WO2000050410A1

WO2000050410A1 - Isoxazoline compounds and processes for the preparation thereof

Info

Publication number: WO2000050410A1
Application number: PCT/JP2000/001063
Authority: WO
Inventors: Tomio Yagihara; Masami Hatano; Tetsushi Ookuchi
Original assignee: Nippon Soda Co., Ltd.
Priority date: 1999-02-25
Filing date: 2000-02-24
Publication date: 2000-08-31
Also published as: AU2691200A; JP2010209115A; JP4558211B2; JP5079849B2

Abstract

3-Halo-2-isoxazoline compounds and 3-sulfonyl-2-isoxazoline compounds; processes for the preparation of both; and processes for preparing 3-alkenyl or alkynyl-2-isoxazolines from 3-sulfonyl-2-isoxazolines.

Description

Specification

Isoxazoline compounds and production method

Technical field:

The present invention relates to a 2-isoxazoline compound having a substituent at the 3-position, and a production method related thereto. More specifically, 3-halo-2-isoxazoline and 3-sulfonyl-2-isoxazoline compounds and methods for producing them, and production of 3-alkenyl or alkynyl-2-isooxazoline from 3-sulfonyl-2-isooxazoline About the law. Background technology:

It is generally known that 3-halo-2-isoxazolines are produced via the corresponding nitriloxide. For example, according to K. Hal 1 in: Liebigs Ann. Chem. 19899985-990, 3-halo-2-isoxazoline having various substituents at the 5-position has been synthesized. .

In addition, SU 177 0 16 (CA 1 179 0 268) has 5-phenyl-2-oxo along with the production of the halo isoxazole having a substituent at the 5-position. The production of chlor-2-isoxazoline is described.

However, there is no description of the unsubstituted 3-halo-2-isoxazoline which is the compound of the present invention in the above-mentioned documents.

It has been reported that 3-sulfonyl-12-isosoxazoline can be obtained by the reaction of 3-nitro-12-isosoxazoline with sodium benzenesulfinate (PA Wade: J. Org. Chem. J_ 220-200-203 (19778)) force \ The applicable range is limited, and the reaction yield is as low as 28%.

In addition, regarding a method for producing 2-isoxazoline having an unsaturated group such as an alkenyl group or an alkynyl group at the 3-position, conventionally, a nitrovinyl compound was generated using phenyl isocyanate as a deoxygenating agent. (A. Baranski: Polish J. Chem., _5_ ^, 1189 (1989)) is a method of obtaining nitrile by reacting nitroloxide with olefin. However, the use of the olefins is not applicable because of the polymerization of the formed nitriloxide, and the substituent at the 3-position is significantly limited.

In addition, the reaction of 3-nitroisoxazoline with 1-propyne lithium (PA Wad e: Tetrah edr on Letters, _3_0_, 5969 (11989) is also known, but is not common in using propyne lithium. DISCLOSURE OF THE INVENTION:

An object of the present invention is to provide a novel 2-isooxazoline compound having a substituent at the 3-position and a method for producing them.

For more information,

1) General formula (1-1)

[In the formula, R ^1, d alkyl group, C ₂ - alkenyl, C ₂ - ₆ alkynyl group, it may also be substituted I Ariru group (. Provided that unsubstituted off alkenyl group is excluded) or substituted even represents an C ₇ one ₁₆ Ararukiru group. A compound represented by the formula:

2) General formula (2)

(Wherein X represents a halogen atom.) And a compound represented by the general formula (3)

RS 0 ₂ Z (3)

(Wherein, R, _d-G alkyl group, C ₂ - ₆ alkenyl group, C ₂ - _G alkynyl group, it may also be substituted I § Li Ichiru group or an optionally substituted C ₇ - _{1 (i} Represents an aralkyl group, and Z represents a hydrogen atom or an alkali metal atom.) A general formula (1) characterized by reacting with a sulfinic acid represented by the formula:

(Wherein, R represents the same meaning as described above.)

3) General formula (2)

(Wherein χ represents a halogen atom.) And a compound represented by the general formula (4)

RSH (4)

(Wherein, R represents the same meaning as described above.) With a thiol represented by the following general formula (5):

(Wherein, R represents the same meaning as described above.) A method for producing a compound represented by the general formula (1), wherein a compound represented by the formula (1) is oxidized.

4) 3-halo-2-isoxazoline represented by the general formula (2),

5) Next equation

XC≡N-0 (wherein X represents a halogen atom.) 3-halo 2 represented by the above general formula (2), wherein ethylene is reacted with halonitriloxide represented by the following formula: —A process for producing isoxazoline,

6) A method for producing 3-halo-2-isooxazoline represented by the general formula (2), characterized by reacting a halogenating agent with 3-isoxazolidone; and

7) General formula (1-2)

(Wherein, R ² represents an alkyl group or an aryl group which may be substituted.) And a compound represented by the general formula (6): R ³ M g -Hal (6)

Wherein R ³ is a C 2 alkenyl group or a 〇 ₂ _-β alkynyl group, and Ha 1 is a halogen atom.

(Wherein, R ³ has the same meaning as described above.)

In the present invention, R and R ¹ are a C alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, etc., ethenyl, 1-probenyl, 2-propenyl and the like. C ₂ - _s alkenyl group, Echiniru, 1-propynyl, 2-pro pair C ₂ such alkenyl - ₆ alkynyl group, the (arbitrary position, fluorine, chlorine, bromine, C androgenic atom such as iodine, methyl, Echiru, C ₆ alkyl groups such as propyl, isopropyl, butyl, t-butyl, C alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, (It may be substituted with d-haloalkyl groups such as difluoromethyl, trifluoromethyl, etc.) (Any position is a halogen atom such as fluorine, chlorine, bromine or iodine, a C alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, methoxy, ethoxy, propoxy, isopropoxy, C-alkoxy groups such as butoxy and t-butoxy, and C i- ₆ haloalkyl groups such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl and trifluoromethyl may be substituted. 2-arphthyl and other unsubstituted phenyl groups such as naphthyl and the like, which may be substituted, except for unsubstituted phenyl groups (any position of the ring may be a halogen atom such as fluorine, chlorine, bromine or iodine, methyl, ethyl, D- ₆ alkyl groups such as propyl, isopropyl, butyl, t-butyl, etc. May be substituted with d alkoxy groups such as toxoxy, propoxy, isopropoxy, butoxy, t-butoxy, and C-haloalkyl groups such as chloromethyl, dichloromethyl, trifluoromethyl, fluoromethyl, difluoromethyl, and trifluoromethyl. , Fuwenechiru, 1-naphthylmethyl, C ₇ such as 2 Na Fuchirumechiru - represents _{a 6} Ararukiru group. Provided that R ¹ is not an unsubstituted phenyl group R ² is methyl, ethyl, propyl, isopropyl, butyl, isoptyl, s-butyl

, alkyl groups such as t-butyl, (at any position, halogen atoms such as fluorine, chlorine, bromine and iodine, C alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, methoxy, May be substituted with a C alkoxy group such as ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, or a C haloalkyl group such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc.) a phenyl group (Halogen atom such as fluorine, chlorine, bromine and iodine, C alkyl group such as methyl, ethyl, propyl, isopropyl, butyl and t_butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, t C butco such as butoxy C!-, Such as xy, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc. (; may be substituted with alkyl, etc.) Naphthyl, etc. Represents an aryl group.

R ³ is Eteniru, 1 one propenyl, 2 - propenyl, 1 Buteniru, 2-butenyl, C _2, such as 3-butenyl - ₆ alkenyl group or Echiniru, 1 one propynyl, 2 - Puropini le, 1 one heptynyl, 2 - heptynyl, 3 - represents an _alkynyl group - C ₂ such heptynyl.

X and Hal represent a halogen atom such as a chlorine atom and a bromine atom. Next, the production method of the present invention will be described.

(a) A process for producing 3-halo-2-isoxoxane represented by the general formula (2).

Production method a— J nitriloxide method

(Wherein, X represents the same meaning as described above.)

In the nitriloxide method, dihaloformaldoxime is generally used to generate halonitriloxide with a base and reacted with ethylene to obtain a product, but the reaction method differs depending on the type of halogen. That is, in the case of chlornitriloxide, it is desirable to perform the reaction under pressure, and in the case of bromonitriloxide, while blowing ethylene into the reaction system, the base It is necessary to attach a sword. In this case, if ethylene is blown in after the addition of the base, the dimer of bromoditolyloxide becomes the main product, and the yield of the desired product decreases. The base used to generate nitriloxide is preferably potassium bicarbonate, and the reaction solvent must be an ether such as tetrahydrofuran (THF), dioxane, or dimethoxetane, and an appropriate amount of water is required. .

Halonitrile oxide is obtained by adding a halogenating agent such as N-chlorosuccinimide (NCS), t-butyl hypochlorite, or N-bromosuccinimide (NBS) to dalioxylic acid in an ether solvent. The reaction is carried out in the presence of a base, but it is usually used directly for the next reaction without removal.

Production method a—2 3 —Method of halogenating isoxazolidone

(Wherein, X represents the same meaning as described above.)

3 Phosphorus pentachloride, phosphorous oxychloride as a chlorinating agent for monoisoxazolidone, and phosphorus tribromide as a brominating agent can be used to carry out the reaction without a solvent.

When a solvent is used, a solvent that does not react with the halogenating agent, for example, an aromatic solvent such as toluene and chlorobenzene, and a halogenated hydrocarbon such as carbon tetrachloride are preferable.

(b) Method for producing 3 -sulfonyl-2-isoxazoline represented by general formula (1)

Crack ffi b 1

(2) (3) (1)

(Wherein, X, Z, and R have the same meanings as described above.) This production method is a direct sulfonylation of 3-halo-2-isoxazoline (2) with a sulfinic acid (3), In the reaction with sulfinic acid, the reaction is carried out in the presence of a hydrogen halide scavenger, and in the case of sulfinate, the reaction can be carried out directly.

As the reaction solvent, alcohols such as methanol, ethanol, and propanol, ethers such as tetrahydrofuran (THF), and polar solvents such as dimethylformamide (DMF) can be used. A mixture thereof may be used. Is also possible.

The reaction temperature can be selected from the range of room temperature to the boiling point of the solvent. Manufacturing method b-2

(2) (4) (5) Oxidizing agent

(1)

(In the formula, X and R represent the same meaning as described above.)

In this production method, sulfides (5) are synthesized by reacting thiols (4) with 3-halo-2-isoxazolines (2) and obtained by oxidation.

Reaction solvents include alcohols such as methanol, ethanol, and propanol, and THF. Ethers, polar solvents such as DMF, acetic acid and the like can be used, and a mixture thereof or water can also be used.

As the oxidizing agent, an organic peroxide such as m-chloroperbenzoic acid and an inorganic peroxide such as hydrogen peroxide can be used.

The reaction temperature can be selected from the range of room temperature to the boiling point of the solvent.

(c) A method for producing a compound represented by the general formula (7).

Manufacturing method c

(1-2) (6) (7)

(Wherein, R ² , R ³ , and Hal represent the same meaning as described above.)

In this production method, a compound represented by the general formula (7) is produced from a reaction of 3-sulfonyl-2-isoxazolines (112) with a Grignard reagent (6).

As the reaction solvent, ethers such as diethyl ether and tetrahydrofuran (THF), aromatic hydrocarbons such as benzene, toluene and xylene, or a mixed solvent thereof are used.

The reaction may be carried out at room temperature or, if necessary, up to the boiling point of the reaction solvent.

In the present invention, after completion of the reaction, the desired product can be obtained by performing ordinary post-treatment.

The structures of the compounds according to the present invention were determined from IR, NMR, MS and the like. BEST MODE FOR CARRYING OUT THE INVENTION:

Next, the present invention will be described more specifically with reference to examples. Example 1

Production of 3-chloro-2-isoxazoline

To a solution of 26.7 g of taloxime daroxilate in 300 ml of dimethoxetane was added 0.1 g of NCS at room temperature, and the mixture was heated under reflux for 20 minutes. Thereafter, the reaction mixture was cooled to room temperature, 120 g of potassium hydrogen carbonate and 6 ml of water were added, and the solution was transferred to a 11-glass container and filled with ethylene. Stirred at room temperature for 20 hours. The insolubles were filtered off, the filtrate was poured into ice water, extracted with getyl ether, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was distilled under reduced pressure to obtain 17.7 g of 3-chloro-2-isoxazoline.

.. b p 7 6 ° C / 2 7 mm H g, n D 2 4 3:.. 1 4 6 2 8 Example 2

3 rk — 2-in production

A mixture of 0.6 g of 3-isoxazolidone and 1.4 g of phosphorus pentachloride was stirred at 60 ° C for 1 hour. Thereafter, the reaction mixture was cooled to room temperature, then poured into iced water, extracted with getyl ether, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was distilled under reduced pressure to obtain 0.3 g of 3-chloro-2-isoxazoline. The product was identical to the product obtained by the method of Example 1. Example 3

3 —Brom-I 2 —Manufacture of isoxane

26.7 g of oxime glyoxylate was dissolved in 300 ml of dimethoxyethane, 90 ml of water was added, 106.8 g of N-bromosuccinic acid imide was added under cooling, and the mixture was stirred at room temperature for 20 minutes. While blowing ethylene gas at room temperature, 120 g of potassium hydrogen carbonate was added over 30 minutes, and the solution was stirred at room temperature for 4 hours. The insolubles were filtered, the filtrate was poured into ice water, extracted with getyl ether, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was distilled under reduced pressure to obtain 13.4 g of 3-bromo-2isoxazoline.

bp 1 0 1 ° C / 3 0 mmH g, n D ] ^{^8.9:} 1.5 3 5 3

[0 0 2 63

Example 4

Production of 3- (4 toluenesulfonyl) 2isoxazoline

After dissolving 1.0 g of 3-promo 2-isoxazoline and 1.8 g of sodium toluenesulfonate tetrahydrate in 10 ml of DMF, the mixture was stirred at 110 ° C for 18 hours. Thereafter, the mixture was cooled to room temperature, the reaction solution was poured into ice water, extracted with ethyl acetate, the organic layer was washed with water, and dried over magnesium sulfate anhydride. The solvent was distilled off under reduced pressure, and the remaining crystals were washed with n-hexane to obtain 1.02 g of 3- (4-toluenesulfonyl) 2isoxazoline. m.p. 75-76 ° C Example 5

Production of 3-benzenesulfonyl 2-isoxazoline

3 1-Promox 2-isoxazoline 10.0 g and sodium benzenesulfonate monohydrate 20.0 g were dissolved in DMF 10 m 7K 40 m 1 and heated to reflux for 24 hours did. Thereafter, the mixture was cooled to room temperature, the reaction solution was poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining crystals were washed with n-hexane to obtain 8.4 g of 3-benzenesulfonyl-2-isoxazoline.

m.p. 9 6-97 ° C Example 6

Preparation of 3-Phenylthio-1-isoxazoline

4.2 g of metal sodium was added in small portions to 70 O ml of methanol under reflux. When the metal sodium disappeared, the mixture was cooled to room temperature, 20.0 g of thiophenol and 12.8 g of 3-chloro-2-isoxazoline were added, and the mixture was refluxed for 18 hours. Thereafter, the mixture was cooled to room temperature, the reaction solution was poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was purified by silica gel column chromatography to obtain 1-8.4 g of 3-phenylthio-12-isoxazoline.

n: 1.5 9 3 5

Preparation of 3-benzenesulfonyl-2-isoxazoline

1-8.0 g of 3-phenylthio-1-isoxazoline was dissolved in 200 ml of acetic acid, and 34.2 g of a 30% aqueous hydrogen peroxide solution was added dropwise at room temperature, followed by heating under reflux for 1 hour. Thereafter, the mixture was cooled to room temperature, the reaction solution was poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure, and the remaining crystals are washed with n-hexane. As a result, 8.4 g of 3-benzenesulfonyl 2-isoxazoline was obtained.

m.p. 9 6-9 7 ° C

Example Ί

Production of 3-methylthio 2-isoxazoline

0.42 g of sodium metal was added in small portions to 7 Oml of methanol under reflux. When the sodium metal disappeared, the mixture was cooled to room temperature, 1.44 g of methanethiol and 1.9 g of 3-chloro-2-isosoxazoline were added, and the mixture was heated under reflux for 1 hour. Thereafter, the reaction solution was cooled to room temperature, poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was purified by silica gel column chromatography to obtain 1.61 g of 3-methylthio-2-isoxazoline. This was used in the reaction.

XH-NMR (CD C 13) s 5 (p pm):

4.39 (t, 2H), 3.05 (t, 2H), 2.51 (s, 3H)

3 _Production of methanesulfonyl-2-isoxazoline

1.6 g of 3-methylthio-2-isoxazoline was dissolved in 20 ml of acetic acid, and 5.0 g of a 30% aqueous hydrogen peroxide solution was added dropwise at room temperature, followed by heating under reflux for 1 hour. After cooling to room temperature, the reaction solution was poured into ice water, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was purified by silica gel column chromatography to obtain 1.5 g of 3-methanesulfonyl-2-isoxazoline.

! 0.9

n _D 1. 4 7 4 6

Example 8

Preparation of 3-(1 propynyl) 2 isoxoxazoline

(3) 10.0 g of 1-benzenesulfonyl 2-isoxazoline is dissolved in 50 ml of dry THF, and 90 ml of a 0.5 M solution of 1-propyne magnesium bromide in THF (190 ml) is added dropwise at room temperature, and the mixture is refluxed for 7 hours. did. After cooling to room temperature, the reaction solution was poured into a 1N aqueous hydrochloric acid solution, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was purified by silica gel column chromatography to obtain 4.9 g of 3- (1-propynyl) -12-isoxazoline.

b.p. 55-57 ° C / 0.2 mmH g Example 9

Production of 3- (1-probenyl) -1-2-isoxazoline

0.46 g of magnesium powder was suspended in 16 ml of dry THF and 8 ml of dry ethyl ether, and 2.3 g of cis-1-probenyl bromide was added dropwise under reflux, and the mixture was heated under reflux for 1 hour. Thereafter, the mixture was cooled to room temperature, a solution of 3-benzenesulfonyl 2-isoxazoline 1.Og dissolved in dry THF (6 ml) was added dropwise under cooling, and the mixture was heated under reflux for 1 hour. Thereafter, the mixture was cooled to room temperature, the reaction solution was poured into a 1N aqueous hydrochloric acid solution, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was purified by silica gel chromatography to obtain 0.4 g of 3- (1-probenyl) -12-isoxazoline. This compound was a mixture of cis: trans = l: l (NMR).

^-MR (CDC 1 δ ρ m):

cis 6.15 (d, 1H, J = 15.0Hz), 5.94 On, 1H), 4.36 (t, 2H, J = 8.7Hz)

3.17 (t, 2H, J = 8.7Hz), 1.95 (d, 3H, J = 7.9Hz) trans 6.42 (d, 1H, J = 16.6Hz), 6.0 (ra, 1H), 4.32 (t, 2H, J = 9.5Hz)

3.13 (t, 2H, J = 9.5Hz), 1.89 (d, 3H, J = 7.9Hz) Example 10

Production of 3- (1-propynyl) -2-yne

Dissolve 1.0 g of 3-methanesulfonyl-2-isoxazoline in 5 ml of dry THF, add dropwise 27 ml of 0.5 M 1-propyne magnesium bromide in THF at room temperature, and heat for 1 hour Refluxed. Thereafter, the mixture was cooled to room temperature, the reaction solution was poured into a 1N aqueous hydrochloric acid solution, extracted with ethyl acetate, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining oil was purified by silica gel column chromatography to obtain 0.7 g of 3- (1-propynyl) 1-2-isoxazoline.

b. p. 5 5-5 7 ° C / 0.2 mmHg Industrial applicability:

In the present invention, 3-halo-2-isoxazoline having no substituent can be provided. In the present invention, the ability to react the 3-halo-2-isoxazoline of the present invention with alkylsulfuric acid, arylsulfuric acid or a salt thereof, and a sulfide which is a reaction product with thiol are used. By oxidation, a 3-sulfonyl-2-isoxazoline compound can be easily obtained.

The 3-sulfonyl-2-isoxazoline compound can be derived into various useful compounds by easily subjecting the sulfonyl group to a nucleophilic substitution reaction.

In the present invention, 2-isooxazoline having an unsaturated group at the 3-position can be easily obtained by using a 3-sulfonyl-2-isoxazoline compound.

The isoxazoline ring is a very important compound as a precursor because it produces amino alcohol by reduction and hydroxyketone by hydrolysis. There are many examples that are known.

For example, the compounds obtained in the present invention are known to be key intermediates for the synthesis of amino sugars having physiological activity. (P. A. Wad e: J. Org. Chem., _6 _, 367 1 (1997))

Also, compounds having isoxazoline as a substituent are known to have a herbicidal action. (WO 96/26206, WO 98Z3168 No.1, etc.)

Further, JP-A-11-249790 discloses a use example as an insecticide / miticidal agent.

Claims

The scope of the claims

1. General formula (1 1)

Wherein, R ¹ represents an alkyl group, C ₂ - ₆ alkenyl group, C 2 alkynyl group, an optionally substituted Ariru group (. Provided that unsubstituted Fuweniru group are excluded) or may be substituted

It represents a ₁₆ Ararukiru group - 〇 _7. ] The compound represented by these.

2. General formula (2)

(Wherein represents a halogen atom.) And a compound represented by the general formula (3)

RS 0 ₂ Z (3)

(Wherein, R, _d-6 alkyl groups, C ₂ - alkenyl, C ₂ - ₆ alkynyl group, which may be a good I § Li Ichiru or substituted be substituted C _{7 1 (5} Ararukiru group And Z represents a hydrogen atom or an alkali metal atom.) A general formula (1) characterized by reacting with sulfinic acid or an alkali metal salt thereof represented by

(Wherein, R represents the same meaning as described above.)

3. General formula (2)

(Wherein, X represents a halogen atom.) And a compound represented by the general formula (4)

RSH (4) [Wherein, R represents the same meaning as above. ) To react with thiols represented by the general formula

(Five)

(Wherein, R represents the same meaning as described above.) A method for producing a compound represented by the general formula (1), comprising obtaining a compound represented by the formula: and oxidizing the compound.

4. General formula (2)

(Wherein represents a halogen atom.) 3-halo-2-isoxazoline.

5. Next equation

XC≡N-> 0 (wherein, X represents a halogen atom.) 3-Halo represented by the above general formula (2), characterized by reacting a halonitrioxide represented by the formula: 2-Method for producing isooxazoline.

6. A process for producing 3-halo-2-isoxazoline represented by the general formula (2), wherein a halogenating agent is reacted with 3-isoxazolidone.

7. General formula (1-2)

(Wherein, R ² represents an alkyl group or an optionally substituted aryl group.) And a compound represented by the general formula (6)

R ³ Mg-Hal (6)

(Wherein, R ³ is C ₂ - ₆ alkenyl group or C ₂ -. _S alkynyl group, Hal is representing a halogen atom) formula which comprises reacting a (7)

(Wherein, R ³ has the same meaning as described above.)