Method for producing 1,2,4-oxadiazole-5(4H)-one derivatives

Abstract

The objective is to provide a method for producing 1,2,4-oxadiazole-5(4H)-one derivatives that have pest control properties, which offers excellent yield and is advantageous for industrial-scale production. [Solution] We have discovered a method for producing 1,2,4-oxadiazole-5(4H)-one derivatives in high yield and on an industrial scale by reacting hydroxyimidamide derivatives with halogenated carbamate compounds in the presence of a base selected from carbonates, hydroxides, metal alkoxides, and metal hydrides.

Description

[Technical Field]

[0001] The present invention relates to a method for producing 1,2,4-oxadiazole-5(4H)-one derivatives. [Background technology]

[0002] Heterocyclic compounds having sulfur-containing substituents that function as control agents for harmful arthropods are known. For example, Patent Document 1 discloses a 1,2,4-oxadiazole-5(4H)-one derivative having a heterocyclic group with a sulfur-containing substituent. Patent Document 1 discloses a method for producing 1,2,4-oxadiazole-5(4H)-one derivatives, which involves reacting a hydroxyimidamide derivative with carbonyldiimidazole in tetrahydrofuran. However, carbonyldiimidazole used in this method is an expensive reagent, and two stoichiometric amounts of imidazole are discharged, requiring further improvement as an industrial production method from the perspective of atom economy. Furthermore, tetrahydrofuran is prone to the generation and accumulation of peroxides, and heating and concentration carry the risk of explosion due to tetrahydrofuran peroxides. Therefore, especially when reusing it for industrial use, it is necessary to strictly isolate it from air, which can be disadvantageous for industrial production. Consequently, there is a need for an industrial production method for 1,2,4-oxadiazole-5(4H)-one derivatives. On the other hand, Non-Patent Documents 1 and 2 describe a method for synthesizing 1,2,4-oxadiazole-5(4H)-one derivatives by reacting a hydroxyimidamide derivative with ethyl chloroformate in xylene in the presence of triethylamine. However, this method yields only a moderate yield of 53% to 72% of the target product, and there is room for improvement; a high-yield manufacturing method is desired. [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] International Publication No. 2023 / 190286 [Non-patent literature]

[0004] [Non-Patent Document 1] Phosphorus, Sulfur and Silicon and the Related Elements(2007),182(2),299-313 [Non-Patent Document 2] Spectrochimica Acta. Part A:Molecular and Biomolecular Spectroscopy(2015),149,920-927 [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] The object of the present invention is to provide a method for producing 1,2,4-oxadiazole-5(4H)-one derivatives that offers excellent yield and is advantageous for industrial-scale production. [Means for solving the problem]

[0006] As a result of diligent research to achieve the above objectives, we have discovered a method for producing 1,2,4-oxadiazole-5(4H)-one derivatives in high yield and advantageous for industrial-scale production by reacting a hydroxyimidamide derivative with a halogenated carbamate compound in the presence of a base. The present invention is based on these findings.

[0007] The present invention relates to, but is not limited to, the following [1] to [4]. [1] A method for producing a 1,2,4-oxadiazole-5(4H)-one derivative of formula (1), which is: [ka] [In formula (1), R2, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, an optionally substituted (C1-C6) alkylcarbonyloxy group, an optionally substituted (C2-C6) alkenylcarbonyloxy group, an optionally substituted (C2-C6) alkynylcarbonyloxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted (C1-C6) alkylsulfonyloxy group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, an optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group, and represents a group selected from the group consisting of When there are a plurality of Y1, each independently represents a group selected from the group consisting of a hydrogen atom and an optionally substituted (C1-C6) alkyl group. If multiple Y2 groups exist, each Y2 group independently represents a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. If multiple Y3 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted phenyl group, and an NY1Y2 group (Y1 and Y2 are as defined above). R a This represents a group selected from the group consisting of optionally substituted (C1-C6) alkyl groups and optionally substituted (C3-C6) cycloalkyl groups. R b , R c and R dis, independently of each other, a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl grrou, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, an optionally substituted (C1-C6) alkylcarbonyloxy group, an optionally substituted (C2-C6) alkenylcarbonyloxy group, an optionally substituted (C2-C6) alkynylcarbonyloxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted (C1-C6) alkylsulfonyloxy group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, an optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group, a group selected from the group consisting of (Y1, Y2, and Y3 are as defined above) is shown.] The hydroxyimidamide derivative represented by formula (2): [Chemical formula] [In the formula, R2, R3, R4, R5, R a , Rb and R c and R d is synonymous with the above.], and The carbamate halide compound represented by formula (3): [Chemical formula] [where R X represents a group selected from the group consisting of an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, an optionally substituted phenyl group, and an optionally substituted heterocyclic group, X represents any one of fluorine, chlorine, bromine and iodine.], and react in the presence of a base selected from the group consisting of an aqueous solution of an alkali metal or alkaline earth metal hydroxide, an alkali metal or alkaline earth metal carbonate, an alkali metal or alkaline earth metal alkoxide, and an alkali metal or alkaline earth metal metal hydride, the production method.

[0008] [2] The production method according to [1], wherein the reaction is carried out in a solvent containing water.

[0009] [3] The production method according to [1] or [2], wherein the reaction solvent is a mixed solvent containing an amide solvent selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone and a hydrocarbon solvent selected from the group consisting of aromatic hydrocarbons and halogenated aliphatic hydrocarbons.

[0010] [4] The manufacturing method according to [3], wherein the mixing ratio of the mixed solvent is 1 part by mass of amide solvent to 3 to 20 parts by mass of hydrocarbon solvent. [Effects of the Invention]

[0011] According to the manufacturing method of the present invention, a 1,2,4-oxadiazole-5(4H)-one derivative represented by formula (1) can be obtained in high yield. The method of the present invention can be implemented on a large scale using inexpensive raw materials, is highly economically efficient, and is suitable for industrial-scale production. [Modes for carrying out the invention]

[0012] The present invention relates to a method for producing a 1,2,4-oxadiazole-5(4H)-one derivative (also referred to as compound (1)) represented by formula (1) from a hydroxyimidamide derivative (also referred to as compound (2)) represented by formula (2).

[0013] [ka]

[0014] [ka]

[0015] The substituents in compound (1) and compound (2) will be described below. R2, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, or an optionally substituted (C2-C6) alkynyloxycarbonyl group. This represents a group selected from the group consisting of a 1-C6 group, an optionally substituted (C1-C6) alkylcarbonyloxy group, an optionally substituted (C2-C6) alkenylcarbonyloxy group, an optionally substituted (C2-C6) alkynylcarbonyloxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted (C1-C6) alkylsulfonyloxy group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, an optionally substituted pyridyloxy group, a NY1Y2 group, a C(O)NY1Y2 group, a C(=NY2)Y3 group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, an amino group, a formyl group, a carboxyl group, a trimethylsilyl group, a C(O)NH2 group, and an SF5 group. If multiple Y1 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom and an alkyl group that may have substituents (C1-C6). If multiple Y2 groups exist, each Y2 group independently represents a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. If multiple Y3 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted phenyl group, and an NY1Y2 group (Y1 and Y2 are as defined above). The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others.

[0016] Preferably, R2, R3, R4, and R5 are each independently selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, and an optionally substituted (C1-C6) alkylsulfonyl group. In this case, the substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. More preferably, R2 and R5 are hydrogen atoms, and R3 and R4 are each independently selected from the group consisting of hydrogen atoms, halogen atoms, and optionally substituted (C1-C6) alkyl groups. Particularly preferably, R2 and R5 are hydrogen atoms, and either R3 or R4 is optionally substituted (C1-C6) alkyl group, and the other is a hydrogen atom. In this case, the optionally substituted groups are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups.

[0017] R a This group is selected from the group consisting of optionally substituted (C1-C6) alkyl groups and optionally substituted (C3-C6) cycloalkyl groups. The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others. Preferably, R a R is an alkyl group which may have substituents (C1-C6). More preferably, a This is a (C1-C3) alkyl group, and more preferably a methyl group or an ethyl group.

[0018] R b , R c and R dEach of these independently comprises a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, or an optionally substituted (C The group is selected from the group consisting of (1-C6) alkylcarbonyloxy group, optionally substituted (C2-C6) alkenylcarbonyloxy group, optionally substituted (C2-C6) alkynylcarbonyloxy group, optionally substituted (C1-C6) alkylthio group, optionally substituted (C1-C6) alkylsulfinyl group, optionally substituted (C1-C6) alkylsulfonyl group, optionally substituted (C1-C6) alkylsulfonyloxy group, optionally substituted phenyl group, optionally substituted heterocyclic group, optionally substituted phenoxy group, optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH2 group, and SF5 group (Y1, Y2, and Y3 are as defined above). The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others.

[0019] Preferably, R b , R c and R d Each of these independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, and an optionally substituted pyridyloxy group. In this case, the substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. Comfortable, R b and R d R is a hydrogen atom, cThis group is selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted phenyl group, and an optionally substituted heterocyclic group. In this case, the optionally substituted groups are a halogen atom, a cyano group, a nitro group, a hydroxyl group, a mercapto group, an amino group, a carboxyl group, a trimethylsilyl group, a C(O)NH2 group, and an SF5 group. More preferably, R b and R d R is a hydrogen atom, c This group is selected from the group consisting of a hydrogen atom, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted phenyl group, and an optionally substituted heterocyclic group. In this case, the optionally substituted groups are a halogen atom, an (C1-C6) alkoxy group, a halo(C1-C6) alkoxy group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, an amino group, a carboxyl group, a trimethylsilyl group, a C(O)NH2 group, and an SF5 group.

[0020] R b , R c and R d Preferred forms of the phenyl group, which may have substituents, include 3-fluorophenyl group, 3-chlorophenyl group, 3-bromophenyl group, 3-iodophenyl group, 3-cyanophenyl group, 3-(trifluoromethyl)phenyl group, 3-(trifluoromethoxy)phenyl group, 4-fluorophenyl group, 4-chlorophenyl group, 4-bromophenyl group, 4-iodophenyl group, 4-cyanophenyl group, 4-(trifluoromethyl)phenyl group, 4-(trifluoromethoxy)phenyl group, 4-cyclopropylphenyl group, 4-(1-cyanocyclopropyl)phenyl group, 2,4-difluorophenyl group, 2,4,6-trifluorophenyl group, and 3,5-difluorophenyl group.

[0021] R2, R3, R4 and R5 in general formula (1) and general formula (2), and R b , R c and R dExamples of "heterocyclic groups" in this context include thiophen-2-yl, thiophen-3-yl, furan-2-yl, furan-3-yl, pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, oxazole-2-yl, oxazole-4-yl, oxazole-5-yl, isoxazole-3-yl, isoxazole-4-yl, isoxazole-5-yl, isoxazolin-3-yl, isoxazolin-4-yl, isoxazolin-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, isothiazo Isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, pyrazole-1-yl, pyrazol-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, 1,3,4-oxadiazole-2-yl, 1,2,4-oxadiazole-3-yl, 1,2,4-oxadiazole-5-yl, 1,3,4-thiadiazole-2-yl, 1,2,4-thiadiazole-3-yl, 1,2,4-thiadiazole-5-yl, 1,2,4-triazole-1-yl 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, 1,2,3-thiadiazole-4-yl, 1,2,3-thiadiazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-2-yl, 1,2,3-triazole-4-yl, 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-2-yl, 1,2,3,4-tetrazol-5-yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5 -yl, pyrazine-2-yl, pyridazine-3-yl, pyridazine-4-yl, 1,3,5-triazine-2-yl, 1,2,4-triazine-3-yl, 1,2,4-triazine-5-yl, 1,2,4-triazine-6-yl, benzothiophene-2-yl, benzothiophene-3-yl, benzothiophene-4-yl, benzothiophene-5-yl, benzothiophene-6-yl, benzothiophene-7-yl, benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl,Benzofuran-7-yl, indole-1-yl, indole-2-yl, indole-3-yl, indole-4-yl, indole-5-yl, indole-6-yl, indole-7-yl, benzothiazole-2-yl, benzothiazole-4-yl, benzothiazole-5-yl, benzothiazole-6-yl, benzothiazole-7-yl, benzimidazole-1-yl, benzimidazole-2-yl, benzimidazole-4-yl, benzimidazole-5-yl, benzimidazole-6-yl, benzimidazole-7-yl, Benzoisoxazole-3-yl, benzoisoxazole-4-yl, benzoisoxazole-5-yl, benzoisoxazole-6-yl, benzoisoxazole-7-yl, benzoisothiazol-3-yl, benzoisothiazol-4-yl, benzoisothiazol-5-yl, benzoisothiazol-6-yl, benzoisothiazol-7-yl, indazole-1-yl, indazole-3-yl, indazole-4-yl, indazole-5-yl, indazole-6-yl, indazole-7-yl, benzooxazole-2-yl , benzoxazole-4-yl, benzoxazole-5-yl, benzoxazole-6-yl, benzoxazole-7-yl, quinoline-2-yl, quinoline-3-yl, quinoline-4-yl, quinoline-5-yl, quinoline-6-yl, quinoline-7-yl, quinoline-8-yl, isoquinoline-1-yl, isoquinoline-3-yl, isoquinoline-4-yl, isoquinoline-5-yl, isoquinoline-6-yl, isoquinoline-7-yl, isoquinoline-8-yl, quinoxaline-2-yl, quinoxaline-3-yl, quinoxaline-5-yl Specific examples include quinoxalin-6-yl, quinoxalin-7-yl, quinoxalin-8-yl, phthalazine-1-yl, phthalazine-4-yl, phthalazine-5-yl, phthalazine-6-yl, phthalazine-7-yl, phthalazine-8-yl, cinnolin-3-yl, cinnolin-4-yl, cinnolin-5-yl, cinnolin-6-yl, cinnolin-7-yl, cinnolin-8-yl, quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl, or quinazolin-8-yl, butThis is not the case.

[0022] The present invention relates to a method for producing a 1,2,4-oxadiazole-5(4H)-one derivative (compound (1)) represented by formula (1) by reacting compound (2) represented by formula (2) with a halogenated carbamate compound (3) in the presence of a base. The method for producing the compound (1) is described below.

[0023] [ka]

[0024] In equation (3), R X This represents an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, an optionally substituted phenyl group, or an optionally substituted heterocyclic group. X represents a halogen atom, specifically one of the following: fluorine, chlorine, bromine, and iodine. Preferably, R X This represents a group selected from the group consisting of optionally substituted (C1-C6) alkyl groups, optionally substituted (C2-C6) alkenyl groups, optionally substituted (C2-C6) alkynyl groups, and optionally substituted (C3-C6) cycloalkyl groups. R XThe substituents that may be present in the compound include halogen atoms, NY1Y2 groups, C(O)NY1Y2 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, C(O)NH2 groups, trimethylsilyl groups, and SF5 groups (Y1 and Y2 are as defined above). When there are two or more substituents, each substituent may be the same or different from the others. Preferably, the substituent is a group selected from the group consisting of halogen atoms, (C1-C6)alkoxy groups, and halo(C1-C6)alkoxy groups.

[0025] Specific examples of halogenated carbamate compounds represented by general formula (3) include methyl formate halide, ethyl formate halide, isopropyl formate halide, butyl formate halide, octyl formate halide, phenyl formate halide, 4-chlorophenyl formate halide, and 4-nitrophenyl formate halide. As halides and halogenated products, chlorides and bromides are preferred, with chlorides being particularly preferred due to the ease of preparation and availability of raw materials.

[0026] The amount of the halogenated carbamate compound represented by general formula (3) used is usually 1 to 20 moles, preferably 1 to 5 moles, per mole of compound (2).

[0027] The manufacturing method of the present invention is carried out in the presence of a base. Examples of bases that can be used include inorganic bases such as alkali metal or alkaline earth metal carbonides and alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal alkoxides, and alkali metal or alkaline earth metal metal hydrides. Examples of alkali metal or alkaline earth metal carbon oxides include potassium carbonate, sodium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate, magnesium carbonate, calcium carbonate, and the like. Examples of alkali metal or alkaline earth metal hydroxides include sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, and the like. Examples of alkali metal or alkaline earth metal alkoxides include sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, and the like. Examples of alkali metal or alkaline earth metal hydrides include sodium hydride and potassium hydride. Preferably, the base is selected from the group consisting of alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal carbonides, and alkali metal or alkaline earth metal alkoxides. More preferably, it is an alkali metal or alkaline earth metal hydroxide, or an alkali metal or alkaline earth metal carbonide. Inorganic bases such as alkali metal or alkaline earth metal carbonides, or their hydroxides, are advantageous in industrial production because they are low-risk, easy to handle, readily available, and inexpensive. From this viewpoint, sodium carbonate, potassium carbonate, or sodium hydroxide, potassium hydroxide are preferred as bases, and sodium hydroxide or potassium hydroxide are more preferred.

[0028] The base is preferably prepared as an aqueous solution and used in the reaction. Suitable bases for the aqueous solution are hydroxides of alkali metals or alkaline earth metals, or carbonides of alkali metals or alkaline earth metals. Specifically, a 1-50% by weight aqueous solution of the base is more preferably used, and a 5-30% by weight aqueous solution is even more preferable. Particularly preferred forms of the base include 5-30% by weight aqueous solutions of sodium hydroxide or potassium hydroxide, or aqueous solutions of sodium carbonate or potassium carbonate. The amount of base used is preferably 0.1 to 10.0 times the molar amount of compound (2), and more preferably 0.5 to 5.0 times the molar amount.

[0029] On the other hand, it is preferable to use an aqueous solution of the base in an amount of 0.01 to 0.5 times the mass of the solvent for dissolving compound (2).

[0030] The manufacturing method of the present invention can typically be carried out in the presence of a solvent that dissolves compound (2). The solvent used is not particularly limited as long as it does not inhibit the reaction. Examples include, but are not limited to, water; aromatic hydrocarbon solvents such as benzene, toluene, xylene, and mesitylene; halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene; alcohol solvents such as methanol, ethanol, and n-butanol; nitrile solvents such as acetonitrile and propylnitrile; halogenated aliphatic hydrocarbon solvents such as methylene chloride, chloroform, and dichloroethane; aliphatic hydrocarbon solvents such as peptane, hexane, heptane, 2-methylbutane, 2-methylpentane, 2-methylhexane, cyclopentane, cyclohexane, and cycloheptane; aprotic polar solvents such as dimethyl sulfoxide and sulfolane; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; ether solvents such as tetrahydrofuran, diethyl ether, 1,4-dioxane, and diisopropyl ether; and ketone solvents such as 2-butanone, or mixtures thereof. These solvents may be used as a single system or in combination as a mixed solvent system, with the mixed solvent system being more preferable. As a mixed solvent system, it is preferable to use a mixture of water and an organic solvent. Even more preferable is the mixture of water and two or more organic solvents.

[0031] Preferably, the solvents include aromatic hydrocarbon solvents such as benzene, toluene, xylene, and mesitylene; halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene; halogenated aliphatic hydrocarbon solvents such as methylene chloride, chloroform, and dichloroethane; aliphatic hydrocarbon solvents such as peptane, hexane, heptane, 2-methylbutane, 2-methylpentane, 2-methylhexane, cyclopentane, cyclohexane, and cycloheptane; aprotic polar solvents such as dimethyl sulfoxide and sulfolane; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; or mixed solvents thereof. More preferably, aprotic polar solvents such as dimethyl sulfoxide and sulfolane, and amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone are used. The amount of solvent used should be an appropriate amount that can dissolve compound (2), preferably 1 to 50 times the mass of compound (2), and more preferably 2 to 30 times the mass.

[0032] More preferably, a mixed solvent is used, comprising a water-immiscible organic solvent selected from the group consisting of aromatic hydrocarbon solvents such as benzene, toluene, xylene, and mesitylene; halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene; halogenated aliphatic hydrocarbon solvents such as methylene chloride, chloroform, and dichloroethane; and aliphatic hydrocarbon solvents such as peptane, hexane, heptane, 2-methylbutane, 2-methylpentane, 2-methylhexane, cyclopentane, cyclohexane, and cycloheptane; and a water-miscible solvent selected from the group consisting of aprotic polar solvents such as dimethyl sulfoxide and sulfolane, and amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone. More preferably, the mixed solvent is a hydrocarbon solvent which is the aromatic hydrocarbon solvent and / or halogenated aliphatic hydrocarbon solvent, and the amide solvent. As the aromatic hydrocarbon solvent or halogenated aliphatic hydrocarbon solvent, toluene, xylene, and methylene chloride are particularly preferred, and a mixed solvent of these with an amide solvent selected from N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone is preferred.

[0033] In the aforementioned mixed solvent system, the mixing ratio is preferably such that 1 part by mass of a water-miscible solvent, such as the aprotic polar solvent or amide solvent, is mixed with 3 to 20 parts by mass of a water-immiscible solvent, such as the aromatic hydrocarbon solvent. Preferably, the solvent is a mixed solvent of a hydrocarbon solvent, which is an aromatic hydrocarbon solvent and / or a halogenated aliphatic hydrocarbon solvent, and the amide solvent, wherein the mixing ratio is preferably 3 to 20 parts by mass of the hydrocarbon solvent, which is an aromatic hydrocarbon and / or a halogenated aliphatic hydrocarbon, per 1 part by mass of the amide solvent, and more preferably 3 to 10 parts by mass of the hydrocarbon solvent, per 1 part by mass of the amide solvent.

[0034] In the manufacturing method of the present invention, it is preferable to contact compound (2) and the halogenated carbamate compound (3) together in the liquid phase in the presence of the base. For example, the condensation reaction is carried out by adding the halogen compound (3) dropwise to compound (2) and the base under an inert gas atmosphere while stirring and mixing the solvent. The dropwise addition time is preferably 0.1 to 10 hours, more preferably 0.5 to 3 hours. The reaction time after the addition is 0.1 to 5 hours, more preferably 0.5 to 2 hours. The reaction temperature is preferably -50 to 100°C, more preferably -10 to 50°C. The condensation reaction is carried out under normal pressure, under pressure, or under reduced pressure. Compound (2) may be used in a state in which it has formed a salt with the base.

[0035] The target product (1) according to the present invention can be isolated after the reaction is complete by simple general post-treatment operations such as extraction and precipitation. As described above, the manufacturing method of the present invention preferably employs a mixed solvent system in which an aromatic hydrocarbon solvent, a halogenated aliphatic hydrocarbon solvent, specifically toluene, xylene, and methylene chloride are used as the main reaction solvent, and a small amount of amide solvent, specifically N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone, are mixed as cosolvents for the purpose of dissolution assistance and correlation transfer assistance. In this case, the target product can be isolated by precipitation of compound (1), the target product, through a simple procedure of distillation and removal of the main solvent. Alternatively, after distillation and removal of the main solvent, the target product can be isolated by adding a small amount of a solvent to which the target product is insoluble or sparingly soluble. In the latter method, the solvent added to precipitate the target product is not particularly limited, but water or the aforementioned alcohol solvents are preferred. The manufacturing method of the present invention is industrially advantageous because it allows the use of a solvent that can be easily removed by distillation as the main reaction solvent, thus simplifying the isolation of the target product, enabling the use of a smaller product precipitation tank, and allowing the target product to be obtained in high yield using compound (2), an inexpensive base, and an inexpensive halogenated carbamate compound (3). Compound (1) produced and isolated by the manufacturing method of the present invention can be obtained as a high-yield, high-purity isolated product by recovering the precipitated solid by filtration. If necessary, it may be separated and purified by recrystallization and used as an agricultural chemical. [Examples]

[0036] Example 1: Method for producing 3-(3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine-2-yl)-4-(4-(trifluoromethyl)pyridine-2-yl)-1,2,4-oxadiazole-5(4H)-one [ka] Under a nitrogen atmosphere, 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (230.01 g, 0.43 mol) was dissolved in a mixed solvent of toluene (775 mL) and N,N-dimethylacetamide (DMAC 129 mL), and cooled to 0°C to 10°C in an ice bath. Then, 12% aqueous sodium hydroxide solution (287 g, 0.86 mol) was added within the range of 0°C to 10°C, followed by methyl chloroformate (61 g, 0.65 mol) within the range of 0°C to 10°C, and the mixture was reacted at 0°C to 10°C for 1 hour. Subsequently, water was added to wash the organic layer, and the mixture was separated. The resulting aqueous layer was extracted by adding toluene. The obtained organic layers were mixed, and the organic layers were washed with water adjusted to pH=4 and with water, and then separated. The obtained organic layers were concentrated under reduced pressure using a rotary evaporator. The resulting residue was dissolved in methanol, and water was added to precipitate crystals, which were then filtered to obtain 231.05 g of the target product (yield: 98.4%). 1 Based on the results of the 1H-NMR measurement, it was confirmed that the obtained compound is compound No. 47 described in International Publication No. 2023 / 190286 (Patent Document 1). 1 H-NMR(CDCl3):δ 9.02(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 8.34(1H, s), 8.15(1H, d, J=5.1Hz), 7.75-7.71(2H, m), 7.43(2H, d, J=8.1Hz), 7.38(1H, d, J=5.1), 3.52(2H, q, J=7.5Hz), 1.39(3H, t, J=7.5Hz)

[0037] Example 2: Method for producing 3-(3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine-2-yl)-4-(4-(trifluoromethyl)pyridine-2-yl)-1,2,4-oxadiazole-5(4H)-one Under a nitrogen atmosphere, 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (0.97 g, 1.82 mmol) was dissolved in a mixed solvent of toluene (3.27 mL) and N-methylpyrrolidone (NMP 0.54 mL), and cooled to 0°C to 10°C in an ice bath. 12% sodium hydroxide aqueous solution (1.21 g, 3.63 mmol) was added dropwise, followed by methyl chloroformate (0.26 g, 2.72 mmol), and the mixture was reacted at 0°C to 10°C for 1 hour. Subsequently, water and ethyl acetate were added, and the organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate. After filtration through Kiriyama filter paper, the resulting filtrate was concentrated under reduced pressure using a rotary evaporator, and the resulting residue was purified by silica gel column chromatography to obtain 0.98 g of the target product as amorphous material (yield 96.3%). 1 Based on the results of the 1H-NMR measurement, it was confirmed that the obtained compound is compound No. 47 described in International Publication No. 2023 / 190286 (Patent Document 1). 1 H-NMR(CDCl3):δ 9.02(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 8.34(1H, s), 8.15(1H, d, J=5.1Hz), 7.75-7.71(2H, m), 7.43(2H, d, J=8.1Hz), 7.38(1H, d, J=5.1), 3.52(2H, q, J=7.5Hz), 1.39(3H, t, J=7.5Hz)

[0038] Example 3: Method for producing 3-(3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine-2-yl)-4-(4-(trifluoromethyl)pyridine-2-yl)-1,2,4-oxadiazole-5(4H)-one Under a nitrogen atmosphere, 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (0.97 g, 1.82 mmol) was dissolved in a mixed solvent of methylene chloride (3.27 mL) and N,N-dimethylacetamide (DMAC 0.54 mL), and cooled to 0°C to 10°C in an ice bath. 12% sodium hydroxide aqueous solution (1.21 g, 3.63 mmol) was added dropwise, followed by methyl chloroformate (0.26 g, 2.72 mmol), and the mixture was reacted at 0°C to 10°C for 1 hour. Subsequently, water and ethyl acetate were added, and the organic layer was washed with water and saturated brine, then dried over anhydrous magnesium sulfate. After filtration through Kiriyama filter paper, the resulting filtrate was concentrated under reduced pressure using a rotary evaporator, and the resulting residue was purified by silica gel column chromatography to obtain 0.96 g of the target product as amorphous material (yield 94.4%). 1 Based on the results of the 1H-NMR measurement, it was confirmed that the obtained compound is compound No. 47 described in International Publication No. 2023 / 190286 (Patent Document 1). 1 H-NMR(CDCl3):δ 9.02(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 8.34(1H, s), 8.15(1H, d, J=5.1Hz), 7.75-7.71(2H, m), 7.43(2H, d, J=8.1Hz), 7.38(1H, d, J=5.1), 3.52(2H, q, J=7.5Hz), 1.39(3H, t, J=7.5Hz)

[0039] Example 4: Method for producing 3-(3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine-2-yl)-4-(4-(trifluoromethyl)pyridine-2-yl)-1,2,4-oxadiazole-5(4H)-one Under a nitrogen atmosphere, 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (0.27 g, 0.50 mmol) was dissolved in N,N-dimethylacetamide (DMAC 4.2 mL) and cooled to 0°C to 10°C in an ice bath. Sodium t-butoxide (96.02 mg, 1.00 mmol) was slowly added, followed by methyl chloroformate (0.26 g, 2.72 mmol) added dropwise, and the mixture was reacted at 0°C to 10°C for 1 hour. Analysis of the reaction mixture by high-performance liquid chromatography (HPLC) revealed that the HPLC area percentage of the target product was 92.6%.

[0040] Comparative example: Under a nitrogen atmosphere, 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide was dissolved in a mixed solvent of solvent 1 and solvent 2 listed in Table 1, and cooled to 0°C to 10°C in an ice bath. A base listed in Table 1 was added within the range of 0°C to 10°C, and then methyl chloroformate, triphosgene, or carbonyl diimidazole were added as a reactant within the range of 0°C to 10°C. The reaction mixture was analyzed by high-performance liquid chromatography (HPLC) one hour after the completion of the dropping process.

[0041] Table 1 summarizes the solvents, bases, and reaction reagents used, as well as the HPLC area percentage of the products. Table 2 shows the HPLC analysis conditions for the examples and comparative examples.

[0042] [Table 1] TIFF2026110533000008.tif33170

[0043] [Table 2] TIFF2026110533000009.tif52170

Claims

1. A method for producing the 1,2,4-oxadiazole-5(4H)-one derivative of formula (1), comprising: 【Chemistry 1】 [In formula (1), R ２ , R ３ , R ４ and R ５ Each of them operates independently. hydrogen atom, halogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, which may have a substituent, a (C ２ -C ６ ) alkynyl group, It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) Alkoxy group, It may have substituents (C ２ ~C ６ ) Alkenyloxy group, It may have substituents (C ２ ~C ６ ) Alkynyloxy group, It may have substituents (C ３ ~C ６ ) Cycloalkoxy group, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, It may have substituents (C １ ~C ６ ) Alkylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkenylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkynylcarbonyloxy group, It may have substituents (C １ ~C ６ ) alkylthio group, It may have substituents (C １ ~C ６ ) alkylsulfinyl group, It may have substituents (C １ ~C ６ ) alkylsulfonyl group, It may have substituents (C １ ~C ６ ) Alkyl sulfonyl oxy group, A phenyl group which may have substituents, A heterocyclic group which may have substituents, A phenoxy group which may have a substituent, A pyridyloxy group which may have substituents, NY １ Y ２ Base, C(O)NY １ Y ２ Base, C (=NY ２ ) Y ３ Group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH ２ Base and SF ５ This represents a group selected from a group consisting of the groups, The aforementioned Y １ If there are multiple such atoms, each may independently have a hydrogen atom and a substituent (C １ ~C ６ ) Represents a group selected from the group consisting of alkyl groups, The aforementioned Y ２ If there are multiple such atoms, each may independently have a hydrogen atom or a substituent (C １ ~C ６ ) alkyl groups may have substituents (C ２ ~C ６ ) may have an alkenyl group, or a substituent (C ３ ~C ６ ) Cycloalkyl groups may have substituents (C １ ~C ６ ) It may have an alkoxy group or substituent (C １ ~C ６ ) an alkylcarbonyl group, which may have substituents (C １ ~C ６ ) Represents a group selected from the group consisting of an alkoxycarbonyl group, a optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. The aforementioned Y ３ If there are multiple such atoms, each may independently have a hydrogen atom, a halogen atom, or a substituent (C １ ~C ６ ) alkyl groups may have substituents (C １ ~C ６ ) It may have an alkoxy group or substituent (C １ ~C ６ ) The alkylthio group may have substituents (C ３ ~C ６ ) Cycloalkyl groups, optionally substituted phenyl groups, and NY １ Y ２ This represents a group selected from a group consisting of (Y １ and Y ２ (This is synonymous with the above.) R ａ teeth, It may have substituents (C １ ~C ６ ) alkyl groups, and It may have substituents (C ３ ~C ６ ) Cycloalkyl groups This represents a group selected from the group consisting of, R ｂ , R ｃ and R ｄ Each of them operates independently. hydrogen atom, halogen atom, which may have a substituent, (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, It may have substituents (C ２ ~C ６ ) Alkynyl group, which may have a substituent, (C ３ ~C ６ ) cycloalkyl group, It may have substituents (C １ ~C ６ ) Alkoxy group, It may have substituents (C ２ ~C ６ ) Alkenyloxy group, It may have substituents (C ２ ~C ６ ) Alkynyloxy group, It may have substituents (C ３ ~C ６ ) Cycloalkoxy group, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, It may have substituents (C １ ~C ６ ) Alkylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkenylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkynylcarbonyloxy group, It may have substituents (C １ ~C ６ ) alkylthio group, It may have substituents (C １ ~C ６ ) alkylsulfinyl group, It may have substituents (C １ ~C ６ ) alkylsulfonyl group, It may have substituents (C １ ~C ６ ) Alkyl sulfonyl oxy group, A phenyl group which may have substituents, A heterocyclic group which may have substituents, A phenoxy group which may have a substituent, A pyridyloxy group which may have substituents, NY １ Y ２ Base, C(O)NY １ Y ２ Base, C (=NY ２ ) Y ３ Group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH ２ Base and SF ５ A group selected from the group consisting of (Y １ , Y ２ , and Y ３ (This is synonymous with the above.) [This indicates...] Hydroxyimidamide derivatives represented by formula (2): 【Chemistry 2】 [In the formula, R ２ , R ３ , R ４ , R ５ , R ａ , R ｂ , R ｃ and R ｄ This is synonymous with the above. and, The halogenated carbamate compound represented by formula (3): 【Transformation 3】 [In the formula R Ｘ teeth It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, It may have substituents (C ２ ~C ６ ) Alkynyl group, It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, A phenyl group which may have substituents, and This represents a group selected from the group consisting of heterocyclic groups that may have substituents, X represents one of the following: fluorine, chlorine, bromine, and iodine. of, The reaction is carried out in the presence of a base selected from the group consisting of alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal carbonides, alkali metal or alkaline earth metal alkoxides, and alkali metal or alkaline earth metal metal hydrides. The aforementioned manufacturing method.

2. The manufacturing method according to claim 1, wherein the reaction is carried out in a solvent containing water.

3. The production method according to claim 1 or 2, wherein the reaction solvent is a mixed solvent comprising an amide solvent selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone, and a hydrocarbon solvent selected from the group consisting of aromatic hydrocarbons and halogenated aliphatic hydrocarbons.

4. The manufacturing method according to claim 3, wherein the mixing ratio of the mixed solvent is 1 part by mass of amide solvent to 3 to 20 parts by mass of hydrocarbon solvent.

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