JP2005145958A - Herbicide composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a herbicide composition having an excellent herbicidal effect and selectivity between crops/weeds. <P>SOLUTION: This herbicide composition contains an isooxazoline derivative expressed by formula [I] [wherein, Q is a group: S(O)<SB>n</SB>-(CR<SB>5</SB>R<SB>6</SB>)<SB>m</SB>; (n) is 0-2 integer; (m) is 1-3 integer; R<SB>5</SB>, R<SB>6</SB>are each H; R<SB>1</SB>, R<SB>2</SB>are each a 1-8C alkyl; R<SB>3</SB>, R<SB>4</SB>are each H; and Y is phenyl which may be substituted] and at least 1 kind of herbicide selected from the following group A. Group A: a sulfonylurea-based herbicide, a pyrimidinyl carboxylic acid-based herbicide, an allyloxyphenoxypropionic acid-based herbicide, a triazine-based herbicide, a diphenylether-based herbicide, an oxadiazole-based herbicide, a pyrazole-based herbicide, a bicyclooctane-based herbicide, an amino acid-based herbicide, an organophosphorus based herbicide, an acidamide-based herbicide, or the like. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention relates to a herbicidal composition that exhibits not only additive effects of individual herbicides but also synergistic effects by mixing isoxazoline derivatives and at least one selected from the following group A.
Group A: sulfonylurea herbicide, pyrimidyl carboxylic acid herbicide, allyloxyphenoxypropionic acid herbicide, triazine herbicide, diphenyl ether herbicide, oxadiazole herbicide, pyrazole herbicide, bicyclooctane Herbicides, amino acid herbicides, organophosphorus herbicides, acid amide herbicides, phenoxy herbicides, carbamate herbicides, phenoxycarboxylic acid herbicides, ACN, indanophane, oxadichromefone, carfentrazone, dithiopyr , Pyraclonyl, phentolazamide, propanyl, penoxthram, bentazone, pentoxazone, benfrate, metamihop, 2 '-(4,6-dimethoxypyrimidin-2-yl) -hydroxymethyl-6'-methoxymethyl-1,1-difluoromethanesulfo Anilide, 2- {2-chloro-4-mesyl-3 - [(tetrahydrofuran-2-ylmethoxy) methyl] benzoyl} cyclohexane-1,3-dione

A wide variety of herbicides have been put to practical use in the research and development of herbicides over the years, and these herbicides have contributed to labor saving in weed control work and improved productivity of agricultural and horticultural crops. However, even today, there is a demand for the development of new drugs with better herbicidal properties.
WO01 / 012613

  It is desired that the herbicide used for useful crops is an agent that is applied to soil or foliage, exhibits a sufficient herbicidal effect at a low dose, and exhibits high selectivity between crops and weeds.

  The isoxazoline compound represented by the formula [I], which is one active ingredient of the herbicidal composition of the present invention, is described in WO 01/016613, and this compound contains rice, wheat, barley, corn, and grain. It is safe for sorghum, soybean, cotton, sugar beet, turf, fruit tree, etc., and has an excellent herbicidal effect by itself.

The present inventors mixed one or more conventionally used herbicides shown in the group A with the isoxazoline derivative represented by the formula [I] at a predetermined ratio, so that each It was found that the herbicidal effect is not only obtained additively, but also a synergistic herbicidal effect appears. In other words, the combined use of two types of drugs expands the herbicidal spectrum compared to the range of herbicidal application of each single agent, and at the same time, the herbicidal effect is achieved at an early stage, the effect is sustained, and the dosage is lower than the single-dose dosage. In addition to exerting sufficient effects, safety against rice, wheat, barley, corn, grain sorghum, soybean, cotton, sugar beet, turf, fruit trees, etc. is also ensured, and sufficient herbicidal effects are demonstrated with a single treatment. The headline and the present invention were completed.
Group A: sulfonylurea herbicide, pyrimidyl carboxylic acid herbicide, allyloxyphenoxypropionic acid herbicide, triazine herbicide, diphenyl ether herbicide, oxadiazole herbicide, pyrazole herbicide, bicyclooctane Herbicides, amino acid herbicides, organophosphorus herbicides, acid amide herbicides, phenoxy herbicides, carbamate herbicides, phenoxycarboxylic acid herbicides, ACN, indanophane, oxadichromefone, carfentrazone, dithiopyr , Pyraclonyl, phentolazamide, propanyl, penoxthram, bentazone, pentoxazone, benfrate, metamihop, 2 '-(4,6-dimethoxypyrimidin-2-yl) hydroxymethyl-6'-methoxymethyl-1,1-difluoromethanesulfone Nirido, 2- {2-chloro-4-mesyl-3 - [(tetrahydrofuran-2-ylmethoxy) methyl] benzoyl} cyclohexane-1,3-dione that is, the present invention has the general formula [I]

{In the formula, Q represents a group —S (O) _n — (CR ₅ R ₆ ) _m —, n represents an integer of 0 to 2, m represents an integer of 1 to 3, R ₅ and R ₆ Independently represent a hydrogen atom, a cyano group, an alkoxycarbonyl group or a C1-C6 alkyl group,
R ₁ and R ₂ are a hydrogen atom, [C3-C8 cycloalkyl group, C1-C6 alkoxy group, C1-C6 alkylcarbonyl group, C1-C6 alkylthio group, C1-C6 alkylsulfinyl group, C1-C6 alkylsulfonyl group, C1-C6 alkylamino group, di (C1-C6 alkyl) amino group, cyano group, C1-C6 alkoxycarbonyl group, C1-C6 alkylaminocarbonyl group, di (C1-C6 alkyl) aminocarbonyl group, (C1-C6) Alkylthio) carbonyl group, carboxyl group, (optionally substituted) benzyloxy group, (optionally substituted) phenoxy group or (optionally substituted) phenyl group optionally substituted] C1 -C8 alkyl group, C3-C8 cycloalkyl group, C1-C6 alkoxycal Alkenyl groups, C1 -C6 alkylaminocarbonyl group, di (C1 -C6 alkyl) aminocarbonyl group, C1 -C6 alkyl thio group, a carboxyl group, or (optionally substituted) phenyl group, or _{R 1} and R ₂ may form a C3-C7 spiro ring together with these bonded carbon atoms,
R ₃ and R ₄ are each a hydrogen atom, a C1-C8 alkyl group (which may be substituted with 1 to 3 halogen atoms which are the same or different, a C3-C8 cycloalkyl group or a C1-C6 alkoxy group) or a C3- Represents a C8 cycloalkyl group, R ₃ and R ₄ together with these bonded carbon atoms may form a C3-C7 spiro ring, or R ₁ , R ₂ , R ₃ and R ₄ may be bonded together You may form a 5-8 membered ring with a carbon atom,
Y is a hydrogen atom, a C1-C6 alkoxycarbonyl group, a carboxyl group, a C2-C6 alkenyl group, [1 to 3 halogen atoms that are the same or different, a C1-C6 alkoxy group, a C2-C6 alkenyloxy group, a C2-C6 An alkynyloxy group, an optionally substituted benzyloxy group, a C1-C6 alkoxycarbonyl group, a carboxyl group, a hydroxyl group or a formyl group] a C1-C10 alkyl group or (1-5 Represents a phenyl group (substituted with the same or different R ₇ ),
R ₇ is a hydrogen atom, [1 to 3 halogen atoms that are the same or different, a C1 to C6 alkoxy group, a hydroxyl group, a C1 to C6 alkylthio group, a C1 to C6 alkylsulfinyl group, a C1 to C6 alkylsulfonyl group, a C1 to C6]. An alkylamino group, a C1-C6 dialkylamino group, a cyano group, or an (optionally substituted) phenoxy-substituted] C1-C6 alkyl group (1-3 halogen atoms, which are the same or different, C1-C6 alkoxy group, optionally substituted with C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxycarbonyl group, C1-C6 alkylcarbonyl group or C3-C8 cycloalkyl group) Group, C2-C6 alkenyl group, C3-C8 cycloalkyloxy group, Is optionally substituted with 1 to 3 different halogen atoms or C1 to C6 alkoxy groups), substituted with 1 to 3 halogen atoms or the same or different C1 to C6 alkoxy groups A C1-C6 alkylsulfinyl group (which may be substituted), a C1-C6 alkylsulfonyl group (which may be substituted with 1 to 3 halogen atoms or C1-C6 alkoxy groups which are the same or different), (substituted) May be substituted with a benzyloxy group, a (C1-C6 alkyl group, a C1-C6 alkylsulfonyl group, a C1-C6 alkylcarbonyl (C1-C6 alkyl) group or a C1-C6 alkylsulfonyl (C1-C6 alkyl) group. Amino group, halogen atom, cyano group, nitro group, C1-C6 alkoxycarbonyl , C3-C8 cycloalkyloxycarbonyl group, carboxyl group, C2-C6 alkenyloxycarbonyl group, C2-C6 alkynyloxycarbonyl group, (optionally substituted) benzyloxycarbonyl group, (optionally substituted) It represents a phenoxycarbonyl group or a C1-C6 alkylcarbonyloxy group. } Isoxazoline derivative or a salt thereof and at least one selected from the following group A: a herbicidal composition.
Group A: sulfonylurea herbicides, pyrimidyl carboxylic acid herbicides, allyloxyphenoxypropionic acid herbicides, triazine herbicides, diphenyl ether herbicides, oxadiazole herbicides, pyrazole herbicides, bicyclooctane Herbicides, amino acid herbicides, organophosphorus herbicides, acid amide herbicides, phenoxy herbicides, carbamate herbicides, phenoxycarboxylic acid herbicides, ACN, indanophane, oxadichromefone, carfentrazone, dithiopyr , Pyraclonyl, phentolazamide, propanyl, penoxthram, bentazone, pentoxazone, benfrate, metamihop, 2 '-(4,6-dimethoxypyrimidin-2-yl) hydroxymethyl-6'-methoxymethyl-1,1-difluoromethanesulfone Nilide, 2- {2-chloro-4-mesyl-3-[(tetrahydrofuran-2-ylmethoxy) methyl] benzoyl} cyclohexane-1,3-dione In this specification, definitions of terms used are shown below. .

  A halogen atom shows a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

  Unless specifically limited, the alkyl group means a linear or branched alkyl group having 1 to 10 carbon atoms, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl. Group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 3,3-dimethylbutyl group, heptyl group or octyl group. .

  The cycloalkyl group indicates a cycloalkyl group having 3 to 8 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.

  The alkoxy group indicates an (alkyl) -O- group in which the alkyl portion has the above meaning, and examples thereof include a methoxy group and an ethoxy group.

Alkylthio group, an alkylsulfinyl group and an alkylsulfonyl group, the alkyl moiety is the meaning of the (alkyl) -S- group, (alkyl) -SO- group, (alkyl) -SO ₂ - represents a group, for example methylthio Group, ethylthio group, methylsulfinyl group, methylsulfonyl group or ethylsulfonyl group.

  The alkenyl group refers to a straight or branched alkenyl group having 2 to 6 carbon atoms, for example, an ethenyl group, a 1-propenyl group, a 2-propenyl group, an isopropenyl group, a 1-butenyl group, and a 2-butenyl group. , 3-butenyl group or 2-pentenyl group.

  The alkynyl group refers to a linear or branched alkynyl group having 2 to 6 carbon atoms, and examples thereof include an ethynyl group, a 2-propynyl group, a 2-butynyl group, and a 3-butynyl group.

  An alkenyloxy group and an alkynyloxy group represent an (alkenyl) -O-group or an (alkynyl) -O-group in which the alkenyl or alkynyl moiety has the above-mentioned meaning, such as a 2-propenyloxy group and a 2-propynyloxy group. Etc.

An alkylamino group and a dialkylamino group indicate an (alkyl) -NH- group or an (alkyl) ₂ N-group in which the alkyl portion has the above meaning, for example, a methylamino group, an ethylamino group, a dimethylamino group, etc. Can be mentioned.

  The alkylcarbonyl group, (alkylthio) carbonyl group, alkoxycarbonyl group, alkylaminocarbonyl group and dialkylaminocarbonyl group are alkyl, alkylthio, alkoxy, alkylamino or dialkylamino moieties as defined above (alkyl) -CO- Group, (alkylthio) -CO- group, (alkoxy) -CO- group, (alkylamino) -CO- group, (dialkylamino) -CO- group, for example, acetyl group, methylthiocarbonyl group, ethoxycarbonyl group, A methoxycarbonyl group, a methylaminocarbonyl group, a dimethylaminocarbonyl group, etc. can be mentioned.

  An alkylaminocarbonylamino group, a dialkylaminocarbonylamino group and an alkoxycarbonylamino group are an (alkylaminocarbonyl) -NH- group wherein the alkylaminocarbonyl, dialkylaminocarbonyl or alkoxycarbonyl moiety has the above meaning, (dialkylaminocarbonyl ) -NH- group and (alkoxycarbonyl) -NH- group, for example, methylaminocarbonylamino group, dimethylaminocarbonylamino group, methoxycarbonylamino group and the like.

  The phenyl group which may be substituted includes a phenyl group having 1 to 5 substituents such as a halogen atom, a C1 to C6 alkyl group or a C1 to C6 alkoxy group on the phenyl ring.

  The phenoxy group which may be substituted includes a phenoxy group having 1 to 5 substituents such as a halogen atom, a C1 to C6 alkyl group or a C1 to C6 alkoxy group on the phenyl ring.

  Examples of the optionally substituted benzyloxy group include a benzyloxy group having 1 to 7 substituents such as a halogen atom, a C1-C6 alkyl group or a C1-C6 alkoxy group on the phenyl ring and at the benzyl position. .

  The phenoxycarbonyl group which may be substituted includes a phenoxycarbonyl group having 1 to 5 substituents such as a halogen atom, a C1 to C6 alkyl group or a C1 to C6 alkoxy group on the phenyl ring.

  In the compound represented by the general formula [I], a salt, when a hydroxyl group, a carboxyl group, an amino group or the like is present in the structure thereof, a salt of these with a metal or an organic base, a mineral acid or an organic acid, and The metal may be an alkali metal such as sodium or potassium, or an alkaline earth metal such as magnesium or calcium, the organic base may be triethylamine or diisopropylamine, and the mineral acid may be Hydrochloric acid or sulfuric acid can be exemplified, and examples of the organic acid include acetic acid, methanesulfonic acid, p-toluenesulfonic acid and the like.

  In Group A, the sulfonylurea herbicides include azimusulfuron, imazosulfuron, ethoxysulfuron, cyclosulfamuron, synosulfuron, halosulfuron methyl, pyrazosulfuron ethyl, bensulfuron methyl and the like.

  A pyrimidylcarboxylic acid herbicide represents bispyribac sodium salt, pyriftalide, pyribenzoxime, pyriminobac-methyl and the like.

  The allyloxyphenoxypropionic acid herbicide represents cihalohop butyl and the like.

  The triazine herbicide represents cimetrine, dimetamethrin, and the like.

  The diphenyl ether herbicide represents bifenox or the like.

  The oxadiazole herbicide represents oxadizason, oxadiargyl and the like.

  Pyrazole herbicides include pyrazoxifene, pyrazolate, benzophenap and the like.

  The bicyclooctane herbicide represents benzobicyclone and the like.

  An amino acid herbicide represents glyphosate and the like.

  Organophosphorus herbicides include butamifos, anilophos and the like.

  The acid amide herbicides include caffentrol, tenyl chlor, butachlor, pretilachlor, mefenacet, etobenzanide, bromobutide and the like.

  The phenoxy herbicide represents naproanilide and the like.

  The carbamate herbicide represents esprocarb, dimethylpiperate, beniocarb, molinate, pilibutycarb and the like.

  The phenoxycarboxylic acid herbicide represents quinclolac, chromeprop, MCPB, and the like.

In the general formula [I], as a preferred compound group, Q represents a group —S (O) _n — (CR ₅ R ₆ ) _m —, n represents 2, m represents 1, R ₅ and R ₆ represents a hydrogen atom, R ₁ and R ₂ represent a C1-C4 alkyl group, R ₃ and R ₄ represent a hydrogen atom, and Y represents (substituted with 1 to 5 identical or different R ₇ And R ₇ represents a hydrogen atom, a C1-C6 alkyl group (which may be substituted with 1 to 3 halogen atoms which are the same or different), and 1 to 3 halogen atoms which are the same or different. Examples thereof include a compound group represented by a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, a C2-C6 alkynyloxy group, a halogen atom, a nitro group, or a cyano group (which may be substituted with an atom).

In the general formula [I], as a more preferable compound group, Q represents a —SO ₂ —CH ₂ — group, R ₁ and R ₂ represent a C1-C2 alkyl group, and R ₃ and R ₄ represent a hydrogen atom. Y represents a phenyl group (substituted with 1 to 4 identical or different R ₇ ), and R ₇ is a hydrogen atom, substituted with 1 to 3 halogen atoms (identical or different). C1-C3 alkyl group, C1-C3 alkoxy group (which may be substituted with 1 to 3 halogen atoms which are the same or different), C2-C4 alkynyloxy group, halogen atom, nitro group or cyano group The compound group represented by these is mentioned.

  The composition of the present invention is generally a compound represented by the above formula [I] per 1 part by weight of at least one compound selected from the group A shown above, depending on the relative activity of each component. 0.001 to 50 parts by weight, preferably 0.001 to 10 parts by weight.

  One active ingredient of the composition of the present invention is a compound represented by the formula [I], which itself has excellent herbicidal activity.

  The composition of the present invention has little phytotoxicity to rice, and in particular, perennial weeds such as Tainubie, Tamagayatsu, Konagi, Azena, etc. that occur in paddy fields, and perennial weeds such as Mitsugayatsuri, Krogwai, Firefly, etc. Can be controlled at low doses over a long period of time.

  Furthermore, wheat, barley, corn, grain sorghum, soybean, cotton, sugar beet, turf, fruit trees, etc. have little phytotoxicity, and various weeds that are problematic in the field, such as barnyardgrass, barnyard grass, green butterfly, hornbill, Johnson grass, hornbill, Perennials such as wild oats such as grass weeds, giant blackbirds, greenfish, white-spotted leaves, leafhoppers, lobsters, broad-leaved weeds of common horned moths, ragweed, morning glory, perennials It exhibits an excellent herbicidal effect over a wide range of growing seasons from before germination of Cyperaceae weeds.

  A typical example of the compound represented by the general formula [I], which is one active ingredient of the composition of the present invention, is a compound selected from the isoxazoline derivatives or salts thereof described in WO01 / 016613, Table 1, Table 2 and Table 3 show typical examples.

  Although the manufacture example of the compound represented by Formula [I] which can be used for this invention composition can be manufactured by the method shown to the following manufacture examples, it is not limited to these.

<Production Example 1>
Preparation of 3-benzylthio-5,5-dimethyl-2-isoxazoline (Compound No. 1) To a solution of 2.8 g (22.5 mmol) of benzyl mercaptan in 50 ml of N, N-dimethylformamide under an atmosphere of nitrogen, anhydrous potassium carbonate 3.2 g (23.2 mmol) and 3.0 g (22.5 mmol) of 3-chloro-5,5-dimethyl-2-isoxazoline were added and stirred at 100 ° C. for 2 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 3-benzylthio-5,5-dimethyl-2-isoxazoline as a yellow oily substance (refractive index n _D ²⁰ = 1.5521). 1 g (yield 62.0%) was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.24-7.39 (5H, m), 4.26 (2H, s), 2.77 (2H, s), 1.40 (6H, s)

<Production Example 2>
Preparation of 5-ethyl-3- (2,6-difluorobenzylsulfinyl) -5-methyl-2-isoxazoline (Compound No. 2) 5-ethyl-3- (2,6-difluorobenzylthio) -5-methyl To a solution of 4.1 g (15.0 mmol) of 2-isoxazoline in 50 ml of chloroform, 4.6 g (purity 70%, 18.8 mmol) of m-chloroperbenzoic acid was added under ice cooling and stirred for 1 hour. The mixture was further stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic phase was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous potassium carbonate solution, water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (solvent hexane-ethyl acetate) to give 5-ethyl-3- (2,6-difluorobenzylsulfinyl) as a white powder (melting point: 30 ° C. or lower). ) -5-methyl-2-isoxazoline (yield 34.8%) was obtained ( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.39-7.28 (1H, m), 7.03-6.94 (2H, m), 4.38 (2H, s), 3.04 (1H, ABq, J = 17.2, Δν = 85.7Hz) +3.12 (1H, s), 1.75 (2H, m), 1.44 (3H, s) +1.41 (3H, s), 0.97 (3H, m)

<Production Example 3>
Preparation of 5-ethyl-3- (2,6-difluorobenzylsulfonyl) -5-methyl-2-isoxazoline (Compound No. 3) 5-ethyl-3- (2,6-difluorobenzylsulfinyl) -5-methyl To a solution of 0.8 g (2.8 mmol) of 2-isoxazoline in 50 ml of chloroform, 1.0 g of m-chloroperbenzoic acid (purity 70%, 4.1 mmol) was added under ice cooling, and the mixture was stirred for 1 hour. The mixture was further stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous potassium carbonate solution, water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (solvent system: hexane-ethyl acetate) to give 5-ethyl-3- (2,6-difluoro) as a white powder (melting point: 64-65 ° C.). 0.6 g (75% yield) of (benzylsulfonyl) -5-methyl-2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.36-7.46 (1H, m), 6.98-7.04 (2H, m), 4.73 (2H, s), 3.04 (2H, ABq, J = 17.2, Δν = 51.1Hz), 1.77 (2H, q), 1.46 (3H, s), 0.97 (3H, t)

<Production Example 4>
Preparation of 3- (2,6-difluorobenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 4) 3- (2,6-difluorobenzylthio) -5,5-dimethyl-2-iso To a solution of 3.9 g (15.2 mmol) of oxazoline in 50 ml of chloroform, 8.5 g (purity 70%, 34.5 mmol) of m-chloroperbenzoic acid was added under ice-cooling and stirred for 1 hour. Stir for hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous potassium carbonate solution, water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was washed with diisopropyl ether, and 3- (2,6-difluorobenzylsulfonyl) -5,5-dimethyl-2-isoxazoline 3 was obtained as a white powder (melting point: 110 to 111 ° C.). 0.4 g (yield 77%) was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.35-7.45 (1H, m), 6.98-7.03 (2H, m), 4.72 (2H, s), 3.06 (2H, s), 1.51 (6H, s)

<Production Example 5>
Preparation of 3- (2,6-difluorobenzylthio) -5,5-dimethyl-2-isoxazoline (Compound No. 5) 5.0 g of 3-methylsulfonyl-5,5-dimethyl-2-isoxazoline (28. 2 mmol) of N, N-dimethylformamide in a 50 ml solution under ice-cooling, sodium hydrosulfide hydrate 4.5 g (purity 70%, 56.1 mmol), anhydrous potassium carbonate 7.8 g (56.4 mmol) Then, 8.7 g (56.5 mmol) of Rongalite was added and stirred for 2 hours. Thereafter, 5.8 g (28.0 mmol) of 2,6-difluorobenzylbenzyl bromide was added, and the mixture was further stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 3- (2,6-difluorobenzylthio) -5,5-dimethyl-2-iso was obtained as a white powder (melting point: 77-80 ° C.). 5.8 g (yield 80%) of oxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.20-7.28 (1H, m), 6.86-6.93 (2H, m), 4.35 (2H, s), 2.81 (2H, s), 1.43 (6H, s)

<Production Example 6>
Preparation of 3-methylsulfonyl-5,5-dimethyl-2-isoxazoline (Compound No. 6) 143.0 g (1.07 mol) of N, N-- 3-chloro-5,5-dimethyl-2-isoxazoline To a 500 ml solution of dimethylformamide, 1000 g (content 15%, 2.14 mol) of an aqueous solution of methyl mercaptan was added dropwise under ice cooling, and then stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 115.0 g (yield 74%) of a crude product of 3-methylthio-5,5-dimethyl-2-isoxazoline. Then, 115.0 g (corresponding to 741.2 mmol) of a crude product of 3-methylthio-5,5-dimethyl-2-isoxazoline was dissolved in 1 l of chloroform, and m-chloroperbenzoic acid (purity 70%) was cooled with ice. ) 392.0 g (1.59 mol) was added and stirred for 1 hour. Thereafter, the mixture was further stirred at room temperature for 12 hours. After completion of the reaction, the precipitated m-chlorobenzoic acid was filtered off, and the filtrate was washed successively with aqueous sodium hydrogen sulfite solution, water, aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was washed with diisopropyl ether, and 77.6 g of 3-methylsulfonyl-5,5-dimethyl-2-isoxazoline (yield: 59.84 ° C.) as a white powder (melting point: 82 to 84 ° C.). 1%) was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 3.26 (3H, s), 3.12 (2H, s), 1.51 (6H, s)

<Production Example 7>
Production of 3- (5-chloro-2-difluoromethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 12) (1) Production of 5-chloro-2-difluoromethoxytoluene 4-Chloro- To a solution of 7.1 g (50.0 mmol) of 2-methylphenol in 100 ml of N, N-dimethylformamide, 10.4 g (75.0 mmol) of anhydrous potassium carbonate was added. While stirring the reaction solution, chlorodifluoromethane was introduced at 50 ° C. After confirming the disappearance of the raw materials, the introduction of chlorodifluoromethane was stopped and the reaction solution was cooled to room temperature. The reaction solution was then poured into water and extracted with diisopropyl ether. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 5.4 g of colorless transparent crystals of 5-chloro-2-difluoromethoxytoluene (yield 56.6%).
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.21 (1H, d), 7.15 (1H, q), 7.01 (1H, d), 6.47 (1H, t, J = 73.8 Hz), 2.26 (3H, s)

(2) Production of 5-chloro-2-difluoromethoxybenzyl bromide N-bromosuccinimide 2. is prepared by adding 2.4 g (12.5 mmol) of 5-chloro-2-difluoromethoxytoluene in 30 ml of carbon tetrachloride. 2 g (12.5 mmol) and 2,2′-azobis (isobutyronitrile) 0.2 g (1.3 mmol) were added and heated under reflux for 2 hours under light irradiation. After completion of the reaction, the reaction mixture was cooled to room temperature and insoluble matters were filtered off. The solvent was distilled off under reduced pressure to obtain a crude product of 5-chloro-2-difluoromethoxybenzyl bromide.

(3) Preparation of 3- (5-chloro-2-difluoromethoxybenzylthio) -5,5-dimethyl-2-isoxazoline 1.9 g of 5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline (10 0.0 mmol) in N, N-dimethylformamide (30 ml) was added sodium hydrosulfide hydrate 1.6 g (purity 70%, 20.0 mmol) and stirred for 1 hour. Thereafter, 1.4 g (10.0 mmol) of anhydrous potassium carbonate, 1.6 g (10.0 mmol) of Rongalite, and a crude product of 5-chloro-2-difluoromethoxybenzyl bromide obtained in the above (2) (12 0.5 mmol), and the mixture was further stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2.4 g of 3- (5-chloro-2-difluoromethoxybenzylthio) -5,5-dimethyl-2-isoxazoline (yield). 74.5%).

(4) Production of 3- (5-chloro-2-difluoromethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 12) 3- (5-Chloro-2-difluoromethoxybenzylthio)- To a solution of 2.4 g (7.5 mmol) of 5,5-dimethyl-2-isoxazoline in 15 ml of chloroform, 4.6 g (purity 70%, 18.6 mmol) of m-chloroperbenzoic acid was added under ice cooling. And stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the precipitated crystals were washed with n-hexane to give 3- (5-chloro-2-difluoromethoxybenzylsulfonyl) -5,5-dimethyl as white crystals (melting point: 53 to 54 ° C.). 1.9 g (yield 72.2%) of 2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.51 (1H, d), 7.39 (1H, q), 7.19 (1H, d), 6.52 (1H, t, J = 73.2 Hz), 4.69 (2H, s), 3.02 (2H, s), 1.49 (6H, s)

<Production Example 8>
Production of 3- (2-difluoromethoxy-5-methylbenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 16) (1) Production of 2-hydroxy-5-methylbenzoic acid methyl ester 5- To a solution of 25.0 g (164.3 mmol) of methyl salicylic acid in 200 ml of N, N-dimethylformamide was added 11.9 g (86.3 mmol) of anhydrous potassium carbonate and 24.5 g (172.5 mmol) of methyl iodide at room temperature. The mixture was stirred overnight. The reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed successively with water and brine and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 27.3 g (yield 100%) of 2-hydroxy-5-methylbenzoic acid methyl ester.

(2) Preparation of 2-difluoromethoxy-5-methylbenzoic acid methyl ester To a solution of 27.3 g (164.3 mmol) of 2-hydroxy-5-methylbenzoic acid methyl ester in 200 ml of N, N-dimethylformamide was added anhydrous carbonic acid. 34.0 g (246.5 mmol) potassium was added at room temperature. While stirring the reaction solution, chlorodifluoromethane was introduced at 100 ° C. After confirming disappearance of the raw materials (after about 4 hours), the introduction of chlorodifluoromethane was stopped and the reaction solution was cooled to room temperature. The reaction solution was poured into water and extracted with ethyl acetate, and the resulting organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 25.3 g (yield 71.3%) of 2-difluoromethoxy-5-methylbenzoic acid methyl ester as a yellow liquid.

(3) Preparation of 2-difluoromethoxy-5-methylphenylmethanol 3.2 g of 2-difluoromethoxy-5-methylbenzoic acid methyl ester in a solution of 0.6 g (15 mmol) of lithium aluminum hydride in 30 ml of tetrahydrofuran at room temperature A solution of (15 mmol) in tetrahydrofuran was added dropwise. After confirming the completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction solution, the solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product of 2-difluoromethoxy-5-methylphenylmethanol.

(4) Preparation of 2-difluoromethoxy-5-methylbenzyl chloride To a 30 ml chloroform solution of the crude product (corresponding to 15 mmol) of 2-difluoromethoxy-5-methylphenylmethanol obtained in (3) above at room temperature. 5.4 g (45 mmol) of thionyl chloride was added and stirred for 3 hours. The solvent was distilled off under reduced pressure to obtain a crude product of 2-difluoromethoxy-5-methylbenzyl chloride.

(5) Production of 3- (2-difluoromethoxy-5-methylbenzylthio) -5,5-dimethyl-2-isoxazoline 1.0 g of 5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline (5 Mmol) in N, N-dimethylformamide (20 ml) was added sodium hydrosulfide hydrate (0.8 g, purity 70%, 10 mmol) and stirred for 1 hour. Thereafter, 0.7 g (5 mmol) of anhydrous potassium carbonate, 0.7 g (5 mmol) of Rongalite and a crude product of 2-difluoromethoxy-5-methylbenzyl chloride obtained in (4) (corresponding to 15 mmol) were added. The mixture was further stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 1.5 g of 3- (2-difluoromethoxy-5-methylbenzylthio) -5,5-dimethyl-2-isoxazoline (yield). : Quantitative).

(6) Preparation of 3- (2-difluoromethoxy-5-methylbenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 16) 3- (2-Difluoromethoxy-5-methylbenzylthio)- To a solution of 1.5 g (5.0 mmol) of 5,5-dimethyl-2-isoxazoline in 30 ml of chloroform, 3.1 g (purity 70%, 12.5 mmol) of m-chloroperbenzoic acid was added under ice cooling. And stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 3- (2-difluoromethoxy-5-methylbenzylsulfonyl) -5,5-dimethyl of pale yellow crystals (melting point 71-73 ° C.). 2-isoxazoline 1.1g (yield 66.0%) was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.31 (1H, d), 7.21 (1H, q), 7.11 (1H, d), 6.50 (1H, t, J = 73.9 Hz), 4.67 (2H, s), 2.99 (2H, s), 2.36 (3H, s), 1.47 (6H, s)

<Production Example 9>
Preparation of 3- (2-difluoromethoxy-5-methoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 17) (1) Preparation of 2-hydroxy-5-methoxybenzoic acid methyl ester 5- To a solution of 25.0 g (148.7 mmol) of methoxysalicylic acid in 200 ml of N, N-dimethylformamide was added 10.8 g (78.1 mmol) of anhydrous potassium carbonate and 21.1 g (148.7 mmol) of methyl iodide at room temperature. The mixture was stirred overnight. The reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 14.6 g of 2-hydroxy-5-methoxybenzoic acid methyl ester (yield 53.9%).

(2) Preparation of 2-difluoromethoxy-5-methoxybenzoic acid methyl ester To a solution of 14.6 g (80.1 mmol) of 2-hydroxy-5-methoxybenzoic acid methyl ester in 100 ml of N, N-dimethylformamide at room temperature 13.3 g (96.2 mmol) of anhydrous potassium carbonate was added. While stirring the reaction solution, chlorodifluoromethane was introduced at 100 ° C. After confirming disappearance of the raw materials (after about 6 hours), the introduction of chlorodifluoromethane was stopped and the reaction solution was cooled to room temperature. The reaction solution was then poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 3.5 g (yield 18.8%) of 2-difluoromethoxy-5-methoxybenzoic acid methyl ester as a yellow liquid.

(3) Production of 2-difluoromethoxy-5-methoxyphenylmethanol 2-difluoromethoxy-5-methoxybenzoic acid methyl ester 3 in a solution of 0.6 g (15.1 mmol) of lithium aluminum hydride in 30 ml of tetrahydrofuran at room temperature A solution of 0.5 g (15.1 mmol) in 10 ml of tetrahydrofuran was added dropwise. After confirming the completion of the reaction, a saturated aqueous ammonium chloride solution was added to the reaction solution, and the solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 2-difluoromethoxy-5-methoxyphenylmethanol.

(4) Production of 2-difluoromethoxy-5-methoxybenzyl chloride To a 30 ml chloroform solution of the crude product (corresponding to 15.1 mmol) of 2-difluoromethoxy-5-methoxyphenylmethanol obtained in (3) above. At room temperature, 5.4 g (45.3 mmol) of thionyl chloride was added and stirred for 3 hours. Thereafter, the solvent was distilled off under reduced pressure to obtain a crude product of 2-difluoromethoxy-5-methoxybenzyl chloride.

(5) Preparation of 3- (2-difluoromethoxy-5-methoxybenzylthio) -5,5-dimethyl-2-isoxazoline 2.9 g of 5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline (15 .1 mmol) in 30 ml of N, N-dimethylformamide was added 2.4 g of sodium hydrosulfide hydrate (purity 70%, 30.2 mmol) and stirred for 1 hour. Thereafter, 2.08 g (15.1 mmol) of anhydrous potassium carbonate and a crude product (corresponding to 15.1 mmol) of 2-difluoromethoxy-5-methoxybenzyl chloride obtained in (4) were added. Stir for hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2.3 g of 3- (2-difluoromethoxy-5-methoxybenzylthio) -5,5-dimethyl-2-isoxazoline (yield) 48.0%).

(6) Production of 3- (2-difluoromethoxy-5-methoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 17) 3- (2-Difluoromethoxy-5-methoxybenzylthio)- To a solution of 0.5 g (1.6 mmol) of 5,5-dimethyl-2-isoxazoline in 10 ml of chloroform was added 1.0 g of m-chloroperbenzoic acid (purity 70%, 3.8 mmol) under ice cooling. And stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was washed with n-hexane to give 3- (2-difluoromethoxy-5-methoxybenzylsulfonyl) -5,5-dimethyl-2 as white crystals (melting point: 70 to 71 ° C.). -0.4 g (yield 63.4%) of isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.17 (1H, d), 7.04 (1H, d), 6.93 (1H, q), 6.47 (1H, t, J = 74.1 Hz), 4.68 (2H, s), 3.81 (3H, s), 2.99 (2H, s), 1.47 (6H, s)

<Production Example 10>
Production of 3- [2,3-bis (difluoromethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (Compound No. 18) (1) Production of 2,3-bis (difluoromethoxy) toluene 3- 12.3 g (89.0 mmol) of anhydrous potassium carbonate was added to a solution of 5.0 g (40.3 mmol) of methylcatechol in 100 ml of N, N-dimethylformamide. While stirring the reaction solution, chlorodifluoromethane was introduced at room temperature. Stir at 70 ° C. for 2 hours. After confirming the disappearance of the raw materials, the introduction of chlorodifluoromethane was stopped and the reaction solution was cooled to room temperature. The reaction solution was then poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 0.82 g (yield 9.1%) of 2,3-bis (difluoromethoxy) toluene.
( ¹ H-NMR value (CDCl ₃ / TMS) δ (ppm)): 7.17-7.09 (3H, m), 6.52 (1H, t, J = 75.0 Hz), 6.50 (1H, t, J = 73.6 Hz) , 2.35 (3H, s)

(2) Preparation of 2,3-bis (difluoromethoxy) benzyl bromide N-bromosuccinimide in a solution of 0.82 g (3.66 mmol) of 2,3-bis (difluoromethoxy) toluene in 20 ml of carbon tetrachloride 0.68 g (3.82 mmol) and 2,6'-azobis (isobutyronitrile) 0.06 g (0.37 mmol) were added, and the reaction solution was refluxed for 3 hours by light irradiation. After completion of the reaction, the reaction mixture was cooled to room temperature and insoluble matters were filtered off. The solvent was distilled off under reduced pressure to obtain a crude product of 2,3-bis (difluoromethoxy) benzyl bromide.

(3) Preparation of 3- [2,3-bis (difluoromethoxy) benzylthio] -5,5-dimethyl-2-isoxazoline 0.73 g of 3,5-dimethyl-3-ethylsulfonyl-2-isoxazoline (3 0.62 g of sodium hydrosulfide hydrate (purity 70%, 7.49 mmol) was added to 30 ml of N, N-dimethylformamide solution of .82 mmol) and stirred for 2 hours. Thereafter, 0.53 g (3.82 mmol) of anhydrous potassium carbonate, 0.59 g (3.82 mmol) of Rongalite, and 2) of the crude product (3.66 mmol) of 2,3-bisdifluoromethoxybenzyl bromide obtained from 2) were obtained. (Equivalent) in 20 ml of N, N-dimethylformamide was added and further stirred at room temperature for 11 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 0.87 g (yield) of 3- [2,3-bis (difluoromethoxy) benzylthio] -5,5-dimethyl-2-isoxazoline. 67.3%).
( ¹ H-NMR value (CDCl _{3 /} TMS) δ (ppm)): 7.46 (1H, dd), 7.24-7.16 (2H, m), 6.60 (1H, t, J = 74.3 Hz), 6.52 (1H, t, J = 73.2Hz), 4.35 (2H, s), 2.78 (2H, s), 1.41 (6H, s)

(4) Preparation of 3- [2,3-bis (difluoromethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (Compound No. 18) 3- (2,3-bis (difluoromethoxy) benzylthio) To a solution of 0.87 g (2.46 mmol) of -5,5-dimethyl-2-isoxazoline in 30 ml of chloroform was added 1.52 g of m-chloroperbenzoic acid (purity 70%, 6.17 mmol) under ice cooling. The mixture was further stirred at room temperature for 14 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the precipitated crystals were washed with n-hexane, and white crystals (melting point: 84 to 86 ° C.) 3- [2,3-bis (difluoromethoxy) benzylsulfonyl] -5,5-dimethyl. 0.84 g (yield 88.5%) of 2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS) δ (ppm)): 7.50-7.46 (1H, m), 7.34-7.32 (2H, m), 6.60 (1H, t, J = 73.6 Hz), 6.52 ( 1H, t, J = 72.8Hz), 4.74 (2H, s), 3.06 (2H, s), 1.49 (6H, s)

<Production Example 11>
Production of 3- (4-chloro-2-difluoromethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 19) (1) Production of 4-chlorosalicylic acid methyl ester 4-chlorosalicylic acid 5.0 g 1 ml of sulfuric acid was added to a solution of (29.0 mmol) in 50 ml of ethanol. The reaction solution was refluxed for 8 hours. After completion of the reaction, ethanol was distilled off under reduced pressure, and the residue was poured into water and extracted with ethyl acetate. The obtained organic layer was washed successively with water, aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 3.05 g (52% yield) of 4-chlorosalicylic acid methyl ester.

(2) Preparation of 4-chloro-2-difluoromethoxybenzoic acid methyl ester 1.71 g of potassium hydroxide powdered in 30 ml of tetrahydrofuran solution of 3.05 g (15.0 mmol) of 4-chlorosalicylic acid methyl ester 0 mmol) and 0.10 g (0.31 mmol) of tetrabutylammonium bromide were added. Chlorodifluoromethane was introduced at room temperature while stirring the reaction solution. After confirming the disappearance of the raw materials, the introduction was stopped. The reaction solution was kept stirring at room temperature overnight. Insolubles were filtered off, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography to obtain 1.33 g of 4-chloro-2-difluoromethoxybenzoic acid methyl ester (yield 35%).
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.86 (1H, d), 7.29 (2H, m), 6.57 (1H, t, J = 74.2 Hz), 4.38 (2H, q), 1.38 (3H, t)

(3) Production of 4-chloro-2-difluoromethoxyphenylmethanol 4-chloro-2-difluoromethoxybenzoic acid methyl ester 1 in a solution of 0.2 g (5.3 mmol) of lithium aluminum hydride in 20 ml of tetrahydrofuran at room temperature A solution of 0.33 g (5.3 mmol) in 5 ml of tetrahydrofuran was added dropwise. After confirming the completion of the reaction, a saturated aqueous ammonium chloride solution was added to the reaction solution. The solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 4-chloro-2-difluoromethoxyphenylmethanol.

(4) Production of 4-chloro-2-difluoromethoxybenzyl chloride To a dichloromethane solution of the crude product of 4-chloro-2-difluoromethoxyphenylmethanol obtained in (3) (corresponding to 5.3 mmol) at room temperature. Then, 0.63 g (5.3 mmol) of thionyl chloride was added and stirred for 2 hours. Thereafter, the solvent was distilled off under reduced pressure to obtain a crude product of 4-chloro-2-difluoromethoxybenzyl chloride.

(5) Production of 3- (4-chloro-2-difluoromethoxybenzidithio) -5,5-dimethyl-2-isoxazoline 5,9-dimethyl-3-ethylsulfonyl-2-isoxazoline 0.89 g (4 0.75 g (purity 70%, 9.3 mmol) was added to a 15 ml solution of N, N-dimethylformamide (.7 mmol) and stirred for 1 hour. Thereafter, 0.65 g (4.7 mmol) of anhydrous potassium carbonate, 0.72 g (4.7 mmol) of Rongalite and 4) obtained as a crude product of 4-chloro-2-difluoromethoxybenzyl chloride (5.3) (Equivalent to mmol) was added, and the mixture was further stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel chromatography to obtain 0.85 g (yield 57) of 3- (4-chloro-2-difluoromethoxybenzylthio) -5,5-dimethyl-2-isoxazoline. %).
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.47 (1H, d), 7.16 (2H, m), 6.55 (1H, t, J = 73.1 Hz), 4.25 (2H, s), 2.75 (2H, s), 1.40 (6H, s)

(6) Preparation of 3- (4-chloro-2-difluoromethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 19) 3- (4-Chloro-2-difluoromethoxybenzylthio)- 1.63 g (purity 70%, 6.6 mmol) of m-chloroperbenzoic acid was added to a solution of 0.85 g (2.6 mmol) of 5,5-dimethyl-2-isoxazoline in 20 ml of chloroform under ice cooling. And stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and 0.80 g (yield) of 3- (4-chloro-2-difluoromethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline as white crystals (melting point: 80 to 82 ° C.) 86%).
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.47 (1H, d), 7.28 (2H, m), 6.54 (1H, t, J = 73.1 Hz), 4.70 (2H, s), 3.02 (2H, s), 1.48 (6H, s)

<Production Example 12>
Production of 2- (5,5-dimethylisoxazolin-3-ylsulfonylmethyl) -3-fluorobenzonitrile (Compound No. 22) (1) Production of 3-fluoro-2-methylbenzoic acid methyl ester 3-Fluoro- To a solution of 4.8 g (31.1 mmol) of 2-methylbenzoic acid in 50 ml of N, N-dimethylformamide, 4.3 g (31.1 mmol) of anhydrous potassium carbonate and 4.4 g (31.1 mmol) of methyl iodide at room temperature. Mmol) and stirred overnight. After confirming the completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 5.2 g (yield 99.4%) of 3-fluoro-2-methylbenzoic acid methyl ester.

(2) Preparation of 2-bromomethyl-3-fluorobenzoic acid methyl ester To a solution of 8.5 g (50.5 mmol) of 3-fluoro-2-methylbenzoic acid methyl ester in 100 ml of carbon tetrachloride at room temperature 9.5 g (53.1 mmol) of acid imide and 0.9 g (5.3 mmol) of 2,2′-azobis (isobutyronitrile) were added. The reaction solution was refluxed for 2.5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and insoluble matters were filtered off. The solvent was distilled off under reduced pressure to obtain a crude product of 2-bromomethyl-3-fluorobenzoic acid methyl ester.

(3) Preparation of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) 3-fluorobenzoic acid methyl ester 9.6 g (50 mmol) of 5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline To 100 ml of N, N-dimethylformamide solution, 8.0 g of sodium hydrosulfide hydrate (purity 70%, 100 mmol) was added and stirred for 1 hour. Thereafter, 6.9 g (50 mmol) of anhydrous potassium carbonate under ice-cooling, 7.9 g (50 mmol) of Rongalite, and a crude product of 2-bromomethyl-3-fluorobenzoic acid methyl ester obtained in (4) (50. 5 mmol equivalent) was added, and the mixture was further stirred at room temperature for 3 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography, and 7.3 g of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzoic acid methyl ester (yield 49.9). %).
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.72 (1H, d), 7.37-7.21 (2H, m), 4.69 (2H, s), 3.94 (3H, s), 2.78 (2H , s), 1.40 (6H, s)

(4) Preparation of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzoic acid 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzoic acid methyl ester 14 10 ml of an aqueous solution in which 2.3 g (57.7 mmol) of sodium hydroxide was dissolved at room temperature was added to a solution of .3 g (48.1 mmol) in 100 ml of tetrahydrofuran and stirred overnight. After confirming the completion of the reaction, the reaction solution was poured into water, the pH was adjusted to 4, and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 10.6 g (yield 77.9%) of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzoic acid.

(5) Preparation of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzamide 0.85 g of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzoic acid ( (3.0 mmol) in 10 ml of tetrahydrofuran was added 0.73 g (4.5 mmol) of N, N′-carbonyldiimidazole at room temperature and stirred for 1 hour. Further, 10 ml of 28% aqueous ammonia was added to the reaction solution and stirred overnight. After confirming the completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 0.84 g (yield 99.3%) of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzamide.

(6) Preparation of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzonitrile 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzamide 0.84 g ( 2.98 mmol) of 1,4-dioxane in 10 ml was added 0.47 g (5.95 mmol) of pyridine at room temperature, 0.75 g (3.57 mmol) of trifluoroacetic anhydride was added under ice cooling, The mixture was further stirred at room temperature for 4 hours. After confirming the completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography, and 0.64 g (yield: 81) of 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3-fluorobenzonitrile as a white powder. 0.0%).

(7) Preparation of 2- (5,5-dimethylisoxazolin-3-ylsulfonylmethyl) -3-fluorobenzonitrile (Compound No. 22) 2- (5,5-dimethylisoxazolin-3-ylthiomethyl) -3 -To a solution of 0.64 g (2.42 mmol) of fluorobenzonitrile in 20 ml of chloroform, 1.49 g (purity 70%, 6.05 mmol) of m-chloroperbenzoic acid was added under ice cooling, and the mixture was stirred at room temperature for 20 hours. did. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and 0.51 g of 2- (5,5-dimethylisoxazolin-3-ylsulfonylmethyl) -3-fluorobenzonitrile as a white crystal (melting point: 112 to 114 ° C.) (yield 71.114). 1%) was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.61-7.41 (3H, m), 4.89 (2H, s), 3.16 (2H, s), 1.54 (6H, s)

<Production Example 13>
Preparation of 3- [2,3-dichloro-6- (2,2,2-trifluoroethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (Compound No. 31) (1) 3,4- Preparation of dichloro-2-hydroxymethylphenol 10.0 g (61.0 mmol) of 3,4-dichlorophenol and 18.4 g (610.0 mmol) of paraformaldehyde were suspended in 50 ml of water, and 25 mg of sodium hydroxide was added thereto. A 49% aqueous solution (310.0 mmol) was added. The reaction solution was stirred at 60 ° C. for 12 hours. The reaction solution was cooled to room temperature, then poured into water, acidified with aqueous citric acid solution, and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2.5 g (yield 21%) of 3,4-dichloro-2-hydroxymethylphenol as white crystals.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 8.42 (1H, s), 7.25 (1H, d), 6.75 (1H, d), 5.15 (2H, s), 2.58 (1H, s )

(2) Preparation of [2,3-dichloro-6- (2,2,2-trifluoroethoxy) phenyl] methanol 1.0 g (5.2 mmol) N of 3,4-dichloro-2-hydroxymethylphenol , N-dimethylformamide 20 ml solution was added anhydrous potassium carbonate 0.72 g (5.2 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate 1.21 g (5.2 mmol). The reaction solution was stirred overnight at room temperature. After confirming the disappearance of the raw materials, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain [2,3-dichloro-6- (2,2,2-trifluoroethoxy) phenyl] methanol.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.41 (1H, d), 6.78 (1H, d), 4.92 (2H, s), 4.41 (2H, q)

(3) Preparation of 2,3-dichloro-6- (2,2,2-trifluoroethoxy) benzyl bromide [2,3-dichloro-6- (2,2,2-trifluoroethoxy) phenyl] methanol 1 To a solution of .43 g (corresponding to 5.2 mmol) in 20 ml of diethyl ether was added 0.71 g (2.6 mmol) of phosphorus tribromide and stirred for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with diethyl ether. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 2,3-dichloro-6- (2,2,2-trifluoroethoxy) benzyl bromide.

(4) Preparation of 3- [2,3-dichloro-6- (2,2,2-trifluoroethoxy) benzylthio] -5,5-dimethyl-2-isoxazoline 5,5-dimethyl-3-ethylsulfonyl To a solution of 1.00 g (5.2 mmol) of 2-isoxazoline in 30 ml of N, N-dimethylformamide, 0.84 g (purity 70%, 10.0 mmol) of sodium hydrosulfide hydrate was added and stirred for 2 hours. . Thereafter, 0.72 g (5.2 mmol) of anhydrous potassium carbonate, 0.80 g (5.2 mmol) of Rongalite (CH ₂ (OH) SO ₂ Na.2H ₂ O) and 2,3 obtained in (3) A solution of a crude product of dichloro-6- (2,2,2-trifluoroethoxy) benzyl bromide (corresponding to 5.2 mmol) in 20 ml of N, N-dimethylformamide was added, and the mixture was further stirred at room temperature for 11 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 3- [2,3-dichloro-6- (2,2,2-trifluoroethoxy)] benzylthio] -5,5-dimethyl. 0.70 g (34% yield) of 2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl _{3 /} TMS) δ (ppm)): 7.38 (1H, dd), 6.76 (1H, d), 4.55 (2H, s), 4.40 (2H, q), 2.82 (2H, s), 1.43 (6H, s)

(5) Production of 3- [2,3-dichloro-6- (2,2,2-trifluoroethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (Compound No. 31) 3- [2 , 3-Dichloro-6- (2,2,2-trifluoroethoxy)] benzylthio] -5,5-dimethyl-2-isoxazoline in a 15 ml chloroform solution under ice-cooling. M-chloroperbenzoic acid (1.11 g, purity 70%, 4.5 mmol) was added, and the mixture was stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the precipitated crystals were washed with n-hexane to give 3- [2,3-dichloro-6- (2,2,2-trifluoro) as white crystals (melting point: 135 to 137 ° C.). Ethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (0.62 g, yield 82%) was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.51 (1H, d), 6.87 (1H, d), 5.06 (2H, s), 4.45 (2H, q), 3.08 (2H, s ), 1.52 (6H, s)

<Production Example 14>
Preparation of 3- [2,3-dichloro-6- (2-propynyloxy) benzylthio] -5,5-dimethyl-2-isoxazoline (Compound No. 33) (1) [2,3-Dichloro-6- ( Preparation of 2-propynyloxy) phenyl] methanol In a solution of 1.0 g (5.2 mmol) of 3,4-dichloro-2-hydroxymethylphenol in 20 ml of N, N-dimethylformamide, 0.72 g (5 0.2 mmol) and 0.62 g (5.2 mmol) of 3-bromopropyne. The reaction solution was stirred overnight at room temperature. After confirming the disappearance of the raw materials, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain [2,3-dichloro-6- (2-propynyloxy) phenyl] methanol.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.38 (1H, d), 6.92 (1H, d), 4.90 (2H, s), 4.76 (2H, d), 2.55 (1H, t ), 2.27 (1H, s)

(2) Preparation of 2,3-dichloro-6- (2-propynyloxy) benzyl bromide 1.20 g (equivalent to 5.2 mmol) of [2,3-dichloro-6- (2-propynyloxy) phenyl] methanol To 20 ml of diethyl ether, 0.71 g (2.6 mmol) of phosphorus tribromide was added and stirred for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with diethyl ether. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 2,3-dichloro-6- (2-propynyloxy) benzyl bromide.

(3) Preparation of 3- [2,3-dichloro-6- (2-propynyloxy) benzylthio] -5,5-dimethyl-2-isoxazoline 5,5-Dimethyl-3-ethylsulfonyl-2-isoxazoline To a solution of 1.00 g (5.2 mmol) of N, N-dimethylformamide in 30 ml was added sodium hydrosulfide hydrate 0.84 g (purity 70%, 10.0 mmol) and stirred for 2 hours. Thereafter, 0.72 g (5.2 mmol) of anhydrous potassium carbonate, 0.80 g (5.2 mmol) of Rongalite (CH ₂ (OH) SO ₂ Na · 2H ₂ O) and 2,3 obtained in (2) A solution of a crude product of dichloro-6- (2-propynyloxy) benzyl bromide (corresponding to 5.2 mmol) in 20 ml of N, N-dimethylformamide was added, and the mixture was further stirred at room temperature for 11 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 3- [2,3-dichloro-6- (2-propynyloxy) benzylthio] -5,5-dimethyl-2-isoxazoline 0 Obtained .81 g (yield 46%).
( ¹ H-NMR value (CDCl _{3 /} TMS) δ (ppm)): 7.38 (1H, d), 6.93 (1H, d), 4.76 (2H, d), 4.54 (2H, s), 2.83 (2H, s), 1.43 (6H, s)

(4) Preparation of 3- [2,3-dichloro-6- (2-propynyloxy) benzylthio] -5,5-dimethyl-2-isoxazoline (Compound No. 33) 3- [2,3-dichloro-6 To a solution of 0.81 g (2.4 mmol) of-(2-propynyloxy) benzylthio] -5,5-dimethyl-2-isoxazoline in 15 ml of chloroform, 1.45 g (purity) of m-chloroperbenzoic acid under ice-cooling. 70%, 5.9 mmol) was added and stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the precipitated crystals were washed with n-hexane, and white crystals (melting point 113 to 115 ° C.) 3- [2,3-dichloro-6- (2-propynyloxy) benzylthio]- 0.67 g (yield 75%) of 5,5-dimethyl-2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.47 (1H, d), 7.02 (1H, d), 5.03 (2H s), 4.77 (2H, d), 3.05 (2H, s) , 2.56 (1H, s), 1.50 (6H, s)

<Production Example 15>
Production of 3- [2,3-dichloro-6- (2,2-difluoroethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (Compound No. 34) (1) Methanesulfonic acid 2,2- Preparation of difluoroethyl To a solution of 0.5 g (6.1 mmol) of 2,2-difluoroethanol and 0.68 g (6.7 mmol) of triethylamine in 15 ml of dichloromethane, 0.77 g (6.7) of methanesulfonyl chloride was added under ice cooling. Mmol) in dichloromethane was added dropwise. After completion of dropping, the reaction solution was stirred at 10 ° C. or lower for 1 hour. The reaction solution was poured into water and extracted with dichloromethane. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 2,2-difluoroethyl methanesulfonate.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 6.01 (1H, tt, J = 3.68, J = 54.59), 4.38 (2H, tt, J = 3.92, J = 13.19), 3.12 (2H , s)

(2) Production of [2,3-dichloro-6- (2,2-difluoroethoxy) phenyl] methanol 1.0 g (5.2 mmol) of 3,4-dichloro-2-hydroxymethylphenol N, N- In 20 ml of dimethylformamide solution, 0.72 g (5.2 mmol) of anhydrous potassium carbonate and 0.98 g (corresponding to 6.1 mmol) of 2,2-difluoroethyl methanesulfonate obtained in (1) were added. The reaction solution was stirred at 70 ° C. for 18 hours. After confirming the disappearance of the raw materials, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of [2,3-dichloro-6- (2,2-difluoroethoxy) phenyl] methanol.

(3) Production of 2,3-dichloro-6- (2,2-difluoroethoxy) benzyl bromide [2,3-dichloro-6- (2,2-difluoroethoxy) phenyl] methanol 1.57 g (6.1 0.83 g (3.1 mmol) of phosphorous tribromide was added to 20 ml of diethyl ether in a solution of 20 ml of diethyl ether and stirred for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with diethyl ether. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 2,3-dichloro-6- (2,2-difluoroethoxy) benzyl bromide.

(4) Production of 3- [2,3-dichloro-6- (2,2-difluoroethoxy) benzylthio] -5,5-dimethyl-2-isoxazoline 5,5-dimethyl-3-ethylsulfonyl-2- To a solution of 1.17 g (6.1 mmol) of isoxazoline in 30 ml of N, N-dimethylformamide was added 0.98 g (purity 70%, 12.0 mmol) of sodium hydrosulfide hydrate and stirred for 2 hours. Thereafter, 0.84 g (6.1 mmol) of anhydrous potassium carbonate, 0.94 g (6.1 mmol) of Rongalite and 2,3-dichloro-6- (2,2-difluoroethoxy) obtained in the above (3) A solution of crude benzyl bromide (corresponding to 6.1 mmol) in 20 ml of N, N-dimethylformamide was added, and the mixture was further stirred at room temperature for 11 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography, and 3- [2,3-dichloro-6- (2,2-difluoroethoxy)] benzylthio] -5,5-dimethyl-2- 0.40 g (18% yield) of isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.38 (1H, d), 6.76 (1H, d), 6.15 (1H, tt, J = 4.02, J = 54.88), 4.55 (1H, s), 4.22 (2H, tt, J = 4.02, J = 12.62), 2.81 (1H, s), 1.43 (6H, s)

(5) Production of 3- [2,3-dichloro-6- (2,2-difluoroethoxy) benzylsulfonyl] -5,5-dimethyl-2-isoxazoline (Compound No. 34) 3- [2,3- To a solution of 0.40 g (1.1 mmol) of dichloro-6- (2,2-difluoroethoxy)] benzylthio] -5,5-dimethyl-2-isoxazoline in 15 ml of chloroform was added m-chloroperbenzoic acid under ice-cooling. 0.67 g of acid (purity 70%, 2.7 mmol) was added, and the mixture was stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the precipitated crystals were washed with n-hexane, and white crystals (melting point: 118 to 120 ° C.) 3- [2,3-dichloro-6- (2,2-difluoroethoxy) benzyl 0.41 g (95% yield) of sulfonyl] -5,5-dimethyl-2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.48 (1H, s), 6.85 (1H, d), 6.16 (1H, tt, J = 4.21, J = 55.06), 5.05 (1H, s), 4.25 (2H, tt, J = 4.20, J = 12.83), 2.81 (1H, s), 1.43 (6H, s)

<Production Example 16>
Production of 3- (2,5-dichloro-4-ethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 54) (1) Production of 2,5-dichloro-4-hydroxymethylphenol 2 , 5-dichlorophenol 5.0 g (31.0 mmol) and paraformaldehyde 9.21 g (310,0 mmol) were suspended in 30 ml of water, and 25 g (150.0 mmol) of 25% aqueous sodium hydroxide solution was added thereto. It was. The reaction solution was stirred at 70 ° C. for 12 hours. The reaction solution was cooled to room temperature, then poured into water, acidified with aqueous citric acid solution, and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2.45 g (yield 41%) of 2,5-dichloro-4-hydroxymethylphenol as white crystals.
( ¹ H-NMR value (DMSO-d ₆ δ (ppm)): 10.51 (1H, s), 7.41 (1H, s), 6.96 (1H, s), 5.30 (1H, s), 4.41 (2H, s )

(2) Production of (2,5-dichloro-4-ethoxyphenyl) methanol In a solution of 1.23 g (6.3 mmol) of 2,5-dichloro-4-hydroxymethylphenol in 25 ml of N, N-dimethylformamide, Anhydrous potassium carbonate 0.88 g (6.3 mmol) and iodoethane 0.99 g (6.3 mmol) were added. The reaction solution was stirred overnight at room temperature. After confirming the disappearance of the raw materials, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain (2,5-dichloro-4-ethoxyphenyl) methanol.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.47 (1H, s), 6.92 (1H, s), 4.68 (2H, s), 4.08 (2H, q), 1.47 (3H, t )

(3) Production of (2,5-dichloro-4-ethoxy) benzyl bromide To a solution of 1.40 g (equivalent to 6.3 mmol) of (2,5-dichloro-4-ethoxyphenyl) methanol in 20 ml of diethyl ether, 0.85 g (3.2 mmol) of phosphorus phosphide was added and stirred for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with diethyl ether. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of (2,5-dichloro-4-ethoxy) benzyl bromide.

(4) Production of 3- (2,5-dichloro-4-ethoxybenzylthio) -5,5-dimethyl-2-isoxazoline 1.20 g of 5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline ( To a solution of 6.3 mmol) in 30 ml of N, N-dimethylformamide, 1.01 g of sodium hydrosulfide hydrate (purity 70%, 13.0 mmol) was added and stirred for 2 hours. Thereafter, 0.87 g (6.3 mmol) of anhydrous potassium carbonate, 0.97 g (6.3 mmol) of Rongalite (CH ₂ (OH) SO ₂ Na.2H ₂ O) and (3) were obtained (2, A solution of a crude product of 5-dichloro-4-ethoxy) benzyl bromide (corresponding to 6.3 mmol) in 20 ml of N, N-dimethylformamide was added, and the mixture was further stirred at room temperature for 11 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The obtained organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 1.53 g of 3- (2,5-dichloro-4-ethoxybenzylthio) -5,5-dimethyl-2-isoxazoline (yield). 73%) was obtained.
( ¹ H-NMR value (CDCl _{3 /} TMS) δ (ppm)): 7.51 (1H, s), 6.92 (1H, s), 4.29 (2H, s), 4.08 (2H, q), 2.77 (2H, s), 1.46 (3H, t), 1.41 (6H, s)

(5) Preparation of 3- (2,5-dichloro-4-ethoxybenzylsulfonyl) -5,5-dimethyl-2-isoxazoline (Compound No. 54) 3- (2,5-dichloro-4-ethoxybenzylthio) ) -5,5-dimethyl-2-isoxazoline (1.53 g, 4.6 mmol) in chloroform (15 ml) under ice-cooling, m-chloroperbenzoic acid (2.82 g, purity 70%, 11.0 mmol) And stirred at room temperature for 20 hours. After completion of the reaction, the reaction solution was poured into water and extracted with chloroform. The obtained organic layer was washed successively with an aqueous sodium hydrogen sulfite solution, an aqueous sodium hydrogen carbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the precipitated crystals were washed with n-hexane, and white crystals (melting point: 155-156 ° C.) 3- (2,5-dichloro-4-ethoxybenzylsulfonyl) -5,5- 1.39 g (yield 83%) of dimethyl-2-isoxazoline was obtained.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 7.51 (1H, s), 6.92 (1H, s), 4.29 (2H, s), 4.07 (2H, q), 2.77 (2H, s ), 1.47 (3H, t), 1.41 (6H, s)

<Intermediate Production Example 1>
Preparation of 3-chloro-5,5-dimethyl-2-isoxazoline 53-g N-chlorosuccinimide at 65-70 ° C. in a solution of 182.7 g (2.05 mol) glyoxylic acid aldoxime in 2 l dimethoxyethane (4.0 mol) was gradually added and then heated to reflux for 1 hour. Under ice cooling, 1440.0 g (14.4 mol) of potassium hydrogen carbonate and 10 ml of water were added, and 360.0 g (6.4 mol) of 2-methylpropene was added to the reaction solution, followed by stirring at room temperature for 24 hours. The reaction solution was poured into water and extracted with isopropyl ether. The obtained organic layer was washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 107.7 g (yield 40.0%) of 3-chloro-5,5-dimethyl-2-isoxazoline as a yellow viscous liquid.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 2.93 (2H, s), 1.47 (6H, s)

<Intermediate Production Example 2>
Preparation of 3-chloro-5-ethyl-5-methyl-2-isoxazoline To a solution of 20.6 g (231.7 mmol) of aldoxime glyoxylate in 500 ml of dimethoxyethane, 61.9 g of N-chlorosuccinimide at 60 ° C. 463.4 mmol) was added slowly. After the addition was complete, the mixture was heated to reflux for 10 minutes. Next, under ice cooling, 50 ml (463.4 mmol) of 2-methyl-1-butene, 98.9 g (1622 mmol) of potassium hydrogen carbonate and 10 ml of water were added and stirred for 12 hours. The reaction solution was poured into water and extracted with n-hexane. The obtained organic layer was washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 13.9 g (yield 40.6%) of 3-chloro-5-ethyl-5-methyl-2-isoxazoline as a pale yellow viscous liquid.
( ¹ H-NMR value (CDCl ₃ / TMS δ (ppm)): 2.91 (2H, Abq, J = 17.0, Δν = 46.1 Hz), 1.73 (2H, q), 1.42 (3H, s), 0.96 (3H , t)

  The composition of the present invention provides an effective herbicidal composition for selectively controlling a wide range of weeds, and is a main weed in transplanted rice cultivation, such as Tainubie, Inubie, Inuhotarui, Taiwan Yamai, Effectively weeds monocotyledonous plants such as chickweed, scallop, and scallops, and dicotyledonous plants such as oak, mizuaoi, azena, azeto pepper, mizuhakobe, mizusakobe, kikuashigusa, abnomome, takasaburo, etc. This does not cause phytotoxicity.

  In order to use the herbicidal composition of the present invention as a herbicide, it may be used in the form of a mixture without adding other components. However, carriers, surfactants, dispersants or adjuvants generally used for formulation, etc. Can be formulated and used in wettable powders, granules, fine granules, powders, emulsions, aqueous solvents, suspensions, flowables and the like.

  Examples of carriers used for formulation include talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, calcium carbonate, slaked lime, silica sand, ammonium sulfate, urea and other solid carriers, isopropyl alcohol, xylene, cyclohexane, methylnaphthalene, etc. Liquid carriers and the like.

  Surfactants and dispersants include, for example, alkylbenzenesulfonic acid metal salts, alkylnaphthalenesulfonic acid formalin condensate metal salts, alcohol sulfate esters, alkylaryl sulfonates, lignin sulfonates, polyoxyethylene glycol ethers, polyoxyethylenes. Examples thereof include ethylene alkyl aryl ether and polyoxyethylene sorbitan monoalkylate. Examples of the auxiliary agent include carboxymethyl cellulose, polyethylene glycol, gum arabic and the like.

  The composition of the present invention can be prepared by formulating each active ingredient by the above-described formulation technique and then mixing them. The composition of the present invention thus formulated is applied to a plant as it is or diluted with water or the like. The composition of the present invention can be further expected to enhance herbicidal efficacy by mixing with other herbicides, and can be used in combination with insecticides, fungicides, plant growth regulators, fertilizers, soil conditioners, etc. it can.

  The application amount of the composition of the present invention is generally such that the total amount of one kind selected from the isoxazoline derivative represented by the formula [I], which is an active ingredient compound, and at least one kind selected from the group A shown above is 0.8. 5 to 90% by weight, preferably 1 to 80% by weight is contained.

  When at least one herbicide selected from the group A shown above is mixed and applied to the compound represented by the general formula [I] at a predetermined ratio, it is not limited to a simple sum of activities obtained by each single agent, but synergistically. Various weeds that are effective in paddy fields, such as grass weeds such as Inobie, Tainubie, Azegaya, Kishuusuzumenohie, Konagi, Mizuaoi, Azena, Azetogarashi, Mizuhakobe, Mizohakobe, Abnome, Kakashigusa It exhibits an excellent herbicidal effect at a low dose over a wide range of perennial and annual perennial weeds such as broad-leaved weeds, fireflies, dog fireflies, Taiwan Yamai, Tamagayatsuri, Hinagoyatsuki and Kogomegatsuri.

  Furthermore, various weeds which are problematic in the field, such as grasses such as Inobie, Agaricus, Enocologosa, Vulgaris, Johnsongrass, Vulgaris, wild oats, etc., Ainu, Aoyu, Shiroza, Jacobe, Ichibibi, American golden deer, Perennial and annual cyperaceae weeds such as broadleaf weeds of American hornweed, ragweed, and morning glory, hamasge, kihamasuge, himekug, cyperus, and komegamegatsutsu can also be controlled at low doses over a wide range of growth periods from before germination.

  On the other hand, the herbicidal composition of the present invention has high safety against crops, and particularly shows high safety against rice, wheat, barley, corn, grain sorghum, soybean, cotton, sugar beet, turf, fruit tree and the like.

  Next, the best mode for carrying out the present invention will be described by way of examples. In the following examples, parts indicate parts by weight.

<Formulation Example 1> Granule 2 parts of Compound 1, 0.5 part of Bensulfuron Methyl, 80 parts of extender in which talc and bentonite are mixed at a ratio of 1: 3, 5 parts of white carbon, surfactant poly After adding 10 parts of water to 5 parts of a mixture of oxyethylene sorbitan alkylate, polyoxyethylene alkylaryl polymer and alkylaryl sulfonate and extruding from a sieve hole with a diameter of 0.7 mm and drying, It was cut into a length of 0.5 to 1 mm to obtain granules.

<Formulation Example 2> Wetting Agent 2 parts of Compound 1, 0.5 part of bensulfuron methyl 0.5 part of polyoxyethylene octylphenyl ether, 0.5 part of β-naphthalenesulfonic acid formalin condensate sodium salt Then, 26.5 parts of diatomaceous earth and 69 parts of clay were mixed and ground to obtain a wettable powder.

  The mixing ratio, weather conditions, formulation form, application time, application method, application location, control target weed, and target crop may vary, but the total amount of active ingredient compounds per 10 are usually 5 to 100 g. Emulsions, wettable powders, suspending agents, etc. are applied by diluting a predetermined amount with 10 to 100 liters of water per 10 ares.

  Next, the effects of the herbicidal composition of the present invention will be described with reference to test examples.

<Test example> Herbicidal effect test by paddy field soil treatment Paddy field soil was filled in a 100 cm ² plastic pot, and after seeding, Tainubie, Konagi and Inuta firefly seeds were sown and submerged to a depth of 3 cm. This was grown in a greenhouse until Tainubier reached approximately 2.0 leaf stage, and a wettable powder prepared according to Formulation Example 2 was diluted with water and subjected to water surface dripping treatment. Thereafter, it was allowed to stand and grown, and the herbicidal effect was examined according to the criteria in Table 4 on the 28th day after treatment. The results are shown in Tables 5 to 15.

Claims (4)

Formula [I]

{In the formula, Q represents a group —S (O) _n — (CR ₅ R ₆ ) _m —, n represents an integer of 0 to 2, m represents an integer of 1 to 3, R ₅ and R ₆ Independently represent a hydrogen atom, a cyano group, an alkoxycarbonyl group or a C1-C6 alkyl group,
R ₁ and R ₂ are a hydrogen atom, [C3-C8 cycloalkyl group, C1-C6 alkoxy group, C1-C6 alkylcarbonyl group, C1-C6 alkylthio group, C1-C6 alkylsulfinyl group, C1-C6 alkylsulfonyl group, C1-C6 alkylamino group, di (C1-C6 alkyl) amino group, cyano group, C1-C6 alkoxycarbonyl group, C1-C6 alkylaminocarbonyl group, di (C1-C6 alkyl) aminocarbonyl group, (C1-C6) Alkylthio) carbonyl group, carboxyl group, (optionally substituted) benzyloxy group, (optionally substituted) phenoxy group or (optionally substituted) phenyl group optionally substituted] C1 -C8 alkyl group, C3-C8 cycloalkyl group, C1-C6 alkoxycal Alkenyl groups, C1 -C6 alkylaminocarbonyl group, di (C1 -C6 alkyl) aminocarbonyl group, C1 -C6 alkyl thio group, a carboxyl group, or (optionally substituted) phenyl group, or _{R 1} and R ₂ may form a C3-C7 spiro ring together with these bonded carbon atoms,
R ₃ and R ₄ are each a hydrogen atom, a C1-C8 alkyl group (which may be substituted with 1 to 3 halogen atoms which are the same or different, a C3-C8 cycloalkyl group or a C1-C6 alkoxy group) or a C3- Represents a C8 cycloalkyl group, R ₃ and R ₄ together with these bonded carbon atoms may form a C3-C7 spiro ring, or R ₁ , R ₂ , R ₃ and R ₄ may be bonded together You may form a 5-8 membered ring with a carbon atom,
Y is a hydrogen atom, a C1-C6 alkoxycarbonyl group, a carboxyl group, a C2-C6 alkenyl group, [1 to 3 halogen atoms that are the same or different, a C1-C6 alkoxy group, a C2-C6 alkenyloxy group, a C2-C6 An alkynyloxy group, an optionally substituted benzyloxy group, a C1-C6 alkoxycarbonyl group, a carboxyl group, a hydroxyl group or a formyl group] a C1-C10 alkyl group or (1-5 Represents a phenyl group (substituted with the same or different R ₇ ),
R ₇ is a hydrogen atom, [1 to 3 halogen atoms that are the same or different, a C1 to C6 alkoxy group, a hydroxyl group, a C1 to C6 alkylthio group, a C1 to C6 alkylsulfinyl group, a C1 to C6 alkylsulfonyl group, a C1 to C6]. An alkylamino group, a C1-C6 dialkylamino group, a cyano group, or an (optionally substituted) phenoxy-substituted] C1-C6 alkyl group (1-3 halogen atoms, which are the same or different, C1-C6 alkoxy group, optionally substituted with C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxycarbonyl group, C1-C6 alkylcarbonyl group or C3-C8 cycloalkyl group) Group, C2-C6 alkenyl group, C3-C8 cycloalkyloxy group, Is optionally substituted with 1 to 3 different halogen atoms or C1 to C6 alkoxy groups), substituted with 1 to 3 halogen atoms or the same or different C1 to C6 alkoxy groups A C1-C6 alkylsulfinyl group (which may be substituted), a C1-C6 alkylsulfonyl group (which may be substituted with 1 to 3 halogen atoms or C1-C6 alkoxy groups which are the same or different), (substituted) May be substituted with a benzyloxy group, a (C1-C6 alkyl group, a C1-C6 alkylsulfonyl group, a C1-C6 alkylcarbonyl (C1-C6 alkyl) group or a C1-C6 alkylsulfonyl (C1-C6 alkyl) group. Amino group, halogen atom, cyano group, nitro group, C1-C6 alkoxycarbonyl , C3-C8 cycloalkyloxycarbonyl group, carboxyl group, C2-C6 alkenyloxycarbonyl group, C2-C6 alkynyloxycarbonyl group, (optionally substituted) benzyloxycarbonyl group, (optionally substituted) It represents a phenoxycarbonyl group or a C1-C6 alkylcarbonyloxy group. } Isoxazoline derivative or a salt thereof and at least one selected from the following group A: a herbicidal composition.
Group A: sulfonylurea herbicides, pyrimidyl carboxylic acid herbicides, allyloxyphenoxypropionic acid herbicides, triazine herbicides, diphenyl ether herbicides, oxadiazole herbicides, pyrazole herbicides, bicyclooctane Herbicides, amino acid herbicides, organophosphorus herbicides, acid amide herbicides, phenoxy herbicides, carbamate herbicides, phenoxycarboxylic acid herbicides, ACN, indanophane, oxadichromefone, carfentrazone, dithiopyr , Pyraclonyl, phentolazamide, propanyl, penoxthram, bentazone, pentoxazone, benfrate, metamihop, 2 '-(4,6-dimethoxypyrimidin-2-yl) hydroxymethyl-6'-methoxymethyl-1,1-difluoromethanesulfone Lido, 2- {2-chloro-4-mesyl-3 - [(tetrahydrofuran-2-ylmethoxy) methyl] benzoyl} cyclohexane-1,3-dione In general formula [I],
Q represents a group —S (O) _n — (CR ₅ R ₆ ) _m —, n represents an integer of 0 to 2, m represents 1, R ₅ and R ₆ represent a hydrogen atom,
R ₁ and R ₂ represent a hydrogen atom, a C1-C8 alkyl group (which may be substituted with a C3-C8 cycloalkyl group or a C1-C6 alkoxy group) or a C3-C8 cycloalkyl group, or R and R ₂ May form a C3-C7 spiro ring with these bonded carbon atoms,
R ₃ and R ₄ represent a hydrogen atom or a C1-C8 alkyl group (which may be substituted with 1 to 3 halogen atoms that are the same or different, a C3C8 loalkyl group, or a C1-C6 alkoxy group), and R ₃ and R 4 ₄ may form a C3-C7 spiro ring with these bonded carbon atoms, or R ₁ , R ₂ , R ₃ and R ₄ may form a 5- to 8-membered ring with these bonded carbon atoms. You can,
Y represents a phenyl group (substituted with 1 to 5 identical or different R ₇ );
R ₇ is a hydrogen atom, [1 to 3 halogen atoms that are the same or different, a C1 to C6 alkoxy group, a hydroxyl group, a C1 to C6 alkylthio group, a C1 to C6 alkylsulfinyl group, a C1 to C6 alkylsulfonyl group, a C1 to C6]. An alkylamino group, a C1-C6 dialkylamino group, a cyano group, or an (optionally substituted) phenoxy-substituted] C1-C6 alkyl group (1-3 halogen atoms, which are the same or different, C1-C6 alkoxy group, optionally substituted with C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxycarbonyl group, C1-C6 alkylcarbonyl group or C3-C8 cycloalkyl group) Group, C3-C8 cycloalkyloxy group, halogen atom, nitro group or cyano group The herbicidal composition according to claim 1, which is an isoxazoline derivative or a salt thereof. In general formula [I],
Q represents a group —S (O) _n — (CR ₅ R ₆ ) _m —, n represents an integer of 0 to 2, m represents 1, R ₅ and R ₆ represent a hydrogen atom,
R ₁ and R ₂ represent a C1-C8 alkyl group,
R ₃ and R ₄ represent a hydrogen atom,
Y represents a phenyl group (substituted with 1 to 5 identical or different R ₇ );
R ₇ is a hydrogen atom, a C1-C6 alkyl group (which may be substituted with the same or different 1 to 3 halogen atoms or a C1 to C6 alkoxy group), or a same or different 1 to 3 halogen atoms. Or a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, a C2-C6 alkenyloxy group, a C2-C6 alkynyloxy group, a halogen atom, a nitro group or a cyano group. The herbicidal composition according to claim 1, which is an isoxazoline derivative or a salt thereof. In general formula [I],
Q represents a group —S (O) _n — (CR ₅ R ₆ ) _m —, n represents 2, m represents 1, R ₅ and R ₆ represent a hydrogen atom,
R ₁ and R ₂ represent a C1-C4 alkyl group,
R ₃ and R ₄ represent a hydrogen atom,
Y represents a phenyl group (substituted with 1 to 5 identical or different R ₇ );
R ₇ is a hydrogen atom, a C1-C6 alkyl group (which may be substituted with 1 to 3 halogen atoms which are the same or different), or a substituent which is substituted with 1 to 3 halogen atoms which are the same or different. The herbicidal composition according to claim 1, which is an isoxazoline derivative or a salt thereof which represents a C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, a C2-C6 alkynyloxy group, a halogen atom, a nitro group or a cyano group. .