Processes for production of oxadiazoline derivatives

专利摘要:
The process represented by the following scheme, advantageous for industrial mass production of Δ 2 -1,2,4-oxadiazoline derivatives or salts thereof having excellent insecticidal effect in high yield: [Wherein X 1 is halogen; R 1 is optionally substituted alkyl, optionally substituted acyl or ClCO; R 2 is a phenyl group optionally substituted with (1) halogen, (2) C 1-6 haloalkyl, (3) C 1-6 haloalkoxy or (4) C 1-6 haloalkyl group; A is a nitrogen atom or = CR 3 -wherein R 3 is Cl or CN; R 4 is C 1-6 alkyl or C 1-6 haloalkyl; n is 0, 1 or 2; X 2 represents halogen.
公开号:KR20020058062A
申请号:KR1020027006958
申请日:2000-11-17
公开日:2002-07-12
发明作者:간도야스유끼；기지도시유끼
申请人:다케다 야쿠힌 고교 가부시키가이샤；
IPC主号:

专利说明:

Process for the preparation of oxadiazoline derivatives {PROCESSES FOR PRODUCTION OF OXADIAZOLINE DERIVATIVES}
[2] So far, known production methods of Δ ² -1,2,4-oxadiazoline derivatives having a pyrazole substituent at the 3 position include, for example, methods for producing derivatives from cyanopyrazole derivatives. (JP-A 10-152476).
[3] However, methods for synthesizing 3-pyrazolyl-Δ ² -1,2,4-oxadiazoline derivatives having various kinds of substituents on the 4-position nitrogen atom of the oxadiazoline ring are not yet known, and insecticides and pesticides are known. There is currently no satisfactory method for general or industrial synthesis of Δ ² -1,2,4-oxadiazoline derivatives useful as mites.
[4] Purpose of the Invention
[5] It is an object of the present invention to provide a method which is satisfactory as a general or industrial synthesis method of Δ ² -1,2,4-oxadiazoline derivatives useful as insecticides and mites.
[6] Summary of the Invention
[7] The present inventors earnestly studied to solve the problems described above, and the 3-pyrazolyl-Δ ² -1, by ring conversion reaction of 3-isoxazolyl-Δ ² -1,2,4-oxadiazoline derivatives, The present invention has been completed by surprisingly finding that 2,4-oxadiazoline derivatives can be obtained in high yield.
[8] That is, the present invention relates to the following 1 to 18:
[9] 1.Method for preparing isoxazole-5-carboxamide oxime represented by formula (I) comprising reacting 5-cyanoisoxazole with hydroxylamine or a salt thereof:
[10]
[11] 2. 3- (5-isoxazolyl) -Δ ² represented by the following formula (II) comprising reacting isoxazole-5-carboxamide oxime or a salt thereof represented by formula (I) with formaldehyde or an equivalent thereof Method for preparing -1,2,4-oxadiazoline or salts thereof:
[12] [Formula I]
[13]
[14]
[15] 3. Reacting 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline or a salt thereof represented by the following formula (II) with a compound represented by the following formula (III) or an equivalent thereof or a salt thereof Method for preparing a compound represented by the following formula (IV) or a salt thereof comprising:
[16] [Formula II]
[17]
[18] R ¹ X ¹ [III]
[19] [Wherein, X ¹ represents a halogen atom, R ¹ represents an optionally substituted alkyl group, an optionally substituted acyl group or a chlorocarbonyl group (ClCO)]
[20]
[21] Wherein R ¹ is as defined above;
[22] 4. A process for preparing a compound represented by the following formula (V) or a salt thereof, which comprises ring-opening a isoxazole ring of a compound represented by the following formula (IV) or a salt thereof:
[23] [Formula IV]
[24]
[25] Wherein R ¹ is as defined in item 3 above.
[26]
[27] Wherein R ¹ is as defined in paragraph 3 above;
[28] 5. A process for preparing a compound represented by the following formula (VII) or a salt thereof, comprising reacting a compound represented by the following formula (V) or a salt thereof with a compound represented by the following formula (VI) or a salt thereof:
[29] [Formula V]
[30]
[31] Wherein R ¹ is as defined in item 3 above.
[32]
[33] [Wherein A is a nitrogen atom or (Wherein R ³ represents a chlorine atom or a cyano group), and R ² represents (1) halogen, (2) C _1-6 haloalkyl group, (3) C _1-6 haloalkoxy group or (4) C Phenyl group optionally substituted with _1-6 haloalkyl group]
[34]
[35] Wherein R ¹ is as defined in paragraph 3 above, and other symbols are as defined above;
[36] 6. A process for preparing a compound represented by the following formula (IX) or a salt thereof, comprising reacting a compound represented by the following formula (VII) or a salt thereof with a compound represented by the following formula (VIII):
[37] [Formula VII]
[38]
[39] Wherein R ¹ is as defined in item 3 above and R ² and A are as defined in item 5 above.
[40] R ⁴ SO _n X ² [VIII]
[41] [Wherein, R ⁴ represents a C _1-6 alkyl group or C _1-6 haloalkyl group, n is 0, 1 or 2, and X ² represents a halogen atom]
[42]
[43] Wherein R ¹ is as defined in paragraph 3 above, R ² and A are as defined in paragraph 5 above and R ⁴ is as defined above;
[44] 7. The method Formula IV which is _a compound or a salt thereof to an amine, which comprises or a salt thereof and reaction of the formula X compounds of the formula IV _b or a salt thereof represented by:
[45]
[46] [Wherein X represents a chlorine atom, a 1-chloroethoxy group, a chloromethoxy group or a phenoxy group]
[47] R ⁵ R ⁶ NH [X]
[48] [Wherein R ⁵ and R ⁶ each represent a C _1-6 alkyl group or R ⁵ and R ⁶ together with an adjacent nitrogen atom represent a cyclic amino group]
[49]
[50] Wherein R ⁵ and R ⁶ are as defined above;
[51] 8. The method for _a compound formula V or a salt thereof represented by the ring-opening reaction which comprises the compound or a salt thereof isoxazole ring of the formula IV _b:
[52] [Formula IVb]
[53]
[54] Wherein R ⁵ and R ⁶ are as defined in paragraph 7 above;
[55]
[56] Wherein R ⁵ and R ⁶ are as defined in item 7 above;
[57] 9. A process for preparing a compound represented by formula VII _a or a salt thereof, comprising reacting a compound represented by formula V _a or a salt thereof with a compound represented by formula VI or _a salt thereof:
[58] [Formula Va]
[59]
[60] Wherein R ⁵ and R ⁶ are as defined in paragraph 7 above;
[61] [Formula VI]
[62]
[63] Wherein R ² and A are as defined in paragraph 5 above;
[64]
[65] Wherein R ² and A are as defined in item 5 above and R ⁵ and R ⁶ are as defined in item 7 above;
[66] 10, _{a process} for preparing a compound represented by formula IX _a or a salt thereof, comprising reacting a compound represented by formula VII _a or a salt thereof with a compound represented by formula VIII:
[67] Formula VIIa]
[68]
[69] Wherein R ² and A are as defined in item 5 above and R ⁵ and R ⁶ are as defined in item 7 above.
[70] [Formula VIII]
[71] R ⁴ SO _n X ² [VIII]
[72] Wherein R ⁴ , n, and X ² are as defined in paragraph 6 above;
[73]
[74] Wherein R ² and A are as defined in item 5 above, R ⁴ and n are as defined in item ⁶ above and R ⁵ and R ⁶ are as defined in item 7 above;
[75] 11. 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline or salt thereof represented by the following formula (II):
[76] [Formula II]
[77]
[78] 12, a compound represented by formula IV or a salt thereof:
[79] [Formula IV]
[80]
[81] Wherein R ¹ is as defined in paragraph 3 above;
[82] 13. A compound represented by the following formula (V) or a salt thereof:
[83] [Formula V]
[84]
[85] Wherein R ¹ is as defined in paragraph 3 above;
[86] 14. A compound represented by the following formula (VII) or a salt thereof:
[87] [Formula VII]
[88]
[89] Wherein R ¹ is as defined in paragraph 3 above and R ² and A are as defined in paragraph 5 above;
[90] 15. A compound represented by formula IV _a or a salt thereof:
[91] [Formula IVa]
[92]
[93] Wherein X is as defined in paragraph 7 above;
[94] 16. A compound represented by formula IV _b or a salt thereof:
[95] [Formula IVb]
[96]
[97] Wherein R ⁵ and R ⁶ are as defined in item 7 above;
[98] 17. A compound represented by the following formula V _a or a salt thereof:
[99] [Formula Va]
[100]
[101] Wherein R ⁵ and R ⁶ are as defined in item 7 above;
[102] 18. A compound or a salt thereof represented by the formula VII _a:
[103] Formula VIIa]
[104]
[105] Wherein R ² and A are as defined in item 5 above and R ⁵ and R ⁶ are as defined in item 7 above.
[1] The present invention relates to a process for the preparation of oxadiazoline derivatives (for example, compounds [IX], [IX _a ], etc., described below), intermediates for synthesizing oxadiazoline derivatives, and methods for preparing such intermediates. Oxadiazoline derivatives are useful as insecticides and acaricides.
[106] In the above formula, the alkyl group in the optionally substituted alkyl group represented by R ¹ is, for example, a C _1-6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl And tert-butyl.
[107] Substituents on alkyl groups include hydroxyl groups, amino groups, mono- or di-C _1-6 alkylamino groups (eg, methylamino, ethylamino, propylamino, dimethylamino, diethylamino, etc.), C _{1 -6} alkoxy groups (eg methoxy, ethoxy, propoxy, isopropoxy, butoxy etc.), C _1-6 alkylthio groups (eg methylthio, ethylthio, n-propylthio, Isopropylthio, butylthio, etc.), halogen atoms (for example, fluorine, chlorine, bromine, iodine), carboxyl groups, nitro groups, cyano groups, and the like. The substituent is particularly preferably a C _1-6 alkoxy group.
[108] The number of substituents is 1 to 6, preferably 1 to 3, in the substitutable range.
[109] Acyl groups in the optionally substituted acyl group represented by R ¹ include C _1-20 acyl groups derived from carboxylic acids, examples of which include (1) formyl, (2) alkanoyl groups, preferably C _2-10 alkanoyl groups (eg, C _1-9 alkyl-carbonyl groups such as acetyl, propionyl, butyryl, isobutyryl, pentanoyl, hexanoyl, heptanoyl, pivaloyl, etc.), (3 ) Cycloalkanoyl groups, preferably C _4-10 cycloalkanoyl groups (eg cyclopropyl carbonyl, cyclobutyl carbonyl, cyclopentyl carbonyl, cyclohexyl carbonyl, etc.), (4) alkenyl carbon Carbonyl groups, preferably C _3-10 alkenyl carbonyl groups (eg acryloyl, allyl carbonyl, isopropenyl carbonyl, isobutenyl carbonyl, 1-methylallyl carbonyl, cinnamoyl, etc.) (5) alkynyl carbonyl groups, preferably C _3-7 alkynyl carbonyl groups (e.g. Ropargyl carbonyl, 2-butynyl carbonyl, 3-butynyl carbonyl, 3-pentynyl carbonyl and the like), (6) aryl carbonyl groups, preferably C _7-14 aryl-carbonyl groups (e.g. For example, benzoyl, 1-naphtholyl, 2-naphtholyl, and the like), (7) alkoxy carbonyl groups, preferably C _2-6 alkoxy-carbonyl groups (eg methoxycarbonyl, ethoxycarbon Carbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, etc.), (8) aryloxy carbonyl groups, preferably Is a C _7-14 aryloxy-carbonyl group (eg phenoxy carbonyl group), (9) aralkyl carbonyl group, preferably a C _8-19 aralkyl-carbonyl group (eg, Phenyl-C _1-4 alkyl carbonyl such as benzyl carbonyl, phenethyl carbonyl and phenyl propyl carbonyl, and naphthyl-C _1-4 alkyl carbonyl such as benzhydryl carbon Carbonyl and 1-naphthyl ethyl carbonyl), (10) aralkyloxy carbonyl groups, preferably C _8-19 aralkyloxy carbonyl groups (eg, phenyl-C _1-4 alkyloxy carbonyl such as Benzyloxy carbonyl, phenethyloxy carbonyl and phenyl propyloxy carbonyl), (11) carbamoyl groups, and (12) cyclic aminocarbonyl groups (eg, 1-pyrrolidinocarbonyl, piperi Dinocarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl and 1-perhydroazinyl carbonyl, and the like).
[110] When the acyl group is an alkanoyl group, an alkenyl carbonyl group or an alkynyl carbonyl group, the acyl group has 1 to 6 (preferably 1 to 3) substituents such as hydroxyl groups, amino groups, mono- or di-C _{1- 6} alkylamino groups (eg methylamino, ethylamino, propylamino, dimethylamino, diethylamino, etc.), C _1-6 alkoxy groups (eg methoxy, ethoxy, propoxy, isopropoxy , Butoxy, etc.), C _1-6 alkylthio groups (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, etc.), halogen atoms (e.g., fluorine, chlorine , Bromine, iodine), carboxyl groups, nitro groups, cyano groups, phenyl groups and the like.
[111] When the acyl group is a cycloalkanoyl group, an aryl carbonyl group, an alkoxycarbonyl group, an aryloxy carbonyl group, an aralkyl carbonyl group or an aralkyloxy carbonyl group, the acyl group is 1 to 5 (preferably 1 to 3) Substituents such as hydroxyl groups, amino groups, mono- or di-C _1-6 alkylamino groups (eg, methylamino, ethylamino, propylamino, dimethylamino, diethylamino, etc.), C _1-6 alkoxy Groups (eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), C _1-6 alkylthio groups (eg, methylthio, ethylthio, n-propylthio, isopropylthio , n-butylthio, etc.), halogen atoms (e.g., fluorine, chlorine, bromine, iodine), carboxyl groups, nitro groups, cyano groups, phenyl groups, C _1-6 alkyl groups (e.g. methyl , Ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc.), C _2-6 alkenyl groups ( For example, vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, etc., C _2-6 alkynyl groups (eg, ethynyl, 1-propynyl, propargyl, 1 -Butynyl and the like).
[112] When the acyl group is a carbamoyl group, the acyl group is one or two substituents such as (1) C _1-6 alkyl groups (eg, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec- Butyl, tert-butyl, etc.), (2) C _3-9 cycloalkyl groups (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), (3) C _2-6 alkenyl groups (e.g. For example, vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, etc., (4) C _2-6 alkynyl groups (eg, ethynyl, 1-propynyl, propargyl, 1-butynyl, etc.), (5) hydroxyl groups, (6) C _1-6 alkoxy groups (eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), (7) amino Groups, (8) mono- or di-C _1-6 alkyl amino groups (e.g. methylamino, ethylamino, propylamino, dimethylamino, diethylamino, etc.), (9) cyclic amino groups (e.g. , 1-pyrrolidino, piperidino, morpholino, 4-methyl-1-piperazino Etc.) or (10) phenyl group, and the substituents, together with the nitrogen atom to which they are attached, include a cyclic amino group (e.g., 1-pyrrolidino, piperidino, morpholino, thiomorpholino, 4-methyl-1-piperazino and the like). In addition, substituents include hydroxyl groups, amino groups, mono- or di-C _1-6 alkylamino groups (eg, methylamino, ethylamino, propylamino, dimethylamino, diethylamino, etc.), C _1-6 Alkoxy groups (eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), C _1-6 alkylthio groups (eg, methylthio, ethylthio, n-propylthio, isopropyl Thio, n-butylthio and the like), 1 to 6 (preferably 1 to 3) selected from halogen atoms (e.g., fluorine, chlorine, bromine, iodine), phenyl groups, carboxyl groups, nitro groups and cyano groups ) Substituents.
[113] Among these groups described above, R ¹ is preferably an optionally substituted alkyl group, an optionally substituted alkanoyl group, an optionally substituted cycloalkanoyl group, an optionally substituted alkenyl carbonyl group, an optionally substituted aryl carbonyl group , An optionally substituted alkoxy carbonyl group or an optionally substituted carbamoyl group, more preferably an optionally substituted carbamoyl group. R ¹ is particularly preferably (1) a C _1-6 alkyl group optionally substituted with 1 to 3 C _1-6 alkoxy, (2) amino optionally substituted with 1 or 2 C _1-6 alkyl groups, C _{1 -6} alkoxy, phenyl or halogen optionally substituted with 1 to 3 C _2-10 alkanoyl groups, (3) C _4-10 cycloalkanoyl groups, (4) C _3-10 alkenyl carbonyl groups, (5) C _1-6 alkyl, C _3-9 cycloalkyl, C which may be substituted with 1 to 3 substituents selected from benzoyl group, (6) amino, phenyl, halogen optionally substituted with 1 or 2 C _1-6 alkyl _2-6 alkenyl, C _2-6 alkynyl, phenyl, amino optionally substituted with 1 or 2 C _1-6 alkyl, cyclic amino (eg pyrrolidino, piperidino), hydroxyl or C Carbamoyl groups optionally substituted with 1 or 2 _1-6 alkoxy (7) cyclic amino-carbonyl groups (e.g., pyrrolidinocarbonyl, piperidinocarbonyl, 1-perhydroazinyl carbonyl , 4-methyl-1-pipe It possesses a carbonyl, morpholinyl carbonyl noka Viterbo), (8) one to three halogen atoms, an optionally substituted C _2-6 alkoxy-carbonyl group, (9) C _7-14 aryloxy-carbonyl group or (10) a formyl It's wheat. More preferred groups represented by R ¹ include di-C _1-6 alkyl carbamoyl groups, morpholinocarbonyl groups, 1-chloroethoxy carbonyl groups, chloromethoxy carbonyl groups, phenoxy carbonyl groups, and the like. This includes.
[114] Halogen atoms in X ¹ and R ² include fluorine, chlorine, bromine and iodine. In particular, chlorine is preferred.
[115] C _1-6 haloalkyl groups represented by R ² include, for example, C _1-6 alkyl substituted with 1 to 10 (preferably 1 to 5) halogens (eg fluorine, chlorine, bromine, iodine) Groups such as chloromethyl, fluoromethyl, bromomethyl, 2-chloroethyl, dichloromethyl, trichloromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, heptafluoro Propyl, nonafluorobutyl, and the like. In particular, trifluoromethyl is preferable.
[116] C _1-6 haloalkoxy groups represented by R ² include, for example, C _1-6 alkoxy substituted with 1 to 10 (preferably 1 to 5) halogens (eg, fluorine, chlorine, bromine, iodine) Groups such as chloromethoxy, fluoromethoxy, bromomethoxy, 2-chloroethoxy, dichloroethoxy, trichloromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, pentafluoro Methoxy, heptafluoropropoxy and nonafluorobutoxy. Trifluoromethoxy is particularly preferred.
[117] C _1-6 haloalkyl group in the "C _1-6 haloalkyl group optionally substituted phenyl group" represented by R ² include groups of the above-described C _1-6 haloalkyl. The number of substituents on the phenyl group is 1 to 5, preferably 1 to 3. In particular, phenyl groups optionally substituted with 1 to 3 trifluoromethyl groups are preferred.
[118] In particular, A is preferably to be.
[119] C _1-6 alkyl groups represented by R ⁴ include C _1-6 alkyl groups are illustrated above with respect to R ^1.
[120] C _1-6 haloalkyl groups represented by R ⁴ may include a group the illustrated C _1-6 haloalkyl for R ^2.
[121] Examples of the halogen atom represented by X ² include fluorine, chlorine, bromine and iodine. In particular, chlorine is preferred.
[122] R ⁵ and C _1-6 alkyl groups represented by R ⁶ include C _1-6 alkyl groups are the above-exemplified in R ^1. In particular, methyl is preferred.
[123] Cyclic amino groups formed by R ⁵ and R ⁶ together with adjacent nitrogen atoms include, for example, cyclic amino groups such as 1-pyrrolidino, piperidino, morpholino and 4-methyl-1-piperazino do. Especially morpholino is preferable.
[124] The reaction scheme in the present invention is as follows.
[125]
[126]
[127] In Scheme 1, 5-cyanoisoxazole is reacted with hydroxylamine or a salt thereof to prepare isoxazole-5-carboxamide oxime represented by compound [I].
[128] Salts of compound [I] generally include salts with acids, and acids include, for example, inorganic protonic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid and sulfuric acid, organic protonic acids such as formic acid, acetic acid, tartaric acid, malic acid, Citric acid, oxalic acid, succinic acid, benzoic acid, trifluoroacetic acid and p-toluene sulfonic acid, and Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, titanium tetrachloride and boron trichloride.
[129] 5-cyanoisoxazole used as starting material is a known compound (Gazz. Chim.ital. 62, 436 (1932), bp. 168 ° C). Such starting compounds can be isolated and used, but can also be produced by the dehydration reaction of their precursor, 5-isoxazole carboxamide, and introduced into the subsequent reaction either directly or after isolation.
[130]
[131] Dehydrating agents in the scheme include known dehydrating agents such as phosphorus pentoxide, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, trifluoroacetic anhydride, phosgene and dicyclohexyl carbodiimide. Dehydration reactions are described, for example, in "Organic Functional Group Preparations Second Edition" Academic Press, Vol. 1, Chapter 17 (1983).
[132] Compound [I] exists as geometric isomers described below, and the present invention includes all isomers and mixtures thereof.
[133]
[134] The hydroxylamines or salts thereof used in this reaction can be used in any form and can be incorporated into the reaction, for example in the form of hydrochloride, sulfate or aqueous solution.
[135] In this reaction, the amount of hydroxylamine or a salt thereof is not particularly limited, and a hydroxylamine or a salt thereof that also functions as a solvent can be used in an excess, preferably in an amount of about 0.8 to 5 equivalents.
[136] Good results can be obtained by coexisting bases or acting before or after the reaction for the purpose of promoting the reaction or reducing the by-products. Bases include, for example, alkali metal alcoholates such as sodium ethylate, sodium methylate and potassium tert-butoxide, organic bases such as ammonia, triethylamine, diisopropylethylamine, pyridine, 4-dimethyl aminopyridine and N, N-dimethylaniline and inorganic bases such as potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate and sodium hydride. The amount of the base used is not particularly limited as long as it does not adversely affect the reaction, and an excessive amount of a base that also functions as a solvent can be used.
[137] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited as long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent. Such solvents include, for example, aliphatic hydrocarbons such as pentane, hexane, heptane and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene, esters such as methyl acetate, ethyl acetate, ethyl formate and ethyl propionate, alcohols such as methanol , Ethanol, propanol, isopropanol and butanol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran and dioxane, nitrile such as acetonitrile and propio Nitriles, acid amides such as dimethyl formamide and dimethyl acetamide, sulfoxides such as dimethyl sulfoxide, sulfones such as sulfolane, phosphate amides such as hexamethyl phosphoramide, halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and As carbon tetrachloride, and aromatic amines such as pyridine, picoline, lutidine and quinoline are included as a mixed solvent, a mixed solvent with water, and water.
[138] The reaction temperature is generally -30 to 150 ° C, preferably -10 to 80 ° C. The reaction time is generally 0.1 to 72 hours, more preferably about 0.1 to 24 hours.
[139] The resulting compound [I] or a salt thereof is in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure concentration, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, recrystallization After separation and purification by chromatography and chromatography, it can be introduced as a starting material in subsequent reactions.
[140] In scheme 1, 3- (5-isoxazolyl)-represented by compound [II] by reacting isoxazole-5-carboxamide oxime represented by compound [I] or a salt thereof with formaldehyde or an equivalent thereof Δ ² -1,2,4-oxadiazoline or salts thereof can be prepared.
[141] Salts of compound [II] include salts with the acids exemplified above in compound [I].
[142] In general, compound [II] exists as the tautomer described below, and the present invention includes all such tautomers and mixtures thereof.
[143]
[144] Formaldehyde or equivalents thereof used in the present invention include formaldehyde, formalin (aqueous solution of formaldehyde), para-formaldehyde and dimethoxymethane. The amount thereof is not particularly limited, and these, which also function as a solvent, can be used in an excess, preferably in an amount of 0.8 to 15 equivalents.
[145] Good results can be obtained by coexisting acids or acting before or after the reaction for the purpose of promoting the reaction or reducing the by-products. Such acid catalysts include, for example, inorganic proton acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid and sulfuric acid, organic protonic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, trifluoroacetic acid and Toluene sulfonic acid, and Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, titanium tetrachloride and boron trichloride. The amount of the acid catalyst used in the reaction is not particularly limited as long as it does not adversely affect the reaction, and an acid catalyst which also functions as a solvent can be used in excess. The acid is particularly preferably acetic acid or p-toluene sulfonic acid.
[146] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited so long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[147] The reaction temperature is generally -30 to 200 ° C, preferably 0 to 150 ° C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
[148] The resulting compound [II] or a salt thereof is in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, recrystallization After separation and purification by chromatography and chromatography, it can be introduced as a starting material in subsequent reactions.
[149] In Scheme 1, compound [IV] or by reacting 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline or a salt thereof represented by compound [II] with compound [III] or Its salts can be prepared.
[150] Salts of compound [IV] include salts with the acids exemplified above in compound [I].
[151] Compound [III] or an equivalent thereof includes, for example, phosgene, trichloromethyl chloroformate (diphosgene), bistrichloromethyl carbonate (triphosgene), 1-chloroethyl chloroformate, and R ¹ COL [ Wherein R ¹ is as defined above and L is a halogen atom (eg fluorine, chlorine, bromine, iodine), an acyloxy group (C _1-10 acyloxy group, eg formyloxy group; C _1-6 alkyl-carbonyloxy groups optionally substituted with 1 to 3 halogen atoms such as acetoxy group, propionyloxy group and trifluoroacetoxy group, and C _1-6 alkoxy-carbonyloxy group such as me Oxycarbonyloxy and t-butoxycarbonyloxy). Compound [III] is a known compound or can be easily prepared from known compounds.
[152] Compound [III] or an equivalent thereof used in this reaction may form a salt. Such salts include, for example, salts with inorganic protonic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid and sulfuric acid, organic protonic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, trifluoroacetic acid And salts with p-toluene sulfonic acid, and salts with Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, titanium tetrachloride and boron trichloride.
[153] The amount of the compound [III] or equivalent thereof used in such a reaction is not particularly limited as long as it does not adversely affect the reaction, and is preferably 0.8 to 5 equivalents.
[154] Good results can be obtained by coexisting bases or acting before or after the reaction for the purpose of promoting the reaction or reducing the by-products. As the base, the bases described above in the preparation of compound [I] can be similarly used. The amount of the base used is not particularly limited as long as it does not adversely affect the reaction, and an excessive amount of a base that also functions as a solvent can be used.
[155] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited so long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[156] The reaction temperature is generally about -50 to 200 ° C, more preferably -30 to 150 ° C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
[157] The resulting compound [IV] or a salt thereof is in the form of a reaction mixture, or by means known per se, for example, concentration, reduced pressure, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, recrystallization After separation and purification by chromatography and chromatography, it can be introduced as a starting material in subsequent reactions.
[158] In Scheme 1, the isoxazole ring of compound [IV] or a salt thereof can be ring-opened if necessary to produce compound [V] or a salt thereof. Salts of compound [V] include salts with the acids exemplified above for compound [I].
[159] In general, compound [V] exists as tautomers described below, and the present invention includes all such tautomers and mixtures thereof.
[160]
[161] As the base used in the present invention, for example, the bases described above in the preparation of compound [I] are similarly used. The amount of the base is not particularly limited as long as it does not adversely affect the reaction, and an amount of the base that also functions as a solvent can be used in an excess, preferably in an amount of 0.8 to 5 equivalents.
[162] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited so long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[163] The reaction temperature is generally -50 to 200 ° C, preferably -30 to 150 ° C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
[164] The resulting compound [V] or a salt thereof is in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, recrystallization After separation and purification by chromatography and chromatography, it can be introduced as a starting material in subsequent reactions.
[165] In Scheme 1, compound [VII] or a salt thereof can be synthesized by reacting compound [V] or a salt thereof with a hydrazine derivative represented by compound [VI] or a salt thereof. Salts of compounds [VI] and [VII] include salts with the acids exemplified above in compound [I]. Compound [VI] is, for example, 2,6-dichloro-4-trifluoromethyl phenyl hydrazine, which is a known compound or can be easily prepared from known compounds. This reaction proceeds via the hydrazone derivative [XI] shown in the following scheme as an intermediate, and intermediate [XI] can also be generally isolated. The base is then acted on [XI] formed as an intermediate to convert it to compound [VII] or a salt thereof.
[166]
[167] In the reaction of compound [V] or a salt thereof with compound [VI], if necessary, the reaction can be promoted in the presence of a suitable acid catalyst. As the acid catalyst, the acids described above are similarly used in the preparation of the compound [II]. The amount of the acid used is not particularly limited as long as it does not adversely affect the reaction, and an acid that also functions as a solvent can be used in excess.
[168] As the base used in the conversion of intermediate [XI] to compound [VII] or a salt thereof via ring closure, the bases described above in the preparation of compound [I] can be similarly used. The amount of the base to be used is not particularly limited as long as it does not adversely affect the reaction, and the base which also functions as a solvent can be used in an excess, preferably in an amount of 0.8 to 5 equivalents.
[169] When this reaction is carried out following the reaction for converting compound [IV] to compound [V], good results can be obtained.
[170] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited so long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[171] The reaction temperature is generally -50 to 200 ° C, preferably -30 to 150 ° C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
[172] The resulting compound [VII] or a salt thereof is in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, recrystallization After separation and purification by chromatography and chromatography, it can be introduced as a starting material in subsequent reactions.
[173] In Scheme 1, compound [VII] or a salt thereof can be reacted with compound [VIII] to prepare compound [IX] or a salt thereof. Salts of compound [IX] include salts with the acids exemplified above in compound [I]. Compound [VIII] is, for example, trifluoromethane sulfen chloride or trifluoromethane sulfinyl chloride, which is a known compound or can be easily prepared from known compounds.
[174] The amount of the compound [VIII] used in such a reaction is not particularly limited, and preferably about 0.8 to 5 equivalents.
[175] Good results can be obtained by coexisting organic base salts for the purpose of promoting reaction or reducing by-products. Organic base salts include, for example, dimethylamine hydrochloride, dimethylamine-p-toluene sulfonate, triethylamine hydrochloride, pyridine hydrochloride, and pyridine-p-toluene sulfonate. In addition, good results can be obtained by coexisting appropriate acid or base catalysts. As the acid or base catalyst, the acid described above in the preparation of the base or compound [II] described above in the preparation of compound [I] is used. The amount of the organic base salt, the acid and the base is not particularly limited as long as it does not adversely affect the reaction, and such salts, acids and bases that also function as solvents can be used in excess, preferably in an amount of 0.8 to 5 equivalents. .
[176] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited so long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[177] The reaction temperature is generally about -50 to 200 ° C, preferably -30 to 150 ° C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
[178] The resulting compound [IX] or a salt thereof is in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, recrystallization After separation and purification by chromatography and chromatography, it can be introduced as a starting material in subsequent reactions.
[179] Scheme 2, in the case where the compound [IV] in Scheme 1 represents a compound [IV _a], a compound with the compound _{[IV b] [V a]} , [VII a] and [IX _a] (the compounds [V ], [VII] and [IX]), and the reaction scheme 2 is included in scheme 1.
[180] In Scheme 2, compound [IV _a ] or a salt thereof can be prepared by reacting compound [II] or a salt thereof with phosgene or an equivalent thereof or 1-chloroethyl chlorocarbonate. In general, compounds [IV _a ] or salts thereof can be isolated, but when compound [IV _a ] is unstable as in the reaction with phosgene or its equivalent (if X = Cl), preferably compound [IV _a] ] Is introduced into the subsequent reaction without isolation. Salts of compound [IV _a ] include the salts described above for compound [IV].
[181] As phosgene or equivalent thereof used in this reaction, phosgene, trichloromethyl chloroformate (diphosgene), bistrichloromethyl carbonate (triphosgene) and the like are used. These amounts are not specifically limited, Preferably they are 0.3-5 equivalents.
[182] Good results can be obtained by coexisting bases or acting before or after the reaction for the purpose of promoting the reaction or reducing the by-products. As the base, the bases described above in the preparation of compound [I] can be similarly used. The amount of the base used is not particularly limited as long as it does not adversely affect the reaction, and is preferably 0.3 to 5 equivalents.
[183] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited as long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[184] The reaction temperature is generally about -50 to 200 ° C, preferably -30 to 150 ° C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
[185] The resulting compound [IV _a ] or a salt thereof in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure concentration, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, After separation and purification by recrystallization and chromatography, it can be introduced into the starting reaction as starting material.
[186] In Scheme 2, compound [IV _b ] or a salt thereof can be prepared by reacting compound [IV _a ] or a salt thereof with an amine represented by R ⁵ R ⁶ NH.
[187] The amines represented by R ⁵ R ⁶ NH are known compounds such as dimethylamine, diethylamine, di-n-propylamine, dibutylamine, di-n-butylamine, methyl ethylamine, ethyl n-propylamine, p It is either lollidine, piperidine, morpholine or N-methyl piperazine, or can be readily prepared from known compounds.
[188] The amount of the amine used in this reaction is not particularly limited and is preferably about 0.8 to 5 equivalents.
[189] This reaction can be carried out in a suitable solvent. The solvent is not particularly limited so long as it does not react with the reaction substrate, the reaction reagent and the product to provide a by-product, and the solvent is preferably one that dissolves both the reaction substrate and the reaction reagent, for example, in the preparation of compound [I]. The solvents described above are similarly used.
[190] The reaction temperature is generally about -50 to 200 ° C, preferably -30 to 150 ° C. The reaction time is generally 0.1 to 72 hours, more preferably about 0.1 to 24 hours.
[191] The resulting compound [IV _b ] or a salt thereof in the form of a reaction mixture or by means known per se, for example, concentration, reduced pressure concentration, liquid conversion, transfer to another solvent, solvent extraction, distillation, crystallization, After separation and purification by recrystallization and chromatography, it can be introduced into the starting reaction as starting material.
[192] The conversion process of compound [IV _b ] → [V _a ] → [VII _a ] → [IX _a ] in Scheme 2 converts compound [IV] → [V] → [VII] → [IX] in Scheme 1. It can be carried out according to the process.
[193] Compounds [IX] and [IX _a ] and salts thereof prepared according to the method of the present invention are effective for the control of hygienic pests, animal and plant parasites, and exhibit strong insecticidal action by application to parasitic animals and plants. Indicates. The compound [I] of the present invention and the salt thereof of the present invention on plants are low, and its toxicity to fish is also low, so it is safe as a pest control agent for medical, animal husbandry, pet, horticultural and agricultural purposes. It has advantageous properties (Japanese Patent Application No. 11-151959).
[194] Compound [IX] and the compound [IX] and [IX _a] or a salt thereof of [IX _a] or as a salt thereof, agricultural chemicals, in particular for use as a pesticide, one or more as an active ingredient (preferably from 1 to 3) Emulsions, liquids, microemulsions, liquid hydrating agents, emulsions, hydrating agents, powders, granules, fine granules, seeds Dissolved or suspended in a suitable liquid carrier, depending on the purpose of use, in the form of a pesticide, medicament or veterinary preparation such as coatings, smokers, tablets, microcapsules, sprays, EWs, ointments, and poisons. Mix with or adsorb to a solid carrier. Such pesticides, medicaments or veterinary preparations can be prepared by methods known per se, if desired, by adding, for example, emulsifiers, suspending agents, electrodeposition agents, penetrants, wetting agents, thickeners and stabilizers.
[195] The liquid carrier (solvent) used is preferably water, alcohol (eg methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, ethylene glycol, etc.), ketones (eg acetone, methyl ethyl ketone Etc.), ethers (eg, dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, etc.), aliphatic hydrocarbons (eg, kerosene, kerosene, Fuel oils, machine oils, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, solvent naphtha, methyl naphthalene, etc.), halogenated hydrocarbons (e.g., dichloromethane, chloroform, carbon tetrachloride, etc.), acid amides (e.g., For example, N, N-dimethylformamide, N, N-dimethyl acetamide, etc.), esters (eg, ethyl acetate, butyl acetate, fatty acid glycerin esters, etc.), nitriles (eg, Acetonitrile, and a solvent such as propionitrile, etc.), it may be used in combination thereof, alone or in appropriate ratios (preferably 1 to 3 solvent).
[196] As solid carriers (diluents and fillers), vegetable powders (e.g. soybean powder, tobacco powder, flour, wood flour, etc.), mineral powders (e.g. clays such as kaolin, bentonite and acid clays, talc such as talc powders and pagodie Powder, silica such as diatomaceous earth and mica powder), alumina, sulfur powder, activated carbon and the like are used, and one or more (preferably 1 to 3) of these carriers may be mixed in a suitable ratio before use.
[197] Examples of appropriately added ointment bases include polyethylene glycols and pectins, higher fatty acid-polyhydric alcohol esters such as monostearic acid glycerin esters, cellulose derivatives such as methyl cellulose, sodium alginate, bentonite, higher alcohols, polyhydric alcohols such as glycerin, One or more (preferably one to three) of petrolatum, white petrolatum, liquid paraffin, lard, various vegetable oils, lanolin, dehydrated lanolin, hydrogenated oils and resins, and the following surfactants may be added if necessary.
[198] Surfactants suitably used as emulsifiers, wetting agents, penetrants, dispersants, and the like are nonionic and anionic surfactants such as soaps, polyoxyethylene alkyl aryl ethers [e.g., Noigen (trade name), E.AI42 (trade name) ( Dai-ichi Kogyo Seiyaku Co., Ltd.), and Nonal (trade name) (manufactured by Toho Chemical Co., Ltd.)], alkyl sulphate [e.g. Emal 10 (trade name), Emal 40 (trade name) ( Kao Corporation)], alkyl sulfonates (e.g., Neogen ™, Neogen T (trade name) (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.) and Neopelex (manufactured by Kao Corporation)], polyethylene glycol ethers [example For example, Nonipol 85 (trade name), Nonipol 100 (trade name), Nonipol 160 (trade name) (manufactured by Sanyo Chemical Industries, Ltd.), a polyhydric alcohol ester [for example, Tween 20 (trade name), Tween 80 (trade name) (Manufactured by Kao Corporation). In addition, the compound [I] or a salt thereof may be used for other insecticides (pyrethroid insecticides, organophosphorus insecticides, carbamate insecticides, neonicotinoid insecticides, natural insecticides, etc.), mites, nematicides, herbicides, plant hormones Plant growth regulators, fungicides (e.g., copper fungicides, organic chloride fungicides, organic sulfur fungicides, phenolic fungicides and the like), synergists, attractants, insect repellents, pigments, fertilizers and the like.
[199] In pesticide compositions (pesticides) containing compounds prepared according to the process of the invention, the content of compounds [IX] and [IX _a ] or salts thereof is generally from about 0.1 to 80% by weight, preferably based on the total weight of the composition Preferably about 1 to 20% by weight. Specifically, when such active ingredients are used in emulsions, liquids, hydrating agents (eg granular hydrates) and the like, their content is generally about 1 to 80% by weight, preferably about 1 to 20% by weight. to be. When these active ingredients are used in emulsions, powders and the like, their content is generally about 0.1 to 50% by weight, preferably about 0.1 to 20% by weight. When the active ingredients are used in the granules, their content is generally about 5 to 50% by weight, preferably about 1 to 20% by weight.
[200] The amount of other pesticide active ingredients (eg, pesticides, herbicides, acaricides and / or fungicides) incorporated into the pesticide composition of the present invention is about 1 to 80% by weight, preferably about 1 to 20% by weight, based on the total weight. % Range.
[201] The content of additives other than the above-mentioned active ingredients varies depending on the type or content of the active ingredient or the form of the formulation, but is generally about 0.001 to 99.9% by weight, preferably about 1 to 99% by weight. Specifically, based on the total weight of the composition, the surfactant is generally in an amount of about 1 to 20% by weight, preferably about 1 to 15% by weight, the flow aid is in an amount of about 1 to 20% by weight, and the carrier is about It is added in an amount of 1 to 90% by weight, preferably about 1 to 70% by weight. Specifically, when preparing a liquid, it is generally preferred to add surfactant in an amount of about 1 to 20% by weight, preferably about 1 to 10% by weight and water in an amount of about 20 to 90% by weight. When using emulsions, wetting agents (eg, granulating wetting agents) and the like, it may be possible to spray, for example, after dilution with water (for example about 100-5000-fold) appropriately.
[202] Typical examples of pesticides, acaricides and fungicides which can be used in admixture with compounds [IX] and [IX _a ] or salts thereof prepared according to the process of the invention are as follows:
[203] EPN, acephate, isoxathion, isofenphos, isoprocarb, etrimfos, oxydeprofos, quinalphos , Cadusafos, chlorethoxyfos, chlorpyrifos, chlorpyrifos-methyl, chlorofenvinphos, salithion, cyanophosph (cyanophos), disulfoton, dimethoate, dimethoate, sulprofos, diazinon, thiometon, tetrachlorvinphos, tebupirimfos ), Trichlorphon, naled, vamidothion, pyraclophos, pyridafenthion, pyrimiphos-methyl, penitro Fenitrothion, fenthion, phenthoate, posti Fosthiazate, butathiofos, prothiofos, propaphos, propenofos, phosalone, fosalone, fosthiazate, malathion (malathion), methidathion, mettocarb, monocrotophos, BPMC, XMC, alanycarb, ethiofencarb, carbaryl , Carbosulfan, carbofuran, xylylcarb, cloethocarb, thiodicarb, triazamate, pyrimikab ( pirimicarb, fenoxycarb, phenoxycarb, fenothiocarb, furathiocarb, propoxur, bendiocarb, benfurcarrb, Methomyl, acrinathrin, imiprothrin, ethofe nprox, cycloprothrin, sigma-cypermethrin, cyhalothrin, cyfluthrin, cypermethrin, silafluofen, teflulute Tefluthrin, deltamethrin, tralomethrin, fenvalerate, fenpropathrin, flucythrinate, fluvalinate, flu Phenoprox, fluproxyfen, flumethrin, prallethrin, beta-cyfluthrin, benfluthrin, permethrin ), Acetamiprid, imidacloprid, cartap, thiocyclam, nitenpyram, clotianidine, tefuranidine, AKD -1022, thiomethoxam, bensultap, aver Averectectin, emamectin-benzoate, clofentezine, chlorfluazuron, cyromazine, diafenthiuron, dienochlor , Dichlorvos, diflubenzuron, spynosyn, sulfluramid, teflubenzuron, tebufenozide, tebufenozide, tebufenpyrad ), Hydroprene, vaniliprole, pymetrozine, pyridaben, pyridaben, pyriproxyfen, pyrimidifen, fipronil, pena Fenazaquin, fenpyroximate, fluazuron, flucycloxuron, flufenoxuron, buprofezin, hexaflumuron, hexaflumuron Hexythiazox, milbemycin, methoxiadia (metoxadiazone), lufenuron, levamisol, chlorphenapyr, NC-184, etoxazole, IBP, ampropylfos, edifenphos, chlor Thiothios, tolclofos-methyl, fosetyl, ipconazole, imazalil, imibenconazole, etaconazole, Epoxyconazole, cyproconazole, diniconazole, difenoconazole, tetraconazole, tebuconazole, triadimenol, Triadimefon, triticonazole, triforine, bitertanol, viconazole, viniconazole, fenarimol, fenbuconazole, fluorotree Fluotrimazole, furconazole-cis, flusilazole ( flusilazole, flutriafol, bromuconazole, propiconazole, hexaconazole, pefurazoate, penconazole, microclobutanyl (myclobutanil), metconazole, carbendazine (cabendazin), debacarb, prothiocarb, benomyl, maneb, TPN, isoprothiolane , Iprodione, iminoctadine-albesil, iminoctadine-triacetate, ethirimol, etridiazole, oxadixyl, Oxycarboxin, Oxolinic Acid, Ofurace, Kasugamycin, Carboxin, Captan, Clozylacon, Cloventia Chlobenthiazone, cyprodinil, cyprofuram, dietofenca Diethofencarb, dichlofluanid, dilomezine, geneb, zineb, dimethirimol, dimethomorph, dimefluazole, Thiabendazole, thiophanate-methyl, thifluzamide, tecloftalam, triazoxide, triclamide, tricyclazole (tricyclazole), tridemorph, triflumizole, valididamycin A, hymexazol, pyracarbolid, pyrazophos, pyrazophos pyrifenox, pyrimethanil, pyroquilon, ferimzone, fenpiclonil, fenpropidin, fenpropidin, fenpropimorph, phthalide ), Furametpyr, furalaxyl, fluazinam, fur Furcarbanil, fluquinconazole, fludioxonil, flusulfamide, flutolanil, butiobate, prochloraz, Procymidone, probenazole, benalaxyl, benodanil, penodacuron, myclozolin, metaclozolin, metalaxyl, metsulfobox (metsulfovax ), Metfuroxam, mepanipyrim, mepronil, kresoxim-methyl, azoxystrobin, SSF-126, and carpropamide ( carpropamid).
[204] Pesticide preparations containing compounds [IX] and [IX _a ] or salts thereof prepared according to the process of the invention are suitable for pests, for example, stink bugs such as Eurydema rugosum, Scotinophara lurida, saws Riptotus clavatus, Steppeitis nashi, Perilla (Laodelphax striatellus), Pleurotus (Nilaparvata lugens), Cicada (Nephotettix cincticeps), Pinnacle (Unaspis yanonensis) , Borderless aphids (Lipaphis erysimi), Cabbage aphids (Brevicoryne brassicae), Cotton aphids (Aphis gossypii), Peach aphids (Myzus persicae), Prickly aphids (Aulacorthum solani), Zodiac aphis (Aphis spigaecira) Louis (Bemisia tabaci), Trialurodes vaporariorum, Solanella furcifera, Onukii larvae (Empoasca onukii), Pseudococus comstocki, Tangerine larvae (Pla) nococcus citri, Icerya purchasi, Brown-winged Stingray (Plautia stali), Eysarcoris parvus, etc., Lepidoptera pests such as Spodoptera litura, Chinese cabbage moth (Plutella xylostella) , Chinese Cabbage Butterfly (Pieris rapae crucivora), Black-tailed Moth (Chilosupppressalis), Black-tailed Night Moth (Autographa nigrisigna), Tobacco Moth (Helicoverpa assulta), Moth Moth (Pseudaletia separata), Thief Moth (Mamestrabrassicaxo) orana fasciata, cotton moth (Notarcha derogata), horned moth (Cnaphalocrocis medinalis), potato horn moth (Phthorimaea operculella), chilopolychrysus, long-winged moth (Typoryza incertulas), pabam moth (Spodoptera) , Agrotis segetum, Agrotisipsilon, Heliothisarmigera, Heliothisvirescens, Heliothis zea, Rice Moth (Narangaaenescens), European lighting moth (Ostrinia nubilalis), Light moth (Ostrinia furnacalis), Parrot butterfly (Parnara guttata), Adoxophyes spp., Camellia moth (Caloptilia theivora) (Phyllonorycter ringoneella), peach moth (Carposina niponensis), Peach pure moth (Grapholita molesta), etc., coleopteran pests such as Epilachna vigintioctopunctata, cucumber leaf beetle (Aulacophorafemorare), flea leaf beetle (Phtri tatata) Leaf beetle (Oulema oryzae), Rice root weevil (Echinocnemus squameus), Rice weevil (Lissorhoptrus oryzophilus), Cotton weevil (Anthonomusgrandis), Red bean weevil (Callosobruchus chinensis) ), Copper beetle (Anomala cuprea), corn root beetle species (Diabrotica spp.), Colorado potato leaf beetle (Leptinotarsa decemlineata), root beetle Species (Agriotes spp.), Beetle (Lasioderma serricorne), anthracnose (Anthrenus verbasci), Tribolium castaneum, Lyctusbrunneus, Anoplophoramalasiaca, Pine needles (Tomicus piniper) Flyworm pests such as Musca domestica, Culex popiens pallens, Tabanus trigonus, Delia antiqua, Delia platura, Anophelessinensis, and rice leaves Agromyza oryzae, Hydrellia griseola, Chlorops oryzae, Dacuscucurbitae, Ceratitis capitata, Liriomyza trifolii, etc. Locustamigratoria, Gryllotalpa africana, Oxya yezoensis, Oxya japonica, etc., Pleuropod pests such as Thripstabaci, Tripps Thrips parmi, Frankliniella occidentalis, Baliothrips biformis, Scirtothrips dorsalis, etc., felling pests such as Athalia rosae, cockroach pests such as German wheels (Blattella germanica), Periplaneta fuliginosa, Periplaneta japonica, Periplaneta americana, etc. Spotted mite (Tetranychuscinnabarinus), apple mite (Panonychus ulmi), tangerine nectar (Aculopspelekassi), dust mite (Polyphagotarsonemus latus), root mite (Rhizoglyphus echinopus), etc. ), Prattylenchus penetrans, Nothotylenchus acris, etc., and termites such as Coptotermes formo. sanus), Yamato termites (Reticulitermes speratus), Taiwan termites (Odontotermes formosanus), and Cryptotermes domesticus.
[205] Pharmaceutical or veterinary preparations containing [IX] and [IX _a ] or salts thereof prepared according to the method of the present invention are also useful in vertebrates such as humans, cattle, sheep, goats, in the field of animal disease treatment or in the livestock industry. It can be used to maintain public health by controlling arthropods or parasites that live on or outside pigs, chickens, dogs, cats and fish. For example, parasites include mite species (Ixodes spp.), Bophillus spp. (E.g., Boophilus Microplus), Amblyomma spp., Hyaloma species (Hyalomma spp.), Lipicephalus spp. (E.g., Rhipicephalus appendiculatus), Haemaphysalis spp., Dermacentor spp. Ornitoodorus spp. (E.g. Ornitoodorus moubata), Dermahyssus gallinae, Sarcoptes spp. (E.g. Sarcoptes scabiei), Psoroptes spp., Chorioptes spp., Demodex spp., Eutrombicula spp., Aedes Species (Aedes spp.), Anopheles spp., Musca spp., Hippoderma species ( Hypoderma spp.), Gasosterophilus spp., Simulium spp., Triatoma spp., Teeth (e.g., Damalinia spp.), Reno Gnotus species (Linognathus spp.), Stenocephalides spp., Monomorium pharaonis, and nematodes (e.g. trichostrongyles) (e.g., Neppostrongylus brasiliensis, nematode (Trichostrongylus axei), filamentous nematode (Trichostrongylus colubriformis), nematode (e.g. Trichinella spiralis), nematode (Haemonchus contortus), Nematodyrus (e.g. For example, Nematotorus battus, Ostertagia circumcincta, Couperia spp., Hymenolepis nana, and the like.
[206] Pesticide compositions containing compounds [IX] and [IX _a ] or salts thereof prepared according to the process of the present invention have excellent pesticidal activity, are very low in toxicity and safe and can be used as excellent pesticide compositions (pesticides). The pesticide composition of the present invention can be used in the same manner as the conventional pesticide composition, as a result, it can exhibit a superior effect than the conventional composition.
[207] For example, the pesticide composition of the present invention is sprayed on rice fields, fields, orchards, non-cultivated land, houses, etc. by methods known per se, thereby contacting or ingesting the above-described growing pests and controlling them. In another manner, arthropods or parasites parasitic in vertebrates can be controlled by administering the pesticide composition of the present invention, for example, internally (in the body) or externally (surface of the vertebrates mentioned above).
[208] Specifically, the pesticide composition of the present invention is, for example, seed treatment, seedling treatment, blood donation treatment, main treatment, soil mixing treatment, foliage. ) It can be used for pests of interest by application of dispersion, infusion, bait, fuming, irrigation, or rice paddy. The amount of the composition may vary widely depending on the time of application, the place of application, the method of application, and the like, but in general, the active ingredient (compounds [IX] and [IX _a ] or a salt thereof) is generally from about 0.3 to 3,000 g, preferably about Apply in amounts of 50 to 1,000 g. In addition, when the pesticide composition is a hydrating agent, it can be used after diluting so that the final concentration of the active ingredient is in the range of about 0.1 to 1,000 ppm, preferably about 10 to 500 ppm.
[209] In the following, the present invention is described in more detail with reference to Examples, but these Examples are not intended to limit the present invention.
[210] Elution in column chromatography in the examples and reference examples was performed while monitoring by TLC (thin layer chromatography). In monitoring by TLC, Kiesel gel 60F254 (70-230 mesh) from Merck was used as the TLC plate; The same developing solvent as in column chromatography was also used as solvent in TLC; UV detectors were used in the detection. As silica gel for the column, Kiesel gel 60 (70-230 mesh) from Merck was also used. NMR spectra representing proton NMR were measured by a Blukar AC-200P (200 MHz) spectrometer with tetramethyl silane as an internal reference and all δ values were expressed in ppm. When using a mixed solvent as the developing solvent, the values in parentheses indicate the mixed volume ratio of each solvent. Abbreviations in Examples and Reference Examples include Me, methyl group; Et, ethyl group; Ph, phenyl group; Pr-n (or n-Pr), n-propyl; Pr-i (or i-Pr), isopropyl; Bu-n (or n-Bu), n-butyl; Bu-i (or i-Bu), isobutyl; Bu-s (or s-Bu), sec-butyl; Bu-t (or t-Bu), tert-butyl; s, singlet; br, wide, brs, wide singlet; d, doublet; t, triplet; q, quadruple; qu, quintet; sep, quartet; m, multiplet; dd, doublet; dt, double triplet; J, coupling constants; Hz, hertz; %, weight%; m.p. By melting point, "room temperature" means about 15 to 25 ° C.
[211] Example 1
[212] Isoxazole-5-carboxamide oxime
[213] To a solution of 2.80 g (25.0 mmol) of 5-isoxazole carboxamide in 30 mL of dimethylformamide was added dropwise 2.80 mL (30.3 mmol) of phosphorus oxychloride under ice-cooling. After this dropping, the mixture was warmed to room temperature and stirred for 1 hour. The reaction mixture was poured into 100 ml of ice water and extracted with 100 ml of ethyl acetate. The aqueous layer was salted out and extracted twice with 100 ml of ethyl acetate. The ethyl acetate extracts were combined, dried over magnesium sulfate anhydride and concentrated to give 5-cyanoisoxazole as a pale yellow oily material. After addition of 30 ml of methanol to dissolve this product, 2.32 g (32.5 mmol) of hydroxylamine hydrochloride are added, an additional 4.55 ml (32.5 mmol) of triethylamine are added, and the mixture is at room temperature. Stir for 18 hours. After methanol was distilled off under reduced pressure, 100 ml of aqueous saturated brine were added and the reaction mixture was extracted three times with 100 ml of ethyl acetate. The ethyl acetate extracts were combined, dried over anhydrous magnesium sulfate and concentrated to give colorless crystals. It was recrystallized from chloroform to give 2.90 g (22.8 mmol) of the title compound as colorless crystals.
[214]
[215] Example 2
[216] 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline
[217] To a solution of 1.76 g (13.8 mmol) of isoxazole-5-carboxamide oxime in 30 mL acetonitrile is added 5.2 mL (69.4 mmol) 37% aqueous formalin and 0.5 mL acetic acid and the mixture is refluxed at 30 Heated for an hour. Acetonitrile was distilled off under reduced pressure, 50 ml of ethyl acetate was added, and then washed twice with 20 ml of aqueous saturated brine. The ethyl acetate extract was dried over anhydrous magnesium sulfate and concentrated to give a yellow oily material. 20 ml of acetonitrile were added to the oil, followed by 1.0 ml (13.4 mmol) of 25% aqueous ammonia. The mixture was stirred at rt for 20 min, the solvent was distilled off, then 50 mL of ethyl acetate was added, followed by washing with 20 mL of aqueous saturated brine. The reaction mixture was dried over magnesium sulfate and concentrated to give yellow crystals. After purification by silica gel column chromatography (ethyl acetate: chloroform = 1: 1), the resulting crystals were washed with a mixed solvent of n-hexane and chloroform (1: 1) to give 1.37 g (9.84 mmol) of the title. The compound was obtained as colorless crystals.
[218]
[219] Example 3
[220] 4-dimethylcarbamoyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline (method of using triphosgene)
[221] To a solution of 2.89 g (9.74 mmol) of bis (trichloromethyl) carbonate (triphosgene) in 5 mL of tetrahydrofuran was added dropwise 3.50 g (44.2 mmol) of pyridine under ice cooling. After stirring for 30 minutes under ice cooling, a solution of 3.37 g (24.2 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxydiazoline in 40 ml of tetrahydrofuran was subjected to ice cooling. Added dropwise. After the mixture was stirred under ice cooling for 1 hour, 7.7 mL (73.4 mmol) of 50% aqueous dimethylamine was added dropwise and the resulting mixture was stirred for 30 minutes, warmed to room temperature and stirred for 16 hours. To the mixture was added 30 ml of water and 30 ml of aqueous saturated brine and the reaction mixture was extracted with 50 ml of ethyl acetate. The ethyl acetate layer was washed twice with 30 ml of aqueous saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off to give a brown oily material. After purification by silica gel column chromatography (acetone: n-hexane = 1: 1), the resulting crystals were washed with a mixed solvent of n-hexane and chloroform (10: 1) to give 4.03 g (19.2 mmol) of the title. The compound was obtained as colorless crystals.
[222]
[223] Example 4
[224] 3-cyanoacetyl-4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazoline
[225] 840 mg (4.0 mmol) of 4-dimethylcarbamoyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxydiazoline in 2 ml of water and 2.16 g (5.4 mmol) of 10 % Aqueous sodium hydroxide was added and the mixture was stirred at rt for 30 min. The pH of the mixture was adjusted to 1 by addition of about 5 mL of 1.2 N hydrochloric acid, followed by extraction once with 30 mL of ethyl acetate and twice with 20 mL of ethyl acetate. The ethyl acetate layers were combined and washed twice with 20 mL aqueous saturated brine. The solution was dried over anhydrous magnesium sulfate and concentrated to give 850 mg (4.0 mmol) of the title compound as a brown oily substance.
[226]
[227] Example 5
[228] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl) pyrazole
[229] 289 mg (1.18 mmol) of 2,6 in a solution of 370 mg (1.76 mmol) of 3-cyanoacetyl-4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazoline in 7 ml of methanol -Dichloro-4-trifluoromethylphenyl hydrazine was added. Three drops of 1.2N hydrochloric acid were added and the mixture was stirred at room temperature for 3 hours and stirred at reflux for 11 hours. 50 ml of ethyl acetate was added to the mixture, and the resulting mixture was washed twice with 30 ml of aqueous saturated brine. The reaction mixture was dried over anhydrous magnesium sulfate and concentrated to give a brown oily material. After purification by silica gel column chromatography (ethyl acetate: n-hexane = 2: 1), the resulting crystals were washed with a mixed solvent of n-hexane and chloroform (10: 1) to give 477 mg (1.09 mmol) of The title compound was obtained as colorless crystals.
[230]
[231] Example 6
[232] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl) pyrazole
[233] 595 mg (2.57 mmol) in a suspension of 500 mg (2.38 mmol) 4-dimethylcarbamoyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 15 mL of methanol A solution of 28% sodium methoxide in methanol was added and the mixture was stirred at rt for 2 h. 0.157 mL (2.82 mmol) of concentrated sulfuric acid and 583 mg (2.38 mmol) of 2,6-dichloro-4-trifluoromethylphenyl hydrazine were added to the reaction mixture, and the mixture was stirred at room temperature for 23 hours. 0.498 mL (3.57 mmol) triethylamine was added to the mixture and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and 50 mL of ethyl acetate was added to the residue, which was then washed with aqueous saturated brine and dried over anhydrous magnesium sulfate. The reaction mixture was concentrated under reduced pressure and the resulting crystals were washed with a mixed solvent of n-hexane and ethyl acetate (3: 1) to afford 720 mg (1.65 mmol) of the title compound as brown crystals.
[234] Yield 69%.
[235] Physical data: see Example 5.
[236] Example 7
[237] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl) -4 -Trifluoromethylsulfinylpyrazole
[238] 5-amino-1 of 301 ㎎ (0.688 mmol) in a 4 ㎖ 1,2- dichloroethane (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl -Δ ² To a solution of -1,2,4-oxadiazolin-3-yl) pyrazole was added 250 mg (2.16 mmol) pyridine hydrochloride. To the resulting mixture was added 226 mg (1.48 mmol) trifluoromethanesulfinylchloride and the mixture was stirred at rt for 4 h. To the mixture was further added 318 mg (2.75 mmol) pyridine hydrochloride and 136 mg (0.89 mmol) trifluoromethanesulfinylchloride. After stirring for 22 hours at room temperature, 40 ml of ethyl acetate were added and the mixture was washed twice with 20 ml of aqueous saturated brine. The mixture was dried over anhydrous magnesium sulfate and then the solvent was distilled off to give a yellowish oily material. After purification by silica gel column chromatography (ethyl acetate: n-hexane = 2: 1), the resulting oily substance was washed with a mixed solvent of n-hexane and chloroform (10: 1) to give 329 mg (0.594 mmol). The title compound of was obtained as colorless crystals.
[239]
[240] Example 8
[241] 4-dimethylcarbamoyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline (method using 1-chloroethyl carlocarbonate)
[242] To a solution of 1.00 g (7.19 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 90 mL of acetonitrile was added 1.26 mL (9.03 mmol) triethylamine. It was. 0.69 mL (9.06 mmol) of 1-chloroethyl chlorocarbonate was added dropwise under ice cooling to the mixture. The mixture was stirred under ice cooling for 1 hour, after which the acetonitrile was distilled off, 100 ml of water were added and the reaction mixture was extracted three times with 200 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated and the resulting residue was dissolved in 40 ml of acetonitrile. To the solution is added 2.10 mL (22.5 mmol) of 50% aqueous dimethylamine dropwise under ice cooling, the temperature of the mixture is raised to room temperature and the mixture is stirred for 3 hours. The reaction mixture was poured into 200 ml of 1% hydrochloric acid under ice cooling and then extracted twice with 200 ml of ethyl acetate. The extract was washed with 300 ml aqueous saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized by adding a mixed solvent of diisopropyl ether and chloroform (10: 1) to give 1.18 g (5.61 mmol) of the title compound as reddish brown crystals.
[243] Yield 78%.
[244] Physical data: see Example 3.
[245] Example 9
[246] 4- (1-Chloroethoxycarbonyl) -3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline
[247] To a solution of 4.20 g (30.0 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 200 mL of acetonitrile, add 5.30 mL (37.9 mmol) triethylamine. It was. To the mixture was added 2.90 mL (37.9 mmol) of 1-chloroethyl chloroacetate under ice cooling. The reaction mixture was stirred for 1 h under ice-cooling, concentrated, and the residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to give 5.69 g (23.2 mmol) of the title compound as light brown. Obtained as an oily material.
[248]
[249] Example 10
[250] 4-dimethylcarbamoyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline (method using chloromethyl chlorocarbonate)
[251] To a solution of 1.00 g (7.19 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 20 mL of acetonitrile, add 1.26 mL (9.03 mmol) triethylamine. It was. To the mixture was added 0.80 mL (9.06 mmol) of chloromethyl chlorocarbonate dropwise under ice cooling. After the reaction mixture was stirred under ice cooling for 1 hour, the insoluble material was removed by filtration and 2.10 mL (22.5 mmol) of 50% aqueous dimethylamine was added dropwise under ice cooling. The mixture was warmed to room temperature and the reaction mixture was stirred for 3 hours, then poured into 200 ml of 1% hydrochloric acid, pre-cooled on ice, and extracted twice with 200 ml of ethyl acetate. The extract was washed with 300 ml aqueous saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized by adding a mixed solvent of diisopropyl ether and chloroform (10: 1) to give 0.89 g (4.23 mmol) of the title compound as light brown crystals.
[252] Yield 59%.
[253] Physical data: see Example 3.
[254] Example 11
[255] 4- (chloromethoxycarbonyl) -3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline
[256] To a solution of 500 mg (3.60 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 45 mL of acetonitrile add 0.63 mL (4.51 mmol) triethylamine dropwise. It was. 0.41 mL (4.51 mmol) of chloromethyl chlorocarbonate was added dropwise under ice cooling to the mixture. The reaction mixture was stirred for 1 h under ice cooling, then concentrated and the residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to give 569 mg (2.46 mmol) of the title compound as colorless. Obtained as an oily substance.
[257]
[258] Example 12
[259] 4-dimethylcarbamoyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline (method using phenyl chlorocarbonate)
[260] To a solution of 1.00 g (7.19 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 20 mL of acetonitrile, add 1.26 mL (9.03 mmol) triethylamine. It was. To the mixture was added 1.14 mL (9.06 mmol) of phenyl chlorocarbonate dropwise under ice cooling. After stirring for 1 hour under ice cooling, the insoluble material was removed by filtration and 2.10 mL (22.5 mmol) of 50% aqueous dimethylamine was added dropwise under ice cooling. The mixture was warmed to room temperature, the mixture was stirred for 3 hours, the reaction mixture was poured into 200 ml of 1% hydrochloric acid, pre-cooled on ice, and extracted twice with 200 ml of ethyl acetate. The extract was washed with 300 ml aqueous saturated brine and dried over anhydrous magnesium sulfate. The resulting black oily material was purified by silica gel column chromatography (ethyl acetate) to afford 0.45 g (2.14 mmol) of the title compound as light yellow crystals.
[261] Yield 30%.
[262] Physical data: see Example 3.
[263] Example 13
[264] 4- (phenoxycarbonyl) -3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline
[265] To a solution of 500 mg (3.60 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 45 ml of acetonitrile add 0.63 ml (4.51 mmol) triethylamine. It was. To the mixture was added 0.57 mL (4.51 mmol) of phenyl chlorocarbonate dropwise under ice cooling. The reaction mixture was stirred for 1 hour under ice cooling, concentrated and the residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to give 890 mg (3.43 mmol) of the title compound as colorless. Obtained as an oily material.
[266]
[267] Example 14
[268] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl) -4 -Trifluoromethylsulfinylpyrazole
[269] 500 mg (1.14 mmol) of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2, in 5 ml of toluene, To a suspension of 4-oxadiazolin-3-yl) pyrazole was added 373 mg (1.72 mmol) of dimethylamine p-toluene sulfonate. To the mixture was added 227 mg (1.49 mmol) trifluoromethanesulfinylchloride and the mixture was stirred at 50 ° C. for 8 hours. After 50 ml of ethyl acetate was added to the reaction mixture, the resulting mixture was washed with 20 ml of aqueous saturated sodium bicarbonate and then 20 ml of aqueous saturated brine. The solution was dried over anhydrous magnesium sulfate and the solvent was distilled off to give 590 mg (1.07 mmol) of the title compound as light brown crystals.
[270] Yield 94%.
[271] Physical data: see Example 7.
[272] Example 14
[273] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl)- 4-trifluoromethylsulfinylpyrazole
[274] 500 mg (1.14 mmol) of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2 in 5 ml of dichloroethane To a solution of, 4-oxadiazolin-3-yl) pyrazole 186 mg (2.29 mmol) of dimethylamine hydrochloride were added. 262 mg (1.72 mmol) trifluoromethanesulfinylchloride was added to the mixture, and the mixture was stirred at room temperature for 48 hours. After 50 ml of ethyl acetate was added to the reaction mixture, the mixture was washed with 20 ml of aqueous saturated sodium bicarbonate and then with 20 ml of aqueous saturated brine. The solution was dried over anhydrous magnesium sulfate and the solvent was distilled off to give 540 mg (0.98 mmol) of the title compound as light brown crystals.
[275] Yield 86%.
[276] Physical data: see Example 7.
[277] Example 16
[278] 4-morpholinocarbonyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline
[279] To a solution of 1.68 g (5.72 mmol) bis (trichloromethyl) carbonate (triphosgene) in 100 mL tetrahydrofuran was added 2.04 g (25.8 mmol) pyridine under ice cooling. The mixture is stirred on ice for 5 minutes under ice cooling and a solution of 2.00 g (14.4 mmol) of 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 60 ml of tetrahydrofuran Was added dropwise under ice-cooling. After an additional 2 hours of stirring under ice cooling, 1.49 g (17.2 mmol) of morpholine were added dropwise under ice cooling, and the mixture was stirred for 2 hours under ice cooling. The solvent was distilled off under reduced pressure, 200 ml of aqueous saturated brine were added and the reaction mixture was extracted twice with 200 ml of ethyl acetate. The ethyl acetate layer was washed with 300 ml of aqueous saturated brine, then dried over anhydrous magnesium sulfate, the solvent was distilled off and the residue was recrystallized from diisopropyl ether and chloroform (5: 1) to give 2.10 g ( 8.33 mmol) of the title compound mole were obtained as colorless crystals.
[280]
[281] Example 17
[282] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-morpholinocarbonyl-Δ ² -1,2,4-oxadiazolin-3-yl) pyra Sol
[283] 918 mg in methanol in a solution of 1 g (3.96 mmol) of 4-morpholinocarbonyl-3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline in 10 ml of acetonitrile A solution of 28% sodium methoxide in (4.76 mmol) methanol was added and the mixture was stirred for 2.5 hours under ice cooling. To the mixture was added a solution of 0.29 mL (5.44 mmol) of concentrated sulfuric acid, and 1.09 g (4.36 mmol) of 2,6-dichloro-4-trifluoromethylphenyl hydrazine in 20 mL of ethanol, and the resulting mixture was 80 ° C. Stirred for 2 h. The reaction mixture was warmed to room temperature, 0.90 mL (13.07 mmol) of 25% ammonia water was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and 200 ml of ethyl acetate was added to the residue, which was then 100 ml of 10% hydrochloric acid, 100 ml of aqueous saturated brine, 100 ml of saturated aqueous sodium bicarbonate and 100 ml of aqueous saturated brine. Washed in this order and dried over anhydrous magnesium sulfate. The reaction mixture was concentrated under reduced pressure and the resulting crystals were washed with a mixed solvent of n-hexane and ethyl acetate (5: 1) to afford 1.84 g (3.84 mmol) of the title compound as brown crystals.
[284]
[285] Example 18
[286] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-morpholinocarbonyl-Δ ² -1,2,4-oxadiazolin-3-yl)- 4-trifluoromethylsulfinylpyrazole
[287] 500 mg (1.04 mmol) of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-morpholinocarbonyl-Δ ^2-1 , in 5 ml of acetonitrile, To a solution of 2,4-oxadiazolin-3-yl) pyrazole was added 122 mg (1.50 mmol) of dimethylamine hydrochloride. To the mixture was added 198 mg (1.30 mmol) trifluoromethanesulfinylchloride and the mixture was stirred at rt for 24 h. The solvent was distilled off under reduced pressure, 100 ml of ethyl acetate was added and the reaction mixture was washed with 100 ml of aqueous saturated sodium bicarbonate and then 100 ml of aqueous saturated brine. After the reaction mixture was dried over anhydrous magnesium sulfate, the solvent was distilled off and the residue was recrystallized from a mixed solvent of n-hexane and ethyl acetate (5: 1) to give 410 mg (0.69 mmol) of the title compound as brown. Obtained by crystals.
[288]
[289] Reference Example 1
[290] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl) -4 -Trifluoromethylsulfinylpyrazole
[291] 1 g (2.07 mmol) of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (Δ ² -1,2,4-oxadiazoline- in 10 ml of acetonitrile 0.442 mg (2.07 mmol) of diisopropylethylamine was added to a solution of 3-yl) -4-trifluoromethylsulfinylpyrazole and the mixture was dried over ice. To the mixture was added 0.233 mL (2.49 mmol) chloromethylchlorocarbonate and 5 mg 4-dimethylaminopyridine and the mixture was stirred at rt for 6 h. To the reaction mixture was added a solution of 1.66 M dimethylamine in 3.75 mL (6.22 mmol) acetonitrile and the mixture was stirred at rt for 1.5 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate: chloroform = 1: 1) to give 430 mg (0.78 mmol) of the title compound as a yellow solution.
[292] Yield 38%.
[293] Physical data: see Example 7.
[294] Reference Example 2
[295] 5-amino-3- (4- (1-chloroethoxycarbonyl) -Δ ² -1,2,4-oxadiazolin-3-yl) -1- (2,6-dichloro-4-trifluoro Romethylphenyl) -4-trifluoromethylsulfinylpyrazole
[296] 5 g (10.4 mmol) of 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (Δ ² -1,2,4-oxadiazoline- in 50 ml of acetonitrile To a solution of 3-yl) -4-triflouromethylsulfinylpyrazole) was added 1.74 mL (12.5 mmol) triethylamine and the mixture was dried over ice. To the mixture was added 1.34 mL (12.5 mmol) 1-chloroethyl chlorocarbonate and 10 mg 4-dimethylaminopyridine and the mixture was stirred at 60 ° C for 24 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 2) to give 2.7 g (4.83 mmol) of the title compound as a yellow amorphous material.
[297] Yield 47%.
[298] Reference Example 3
[299] 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3- (4-dimethylcarbamoyl-Δ ² -1,2,4-oxadiazolin-3-yl) -4 -Trifluoromethylsulfinylpyrazole
[300] 500 mg (0.895 mmol) in 5 ml of acetonitrile 5-amino-3- (4- (1-chloroethoxycarbonyl) -Δ ² -1,2,4-oxadiazoline obtained in Reference Example 2 1.66 M dimethylamine in 2.69 mL (4.46 mmol) of acetonitrile in a solution of -3-yl) -1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole The solution was added and the mixture was stirred at rt for 29 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate: chloroform = 2: 1) to give 197 mg (0.358 mmol) of the title compound as a yellow solution.
[301] Yield 40%.
[302] Physical data: see Example 7.
[303] As described above, according to the present invention, there is provided a method which is advantageous for the industrial mass production of Δ ² -1,2,4-oxadiazoline derivatives or salts thereof having a high pesticidal effect in high yield.

权利要求:
Claims (18)
[1" claim-type="Currently amended] Process for preparing isoxazole-5-carboxamide oxime represented by formula (I) comprising reacting 5-cyanoisoxazole with hydroxylamine or a salt thereof:
[Formula I]
[2" claim-type="Currently amended] 3- (5-isoxazolyl) -Δ ² -1 represented by the following formula (II) comprising reacting isoxazole-5-carboxamide oxime or a salt thereof represented by formula (I) with formaldehyde or an equivalent thereof Method for preparing 2,4-oxadiazoline or salts thereof:
[Formula I]
[Formula II]
[3" claim-type="Currently amended] Comprising reacting 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline or a salt thereof represented by the following formula (II) with a compound represented by the following formula (III) or an equivalent thereof or a salt thereof Method for preparing a compound represented by the following general formula (IV) or a salt thereof:
[Formula II]
[Formula III] R ¹ X ¹ [III] [Wherein, X ¹ represents a halogen atom, R ¹ represents an optionally substituted alkyl group, an optionally substituted acyl group or a chlorocarbonyl group (ClCO)] [Formula IV]
Wherein R ¹ is as defined above.
[4" claim-type="Currently amended] Method for preparing a compound represented by the following formula (V) or a salt thereof including ring-opening the isoxazole ring of the compound represented by the formula (IV) or a salt thereof:
[Formula IV]
[Wherein R ¹ is as defined in paragraph 3] [Formula V]
Wherein R ¹ is as defined in claim 3.
[5" claim-type="Currently amended] A process for preparing a compound represented by the following formula (VII) or a salt thereof, comprising reacting a compound represented by the following formula (V) or a salt thereof with a compound represented by the following formula (VI) or a salt thereof:
[Formula V]
[Wherein R ¹ is as defined in paragraph 3] [Formula VI]
[Wherein A is a nitrogen atom or (Wherein R ³ represents a chlorine atom or a cyano group), and R ² represents (1) halogen, (2) C _1-6 haloalkyl group, (3) C _1-6 haloalkoxy group or (4) C Phenyl group optionally substituted with _1-6 haloalkyl group] [Formula VII]
[Wherein R ¹ is as defined in claim 3 and other symbols are as defined above].
[6" claim-type="Currently amended] A process for preparing a compound represented by formula (IX) or a salt thereof, comprising reacting a compound represented by formula (VII) or a salt thereof with a compound represented by formula (VIII):
[Formula VII]
Wherein R ¹ is as defined in claim 3 and R ² and A are as defined in claim 5
[Formula VIII] R ⁴ SO _n X ² [VIII] [Wherein, R ⁴ represents a C _1-6 alkyl group or C _1-6 haloalkyl group, n is 0, 1 or 2, and X ² represents a halogen atom] [Formula IX]
Wherein R ¹ is as defined in claim 3, R ² and A are as defined in claim 5 and R ⁴ is as defined above.
[7" claim-type="Currently amended] A process for preparing a compound represented by formula IV _b or a salt thereof, comprising reacting a compound represented by formula IV _a or a salt thereof with an amine represented by formula X or a salt thereof:
[Formula IVa]
[Wherein X represents a chlorine atom, a 1-chloroethoxy group, a chloromethoxy group or a phenoxy group] [Formula X] R ⁵ R ⁶ NH [X] [Wherein R ⁵ and R ⁶ each represent a C _1-6 alkyl group or R ⁵ and R ⁶ together with an adjacent nitrogen atom represent a cyclic amino group] [Formula IVb]
Wherein R ⁵ and R ⁶ are as defined above.
[8" claim-type="Currently amended] To _a method of manufacturing the formula V compound or a salt thereof represented by the ring-opening reaction which comprises the compound or a salt thereof isoxazole ring of the formula IV _b:
[Formula IVb]
Wherein R ⁵ and R ⁶ are as defined in claim 7
[Formula Va]
Wherein R ⁵ and R ⁶ are as defined in claim 7.
[9" claim-type="Currently amended] A process for preparing a compound represented by the following formula (VIIa) or a salt thereof, comprising reacting a compound represented by the following formula (V _a ) or a salt thereof with a compound represented by the following formula (VI) or _a salt thereof:
[Formula Va]
Wherein R ⁵ and R ⁶ are as defined in claim 7
[Formula VI]
Wherein R ² and A are as defined in claim 5
Formula VIIa]
Wherein R ² and A are as defined in claim ⁵ and R ⁵ and R ⁶ are as defined in claim 7.
[10" claim-type="Currently amended] A process for preparing a compound represented by formula IX _a or a salt thereof comprising reacting a compound represented by formula VII _a or a salt thereof with a compound represented by formula VIII:
Formula VIIa]
Wherein R ² and A are as defined in claim ⁵ and R ⁵ and R ⁶ are as defined in claim 7
[Formula VIII] R ⁴ SO _n X ² [VIII] Wherein R ⁴ , n, and X ² are as defined in claim 6
Formula IXa

Wherein R ² and A are as defined in claim 5, R ⁴ and n are as defined in claim ⁶ and R ⁵ and R ⁶ are as defined in claim 7.
[11" claim-type="Currently amended] 3- (5-isoxazolyl) -Δ ² -1,2,4-oxadiazoline or a salt thereof represented by Formula II:
[Formula II]
[12" claim-type="Currently amended] A compound represented by formula IV or a salt thereof:
[Formula IV]
Wherein R ¹ is as defined in claim 3.
[13" claim-type="Currently amended] A compound represented by formula V or a salt thereof:
[Formula V]
Wherein R ¹ is as defined in claim 3.
[14" claim-type="Currently amended] A compound represented by formula (VII) or a salt thereof:
[Formula VII]
Wherein R ¹ is as defined in claim 3 and R ² and A are as defined in claim 5.
[15" claim-type="Currently amended] A compound represented by formula IV _a or a salt thereof:
[Formula IVa]
Wherein X is as defined in claim 7.
[16" claim-type="Currently amended] A compound represented by formula IV _b or a salt thereof:
[Formula IVb]
Wherein R ⁵ and R ⁶ are as defined in claim 7.
[17" claim-type="Currently amended] A compound represented by formula V _a or a salt thereof:
[Formula Va]
Wherein R ⁵ and R ⁶ are as defined in claim 7.
[18" claim-type="Currently amended] A compound or a salt thereof represented by the formula VII _a:
Formula VIIa]
Wherein R ² and A are as defined in claim ⁵ and R ⁵ and R ⁶ are as defined in claim 7.

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同族专利:

---

公开号 | 公开日

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TWI221840B|2004-10-11|

---

CA2390420A1|2001-06-07|

---

EP1234819A4|2003-01-22|

---

AU1414601A|2001-06-12|

---

BR0015990A|2002-10-29|

---

EP1234819A1|2002-08-28|

---

DE60010319T2|2005-05-04|

---

JP2001220386A|2001-08-14|

---

CN1402715A|2003-03-12|

---

DE60010319D1|2004-06-03|

---

US6630592B1|2003-10-07|

---

AT265441T|2004-05-15|

---

EP1234819B1|2004-04-28|

---

IL149647D0|2002-11-10|

---

WO2001040203A1|2001-06-07|

引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
1999-11-30|Priority to JPJP-P-1999-00340606

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1999-11-30|Priority to JP34060699

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2000-08-01|Priority to JPJP-P-2000-00233264

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2000-08-01|Priority to JP2000233264A

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2000-11-17|Application filed by 다케다 야쿠힌 고교 가부시키가이샤

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2000-11-17|Priority to PCT/JP2000/008108

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2002-07-12|Publication of KR20020058062A

优先权:

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申请号 | 申请日 | 专利标题

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JPJP-P-1999-00340606|1999-11-30|

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JP34060699|1999-11-30|

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JPJP-P-2000-00233264|2000-08-01|

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JP2000233264A|JP2001220386A|1999-11-30|2000-08-01|Method for producing oxadiazoline derivative|

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PCT/JP2000/008108|WO2001040203A1|1999-11-30|2000-11-17|Processes for production of oxadiazoline derivatives|