.

[0311] Raw material: compound of formula (1)

[0312] The compound of formula (1) is used as a raw material. The compound of formula (1) is a known compound or can be manufactured from a known compound using a known method. A particularly preferred example of the compound of formula (1) is as follows:

[0313]

[0314]

[0315] (Product: Compound of formula (2))

[0316] The product is a compound of formula (2) corresponding to the compound of formula (1) used as a raw material. A particularly preferred example of the compound of formula (2) is as follows:

[0317]

[0318]

[0319] The intermediate of the oxidation reaction is the compound of formula (3) corresponding to the compound of formula (1) used as a raw material. Specific examples of compounds of formula (3) are as follows:

[0320]

[0321]

[0322] As previously described, in the method for producing compound (SO2 derivative) of formula (2) from compound (S derivative) of formula (1), the oxidation reaction proceeds fully, and it is expected that the proportion of compound (SO derivative) of formula (3) in the product is very low. For example, the proportion of compound (SO derivative) of formula (3) 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.

[0323] Equation (1) can be oxidized to obtain equation (3), and then oxidized back to equation (2).

[0324] (Oxidizing agent: hydrogen peroxide)

[0325] Examples of oxidants include, but are not limited to, peroxides, hypochlorites (e.g., sodium hypochlorite, potassium hypochlorite), manganates, and manganese dioxide. Examples of peroxides include, but are not limited to, hydrogen peroxide, peroxyacids and their salts (e.g., peracetic acid), persulfates and their salts (e.g., potassium persulfate (Oxone (registered trademark)), sodium persulfate), etc. From the viewpoint of safety and economic efficiency, hydrogen peroxide is a preferred example of an oxidant.

[0326] The form of hydrogen peroxide can be any form, provided the reaction can proceed. The form of hydrogen peroxide can be appropriately chosen by those skilled in the art. However, considering safety, hazard, and economic efficiency, preferred forms of hydrogen peroxide include 10 to 70 wt% aqueous solutions, more preferably 20 to 65 wt% aqueous solutions, even more preferably 25 to 65 wt% aqueous solutions, even more preferably 30 to 65 wt% aqueous solutions, and most preferably 30 to 60 wt% aqueous solutions. Specific examples of hydrogen peroxide forms include 30 wt% aqueous solutions, 35 wt% aqueous solutions, 50 wt% aqueous solutions, and 60 wt% aqueous solutions, but are not limited to these. The range of hydrogen peroxide concentration can be exemplified by any combination of the lower and upper limits described in this specification.

[0327] The amount of oxidant (preferably hydrogen peroxide) used can be any amount as long as the reaction can proceed. The amount used can be appropriately adjusted by those skilled in the art to which the invention pertains. However, from the viewpoints of yield, byproduct suppression, economic efficiency, safety, and hazard, the amount used is, for example, 2 mol or more for 1 mol of the compound (raw material) of formula (1), preferably 2 to 8 mol, more preferably 2 to 6 mol, even more preferably 2 to 5 mol, and even more preferably 2 to 4 mol.

[0328] (Metal catalyst)

[0329] The metal catalyst can be any metal catalyst, provided the reaction can proceed. Examples of metal catalysts include, but are not limited to, the following:

[0330] 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 oxide (e.g., tungsten oxide (VI), tungsten oxide (VI) is also called tungsten trioxide), tungsten carbide, tungsten chloride (e.g., tungsten chloride (VI), tungsten chloride (VI) is also called tungsten hexachloride), tungsten bromide (e.g., tungsten bromide (V)), tungsten sulfide (e.g., tungsten sulfide (IV), tungsten sulfide (IV) is also called tungsten disulfide), phosphotungstic acid and its salts (e.g., phosphotungstic acid, sodium phosphotungstate, ammonium phosphotungstate, etc.), silicottitic acid and its salts (e.g., silicottitic acid, sodium silicottate, etc.) and mixtures thereof),

[0331] 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 oxide (e.g., molybdenum oxide (VI), molybdenum oxide (VI) is also called molybdenum trioxide), molybdenum chloride (molybdenum chloride (V), molybdenum chloride (V) is also called molybdenum pentachloride), molybdenum sulfide (e.g., molybdenum sulfide (IV), molybdenum sulfide (IV) 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-pentanedione)molybdenum dioxide (VI), etc., and mixtures thereof),

[0332] Iron catalysts (e.g., ferric(I) acetoacetone, ferric chloride(I), ferric nitrate(I), and mixtures thereof),

[0333] Manganese catalysts (e.g., potassium permanganate, manganese(II) oxide, manganese(II) chloride, and mixtures thereof),

[0334] Vanadium catalysts (e.g., vanadium oxyacetone, vanadium oxide (V), vanadium trichloride (V), vanadium triethanolamine (V), vanadium triisopropoxide (V), and mixtures thereof),

[0335] Niobium catalysts (e.g., niobium carbide, niobium chloride (V), niobium pentaethanol (V), and mixtures thereof),

[0336] Tantalum catalysts (e.g., tantalum carbide (TaC), tantalum chloride (V) (TaCl5), tantalum pentaethanol (V) (Ta(OEt)5), and mixtures thereof),

[0337] Titanium catalysts (e.g., titanium tetrachloride, titanium trichloride, titanium tetraisopropoxide (IV), and mixtures thereof),

[0338] Zirconium catalysts (e.g., zirconium dioxide, zirconium chloride (I), zirconium chloride (IV), zirconium oxychloride, and mixtures thereof),

[0339] Copper catalysts (e.g., copper acetate (I), copper acetate (II), copper bromide (I), copper iodide (I), and mixtures thereof),

[0340] Thallium catalysts (e.g., thallium nitrate (I), thallium acetate (I), thallium trifluoroacetate (I), and mixtures thereof).

[0341] In this specification, acids and their salts that can be in hydrate form can be in the form of their hydrates, and any form is also within the scope of this invention.

[0342] Therefore, for example, "sodium tungstate" includes "sodium tungstate dihydrate" and "sodium tungstate decahydrate".

[0343] In this specification, acids and their salts that can be in polyacid form (such as tungstic acid and its salts) can be in polyacid form, and any form is also within the scope of this invention.

[0344] The metal used in metal catalysts is preferably a transition metal. Specifically, examples include 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).

[0345] The transition metal of the metal catalyst is preferably a metal from Group 4, Group 5, or Group 6 of the periodic table, more preferably Group 5 or Group 6, and even more preferably Group 5.

[0346] Preferred examples of metal catalysts are tungsten catalysts and molybdenum catalysts.

[0347] In one respect, a preferred example of a metal catalyst is a tungsten catalyst.

[0348] Among other types of metal catalysts, molybdenum catalysts are preferred examples.

[0349] From the perspectives of yield, byproduct suppression, and economic efficiency, preferred examples of tungsten catalysts include the following:

[0350] Tungstic acid, tungstates, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten sulfide, phosphotungstic acid, silicottitic acid and their salts, and mixtures thereof.

[0351] More preferably, tungstic acid, tungstate, metallic tungsten, tungsten oxide, tungsten carbide, tungsten chloride, their salts, and mixtures thereof.

[0352] More preferably, tungstic acid, tungstate, metallic tungsten, tungsten oxide, tungsten carbide, and mixtures thereof.

[0353] More preferably, tungstate, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metallic tungsten, tungsten oxide (VI), tungsten carbide, and mixtures thereof.

[0354] More preferably, tungstic acid, sodium tungstate, metallic tungsten, tungsten carbide, and mixtures thereof.

[0355] The preferred alternatives are tungstate and sodium tungstate, with sodium tungstate being the most preferred.

[0356] From the perspectives of yield, byproduct suppression, and economic efficiency, preferred examples of molybdenum catalysts include the following:

[0357] Molybdic acid, molybdates, metallic molybdenum, molybdenum oxide, molybdenum carbide, molybdenum chloride, molybdenum sulfide, molybdenum bromide, phosphomolybdic acid, silicomolybdic acid and their salts, and mixtures thereof.

[0358] More preferably, it is molybdic acid, molybdate, metallic molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and mixtures thereof.

[0359] More preferably, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum oxide (VI), molybdenum carbide, molybdenum chloride (V), molybdenum sulfide (IV), phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and mixtures thereof.

[0360] More preferably, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum oxide (VI), molybdenum chloride (V), and mixtures thereof.

[0361] Sodium molybdate, potassium molybdate, and ammonium molybdate are also preferred.

[0362] The best is ammonium molybdate.

[0363] From the perspectives of yield, byproduct suppression, and economic efficiency, the following are further examples of preferred metal catalysts:

[0364] Tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metallic tungsten, tungsten oxide, tungsten carbide,

[0365] Sodium molybdate, potassium molybdate, ammonium molybdate.

[0366] Further preferred examples of metal catalysts include the following:

[0367] Tungstic acid, sodium tungstate,

[0368] Sodium molybdate, potassium molybdate, ammonium molybdate.

[0369] Further preferred examples of metal catalysts include the following:

[0370] Sodium tungstate, ammonium molybdate.

[0371] For other types of catalysts, preferred metal catalysts are those described in [A-101] to [A-113] of this specification.

[0372] Metal catalysts can be used alone or in combination of two or more in any proportion. The form of the metal catalyst can be any form as long as the reaction can proceed. Its form can be appropriately selected by those skilled in the art to which the invention pertains. The amount of metal catalyst used can be any amount as long as the reaction can proceed. Its amount can be appropriately adjusted by those skilled in the art to which the invention pertains. However, from the viewpoints of yield, byproduct suppression, and economic efficiency, its amount used is, for example, 0.001 to 0.1 mol for 1 mol of the compound (starting material) of formula (1), preferably 0.01 to 0.1 mol, more preferably 0.01 to 0.05 mol, and even more preferably 0.03 to 0.05 mol.

[0373] In a given state, examples of carboxylic acids include, but are not limited to, the following.

[0374] Carboxylic acids of formula (a);

[0375]

[0376] A-COOH (a)

[0377] (Where A is hydrogen, a (C1-C6) alkyl group that can be substituted by one or more substituents, a (C3-C6) cycloalkyl group that can be substituted by one or more substituents, a (C2-C6) alkenyl group that can be substituted by one or more substituents, or a (C2-C6) alkynyl group that can be substituted by one or more substituents)

[0378] From the viewpoints of yield, byproduct suppression, and economic efficiency, in a particular state, example A preferably contains a (C1-C4) alkyl group that can be substituted by one or more substituents, more preferably a (C1-C4) alkyl group that can be substituted by one to nine halogen atoms, even more preferably a (C1-C4) alkyl group that can be substituted by one to nine substituents selected from fluorine and chlorine atoms (in other words, a (C1-C4) alkyl group that can be substituted by one to nine fluorine or chlorine atoms), and even more preferably a (C1-C4) alkyl group that can be substituted by chlorine atoms.

[0379] From the same viewpoint, among other states, preferred examples of A include methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, and trichloromethyl. More preferred examples of A include methyl, ethyl, trifluoromethyl, and trichloromethyl. Still more preferred examples of A include methyl, trifluoromethyl, and trichloromethyl. Still more preferred examples of A include methyl and trifluoromethyl. From the same viewpoint, among other states, preferred examples of A include methyl, ethyl, difluoromethyl, trifluoromethyl, dichloromethyl, and trichloromethyl. More preferred examples of A include methyl, difluoromethyl, trifluoromethyl, dichloromethyl, and trichloromethyl. Still more preferred examples of A include methyl, dichloromethyl, and trichloromethyl. In other states, A is trifluoromethyl. In other states, A is trichloromethyl. In other states, A is dichloromethyl. In other states, A is methyl.

[0380] In other forms, examples of carboxylic acids include, but are not limited to, the following: substituted 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 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); substituted saturated or unsaturated aliphatic tricarboxylic acids (e.g., citric acid). In this specification, formic acid is understood to be one type of aliphatic monocarboxylic acid. Preferred examples of carboxylic acids include, but are not limited to, the following: acetic acid, trifluoroacetic acid, trichloroacetic acid, and more preferably acetic acid. In other forms, preferred examples of carboxylic acids include acetic acid, difluoroacetic acid, trifluoroacetic acid, dichloroacetic acid, and trichloroacetic acid. More preferred examples of carboxylic acids include acetic acid, dichloroacetic acid, and trichloroacetic acid. Preferred examples of carboxylic acids include acetic acid and dichloroacetic acid.

[0381] The amount of carboxylic acid used is not particularly limited as long as the effects of the present invention can be demonstrated. However, from the viewpoints of yield, byproduct suppression, and economic efficiency, in one embodiment, the lower limit of the amount of carboxylic acid used for 1 mol of, for example, the compound (raw material) of formula (1) is more than 0 (zero) mol, preferably 0.01 mol or more, more preferably 0.05 mol or more, and even more preferably 0.1 mol or more, 0.3 mol or more, 0.5 mol or more, 1 mol or more, 2 mol or more, 3 mol or more, and 5 mol or more. In other embodiments, the lower limit of the amount of carboxylic acid used for 1 mol of, for example, the compound (raw material) of formula (1) is preferably 8 mol or more, 10 mol or more, 12 mol or more, 15 mol or more, 18 mol or more, and 20 mol or more. In other cases, the lower limit of the amount of carboxylic acid used is 26 mol or more for 1 mol of, for example, the compound (raw material) of formula (1), preferably more than 26 mol, more preferably 27 mol or more, 28 mol or more, even more preferably 30 mol or more, 32 mol or more, and even more preferably 35 mol or more. From the same point of view as above, in one case, the upper limit of the amount of carboxylic acid used is 90 mol or less, 70 mol or less, or 55 mol or less for 1 mol of, for example, the compound (raw material) of formula (1). In other cases, the upper limit of the amount of carboxylic acid used is 30 mol or less, 20 mol or less, 10 mol or less, or 9 mol or less for 1 mol of, for example, the compound (raw material) of formula (1). In yet another case, the upper limit of the amount of carboxylic acid used is 5 mol or less, or 0.3 mol or less for 1 mol of, for example, the compound (raw material) of formula (1). The range of the amount of carboxylic acid used can be, for example, the appropriate and arbitrary combination of the lower and upper limits mentioned above. For example, the combination of the upper and lower limits is as described below, but not limited to these: From the same point of view as above, in one state, relative to 1 mol of compound (raw material) of, for example, formula (1), the amount of carboxylic acid used is more than 0 (zero) mol to less than 70 mol, more than 0 (zero) mol to less than 55 mol, more than 0 (zero) mol to less than 30 mol, preferably more than 0.01 mol to less than 70 mol, more than 0.01 mol to less than 55 mol, more than 0.01 mol to less than 30 mol, more preferably more than 0.05 mol to less than 70 mol, more than 0.05 mol to less than 55 mol, more than 0.05 mol to less than 30 mol, and even more preferably more than 0.1 mol to less than 70 mol, more than 0.1 mol to less than 55 mol, more than 0.1 mol to less than 30 mol. In other cases, relative to 1 mol of the compound (raw material) of formula (1), for example, the amount of carboxylic acid used is more than 26 mol and less than 70 mol, more than 26 mol and less than 55 mol, preferably more than 30 mol and less than 70 mol, more than 30 mol and less than 55 mol, and even more preferably more than 35 mol and less than 70 mol, more than 35 mol and less than 55 mol. Depending on the purpose and circumstances, the above-mentioned amount of carboxylic acid can be used as a solvent.

[0382] As long as the effects of the present invention can be demonstrated, one or all of the carboxylic acid may be a salt and / or anhydride.

[0383] (Acid catalyst)

[0384] The oxidation reaction of this invention can be carried out in the presence of an acid catalyst or in the absence of an acid catalyst. Whether to use an acid catalyst can be appropriately determined by those skilled in the art to which this invention pertains. The acid catalyst is an acid other than a carboxylic acid. Examples of acid catalysts include, but are not limited to, the following: inorganic 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 can be a salt of these.

[0385] Acid catalysts can be used alone or in combination of two or more in any proportion. The form of the acid catalyst can be any form as long as the reaction can proceed. For example, sulfuric acid can be 50% to 98% sulfuric acid, 50% to 100% sulfuric acid, preferably 90% to 98% sulfuric acid, or 90% to 100% sulfuric acid (concentrated sulfuric acid), but is not limited to these. The form of the acid catalyst can be appropriately selected by those skilled in the art to which this invention pertains. The amount of acid catalyst used can be any amount as long as the reaction can proceed. The amount of acid catalyst used can be appropriately adjusted by those skilled in the art to which this invention pertains. However, from the viewpoints of yield, byproduct suppression, and economic efficiency, for a given sample, relative to 1 mol of compound (raw material) of, for example, formula (1), the amount of acid catalyst used is 0 (zero) to 0.5 mol, more than 0 (zero) 0.5 mol, 0.005 to 0.5 mol, 0.01 to 0.5 mol, 0.05 to 0.5 mol, preferably 0 (zero) to 0.2 mol, more than 0 (zero) 0.2 mol, 0.005 to 0.2 mol, 0.01 to 0.2 mol, 0.05 to 0.2 mol.

[0386] (Phase transfer catalyst)

[0387] The oxidation reaction of this invention can be carried out in the presence of a phase transfer catalyst, or in the absence of a phase transfer catalyst. Whether or not to use a phase transfer catalyst can be appropriately determined by someone skilled in the art to which this invention pertains. Examples of phase transfer catalysts include, but are not limited to, those comprising quaternary ammonium salts (e.g., tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, octyltrimethylammonium chloride, octyltrimethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, benzyllauryl dimethylammonium chloride (benzyl dodecyl dimethylammonium chloride), benzyllauryl dimethylammonium bromide (benzyl dodecyl dimethylammonium chloride)). Phase transfer catalysts include methyl ammonium bromide, myristyltrimethylammonium chloride (tetradecyltrimethylammonium chloride), myristyltrimethylammonium bromide (tetradecyltrimethylammonium bromide), benzyl dimethylstearylammonium chloride (benzyl octadecyl dimethylammonium chloride), benzyl dimethylstearylammonium bromide (benzyl octadecyl dimethylammonium 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 viewpoints of yield, by-product suppression, and economic efficiency, preferred examples of phase transfer catalysts are tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium hydrogen sulfate, with tetrabutylammonium hydrogen sulfate being more preferred. Tetrabutylammonium hydrogen sulfate is abbreviated as TBAHS.

[0388] Phase transfer catalysts can be used alone or in combination of two or more in any proportion. The form of the phase transfer catalyst can be any form, provided the reaction can proceed. The form of the phase transfer catalyst can be appropriately selected by those skilled in the art to which this invention pertains. The amount of phase transfer catalyst used can be any amount, provided the reaction can proceed. The amount of phase transfer catalyst used can be appropriately adjusted by those skilled in the art to which this invention pertains. However, from the viewpoints of yield, byproduct suppression, and economic efficiency, for a given state, relative to 1 mol of compound (raw material) such as formula (4), the amount of phase transfer catalyst used is 0 (zero) to 0.5 mol, more than 0 (zero) 0.5 mol, 0.005 to 0.5 mol, 0.01 to 0.5 mol, 0.05 to 0.5 mol, preferably 0 (zero) to 0.2 mol, more than 0 (zero) 0.2 mol, 0.005 to 0.2 mol, 0.01 to 0.2 mol, 0.05 to 0.2 mol.

[0389] (Reaction solvent)

[0390] From the viewpoint of facilitating the reaction, the oxidation reaction of the present invention is preferably carried out in the presence of a solvent. The reaction solvent can be any solvent, provided the reaction can proceed. The reaction solvent can be a carboxylic acid or an organic solvent other than a carboxylic acid. In any case, it can also be carried out in the presence of an aqueous solvent.

[0391] In one embodiment, the reaction solvent may include, but is not limited to, the following: aromatic hydrocarbon derivatives (e.g., benzenes substituted with 1 to 3 (preferably 1 or 2) 4 (C1-C4) alkyl groups (preferably (C1-C3) alkyl groups, more preferably (C1-C2) alkyl groups) and chlorine atoms, specifically, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene. Specific examples of aromatic hydrocarbon derivatives may include nitrobenzene), halogenated aliphatic hydrocarbons (e.g., (C1-C4) alkanes substituted with 1 to 10 halogen atoms (preferably chlorine atoms), preferably (C1-C2) alkanes substituted with 1 to 6 chlorine atoms, specifically, dichloromethane, 1,2-dichloroethane (EDC) (e.g., (C1-C6) alcohols, specifically, for example, methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, pentanol, dipentanol, 3-pentanol, 2-methyl-1-butanol, isopentanol, terpentanol, hexanol. Alcohols are preferably (C1-C5) alcohols, more preferably (C1-C4) alcohols, and specific examples of these are included in suitable examples in the above examples. Examples of alcohols may include cyclohexanol), nitrile (e.g., (C2-C5) alkyl nitrile, preferably (C2-C3) alkyl nitrile, specifically, for example, acetonitrile, propionitrile, butyronitrile, isobutyronitrile, succinate, preferably acetonitrile. In this specification, C2 alkyl nitrile is acetonitrile. Examples of nitrile may include benzonitrile), carboxylic acids (acetic acid, chloroform), Propionic acid, trifluoroacetic acid, dichloroacetic acid, trichloroacetic acid), carboxylic acid esters (e.g., (C1-C4) alkyl (C2-C6) carboxylic acid esters, preferably (C1-C4) alkyl (C2-C3) carboxylic acid esters, specifically such as methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers, etc. (in this invention, "isomers of butyl acetate" are equivalent to "butyl acetate", and "isomers of pentyl acetate" are equivalent to "pentyl acetate")), ethers (e.g., tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentylmethyl ether (CPME) The following are permitted compounds: methyl tributyl ether, 1,2-dimethoxyethane (DME), diethylene glycol dimethyl ether (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)alkylamides, specifically, for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC). Examples of amides may include N-methylpyrrolidone (NMP)); ureas (e.g., N,N'-dimethylimidazolinone (DMI), tetramethylurea); sulfides (e.g., cyclobutane); water; and any combination thereof in any proportion.

[0392] 2-Propanol is also known as isopropyl alcohol or isopropanol.

[0393] Tertiary butanol is also known as tertiary butyl alcohol.

[0394] From the perspectives of yield, byproduct suppression, 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.

[0395] Preferred reaction solvents include alcohols, nitriles, carboxylic acids, amides, water, and any combination thereof in any proportion.

[0396] Further preferred examples of reaction solvents are alcohols, nitriles, carboxylic acids, water, and any combination thereof in any proportion.

[0397] From the same viewpoint as above, preferred examples of reaction solvents include methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, pentanol, dipentanol, 3-pentanol, 2-methyl-1-butanol, isopentanol, terpentanol, 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.

[0398] More specific examples of reaction solvents include methanol, ethanol, propanol, 2-propanol, butanol, dibutanol, isobutanol, terbutanol, pentanol, dipentanol, 3-pentanol, 2-methyl-1-butanol, isopentanol, terpentanol, acetonitrile, acetic acid, dichloroacetic acid, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), water, and any combination thereof in any proportion.

[0399] Further preferred examples of reaction solvents are methanol, ethanol, propanol, 2-propanol, butanol, acetonitrile, acetic acid, dichloroacetic acid, N,N-dimethylformamide (DMF), water, and any combination thereof in any proportion.

[0400] Further preferred examples of reaction solvents are methanol, acetonitrile, acetic acid, dichloroacetic acid, N,N-dimethylformamide (DMF), water, and any combination thereof in any proportion.

[0401] Further preferred examples of reaction solvents are methanol, acetonitrile, acetic acid, dichloroacetic acid, water, and any combination thereof in any proportion.

[0402] In other cases, preferred reaction solvents are those described in this specification, for example, those specified in [A-40] to [A-70] and [A-78] of this specification. These examples and specific cases are as described in this specification. All methods described in this specification, such as those specified in [A-40] to [A-70] and [A-78], may be performed "in the presence of an aqueous solvent".

[0403] Examples of preferred organic solvents include those defined in this specification by the following parameters.

[0404] (Number of receptors)

[0405] The acceptor number in this specification can be referred to, for example, the following literature. The definition of the acceptor number based on the 31P-NMR chemical shift value is described in the aforementioned literature and is incorporated herein by reference. Examples of solvents with specified values ​​are described in the aforementioned literature and are incorporated herein by reference.

[0406] (Relative permittivity)

[0407] In this specification, references to relative permittivity (also commonly known as "dielectric constant") can be made to the following documents, for example: Japan Chemical Society, "Chemistry Handbook (Basic Edition)," Maruzen Co., Ltd., Revised 5th 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 herein by reference. Examples of solvents with specified values ​​are described in the foregoing documents. These are incorporated herein by reference.

[0408] (Rohrschneider's polarity parameters)

[0409] For information regarding Rallsneider's polarity parameters, please refer to, for example, the following website: https: / / www.shodex.com / ja / dc / 06 / 0117.html, which is incorporated herein by reference. Examples of solvents with specified values ​​are described in the foregoing literature, which is incorporated herein by reference.

[0410] Examples of organic solvents other than carboxylic acids are as described in this specification. When using organic solvents other than carboxylic acids, from the viewpoints of yield, byproduct suppression, and economic efficiency, the following examples of amounts are used: In one state, the lower limit of the amount of organic solvent other than carboxylic acids used for 1 mol of compound (1) is more than 0 (zero) liters, more than 0.1 liters, preferably more than 0.2 liters, more preferably more than 0.3 liters, more than 0.4 liters, and even more preferably more than 0.5 liters, more than 0.8 liters. In one state, the upper limit of the amount of organic solvent other than carboxylic acids used for 1 mol of compound (1) is less than 5 liters, preferably less than 3 liters, more preferably less than 2 liters, and even more preferably less than 1 liter. The range of the amount of organic solvent other than carboxylic acids used is, for example, an appropriate and arbitrary combination of the above-mentioned lower and upper limits. For example, the combination of the upper and lower limits is as follows, but not limited to these: From the same point of view as above, in one state, relative to 1 mole of compound (raw material) of, for example, formula (1), the amount of organic solvent used, excluding carboxylic acid, is 0.3 liters to 3 liters, preferably 0.5 liters to 2 liters.

[0411] In any case, as long as the reaction can proceed, the solvent can be a single layer or can be separated into two layers. On the other hand, when examining the present invention after its completion, when using carboxylic acids and specific organic solvents, it is determined from the viewpoints of solubility and the affinity between organic solvents and water solvents that the invention of this patent application obtains better conditions (reaction system).

[0412] In addition, it is determined that, in accordance with the present invention, by using carboxylic acids, appropriate conditions can be selected corresponding to the purposes and conditions of industrial implementation. These are the advantageous effects of the present invention.

[0413] "Reaction solvent" refers to all organic solvents other than carboxylic acids, carboxylic acids used as solvents, and aqueous solvents used in the reaction. "Reaction solvent" does not include organic solvents and aqueous solvents used in post-reaction processing (e.g., separation, purification). "Organic solvents" used in the reaction include organic solvents in the reactant solution and the reactant solution. "Aqueous solvents" used in the reaction include water (e.g., water in an aqueous hydrogen peroxide solution) in the reactant solution and the reactant solution.

[0414] The amount of reaction solvent used is not particularly limited as long as it can sufficiently stir the reaction system. However, from the viewpoints of yield, byproduct suppression, and economic efficiency, for one state, relative to 1 mole of, for example, the compound (starting material) of formula (1), the amount of reaction solvent used is 0 (zero) to 10 L (liters), 0 (zero) to 5 L (liters), more than 0 (zero) to 10 L (liters), more than 0 (zero) to 5 L (liters), 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, 0.4 to 2 L. When two or more solvents are used in combination, the ratio of the two or more solvents can be any ratio as long as the reaction can proceed.

[0415] (Reaction temperature)

[0416] The reaction temperature is not particularly limited as long as the effects of the present invention are demonstrated. However, from the viewpoints of yield, byproduct suppression, and economic efficiency, in one state, 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, exceeding 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, or 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, or 60°C, 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, a suitable and arbitrary combination of the above-mentioned lower and upper limits. For example, the combination of the upper and lower limits is as described below, but is not limited to these. From the same viewpoint as above, in other states, the reaction temperature is, for example, 10°C to 100°C, preferably 20°C to 100°C, more preferably 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 other states, the reaction temperature is, for example, 10°C to 80°C, preferably 20°C to 80°C, more preferably 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 perspective as above, in other scenarios, the reaction temperature is, for example, between 10°C and 60°C, preferably between 20°C and 60°C, more preferably between 35°C and 60°C, even more preferably between 40°C and 60°C, even more preferably between 45°C and 60°C, and even more preferably between 50°C and 60°C. Lower reaction temperatures offer better safety, and temperatures closer to room temperature (normal temperature) are more advantageous, contributing to sustainability, but are not limited to these conditions.

[0417] (Reaction time)

[0418] The reaction time is not particularly limited as long as the effects of the present invention can be demonstrated. However, from the viewpoints of yield, by-product suppression, and economic efficiency, the lower limit of the reaction time for one embodiment is, for example, more than 1 hour, more than 1 hour and 30 minutes, or more than 2 hours, but is not limited to these. The upper limit of the reaction time for one embodiment is, for example, less than 48 hours, less than 36 hours, preferably less than 24 hours, less than 16 hours, or less than 12 hours, but is not limited to these. For other embodiments, the upper limit of the reaction time is, for example, less than 8 hours, less than 6 hours, less than 5 hours, or less than 4 hours, but is not limited to these. The range of reaction time is, for example, a suitable and arbitrary combination of the above lower and upper limits. For example, from 1 hour to 48 hours, from 1 hour to 36 hours, more preferably from 1 hour to 24 hours, but is not limited to these. However, the manufacturer may adjust the reaction time appropriately according to the purpose and conditions.

[0419] The present invention will now be described in more detail by way of examples, but the present invention is not limited to these examples.

[0420] In this specification, the determination of the physical properties and yields of the examples, comparative examples, and reference examples was performed using the following machines and conditions. Furthermore, the products obtained in this invention are known compounds and can be identified by conventional methods known to those skilled in the art to which this invention pertains.

[0421] (HPLC analysis: High-speed liquid chromatography)

[0422] (HPLC analysis conditions)

[0423] Machine: LC2010 series manufactured by Shimadzu Corporation or based on this model.

[0424] Column: YMC-Pack, ODS-A, A-312 (150mm x 6.0mm ID, S-5μm, 120A)

[0425] Eluate:

[0426] [Table 1]

[0427] Flow rate: 1.0 ml / min

[0428] Detected: UV 230nm

[0429] Column temperature: 40℃

[0430] Injection volume: 5μL

[0431] For HPLC analysis methods, please refer to the following literature if necessary.

[0432] Reference (a): Japan Chemical Society (ed.), "New Experimental Chemistry Lectures 9: Analytical Chemistry II", pp. 86-112 (1977), published by Shingo Iizumi and Maruzen Co., Ltd.

[0433] Reference (b): Japan Chemical Society (ed.), "Lectures on Experimental Chemistry 20-1: Analytical Chemistry", 5th edition, pp. 130-151 (2007), published by Seishiro Murata and Maruzen Co., Ltd.

[0434] (1H-NMR: 1H nuclear magnetic resonance spectrum)

[0435] Machine: JEOL JMN-ECS-300 or JEOL JMN-Lambda-400 (manufactured by JEOL RESONANCE)

[0436] Solvents: CDCl3 and / or DMSO-d6

[0437] Internal reference material: tetramethylsilane (TMS) and other substances known to those skilled in the art to which this invention pertains.

[0438] (Yield and Purity)

[0439] Unless otherwise specified, the yield of this invention can be calculated from the mole number of the target compound obtained from the mole number of the starting compound.

[0440] In other words, the term "yield" refers to "Moore's yield".

[0441] Therefore, the yield is expressed by the following formula:

[0442] Yield (%) = (number of moles of the desired compound obtained) / (number of moles of the starting compound) × 100

[0443] However, HPLC area percentage analysis or GC area percentage analysis can also be used to evaluate, for example, the reaction yield of the target substance, the yield of impurities, and the purity of the product.

[0444] In this instruction manual, room temperature and ambient temperature are defined as 10°C to 35°C.

[0445] In this manual, the term "over night" refers to 8 to 16 hours.

[0446] In this specification, the operation of "aging" includes stirring a mixture by means of conventional methods known to those skilled in the art to which this invention pertains.

[0447] Unless otherwise specified, "sulfuric acid" in the examples described herein refers to concentrated sulfuric acid. Examples of concentrated sulfuric acid include 98% sulfuric acid, but are not limited to these.

[0448] [Example]

[0449] [Example 1]

[0450] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0451]

[0452]

[0453] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetonitrile 10.0 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. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 for 6 hours.

[0454] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 2.51% at this point (HPLC area percentage; 230 nm). The mixture was homogeneous.

[0455] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 95.6% for the target compound (2-a).

[0456] 1H-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)

[0457] [Example 2]

[0458] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0459]

[0460]

[0461] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetonitrile 10.0 g (1.5 L / mol), acetic acid (0.26 g, 4.25 mmol, 50 mol%), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 allowed to mature for 12 hours.

[0462] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 1.90% at this point (HPLC area percentage; 230 nm).

[0463] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 97.4% for the target compound (2-a).

[0464] [Example 3]

[0465] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0466]

[0467]

[0468] Under a nitrogen atmosphere, compound (1-a) (3.05 g, purity: 100%, 8.5 mmol, 100 mol%), acetonitrile 10.0 g (1.5 L / mol), acetic acid (0.051 g, 0.85 mmol, 10 mol%), and sodium tungstate dihydrate (0.084 g, 0.26 mmol, 3 mol%) were added to a reaction flask. A 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 allowed to mature for 12 hours.

[0469] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 2.87% at this point (HPLC area percentage; 230 nm).

[0470] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 96.4% for the target compound (2-a).

[0471] [Reference Example 1]

[0472] Japanese Patent Application Publication No. 2013-512201 (JP2013-512201A) (Patent Document 3) Example 9C Reproduction Experiment

[0473] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0474]

[0475]

[0476] 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 over 20 minutes at an internal temperature of 26°C to 35°C. The mixture was then matured for 16 hours while maintaining the internal temperature at 26°C to 35°C.

[0477] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 5.0% (HPLC area percentage) at 16 hours of aging.

[0478] Add 4g of water to the reaction mixture and allow it to mature at 10°C for 1 hour. Filter out the precipitated crystals. Wash the obtained crystals sequentially with 20ml of petroleum ether and 20ml of water. HPLC analysis (area percentage; 230nm) showed that the obtained crystals were 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative), the reaction intermediate, with an HPLC area percentage of 5.5%.

[0479] Reference Example 1 is a reproduction experiment of Example 9C in Japanese Patent Application Publication No. 2013-512201 (JP2013-512201A) (Patent Document 3). Even after 16 hours of maturation, the compound (3-a) of the reaction intermediate still retained 5.0% of the product according to the manufacturing method described in Japanese Patent Application Publication No. 2013-512201 (JP2013-512201A) (Patent Document 3). Furthermore, even after purification, the proportion of compound (3-a) did not decrease. This again confirms that purifying the compound of formula (2) is difficult by separating the compound of formula (2) from the compound of formula (3).

[0480] [Reference Example 2]

[0481] Chinese Patent Publication No. 111574511 (CN111574511A) (Patent Document 5): Reproduction Experiment of Example 5

[0482] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0483]

[0484]

[0485] 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. Meanwhile, a 30% aqueous solution of hydrogen peroxide (containing 2.75 g, 24.2 mmol, 285 mol%, and 1.9 g of water (0.23 L / mol)) was added dropwise over 1 hour at room temperature (internal temperature 25°C to 30°C). The mixture was stirred at room temperature (internal temperature 25°C to 30°C) for 6 hours.

[0486] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 12.74% at this point (HPLC area percentage; 230 nm).

[0487] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 79.9% for the target compound (2-a).

[0488] Reference Example 2 is a reproduction experiment of Example 5 in Chinese Patent Publication No. 111574511 (CN111574511A) (Patent Document 5). Even when using a large amount of carboxylic acid (acetic acid), the manufacturing method described in Chinese Patent Publication No. 111574511 (CN111574511A) (Patent Document 5) still leaves the reaction intermediate compound (3-a).

[0489] [Example 4]

[0490] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0491]

[0492]

[0493] 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. Meanwhile, a 30% aqueous solution of hydrogen peroxide (containing 2.75 g, 24.2 mmol, 285 mol%, and 1.9 g of water (0.23 L / mol)) was added dropwise at an internal temperature of 71 °C over 1 hour. The mixture was stirred at 71 °C for 6 hours.

[0494] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 6-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0495] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 88.0% for the target compound (2-a).

[0496] [Example 5]

[0497] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0498]

[0499]

[0500] 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 a 35% hydrogen peroxide aqueous solution (containing 0.69 g, 7.13 mmol, 285 mol%, and 0.45 g (0.18 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C for 2 hours, during which crystals precipitated, forming a suspension. The suspension was then further aged at an internal temperature of 50°C to 55°C for 2 hours.

[0501] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0.4% at this point (HPLC area percentage; 230 nm).

[0502] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 89.6% for the target compound (2-a).

[0503] [Example 6]

[0504] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0505]

[0506]

[0507] 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 solution of hydrogen peroxide (containing 0.71 g, 6.25 mmol, 250 mol%, and 0.50 g (0.2 L / mol) of water) was 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 matured for 2 hours until crystallization occurred, forming a suspension. This suspension was then matured again at an internal temperature of 50°C to 55°C for 2 hours.

[0508] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 1.1% at this point (HPLC area percentage; 230 nm).

[0509] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 90.0% for the target compound (2-a).

[0510] [Example 7]

[0511] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0512]

[0513]

[0514] 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. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 allowed to mature for 9 hours.

[0515] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 2.15% at this point (HPLC area percentage; 230 nm).

[0516] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 94.1% for the target compound (2-a).

[0517] [Example 8]

[0518] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0519]

[0520]

[0521] 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. The mixture was heated to an internal temperature of 50°C to 55°C. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 allowed to mature for 5 hours. The mixture was homogeneous.

[0522] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0.22% at this point (HPLC area percentage; 230 nm).

[0523] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 91.3% for the target compound (2-a).

[0524] [Example 9]

[0525] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0526]

[0527]

[0528] 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), 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. The mixture was heated to an internal temperature of 50°C to 55°C. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 allowed to mature for 3 hours.

[0529] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0530] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 95.5% for the target compound (2-a).

[0531] [Example 10]

[0532] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0533]

[0534]

[0535] 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. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 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 allowed to mature for 5 hours.

[0536] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 1.98% at this point (HPLC area percentage; 230 nm).

[0537] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 96.2% for the target compound (2-a).

[0538] [Example 11]

[0539] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0540]

[0541]

[0542] 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. Meanwhile, a 35% aqueous solution of hydrogen peroxide (containing 2.48 g, 25.5 mmol, 300 mol%, and 1.6 g of water (0.2 L / mol)) was 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 allowed to mature for 24 hours.

[0543] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 1.88% at this point (HPLC area percentage; 230 nm).

[0544] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 93.0% for the target compound (2-a).

[0545] [Example 12]

[0546] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0547]

[0548]

[0549] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 3 hours.

[0550] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0.61% at this point (HPLC area percentage; 230 nm).

[0551] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 94.3% for the target compound (2-a).

[0552] [Example 13]

[0553] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0554]

[0555]

[0556] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 3 hours.

[0557] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0.95% at this point (HPLC area percentage; 230 nm).

[0558] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 91.0% for the target compound (2-a).

[0559] [Example 14]

[0560] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0561]

[0562]

[0563] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 4 hours.

[0564] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 1.71% at this point (HPLC area percentage; 230 nm).

[0565] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 95.6% for the target compound (2-a).

[0566] [Example 15]

[0567] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0568]

[0569]

[0570] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 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 allowed to mature for 3 hours.

[0571] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0572] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 97.8% for the target compound (2-a).

[0573] [Example 16]

[0574] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0575]

[0576]

[0577] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 6 hours.

[0578] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0.45% at this point (HPLC area percentage; 230 nm).

[0579] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 97.5% for the target compound (2-a).

[0580] [Example 17]

[0581] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0582]

[0583]

[0584] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and matured for 6 hours.

[0585] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0.16% at this point (HPLC area percentage; 230 nm).

[0586] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 98.1% for the target compound (2-a).

[0587] [Example 18]

[0588] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0589]

[0590]

[0591] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and matured for 8 hours.

[0592] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 2.87% at this point (HPLC area percentage; 230 nm).

[0593] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 93.3% for the target compound (2-a).

[0594] [Example 19]

[0595] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0596]

[0597]

[0598] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 4 hours. From the start of the reaction until its completion, the mixture was a homogeneous solution.

[0599] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0600] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 89.9% for the target compound (2-a).

[0601] [Example 20]

[0602] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0603]

[0604]

[0605] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 2 hours. From the start of the reaction until its completion, the mixture was a homogeneous solution.

[0606] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0607] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 91.7% for the target compound (2-a).

[0608] [Example 21]

[0609] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0610]

[0611]

[0612] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 2 hours. From the start of the reaction until its completion, the mixture was a homogeneous solution.

[0613] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0614] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 91.3% for the target compound (2-a).

[0615] [Example 22]

[0616] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0617]

[0618]

[0619] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 3.5 hours. From the start of the reaction until its completion, the mixture was a homogeneous solution.

[0620] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0621] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 91.7% for the target compound (2-a).

[0622] [Example 23]

[0623] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0624]

[0625]

[0626] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was matured at an internal temperature of 41 °C under stirring under reflux for 5.5 hours. From the start of the reaction until its completion, the mixture was an emulsion.

[0627] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0628] Acetonitrile was added to the reaction mixture to prepare a homogeneous solution. Analysis using HPLC with external standards showed a yield of 86.5% for the target compound (2-a).

[0629] [Example 24]

[0630] Preparation of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methanesulfonyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 2-a)

[0631]

[0632]

[0633] 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 a 35% aqueous solution of hydrogen peroxide (containing 0.73 g, 7.50 mmol, 300 mol%, and 0.47 g (0.2 L / mol) of water) were added to a reaction flask. The mixture was stirred at an internal temperature of 50°C to 55°C and allowed to mature for 2 hours. From the start of the reaction until its completion, the mixture was a homogeneous solution.

[0634] The reaction intermediate 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)methylsulfinyl]-4,5-dihydro-5,5-dimethylisoxazole (compound 3-a; SO derivative) was 0% at this point (HPLC area percentage; 230 nm).

[0635] Acetonitrile was added to the reaction mixture. Analysis using HPLC with external standards showed a yield of 89.3% for the target compound (2-a).

[0636] All publications, patents, and patent applications described in this specification are incorporated herein in their entirety for the purpose of illustrating and disclosing the methods described in those publications, patents, and patent applications that may be used in connection with the descriptions herein. For the purpose of understanding or to make the disclosure of this invention complete, all publications, patents, and patent applications described in this specification are explicitly incorporated herein by reference to the extent necessary, as if individually incorporated. All publications, patents, and patent applications mentioned above and discussed in their entirety in this specification are provided only for disclosures prior to the filing date of this patent application.

[0637] All methods described in this specification can be combined arbitrarily, except in cases where there are obvious contradictions in the content. However, the combinations of methods described in this specification exclude such contradictory combinations.

[0638] Any methods and reagents that are identical or equivalent to those described in this specification may also be used in the methods and practices of this invention. Therefore, this invention is not intended to be bound by the foregoing description, but rather to be defined according to the claims and their equivalents. These equivalents are included within the scope of this invention as defined by the appended claims.

Claims

1. A method for producing a compound of formula (2), comprising reacting a compound of formula (1) with an oxidizing agent in the presence of a metal catalyst and in the presence of a carboxylic acid selected from dichloroacetic acid and trichloroacetic acid, wherein, The reaction is carried out at temperatures above 35°C; wherein R1, R2, and R3 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents. R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C1-C6) alkoxy group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or R4 and R5 together with the carbon atoms linked thereto form a 3 to 12-membered carbon ring, wherein the ring formed herein can be substituted with one or more substituents.

2. The manufacturing method as described in claim 1, wherein, The reaction was carried out at temperatures above 40°C.

3. The manufacturing method as described in claim 1, wherein, The reaction was carried out at a temperature above 45°C.

4. The manufacturing method as described in any one of claims 1 to 3, wherein, The reaction was carried out at temperatures below 60°C.

5. The manufacturing method as described in any one of claims 1 to 3, wherein, The reaction was carried out at temperatures below 55°C.

6. A method for producing a compound of formula (2), comprising reacting a 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, wherein, The amount of carboxylic acid is 18 mol or more relative to 1 mol of compound (1); wherein R1, R2 and R3 are each independently a (C1-C6) alkyl group that can be substituted by one or more substituents; a (C3-C6) cycloalkyl group that can be substituted by one or more substituents; a (C2-C6) alkenyl group that can be substituted by one or more substituents; a (C2-C6) alkynyl group that can be substituted by one or more substituents; or a (C6-C10) aryl group that can be substituted by one or more substituents. R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C1-C6) alkoxy group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or R4 and R5 together with the carbon atoms linked thereto form a 3 to 12-membered carbon ring, wherein the ring formed herein can be substituted with one or more substituents.

7. A method for producing a compound of formula (2), comprising reacting a 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, wherein, The reaction is carried out in the presence of an organic solvent other than a carboxylic acid; wherein R1, R2, and R3 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents. R4 and R5 are each independently a (C1-C6) alkyl group that can be substituted with one or more substituents; a (C3-C6) cycloalkyl group that can be substituted with one or more substituents; a (C2-C6) alkenyl group that can be substituted with one or more substituents; a (C1-C6) alkoxy group that can be substituted with one or more substituents; or a (C6-C10) aryl group that can be substituted with one or more substituents; or R4 and R5 together with the carbon atoms linked thereto form a 3 to 12-membered carbon ring, wherein the ring formed herein can be substituted with one or more substituents.

8. The manufacturing method as described in claim 7, wherein, The organic solvent is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, and acetamines.

9. The manufacturing method as described in claim 7, wherein, The organic solvent is selected from halogenated aliphatic hydrocarbons, alcohols, and nitriles.

10. The manufacturing method as described in claim 7, wherein, The organic solvent is selected from (C1-C4) alkanes, (C1-C6) alcohols, and (C2-C5) alkyl nitriles that can be substituted with 1 to 10 halogen atoms.

11. The manufacturing method as described in claim 7, wherein, The organic solvent is selected from dichloromethane, methanol, and acetonitrile.

12. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, The carboxylic acid is dichloroacetic acid.

13. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, The carboxylic acid is trichloroacetic acid.

14. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, The metal catalyst is selected from tungsten catalysts and molybdenum catalysts.

15. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, The metal catalyst is a tungsten catalyst.

16. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, The metal catalyst is a molybdenum catalyst.

17. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, The oxidant is hydrogen peroxide.

18. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, R1 is a (C1-C4) alkyl, R2 is a (C1-C4) perfluoroalkyl, R3 is a (C1-C4) alkyl that can be substituted with 1 to 9 fluorine atoms, and R4 and R5 are each independently (C1-C4) alkyl.

19. A manufacturing method as described in any one of claims 1 to 3 or claims 6 to 11, wherein, R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, and R4 and R5 are methyl.

20. The manufacturing method as described in claim 4, wherein, R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, and R4 and R5 are methyl.

21. The manufacturing method as described in claim 5, wherein, R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, and R4 and R5 are methyl.

22. The manufacturing method as described in claim 14, wherein, R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, and R4 and R5 are methyl.

23. The manufacturing method as described in claim 17, wherein, R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, and R4 and R5 are methyl.

Images