Process for producing herbicide and intermediate thereof

Abstract

The disclosure relates to a sulfone derivative that is useful as a herbicide, and an industrially preferable production method for an intermediate of said derivative. Also disclosed is a production method for a compound of formula (4) , the method including step ii, wherein step ii is a step for producing a compound of formula (4) by reacting a compound of formula (2) with a compound of formula (3) in the presence of a base. Also disclosed is a production method for a compound of formula (5) , the method including step iii, wherein step iii is a step for producing a compound of formula (5) by reacting a compound of formula (4) with hydrogen peroxide in the presence of a metal catalyst. o R4 N R5 R2 x1 R44 oN R5 Step ii R2 S11 N. 3 + O-R HN / / N S Base N. O-R³ R1 HX2.H2N N (2) (3) R1 (4) 20 24 21 96 74 12 S ep 2 02 4 S e p 2 0 2 4 P R O C E S S F O R P R O D U C I N G H E R B I C I D E A N D I N T E R M E D I A T E T H E R E O F 2 0 2 4 2 1 9 6 7 4 1 2 T h e d i s c l o s u r e r e l a t e s t o a s u l f o n e d e r i v a t i v e t h a t i s O N 0 N S N . + N H N S B a s e N . N R4 R4 N NR5 R5 R2 S Step iii R2 S=0 N. N O-R³ Metal catalyst N. O-R³ Hydrogen peroxide NO R° R° (4) (5) 20 24 21 96 74 12 S ep 2 02 4 1 2 S e p 2 0 2 4 N N S N . N . 2 0 2 4 2 1 9 6 7 4

Description

Cross-Reference to Related Applications The present application is a divisional of Australian Patent Application No 2023201945, which is a divisional of Australian Patent Application No 2020300922, which is the national phase application of International Patent Application No PCT / JP2020 / 040748, which claims priority from Japanese Application No JP2019-198600 filed 31-Oct-2019, the disclosures of which are herein incorporated by reference in their entirety for all purposes. Technical Field

[0001] The present invention relates to a process for producing a sulfone derivative useful as a herbicide, that is, a compound of the following formula (5):

[0002] [Chemical Formula 1] (5)

[0003] 2024219674   12 Sep 2024 wherein R1, R2, R3, R4 and R5 are as described herein. Background Art

[0004] It is known that sulfone derivatives of the above formula (5) have a herbicidal activity as disclosed in WO 2002 / 062770 A1 (Patent Document 1). Among them, pyroxasulfone is well known as a superior herbicide.

[0005] As a process for producing the compound of the formula (5), a process by the oxidation of a sulfide derivative, i.e., a compound of the following formula (4) has been known, which is shown below.

[0006] [Chemical Formula 2]

[0007] As shown in the following scheme, in Reference Example 3 in WO 2004 / 013106 A1 (Patent Document 2) is disclosed a process for producing 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazoline (5-a) (pyroxasulfone) by oxidizing 2024219674   12 Sep 2024 3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline (4-a) (ISFP) with m-chloroperoxybenzoic acid (mCPBA).

[0008] [Chemical Formula 3] WO2004 / O13106A1. Reference Example 3

[0009] In addition, WO 2004 / 013106 A1 (Patent Document 2) and JP 2008-544966 A (corresponding to US 2007 / 015805 A1) (Patent Document 9) describe a process for producing the compound of the formula (4-a). However, the process described in WO 2004 / 013106 A1 (Patent Document 2) and JP 2008-544966 A (corresponding to US 2007 / 015805 A1) (Patent Document 9) has a plurality of problems, e.g., the yield is poor and the preparation of starting materials is inefficient.

[0010] On the other hand, the preparation of the compound of the formula (4-a) is also disclosed in WO 2005 / 095352 A1 2024219674   12 Sep 2024 (Patent Document 3) and WO 2005 / 105755 A1 (Patent Document 4), and these are shown below.

[0011] [Chemical Formula 4]

[0012] The process described in WO 2005 / 095352 A1 (Patent Document 3) and WO 2005 / 105755 A1 (Patent Document 4) is a superior process that has solved the problems in the preparation of the compound of the formula (4-a) described in WO 2004 / 013106 A1 (Patent Document 2) and JP 2008-544966 A (corresponding to US 2007 / 015805 A1) (Patent Document 9). On the other hand, there is still room for improvement in this process because a special manufacturing equipment (hermetically closed equipment) is required for the sensitization of the intermediate (ISHP in the above scheme).

[0013] 2024219674   12 Sep 2024 As a further problem, in the process for producing the compound of the formula (5) from the compound of the formula (4), m-chloroperoxybenzoic acid (mCPBA) disclosed in WO 2004 / 013106 A1 (Patent Document 2) is expensive for industrial use and has problems in handling and waste. Therefore, the process for producing described in WO 2004 / 013106 A1 (Patent Document 2) is not practical for production on an industrial scale.

[0014] In addition, in the process for producing the compound of the formula (5) (sulfone derivative: SO2 derivative) from the compound of the formula (4) (sulfide derivative: S derivative), there is a possibility that the reaction stops at a sulfoxide derivative (SO intermediate of the oxidation the following formula (6):

[0015] [Chemical Formula 5] derivative) that is an reaction, i.e., a compound of

[0016] wherein R1, R2, R3, R4 and R5 are as described herein. 2024219674   12 Sep 2024 Therefore, the compound of the formula (6) sometimes remains in the product as a by-product. The compound of the formula (6) that has contaminated a product such as a herbicide leads to the possibility of reduced quality and crop injury. However, the physical and chemical properties of the compound of the formula (6) are very similar to those of the compound of the formula (5), so that it is difficult to separate the compound of the formula (6) to purify the compound of the formula (5). Therefore, regarding the process for producing the compound of the formula (5) from the compound of the formula (4), there has been desired a process in which the oxidation reaction sufficiently proceeds and substantially no compound of the formula (6) remains in the product.

[0017] Patent Document 7 (JP 2013-512201 A) corresponds to Patent Document 10 (US 2012 / 264947 A1).

[0018] Patent Document 9 (JP 2008-544996 A) corresponds to Patent Document 11 (US 2007 / 015805 A1). Citation List Patent Document

[0019] Patent Document 1: WO 2002 / 062770 A1 2024219674   12 Sep 2024 Patent Document 2: WO 2004 / 013106 A1 Patent Document 3: WO 2005 / 095352 A1 Patent Document 4: WO 2005 / 105755 A1 Patent Document 5: WO 2007 / 094225 A1 Patent Document 6: WO 2006 / 068092 A1 Patent Document 7: JP 2013-512201 A Patent Document 8: WO 2019 / 131715 A1 Patent Document 9: JP 2008-544996 A Patent Document 10: US 2012 / 264947 A1 Patent Document 11: US 2007 / 015805 A1 [0019a] Any reference to or discussion of any document, act or item of knowledge in this specification is included solely for the purpose of providing a context for the present invention. It is not suggested or represented that any of these matters or any combination thereof formed at the priority date part of the common general knowledge, or was known to be relevant to an attempt to solve any problem with which this specification is concerned. Summary of Invention

[0020] Embodiments of the invention disclosed herein relate to a process for producing the compound of the formula (4) 2024219674   12 Sep 2024 that can safely and simply produce the compound of the formula (4), is superior in yield and is novel and industrially advantageous.

[0021] Other embodiments of the invention disclosed herein relate to a process for producing the compound of the formula (5) from the compound of the formula (4) that affords a product containing the compound of the formula (6) in a sufficiently low percentage, is superior in yield, advantageous for the production on an industrial scale, and industrially advantageous.

[0022] Further embodiments of the invention disclosed herein relate to an improved agrochemical formulation comprising pyroxasulfone (the compound of the formula (5-a)). Accordingly, further embodiments of the invention disclosed herein relate to a solid formulation comprising pyroxasulfone which does not form a lump when diluted in water, and also aims to provide a pyroxasulfone-containing liquid formulation, a sprinkling liquid of which does not form a hard cake.

[0023] As a result of earnest study, the present inventors have found that the compound of the formula (4) can be 2024219674   12 Sep 2024 efficiently produced by reacting the compound of the formula (2) with the compound of the formula (3) in the presence of a base as shown in the step ii below. Based on this finding, the present inventors have accomplished embodiments of the present invention, which overcome or ameliorate at least one of the disadvantages of the prior art, or provides a useful alternative.

[0024] [Chemical Formula 6]

[0025] wherein R1, R2, R3, R4, R5, X1 and X2 are as described herein.

[0026] Furthermore, the present inventors have found that, in the process for producing the compound of the formula (5) from the compound of the formula (4), even when an excessive amount of hydrogen peroxide is used in a reaction system of a hydrogen peroxide-tungsten catalyst, the compound of the formula (6), which is a reaction intermediate that is not completely oxidized, surprisingly 2024219674   12 Sep 2024 remains in a product (see Reference Examples). On the other hand, it has been found that the oxidation reaction can be sufficiently advanced by performing the reaction with hydrogen peroxide in the presence of a metal catalyst in a mixed solvent composed of water and a certain organic solvent. Based on these findings, the present inventors have accomplished further embodiments which relate to a production process in which substantially no compound of the formula (6) remains in the target product.

[0027] Other aspects of the invention disclosed herein relate to a novel crystal of pyroxasulfone (the compound of the formula (5-a)) and a process for producing the same. This crystal exhibits a powder X-ray diffraction spectrum having characteristics different from conventional ones, and has good wettability and redispersibility.

[0028] Conventional agrochemical formulations containing pyroxasulfone have sometimes shown physicochemical defects.

[0029] Specifically, for example, when a solid formulation such as a wettable powder is diluted in water in order to prepare a sprinkling liquid, the powder is slow to blend with water, and thus, there was a case where lumps are formed. Sprinkling cannot be performed unless a 2024219674   12 Sep 2024 homogeneous sprinkling liquid is obtained. Therefore, in such a case, it is necessary to continue stirring the sprinkling liquid until the lumps are loosened. As a result, the operation time for sprinkling agrochemicals is prolonged, which is inconvenient.

[0030] Also as for a liquid formulation such as an aqueous suspension concentrate (SC) or an oil dispersion (OD), a diluted liquid is prepared by dispersing such an agrochemical formulation in water in order to sprinkle the formulation. Once stirring is stopped after the preparation and a deposit layer of solid matter is formed, the solid matter is not easily redispersed even if stirring is resumed and there was a case where a homogeneous suspension state cannot be recovered. In order to prevent such a situation, it is necessary to continue stirring the prepared sprinkling liquid until sprinkling is actually completed, which is disadvantageous in terms of operation cost.

[0031] The agrochemical formulation prepared using the crystal of pyroxasulfone of the present invention overcomes, ameliorates or avoids at least one of the above-mentioned problems, or provides a useful alternative, and is industrially advantageous. 2024219674   17 Sep 2026 [0031a] An aspect of the present invention relates to a process for producing a crystal of pyroxasulfone, wherein an organic solvent is distilled off from a solution of pyroxasulfone comprising the organic solvent as a main component to form a solvent medium from which the crystal of pyroxasulfone precipitates, the organic solvent being one selected from the group consisting of nitriles, carboxylic acids, carboxylic acid esters, ketones, amides and dihalogenated aliphatic hydrocarbons, wherein the crystal of pyroxasulfone exhibits a spectrum having peaks at diffraction angles 20 at least in the range of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° in powder X-ray diffraction measurement by a transmission method using Cu-Ka ray, and the peak height of 19.9 to 20.0° is maximum among the three peaks. [0031b] In an embodiment of the process described in paragraph [0031a], the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkanes. 2024219674   17 Sep 2026 [0031c] Another aspect of the present invention relates to a process for producing a crystal of pyroxasulfone, wherein an antisolvent for pyroxasulfone selected from the group consisting of ethers, carboxylic acid esters, ketones, aromatic hydrocarbon derivatives, aliphatic hydrocarbons, alcohols and water is added to a solution of pyroxasulfone comprising one organic solvent selected from the group consisting of nitriles, ketones and carboxylic acid esters as a main component to precipitate pyroxasulfone, wherein the crystal of pyroxasulfone exhibits a spectrum having peaks at diffraction angles 20 at least in the range of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° in powder X-ray diffraction measurement by a transmission method using Cu-Ka ray, and the peak height of 19.9 to 20.0° is maximum among the three peaks. [0031d] In an embodiment of the process described in paragraph [0031c], the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 alkyl ketones and C1-C4 alkyl C1-C4 carboxylates. [0031e] In an embodiment of the process described in paragraph [0031c] or [0031d], the antisolvent for pyroxasulfone is C1-C4 alcohol. 2024219674   17 Sep 2026 [0031f] Another aspect of the present invention relates to a process for producing an agrochemical composition having a dosage form of a wettable powder, comprising: a step of pulverizing a powder comprising a crystal of pyroxasulfone prepared by the process described in any one of paragraphs [0031a] to [0031e], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and a solid carrier to homogenize the mixture. [0031g] Another aspect of the present invention relates to a process for producing an agrochemical composition having a dosage form of a water-dispersible granule, comprising: 2024219674   12 Sep 2024 a step of pulverizing a powder or a slurry comprising a crystal of pyroxasulfone prepared by the process described in any one of paragraphs [0031a] to [0031e], a step of, while homogenizing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and a solid carrier, further adding a slight amount of water and kneading the mixture, a step of granulating the kneaded product obtained in the preceding step, and a step of drying the granulated product obtained in the preceding step. [0031h] Another aspect of the present invention relates to a process for producing an agrochemical composition having a dosage form of an aqueous suspension concentrate, the process comprising: a step of pulverizing a powder or a slurry comprising a crystal of pyroxasulfone prepared by the process described in any one of paragraphs [0031a] to [0031e], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and water to homogenize the mixture. [0031i] Another aspect of the present invention relates to a process for producing an agrochemical composition having a 2024219674   12 Sep 2024 dosage form of an oil dispersion, the process comprising: a step of pulverizing a powder or slurry comprising a crystal of pyroxasulfone prepared by the process described in any one of paragraphs [0031a] to [0031e], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and an oil-based dispersion medium to homogenize the mixture. Advantageous Effects of Invention

[0032] Embodiments of the invention disclosed herein relate to a novel process for producing the compound of the formula (4), that can safely and simply produce the compound of the formula (4), is superior in yield and is novel.

[0033] Furthermore, other embodiments of the invention disclosed herein relate to a process for producing the compound of the formula (5)  (sulfone derivative: SO2 derivative) from the compound of the formula (4) (sulfide derivative: S derivative), wherein the proportion of the compound of the formula (6)  (sulfoxide derivative: SO derivative) in the product is sufficiently low, the yield is superior, and the process is advantageous for production on an industrial scale. The compound of the formula (5) 2024219674   12 Sep 2024 produced by the process of the present invention contains substantially no compound of the formula (6) that can cause the loss of quality as a herbicide and crop injury, and therefore it is useful as a herbicide.

[0034] The process of the invention can be implemented on a large scale using low-cost materials, and is superior in economic efficiency, and is suitable for production on an industrial scale.

[0035] Another aspect of the invention disclosed herein relates to a crystal of pyroxasulfone suitable as a raw material of an agrochemical formulation. The solid formulation containing pyroxasulfone formulated using this crystal does not form lumps when diluted in water, and is practically convenient. In addition, a liquid formulation containing pyroxasulfone formulated using this crystal has an improved hard cake tendency of a sprinkling liquid and is practically convenient. Brief Description of Drawings

[0036] FIG. 1 is a powder X-ray diffraction spectrum of a crystal of pyroxasulfone produced by a process according to one embodiment of the present invention. Of the two upper 2024219674   12 Sep 2024 and lower charts shown in the figure, the upper one is a powder X-ray diffraction spectrum measured by a transmission method, and the lower one is a powder X-ray diffraction spectrum measured by a reflection method. FIG. 2 is a powder X-ray diffraction spectrum of a crystal of pyroxasulfone produced by the process disclosed in Patent Document 2. Of the two upper and lower charts shown in the figure, the upper one is a powder X-ray diffraction spectrum measured by a transmission method, and the lower one is a powder X-ray diffraction spectrum measured by a reflection method. FIG. 3 is a powder X-ray diffraction spectrum of a crystal of pyroxasulfone produced by the process disclosed in Patent Document 7. Of the two upper and lower charts shown in the figure, the upper one is a powder X-ray diffraction spectrum measured by a transmission method, and the lower one is a powder X-ray diffraction spectrum measured by a reflection method. FIG. 4 is a microscopic photograph of a crystal of pyroxasulfone of one embodiment of the present invention. FIG. 5 is a microscopic photograph of a crystal of pyroxasulfone produced by the process disclosed in Patent Document 2. 2024219674   12 Sep 2024 FIG. 6 is a microscopic photograph of a crystal of pyroxasulfone produced by the process disclosed in Patent Document 7. Description of Embodiments

[0037] In one aspect, the present invention is as follows:

[0038] [I-1] A process for producing a compound of the formula (4), the process comprising the following step ii: (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4);

[0039] [Chemical Formula 7]

[0040] wherein in the formula (2), R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more 2024219674   12 Sep 2024 substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, and X1 is a leaving group, in the formula (3), R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more substituents, or R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents, X2 is an atom or an atomic group that forms an acid, in the formula (4), R1, R2, R3, R4 and R5 are as defined above. 2024219674   12 Sep 2024 [I-2] The process according to [I-1], further comprising the following step i before the step ii: (step i) a step of reacting a compound of the formula (1) with a halogenating agent to produce the compound of the formula (2):

[0042] [Chemical Formula 8]

[0043] wherein in the formula (1), R1, R2 and R3 are as defined in [I-1], in the formula (2), R1, R2 and R3 are as defined in [I- 1], and X1 is a halogen atom.

[0044] [I-3] The process according to [I-1], wherein the compound of the formula (2) is produced by a process comprising the following step i: (step i) a step of reacting a compound of the formula (1) with a halogenating agent to produce the compound of the formula (2): 2024219674   12 Sep 2024

[0046] wherein in the formula (1), R1, R2 and R3 are as defined in [I-1], in the formula (2), R1, R2 and R3 are as defined in [I- 1], and X1 is a halogen atom.

[0047] [I-4] The process according to [I-1], wherein as the compound of the formula (2), a compound of the formula (2) produced by a process comprising the following step i is used: (step i) a step of reacting a compound of the formula (1) with a halogenating agent to produce the compound of the formula (2):

[0048] [Chemical Formula 10] 2024219674   12 Sep 2024 wherein in the formula (1), R1, R2 and R3 are as defined in [I-1], in the formula (2), R1, R2 and R3 are as defined in [I- 1], and X1 is a halogen atom.

[0050] [I-5] The process according to [I-1] further comprising the following step iii after the step ii: (step iii) a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of the formula (5):

[0051] [Chemical Formula 11]

[0052] wherein R1, R2, R3, R4 and R5 in the formula (4) and the formula (5) are as defined in [I-1].

[0053] [I-6] A process for producing a compound of the formula (4): 2024219674   12 Sep 2024

[0055] wherein in the formula (4), R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more 2024219674   12 Sep 2024 R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents, the process comprising the following step i and step ii: (step i) a step of reacting a compound of the formula (1) with a halogenating agent to produce the compound of the formula (2):

[0056] [Chemical Formula 13]

[0057] wherein in the formula (1), R1, R2 and R3 are as defined above, in the formula (2), R1, R2 and R3 are as defined above, and X1 is a halogen atom, (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4); 2024219674   12 Sep 2024

[0059] wherein in the formula (2), R1, R2, R3 and X1 are as defined above, in the formula (3), R4 and R5 are as defined above, and X2 is an atom or an atomic group that forms an acid, in the formula (4), R1, R2, R3, R4 and R5 are as defined above.

[0060] [I-7] A process for producing a compound of the formula (5):

[0061] [Chemical Formula 15]

[0062] wherein in the formula (5), 2024219674   12 Sep 2024 R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more substituents, or R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents, the process comprising the following step ii and step iii: 2024219674   12 Sep 2024 (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4);

[0063] [Chemical Formula 16]

[0064] wherein in the formula (2), R1, R2 and R3 are as defined above, and X1 is a leaving group, in the formula (3), R4 and R5 are as defined above, and X2 is an atom or an atomic group that forms an acid, in the formula (4), R1, R2, R3, R4 and R5 are as defined above, (step iii) a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of the formula (5):

[0065] [Chemical Formula 17] 2024219674   12 Sep 2024

[0066] wherein in the formula (4) and the formula (5), R1,  R2, R3, R4 and R5 are as defined above.

[0067] [I-8] A process for producing a compound of the formula (5):

[0068] [Chemical Formula 18]

[0069] wherein in the formula (5), R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally 2024219674   12 Sep 2024 substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more substituents, or R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents, the process comprising the following step i, step ii and step iii: (step i) a step of reacting a compound of the formula (1) with a halogenating agent to produce the compound of the formula (2):

[0070] 2024219674   12 Sep 2024

[0071] wherein in the formula (1), R1, R2 and R3 are as defined above, in the formula (2), R1, R2 and R3 are as defined above, and X1 is a halogen atom, (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4);

[0072] [Chemical Formula 20]

[0073] wherein in the formula (2), R1, R2 and R3 are as defined above, and X1 is a halogen atom, in the formula (3), R4 and R5 are as defined above, and X2 is an atom or an atomic group that forms an acid, 2024219674   12 Sep 2024 in the formula (4), R1, R2, R3, R4 and R5 are as defined above, (step iii) a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of the formula (5):

[0074] [Chemical Formula 21]

[0075] wherein in the formula (4) and the formula (5), R1,  R2, R3, R4 and R5 are as defined above.

[0076] [I-9] A process for producing a compound of the formula (5), the process comprising the following step iii: (step iii) a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of the formula (5):

[0077] [Chemical Formula 22] 2024219674   12 Sep 2024

[0078] wherein R1, R2 and R3 in the formula (4) and the formula (5) are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more 2024219674   12 Sep 2024 R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents.

[0079] [I-10] The process according to [I-9], wherein the compound of the formula (4) is produced by a process comprising the following step ii: (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4);

[0080] [Chemical Formula 23]

[0081] wherein in the formula (2), R1, R2 and R3 are as defined above, and X1 is a leaving group, in the formula (3), R4 and R5 are as defined above, and X2 is an atom or an atomic group that forms an acid, in the formula (4), R1, R2, R3, R4 and R5 are as defined above. 2024219674   12 Sep 2024

[0082] [I-11] The process according to [I-9], wherein as the compound of the formula (4), a compound of the formula (4) produced by a process comprising the following step ii is used: (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4);

[0083] [Chemical Formula 24]

[0084] wherein in the formula (2), R1, R2 and R3 are as defined above, and X1 is a leaving group, in the formula (3), R4 and R5 are as defined above, and X2 is an atom or an atomic group that forms an acid, in the formula (4), R1, R2, R3, R4 and R5 are as defined above.

[0085] [I-12] The process according to any one of [I-2] to [I-11], wherein the halogenating agent in the step i is a 2024219674   12 Sep 2024 chlorinating agent, with the proviso that any process not comprising the step i is excluded.

[0086] [I-13] The process according to any one of [I-2] to [I-11], wherein the halogenating agent in the step i is chlorine, thionyl chloride, sulfuryl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfonyl chloride, phosgene, or benzoyl chloride, with the proviso that any process not comprising the step i is excluded.

[0087] [I-14] The process according to any one of [I-2] to [I-11], wherein the halogenating agent in the step i is chlorine, thionyl chloride, sulfuryl chloride, phosphorus trichloride, phosphorus pentachloride, or phosphorus oxychloride, with the proviso that any process not comprising the step i is excluded.

[0088] [I-15] The process according to any one of [I-2] to [I-11], wherein the halogenating agent is thionyl chloride, with the proviso that any process not comprising the step i is excluded.

[0089] [I-16] The process according to any one of [I-2] to [I-15], wherein the amount of the halogenating agent used in the 2024219674   12 Sep 2024 step i is 1.0 to 2.0 mol based on 1 mol of the compound of the formula (1), with the proviso that any process not comprising the step i is excluded.

[0090] [I-17] The process according to any one of [I-2] to [I-15], wherein the amount of the halogenating agent used in the step i is 1.0 to 1.1 mol based on 1 mol of the compound of the formula (1), with the proviso that any process not comprising the step i is excluded.

[0091] [I-18] The process according to any one of [I-2] to [I-17], wherein the reaction in the step i is performed in the absence of a catalyst, with the proviso that any process not comprising the step i is excluded.

[0092] [I-19] The process according to any one of [I-2] to [I-17], wherein the reaction in the step i is performed in the presence of a catalyst, with the proviso that any process not comprising the step i is excluded.

[0093] [I-20] The process according to [I-19], wherein the catalyst is an amide.

[0094] [I-21] The process according to [I-19], wherein the catalyst is N,N-dimethylformamide. 2024219674   12 Sep 2024

[0095] [I-22] The process according to any one of [I-19] to [I-21], wherein the amount of the catalyst used is 0 to 0.1 mol based on 1 mol of the compound of the formula (4).

[0096] [I-23] The process according to any one of [I-19] to [I- 21], wherein the amount of the catalyst used is 0.001 to 0.1 mol based on 1 mol of the compound of the formula (4).

[0097] [I-24] The process according to any one of [I-2] to [I-23], wherein the reaction in the step i is performed in the absence of a solvent, with the proviso that any process not comprising the step i is excluded.

[0098] [I-25] The process according to any one of [I-2] to [I-23], wherein the reaction in the step i is performed in the presence of a solvent, with the proviso that any process not comprising the step i is excluded.

[0099] [I-26] The process according to [I-25], wherein the solvent in the reaction in the step i is one or more organic solvents selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and nitriles. 2024219674   12 Sep 2024 [I-27] The process according to [I-25], wherein the solvent in the reaction in the step i is one or two organic solvents selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and nitriles.

[0101] [I-28] The process according to [I-25], wherein the solvent in the reaction in the step i is one organic solvent selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and nitriles.

[0102] [I-29] The process according to [I-25], wherein the solvent in the reaction in the step i is one or more organic solvents selected from halogenated aromatic hydrocarbons, halogenated aliphatic hydrocarbons and nitriles.

[0103] [I-30] The process according to [I-25], wherein the solvent in the reaction in the step i is one or two organic solvents selected from halogenated aromatic hydrocarbons, halogenated aliphatic hydrocarbons and nitriles. 2024219674   12 Sep 2024 [I-31] The process according to [I-25], wherein the solvent in the reaction in the step i is one organic solvent selected from halogenated aromatic hydrocarbons, halogenated aliphatic hydrocarbons and nitriles.

[0105] [I-32] The process according to [I-25], wherein the solvent in the reaction in the step i is one or more organic solvents selected from chlorobenzene, dichlorobenzene, trichlorobenzene, dichloromethane, 1,2-dichloroethane and acetonitrile.

[0106] [I-33] The process according to [I-25], wherein the solvent in the reaction in the step i is one or two organic solvents selected from chlorobenzene, dichlorobenzene, trichlorobenzene, dichloromethane, 1,2-dichloroethane and acetonitrile.

[0107] [I-34] The process according to [I-25], wherein the solvent in the reaction in the step i is one organic solvent selected from chlorobenzene, dichlorobenzene, trichlorobenzene, dichloromethane, 1,2-dichloroethane and acetonitrile. 2024219674   12 Sep 2024 [I-35] The process according to [I-25], wherein the solvent in the reaction in the step i is dichloromethane or acetonitrile.

[0109] [I-36] The process according to [I-25], wherein the solvent in the reaction in the step i is acetonitrile.

[0110] [I-37] The process according to any one of [I-25] to [I-36], wherein the amount of the organic solvent used in the reaction in the step i is 0 to 2 liters based on 1 mol of the compound of the formula (1).

[0111] [I-38] The process according to any one of [I-25] to [I-36], wherein the amount of the organic solvent used in the reaction in the step i is 0 to 1.5 liters based on 1 mol of the compound of the formula (1).

[0112] [I-39] The process according to any one of [I-25] to [I-36], wherein the amount of the organic solvent used in the reaction in the step i is 0.4 to 2 liters based on 1 mol of the compound of the formula (1).

[0113] [I-40] The process according to any one of [I-25] to [I- 36], wherein the amount of the organic solvent used in the 2024219674   12 Sep 2024 reaction in the step i is 0.6 to 1.2 liters based on 1 mol of the compound of the formula (1).

[0114] [I-41] The process according to any one of [I-2] to [I-40], wherein the reaction in the step i is performed at -5°C to 80°C, with the proviso that any process not comprising the step i is excluded.

[0115] [I-42] The process according to any one of [I-2] to [I-40], wherein the reaction in the step i is performed at 0°C to 30°C, with the proviso that any process not comprising the step i is excluded.

[0116] [I-43] The process according to any one of [I-2] to [I-42], wherein the reaction in the step i is performed in 1 hour to 48 hours, with the proviso that any process not comprising the step i is excluded.

[0117] [I-44] The process according to any one of [I-2] to [I-42], wherein the reaction in the step i is performed in 1 hour to 24 hours, with the proviso that any process not comprising the step i is excluded.

[0118] [I-45] The process according to any one of [I-2] to [I-42], wherein the reaction in the step i is performed in 2 hours 2024219674   12 Sep 2024 to 12 hours, with the proviso that any process not comprising the step i is excluded.

[0119] [I-46] The process according to any one of [I-1] to [I-45], wherein the amount of the compound of the formula (3) used in the step ii is 0.8 to 1.5 mol based on 1 mol of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded.

[0120] [I-47] The process according to any one of [I-1] to [I-45], wherein the amount of the compound of the formula (3) used in the step ii is 1.0 to 1.5 mol based on 1 mol of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded.

[0121] [I-48] The process according to any one of [I-1] to [I-45], wherein the amount of the compound of the formula (3) used in the step ii is 1.0 to 1.1 mol based on 1 mol of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded.

[0122] [I-49] The process according to any one of [I-1] to [I-45], wherein the base in the step ii is an alkali metal hydroxide, an alkali metal carbonate, or a mixture thereof, 2024219674   12 Sep 2024 with the proviso that any process not comprising the step ii is excluded.

[0123] [I-50] The process according to any one of [I-1] to [I-45], wherein the base in the step ii is an alkali metal hydroxide, with the proviso that any process not comprising the step ii is excluded.

[0124] [I-51] The process according to any one of [I-1] to [I-45], wherein the base in the step ii is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, or a mixture thereof, with the proviso that any process not comprising the step ii is excluded.

[0125] [I-52] The process according to any one of [I-1] to [I-45], wherein the base in the step ii is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or a mixture thereof, with the proviso that any process not comprising the step ii is excluded.

[0126] [I-53] The process according to any one of [I-1] to [I-45], wherein the base in the step ii is sodium hydroxide, potassium hydroxide, or a mixture thereof, with the proviso that any process not comprising the step ii is excluded. 2024219674   12 Sep 2024

[0127] [I-54] The process according to any one of [I-1] to [I-45], wherein the base in the step ii is sodium hydroxide, with the proviso that any process not comprising the step ii is excluded.

[0128] [I-55] The process according to any one of [I-1] to [I-45], wherein the amount of the base used in the step ii is 1 to 10 equivalents based on 1 equivalent of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded.

[0129] [I-56] The process according to any one of [I-1] to [I-45], wherein the amount of the base used in the step ii is 5 to 10 equivalents based on 1 equivalent of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded.

[0130] [I-57] The process according to any one of [I-1] to [I-45], wherein the amount of the base used in the step ii is 5 to 8 equivalents based on 1 equivalent of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded. 2024219674   12 Sep 2024 [I-58] The process according to any one of [I-1] to [I-45], wherein the reaction in the step ii is 5 to 6 equivalents based on 1 equivalent of the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded.

[0132] [I-59] The process according to any one of [I-1] to [I-58], wherein the reaction in the step ii is performed in the presence of an organic solvent and a water solvent, with the proviso that any process not comprising the step ii is excluded.

[0133] [I-60] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 0 to 50.

[0134] [I-61] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 3 to 45.

[0135] [I-62] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 5 to 45. 2024219674   12 Sep 2024 [I-63] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 5 to 35.

[0137] [I-64] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 5 to 30.

[0138] [I-65] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 5 to 20.

[0139] [I-66] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is an organic solvent having an acceptor number of 8 to 20.

[0140] [I-67] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, sulfoxides and sulfones.

[0141] [I-68] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic 2024219674   12 Sep 2024 solvents selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, sulfoxides and sulfones.

[0142] [I-69] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers, amides and sulfones.

[0143] [I-70] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers and amides.

[0144] [I-71] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from alcohols, nitriles, carboxylic acid esters and amides.

[0145] [I-72] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from alcohols, nitriles, carboxylic acid esters and amides. 2024219674   12 Sep 2024

[0146] [I-73] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from alcohols, nitriles, carboxylic acid esters and amides.

[0147] [I-74] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from alcohols, nitriles, carboxylic acid esters and amides.

[0148] [I-75] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from alcohols, nitriles and carboxylic acid esters.

[0149] [I-76] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from alcohols, nitriles and carboxylic acid esters.

[0150] [I-77] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from alcohols, nitriles and carboxylic acid esters. 2024219674   12 Sep 2024 [I-78] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from alcohols, nitriles and carboxylic acid esters.

[0152] [I-79] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from nitriles and carboxylic acid esters.

[0153] [I-80] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from nitriles and carboxylic acid esters.

[0154] [I-81] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from nitriles and carboxylic acid esters.

[0155] [I-82] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from nitriles and carboxylic acid esters.

[0156] [I-83] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is a nitrile. 2024219674   12 Sep 2024

[0157] [I-84] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from nitriles.

[0158] [I-85] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from nitriles.

[0159] [I-86] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from nitriles.

[0160] [I-87] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from nitriles.

[0161] [I-88] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is a carboxylic acid ester.

[0162] [I-89] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from carboxylic acid esters. 2024219674   12 Sep 2024 [I-90] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from carboxylic acid esters.

[0164] [I-91] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is preferably one to five organic solvents selected from carboxylic acid esters.

[0165] [I-92] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is preferably one or two organic solvents selected from carboxylic acid esters.

[0166] [I-93] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from carboxylic acid esters.

[0167] [I-94] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from (C1-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1- C4)alkaneamides.

[0168] [I-95] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from (C1-C6)alcohols, (C2- 2024219674   12 Sep 2024 C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides.

[0169] [I-96] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from (C1-C6)alcohols,  (C2- C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides.

[0170] [I-97] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from among (C1-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides.

[0171] [I-98] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides.

[0172] [I-99] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic 2024219674   12 Sep 2024 solvents selected from (C1-C4)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides.

[0173] [I-100] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C4)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides.

[0174] [I-101] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0175] [I-102] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0176] [I-103] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from (C1-C6)alcohols, (C2- C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates. 2024219674   12 Sep 2024

[0177] [I-104] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0178] [I-105] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0179] [I-106] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from (C1-C4)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0180] [I-107] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C4)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates. 2024219674   12 Sep 2024 [I-108] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is selected from (C2-C5)alkane nitriles and (C1-C4)alkyl (C1- C4)carboxylates.

[0182] [I-109] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more organic solvents selected from (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0183] [I-110] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two organic solvents selected from (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0184] [I-111] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates.

[0185] [I-112] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, 1,2-dichloroethane, 2024219674   12 Sep 2024 methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, diglyme, acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl isobutyl ketone, N,N-dimethylformamide, N,N- dimethylacetamide, N-methylpyrrolidone, N,N'-dimethylimidazolidinone, tetramethylurea, dimethyl sulfoxide and sulfolane.

[0186] [I-113] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, diglyme, N,N-dimethylformamide, N,N-dimethylacetamide, N- methylpyrrolidone and sulfolane. 2024219674   12 Sep 2024 [I-114] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, diglyme, N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

[0188] [I-115] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

[0189] [I-116] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from methanol, ethanol, 2- propanol, butanol, tert-butanol, acetonitrile, ethyl 2024219674   12 Sep 2024 acetate, propyl acetate, isopropyl acetate, butyl acetate and N,N-dimethylformamide.

[0190] [I-117] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof.

[0191] [I-118] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from methanol, ethanol, 2- propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate.

[0192] [I-119] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate. 2024219674   12 Sep 2024 [I-120] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or more (preferably one or two, more preferably one) organic solvents selected from acetonitrile, ethyl acetate, isopropyl acetate and butyl acetate.

[0194] [I-121] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one organic solvent selected from acetonitrile, ethyl acetate, isopropyl acetate and butyl acetate.

[0195] [I-122] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is one or two (preferably one) organic solvents selected from acetonitrile and butyl acetate.

[0196] [I-123] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is acetonitrile or butyl acetate.

[0197] [I-124] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is acetonitrile. 2024219674   12 Sep 2024 [I-125] The process according to [I-59], wherein the organic solvent in the reaction in the step ii is butyl acetate.

[0199] [I-126] The process according to any one of [I-59] to [I-125], wherein the total amount of the solvent used in the reaction in the step ii is 1 to 3 liters based on 1 mol of the compound of the formula (2).

[0200] [I-127] The process according to any one of [I-59] to [I-125], wherein the total amount of the solvent used in the reaction in the step ii is 1.5 to 3.0 liters based on 1 mol of the compound of the formula (2).

[0201] [I-128] The process according to any one of [I-59] to [I-125], wherein the total amount of the solvent used in the reaction in the step ii is 1.5 to 2.5 liters based on 1 mol of the compound of the formula (2).

[0202] [I-129] The process according to any one of [I-59] to [I-125], wherein the total amount of the solvent used in the reaction in the step ii is 1.7 to 2.0 liters based on 1 mol of the compound of the formula (2). 2024219674   12 Sep 2024 [I-130] The process according to any one of [I-59] to [I-129], wherein the amount of the organic solvent used in the reaction in the step ii is 0.5 to 1.5 liters based on 1 mol of the compound of the formula (2).

[0204] [I-131] The process according to any one of [I-59] to [I-129], wherein the amount of the organic solvent used in the reaction in the step ii is 0.7 to 0.9 liters based on 1 mol of the compound of the formula (2).

[0205] [I-132] The process according to any one of [I-59] to [I-129], wherein the amount of the organic solvent used in the reaction in the step ii is 0.3 to 2.0 liters based on 1 mol of the compound of the formula (2).

[0206] [I-133] The process according to any one of [I-59] to [I-129], wherein the amount of the organic solvent used in the reaction in the step ii is 0.6 to 0.8 liters based on 1 mol of the compound of the formula (2).

[0207] [I-134] The process according to any one of [I-59] to [I- 133], wherein the amount of the water solvent used in the reaction in the step ii is 0.5 to 2.0 liters based on 1 mol of the compound of the formula (2). 2024219674   12 Sep 2024 [I-135] The process according to any one of [I-59] to [I- 133], wherein the amount of the water solvent used in the reaction in the step ii is 0.5 to 1.5 liters based on 1 mol of the compound of the formula (2).

[0209] [I-136] The process according to any one of [I-59] to [I- 133], wherein the amount of the water solvent used in the reaction in the step ii is 0.7 to 1.4 liters based on 1 mol of the compound of the formula (2).

[0210] [I-137] The process according to any one of [I-59] to [I- 133], wherein the amount of the water solvent used in the reaction in the step ii is 0.9 to 1.2 liters based on 1 mol of the compound of the formula (2).

[0211] [I-138] The process according to any one of [I-59] to [I- 137], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step ii is 90 : 10 to 0  :  100.

[0212] [I-139] The process according to any one of [I-59] to [I- 137], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step ii is 70 : 30 to 30  :  70. 2024219674   12 Sep 2024 [I-140] The process according to any one of [I-59] to [I- 137], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step ii is 50 : 50 to 35  :  65.

[0214] [I-141] The process according to any one of [I-59] to [I- 137], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step ii is 50 : 50 to 40  :  60.

[0215] [I-142] The process according to any one of [I-59] to [I- 137], wherein in the reaction in the step ii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 10 vol% to 100 vol% based on the amount of the whole solvent.

[0216] [I-143] The process according to any one of [I-59] to [I- 137], wherein in the reaction in the step ii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 30 vol% to 70 vol% based on the amount of the whole solvent.

[0217] [I-144] The process according to any one of [I-59] to [I- 137], wherein in the reaction in the step ii, the amount of the water solvent in the whole solvent composed of the 2024219674   12 Sep 2024 organic solvent and the water solvent is 50 vol% to 65 vol% based on the amount of the whole solvent.

[0218] [I-145] The process according to any one of [I-59] to [I- 72], wherein in the reaction in the step ii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 50 vol% to 60 vol% based on the amount of the whole solvent.

[0219] [I-146] The process according to any one of [I-1] to [I- 145], wherein the reaction in the step ii is performed at - 10°C to 100°C, with the proviso that any process not comprising the step ii is excluded.

[0220] [I-147] The process according to any one of [I-1] to [I- 145], wherein the reaction in the step ii is performed at - 10°C to 70°C, with the proviso that any process not comprising the step ii is excluded.

[0221] [I-148] The process according to any one of [I-1] to [I- 145], wherein the reaction in the step ii is performed at - 10°C to 50°C, with the proviso that any process not comprising the step ii is excluded. 2024219674   12 Sep 2024 [I-149] The process according to any one of [I-1] to [I- 145], wherein the reaction in the step ii is performed at 0°C to 40°C, with the proviso that any process not comprising the step ii is excluded.

[0223] [I-150] The process according to any one of [I-1] to [I- 145], wherein the reaction in the step ii is performed at 0°C to 30°C, with the proviso that any process not comprising the step ii is excluded.

[0224] [I-151] The process according to any one of [I-1] to [I- 150], wherein the reaction in the step ii is performed in 1 hour to 48 hours, with the proviso that any process not comprising the step ii is excluded.

[0225] [I-152] The process according to any one of [I-1] to [I- 150], wherein the reaction in the step ii is performed in 4 hours to 24 hours, with the proviso that any process not comprising the step ii is excluded.

[0226] [I-153] The process according to any one of [I-1] to [I- 152], wherein the reaction in the step ii is performed by adding dropwise the base to a mixture of the compound of the formula (2), the compound of the formula (3) and a 2024219674   12 Sep 2024 solvent, with the proviso that any process not comprising the step ii is excluded.

[0227] [I-154] The process according to any one of [I-1] to [I- 152], wherein the reaction in the step ii is performed by adding dropwise the compound of the formula (2) to a mixture of the compound of the formula (3), the base and a solvent, with the proviso that any process not comprising the step ii is excluded.

[0228] [I-155] The process according to any one of [I-1] to [I- 152], wherein the reaction in the step ii is performed by adding dropwise successively the compound of the formula (2) and the compound of the formula (3) to a mixture of the base and a solvent, with the proviso that any process not comprising the step ii is excluded.

[0229] [I-156] The process according to any one of [I-1] to [I- 152], wherein the reaction in the step ii is performed by adding dropwise the compound of the formula (3) to a mixture of the base and a solvent and then adding the compound of the formula (2), with the proviso that any process not comprising the step ii is excluded. 2024219674   12 Sep 2024 [I-157] The process according to any one of [I-1] to [I- 156], wherein the hydrogen peroxide in the step iii is a 10 to 70 wt% aqueous hydrogen peroxide solution, with the proviso that any process not comprising the step iii is excluded.

[0231] [I-158] The process according to any one of [I-1] to [I- 156], wherein the hydrogen peroxide in the step iii is a 25 to 65 wt% aqueous hydrogen peroxide solution, with the proviso that any process not comprising the step iii is excluded.

[0232] [I-159] The process according to any one of [I-1] to [I- 156], wherein the amount of the hydrogen peroxide used in the step iii is 2 to 8 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0233] [I-160] The process according to any one of [I-1] to [I- 156], wherein the amount of the hydrogen peroxide used in the step iii is 2 to 6 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-161] The process according to any one of [I-1] to [I- 156], wherein the amount of the hydrogen peroxide used in the step iii is 2 to 5 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0235] [I-162] The process according to any one of [I-1] to [I- 156], wherein the amount of the hydrogen peroxide used in the step iii is 2 to 4 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0236] [I-163] The process according to any one of [I-1] to [I- 156], wherein the amount of the hydrogen peroxide used in the step iii is 2 to 3 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0237] [I-164] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is a tungsten catalyst, with the proviso that any process not comprising the step iii is excluded.

[0238] [I-165] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is 2024219674   12 Sep 2024 tungstic acid, a tungstic acid salt, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten bromide, tungsten sulfide, phosphotungstic acid or a salt thereof, silicotungstic acid or a salt thereof, or a mixture of them, with the proviso that any process not comprising the step iii is excluded.

[0239] [I-166] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, or a mixture thereof, with the proviso that any process not comprising the step iii is excluded.

[0240] [I-167] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is sodium tungstate, with the proviso that any process not comprising the step iii is excluded.

[0241] [I-168] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is sodium tungstate dihydrate, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-169] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from a tungsten catalyst and a molybdenum catalyst, with the proviso that any process not comprising the step iii is excluded.

[0243] [I-170] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is a tungsten catalyst or a molybdenum catalyst, with the proviso that any process not comprising the step iii is excluded.

[0244] [I-171] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, with the proviso that any process not comprising the step iii is excluded.

[0245] [I-172] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from sodium tungstate and ammonium molybdate, with 2024219674   12 Sep 2024 the proviso that any process not comprising the step iii is excluded.

[0246] [I-173] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from sodium tungstate dihydrate and ammonium molybdate tetrahydrate, with the proviso that any process not comprising the step iii is excluded.

[0247] [I-174] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is sodium tungstate or ammonium molybdate, with the proviso that any process not comprising the step iii is excluded.

[0248] [I-175] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is sodium tungstate dihydrate or ammonium molybdate tetrahydrate, with the proviso that any process not comprising the step iii is excluded.

[0249] [I-176] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from a tungsten catalyst, a molybdenum catalyst and a niobium catalyst, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024

[0250] [I-177] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, etc., and a mixture thereof, with the proviso that any process not comprising the step iii is excluded.

[0251] [I-178] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from sodium tungstate, ammonium molybdate and sodium niobate, with the proviso that any process not comprising the step iii is excluded.

[0252] [I-179] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from a tungsten catalyst, a molybdenum catalyst, a niobium catalyst, a tantalum catalyst, a titanium catalyst and a zirconium catalyst, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024

[0253] [I-180] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, etc., and a mixture thereof, tantalic acid, tantalic acid salts, tantalum oxide, tantalum carbide, tantalum chloride, and a mixture thereof, titanic acid, titanic acid salts, titanium oxide, titanium carbide, titanium chloride, and a mixture thereof, zirconic acid, zirconic acid salts, zirconium oxide, zirconium carbide, zirconium chloride, and a mixture thereof, with the proviso that any process not comprising the step iii is excluded.

[0254] [I-181] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal 2024219674   12 Sep 2024 tungsten, tungsten(VI) oxide, tungsten carbide, and a mixture thereof, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and a mixture thereof, sodium niobate, potassium niobate, niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and a mixture thereof, lithium tantalate, potassium tantalate, tantalum pentoxide, tantalum carbide, tantalum(V) chloride, tantalum(V) pentaethoxide, etc., and a mixture thereof, titanium acetylacetonate, titanium tetrachloride, titanium trichloride, titanium(IV) tetraisopropoxide, etc., and a mixture thereof, zirconium dioxide, zirconium(I) chloride, zirconium(IV) chloride and zirconium chloride oxide, with the proviso that any process not comprising the step iii is excluded.

[0255] [I-182] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, sodium tungstate, potassium 2024219674   12 Sep 2024 tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, sodium molybdate, potassium molybdate, ammonium molybdate, sodium niobate, potassium niobate, lithium tantalate and potassium tantalate, with the proviso that any process not comprising the step iii is excluded.

[0256] [I-183] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, sodium molybdate, potassium molybdate, ammonium molybdate, sodium niobate and potassium niobate, with the proviso that any process not comprising the step iii is excluded.

[0257] [I-184] The process according to any one of [I-1] to [I- 156], wherein the metal catalyst in the step iii is selected from tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, 2024219674   12 Sep 2024 sodium molybdate, potassium molybdate and ammonium molybdate, with the proviso that any process not comprising the step iii is excluded.

[0258] [I-185] The process according to any one of [I-1] to [I-156], wherein the amount of the metal catalyst used is 0.001 to 0.1 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0259] [I-186] The process according to any one of [I-1] to [I- 156], wherein the amount of the metal catalyst used is 0.01 to 0.1 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0260] [I-187] The process according to any one of [I-1] to [I- 156], wherein the amount of the metal catalyst used is 0.03 to 0.05 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0261] [I-188] The process according to any one of [I-1] to [I-156], wherein the reaction in the step iii is performed in 2024219674   12 Sep 2024 the absence of an acid catalyst, with the proviso that any process not comprising the step iii is excluded.

[0262] [I-189] The process according to any one of [I-1] to [I- 156], wherein the reaction in the step iii is performed in the presence or absence of an acid catalyst, with the proviso that any process not comprising the step iii is excluded.

[0263] [I-190] The process according to any one of [I-1] to [I-156], wherein the reaction in the step iii is performed in the presence of an acid catalyst, with the proviso that any process not comprising the step iii is excluded.

[0264] [I-191] The process according to [I-189] or [I-190], wherein the acid catalyst is hydrochloric acid, sulfuric acid, phosphoric acid, methyl phosphate, ethyl phosphate, or phenyl phosphate, with the proviso that any process not comprising the step iii is excluded.

[0265] [I-192] The process according to [I-189] or [I-190], wherein the acid catalyst is hydrochloric acid, sulfuric acid, phosphoric acid, or phenyl phosphate, with the proviso that any process not comprising the step iii is 2024219674   12 Sep 2024

[0266] [I-193] The process according to [I-189] or [I-190], wherein the acid catalyst is sulfuric acid or phenyl phosphate, with the proviso that any process not comprising the step iii is excluded.

[0267] [I-194] The process according to [I-189] or [I-190], wherein the acid catalyst is phenyl phosphate, with the proviso that any process not comprising the step iii is excluded.

[0268] [I-195] The process according to [I-189] or [I-190], wherein the acid catalyst is sulfuric acid, with the proviso that any process not comprising the step iii is excluded.

[0269] [I-196] The process according to any one of [I-188] to [I-190], wherein the amount of the acid catalyst used is 0 (zero) to 0.2 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0270] [I-197] The process according to any one of [I-188] to [I-190], wherein the amount of the acid catalyst used is 0 (zero) to 0.1 mol based on 1 mol of the compound of the 2024219674   12 Sep 2024 formula (4), with the proviso that any process not comprising the step iii is excluded.

[0271] [I-198] The process according to [I-189] or [I-190], wherein the amount of the acid catalyst used is 0.001 to 0.1 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0272] [I-199] The process according to [I-189] or [I-190], wherein the amount of the acid catalyst used is 0.005 to 0.05 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0273] [I-200] The process according to any one of [I-1] to [I- 199], wherein the reaction in the step iii is performed in the absence of a phase transfer catalyst, with the proviso that any process not comprising the step iii is excluded.

[0274] [I-201] The process according to any one of [I-1] to [I- 199], wherein the reaction in the step iii is performed in the presence or absence of a phase transfer catalyst, with the proviso that any process not comprising the step iii is 2024219674   12 Sep 2024

[0275] [I-202] The process according to any one of [I-1] to [I- 199], wherein the reaction in the step iii is performed in the presence of a phase transfer catalyst, with the proviso that any process not comprising the step iii is excluded.

[0276] [I-203] The process according to [I-202], wherein the phase transfer catalyst is tetrabutylammonium chloride, tetrabutylammonium bromide, or tetrabutylammonium hydrogen sulfate, with the proviso that any process not comprising the step iii is excluded.

[0277] [I-204] The process according to [I-202], wherein the phase transfer catalyst is tetrabutylammonium hydrogen sulfate, with the proviso that any process not comprising the step iii is excluded.

[0278] [I-205] The process according to any one of [I-200] to [I-204], wherein the amount of the phase transfer catalyst used is 0 (zero) to 0.1 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0279] [I-206] The process according to any one of [I-201] to [I-204], wherein the amount of the phase transfer catalyst 2024219674   12 Sep 2024 used is 0.001 to 0.1 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0280] [I-207] The process according to any one of [I-201] to [I-204], wherein the amount of the phase transfer catalyst used is 0.005 to 0.05 mol based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0281] [I-208] The process according to any one of [I-1] to [I- 207], wherein the reaction in the step iii is performed in the presence of an organic solvent and a water solvent, with the proviso that any process not comprising the step iii is excluded.

[0282] [I-209] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an organic solvent having an acceptor number of 0 to 50, with the proviso that any process not comprising the step iii is excluded.

[0283] [I-210] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an 2024219674   12 Sep 2024 the proviso that any process not comprising the step iii is excluded.

[0284] [I-211] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an organic solvent having an acceptor number of 5 to 45, with the proviso that any process not comprising the step iii is excluded.

[0285] [I-212] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an organic solvent having an acceptor number of 5 to 35, with the proviso that any process not comprising the step iii is excluded.

[0286] [I-213] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an organic solvent having an acceptor number of 5 to 30, with the proviso that any process not comprising the step iii is excluded.

[0287] [I-214] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an organic solvent having an acceptor number of 5 to 20, with 2024219674   12 Sep 2024 the proviso that any process not comprising the step iii is excluded.

[0288] [I-215] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is an organic solvent having an acceptor number of 8 to 20, with the proviso that any process not comprising the step iii is excluded.

[0289] [I-216] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, sulfoxides and sulfones, with the proviso that any process not comprising the step iii is excluded.

[0290] [I-217] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, sulfoxides and sulfones, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024

[0291] [I-218] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers, amides and sulfones, with the proviso that any process not comprising the step iii is excluded.

[0292] [I-219] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers and amides, with the proviso that any process not comprising the step iii is excluded.

[0293] [I-220] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from alcohols, nitriles, carboxylic acid esters and amides, with the proviso that any process not comprising the step iii is excluded.

[0294] [I-221] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from alcohols, nitriles, 2024219674   12 Sep 2024 carboxylic acid esters and amides, with the proviso that any process not comprising the step iii is excluded.

[0295] [I-222] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from alcohols, nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0296] [I-223] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0297] [I-224] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two organic solvents selected from alcohols, nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0298] [I-225] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from alcohols, nitriles and 2024219674   12 Sep 2024 carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0299] [I-226] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0300] [I-227] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0301] [I-228] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two organic solvents selected from nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0302] [I-229] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from nitriles and carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024

[0303] [I-230] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is a nitrile, with the proviso that any process not comprising the step iii is excluded.

[0304] [I-231] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from nitriles, with the proviso that any process not comprising the step iii is excluded.

[0305] [I-232] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from nitriles, with the proviso that any process not comprising the step iii is excluded.

[0306] [I-233] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two organic solvents selected from nitriles, with the proviso that any process not comprising the step iii is excluded.

[0307] [I-234] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one 2024219674   12 Sep 2024 organic solvent selected from nitriles, with the proviso that any process not comprising the step iii is excluded.

[0308] [I-235] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is a carboxylic acid ester, with the proviso that any process not comprising the step iii is excluded.

[0309] [I-236] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0310] [I-237] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0311] [I-238] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is preferably one to five organic solvents selected from carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-239] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is preferably one or two organic solvents selected from carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0313] [I-240] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from carboxylic acid esters, with the proviso that any process not comprising the step iii is excluded.

[0314] [I-241] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from (C1-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1- C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded.

[0315] [I-242] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from (C1-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024

[0316] [I-243] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two organic solvents selected from (C1-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded.

[0317] [I-244] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from (C1-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded.

[0318] [I-245] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C6)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded.

[0319] [I-246] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or 2024219674   12 Sep 2024 more (preferably one or two, more preferably one) organic solvents selected from (C1-C4)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded.

[0320] [I-247] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C4)alcohols, (C2-C5)alkane nitriles, (C1-C4)alkyl (C1-C4)carboxylates and N,N-di((C1-C4)alkyl)(C1-C4)alkaneamides, with the proviso that any process not comprising the step iii is excluded.

[0321] [I-248] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded.

[0322] [I-249] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, 2024219674   12 Sep 2024 with the proviso that any process not comprising the step iii is excluded.

[0323] [I-250] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two organic solvents selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded.

[0324] [I-251] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from (C1-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded.

[0325] [I-252] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C6)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-253] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from (C1-C4)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded.

[0327] [I-254] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from (C2-C4)alcohols, (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded.

[0328] [I-255] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is selected from (C2-C5)alkane nitriles and (C1-C4)alkyl (C1-C4)carboxylates, with the proviso that any process not comprising the step iii is excluded.

[0329] [I-256] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or 2024219674   12 Sep 2024 and (C1-C4) alkyl (C1-C4) carboxylate, with the proviso that any process not comprising the step iii is excluded.

[0330] [I-257] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two organic solvents selected from (C2-C5) alkane nitrile and (C1-C4) alkyl (C1-C4) carboxylate, with the proviso that any process not comprising the step iii is excluded.

[0331] [I-258] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from (C2-C5) alkane nitrile and (C1-C4) alkyl (C1-C4) carboxylate, with the proviso that any process not comprising the step iii is excluded.

[0332] [I-259] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, 2024219674   12 Sep 2024 methyl-tert-butyl ether, 1,2-dimethoxyethane, diglyme, acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl isobutyl ketone, N,N-dimethylformamide, N,N- dimethylacetamide, N-methylpyrrolidone, N,N'-dimethylimidazolidinone, tetramethylurea, dimethyl sulfoxide and sulfolane, with the proviso that any process not comprising the step iii is excluded.

[0333] [I-259] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, diglyme, N,N-dimethylformamide, N,N-dimethylacetamide, N- methylpyrrolidone and sulfolane, with the proviso that any process not comprising the step iii is excluded.

[0334] [I-260] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, 2024219674   12 Sep 2024 butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, diglyme, N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone, with the proviso that any process not comprising the step iii is excluded.

[0335] [I-261] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone, with the proviso that any process not comprising the step iii is excluded.

[0336] [I-262] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from methanol, ethanol, 2- propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate 2024219674   12 Sep 2024 and N,N-dimethylformamide, with the proviso that any process not comprising the step iii is excluded.

[0337] [I-263] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, with the proviso that any process not comprising the step iii is excluded.

[0338] [I-264] The process according to [I-208], wherein the organic solvent of the reaction in the step iii is one organic solvent selected from methanol, ethanol, 2- propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate, with the proviso that any process not comprising the step iii is excluded.

[0339] [I-265] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from ethanol, 2-propanol, butanol, tertbutanol, acetonitrile, ethyl acetate, propyl acetate, 2024219674   12 Sep 2024 isopropyl acetate, butyl acetate and isomers thereof (preferably one or more (preferably one or two, more preferably one) organic solvents selected from ethanol, 2-propanol, butanol, tert-butanol and acetonitrile), with the proviso that any process not comprising the step iii is excluded.

[0340] [I-266] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate, with the proviso that any process not comprising the step iii is excluded.

[0341] [I-267] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or more (preferably one or two, more preferably one) organic solvents selected from acetonitrile, ethyl acetate, isopropyl acetate and butyl acetate, with the proviso that any process not comprising the step iii is excluded.

[0342] [I-268] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one organic solvent selected from acetonitrile, ethyl acetate, 2024219674   12 Sep 2024 isopropyl acetate and butyl acetate, with the proviso that any process not comprising the step iii is excluded.

[0343] [I-269] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is one or two (preferably one) organic solvents selected from acetonitrile and butyl acetate, with the proviso that any process not comprising the step iii is excluded.

[0344] [I-270] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is acetonitrile or butyl acetate, with the proviso that any process not comprising the step iii is excluded.

[0345] [I-271] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is acetonitrile, with the proviso that any process not comprising the step iii is excluded.

[0346] [I-272] The process according to [I-208], wherein the organic solvent in the reaction in the step iii is butyl acetate, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-273] The process according to any one of [I-208] to [I- 272], wherein the total amount of the solvent used in the reaction in the step iii is 0.3 to 3 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0348] [I-274] The process according to any one of [I-208] to [I- 272], wherein the total amount of the solvent used in the reaction in the step iii is 0.5 to 3 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0349] [I-275] The process according to any one of [I-208] to [I- 272], wherein the total amount of the solvent used in the reaction in the step iii is 0.5 to 2 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0350] [I-276] The process according to any one of [I-208] to [I- 272], wherein the total amount of the solvent used in the reaction in the step iii is 0.7 to 1.8 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-277] The process according to any one of [I-208] to [I- 276], wherein the amount of the organic solvent used in the reaction in the step iii is 0.3 to 2 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0352] [I-279] The process according to any one of [I-208] to [I- 276], wherein the amount of the organic solvent used in the reaction in the step iii is 0.4 to 1.5 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0353] [I-280] The process according to any one of [I-208] to [I- 276], wherein the amount of the organic solvent used in the reaction in the step iii is 0.4 to 1.3 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0354] [I-281] The process according to any one of [I-208] to [I- 276], wherein the amount of the organic solvent used in the reaction in the step iii is 0.5 to 1.3 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-282] The process according to any one of [I-208] to [I- 281], wherein the amount of the water solvent used in the reaction in the step iii is 0.05 to 1 liter based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0356] [I-283] The process according to any one of [I-208] to [I-281], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 1 liter based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0357] [I-284] The process according to any one of [I-208] to [I-281], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 0.8 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0358] [I-285] The process according to any one of [I-208] to [I-281], wherein the amount of the water solvent used in the reaction in the step iii is 0.2 to 0.5 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-286] The process according to any one of [I-208] to [I-281], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 0.3 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0360] [I-287] The process according to any one of [I-208] to [I- 286], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 90 : 10 to 50 : 50 by volume ratio, with the proviso that any process not comprising the step iii is excluded.

[0361] [I-288] The process according to any one of [I-208] to [I- 286], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 85 : 15 to 55 : 45 by volume ratio, with the proviso that any process not comprising the step iii is excluded.

[0362] [I-289] The process according to any one of [I-208] to [I- 286], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 80 : 20 to 60 : 40 by volume ratio, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-290] The process according to any one of [I-208] to [I- 286], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 75 : 25 to 60 : 40 by volume ratio, with the proviso that any process not comprising the step iii is excluded.

[0364] [I-291] The process according to any one of [I-208] to [I- 286], wherein in the reaction in the step iii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 10 vol% to 50 vol% based on the amount of the whole solvent, with the proviso that any process not comprising the step iii is excluded.

[0365] [I-292] The process according to any one of [I-208] to [I- 286], wherein in the reaction in the step iii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 15 vol% to 45 vol% based on the amount of the whole solvent, with the proviso that any process not comprising the step iii is excluded.

[0366] [I-293] The process according to any one of [I-208] to [I- 286], wherein in the reaction in the step iii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 20 vol% to 40 vol% 2024219674   12 Sep 2024 based on the amount of the whole solvent, with the proviso that any process not comprising the step iii is excluded.

[0367] [I-294] The process according to any one of [I-208] to [I- 286], wherein in the reaction in the step iii, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is 25 vol% to 40 vol% based on the amount of the whole solvent, with the proviso that any process not comprising the step iii is excluded.

[0368] [I-295] The process according to any one of [I-1] to [I- 294], wherein the step iii comprises the following steps: (step iii-1) adding a compound of the formula (4), an organic solvent, a water solvent and a metal catalyst; (step iii-2) adding hydrogen peroxide thereto to react the compound of the formula (4) with the hydrogen peroxide, with the proviso that any process not comprising the step iii is excluded.

[0369] [I-296] The process according to any one of [I-1] to [I- 294], wherein the step iii comprises the following steps: (step iii-1) adding a compound of the formula (4), an organic solvent, a water solvent and a tungsten catalyst; (step iii-2) adding hydrogen peroxide thereto to react the compound of the formula (4) with the hydrogen peroxide, 2024219674   12 Sep 2024 with the proviso that any process not comprising the step iii is excluded and any process not including a tungsten catalyst is excluded.

[0370] [I-297] The process according to any one of [I-1] to [I- 294], wherein the step iii comprises the following steps: (step iii-1) adding a compound of the formula (4), an organic solvent, a water solvent and a molybdenum catalyst; (step iii-2) adding hydrogen peroxide thereto to react the compound of the formula (4) with the hydrogen peroxide, with the proviso that any process not comprising the step iii is excluded and any process not including a molybdenum catalyst is excluded.

[0371] [I-298] The process according to any one of [I-295] to [I- 297], wherein the amount of the water solvent added in the step iii-1 is 0 to 0.5 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0372] [I-299] The process according to any one of [I-295] to [I- 297], wherein the amount of the water solvent added in the step iii-1 is 0.05 to 0.5 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024

[0373] [I-300] The process according to any one of [I-295] to [I- 297], wherein the amount of the water solvent added in the step iii-1 is 0.05 to 0.4 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0374] [I-301] The process according to any one of [I-295] to [I- 297], wherein the amount of the water solvent added in the step iii-1 is 0.08 to 0.2 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0375] [I-302] The process according to any one of [I-295] to [I- 297], wherein the amount of the water solvent added in the step iii-1 is 0.1 to 0.3 liters based on 1 mol of the compound of the formula (4), with the proviso that any process not comprising the step iii is excluded.

[0376] [I-303] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 50°C to 150°C, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-304] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 50°C to 90°C, with the proviso that any process not comprising the step iii is excluded.

[0378] [I-305] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 60°C to 120°C, with the proviso that any process not comprising the step iii is excluded.

[0379] [I-306] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 60°C to 100°C, with the proviso that any process not comprising the step iii is excluded.

[0380] [I-307] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 60°C to 90°C, with the proviso that any process not comprising the step iii is excluded.

[0381] [I-308] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 70°C to 90°C, with the proviso that any process not comprising the step iii is excluded. 2024219674   12 Sep 2024 [I-309] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 75°C to 90°C, with the proviso that any process not comprising the step iii is excluded.

[0383] [I-310] The process according to any one of [I-1] to [I- 302], wherein the reaction in the step iii is performed at 75°C to 80°C, with the proviso that any process not comprising the step iii is excluded.

[0384] [I-311] The process according to any one of [I-1] to [I-310], wherein the reaction in the step iii is performed in 3 hours to 48 hours, with the proviso that any process not comprising the step iii is excluded.

[0385] [I-312] The process according to any one of [I-1] to [I-310], wherein the reaction in the step iii is performed in 4 hours to 24 hours, with the proviso that any process not comprising the step iii is excluded.

[0386] [I-313] The process according to any one of [I-1] to [I-312], wherein R1 is a (C1-C4)alkyl, R2 is a (C1-C4)perfluoroalkyl, and 2024219674   12 Sep 2024 R3 is a (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms.

[0387] [I-314] The process according to any one of [I-1] to [I-312], wherein R1 is methyl, R2 is trifluoromethyl, and R3 is difluoromethyl.

[0388] [I-315] The process according to any one of [I-1] to [I-312], wherein R4 and R5 are each independently a (C1-C4)alkyl.

[0389] [I-316] The process according to any one of [I-1] to [I-312], wherein R4 and R5 are methyl.

[0390] [I-317] The process according to any one of [I-1] to [I- 312], wherein X1 is a chlorine atom or a bromine atom.

[0391] [I-318] The process according to any one of [I-1] to [I-312], wherein X1 is a chlorine atom. 2024219674   12 Sep 2024 [I-319] The process according to any one of [I-1] to [I-312], wherein X2 is a chlorine atom, a bromine atom, a sulfate group, a hydrogen sulfate group, a phosphate group, a monohydrogen phosphate group, methanesulfonyloxy, p-toluenesulfonyloxy, or a mixture of two or more (preferably two or three, more preferably two) thereof.

[0393] [I-320] The process according to any one of [I-1] to [I-312], wherein X2 is a halogen atom.

[0394] [I-321] The process according to any one of [I-1] to [I-312], wherein X2 is a chlorine atom, a bromine atom, or a mixture thereof.

[0395] [I-322] The process according to any one of [I-1] to [I-312], wherein X2 is a chlorine atom.

[0396] [I-323] The process according to any one of [I-1] to [I-312], wherein X2 is a bromine atom. 2024219674   12 Sep 2024 [I-324] Use of a compound of the formula (5) produced by the process according to any one of [I-1] to [I-312] as an agrochemical.

[0398] In another aspect, the present invention is as follows.

[0399] [II-1] A process for producing a compound of the formula (4), the process comprising the following step ii: (step ii) a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce the compound of the formula (4);

[0400] [Chemical Formula 25]

[0401] wherein in the formula (2), R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally 2024219674   12 Sep 2024 substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, and X1 is a leaving group, in the formula (3), R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more substituents, or R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents, X2 is an atom or an atomic group that forms an acid, in the formula (4), R1, R2, R3, R4 and R5 are as defined above.

[0402] [II-2] The process according to [II-1], wherein the base in the step ii is an alkali metal hydroxide. 2024219674   12 Sep 2024 [II-3] The process according to [II-1], wherein the base in the step ii is sodium hydroxide.

[0404] [II-4] The process according to any one of [II-1] to [II-3], wherein in the formula (2), R1 is a (C1-C4)alkyl, R2 is a (C1-C4)perfluoroalkyl, R3 is a (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms, X1 is a chlorine atom or a bromine atom, in the formula (3), R4 and R5 are each independently a (C1-C4)alkyl, X2 is a chlorine atom, a bromine atom, a sulfate group, a hydrogen sulfate group, a phosphate group, a monohydrogen phosphate group, methanesulfonyloxy, p-toluenesulfonyloxy, or a mixture of two or more thereof, and in the formula (4), R1, R2, R3, R4 and R5 are as defined above.

[0405] [II-5] The process according to any one of [II-1] to [II-3], wherein in the formula (2), R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, X1 is a chlorine atom, in the formula (3), 2024219674   12 Sep 2024 R4 and R5 are methyl, X2 is a chlorine atom, a bromine atom, or a mixture thereof, in the formula (4), R1, R2, R3, R4 and R5 are as defined above.

[0406] [II-6] The process according to any one of [II-1] to [II- 5], the process further comprising the following step i before the step ii: (step i) a step of reacting a compound of the formula (1) with a halogenating agent to produce the compound of the formula (2):

[0407] [Chemical Formula 26]

[0408] wherein in the formula (1), R1, R2 and R3 are as defined in [II-1], in the formula (2), R1, R2 and R3 are as defined in [II- 1], and X1 is a halogen atom. 2024219674   12 Sep 2024 [II-7] The process according to [II-6], wherein the halogenating agent in the step i is a chlorinating agent.

[0410] [II-8] The process according to [II-6], wherein the halogenating agent in the step i is thionyl chloride.

[0411] [II-9] The process according to [II-7] or [II-8], wherein in the formula (1), R1 is a (C1-C4)alkyl, R2 is a (C1-C4)perfluoroalkyl, R3 is a (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms, in the formula (2), R1, R2 and R3 are as defined above, X1 is a chlorine atom.

[0412] [II-10] The process according to [II-7] or [II-8], wherein in the formula (1), R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, in the formula (2), R1, R2 and R3 are as defined above, X1 is a chlorine atom. 2024219674   12 Sep 2024 [II-11] The process according to any one of [II-1] to [II-10], the process further comprising the following step iii after the step ii: (step iii) a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of the formula (5):

[0414] [Chemical Formula 27]

[0415] wherein R1, R2, R3, R4 and R5 in the formula (4) and the formula (5) are as defined in [II-1]. [II-12] A process for producing a compound of the formula (5): 2024219674   12 Sep 2024 the process comprising the following steps: (step ii) producing a compound of the formula (4) by the process according to any one of [II-1] to [II-10]:

[0416] [Chemical Formula 29] (step iii) reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of formula (5): [Chemical Formula 30] 2024219674   12 Sep 2024 wherein R1, R2, R3, R4 and R5 in the formula (4) and the formula (5) are as defined in [II-1].

[0417] [II-13] A process for producing a compound of the formula (5): [Chemical Formula 31] using a compound of the formula (4):

[0418] 2024219674   12 Sep 2024 wherein the compound of the formula (4) is produced by the process according to any one of [II-1] to [II-10], wherein R1, R2, R3, R4 and R5 in the formula (4) and the formula (5) are as defined in [II-1].

[0419] [II-14] A process for producing a compound of the formula (5): [Chemical Formula 33] using a compound of the formula (4):

[0420] 2024219674   12 Sep 2024 wherein as the compound of the formula (4), a compound of the formula (4) produced by the process according to any one of [II-1] to [II-10] is used, wherein R1, R2, R3, R4 and R5 in the formula (4) and the formula (5) are as defined in [II-1].

[0421] [II-15] The process according to [II-11] or [II-12], wherein the hydrogen peroxide in the step iii is a 10 to 70 wt% aqueous hydrogen peroxide solution.

[0422] [II-16] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is a tungsten catalyst, a molybdenum catalyst, a niobium catalyst, a tantalum catalyst, a titanium catalyst, or a zirconium catalyst.

[0423] [II-17] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is a 2024219674   12 Sep 2024 tungsten catalyst, a molybdenum catalyst, or a niobium catalyst.

[0424] [II-18] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is a tungsten catalyst.

[0425] [II-19] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is tungstic acid, a tungstic acid salt, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten bromide, tungsten sulfide, phosphotungstic acid or a salt thereof, silicotungstic acid or a salt thereof, or a mixture of them.

[0426] [II-20] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is sodium tungstate dihydrate, ammonium molybdate tetrahydrate, sodium niobate, lithium tantalate, titanium acetylacetonate, or zirconium chloride oxide.

[0427] [II-21] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is sodium tungstate dihydrate, ammonium molybdate tetrahydrate, or sodium niobate. 2024219674   12 Sep 2024

[0428] [II-22] The process according to [II-11],  [II-12], or [II- 15], wherein the metal catalyst in the step iii is sodium tungstate dihydrate or ammonium molybdate tetrahydrate.

[0429] [II-23] The process according to any one of [II-11], [II-12] and [II-15] to [II-22], wherein the reaction in the step iii is performed in the presence of an organic solvent and a water solvent.

[0430] [II-24] The process according to [II-23], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers and amides.

[0431] [II-25] The process according to [II-23], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from alcohols, nitriles, carboxylic acid esters and amides.

[0432] [II-26] The process according to [II-23], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from alcohols, nitriles and carboxylic acid esters.

[0433] 2024219674   12 Sep 2024 [II-27] The process according to [II-23], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate.

[0434] [II-28] The process according to [II-23], wherein the organic solvent in the reaction in the step iii is acetonitrile or butyl acetate.

[0435] [II-29] The process according to any one of [II-11] to [II-26], wherein in the formula (4), R1 is a (C1-C4)alkyl, R2 is a (C1-C4)perfluoroalkyl, R3 is a (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms, R4 and R5 are each independently a (C1-C4)alkyl, in the formula (5), R1, R2, R3, R4 and R5 are as defined above.

[0436] [II-30] The process according to any one of [II-11] to [II-26], wherein in the formula (4), R1 is methyl, 2024219674   12 Sep 2024 R2 is trifluoromethyl, R3 is difluoromethyl, R4 and R5 are methyl, in the formula (5), R1, R2, R3, R4 and R5 are as defined above.

[0437] [II-31] A process for producing a compound of the formula (5), the process comprising the following step iii, wherein the reaction in the step iii is performed in the presence of an organic solvent having an acceptor number of 0 to 50 and a water solvent: (step iii) a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce a compound of the formula (5):

[0438] [Chemical Formula 35] wherein in the formula (4) and the formula (5), 2024219674   12 Sep 2024 R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents, R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents; or a (C6-C10)aryl optionally substituted with one or more substituents, or R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12-membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents.

[0440] [II-32] The process according to [II-31], wherein the hydrogen peroxide in the step iii is a 10 to 70 wt% aqueous hydrogen peroxide solution. 2024219674   12 Sep 2024

[0441] [II-33] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is a tungsten catalyst, a molybdenum catalyst or a niobium catalyst, a tantalum catalyst, a titanium catalyst, a zirconium catalyst.

[0442] [II-34] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is a tungsten catalyst, a molybdenum catalyst, or a niobium catalyst.

[0443] [II-35] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is a tungsten catalyst.

[0444] [II-36] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is tungstic acid, a tungstic acid salt, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten bromide, tungsten sulfide, phosphotungstic acid or a salt thereof, silicotungstic acid or a salt thereof, or a mixture of them.

[0445] [II-37] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is sodium 2024219674   12 Sep 2024 tungstate dihydrate, ammonium molybdate tetrahydrate, sodium niobate, lithium tantalate, titanium acetylacetonate, or zirconium chloride oxide.

[0446] [II-38] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is sodium tungstate dihydrate, ammonium molybdate tetrahydrate, or sodium niobate.

[0447] [II-39] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is sodium tungstate dihydrate or ammonium molybdate tetrahydrate.

[0448] [II-40] The process according to [II-31] or [II-32], wherein the metal catalyst in the step iii is sodium tungstate dihydrate.

[0449] [II-41] The process according to any one of [II-31] to [II- 40], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers and amides.

[0450] [II-42] The process according to any one of [II-31] to [II- 40], wherein the organic solvent in the reaction in the 2024219674   12 Sep 2024 step iii is one or more organic solvents selected from alcohols, nitriles, carboxylic acid esters and amides.

[0451] [II-43] The process according to any one of [II-31] to [II- 40], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from alcohols, nitriles and carboxylic acid esters.

[0452] [II-44] The process according to any one of [II-31] to [II- 40], wherein the organic solvent in the reaction in the step iii is one or more organic solvents selected from butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate.

[0453] [II-45] The process according to any one of [II-31] to [II-40], wherein the organic solvent in the reaction in the step iii is acetonitrile or butyl acetate.

[0454] [II-46] The process according to any one of [II-31] to [II-45], wherein in the formula (4), R1 is a (C1-C4)alkyl, R2 is a (C1-C4)perfluoroalkyl, R3 is a (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms, 2024219674   12 Sep 2024 R4 and R5 are each independently a (C1-C4)alkyl, in the formula (5), R1, R2, R3, R4 and R5 are as defined above.

[0455] [II-47] The process according to any one of [II-31] to [II-45], wherein in the formula (4), R1 is methyl, R2 is trifluoromethyl, R3 is difluoromethyl, R4 and R5 are methyl, in the formula (5), R1, R2, R3, R4 and R5 are as defined above.

[0456] [II-48] The process according to any one of [II-23] to [II-30], wherein the total amount of the solvent used in the reaction in the step iii is 0.3 to 3 liters based on 1 mol of the compound of the formula (4).

[0457] [II-49] The process according to any one of [II-23] to [II-30], wherein the total amount of the solvent used in the reaction in the step iii is 0.5 to 2 liters based on 1 mol of the compound of the formula (4). 2024219674   12 Sep 2024 [II-50] The process according to any one of [II-23] to [II-30], [II-48] and [II-49], wherein the amount of the organic solvent used in the reaction in the step iii is 0.3 to 2 liters based on 1 mol of the compound of the formula (4).

[0459] [II-51] The process according to any one of [II-23] to [II-30], [II-48] and [II-49], wherein the amount of the organic solvent used in the reaction in the step iii is 0.4 to 1.5 liters based on 1 mol of the compound of the formula (4).

[0460] [II-52] The process according to any one of [II-23] to [II- 30] and [II-48] to [II-51], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 1 liter based on 1 mol of the compound of the formula (4).

[0461] [II-53] The process according to any one of [II-23] to [II- 30] and [II-48] to [II-51], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 0.3 liters based on 1 mol of the compound of the formula (4).

[0462] [II-54] The process according to any one of [II-23] to [II- 30] and [II-48] to [II-53], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 90 : 10 to 50 : 50 by volume ratio. 2024219674   12 Sep 2024 [II-55] The process according to any one of [II-23] to [II- 30] and [II-48] to [II-53], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 80 : 20 to 60 : 40 by volume ratio.

[0464] [II-56] The process according to any one of [II-23] to [II- 30] and [II-48] to [II-55], wherein the step iii comprises the following steps: (step iii-1) adding the compound of the formula (4), the organic solvent, the water solvent and a tungsten catalyst; (step iii-2) adding hydrogen peroxide thereto to react the compound of the formula (4) with the hydrogen peroxide.

[0465] [II-57] The process according to [II-56], wherein the amount of the water solvent added in the step iii-1 is 0.05 to 0.4 liters based on 1 mol of the compound of the formula (4).

[0466] [II-58] The process according to [II-56], wherein the amount of the water solvent added in the step iii-1 is 0.08 to 0.2 liters based on 1 mol of the compound of the formula (4). 2024219674   12 Sep 2024 [II-59] The process according to any one of [II-31] to [II-47], wherein the total amount of the solvent used in the reaction in the step iii is 0.3 to 3 liters based on 1 mol of the compound of the formula (4).

[0468] [II-60] The process according to any one of [II-31] to [II-47], wherein the total amount of the solvent used in the reaction in the step iii is 0.5 to 2 liters based on 1 mol of the compound of the formula (4).

[0469] [II-61] The process according to any one of [II-31] to [II-47], [II-59] and [II-60], wherein the amount of the organic solvent used in the reaction in the step iii is 0.3 to 2 liters based on 1 mol of the compound of the formula (4).

[0470] [II-62] The process according to any one of [II-31] to [II-47], [II-59] and [II-60], wherein the amount of the organic solvent used in the reaction in the step iii is 0.4 to 1.5 liters based on 1 mol of the compound of the formula (4).

[0471] [II-63] The process according to any one of [II-31] to [II- 47] and [II-59] to [II-62], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 1 liter based on 1 mol of the compound of the formula (4). 2024219674   12 Sep 2024 [II-64] The process according to any one of [II-31] to [II-47] and [II-59] to [II-62], wherein the amount of the water solvent used in the reaction in the step iii is 0.1 to 0.3 liters based on 1 mol of the compound of the formula (4).

[0473] [II-65] The process according to any one of [II-31] to [II- 47] and [II-59] to [II-64], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 90 : 10 to 50 : 50 by volume ratio.

[0474] [II-66] The process according to any one of [II-31] to [II- 47] and [II-59] to [II-64], wherein the ratio of the organic solvent to the water solvent used in the reaction in the step iii is 80 : 20 to 60 : 40 by volume ratio.

[0475] [II-67] The process according to any one of [II-31] to [II- 47] and [II-59] to [II-66], wherein the step iii comprises the following steps: (step iii-1) adding the compound of the formula (4), the organic solvent, the water solvent and a tungsten catalyst; (step iii-2) adding hydrogen peroxide thereto to react the compound of the formula (4) with the hydrogen peroxide. 2024219674   12 Sep 2024 [II-68] The process according to [II-67], wherein the amount of the water solvent added in the step iii-1 is 0.05 to 0.4 liters based on 1 mol of the compound of the formula (4).

[0477] [II-69] The process according to [II-67], wherein the amount of the water solvent added in the step iii-1 is 0.08 to 0.2 liters based on 1 mol of the compound of the formula (4).

[0478] In another aspect, the present invention is as follows.

[0479] [III-1] A crystal of pyroxasulfone wherein the crystal exhibits a spectrum having peaks at diffraction angles 20 at least in the range of 17.8 to 17.9°, 18.0 to 18.1° and 19.9 to 20.0° in powder X-ray diffraction measurement by a transmission method using Cu-Ka ray, and the peak height of 19.9 to 20.0° is maximum among the three peaks.

[0480] [III-2] The crystal according to [III-1], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 9.9 to 10.0°, 20.6 to 20.7° and 30.1 to 30.3° in the powder X-ray diffraction measurement.

[0481] 2024219674   12 Sep 2024 [III-3] The crystal according to [III-1] or [III-2], wherein the crystal exhibits a spectrum having further peaks at diffraction angles 20 of 4.9 to 5.0° in the powder X-ray diffraction measurement. [III-4] The crystal according to any one of [III-1] to [III-3], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 20.3 to 20.4° in the powder X-ray diffraction measurement.

[0482] [III-5] The crystal according to any one of [III-1] to [III-4], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 21.8 to 21.9° in the powder X-ray diffraction measurement.

[0483] [III-6] The crystal according to any one of [III-1] to [III-5], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 22.3 to 22.4° in the powder X-ray diffraction measurement.

[0484] [III-7] The crystal according to any one of [III-1] to [III-6], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 25.4 to 25.5° in the powder X-ray diffraction measurement. 2024219674   12 Sep 2024 [III-8] The crystal according to any one of [III-1] to [III-7], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 26.6 to 26.7° in the powder X-ray diffraction measurement.

[0486] [III-9] The crystal according to any one of [III-1] to [III-8], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 26.9 to 27.0° in the powder X-ray diffraction measurement.

[0487] [III-10] The crystal according to any one of [III-1] to [III-9], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 27.1 to 27.2° in the powder X-ray diffraction measurement.

[0488] [III-11] The crystal according to any one of [III-1] to [III-10], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 35.5 to 35.6° in the powder X-ray diffraction measurement.

[0489] [III-12] The crystal according to any one of [III-1] to [III-11], wherein the crystal exhibits a spectrum further having peaks at diffraction angles 20 of 14.3 to 14.4°, 20.8 to 20.9°, 26.2 to 26.3°, 28.3 to 28.4°, 32.4 to 32.5°, 2024219674   12 Sep 2024 35.3 to 35.4°, 36.1 to 36.2°, 38.0 to 38.1° and 38.6 to 38.7° in the powder X-ray diffraction measurement.

[0490] [III-13] The crystal according to any one of [III-1] to [III-12], wherein the ratio of the peak height at 19.9 to 20.0° to the peak height at 17.7 to 17.8° is 1 : 0.02 to 1 : 0.95 in the powder X-ray diffraction measurement.

[0491] [III-14] The crystal according to [III-13], wherein the ratio of the peak height of 19.9 to 20.0° to the peak height of 17.7 to 17.8° is 1 : 0.1 to 1 : 0.85 in the powder X-ray diffraction measurement.

[0492] [III-15] The crystal according to [III-14], wherein the ratio of the peak height at 19.9 to 20.0° to the peak height at 17.7 to 17.8° is 1 : 0.3 to 1 : 0.75 in the powder X-ray diffraction measurement.

[0493] [III-16] The crystal according to any one of [III-13] to [III-15], wherein the ratio of the peak height at 19.9 to 20.0° to the peak height at 18.0 to 18.1° is 1 : 0.02 to 1 : 0.95 in the powder X-ray diffraction measurement.

[0494] [III-17] The crystal according to [III-16], wherein the ratio of the peak height at 19.9 to 20.0° to the peak 2024219674   12 Sep 2024 height at 18.0 to 18.1° is 1 : 0.04 to 1 : 0.8 in the powder X-ray diffraction measurement.

[0495] [III-18] The crystal according to [III-17], wherein the ratio of the peak height at 19.9 to 20.0° to the peak height at 18.0 to 18.1° is 1 : 0.07 to 1 : 0.6 in the powder X-ray diffraction measurement.

[0496] [III-19] The crystal according to any one of [III-1] to [III-18], wherein the crystal is obtained by distilling off an organic solvent from a solution of pyroxasulfone in a medium composed of a liquid comprising the organic solvent as a main component to precipitate pyroxasulfone, the organic solvent being one selected from the group consisting of nitriles, carboxylic acids, carboxylic acid esters, ketones, amides and dihalogenated aliphatic hydrocarbons.

[0497] [III-20] The crystal according to [III-19], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkanes. 2024219674   12 Sep 2024 [III-21] The crystal according to [III-20], wherein the organic solvent is one selected from the group consisting of acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N- dimethylacetamide and dichloromethane.

[0499] [III-22] The crystal according to [III-19], wherein the medium is one selected from the group consisting of C2-C5 alkanenitrile / C1-C4 alcohol mixtures, hydrous C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkane / C1-C4 alcohol mixtures.

[0500] [III-23] The crystal according to [III-22], wherein the medium is one selected from the group consisting of an acetonitrile / methanol mixture, hydrous acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide and a dichloromethane / ethanol mixture.

[0501] [III-24] The crystal according to any one of [III-1] to [III-18], wherein the crystal is one obtained by adding an antisolvent for pyroxasulfone selected from the group consisting of ethers, carboxylic acid esters, ketones, 2024219674   12 Sep 2024 aromatic hydrocarbon derivatives, aliphatic hydrocarbons, alcohols and water to the solution of pyroxasulfone in a medium composed of a liquid comprising one organic solvent selected from the group consisting of nitriles, ketones and carboxylic acid esters as a main component, and precipitating pyroxasulfone.

[0502] [III-25] The crystal according to [III-24], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 alkyl ketones and C1-C4 alkyl C1-C4 carboxylates.

[0503] [III-26] The crystal according to [III-25], wherein the organic solvent is one selected from the group consisting of acetonitrile, acetone and ethyl acetate.

[0504] [III-27] The crystal according to any one of [III-24] to [III-26], wherein the antisolvent for pyroxasulfone is C1- C4 alcohol.

[0505] [III-28] The crystal according to [III-27], wherein the antisolvent for pyroxasulfone is one selected from the group consisting of ethanol and isopropanol. 2024219674   12 Sep 2024 [III-29] The crystal according to any one of [III-19] to [III-28], wherein the solution of pyroxasulfone is a reaction solution prepared by producing pyroxasulfone by reacting 3-[(5-difluoromethoxy-1-methyl-3- trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole with hydrogen peroxide in the presence of a metal catalyst in the liquid comprising the organic solvent described above as a main component.

[0507] [III-30] The crystal according to any one of [III-1] to [III-29], wherein the crystal has a short columnar or columnar appearance.

[0508] [III-31] An agrochemical composition comprising the crystal of pyroxasulfone according to any one of [III-1] to [III-30] and a surfactant.

[0509] [III-32] The agrochemical composition according to [III- 31], further comprising water or an oil-based dispersion medium and having a dosage form of an aqueous suspension concentrate or an oil dispersion.

[0510] [III-33] The agrochemical composition according to [III- 31], further comprising a solid carrier and having a dosage form of a wettable powder or a water-dispersible granule. 2024219674   12 Sep 2024

[0511] [III-34] The agrochemical composition comprising a crystal of pyroxasulfone and a surfactant, wherein the composition is one produced using the crystal of pyroxasulfone according to any one of [III-1] to [III-30].

[0512] [III-35] The agrochemical composition according to [III-34], further comprising water or an oil-based dispersion medium and having a dosage form of an aqueous suspension concentrate or an oil dispersion.

[0513] [III-36] The agrochemical composition according to [III- 34], further comprising a solid carrier and having a dosage form of a wettable powder or a water-dispersible granule.

[0514] [III-37] A process for producing a crystal of pyroxasulfone, wherein an organic solvent is distilled off from a solution of pyroxasulfone in a medium composed of a liquid comprising the organic solvent as a main component to precipitate pyroxasulfone, the organic solvent being one selected from the group consisting of nitriles, carboxylic acids, carboxylic acid esters, ketones, amides and dihalogenated aliphatic hydrocarbons. 2024219674   12 Sep 2024 [III-38] The process for producing according to [III-37], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkanes.

[0516] [III-39] The process for producing according to [III-38], wherein the organic solvent is acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide or dichloromethane.

[0517] [III-40] The process for producing according to [III-37], wherein the medium is one selected from the group consisting of C2-C5 alkanenitrile / C1-C4 alcohol mixtures, hydrous C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkane / C1-C4 alcohol mixtures.

[0518] [III-41] The process for producing according to [III-40], wherein the medium is one selected from the group consisting of an acetonitrile / methanol mixture, hydrous acetonitrile, acetic acid, ethyl acetate, methyl isobutyl 2024219674   12 Sep 2024 ketone, N,N-dimethylformamide, N,N-dimethylacetamide and a dichloromethane / ethanol mixture.

[0519] [III-42] A process for producing a crystal of pyroxasulfone, wherein an antisolvent for pyroxasulfone selected from the group consisting of ethers, carboxylic acid esters, ketones, aromatic hydrocarbon derivatives, aliphatic hydrocarbons, alcohols and water is added to a solution of pyroxasulfone in a medium composed of a liquid comprising one organic solvent selected from the group consisting of nitriles, ketones and carboxylic acid esters as a main component to precipitate pyroxasulfone.

[0520] [III-43] The process for producing according to [III-42], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 alkyl ketones and C1-C4 alkyl C1-C4 carboxylates.

[0521] [III-44] The process for producing according to [III-43], wherein the organic solvent is one selected from the group consisting of acetonitrile, acetone and ethyl acetate.

[0522] [III-45] The process for producing according to any one of [III-42] to [III-44], wherein the antisolvent for pyroxasulfone is C1-C4 alcohol. 2024219674   12 Sep 2024

[0523] [III-46] The crystal according to [III-45], wherein the antisolvent for pyroxasulfone is one selected from the group consisting of ethanol and isopropanol.

[0524] [III-47] A process for producing a crystal of pyroxasulfone, wherein 3-[(5-difluoromethoxy-1-methyl-3- trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole is reacted with hydrogen peroxide in the presence of a metal catalyst in a liquid comprising one organic solvent selected from the group consisting of nitriles, carboxylic acids, carboxylic acid esters, ketones, amides and dihalogenated aliphatic hydrocarbons as a main component to produce pyroxasulfone, and the organic solvent is distilled off from the obtained reaction solution of pyroxasulfone to precipitate pyroxasulfone.

[0525] [III-48] The process for producing according to [III-47], further comprising the step of producing pyroxasulfone by the step (iii) described in [I-1].

[0526] [III-49] The process for producing according to [III-47] or [III-48], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 2024219674   12 Sep 2024 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl)C1-C4 alkanamides and C1-C4 dihaloalkanes.

[0527] [III-50] The process for producing according to [III-49], wherein the organic solvent is one selected from the group consisting of acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide and dichloromethane.

[0528] [III-51] The process for producing according to [III-47] or [III-48], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 carboxylates and N,N-di(C1-C4 alkyl)C1-C4 alkanamides.

[0529] [III-52] The process for producing according to [III-51], wherein the organic solvent is one selected from the group consisting of acetonitrile, ethyl acetate and N,N-dimethylformamide.

[0530] [III-53] The process for producing according to [III-47] or [III-48], wherein the liquid is one selected from the group consisting of C2-C5 alkanenitrile / C1-C4 alcohol mixtures, hydrous C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, 2024219674   12 Sep 2024 N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkane / C1-C4 alcohol mixtures.

[0531] [III-54] The process for producing according to [III-53], wherein the liquid is one selected from the group consisting of acetonitrile / methanol mixtures, hydrous acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide and dichloromethane / ethanol mixtures.

[0532] [III-55] The process for producing according to [III-47] or [III-48], wherein the liquid is one selected from the group consisting of C2-C5 alkanenitrile / C1-C4 alcohol mixtures, hydrous C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 carboxylates and N,N-di(C1-C4 alkyl)C1-C4 alkanamides.

[0533] [III-56] The process for producing according to [III-55], wherein the liquid is one selected from the group consisting of acetonitrile / methanol mixtures, hydrous acetonitrile, ethyl acetate and N,N-dimethylformamide.

[0534] [III-57] A process for producing a crystal of pyroxasulfone, wherein 3-[(5-difluoromethoxy-1-methyl-3- trifluoromethylpyrazol-4-yl)methylthio]-4,5-dihydro-5,5-dimethylisoxazole is reacted with hydrogen peroxide in the 2024219674   12 Sep 2024 presence of a metal catalyst in a liquid comprising one organic solvent selected from the group consisting of nitriles, ketones and carboxylic acid esters as a main component to produce pyroxasulfone, and then an antisolvent for pyroxasulfone selected from the group consisting of ethers, carboxylic acid esters, ketones, aromatic hydrocarbon derivatives, aliphatic hydrocarbons, alcohols and water is added to the obtained solution of pyroxasulfone to precipitate pyroxasulfone.

[0535] [III-58] The process for producing according to [III-57], further comprising the step of producing pyroxasulfone by the step (iii) defined in [I-1].

[0536] [III-59] The process for producing according to [III-57] or [III-58], wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 alkyl ketones and C1-C4 alkyl C1-C4 carboxylates.

[0537] [III-60] The process for producing according to [III-59], wherein the organic solvent is one selected from the group consisting of acetonitrile, acetone and ethyl acetate.

[0538] [III-61] The process for producing according to [III-57] or [III-58], wherein the organic solvent is one selected from 2024219674   12 Sep 2024 the group consisting of C2-C5 alkanenitriles and C1-C4 alkyl C1-C4 carboxylates.

[0539] [III-62] The process for producing according to [III-61], wherein the organic solvent is one selected from the group consisting of acetonitrile and ethyl acetate.

[0540] [III-63] The process for producing according to any one of [III-57] to [III-62], wherein the antisolvent for pyroxasulfone is C1-C4 alcohol.

[0541] [III-64] The process for producing according to [III-63], wherein the antisolvent for pyroxasulfone is one selected from the group consisting of ethanol and isopropanol.

[0542] [III-65] A process for producing an agrochemical composition having a dosage form of a wettable powder, the process comprising a step of pulverizing a powder comprising the crystal of pyroxasulfone according to any one of [III-1] to [III-30], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and a solid carrier to homogenize the mixture.

[0543] 2024219674   12 Sep 2024 [III-66] A process for producing an agrochemical composition having a dosage form of a water-dispersible granule, the process comprising a step of pulverizing a powder or a slurry comprising the crystal of pyroxasulfone according to any one of [III-1] to [III-30], a step of, while homogenizing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and a solid carrier, further adding a slight amount of water and kneading the mixture, a step of granulating the kneaded product obtained in the preceding step, and a step of drying the granulated product obtained in the preceding step.

[0544] [III-67] A process for producing an agrochemical composition having a dosage form of an aqueous suspension concentrate, the process comprising a step of pulverizing a powder or slurry comprising the crystal of pyroxasulfone according to any one of [III-1] to [III-30], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and water to homogenize the mixture.

[0545] [III-68] A process for producing an agrochemical composition having a dosage form of an oil dispersion, the process comprising a step of pulverizing a powder or slurry 2024219674   12 Sep 2024 comprising the crystal of pyroxasulfone according to any one of [III-1] to [III-30], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and an oil-based dispersion medium to homogenize the mixture.

[0546] [III-69] A process for producing an agrochemical composition having a dosage form of a wettable powder, the process comprising a step of pulverizing a powder comprising a crystal of pyroxasulfone prepared by the process for producing according to any one of [III-37] to [III-64], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and a solid carrier to homogenize the mixture.

[0547] [III-70] A process for producing an agrochemical composition having a dosage form of a water-dispersible granule, the process comprising a step of pulverizing a powder or a slurry comprising a crystal of pyroxasulfone prepared by the process for producing according to any one of [III-37] to [III-64], a step of, while homogenizing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and a solid carrier, further adding a slight amount of water and kneading the mixture, a step of granulating the kneaded product obtained in the 2024219674   12 Sep 2024 preceding step, and a step of drying the granulated product obtained in the preceding step.

[0548] [III-71] A process for producing an agrochemical composition having a dosage form of an aqueous suspension concentrate, the process comprising a step of pulverizing a powder or a slurry comprising a crystal of pyroxasulfone prepared by the process for producing according to any one of [III-37] to [III-64] and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and water to homogenize the mixture.

[0549] [III-72] A process for producing an agrochemical composition having a dosage form of an oil dispersion, the process comprising a step of pulverizing a powder or slurry comprising a crystal of pyroxasulfone prepared by the process for producing according to any one of [III-37] to [III-64], and a step of mixing the whole raw material comprising the pulverized crystal of pyroxasulfone, a surfactant and an oil-based dispersion medium to homogenize the mixture.

[0550] The symbols and terms described in the present description will be explained. 2024219674   12 Sep 2024

[0551] Herein, the following abbreviations and prefixes may be used, and their meanings are as follows: Me: methyl Et: ethyl Pr, n-Pr and Pr-n: propyl (i.e., normal propyl) i-Pr and Pr-i: isopropyl Bu, n-Bu and Bu-n: butyl (i.e., normal butyl) s-Bu and Bu-s: sec-butyl (i.e., secondary butyl) i-Bu and Bu-i: isobutyl t-Bu and Bu-t: tert-butyl (i.e., tertiary butyl) Ph: phenyl n-: normal s- and sec-: secondary i- and iso-: iso t- and tert-: tertiary c- and cyc-: cyclo o-: ortho m-: meta p-: para

[0552] The term “nitro” means the substituent “-NO2”. The term “cyano” or “nitrile” means the substituent “- CN”. The term “hydroxy” means the substituent “-OH”. 2024219674   12 Sep 2024 The term “amino” means the substituent “-NH2”.

[0553] (Ca-Cb) means that the number of carbon atoms is a to b. For example, “(C1-C4)” in “(C1-C4)alkyl" means that the number of the carbon atoms in the alkyl is 1 to 4, and “(C2-C5)” means that the number of the carbon atoms in the alkyl is 2 to 5. “(Ca-Cb)” meaning the number of carbon atoms may be written as “Ca-Cb” without parentheses. Thus, for example, “C1-C4” in "C1-C4 alkyl” means that the number of the carbon atoms in the alkyl is 1 to 4.

[0554] Herein, it is to be interpreted that generic terms such as “alkyl” include both the straight chain and the branched chain such as butyl and tert-butyl. Meanwhile, for example, the specific term “butyl” refers to straight “normal butyl”, and does not refer to branched “tert butyl”. Branched chain isomers such as “tert-butyl” are referred to specifically when intended.

[0555] Examples of the halogen atom include fluorine atom, chlorine atom, bromine atom and iodine.

[0556] The (C1-C6)alkyl means a straight or branched alkyl having 1 to 6 carbon atoms. Examples of the (C1-C6)alkyl include, but are not limited to, methyl, ethyl, propyl, 2024219674   12 Sep 2024 isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl and hexyl.

[0557] The (C1-C4)alkyl means a straight or branched alkyl having 1 to 4 carbon atoms. Examples of the (C1-C4)alkyl include, appropriate examples of the examples of the (C1-C6)alkyl above-mentioned.

[0558] The (C3-C6)cycloalkyl means a cycloalkyl having 3 to 6 carbon atoms. Examples of the (C3-C6)cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0559] The (C2-C6)alkenyl means a straight or branched alkenyl having 2 to 6 carbon atoms. Examples of the (C2-C6)alkenyl include, but are not limited to, vinyl, 1-propenyl, isopropenyl, 2-propenyl, 1-butenyl, 1-methyl-1-propenyl, 2- methyl-1-propenyl, 2-butenyl, 3-butenyl, 1,3-butadienyl, 1- pentenyl and 1-hexenyl.

[0560] The (C2-C6)alkynyl means a straight or branched alkynyl having 2 to 6 carbon atoms. Examples of the (C2-C6)alkynyl include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, 1-pentynyl and 1-hexynyl. 2024219674   12 Sep 2024 Examples of the (C6-C10)aryl are phenyl, 1-naphthyl and 2-naphthyl.

[0562] The (C1-C6)haloalkyl means a straight or branched alkyl having 1 to 6 carbon atoms which is substituted with 1 to 13 same or different halogen atoms, wherein the halogen atoms have the same meaning as defined above. Examples of the (C1-C6)haloalkyl include, but are not limited to, 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, undecafluoropentyl and tridecafluorohexyl.

[0563] The (C1-C4)perfluoroalkyl means a straight or branched alkyl having 1 to 4 carbon atoms, wherein all hydrogen atoms are substituted with fluorine atoms. Examples of the 2024219674   12 Sep 2024 (C1-C4)perfluoroalkyl 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).

[0564] The (C1-C6)alkoxy means a (C1-C6)alkyl-O-, wherein the (C1-C6)alkyl moiety has the same meaning as defined above. Examples of the (C1-C6)alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, secbutoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy and hexyloxy.

[0565] The (C1-C6)alcohol means a (C1-C6)alkyl-OH, wherein the (C1-C6)alkyl moiety has the same meaning as defined above. Examples of the (C1-C4)alcohol include, but are not limited to, methanol, ethanol, propanol (i.e., 1-propanol), 2-propanol, butanol (i.e., 1-butanol), sec-butanol, isobutanol, tert-butanol, pentanol (i.e., 1-pentanol), secamyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol (i.e., 1-hexanol) and cyclohexanol. Polyols having 1 to 6 carbons (e.g., diols 2024219674   12 Sep 2024 and triols) such as ethylene glycol, propylene glycol and glycerol are equivalents of (C1-C6)alcohols.

[0566] The (C1-C4)alcohol means a (C1-C4)alkyl-OH, wherein the (C1-C4)alkyl moiety has the same meaning as defined above. Examples of the (C1-C4)alcohol include, but are not limited to, methanol, ethanol, propanol (i.e., 1-propanol), 2-propanol, butanol, sec-butanol, isobutanol and tertbutanol. Polyols having 1 to 4 carbons (e.g., diols and triols) such as ethylene glycol, propylene glycol and glycerol are equivalents of (C1-C4)alcohols.

[0567] The (C2-C5)alkanenitrile means (C1-C4)alkyl-CN, wherein the (C1-C4)alkyl moiety means a linear or branched alkyl having 1 to 5 carbon atoms; examples of the (C1-C5)alkyl include appropriate examples among the examples of the (C1- C6)alkyl described above. Examples of the (C2-C5)alkanenitrile include, but are not limited to, acetonitrile and propionitrile. Herein, the (C2-C5)alkanenitrile is also referred to as C2-C5 alkanenitrile. C2 alkanenitrile is acetonitrile. In other words, acetonitrile is ethanenitrile in accordance with the IUPAC nomenclature and is a C2 alkanenitrile having two carbon atoms. Similarly, propionitrile is a C3 alkanenitrile. 2024219674   12 Sep 2024

[0568] Examples of the (C1-C4)alkyl (C1-C4)carboxylates include, but are not limited to, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof, ethyl propionate, propyl propionate, isopropyl propionate, butyl propionate and isomers thereof, and preferably ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof. Herein, (C1-C4)alkyl (C1-C4)carboxylate is also referred to as C1-C4 alkyl C1-C4 carboxylate.

[0569] Examples of the N,N-di((C1-C4)alkyl)(C1-C4)alkanamides include, but are not limited to, N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide and N,N-diethylacetamide, and preferably N,N-dimethylformamide and N,N-dimethylacetamide. Herein, N,N-di((C1-C4)alkyl)(C1-C4)alkanamide is also referred to as N,N-di(C1-C4 alkyl)C1-C4 alkanamide. N,N-di(C1 alkyl)C1 alkanamide is N,N-dimethylformamide. N,N-di(C1 alkyl)C2 alkanamide is N,N-dimethylacetamide.

[0570] The (C1-C4)carboxylic acid means a (C1-C4)alkyl-COOH, i.e., (C1-C4)alkyl-C(=O)-OH, wherein the (C1-C4)alkyl moiety has the same meaning as defined above. Examples of the (C1-C4)carboxylic acids include, but are not limited 2024219674   12 Sep 2024 to, acetic acid and propionic acid, and preferably acetic acid. Herein, (C1-C4)carboxylic acid is also referred to as C1-C4 carboxylic acid.

[0571] Examples of the (C1-C4)alkyl (C1-C4)alkyl ketones include, but are not limited to, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK) and methyl isobutyl ketone (MIBK). Herein, (C1-C4) alkyl (C1-C4) alkyl ketone is also referred to as C1-C4 alkyl C1-C4 alkyl ketone.

[0572] Examples of the (C1-C4)dihaloalkanes include, but are not limited to, dichloromethane and 1,2-dichloroethane. Herein, (C1-C4)dihaloalkane is also referred to as C1-C4 dihaloalkane.

[0573] The cyclic hydrocarbon group means a cyclic group which is monocyclic or multicyclic, wherein all of the ringconstituting atoms are carbon atoms. In one embodiment, examples of the cyclic hydrocarbon group include, but are not limited to, a 3- to 14-membered (preferably 5- to 14 membered, more preferably 5- to 10-membered) cyclic hydrocarbon group which is aromatic or non-aromatic and is monocyclic, bicyclic or tricyclic. In another embodiment, examples of the cyclic hydrocarbon group include, but are 2024219674   12 Sep 2024 not limited to, a 4- to 8-membered (preferably 5- to 6membered) cyclic hydrocarbon group which is aromatic or non-aromatic and is monocyclic or bicyclic (preferably monocyclic). Examples of the cyclic hydrocarbon group include, but are not limited to, cycloalkyls and aryls. Examples of the cycloalkyl include the examples of the (C3-C6)cycloalkyl described above. The aryls are aromatic cyclic groups among the cyclic hydrocarbon groups as defined above. Examples of the aryl include the examples of the (C6-C10)aryl described above. The cyclic hydrocarbon group as defined or exemplified above may include a non-condensed cyclic group (e.g., a monocyclic group or a spirocyclic group) and a condensed cyclic group, when possible. The cyclic hydrocarbon group as defined or exemplified above may be unsaturated, partially saturated or saturated, when possible. The cyclic hydrocarbon group as defined or exemplified above is also referred to as a carbocyclic ring group. The carbocyclic ring is a ring which corresponds to the cyclic hydrocarbon group as defined or exemplified above. Examples of the carbocyclic ring include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cyclopentene and cyclohexene. 2024219674   12 Sep 2024 Herein, there are no particular limitations on the “substituent(s)” for the phrase “optionally substituted with one or more substituents” as long as they are chemically acceptable and exhibit the effects of the present invention.

[0575] Herein, examples of the “substituent(s)” for the phrase “optionally substituted with one or more substituent(s)” include, but are not limited to, one or more substituents (preferably 1 to 3 substituents) selected independently from Substituent Group (a).

[0576] Substituent Group (a) is a group consisting of a halogen atom; a nitro group, a cyano group, a hydroxy group, an amino group, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, phenyl and phenoxy.

[0577] In addition, one or more substituents (preferably 1 to 3 substituents) selected independently from Substituent Group (a) may each independently be substituted with one or more substituents (preferably 1 to 3 substituents) selected independently from Substituent Group (b). In this context, Substituent Group (b) is the same as Substituent Group (a). 2024219674   12 Sep 2024 Examples of the “(C1-C6)alkyl optionally substituted with one or more substituents” include, but are not limited to, (C1-C6)haloalkyl, (C1-C4)perfluoroalkyl and (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms.

[0579] Examples of the (C1-C4)alkyl optionally substituted with 1 to 9 fluorine atoms include, but are not limited to, fluoromethyl (i.e., -CH2F), difluoromethyl (i.e., -CHF2), trifluoromethyl (i.e., -CF3), 2-fluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 2,2,3,3,3-pentafluoropropyl, 2,2,2-trifluoro-1-trifluoromethylethyl, heptafluoropropyl, 1,2,2,2-tetrafluoro-1-trifluoromethylethyl, 4-fluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, nonafluorobutyl, 1,1,2,3,3,3-hexafluoro-2 trifluoromethylpropyl and 2,2,2-trifluoro-1,1-di(trifluoromethyl)ethyl.

[0580] Herein, the phrase “as described herein” and similar phrases used when referring to substituents (for example, R1, R2, R3, R4, R5, X1 and X2) incorporate by reference all definitions of the substituents and, if any, all of their examples, preferred examples, more preferred examples, further preferred examples and particularly preferred examples in this specification.

[0581] 2024219674   12 Sep 2024 (Acceptor Number) Herein, regarding the acceptor number, the following document can be referred to, for example, Christian Reichardt, "Solvents and Solvent Effects in Organic Chemistry", 3rd, updated and enlarged edition, WILEY-VCH, 2003, p. 25-26

[0582] The definition of the acceptor number utilizing 31P-NMR chemical shift values are described in the above document, which is incorporated into the present invention by reference.

[0583] Examples of the solvent having a specified acceptor number are described in the above document, which are incorporated into the present invention by reference, but are not limited thereto. The acceptor numbers of typical solvents are as follows: hexane: 0.0, ethyl acetate: 9.3, acetonitrile: 18.9, butanol: 32.2, ethanol, 37.1, acetic acid: 52.9, and water: 54.8.

[0584] As used herein, the non-limiting term “comprise(s) / comprising” can each optionally be replaced by the limiting phrase “consist(s) of / consisting of”. 2024219674   12 Sep 2024 Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art to which the present disclosure belongs.

[0586] Unless otherwise indicated, it is understood that numbers used herein to express characteristics such as quantities, sizes, concentrations, and reaction conditions are modified by the term “about”. In some embodiments, disclosed numerical values are interpreted applying the reported number of significant digits and conventional rounding techniques. In some embodiments, disclosed numerical values are interpreted as containing certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0587] (Step i) The step i will be described.

[0588] The step i is one of the processes for producing the compound of the formula (2) when X1 in the formula (2) is a halogen atom.

[0589] The step i is a step of reacting a compound of the formula (1) with a halogenating agent to produce the 2024219674   12 Sep 2024 compound of the formula (2), with the proviso that X1 in the formula (2) is a halogen atom:

[0590] [Chemical Formula 36] wherein R1, R2 and R3 are as described herein and X1 is a halogen atom.

[0591] The reaction in the step i is a halogenation reaction of a hydroxy group.

[0592] (Raw Material in Step i; Compound of Formula (1)) A compound of the formula (1) is used as a raw material in the step i. The compound of the formula (1) may be a known compound or may be produced from a known compound according to a known process. For example, the preparation of the compound of the formula (1) can be performed by the process described in WO 2007 / 094225 A1 (Patent Document 5), Example 1 as shown below, or by a process similar thereto. [Chemical Formula 37] 2024219674   12 Sep 2024 WO2007 / 094225A1. Example I BC__ 24%KOH 3 7%HCHO N.            ► N UH CH3 MTP 24%KOH CHF£CI CHiCN FMTP (1-a)

[0594] WO 2007 / 094225 A1 (Patent Document 5) is summarized below. For example, WO 2007 / 094225 A1 (Patent Document 5) discloses that the compound of the formula (1-a) has been produced from an acetoacetic acid ester derivative as shown in the following scheme.

[0595] [Chemical Formula 38] (MMH. W02OO7-O94225A' Reference Example I WO2007,094225A1 Example 1

[0596] In the formula (1) R1, R2 and R3 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, or a 2024219674   12 Sep 2024 (C6-C10)aryl optionally substituted with one or more substituents.

[0597] From the viewpoints of yield, availability, price, usefulness of the product, etc., preferred examples of R1 in the formula (1) include (C1-C6)alkyls optionally substituted with one or more substituents, more preferably (C1-C6)alkyls, further preferably (C1-C4)alkyls, and particularly preferably methyl.

[0598] From the same viewpoints as described above, preferred examples of R2 in the formula (1) include (C1-C6)alkyls optionally substituted with one or more substituents, more preferably (C1-C6)haloalkyls, further preferably (C1-C4)perfluoroalkyls, and particularly preferably trifluoromethyl.

[0599] From the same viewpoints as described above, preferred examples of R3 in the formula (1) include (C1-C6)alkyls optionally substituted with one or more substituents, more preferably (C1-C6)haloalkyls, further preferably (C1-C4)alkyls optionally substituted with 1 to 9 fluorine atoms, and particularly preferably difluoromethyl. 2024219674   12 Sep 2024 A particularly preferred example of the compound of the formula (1) is as follows:

[0601] [Chemical Formula 39] f3c .^oh n'n^ochf2 ch3 FMTP (1-a)

[0602] (Product in Step i; Compound of Formula (2))

[0603] The product in the step i is a compound of the formula (2) corresponding to the compound of the formula (1) used as a raw material.

[0604] In the formula (2), R1, R2 and R3 are as defined in the formula (1). In the formula (2), examples, preferred examples, more preferred examples, and particularly preferred examples of R1, R2 and R3 are the same as those in the formula (1) described above, respectively.

[0605] In the step i, in the formula (2), X1 is a halogen atom. From the viewpoint of yield, availability, price, etc., more preferred examples of X1 in the formula (2) 2024219674   12 Sep 2024 include chlorine atom and bromine atom, and particularly preferably chlorine atom.

[0606] Specific examples of the compound of the formula (2) include, but are not limited to, the following:

[0607] [Chemical Formula 40]

[0608] Particularly preferred specific examples of the compound of the formula (2) are as follows:

[0609] [Chemical Formula 41]

[0610] (Halogenating Agent in Step i) The halogenating agent may be any halogenating agent as long as the reaction proceeds. Examples of the halogenating agent include, but are not limited to, 2024219674   12 Sep 2024 chlorinating agents and brominating agents, and preferably chlorinating agents.

[0611] Specific examples of the halogenating agent include, but are not limited to, chlorine (Cl2), hydrogen chloride (e.g., hydrogen chloride gas, 30% to 35% hydrochloric acid), thionyl chloride, sulfuryl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, oxalyl chloride, bromine (Br2), hydrogen bromide (e.g., 48% hydrobromic acid), thionyl bromide, phosphorus tribromide, phosphorus oxybromide, etc.), phosgene and benzoyl chloride. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., preferred specific examples of the halogenating agent include chlorine, hydrogen chloride, thionyl chloride, sulfuryl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, bromine, hydrogen bromide and phosphorus tribromide, more preferably chlorine, thionyl chloride, sulfuryl chloride, phosphorus trichloride, phosphorus pentachloride and phosphorus oxychloride, further preferably thionyl chloride and sulfuryl chloride, and further preferably thionyl chloride.

[0612] The halogenating agent in the step i may be used singly or in a combination of two or more kinds thereof in any 2024219674   12 Sep 2024 ratio. The form of the halogenating agent in the step i may be any form as long as the reaction proceeds. The form of the halogenating agent in the step i can be appropriately selected by a person skilled in the art. The amount of the halogenating agent used in the step i may be any amount as long as the reaction proceeds. The amount of the halogenating agent used in the step i may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by products, economic efficiency, etc., the amount of the halogenating agent used in the step i is, for example, 1.0 to 3.0 mol, preferably 1.0 to 2.0 mol, more preferably 1.0 to 1.5 mol, and still more preferably 1.0 to 1.1 mol, based on 1 mol of the compound of the formula (1) (raw material).

[0613] (Catalyst in Step i: Amide, etc.) The reaction in the step i may be performed in the presence or absence of a catalyst. Whether or not to use a catalyst in the reaction in the step i can be appropriately determined by a person skilled in the art. However, it is apparent from the Examples disclosed herein that the reaction proceeds sufficiently in the absence of a catalyst. When a catalyst is used in the step i, any catalyst may be used as long as the reaction proceeds. Examples of the catalyst in the step i include, but are not 2024219674   12 Sep 2024 limited to, amides (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC) and N-methylpyrrolidone (NMP)) and ureas (e.g., N,N'-dimethylimidazolidinone (DMI) and tetramethylurea). From the viewpoint of yield, suppression of by-products, economic efficiency, etc., preferred examples of the catalyst in the step i include N,N- dimethylformamide (DMF) and N-methylpyrrolidone (NMP), and more preferably N,N-dimethylformamide (DMF).

[0614] The catalyst in the step i may be used singly or in a combination of two or more kinds thereof in any ratio. The catalyst in the step i may be in any form as long as the reaction proceeds. The form of the catalyst in the step i can be appropriately selected by a person skilled in the art. The amount of the catalyst used in the step i may be any amount as long as the reaction proceeds. In the step i, no catalyst may be used. When a catalyst is used in the step i, the amount of the catalyst used in the step i may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of byproducts, economic efficiency, etc., in one embodiment, the amount of the catalyst used in the step i is, for example, 0 (zero) to 0.1 mol, and preferably 0 (zero) to 0.05 mol, based on 1 mol of the compound of the formula (1) (raw material). In another embodiment, the amount of the 2024219674   12 Sep 2024 catalyst used in the step i is, for example, 0.001 to 0.1 mol, and preferably 0.01 to 0.05 mol, based on 1 mol of the compound of the formula (1) (raw material).

[0615] (Reaction Solvent in Step i) The reaction in the step i may be performed in the absence or presence of a solvent. Whether or not to use a solvent in the reaction in the step i can be appropriately determined by a person skilled in the art. When a solvent is used in the reaction in the step i, the solvent may be any solvent as long as the reaction proceeds. The solvent in the reaction in the step i can be selected appropriately by a person skilled in the art. Examples of the solvent in the reaction in the step i include, but are not limited to, the following: aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, trichlorobenzenes and nitrobenzene), halogenated aliphatic hydrocarbons (e.g., dichloromethane and 1,2-dichloroethane (EDC)), aliphatic hydrocarbons (e.g., hexane, cyclohexane and ethylcyclohexane), nitriles (e.g., acetonitrile and propionitrile), ethers (e.g., tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME) and diglyme), and any combination thereof in any ratio. Among the aromatic 2024219674   12 Sep 2024 hydrocarbon derivatives, halogenated aromatic hydrocarbons (e.g., chlorobenzene, dichlorobenzene and trichlorobenzene) are preferable.

[0616] From the viewpoint of yield, suppression of by products, economic efficiency, etc., preferably, the reaction in the step i is performed in the absence of a solvent or in the presence of a solvent selected from the following: aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, nitriles, and any combination thereof in any ratio. More preferably, the reaction in the step i is performed in the absence of a solvent or in the presence of a solvent selected from the following: chlorobenzene, dichlorobenzenes, trichlorobenzenes, dichloromethane, 1,2-dichloroethane, acetonitrile, and any combination thereof in any ratio. More preferably, the reaction in the step i is performed in the absence of a solvent or in the presence of a solvent selected from the following: dichloromethane and acetonitrile. More preferably, the reaction in the step i is performed in the absence of a solvent or in the presence of acetonitrile as a solvent. Particularly preferably, the reaction in the step i is performed in the presence of acetonitrile as a solvent. 2024219674   12 Sep 2024 The amount of the solvent used in the reaction in the step i is not particularly limited as long as the reaction system can be sufficiently stirred. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the amount of the solvent used in the reaction in the step i is, for example, 0 (zero) to 3 L (liters), preferably 0 (zero) to 2 L, more preferably 0 (zero) to 1.5 L, further preferably 0 (zero) to 1 L, and further preferably 0 (zero) to 0.8 L, based on 1 mol of the compound of the formula (1)  (raw material). In another embodiment, the amount of the solvent used in the reaction is, for example, 0.3 to 3 L (liters), preferably 0.4 to 2 L, more preferably 0.5 to 1.5 L, and further preferably 0.6 to 1.2 L, based on 1 mol of the compound of the formula (1) (raw material). When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

[0618] (Reaction Temperature in Step i) The reaction temperature in the step i is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the reaction temperature in the step i is, for example, -10°C (minus 10°C) to 100°C, preferably -5°C (minus 2024219674   12 Sep 2024 5°C) to 80°C, more preferably 0°C (zero °C) to 50°C, further preferably 0°C (zero °C) to 40°C, and further preferably 0°C (zero °C) to 30°C.

[0619] (Reaction Time in Step i) The reaction time in the step i is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the reaction time in the step i is, for example, 0.5 hours to 48 hours, preferably 1 hour to 24 hours, more preferably 1 hour to 12 hours, and further preferably 2 hours to 12 hours. However, the reaction time can be adjusted appropriately by a person skilled in the art.

[0620] (Working-up in Step i; Isolation and / or Purification) The compound of the formula (2), especially the compound (2-a), which is the product in the step i, can be used as a raw material in the step ii. The compound of the formula (2) obtained in the step i may be used in the next step after isolation and / or purification, or may be used in the next step without isolation. Whether or not to perform the working-up (isolation and / or purification) can be appropriately determined by a person skilled in the art according to the purpose and situation.

[0621] 2024219674   12 Sep 2024 In the step i, after the completion of the reaction, the gas, the volatile components and the low-boiling components may be removed by purging with an inert gas (e.g., nitrogen), bubbling and / or reducing pressure. For example, acidic components may be removed.

[0622] The compound of the formula (2), especially the compounds (2-a), which is the target product in the step i, may be isolated and purified from the reaction mixture, if possible, by a method known to a person skilled in the art (e.g., if possible, distillation, extraction, washing, crystallization including recrystallization, crystal washing and / or other procedures) and an improved method thereof, and any combination thereof.

[0623] If possible, the product dissolved or suspended in an organic solvent may be washed with water, hot water, an aqueous alkaline solution (e.g., a 5% or more saturated aqueous sodium hydrogen carbonate solution), or an acidic aqueous solution (e.g., 5 to 35% hydrochloric acid or 5 to 35% sulfuric acid). Such washing procedures may be combined.

[0624] When performing crystallization of the product including recrystallization and washing of crystals, the 2024219674   12 Sep 2024 description in the step iii described later may be referred to.

[0625] In any of the above procedures, the temperature can be appropriately adjusted by a person skilled in the art according to the purpose and situation.

[0626] In any procedure of the working-up and the procedure of using the product in the next step, the amount of a solvent can be appropriately adjusted by a person skilled in the art by addition and removal thereof. Furthermore, recovery and recycle of the solvent may be optionally performed. For example, the recovery and recycle of the solvent used in the reaction may be performed, and the recovery and recycle of the solvent used in the working-up (isolation and / or purification) may be performed.

[0627] Working-up (isolation and / or purification) can be performed by appropriately combining all or some of the procedures described above. Optionally, the above procedure may be repeated according to the purpose. In addition, a person skilled in the art can appropriately select a combination of any of the above procedures and their order. 2024219674   12 Sep 2024 (Step ii) The step ii will be described.

[0629] The step ii is a step of reacting a compound of the formula (2) with a compound of the formula (3) in the presence of a base to produce a compound of the formula (4):

[0630] [Chemical Formula 42]

[0631] wherein R1, R2, R3, R4, R5, X1 and X2 are as described herein.

[0632] The reaction in the step ii is a condensation reaction.

[0633] (Raw Material in Step ii; Compound of Formula (2)) A compound of the formula (2) is used as a raw material in the step ii. The compound of the formula (2) may be a known compound or may be produced from a known compound according to a known process. For example, the preparation 2024219674   12 Sep 2024 of the compounds of the formula (2) is described in WO 2004 / 013106 A1 (Patent Document 2), Examples 13 and 14, which are shown below.

[0634] [Chemical Formula 43] WO2004 / 013106A1, Example 13 SOpCI? F3C CH3 Al BN F3Cy / ~CI h NYT OCHF? *“ N-n^OCHF? ch3                   ch5 CMTP (2-a) Yield’ 83¾. Purity 30¾ (Isolated)

[0635] [Chemical Formula 44] WO2004 / 013106 AI Example 14 Cl? gas F3C CH3    NaHCO3 F3Cy y— Cl w    cc4.hy N‘N^0CHF2 ** NYr OCHF? ch3                   ch3 CMTP (2-a) Yield 62¾ (GC-Area^

[0636] However, it is preferred that the compound of the formula (2) is produced by the process of the present invention. That is, when X1 in the formula (2) is a halogen atom, the compound of the formula (2) is preferably 2024219674   12 Sep 2024 produced by the process comprising the step i described herein.

[0637] In the formula (2), R1, R2 and R3 are as defined above. In the formula (2), examples, preferred examples, more preferred examples, and particularly preferred examples of R1, R2 and R3 are the same as those described above.

[0638] X1 in the formula (2) is a leaving group. X1 in the formula (2) may be any atom or atomic group as long as it functions as a leaving group in the reaction in the step ii.

[0639] From the viewpoint of yield, availability, price, etc., preferred examples of X1 in the formula (2) include halogen atoms, (C1-C4)alkylsulfonyloxys, (C1-C4)haloalkylsulfonyloxys, (C1-C4)alkyls, or benzenesulfonyloxy optionally having a halogen atom, more preferably a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy and p-chlorobenzenesulfonyloxy, further preferably a chlorine atom and a bromine atom, and particularly preferably a chlorine atom.

[0640] 2024219674   12 Sep 2024 Specific examples and particularly preferred specific examples of the compound of the formula (2) are as described above.

[0641] (Raw Material in Step ii; Compound of Formula (3)) A compound of the formula (3) is used as a raw material in the step ii.

[0642] The compound of the formula (3) may be a known compound or may be produced from a known compound according to a known process. For example, the preparation of the compound of the formula (3) can be performed by the processes described in WO 2006 / 068092 A1 (Patent Document 6), JP 2013-512201 A (Patent Document 7) and WO 2019 / 131715 A1 (Patent Document 8), or by processes similar thereto. JP 2013-512201 A, paragraph 0004 (US 2012 / 264947 A1, paragraph 0007) (Patent Document 7) disclose a process for producing the raw material used in the process described in WO 2006 / 068092 A1 (Patent Document 6) by citing JP 2008001597 A and WO 2006 / 038657 A1. These are summarized in the following scheme.

[0643] [Chemical Formula 45] 2024219674   12 Sep 2024 WO2006 / 069392A1 Reference Example 2 WO2096 068392A1 Reference 2. 3 and 7 to 13 JP20C8 0C1597A and WO2006' 033657A1 Reference Example 1 and 2 WO 2906-968092Al Reference 1 and 4 to 6 HBr.'H^N rfCA. HB, (3 b) HCI was used instead of H3r in taxmple 14 and 17. It was estimated that the mixture of ITCA / HBr and ITCA / HCI was produced W02OO6-O6S092A1 Reference Exarrpe 1

[0644] In the formula (3), R4 and R5 are each independently a (C1-C6)alkyl optionally substituted with one or more substituents, a (C3-C6)cycloalkyl optionally substituted with one or more substituents, a (C2-C6)alkenyl optionally substituted with one or more substituents, a (C2-C6)alkynyl optionally substituted with one or more substituents, a (C1-C6)alkoxy optionally substituted with one or more substituents, or a (C6-C10)aryl optionally substituted with one or more substituents; or R4 and R5, together with the carbon atom to which they are attached, form a 4- to 12membered carbocyclic ring, wherein the formed ring is optionally substituted with one or more substituents.

[0645] 2024219674   12 Sep 2024 From the viewpoints of yield, availability, price, usefulness of the product, etc., preferred examples of R4 and R5 in the formula (1) each independently include (C1-C6)alkyls optionally substituted with one or more substituents, more preferably (C1-C6)alkyls, further preferably (C1-C4)alkyls, and particularly preferably methyl.

[0646] X2 in the formula (3) is an atom or an atomic group that forms an acid. Thus, HX2 is an acid.

[0647] From the viewpoint of yield, availability, price, usefulness of the product, etc., preferred examples of X1 in the formula (2) include: halogen atoms, a sulfate group, a hydrogen sulfate group, a phosphate group, a monohydrogen phosphate group, a dihydrogen phosphate group, (C1-C4)alkylsulfonyloxys, (C1-C4)haloalkylsulfonyloxys, benzenesulfonyloxys optionally having an (C1-C4)alkyl or a halogen atom, and mixtures of two or more (preferably two or three, more preferably two) thereof, more preferably a chlorine atom, a bromine atom, an iodine atom, a sulfate group, a hydrogen sulfate group, a phosphate group, a monohydrogen phosphate group, a dihydrogen phosphate group, methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy, 2024219674   12 Sep 2024 benzenesulfonyloxy, p-toluenesulfonyloxy, p-chlorobenzenesulfonyloxy and mixtures of two or more (preferably two or three, more preferably two) thereof, still more preferably a chlorine atom, a bromine atom, a sulfate group, a hydrogen sulfate group, a phosphate group, a monohydrogen phosphate group, methanesulfonyloxy, p-toluenesulfonyloxy, and mixtures of two or more (preferably two or three, more preferably two) thereof, and particularly preferably a chlorine atom, a bromine atom and a mixture thereof.

[0648] Particularly preferred specific examples of the compound of the formula (3) are the following compounds and O^CHj CH3 a mixture thereof.

[0649] [Chemical Formula 46] ,okzch3 N X              1 HN        CH3       HN HOHjN             HBr-H2N [TCA-HCI              ITCA-HBr (3-a)                        (3 b)

[0650] In addition, when “X2H” is a polyvalent acid such as sulfuric acid or phosphoric acid, it is within the scope of the present invention that the ratio between “X2 of the acid moiety” and “(4,5-dihydroisoxazolo-3- 2024219674   12 Sep 2024 yl)thiocarboxamidine moiety in the following formula (3-1)” can be a ratio corresponding to all possible valences of the polyvalent acid.

[0651] [Chemical Formula 47] ,OvZCH3 HN (3-0

[0652] In other words, for example, the compound of the following formula (3-c) is an equivalent of the compound of the formula (3).

[0653] [Chemical Formula 48]

[0654] In the reaction in the step ii, it was presumed that the isothiouronium group in the compound of the formula (3) produced the corresponding thiol group and / or a salt thereof (e.g., generally -S-Na+ or -S-K+) and / or an analog thereof. Compounds having thiol groups and / or salts thereof and / or analogs thereof corresponding to the 2024219674   12 Sep 2024 compounds of the formula (3) are equivalents of the compounds of the formula (3), and processes using the equivalents are within the scope of the present invention as defined by the appended claims.

[0655] (Raw material in Step ii: Amount of Compound of Formula (3) Used) The amount of the formula (3) used in the step ii may be any amount as long as the reaction proceeds. The amount of the formula (3) used in the step ii may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the amount of the compound of the formula (3) used in the step ii is, for example, 0.5 to 2.0 mol or more, preferably 0.8 to 1.5 mol, more preferably 1.0 to 1.5 mol, and still more preferably 1.0 to 1.1 mol, based on 1 mol of the compound of the formula (2) (raw material).

[0656] (Product in Step ii; Compound of Formula (4))

[0657] The product in the step ii is a compound of the formula (4) corresponding to the compound of the formula (2) and the compound of the formula (3) used as raw materials. 2024219674   12 Sep 2024 In the formula (4), R1, R2 and R3 are as defined in the formula (1). In the formula (4), R4 and R5 are as defined in the formula (3). In the formula (4), examples, preferred examples, more preferred examples, and particularly preferred examples of R1, R2, R3, R4 and R5 are the same as those in the formula (1) and the formula (3) described above, respectively.

[0659] Particularly preferred specific examples of the compound of the formula (4) are as follows:

[0660] [Chemical Formula 49]

[0661] (Base in Step ii) The reaction in the step ii is performed in the presence of a base. The base may be any base as long as the reaction proceeds. Examples of the base in the step ii include, but are not limited to, the following: 2024219674   12 Sep 2024 alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide and potassium hydroxide), alkaline earth metal hydroxides (e.g., magnesium hydroxide, calcium hydroxide and barium hydroxide), alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, potassium carbonate and cesium carbonate), alkaline earth metal carbonates (e.g., magnesium carbonate and calcium carbonate), alkali metal hydrogen carbonates (e.g., lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate), alkaline earth metal hydrogen carbonates (e.g., calcium hydrogen carbonate), phosphate salts (e.g., sodium phosphate, potassium phosphate and calcium phosphate), hydrogen phosphate salts (e.g., sodium hydrogen phosphate, potassium hydrogen phosphate and calcium hydrogen phosphate), amines (e.g., triethylamine, tributylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]-7-undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), pyridine and 4-(dimethylamino)-pyridine (DMAP)), ammonia, and a mixture thereof.

[0662] From the viewpoint of yield, suppression of by products, economic efficiency, etc., preferred examples of the base in the step ii include alkali metal hydroxides, alkali metal carbonates, alkali metal hydrogen carbonates, 2024219674   12 Sep 2024 and a mixture thereof, more preferably alkali metal hydroxides, alkali metal carbonates, and a mixture thereof, and still more preferably alkali metal hydroxides.

[0663] From the same viewpoint as above, preferred specific examples of the base in the step ii include lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and a mixture thereof, more preferably lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate and a mixture thereof, still more preferably sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and a mixture thereof, further preferably sodium hydroxide, potassium hydroxide and a mixture thereof, and particularly preferably sodium hydroxide.

[0664] The base in the step ii may be used singly or in a combination of two or more kinds thereof in any ratio. The base in the step ii may be in any form as long as the reaction proceeds. Examples of the form of the base in the step ii include a base-only solid and an aqueous solution with any concentration. Specific examples of the form of the base include, but are not limited to, flake, pellet, 2024219674   12 Sep 2024 bead, powder and 10 to 50% aqueous solution, and preferably 20 to 50% aqueous solution (e.g., 25% aqueous sodium hydroxide solution and 48% aqueous sodium hydroxide solution, preferably 48% aqueous sodium hydroxide solution). The form of the base in the step ii can be appropriately selected by a person skilled in the art.

[0665] The amount of the base used in the step ii may be any amount as long as the reaction proceeds. The amount of the base used in the step ii may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the amount of the base used in the step ii is, for example, 5 to 10 equivalents, preferably 5 to 8 equivalents, more preferably 5 to 7 equivalents, and still more preferably 5 to 6 equivalents, based on 1 equivalent of the compound of the formula (2) (raw material). In another embodiment, for example, the amount of the base used in the step ii is 1 to 15 equivalents, preferably 1 to 10 equivalents, more preferably 2 to 9 equivalents, still more preferably 4 to 8 equivalents, and further preferably 5 to 6 equivalents, based on 1 equivalent of the compound of the formula (2) (raw material). 2024219674   12 Sep 2024 (Reaction Solvent in Step ii) From the viewpoint of allowing the reaction to smoothly proceed, the reaction in the step ii is preferably performed in the presence of a solvent. The solvent in the reaction in the step ii may be any solvent as long as the reaction proceeds.

[0667] In one embodiment, examples of the solvent in the reaction in the step ii include, but are not limited to, the following: organic solvents having an acceptor number from 0 (zero) to 50 (preferably 3 to 45, more preferably 5 to 45, still more preferably 5 to 35, further preferably 5 to 30, further preferably 5 to 20, and further preferably 8 to 20), water, and any combination thereof in any ratio.

[0668] In another embodiment, examples of the solvent in the reaction in the step ii include, but are not limited to, the following: aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, trichlorobenzenes and nitrobenzene), halogenated aliphatic hydrocarbons (e.g., dichloromethane and 1,2-dichloroethane (EDC)), alcohols (e.g., methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol and tert-butanol (tertbutanol is also referred to as tert-butyl alcohol), 2024219674   12 Sep 2024 pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol and cyclohexanol), nitriles (e.g., acetonitrile and propionitrile), carboxylic acid esters (e.g., methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof and pentyl acetate and isomers thereof), ethers (e.g., tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl tert-butyl ether, 1,2-dimethoxyethane (DME) and diglyme), ketones (e.g., acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK) and methyl isobutyl ketone (MIBK)), amides (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC) and N-methylpyrrolidone (NMP)), ureas (e.g., N,N'- dimethylimidazolidinone (DMI) and tetramethylurea), sulfoxides (e.g., dimethyl sulfoxide (DMSO)), sulfones (e.g., sulfolane), water, and any combination thereof in any ratio. “2-Propanol” is also referred to as “isopropyl alcohol” or “isopropanol”.

[0669] However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., preferred examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from aromatic 2024219674   12 Sep 2024 hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, sulfoxides, and sulfones, with a water solvent in any ratio.

[0670] More preferred examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers, amides and sulfones with a water solvent in any ratio.

[0671] More preferred examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers and amides with a water solvent in any ratio.

[0672] More preferred examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters and amides with a water solvent in any ratio. 2024219674   12 Sep 2024 More preferred examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles and carboxylic acid esters with a water solvent in any ratio.

[0674] More preferred examples of the solvent in the reaction of the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from nitriles and carboxylic acid esters with a water solvent in any ratio.

[0675] In one embodiment, particularly preferred examples of the solvent in the reaction in the step ii include combinations of nitriles with a water solvent in any ratio.

[0676] In another embodiment, particularly preferred examples of the solvent in the reaction in the step ii include combinations of carboxylic acid esters with a water solvent in any ratio.

[0677] From the same viewpoint as described above, preferred specific examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one 2024219674   12 Sep 2024 toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent of “butyl acetate”), tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), N,N-dimethylformamide (DMF), N,N- dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N,N'- dimethylimidazolidinone (DMI), tetramethylurea, dimethyl sulfoxide (DMSO) and sulfolane with a water solvent in any ratio.

[0678] From the same viewpoint as described above, more preferred specific examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, 2024219674   12 Sep 2024 methanol, ethanol, propanol, 2-propanol, butanol, secbutanol, isobutanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent of “butyl acetate”), tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N,N'-dimethylimidazolidinone (DMI), tetramethylurea, dimethyl sulfoxide (DMSO) and sulfolane with a water solvent in any ratio.

[0679] From the same viewpoint as described above, still more preferred specific examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent 2024219674   12 Sep 2024 of “butyl acetate”), tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), N,N-dimethylformamide (DMF), N,N- dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N,N'- dimethylimidazolidinone (DMI), tetramethylurea, dimethyl sulfoxide (DMSO) and sulfolane with a water solvent in any ratio.

[0680] More preferred specific examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof with a water solvent in any ratio.

[0681] Still more preferred specific examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate with a water solvent in any ratio. 2024219674   12 Sep 2024

[0682] Further preferred specific examples of the solvent in the reaction in the step ii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from acetonitrile, ethyl acetate, isopropyl acetate and butyl acetate with a water solvent in any ratio.

[0683] Further preferred specific examples of the solvent in the reaction in the step ii include combinations of one or two (preferably one) organic solvents selected from acetonitrile and butyl acetate with a water solvent in any ratio.

[0684] In one embodiment, particularly preferred specific examples of the solvent in the reaction in the step ii include combinations of an acetonitrile solvent with a water solvent in any ratio.

[0685] In another embodiment, particularly preferred specific examples of the solvent in the reaction in the step ii include combinations of a butyl acetate solvent with a water solvent in any ratio. 2024219674   12 Sep 2024 In any case, the solvent may be in a single layer or may be separated into two layers as long as the reaction proceeds.

[0687] The amount of the solvent used in the reaction in the step ii will be described. The “total amount of the solvent used in the reaction” is the sum total of the amounts of all the organic solvents and the amount of the water solvent used in the reaction. The organic solvent and the water solvent used in the working-up (e.g., isolation and purification) after the reaction are not included. The “organic solvent” used in the reaction includes the organic solvent in the raw material solution and that in the reactant solution. The “water solvent” used in the reaction includes the water in the raw material solution and that in the reactant solution (e.g., the water in a 48% aqueous sodium hydroxide solution).

[0688] The total amount of the solvent used in the reaction in the step ii is not particularly limited as long as the reaction system can be sufficiently stirred. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the total amount of the solvent used in the reaction in the step ii is, for example, 0.1 to 10 L (liters), preferably 0.5 to 5 2024219674   12 Sep 2024 L, more preferably 1 to 5 L, still more preferably 1 to 3 L, and further preferably 1 to 2 L, based on 1 mol of the compound of the formula (2) (raw material). In another embodiment, the total amount of the solvent used in the reaction in the step ii is, for example, 1.5 to 3.0 L (liters), preferably 1.5 to 2.5 L, and more preferably 1.5 to 2.0 L, based on 1 mol of the compound of the formula (2) (raw material). In another embodiment, the total amount of the solvent used in the reaction in the step ii is, for example, 1.7 to 3.0 L (liters), preferably 1.7 to 2.5 L, and more preferably 1.7 to 2.0 L, based on 1 mol of the compound of the formula (2) (raw material).

[0689] From the same viewpoint as described above, in one embodiment, the amount of the organic solvent used in the reaction in the step ii is, for example, 0 (zero) to 5 L (liters), preferably 0.4 to 2.0 L, more preferably 0.5 to 1.5 L, still more preferably 0.6 to 1.0 L, and further preferably 0.7 to 0.9 L, based on 1 mol of the compound of the formula (2) (raw material). In another embodiment, the amount of the organic solvent used in the reaction in the step ii is, for example, 0.1 to 5 L (liters), preferably 0.3 to 2.0 L, more preferably 0.4 to 1.5 L, still more preferably 0.5 to 1.0 L, and further preferably 0.6 to 0.8 2024219674   12 Sep 2024 L, based on 1 mol of the compound of the formula (2) (raw material).

[0690] From the same viewpoint as described above, the amount of the water solvent used in the reaction in the step ii is, for example, 0.1 to 5 L (liters), preferably 0.5 to 2.0 L, more preferably 0.5 to 1.5 L, still more preferably 0.7 to 1.4 L, and further preferably 0.9 to 1.2 L, based on 1 mol of the compound of the formula (2) (raw material).

[0691] When a combination of two or more organic solvents is used, the ratio of the two or more organic solvents may be any ratio as long as the reaction proceeds.

[0692] When a combination of an organic solvent and a water solvent is used, the ratio of the organic solvent to the water solvent may be any ratio as long as the reaction proceeds. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the ratio of the organic solvent to the water solvent is, for example, 90 : 10 to 0 : 100 by volume ratio, preferably 90 : 10 to 10 : 90 by volume ratio, more preferably 70 : 30 to 30 : 70 by volume ratio, still more preferably 50 : 50 to 35 : 65 by volume ratio, and further preferably 50 : 50 to 40 : 60 by volume ratio. 2024219674   12 Sep 2024

[0693] In other words, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is, for example, 10 vol% to 100 vol%, preferably 10 vol% to 90 vol%, more preferably 30 vol% to 70 vol%, still more preferably 50 vol% to 65 vol%, and further preferably 50 vol% to 60 vol%, based on the amount of the whole solvent (100 vol%).

[0694] (Reaction Temperature in Step ii) The reaction temperature in the step ii is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the reaction temperature in the step ii is, for example, -10 (minus 10)°C to 100°C, preferably -10°C to 70°C, more preferably -10°C to 50°C, still more preferably 0 (zero) °C to 40°C, further preferably 0°C to 30°C, and further preferably 0°C to 25°C.

[0695] (Reaction Time in Step ii) The reaction time in the step ii is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the reaction time in the step ii is, for example, 4 hours to 48 hours, preferably 4 hours to 24 2024219674   12 Sep 2024 hours, more preferably 4 hours to 18 hours, and still more preferably 4 hours to 12 hours. In another embodiment, the reaction time in the step ii is, for example, 1 hour to 48 hours, preferably 1 hour to 24 hours, more preferably 3 hours to 18 hours, and still more preferably 3 hours to 12 hours. However, the reaction time can be adjusted appropriately by a person skilled in the art.

[0696] (Adding Method in Step ii) The order of adding the compound of the formula (2), the compound of the formula (3), the base, the solvent, etc. is not particularly limited. As long as the reaction proceeds, the addition order thereof may be any order. For example, the base may be added dropwise to a mixture comprising the compound of the formula (2), the compound of the formula (3) and the solvent in a reaction vessel. As another example, the compound of the formula (2) may be added dropwise to the reaction vessel after adding the compound of the formula (3), the base and the solvent. As still another example, the compound of the formula (2) and the compound of the formula (3) may be successively added dropwise to the reaction vessel after adding the base and the solvent.

[0697] (Working-up in Step ii; Isolation and / or Purification) 2024219674   12 Sep 2024 The compound of the formula (4), especially the compound (4-a), which is the product in the step ii, can be used as a raw material in the step iii. The compound of the formula (4) obtained in the step ii may be isolated and / or purified and then used in the next step, or may be used in the next step without being isolated. Whether or not to perform the working-up (isolation and / or purification) can be appropriately determined by a person skilled in the art according to the purpose and situation.

[0698] The compounds of the formula (4), especially the compound (4-a), which is the target product in the step ii, can be isolated and purified from the reaction mixture by methods known to a person skilled in the art (e.g., extraction, washing, crystallization including recrystallization, crystal washing and / or other procedures) and improved methods thereof, and any combination thereof.

[0699] In the working-up step (isolation and / or purification), the following procedures may be performed, but are not limited thereto: in the working-up, an extraction procedure and a washing procedure which include separation of an organic layer and an aqueous layer may be performed. When the mixture is separated into an organic layer and an aqueous layer, the mixture may be separated while being 2024219674   12 Sep 2024 hot. For example, when separating the organic layer from the aqueous layer, a hot mixture may be used, or the mixture may be heated. Impurities may be removed by a filtration procedure including hot filtration.

[0700] In the washing procedure, if possible, the product dissolved or suspended in an organic solvent may be washed with water, hot water, an aqueous alkaline solution (e.g., a 5% to saturated aqueous sodium hydrogen carbonate solution or a 1 to 10% aqueous sodium hydroxide solution), or an acidic aqueous solution (e.g., 5 to 35% hydrochloric acid or 5 to 35% sulfuric acid). Such washing procedures may be combined.

[0701] When performing crystallization of the product including recrystallization and washing of crystals, the description in the step iii described later may be referred to.

[0702] In any of the above procedures, the temperature can be appropriately adjusted by a person skilled in the art according to the purpose and situation.

[0703] In any procedure of the working-up and the procedure of using the product in the next step, the amount of a solvent 2024219674   12 Sep 2024 can be appropriately adjusted by a person skilled in the art by addition and removal thereof. Furthermore, recovery and recycle of the solvent may be optionally performed. For example, the recovery and recycle of the solvent used in the reaction may be performed, and the recovery and recycle of the solvent used in the working-up (isolation and / or purification) may be performed.

[0704] Working-up (isolation and / or purification) can be performed by appropriately combining all or some of the procedures described above. Optionally, the above procedure may be repeated according to the purpose. In addition, a person skilled in the art can appropriately select a combination of any of the above procedures and their order.

[0705] (Step iii) The step iii will be described.

[0706] The reaction in the step iii is a step of producing a compound of the formula (5) from a compound of the formula (4) by an oxidation reaction in the presence of a metal catalyst.

[0707] 2024219674   12 Sep 2024 Examples of the oxidation reaction in the step iii include a method using an oxidizing agent such as hydrogen peroxide, hypochlorite, peroxide, permanganate, manganese dioxide, or chromic acid, dimethyl sulfoxide oxidation such as Jones oxidation, ozone oxidation, or Swern oxidation, and Oxone oxidation. Performing the reaction in the step iii using a hypochlorite such as sodium hypochlorite or potassium hypochlorite, sodium peroxodisulfate, potassium peroxymonosulfate (Oxone (registered trademark)), or the like in place of hydrogen peroxide is an equivalent of the present invention and is within the scope of the present invention.

[0708] The step iii is preferably a step of reacting the compound of the formula (4) with hydrogen peroxide in the presence of a metal catalyst to produce the compound of the formula (5):

[0709] [Chemical Formula 50]

[0710] 2024219674   12 Sep 2024 wherein R1, R2, R3, R4 and R5 are as described herein.

[0711] (Raw Material in Step iii; Compound of Formula (4)) A compound of the formula (4) is used as a raw material in the step iii. The compound of the formula (4) may be a known compound or may be produced from a known compound according to a known process. As described above, for example, the preparation of the compound of the formula (4) is described in WO 2004 / 013106 A1 (Patent Document 2), Reference Examples 1-1, 1-2 and 1-3, WO 2005 / 105755 A1 (Patent Document 3), Examples 3 to 5 and WO 2005 / 095352 A1 (Patent Document 4), Examples 1 to 5. In addition, the preparation of the compound of the formula (4) can be performed by a similar method. However, it is preferred that the compound of the formula (4) is produced by the process of the present invention. That is, the compound of the formula (4) is preferably produced by the process comprising the step ii described herein.

[0712] In the formula (4), R1, R2 and R3 are as defined in the formula (1). In the formula (4), R4 and R5 are as defined in the formula (3). In the formula (4), examples, preferred examples, more preferred examples, and particularly preferred examples of R1, R2, R3, R4 and R5 are the same as those in the formula (1) and the formula (3) 2024219674   12 Sep 2024 described above, respectively. Particularly preferred specific examples of the compound of the formula (4) are as described above.

[0713] (Product in Step iii; Compound of Formula (5))

[0714] The product in the step iii is a compound of the formula (5) corresponding to the compound of the formula (4) used as a raw material.

[0715] In the formula (5), R1, R2 and R3 are as defined in the formula (1). In the formula (5), R4 and R5 are as defined in the formula (3). In the formula (5), examples, preferred examples, more preferred examples, and particularly preferred examples of R1, R2, R3, R4 and R5 are the same as those in the formula (1) and the formula (3) described above, respectively.

[0716] [Chemical Formula 51] 2024219674   12 Sep 2024 After the formula (4) is oxidized to afford the formula (6), oxidation to the formula (5) may be performed.

[0717] Particularly preferred specific examples of the compound of the formula (5) are as follows:

[0718] [Chemical Formula 52]

[0719] As described above, in the process of producing the compound of the formula (5) (SO2 derivative) from the compound of the formula (4) (S derivative), it is desired that the oxidation reaction sufficiently proceeds and the proportion of the compound of the formula (6) (SO derivative) in the product is sufficiently low. For example, in the reaction mixture after the reaction in the step iii, the ratio of the compound of the formula (6) (SO derivative) is preferably 10% or less, more preferably 5% or less, still more preferably 3% or less, further preferably 2% or less, and further preferably 1% or less. 2024219674   12 Sep 2024

[0720] (Oxidizing Agent in Step iii: Hydrogen Peroxide) In the reaction in the step iii, the hypochlorite, peroxide, permanganate, manganese dioxide, chromic acid, etc. described above can be used as an oxidizing agent. Preferably, hydrogen peroxide is used.

[0721] The form of the hydrogen peroxide in the step iii may be any form as long as the reaction proceeds. The form of the hydrogen peroxide in the step iii can be suitably selected by a person skilled in the art. However, in view of safety, danger, economic efficiency, etc., preferred examples of the form of the hydrogen peroxide include a 10 to 70 wt% aqueous hydrogen peroxide solution, more preferably a 25 to 65 wt% aqueous hydrogen peroxide solution, still more preferably a 30 to 65 wt% aqueous hydrogen peroxide solution, and particularly preferably a 30 to 60 wt% aqueous hydrogen peroxide solution. Specific examples of the form of the hydrogen peroxide include, but are not limited to, a 30 wt% aqueous hydrogen peroxide solution, a 35 wt% aqueous hydrogen peroxide solution, a 50 wt% aqueous hydrogen peroxide solution and a 60 wt% aqueous hydrogen peroxide solution.

[0722] 2024219674   12 Sep 2024 The amount of the hydrogen peroxide used in the step iii may be any amount as long as the reaction proceeds. The amount of the hydrogen peroxide used in the step iii may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by-products, economic efficiency, safety, risk, etc., the amount of the hydrogen peroxide used in the step iii is, for example, 2 mol or more, preferably 2 to 8 mol, more preferably 2 to 6 mol, still more preferably 2 to 5 mol, further preferably 2 to 4 mol, further preferably 2 to 3, and further preferably 2.3 to 3 mol, based on 1 mol of the compound of the formula (4) (raw material).

[0723] (Catalyst in Step iii: Metal Catalyst) The reaction in the step iii is performed in the presence of a metal catalyst. The metal catalyst may be any metal catalyst as long as the reaction proceeds. Examples of the metal catalyst in the step iii include, but are not limited to, the following: tungsten catalysts (e.g., tungstic acid, tungstic acid salts (e.g., sodium tungstates (including sodium tungstate dihydrate and sodium tungstate decahydrate), potassium tungstate, calcium tungstate and ammonium tungstate), metal tungsten, tungsten oxides (e.g., tungsten(VI) oxide; tungsten(VI) oxide is also called tungsten trioxide), 2024219674   12 Sep 2024 tungsten carbide, tungsten chlorides (e.g., tungsten(VI) chloride; tungsten(VI) chloride is also called tungsten hexachloride), tungsten bromides (e.g., tungsten(V) bromide), tungsten sulfides (e.g., tungsten(IV) sulfide; tungsten(IV) sulfide is also called tungsten disulfide), phosphotungstic acid and salts thereof (e.g., phosphotungstic acid, sodium phosphotungstate and ammonium phosphotungstate), silicotungstic acid and salts thereof (e.g., silicotungstic acid and sodium silicotungstate), and a mixture thereof), molybdenum catalysts (e.g., molybdic acid, molybdic acid salts, (e.g., sodium molybdate (including sodium molybdate dihydrate), potassium molybdate, ammonium molybdate (including ammonium molybdate tetrahydrate), metal molybdenum, molybdenum oxides (e.g., molybdenum(VI) oxide; molybdenum(VI) oxide is also called molybdenum trioxide), molybdate chlorides (molybdenum(V) chloride; molybdenum(V) chloride is also called molybdenum pentachloride), molybdenum sulfides (e.g., molybdenum(IV) sulfide; molybdenum(IV) sulfide is also called molybdenum disulfide), phosphomolybdic acid and salts thereof (e.g., phosphomolybdic acid, sodium phosphomolybdate and ammonium phosphomolybdate), silicomolybdic acid and salts thereof (e.g., silicomolybdic acid and sodium silicomolybdate), 2024219674   12 Sep 2024 bis(2,4-pentandionato)molybdenum(VI) dioxide, and a mixture thereof), iron catalysts (e.g., iron(I) acetylacetoneate, iron(I) chloride and iron(I) nitrate, and a mixture thereof), manganese catalysts (e.g., potassium permanganate, manganese(II) oxide and manganese(II) chloride, and a mixture thereof), vanadium catalysts (e.g., vanadyl acetylacetonate, vanadium(V) oxide, vanadium(V) oxytrichloride, vanadium(V) oxytriethoxyde and vanadium(V) oxytriisopropoxide, and a mixture thereof), niobium catalysts (e.g., niobium carbide, niobium(V) chloride and niobium(V) pentaethoxyde, and a mixture thereof), tantalum catalysts (e.g., tantalum carbide (TaC), tantalum(V) chloride (TaCl5) and tantalum(V) pentaethoxyde (Ta(OEt)5), and a mixture thereof), titanium catalysts (e.g., titanium tetrachloride, titanium trichloride and titanium(IV) tetraisopropoxide, and a mixture thereof), zirconium catalysts (e.g., zirconium dioxide, zirconium(I) chloride, zirconium(IV) chloride, zirconium chloride oxide, and a mixture thereof), 2024219674   12 Sep 2024 copper catalysts (e.g., copper(I) acetate, copper(II) acetate, copper(I) bromide and copper(I) iodide, and a mixture thereof), thallium catalysts (e.g., thallium(I) nitrate, thallium(I) acetate and thallium (I) trifluoroacetate, and a mixture thereof).

[0724] Herein, an acid that can be in the form of a hydrate and a salt thereof may be in the form of a hydrate thereof, and any form is within the scope of the present invention. Thus, for example, “sodium tungstate” encompasses “sodium tungstate dihydrate” and “sodium tungstate decahydrate”. Herein, an acid that can be in the form of a polyacid and a salt thereof (e.g., tungstic acid and salts thereof) may be in the form of a polyacid, and any form is within the scope of the present invention. “Bis(2,4-pentanedionato)molybdenum(VI) dioxide” is also referred to as “MoO2(acac)2”, “molybdenum(VI) dioxyacetylacetonate”, or “bis(acetylacetonato)molybdenum(IV) oxide”. “Iron(I) acetylacetonate” is also referred to as “Fe(acac)3” or “tris(2,4-pentanedionato)iron(I)”. “Vanadyl acetylacetonate” is also referred to as “VO(acac)2”, “bis(2,4-pentanedionato)vanadium(IV) oxide”, 2024219674   12 Sep 2024 “vanadium(IV) oxyacetylacetonate”, or “vanadium(IV) bis(acetylacetonate)oxide”. “Vanadium(V) oxytrichloride” is also referred to as “VOCl3”, “vanadium(V) trichloride oxide”, or “vanadyl trichloride”. “Vanadium(V) oxytriethoxide” is also referred to as “VO(OEt)3”, “vanadium(V) triethoxide”, or “triethoxyvanadium(V) oxide”. “Vanadium(V) oxytriisopropoxide” is also referred to as (VO(OPr-i)3", “vanadium(V) triisopropoxide oxide" or ”triisopropoxyvanadium(V) oxide". Titanium(IV) tetraisopropoxide is also referred to as titanium(IV) isopropoxide or tetraisopropoxytitanium(IV)).

[0725] The metal of the metal catalyst in the step iii is preferably a transition metal. Specific examples thereof 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).

[0726] 2024219674   12 Sep 2024 The transition metal of the metal catalyst in the step iii is preferably a metal of Group 4, 5, or 6 of the periodic table.

[0727] The transition metal of the metal catalyst in the step iii is preferably Group 5 or Group 6.

[0728] The transition metal of the metal catalyst in the step iii is preferably Group 5 or Group 6 rather than Group 7, Group 8 and Group 9.

[0729] Preferred examples of the metal catalyst in the step iii are tungsten catalysts, molybdenum catalysts, niobium catalysts, tantalum catalysts, titanium catalysts and zirconium catalysts.

[0730] Preferred examples of the metal catalyst in the step iii are tungsten catalysts, molybdenum catalysts, niobium catalysts and tantalum catalysts.

[0731] Preferred examples of the metal catalyst in the step iii are tungsten catalysts, molybdenum catalysts and niobium catalysts. 2024219674   12 Sep 2024 Preferred examples of the metal catalyst in the step iii are tungsten catalysts and molybdenum catalysts.

[0733] Preferred examples of the metal catalyst in the step iii are tungsten catalysts.

[0734] Preferred examples of the metal catalyst in the step iii are molybdenum catalysts.

[0735] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., preferred examples of the tungsten catalyst in the step iii include tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride, tungsten sulfide, phosphotungstic acid, silicotungstic acid and salts thereof, and a mixture thereof, more preferably tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, still more preferably tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, and a mixture thereof, further preferably tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, 2024219674   12 Sep 2024 metal tungsten, tungsten(VI) oxide, tungsten carbide, and a mixture thereof, further preferably tungstic acid, sodium tungstate, metal tungsten, tungsten carbide, and a mixture thereof, further preferably tungstic acid and sodium tungstate, and particularly preferably sodium tungstate.

[0736] The metal catalyst (especially, a tungsten catalyst) in the step iii may be used singly or in a combination of two or more kinds thereof in any ratio. The form of the metal catalyst (especially, a tungsten catalyst) in the step iii may be any form as long as the reaction proceeds. The form thereof can be appropriately selected by a person skilled in the art. The amount of the metal catalyst (especially, a tungsten catalyst) used may be any amount as long as the reaction proceeds. The use amount may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the use amount thereof is, for example, 0.001 to 0.1 mol, preferably 0.01 to 0.1 mol, more preferably 0.01 to 0.05 mol, and still more preferably 0.03 to 0.05 mol, based on 1 mol of the compound of the formula (4) (raw material). 2024219674   12 Sep 2024 From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., preferred examples of the molybdenum catalyst in the step iii include molybdic acid, molybdic acid salts, metal molybdenum, molybdenum oxide, molybdenum carbide, molybdenum chloride, molybdenum sulfide, molybdenum bromide, phosphomolybdic acid, silicomolybdic acid and salts thereof, and a mixture thereof, more preferably molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, still more preferably molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and a mixture thereof, further preferably molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum(V) chloride, and a mixture thereof, further preferably sodium molybdate, potassium molybdate and ammonium molybdate, and particularly preferably ammonium molybdate. 2024219674   12 Sep 2024 From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., preferred examples of the niobium catalyst in the step iii include niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, niobium nitride, niobium silicide, niobium boride, and a mixture thereof, more preferably niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, etc., and a mixture thereof, still more preferably sodium niobate, potassium niobate, niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and a mixture thereof, further preferably sodium niobate and potassium niobate, and particularly preferably sodium niobate.

[0739] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., preferred examples of the tantalum catalyst in the step iii include tantalic acid, tantalic acid salts, tantalum oxide, tantalum carbide, tantalum chloride, tantalum nitride, tantalum silicide, tantalum boride, and a mixture thereof, more preferably tantalic acid, tantalic acid salts, tantalum oxide, tantalum carbide, tantalum chloride, and a 2024219674   12 Sep 2024 more preferably lithium tantalate, potassium tantalate, tantalum pentoxide, tantalum carbide, tantalum(V) chloride, tantalum(V) pentaethoxide, etc., and a mixture thereof, still more preferably lithium tantalate and potassium tantalate, and particularly preferably lithium tantalate.

[0740] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., preferred examples of the titanium catalyst in the step iii are titanic acid, titanic acid salts, titanium oxide, titanium carbide, titanium chloride, titanium nitride, and a mixture thereof, more preferably titanic acid, titanic acid salts, titanium oxide, titanium carbide, titanium chloride, and a mixture thereof, still more preferably titanium acetylacetonate, titanium tetrachloride, titanium trichloride, titanium(IV) tetraisopropoxide, etc., and a mixture thereof, and particularly preferably titanium acetylacetonate.

[0741] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the zirconium catalyst in the step iii include zirconic acid, zirconic acid salts, zirconium oxide, zirconium carbide, zirconium chloride, and a mixture thereof, 2024219674   12 Sep 2024 still more preferably zirconium dioxide, zirconium(I) chloride, zirconium(IV) chloride, zirconium chloride oxide, etc., and a mixture thereof, and particularly preferably zirconium chloride oxide.

[0742] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, tungstic acid salts, metal tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, etc., and a mixture thereof, tantalic acid, tantalic acid salts, tantalum oxide, tantalum carbide, tantalum chloride, and a mixture thereof, titanic acid, titanic acid salts, titanium oxide, titanium carbide, titanium chloride, and a mixture thereof, zirconic acid, zirconic acid salts, zirconium oxide, zirconium carbide, zirconium chloride, and a mixture thereof. 2024219674   12 Sep 2024 From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, tungstic acid salts, metal tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, etc., and a mixture thereof, tantalic acid, tantalic acid salts, tantalum oxide, tantalum carbide, tantalum chloride, and a mixture thereof.

[0744] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, tungstic acid salts, metal tungsten, tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof, 2024219674   12 Sep 2024 niobic acid, niobic acid salts, metal niobium, niobium carbide, niobium oxide, niobium chloride, etc., and a mixture thereof.

[0745] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, tungstic acid salts, metal tungsten oxide, tungsten carbide, tungsten chloride and salts thereof, and a mixture thereof, molybdic acid, molybdic acid salts, metal molybdenum, molybdenum carbide, molybdenum oxide, molybdenum chloride, and a mixture thereof.

[0746] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten(VI) oxide, tungsten carbide, and a mixture thereof, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium 2024219674   12 Sep 2024 phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and a mixture thereof, sodium niobate, potassium niobate, niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and a mixture thereof, lithium tantalate, potassium tantalate, tantalum pentoxide, tantalum carbide, tantalum(V) chloride, tantalum(V) pentaethoxide, etc., and a mixture thereof, titanium acetylacetonate, titanium tetrachloride, titanium trichloride, titanium(IV) tetraisopropoxide, etc., and a mixture thereof, zirconium dioxide, zirconium(I) chloride, zirconium(IV) chloride, zirconium chloride oxide, etc., and a mixture thereof.

[0747] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten(VI) oxide, tungsten carbide, and a mixture thereof, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, 2024219674   12 Sep 2024 phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and a mixture thereof, sodium niobate, potassium niobate, niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and a mixture thereof, lithium tantalate, potassium tantalate, tantalum pentoxide, tantalum carbide, tantalum(V) chloride, tantalum(V) pentaethoxide, etc., and a mixture thereof.

[0748] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten(VI) oxide, tungsten carbide, and a mixture thereof, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and a mixture thereof, 2024219674   12 Sep 2024 sodium niobate, potassium niobate, niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and a mixture thereof.

[0749] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten(VI) oxide, tungsten carbide, and a mixture thereof, molybdic acid, sodium molybdate, potassium molybdate, ammonium molybdate, molybdenum(VI) oxide, molybdenum carbide, molybdenum(V) chloride, molybdenum(IV) sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, sodium silicomolybdate, and a mixture thereof.

[0750] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, sodium molybdate, potassium molybdate, ammonium molybdate, 2024219674   12 Sep 2024 sodium niobate, potassium niobate, lithium tantalate and potassium tantalate.

[0751] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, sodium molybdate, potassium molybdate, ammonium molybdate, sodium niobate and potassium niobate.

[0752] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, potassium tungstate, calcium tungstate, ammonium tungstate, metal tungsten, tungsten oxide, tungsten carbide, sodium molybdate, potassium molybdate and ammonium molybdate.

[0753] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, 2024219674   12 Sep 2024 sodium molybdate, potassium molybdate, ammonium molybdate, sodium niobate, potassium niobate, lithium tantalate and potassium tantalate.

[0754] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, sodium molybdate, potassium molybdate, ammonium molybdate, sodium niobate and potassium niobate.

[0755] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., more preferred examples of the metal catalyst in the step iii include tungstic acid, sodium tungstate, sodium molybdate, potassium molybdate and ammonium molybdate.

[0756] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., particularly preferred examples of the metal catalyst in the step iii include sodium tungstate, ammonium molybdate and sodium niobate.

[0757] From the viewpoint of yield, suppression of byproducts, economic efficiency, etc., sodium tungstate and 2024219674   12 Sep 2024 ammonium molybdate are particularly preferred as the metal catalyst in the step iii.

[0758] (Acid Catalyst in Step iii)

[0759] The reaction in the step iii may be performed in the presence of an acid catalyst. The acid catalyst may not be used. Whether or not to use an acid catalyst can be appropriately determined by a person skilled in the art. Examples of the acid catalyst in the step iii include, but are not limited to, the following: hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, methyl phosphate, ethyl phosphate or phenyl phosphate, preferably sulfuric acid, phosphoric acid or phenyl phosphate, more preferably sulfuric acid or phenyl phosphate, and still more preferably phenyl phosphate.

[0760] The acid catalyst in the step iii may be used singly or in a combination of two or more kinds thereof in any ratio. The form of the acid catalyst in the step iii may be any form as long as the reaction proceeds. The form of the acid catalyst can be appropriately selected by a person skilled in the art. The amount of the acid catalyst used 2024219674   12 Sep 2024 in the step iii may be any amount as long as the reaction proceeds. The amount of the acid catalyst used may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by products, economic efficiency, etc., in one embodiment, the amount of the acid catalyst used is, for example, 0 (zero) to 0.1 mol, and preferably 0 (zero) to 0.05 mol, based on 1 mol of the compound of the formula (4) (raw material). In another embodiment, the amount of the acid catalyst used is, for example, 0.001 to 0.1 mol, preferably 0.005 to 0.1 mol, more preferably 0.005 to 0.05 mol, and still more preferably 0.01 to 0.05 mol, based on 1 mol of the compound of the formula (4) (raw material).

[0761] (Phase Transfer Catalyst in Step iii)

[0762] The reaction in the step iii may be performed in the presence of a phase transfer catalyst. The phase transfer catalyst may not be used. Whether or not to use a phase transfer catalyst can be appropriately determined by a person skilled in the art. Examples of the phase transfer catalyst in the step iii include, but are not limited to, the following: quaternary ammonium salts (e.g., tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogen 2024219674   12 Sep 2024 sulfate, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, octyltrimethylammonium chloride, octyltrimethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, benzyllauryldimethylammonium chloride (benzyldodecyldimethylammonium chloride), benzyllauryldimethylammonium bromide (benzyldodecyldimethylammonium bromide), myristyltrimethylammonium chloride (tetradecyltrimethylammonium chloride), myristyltrimethylammonium bromide (tetradecyltrimethylammonium bromide), benzyldimethylstearylammonium chloride (benzyloctadecyldimethylammonium chloride), benzyldimethylstearylammonium bromide (benzyloctadecyldimethylammonium bromide), etc.), quaternary phosphonium salts (tetrabutylphosphonium bromide, tetraoctylphosphonium bromide, tetraphenylphosphonium bromide, etc.) and crown ethers (e.g., 12-crown-4, 15-crown-5 and 18-crown-6). From the viewpoint of yield, suppression of by-products, economic efficiency, etc., preferred examples of the phase transfer catalyst in the step iii include tetrabutylammonium chloride, tetrabutylammonium bromide and tetrabutylammonium hydrogen sulfate, and more preferably tetrabutylammonium 2024219674   12 Sep 2024 hydrogen sulfate. Tetrabutylammonium hydrogen sulfate may be abbreviated as TBAHS.

[0763] The phase transfer catalyst in the step iii may be used singly or in a combination of two or more kinds thereof in any ratio. The form of the phase transfer catalyst in the step iii may be any form as long as the reaction proceeds. The form of the phase transfer catalyst can be appropriately selected by a person skilled in the art. The amount of the phase transfer catalyst used in the step iii may be any amount as long as the reaction proceeds. The amount of the phase transfer catalyst used may be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, suppression of by products, economic efficiency, etc., in one embodiment, the amount of the phase transfer catalyst used is, for example, 0 (zero) to 0.1 mol, and preferably 0 (zero) to 0.05 mol, based on 1 mol of the compound of the formula (4) (raw material). In another embodiment, the amount of the phase transfer catalyst used is, for example, 0.001 to 0.1 mol, preferably 0.005 to 0.05 mol, and more preferably 0.01 to 0.05 mol, based on 1 mol of the compound of the formula (4) (raw material).

[0764] 2024219674   12 Sep 2024 For example, when water and an alcohol-based solvent such as butanol are used as the solvent in the step iii, the reaction is preferably performed in the presence of an acid catalyst and a phase transfer catalyst. However, in a mixed solvent of water and a certain organic solvent, the reaction sufficiently proceeds in the absence of an acid catalyst and a phase transfer catalyst.

[0765] (Reaction Solvent in Step iii) From the viewpoint of allowing the reaction to smoothly proceed, the reaction in the step iii is preferably performed in the presence of a solvent. The solvent in the reaction in the step iii may be any solvent as long as the reaction proceeds.

[0766] In one embodiment, examples of the solvent in the reaction in the step iii include, but are not limited to, the following: organic solvents having an acceptor number from 0 (zero) to 50 (preferably 3 to 45, more preferably 5 to 45, still more preferably 5 to 35, further preferably 5 to 30, further preferably 5 to 20, and further preferably 8 to 20), water, and any combination thereof in any ratio.

[0767] In another aspect, examples of the solvent in the reaction in the step iii include, but are not limited to, 2024219674   12 Sep 2024 the following: aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, trichlorobenzenes and nitrobenzene), halogenated aliphatic hydrocarbons (e.g., dichloromethane and 1,2-dichloroethane (EDC)), alcohols (e.g., methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol and tert-butanol (tert-butanol is also referred to as tert-butyl alcohol), pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, hexanol and cyclohexanol), nitriles (e.g., acetonitrile and propionitrile), carboxylic acid esters (e.g., methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof and pentyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent of “butyl acetate” and the “isomer of pentyl acetate” is an equivalent of “pentyl acetate”)), ethers (e.g., tetrahydrofuran (THF), 1,4- dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl tert-butyl ether, 1,2-dimethoxyethane (DME) and diglyme), ketones (e.g., acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK) and methyl isobutyl ketone (MIBK)), amides (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC) and N-methylpyrrolidone (NMP)), ureas (e.g., N,N'- dimethylimidazolidinone (DMI) and tetramethylurea), 2024219674   12 Sep 2024 sulfoxides (e.g., dimethyl sulfoxide (DMSO)), sulfones (e.g., sulfolane), water, and any combination thereof in any ratio. “2-Propanol” is also referred to as “isopropyl alcohol” or “isopropanol”.

[0768] However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., preferred examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, alcohols, nitriles, carboxylic acid esters, ethers, ketones, amides, ureas, sulfoxides and sulfones with a water solvent in any ratio.

[0769] More preferred examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers, amides and sulfones with a water solvent in any ratio.

[0770] More preferred examples of the solvent in the reaction in the step iii include combinations of one or more 2024219674   12 Sep 2024 (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters, ethers and amides with a water solvent in any ratio.

[0771] More preferred examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles, carboxylic acid esters and amides with a water solvent in any ratio.

[0772] More preferred examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from alcohols, nitriles and carboxylic acid esters with a water solvent in any ratio.

[0773] Still more preferred examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from nitriles and carboxylic acid esters with a water solvent in any ratio. 2024219674   12 Sep 2024 In one embodiment, particularly preferred examples of the solvent in the reaction in the step iii include combinations of nitriles with a water solvent in any ratio.

[0775] In another embodiment, particularly preferred examples of the solvent in the reaction in the step iii include combinations of carboxylic acid esters with a water solvent in any ratio.

[0776] From the same viewpoint as described above, preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-amyl alcohol, 3-pentanol, 2-methyl-1-butanol, isoamyl alcohol, tert-amyl alcohol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent of “butyl acetate”), tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, acetone, methyl ethyl 2024219674   12 Sep 2024 ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), N,N-dimethylformamide (DMF), N,N- dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N,N'- dimethylimidazolidinone (DMI), tetramethylurea, dimethyl sulfoxide (DMSO) and sulfolane with a water solvent in any ratio.

[0777] From the same viewpoint as described above, more preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, methanol, ethanol, propanol, 2-propanol, butanol, secbutanol, isobutanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent of “butyl acetate”), tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N,N'-dimethylimidazolidinone 2024219674   12 Sep 2024 (DMI), tetramethylurea, dimethyl sulfoxide (DMSO) and sulfolane with a water solvent in any ratio.

[0778] From the same viewpoint as described above, still more preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from toluene, xylenes, chlorobenzene, dichlorobenzenes, dichloromethane, 1,2-dichloroethane, methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof (in the present invention, the “isomer of butyl acetate” is an equivalent of “butyl acetate”), tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), N,N-dimethylformamide (DMF), N,N- dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N,N'- dimethylimidazolidinone (DMI), tetramethylurea, dimethyl sulfoxide (DMSO) and sulfolane with a water solvent in any ratio. 2024219674   12 Sep 2024 More preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, 1,4-dioxane, diglyme, N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), sulfolane and isomers thereof with a water solvent in any ratio.

[0780] More preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP) and isomers thereof with a water solvent in any ratio.

[0781] More preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from methanol, ethanol, 2-propanol, butanol, tert-butanol, acetonitrile, ethyl acetate, propyl 2024219674   12 Sep 2024 acetate, isopropyl acetate, butyl acetate and isomers thereof with a water solvent in any ratio.

[0782] Still more preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from butanol, acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate and butyl acetate with a water solvent in any ratio.

[0783] Still more preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from ethanol, 2-propanol, butanol, tert-butanol and acetonitrile with a water solvent in any ratio.

[0784] Further preferred specific examples of the solvent in the reaction in the step iii include combinations of one or more (preferably one or two, more preferably one) organic solvents selected from acetonitrile, ethyl acetate, isopropyl acetate and butyl acetate with a water solvent in any ratio.

[0785] 2024219674   12 Sep 2024 Further preferred specific examples of the solvent in the reaction in the step iii include combinations of one or two (preferably one) organic solvents selected from acetonitrile and butyl acetate with a water solvent in any ratio.

[0786] In one embodiment, particularly preferred specific examples of the solvent in the reaction in the step iii include combinations of an acetonitrile solvent with a water solvent in any ratio.

[0787] In another embodiment, particularly preferred specific examples of the solvent in the reaction in the step iii include combinations of a butyl acetate with a water solvent in any ratio.

[0788] In any case, the solvent may be in a single layer or may be separated into two layers as long as the reaction proceeds.

[0789] The amount of the solvent used in the reaction in the step iii will be described. The “total amount of the solvent used in the reaction” is the sum total of the amounts of all the organic solvents and the amount of the water solvent used in the reaction. The organic solvent 2024219674   12 Sep 2024 and the water solvent used in the working-up (e.g., isolation and purification) after the reaction are not included. The “organic solvent” used in the reaction includes the organic solvent in the raw material solution and that in the reactant solution. The “water solvent” used in the reaction includes the water in the raw material solution and that in the reactant solution (e.g., water in an aqueous hydrogen peroxide solution).

[0790] The total amount of solvent used in the reaction in the step iii is not particularly limited as long as the reaction system can be sufficiently stirred. However, from the viewpoints of yield, suppression of by-products, economic efficiency, etc., the total amount of the solvent used in the reaction in the step iii is, for example, 0.1 to 10 L (liters) 0.3 to 5 L, preferably 0.3 to 3 L, more preferably 0.5 to 3 L, still more preferably 0.5 to 2 L, and further preferably 0.7 to 1.8 L, based on 1 mol of the compound of the formula (4) (raw material).

[0791] From the same viewpoint as described above, in one embodiment, the amount of the organic solvent used in the reaction in the step iii is, for example, 0.1 to 10 L (liters), preferably 0.2 to 5 L, more preferably 0.3 to 2 2024219674   12 Sep 2024 L, and still more preferably 0.3 to 1 L, based on 1 mol of the compound of the formula (4) (raw material).

[0792] In another embodiment, the amount of the organic solvent used in the reaction in the step iii is, for example, 0.4 to 5 L, preferably 0.4 to 2 L, more preferably 0.4 to 1.5 L, and still more preferably 0.4 to 1.3 L, based on 1 mol of the compound of the formula (4) (raw material). In another embodiment, the amount of the organic solvent used in the reaction in the step iii is, for example, 0.5 to 5L (liters), preferably 0.5 to 2 L, more preferably 0.5 to 1.5 L, and still more preferably 0.5 to 1.3 L, based on 1 mol of the compound of the formula (4) (raw material).

[0793] From the same viewpoint as described above, in one embodiment, the amount of the water solvent used in the reaction in the step iii is, for example, 0.01 to 2 L (liters), preferably 0.05 to 1 L, more preferably 0.1 to 1 L, and still more preferably 0.2 to 1 L, based on 1 mol of the compound of the formula (4) (raw material).

[0794] In another embodiment, the amount of the water solvent used in the reaction in the step iii is, for example, 0.05 to 0.8 L (liters), preferably 0.1 to 0.8 L, more preferably 2024219674   12 Sep 2024 on 1 mol of the compound of the formula (4) (raw material). In another embodiment, the amount of the water solvent used in the reaction in the step iii is, for example, 0.05 to 0.5 L (liters), preferably 0.1 to 0.5 L, more preferably 0.2 to 0.5 L, and still more preferably 0.3 to 0.5 L, based on 1 mol of the compound of the formula (4) (raw material). In another embodiment, the amount of the water solvent used in the reaction in the step iii is, for example, 0.1 to 0.3 L (liters), and preferably 0.2 to 0.3 L, based on 1 mol of the compound of the formula (4) (raw material).

[0795] When a combination of two or more organic solvents is used, the ratio of the two or more organic solvents may be any ratio as long as the reaction proceeds.

[0796] When a combination of an organic solvent and a water solvent is used, the ratio of the organic solvent to the water solvent may be any ratio as long as the reaction proceeds. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the ratio of the organic solvent to the water solvent is, for example, 90 : 10 to 10 : 90 by volume ratio, preferably 90 : 10 to 50 : 50 by volume ratio, more preferably 85 : 15 to 55 : 45 by volume ratio, still more preferably 80 : 20 2024219674   12 Sep 2024 to 60 : 40 by volume ratio, and further preferably 75 : 25 to 60 : 40 by volume ratio.

[0797] In other words, the amount of the water solvent in the whole solvent composed of the organic solvent and the water solvent is, for example, 10 vol% to 90 vol%, preferably 10 vol% to 50 vol%, more preferably 15 vol% to 45 vol%, still more preferably 20 vol% to 40 vol%, and further preferably 25 vol% to 40 vol%, based on the amount of the whole solvent (100 vol%).

[0798] (Pre-added Water in Step iii) The “pre-added water” means water previously added as a solvent in the reaction system before the aqueous hydrogen peroxide solution is added.  From the viewpoint of safety, smooth start of reaction, stable reaction, etc., and from the viewpoint described later, in one embodiment, the amount of the pre-added water used is, for example, 0 (zero) to 1 L (liter), preferably 0.01 to 1 L, more preferably 0.05 to 1 L, still more preferably 0.08 to 1 L, and further preferably 0.1 to 1 L, based on 1 mol of the compound of the formula (4). In another embodiment, the amount of the pre-added water used is, for example, 0 (zero) to 0.5 L (liters), preferably 0.01 to 0.5 L, more 2024219674   12 Sep 2024 L, and further preferably 0.1 to 0.5 L, based on 1 mol of the compound of the formula (4). In another embodiment, the amount of the pre-added water used is, for example, 0 (zero) to 0.4 L (liters), preferably 0.01 to 0.4 L, more preferably 0.05 to 0.4 L, still more preferably 0.08 to 0.2 L, and further preferably 0.1 to 0.2 L, based on 1 mol of the compound of the formula (4). In another embodiment, the amount of the pre-added water used is, for example, 0 (zero) to 0.3 L (liters), preferably 0.01 to 0.3 L, more preferably 0.05 to 0.3 L, still more preferably 0.08 to 0.3 L, and further preferably 0.1 to 0.3 L, based on 1 mol of the compound of the formula (4).

[0799] (Reaction Temperature in Step iii) The reaction temperature in the step iii is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the reaction temperature in the step iii is, for example, 0 (zero) °C to 100°C, preferably 20°C to 100°C, more preferably 50°C to 90°C, preferably 60°C to 90°C, still more preferably 70°C to 90°C, further preferably 75°C to 90°C, and further preferably 75°C to 80°C. From the same viewpoint, in another embodiment, the reaction temperature in the step iii is, for example, 50°C 2024219674   12 Sep 2024 to 150°C, 50°C to 120°C, or 50°C to 100°C, and preferably 60°C to 150°C,  60°C to 120°C, or 60°C to 100°C.

[0800] (Reaction Time in Step iii) The reaction time in the step iii is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., the reaction time in the step iii is, for example, 1 hour to 48 hours, preferably 3 hours to 48 hours, more preferably 3 hours to 24 hours, still more preferably 4 hours to 24 hours, further preferably 4 hours to 12 hours, and further preferably 4 hours to 8 hours. However, the reaction time can be adjusted appropriately by a person skilled in the art.

[0801] (Adding Method in Step iii) The order of adding the raw materials, the oxidizing agent, the catalyst, the solvent, etc. is not particularly limited. As long as the reaction proceeds, the addition order thereof may be any order. However, it has been found that when water as a solvent and a catalyst are added in advance into the reaction system before an aqueous hydrogen peroxide solution is added, the reaction can be smoothly started and the initial stage of the reaction is stabilized. This means that a safer and industrially 2024219674   12 Sep 2024 preferable process has been found. Therefore, it is preferable to add water as a solvent into the reaction system before adding an aqueous hydrogen peroxide solution. That is, it is preferable to use the above-described “preadded water”.

[0802] (Working-up in Step iii; Isolation and Purification) The compounds of the formula (5), especially pyroxasulfone (5-a), which is the target product in the step iii, can be isolated and purified from the reaction mixture by methods known to a person skilled in the art (e.g., extraction, washing, crystallization including recrystallization, crystal washing and / or other procedures) and improved methods thereof, and any combination thereof.

[0803] In the step iii, as shown in Examples, it is preferable to decompose an unreacted peroxide such as hydrogen peroxide by treating the reaction mixture with a reducing agent (e.g., an aqueous sodium sulfite solution) after the reaction.

[0804] In the working-up step (isolation and / or purification), the following procedures may be performed, but are not limited thereto: in the working-up, an extraction procedure and / or a washing procedure including separation of an 2024219674   12 Sep 2024 organic layer and an aqueous layer may be performed. When the mixture is separated into an organic layer and an aqueous layer, the mixture may be separated while being hot. For example, when separating the organic layer from the aqueous layer, a hot mixture may be used, or the mixture may be heated. Impurities may be removed by a filtration procedure including hot filtration.

[0805] In the working-up, crystallization of the target product including recrystallization and washing of crystals may be performed. The crystallization of the target product including recrystallization may be performed by a conventional method known to a person skilled in the art. For example, an antisolvent may be added to a solution of the target product in a good solvent. As another example, a saturated solution of the target product may be cooled.

[0806] For still another example, from the solution of the target product in an organic solvent (including the reaction mixture), the solvent may be removed. In this case, examples of the organic solvent that can be used include the examples, the preferred examples, the more preferred examples, and the further preferred examples of the water-miscible organic solvent described later. The organic solvent may be removed after adding water in 2024219674   12 Sep 2024 advance into the system. In this case, the organic solvent may be removed by azeotropy with the water. The organic solvent may be removed under heating, under reduced pressure and under normal pressure. As still another example, water may be added to a solution of the target product in a water-miscible organic solvent. Examples of the water-miscible organic solvent include, but are not limited to, alcohols (e.g., methanol, ethanol, 2-propanol, butanol and t-butanol), nitriles (e.g., acetonitrile), ethers (e.g., tetrahydrofuran (THF) and 1,4-dioxane), ketones (e.g., acetone), amides (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC) and N-methylpyrrolidone (NMP)), sulfoxides (e.g., dimethyl sulfoxide (DMSO)), and combinations thereof, preferably methanol, ethanol, 2-propanol, butanol, acetonitrile, acetone, and combinations thereof, and more preferably ethanol, 2-propanol, butanol, acetonitrile, and combinations thereof. The “water-miscible organic solvent” has the same meaning as “water-soluble organic solvent”. “2-Propanol” is also referred to as “isopropyl alcohol” or “isopropanol”.

[0807] In any of the above cases, a seed crystal may be used.

[0808] 2024219674   12 Sep 2024 In the crystal washing procedure, the crystals collected by filtration may be washed with a solvent. A suspension (slurry) of crystals may be stirred and then filtered. In any case, examples of the solvent that can be used include the examples, the preferred examples, the more preferred examples, the further preferred examples of the water-miscible organic solvent described above and water.

[0809] In any of the above cases (crystallization procedures including recrystallization, crystal washing procedure, etc.), the amount of the solvent such as the water-miscible organic solvent and the amount of water may be at any ratio as long as the purpose is achieved.  When a combination of a water-miscible organic solvent and water is employed, the ratio thereof may be any ratio as long as the purpose is achieved.  When a combination of two or more solvents such as water-miscible organic solvents is employed, the ratio thereof may be any ratio as long as the purpose is achieved. Their amounts and ratios can be appropriately adjusted by a person skilled in the art depending on the purpose and situation.

[0810] In any of the above procedures (extraction procedure, washing procedure, crystallization procedures including recrystallization, crystal washing procedure, etc.), the 2024219674   12 Sep 2024 temperature can be appropriately adjusted by a person skilled in the art. However, from the viewpoint of yield, purity, economic efficiency, etc., for example, the temperature is 0°C (zero °C) to 100°C, preferably 5°C to 90°C, and more preferably 10°C to 80°C. Heating and cooling may be performed in these temperature ranges.

[0811] In any of the above procedures (extraction procedure, washing procedure, crystallization procedures including recrystallization, crystal washing procedure, etc.), the amount of the organic solvent (including the water-miscible organic solvent) and / or water can be appropriately adjusted by a person skilled in the art by addition and removal thereof. Furthermore, recovery and recycling of the solvent may be optionally performed. For example, the recovery and recycle of the solvent used in the reaction may be performed, and the recovery and recycle of the solvent used in the working-up (isolation and / or purification) may be performed.

[0812] Working-up (isolation and / or purification) can be performed by appropriately combining all or some of the procedures described above. Optionally, the above procedures may be repeated according to the purpose such as isolation and / or purification. In addition, a person 2024219674   12 Sep 2024 skilled in the art can appropriately select a combination of any of the above procedures and their order.

[0813] (Crystal of Pyroxasulfone) One aspect of the present invention includes a novel crystal of pyroxasulfone and a process for producing the same. The process of crystallization of the pyroxasulfone is described below.

[0814] The crystal of pyroxasulfone of the present invention is identified by a characteristic pattern observed in a powder X-ray diffraction spectrum obtained by measurement by the transmission method using Cu-Ka rays.

[0815] One example of a powder X-ray diffraction spectrum of a crystal of pyroxasulfone of the present invention is shown in FIG. 1. In addition, powder X-ray diffraction spectra of crystals of pyroxasulfone produced by the processes disclosed in Patent Documents 2 and 10 are shown in FIGs. 2 and 3. Of the upper and lower two charts shown in each figure, the upper one is a powder X-ray diffraction spectrum measured by the transmission method, and the lower one is a powder X-ray diffraction spectrum measured by the reflection method. In the present invention, powder X-ray 2024219674   12 Sep 2024 diffraction spectra measured by the transmission method are employed in the discussion.

[0816] Comparing the powder X-ray diffraction spectrum measured by the transmission method for the crystal of pyroxasulfone of the present invention and that measured for the crystal of pyroxasulfone produced by a known process, they are common in that characteristic peaks are observed at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0°, but they are different in terms of the order of the peak heights. Specifically, the crystal of pyroxasulfone produced by the known process has a maximum peak height at the peak of 17.7 to 17.8°, whereas the crystal of pyroxasulfone of the present invention has a maximum peak height at the peak of 19.9 to 20.0°. Herein, when there is a plurality of peaks at a peak position designated by a range, the highest peak among the plurality of peaks is recognized as the peak at the position.

[0817] Surprisingly, the difference in the order of peak intensities between those crystals of pyroxasulfone affects the physicochemical properties of the agrochemical formulations prepared using such crystals. Details of this 2024219674   12 Sep 2024 point will be described in the section of agrochemical formulation described later.

[0818] In one embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0°, and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks.

[0819] The ratio of the peak height at 19.9 to 20.0° to the peak height at 17.7 to 17.8° in the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention is not particularly limited, but usually includes a range of 1 : 0.01 to 1 : 0.99, preferably 1 : 0.02 to 1 : 0.95, more preferably 1 : 0.1 to 1 : 0.85, still more preferably 1 : 0.3 to 1 : 0.75, and particularly preferably 1 : 0.4 to 1 : 0.65.

[0820] The ratio of the peak height at 19.9 to 20.0° to the peak height at 18.0 to 18.1° in the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention is not particularly limited, but usually includes a range of 1 : 0.01 to 1 : 0.99, preferably 1 : 0.02 to 1 : 0.95, more preferably 1 : 0.04 to 1 : 0.8, even 2024219674   12 Sep 2024 more preferably 1 : 0.07 to 1 : 0.6, and particularly preferably 1 : 0.1 to 1 : 0.5.

[0821] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7° and 30.1 to 30.3°.

[0822] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 4.9 to 5.0°, 9.9 to 10.0°, 20.6 to 20.7° and 30.1 to 30.3°.

[0823] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 2024219674   12 Sep 2024 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.3 to 20.4°, 20.6 to 20.7° and 30.1 to 30.3°.

[0824] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 21.8 to 21.9° and 30.1 to 30.3°.

[0825] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 22.3 to 22.4° and 30.1 to 30.3°.

[0826] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present 2024219674   12 Sep 2024 invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 25.4 to 25.5° and 30.1 to 30.3°.

[0827] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 26.6 to 26.7° and 30.1 to 30.3°.

[0828] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 26.9 to 27.0° and 30.1 to 30.3°.

[0829] 2024219674   12 Sep 2024 In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 27.1 to 27.2° and 30.1 to 30.3°.

[0830] In another embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 at least in the ranges of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° and the peak height at the peak of 19.9 to 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 at least in the ranges of 9.9 to 10.0°, 20.6 to 20.7°, 30.1 to 30.3° and 35.5 to 35.6°.

[0831] In any of the above embodiments, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention may further have peaks at one or two or more of diffraction angles 20 of 11.2 to 11.4°, 14.3 to 14.4°, 14.9 to 15.1°, 17.1 to 17.3°, 19.6 to 19.7°, 20.1 to 20.2°, 20.8 to 20.9°, 22.0 to 22.1°, 22.5 to 22.6°, 22.7 to 22.8°, 23.1 to 23.3°, 24.3 to 24.5°, 25.1 to 25.2°, 26.2 to 2024219674   12 Sep 2024 26.3°, 26.9 to 27.0°, 27.1 to 27.2°, 27.3 to 27.4°, 27.7 to 27.9°, 28.3 to 28.4°, 28.5 to 28.6°, 29.7 to 29.8°, 30.4 to 30.5°, 31.5° to 31.6°, 32.1 to 32.3°, 32.4 to 32.5°, 32.8 to 33.0°, 33.3 to 33.4°, 34.5 to 34.7°, 34.8 to 34.9°, 35.3 to 35.4°, 36.1 to 36.2°, 36.3 to 36.4°, 36.6 to 36.7°, 37.2 to 37.3°, 38.0 to 38.1° and 38.6 to 38.7°.

[0832] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.8°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 5.0°, 9.9°, 11.3°,  14.4°,  15.0°,  19.7°,  20.2°,  20.4°,  20.6°,  20.8°,  21.8°, 22.1°, 22.3°, 22.8°, 23.2°, 24.4°, 25.1°, 25.4°, 26.3°, 26.6°, 27.0°, 27.1°, 28.3°, 28.5°, 29.7°, 30.1°, 30.3°, 30.6°, 31.6°, 32.5°, 32.9°, 34.6°, 35.4°, 35.5°, 36.1°, 36.7°, 37.2°, 38.0° and 38.7°.

[0833] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 9.9°, 14.4°, 2024219674   12 Sep 2024 20.4°, 20.6°, 20.8°, 21.8°, 22.4°, 22.5°, 25.5°, 26.3°, 26.6°, 27.0°, 27.1°, 28.4°, 30.1°, 30.3°,  32.4°,  34.7°, 35.3°, 36.1°, 36.4°, 38.0° and 38.7°.

[0834] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.8°, 18.1° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 5.0°, 9.9°, 17.2°, 20.6°, 21.8°, 22.4°, 23.2°, 25.2°, 25.5°, 26.3°, 26.7°, 26.9°, 27.1°, 29.8°, 30.1°, 30.2°, 34.7°, 34.8° and 36.2°.

[0835] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 9.9°, 20.3°, 20.6°, 20.7°, 21.8°, 22.4°, 25.4°, 27.0°, 27.1°, 30.1°, 30.4°, 31.5°, 32.4°, 33.3°, 35.5°, 36.1°, 36.2° and 36.3°.

[0836] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction 2024219674   12 Sep 2024 angles 29 of 17.8°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 29 of 5.0°, 9.9°, 20.4°, 20.6°, 20.8, 21.8°, 22.4°, 22.8°, 25.4°, 26.6°, 27.0°, 27.1°, 28.5°, 29.8°, 30.3°, 31.6°, 34.7° and 35.6°.

[0837] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 29 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 29 of 4.9°, 5.0°, 9.9°, 19.6°, 20.2°, 20.4°, 20.6°, 21.8°, 22.4°, 22.7°, 23.2°, 25.1°, 25.4°, 26.6°, 27.0°, 27.1°, 28.5°, 30.1°, 31.5°, 34.6°, 34.8°, 35.5° and 36.1°.

[0838] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 29 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 29 of 4.9°, 9.9°, 14.4°, 20.4°, 20.6°, 21.8°, 22.3°, 22.8°, 24.4°, 25.1°, 25.4°, 26.3°, 26.6°, 27.1°, 28.5°, 29.7°, 30.2°, 31.6°, 32.4°, 33.3°, 34.6°, 34.7°, 35.6°, 36.1°, 36.3°, 36.4° and 36.7°. 2024219674   12 Sep 2024

[0839] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 5.0°, 9.9°, 20.6°, 20.7°, 22.3°, 26.3°, 26.6°, 26.7°, 27.0°, 27.1°, 30.1°, 30.2°, 31.5°, 34.7°, 34.8°, 35.3°, 35.4°, 36.1° and 36.2°.

[0840] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.8°, 18.0° and 20.0° and the peak height at the peak of 20.0° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 4.9°, 5.0°, 9.9°, 14.4°, 15.0°, 19.7°, 20.2°, 20.3°, 20.6°, 20.8°, 21.8°, 22.0°, 22.3°, 22.7°, 23.2°, 24.4°, 25.1°, 25.5°, 26.6°, 27.0°, 27.3°, 28.5°, 29.7°, 30.2°, 30.3°, 31.5°,  32.4°,  32.9°,  33.4°, 34.7°, 35.6°, 36.1°, 36.7°, 38.1° and 38.7°.

[0841] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.7°, 18.0° and 19.9° and the peak height at 2024219674   12 Sep 2024 the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 5.0°, 9.9°, 14.4°,  19.6°,  20.4°,  20.6°,  20.7°,  21.8°,  22.3°,  22.4°,  22.8°, 23.2°, 25.1°, 25.4°, 26.6°, 27.0°, 28.5°, 30.1°, 30.3°, 31.5°, 32.2°, 34.6° and 35.6°.

[0842] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 5.0°, 9.9°, 14.4°, 20.4°, 20.6°, 20.8°, 21.8°, 22.3°, 22.8°, 23.2°, 25.1°, 25.5°, 26.3°, 26.6°, 27.0°, 27.1°, 28.5°, 29.8°, 30.1°, 32.4°, 34.6°, 34.7°, 35.5°, 36.1°, 38.1° and 38.6°.

[0843] In another preferred embodiment, the powder X-ray diffraction spectrum of the crystal of pyroxasulfone of the present invention has characteristic peaks at diffraction angles 20 of 17.7°, 18.0° and 19.9° and the peak height at the peak of 19.9° is maximum among the three peaks, and also has peaks at diffraction angles 20 of 5.0°, 9.9°, 14.4°, 15.0°, 20.3°, 20.6°, 20.8°, 21.8°, 22.0°, 22.4°, 22.8°, 23.2°, 24.4°, 25.1°, 25.5°, 26.2°, 26.6°, 27.1°, 27.8°, 28.5°, 29.8°, 30.3°, 31.5°, 32.4°, 34.5°, 35.6°, 37.2° and 38.1°. 2024219674   12 Sep 2024

[0844] As one embodiment, the process for obtaining a crystal of pyroxasulfone of the present invention includes a known crystallization technique such as a concentration method, an antisolvent addition method, a vapor diffusion method (including a sitting drop method, a hanging drop method and a sandwich drop method), a batch method (including an oil batch method), a dialysis method, a liquid-liquid diffusion method (a counter diffusion method), a cooling method, a pressure method, a melt quenching method, a temperature cycling method, a slurry stirring method, and an ultrasonic method. As one preferred embodiment, the process for obtaining a crystal of pyroxasulfone of the present invention includes a concentration method, i.e., a method in which an organic solvent is distilled off from a solution of pyroxasulfone comprising a solvent mainly composed of the organic solvent and pyroxasulfone as a solute to precipitate the pyroxasulfone. As another preferred embodiment, the process for obtaining a crystal of pyroxasulfone of the present invention includes an antisolvent addition method, i.e., a method in which an antisolvent for pyroxasulfone is added to a solution of pyroxasulfone comprising a solvent mainly composed of an organic solvent and pyroxasulfone as a solute to precipitate the pyroxasulfone. 2024219674   12 Sep 2024

[0845] Distillation refers to removal of a part or all of the organic solvent constituting the solvent from the solution by evaporating it by volatilizing or boiling it. When the organic solvent constituting the solution of pyroxasulfone is distilled off, the solution is concentrated, resulting in a supersaturated state, so that the pyroxasulfone excess with respect to the medium precipitates as a crystal. The distillation may be performed under normal pressure, or may be performed under reduced pressure or increased pressure as desired. The distillation may be performed at room temperature, or may be performed by heating or cooling the system as desired.

[0846] The antisolvent refers to a solvent having a low ability to dissolve a solute. When an antisolvent is added to the medium constituting the solution of pyroxasulfone, the solubility of the pyroxasulfone decreases as the amount of the antisolvent increases, so that the solution results in a supersaturated state and pyroxasulfone excess with respect to the medium precipitates as a crystal. The addition of the antisolvent may be performed at room temperature, or may be performed by heating or cooling the system as desired.

[0847] 2024219674   12 Sep 2024 In any of the above embodiments, any organic solvent cannot necessarily be used in the process for obtaining a crystal of pyroxasulfone of the present invention, and selection of an organic solvent is extremely important. When the selection of an organic solvent is wrong, crystals of pyroxasulfone having the characteristic pattern observed in the desired powder X-ray diffraction spectrum cannot be obtained.

[0848] In an embodiment in which the organic solvent is distilled off to precipitate the pyroxasulfone of the present invention, organic solvents that can be used include at least the following: aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, trichlorobenzenes and nitrobenzene), halogenated aliphatic hydrocarbons (e.g., dichloromethane and tetrachloroethylene), alcohols (e.g., methanol, ethanol, isopropanol, butanol and tert-butanol), nitriles (e.g., acetonitrile and propionitrile), carboxylic acids (e.g., formic acid, acetic acid, propionic acid, and butyric acid), carboxylic acid esters (e.g., methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof and pentyl acetate and isomers thereof), ethers (e.g., tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, diisopropyl ether, 2024219674   12 Sep 2024 dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether, methyl tert-butyl ether, 1,2-dimethoxyethane and diglyme), ketones (e.g., methyl isopropyl ketone and methyl isobutyl ketone), amides (e.g., N,N-dimethylformamide and N,N-dimethylacetamide), ureas (e.g., N,N'- dimethylimidazolidinone and tetramethylurea), sulfoxides (e.g., diethyl sulfoxide), sulfones (e.g., sulfolane), and any combination thereof in any ratio. In particular, nitriles, carboxylic acids, carboxylic acid esters, ketones, amides and dihalogenated aliphatic hydrocarbons are included.

[0849] Among the above, preferable organic solvents include the following: C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl)C1-C4 alkanamides, C1-C4 dihaloalkanes. In particular, acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide and dichloromethane are included.

[0850] In the above embodiment, the medium constituting the solution of pyroxasulfone may be a hydrous medium further comprising water. It is noted that from the viewpoint of making the solubility of pyroxasulfone in the hydrous 2024219674   12 Sep 2024 medium sufficiently high, the medium preferably comprises an organic solvent as a main component. Herein, “to comprise a certain component as a main component” means that the volume of the component occupies 1 / 3 or more of the total volume of the components constituting the composition to be discussed.

[0851] Among the above, preferable medium include the following: C1-C4 alcohol / C2-C5 alkanenitrile mixtures, hydrous C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, N,N-di(C1-C4 alkyl)C1-C4 alkaneamides and C1-C4 dihaloalkane / C1-C4 alcohol mixtures. In particular, acetonitrile / methanol mixtures, hydrous acetonitrile, acetic acid, ethyl acetate, methyl isobutyl ketone, N,N-dimethylformamide, N,N-dimethylacetamide and dichloromethane / ethanol mixtures are included.

[0852] On the other hand, among the above, organic solvents that should be avoided from being used singly include the following: chloroform, dimethyl sulfoxide, 1,4-dioxane, 2-methyltetrahydrofuran, N-methylpyrrolidone, tetrahydrofuran, trifluoroethanol and carbon disulfide. It is noted that an embodiment in which these organic solvents are used in combination with other organic solvents and an embodiment in which the solvent is a hydrous medium 2024219674   12 Sep 2024 comprising such an organic solvent and water are not excluded.

[0853] In an embodiment in which an antisolvent is added to precipitate the pyroxasulfone of the present invention, organic solvents that can be used include at least the following: aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, trichlorobenzenes and nitrobenzene), halogenated aliphatic hydrocarbons (e.g., dichloromethane and tetrachloroethylene), alcohols (e.g., methanol, ethanol, isopropanol, butanol and tert-butanol), nitriles (e.g., acetonitrile and propionitrile), carboxylic acids (e.g., formic acid, acetic acid, propionic acid, and butyric acid), carboxylic acid esters (e.g., methyl ace...

Claims

1. A process for producing a crystal of pyroxasulfone,wherein an organic solvent is distilled off from a solution of pyroxasulfone comprising the organic solvent as a main component to form a solvent medium from which the crystal of pyroxasulfone precipitates, the organic solvent being one selected from the group consisting of nitriles, carboxylic acids, carboxylic acid esters, ketones, amides and dihalogenated aliphatic hydrocarbons,wherein the crystal of pyroxasulfone exhibits a spectrum having peaks at diffraction angles 20 at least in the range of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° in powder X-ray diffraction measurement by a transmission method using Cu-Ka ray, and the peak height of 19.9 to 20.0° is maximum among the three peaks.

2. The process according to claim 1, wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 carboxylic acids, C1-C4 alkyl C1-C4 carboxylates, C1-C4 alkyl C1-C4 alkyl ketones, N,N-di(C1-C4 alkyl) C1-C4 alkanamides and C1-C4 dihaloalkanes.2024219674   17 Sep 20263. A process for producing a crystal of pyroxasulfone, wherein an antisolvent for pyroxasulfone selected from the group consisting of ethers, carboxylic acid esters, ketones, aromatic hydrocarbon derivatives, aliphatic hydrocarbons, alcohols and water is added to a solution of pyroxasulfone comprising one organic solvent selected from the group consisting of nitriles, ketones and carboxylic acid esters as a main component to precipitate pyroxasulfone, wherein the crystal of pyroxasulfone exhibits aspectrum having peaks at diffraction angles 20 at least in the range of 17.7 to 17.8°, 18.0 to 18.1° and 19.9 to 20.0° in powder X-ray diffraction measurement by a transmission method using Cu-Ka ray, and the peak height of 19.9 to 20.0° is maximum among the three peaks.

4. The process according to claim 3, wherein the organic solvent is one selected from the group consisting of C2-C5 alkanenitriles, C1-C4 alkyl C1-C4 alkyl ketones and C1-C4 alkyl C1-C4 carboxylates.

5. The process according to claim 3 or 4, wherein the antisolvent for pyroxasulfone is C1-C4 alcohol.

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