Patent Grant
7875606
This application is a National Phase Application (35 USC 371) of PCT/JP02/006183 and claims priority of Japanese Application No. 2001-187679, filed Jun. 21, 2001.
The present invention relates to a novel isoxazoline derivative and a herbicide containing the isoxazoline derivative as an active ingredient.
The herbicidal activities of isoxazoline derivatives having a haloalkyl group at the 5-position of the isoxazoline ring are reported in, for example, JP-A-8-225548, JP-A-9-328477 and JP-A-9-328483. The compound of the present invention, however, is not described in these literatures.
Herbicides applied to useful crops are desired, when applied to soil or stems and leaves, to show a sufficient herbicidal effect at a low ingredient amount and, moreover, exhibit a high selectivity between crop and weed. In these respects, the compounds described in the above literatures are not fully satisfactory.
In view of the above situation, the present inventors made a study on the herbicidal effect and selectivity between crop and weed, of various compounds. As a result, the present inventors found out that a novel isoxazoline derivative has an excellent herbicidal effect and an excellent selectivity between crop and weed. The above finding has led to the completion of the present invention.
The present invention provides the followings.
Hydroxyl group; halogen atoms; C1 to C10 alkyl groups; C1 to C10 alkyl groups each mono-substituted with a group selected from the following substituent group β, C1 to C4 haloalkyl groups; C3 to C8 cycloalkyl groups; C1 to C10 alkoxy groups; C1 to C10 alkoxy groups each mono-substituted with a group selected from the following substituent group γ; C1 to C4 haloalkoxy groups; C3 to C8 cycloalkyloxy groups; C3 to C8 cycloalkyl C1 to C3 alkyloxy groups; C1 to C10 alkylthio groups; C1 to C10 alkylthio groups each mono-substituted with a group selected from the substituent group γ; C1 to C4 haloalkylthio groups; C2 to C6 alkenyl groups; C2 to C6 alkenyloxy groups; C2 to C6 alkynyl groups; C2 to C6 alkynyloxy groups; C1 to C10 alkylsulfinyl groups; C1 to C10 alkylsulfonyl groups; C1 to C10 alkylsulfonyl groups each mono-substituted with a group selected from the substituent group γ; C1 to C4 haloalkylsulfinyl groups; C1 to C4 haloalkylsulfonyl groups; C1 to C10 alkylsulfonyloxy groups; C1 to C4 haloalkylsulfonyloxy groups; optionally substituted phenyl group; optionally substituted phenoxy group; optionally substituted phenylthio group; optionally substituted aromatic heterocyclic groups; optionally substituted aromatic heterocyclic oxy groups; optionally substituted aromatic heterocyclic thio groups; optionally substituted phenylsulfinyl groups; optionally substituted phenylsulfonyl groups; optionally substituted aromatic heterocyclic sulfinyl groups; optionally substituted aromatic heterocyclic sulfonyl groups; optionally substituted phenylsulfonyloxy groups; C1 to C6 acyl groups; C1 to C4 haloalkylcarbonyl groups; optionally substituted benzylcarbonyl group; optionally substituted benzoyl group; carboxyl group; C1 to C10 alkoxycarbonyl groups; optionally substituted benzyloxycarbonyl group; optionally substituted phenoxycarbonyl group; cyano group; carbamoyl group (its nitrogen atom may be substituted with same or different groups selected from C1 to C10 alkyl groups and optionally substituted phenyl group); C1 to C6 acyloxy groups; C1 to C4 haloalkylcarbonyloxy groups; optionally substituted benzylcarbonyloxy group; optionally substituted benzoyloxy group; nitro group; and amino group (its nitrogen atom may be substituted with same or different groups selected from C1 to C10 alkyl groups, optionally substituted phenyl group, C1 to C6 acyl groups, C1 to C4 haloalkylcarbonyl groups, optionally substituted benzylcarbonyl group, optionally substituted benzoyl group, C1 to C10 alkylsulfonyl group, C1 to C4 haloalkylsulfonyl groups, optionally substituted benzylsulfonyl group, and optionally substituted phenylsulfonyl group).
[Substituent Group β]
Hydroxyl group; C3 to C8 cycloalkyl groups (which may be substituted with halogen atoms or C1 to C10 alkyl groups); C1 to C10 alkoxy groups; C1 to C10 alkylthio groups; C1 to C10 alkylsulfonyl groups; C1 to C10 alkoxycarbonyl groups; C2 to C6 haloalkenyl groups; amino group (its nitrogen atom may be substituted with same or different groups selected from C1 to C10 alkyl groups, C2 to C6 acyl groups; C1 to C4 haloalkylcarbonyl groups, C1 to C10 alkylsulfonyl groups and C1 to C4 haloalkylsulfonyl groups); carbamoyl group (its nitrogen atom may be substituted with same or different groups selected from C1 to C10 alkyl groups and optionally substituted phenyl group); C2 to C6 acyl groups; C1 to C4 haloalkylcarbonyl groups; C1 to C10 alkoxyimino groups; cyano group; optionally substituted phenyl group; and optionally substituted phenoxy group.
[Substituent Group γ]
C1 to C10 alkoxycarbonyl groups; optionally substituted phenyl group; optionally substituted aromatic heterocyclic groups; cyano group; and carbamoyl group (its nitrogen atom may be substituted with same or different C1 to C10 alkyl groups).
The definitions of the terms used in the present specification are given below.
The expression of “C1 to C10”, etc. indicates that the substituent appearing after the expression has 1 to 10 carbon atoms in the case of “C1 to C10”.
Halogen atom refers to a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
C1 to C10 alkyl group refers, unless otherwise specified, to a straight or branched chain alkyl group of 1 to 10 carbon atoms; and there can be mentioned, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, n-hexyl group, isohexyl group, 3,3-dimethylbutyl group, heptyl group and octyl group.
C3 to C8 cycloalkyl group refers to a cycloalkyl group of 3 to 8 carbon atoms; and there can be mentioned, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group and cyclohexyl group.
C3 to C8 cycloalkyl C1 to C3 alkyl group (which may be substituted with halogen atom or alkyl group) refers, unless otherwise specified, to a C1 to C3 alkyl group substituted with a C3 to C8 cycloalkyl group which may be substituted with 1 to 4 same or different halogen atoms or C1 to C3 alkyl group; and there can be mentioned, for example, cyclopropylmethyl group, 1-cyclopropylethyl group, 2-cyclopropylethyl group, 1-cyclopropylpropyl group, 2-cyclopropylpropyl group, 3-cyclopropylpropyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, 2-chlorocyclopropylmethyl group, 2,2-dichlorocyclopropylmethyl group, 2-fluorocyclopropylmethyl group, 2,2-difluorocyclopropylmethyl group, 2-methylcyclopropylmethyl group, 2,2-dimethylcyclopropylmethyl group and 2-methylcyclopropylethyl group.
C3 to C8 cycloalkyl C1 to C3 alkyl group refers to a alkyl group of 1 to 3 carbon atoms, substituted with a cycloalkyl group of 3 to 8 carbon atoms; and there can be mentioned, for example, cyclopropylmethyl group, 1-cyclopropylethyl group, 2-cyclopropylethyl group, 1-cyclopropylpropyl group, 2-cyclopropylpropyl group, 3-cyclopropylpropyl group, cyclobutylmethyl group, cyclopentylmethyl group and cyclohexylmethyl group.
C1 to C4 haloalkyl group refers, unless otherwise specified, to a straight or branched chain alkyl group of 1 to 4 carbon atoms, substituted with 1 to 9 same or different halogen atoms; and there can be mentioned, for example, fluoromethyl group, chloromethyl group, bromomethyl group, difluoromethyl group, trifluoromethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group and pentafluoroethyl group.
C2 to C6 alkenyl group refers to a straight or branched chain alkenyl group of 2 to 6 carbon atoms; and there can be mentioned, for example, ethenyl group, 1-propenyl group, 2-propenyl group, isopropenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group and 2-pentenyl group.
C2 to C6 alkynyl group refers to a straight or branched chain alkynyl group of 2 to 6 carbon atoms; and there can be mentioned, for example, ethynyl group, 2-propynyl group, 1-methyl-2-propynyl group, 2-butynyl group, 3-butynyl group and 2-methyl-3-butynyl group.
C2 to C6 haloalkenyl group refers, unless otherwise specified, to a straight or branched alkenyl group of 2 to 6 carbon atoms, substituted with 1 to 4 same or different halogen atoms; and there can be mentioned, for example, 3-chloro-2-propenyl group and 2-chloro-2-propenyl group.
C1 to C10 alkoxy group refers to an (alkyl)-O— group wherein the alkyl moiety has the above definition; and there can be mentioned, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, tert-butoxy group, n-butoxy group, sec-butoxy group and isobutoxy group.
C1 to C10 alkoxy C1 to C3 alkyl group refers to an (alkyl)-O-(alkyl) group wherein the alkoxy moiety and the alkyl moiety have the above definitions; and there can be mentioned, for example, methoxymethyl group, ethoxymethyl group, methoxyethyl group and ethoxyethyl group.
C1 to C4 haloalkoxy group refers to a (haloalkyl)-O— group wherein the haloalkyl moiety has the above definition; and there can be mentioned, for example, difluoromethoxy group, trifluoromethoxy group, 2,2-difluoroethoxy group and 2,2,2-trifluoroethoxy group.
C3 to C8 cycloalkyloxy group refers to a (cycloalkyl)-O— group wherein the cycloalkyl moiety has the above definition; and there can be mentioned, for example, cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group and cyclohexyloxy group.
C3 to C8 cycloalkyl C1 to C3 alkyloxy group refers to a (cycloalkylalkyl)-O— group wherein the cycloalkylalkyl moiety has the above definition; and there can be mentioned, for example, cyclopropylmethoxy group, 1-cyclopropylethoxy group, 2-cyclopropylethoxy group, 1-cyclopropylpropoxy group, 2-chclopropylpropoxy group, 3-cyclopropylpropoxy group, cyclobutylmethoxy group, cyclopentylmethoxy group and cyclohexylmethoxy group.
C2 to C6 alkenyloxy group and C2 to C6 alkynyloxy group refer, respectively, to an (alkenyl)-O— group and an (alkynyl)-O— group, in each of which the alkenyl or alkynyl moiety has the above definition; and there can be mentioned, for example, 2-propenyloxy group and 2-propynyloxy group.
C1 to C10 alkoxyimino group refers to an (alkoxy)-N═ group wherein the alkoxy moiety has the above definition; and there can be mentioned, for example, methoxyimino group and ethoxyimino group.
C1 to C10 alkylthio group, C1 to C10 alkylsulfinyl group and C1 to C10 alkylsulfonyl group refer, respectively, to an (alkyl)-S— group, an (alkyl)-SO— group and an (alkyl)-SO2— group, in each of which the alkyl moiety has the above definition; and there can be mentioned, for example, methylthio group, ethylthio group, n-propylthio group, isopropylthio group, methylsulfinyl group, methylsulfonyl group, ethylsulfonyl group, n-propylsulfonyl group and isopropylsulfonyl group.
C1 to C10 alkylsulfonyloxy group refers to an (alkylsulfonyl)-O— group wherein the alkylsulfonyl moiety has the above definition, and there can be mentioned, for example, methylsulfonyloxy group and ethylsulfonyloxy group.
C1 to C10 alkoxycarbonyl group refers to an (alkoxy)-CO— group wherein the alkoxy moiety has the above definition, and there can be mentioned, for example, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group and isopropoxycarbonyl group.
C1 to C6 acyl group refers to a straight or branched chain aliphatic acyl group of 1 to 6 carbon atoms, and there can be mentioned, for example, formyl group, acetyl group, propionyl group, isopropionyl group, butyryl group and pivaloyl group.
C1 to C10 acyloxy group refers to an (acyl)-O— group wherein the acyl moiety has the above definition; and there can be mentioned, for example, acetoxy group, propionyloxy group, isopropionyloxy group and pivaloyloxy group.
C1 to C4 haloalkylcarbonyl group, C1 to C4 haloalkylthio group, C1 to C4 haloalkylsulfinyl group and C1 to C4 haloalkylsulfonyl group refers, respectively, to a (haloalkyl)-CO— group, a (haloalkyl)-S— group, a (haloalkyl)-SO— group and a (haloalkyl)-SO2— group, in each of which the haloalkyl moiety has the above definition; and there can be mentioned, for example, chloroacetyl group, trifluoroacetyl group, pentafluoropropionyl group, difluoromethylthio group, trifluoromethylthio group, chloromethylsulfinyl group, difluoromethylsulfinyl group, trifluoromethylsulfinyl group, chloromethylsulfonyl group, difluoromethylsulfonyl group and trifluoromethylsulfonyl group.
C1 to C4 haloalkylcarbonyloxy group and C1 to C4 haloalkylsulfonyloxy group refer, respectively, to a (haloalkylcarbonyl)-O— group and a (haloalkylsulfonyl)-O— group, in each of which the haloalkylcarbonyl moiety or the haloalkylsulfonyl moiety has the above definition; and there can be mentioned, for example, chloroacetyloxy group, trifluoroacetyloxy group, chloromethylsulfonyloxy group and trifluoromehtylsulfonyloxy group.
“Optionally substituted” in (optionally substituted) phenyl group, (optionally substituted) aromatic heterocyclic group, (optionally substituted) phenoxy group, (optionally substituted aromatic heterocyclic oxy group, (optionally substituted) phenylthio group, (optionally substituted) aromatic heterocyclic thio group, (optionally substituted) phenylsulfinyl group, (optionally substituted) phenylsulfonyl group, (optionally substituted) phenylsulfonyloxy group, (optionally substituted) aromatic heterocyclic sulfinyl group, (optionally substituted) aromatic heterocyclic sulfonyl group, (optionally substituted) benzylcarbonyl group, (optionally substituted) benzylcarbonyloxy group, (optionally substituted) benzylsulfonyl group, (optionally substituted) benzoyl group, (optionally substituted) benzoyloxy group, (optionally substituted) benzyloxycarbonyl group and (optionally substituted) phenoxycarbonyl group, refers to being optionally substituted with, for example, halogen atom, C1 to C10 alkyl group, C1 to C4 haloalkyl group, C1 to C10 alkoxy C1 to C3 alkyl group, C1 to C10 alkoxy group, C1 to C10 alkylthio group, C1 to C10 alkylsulfonyl group, acyl group, C1 to C10 alkoxycarbonyl group, cyano group, carbamoyl group (its nitrogen atom may be substituted with same or different C1 to C10 alkyl groups), nitro group, or amino group (its nitrogen atom may be substituted with same or different groups selected from C1 to C10 alkyl groups, C1 to C6 acyl groups, C1 to C4 haloalkylcarbonyl groups, C1 to C10 alkylsulfonyl groups and C1 to C4 haloalkylsulfonyl groups).
Aromatic heterocycle in (optionally substituted) aromatic heterocyclic group, (optionally substituted) aromatic heterocyclic oxy group, (optionally substituted) aromatic heterocyclic thio group, (optionally substituted) aromatic heterocyclic sulfinyl group and (optionally substituted) aromatic heterocyclic sulfonyl group, refers to a 5- to 6-membered group having 1 to 3 hetero atoms randomly selected from nitrogen atom, oxygen atom and sulfur atom; and there can be mentioned, for example, furyl group, thienyl group, pyrrolyl group, pyrazolyl group, isoxazolyl group, isothiazolyl group, oxazolyl group, thiazolyl group, imidazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, triazinyl group, triazolyl group, oxadiazolyl group and thiadiazolyl group.
Pharmaceutically acceptable salt is a salt of a compound of the general formula [I] having, in the structure, hydroxyl group, carboxyl group, amino group or the like, with a metal or an organic base or with a mineral acid or an organic acid. As the metal, there can be mentioned alkali metals such as sodium, potassium and the like; and alkaline earth metals such as magnesium, calcium and the like. As the organic base, there can be mentioned triethylamine, diisopropylamine, etc. As the mineral acid, there can be mentioned hydrochloric acid, sulfuric acid, etc. As the organic acid, there can be mentioned acetic acid, methanesulfonic acid, p-toluenesulfonic acid, etc.
Of the compounds represented by the general formula [I], preferred is an isoxazoline derivative wherein
Next, representative examples of the present compound represented by the general formula [I] are shown in Tables 1 to 57. However, the present compound is not restricted to these examples.
The following abbreviated expressions used in the Tables of the present invention refer to the following groups.
When the present compound of the general formula [I] contains hydroxyl group as a substituent, there may exist keto-enol tautomers. Any of these tautomers and any mixture of these tautomers are included in the present compound.
The compound of the present invention having the general formula [I] can be produced by the processes shown below. However, the production is not restricted to these processes alone.
[Production Process 1]
(Step 1 to Step 5)
wherein R1, R2, R3, R4, R5, R6 and Y have the same meanings as given above; X1 is a halogen atom; R7 is a C1 to C4 alkyl group, an optionally substituted phenyl group or an optionally substituted benzyl group; L is an eliminatable group such as halogen atom, C1 to C4 alkylsulfonyl group, optionally substituted phenylsulfonyl group, optionally substituted benzylsulfonyl group or the like; and x is a number of 1 or more.
The individual steps of the above production process are described in detail below.
(Step 1)
A sulfide derivative represented by the general formula [5] can be produced by reacting a compound represented by the genera formula [1] with a sodium hydrosulfide hydrate represented by the general formula [2] in a solvent or in the absence of a solvent (preferably in an appropriate solvent) in the presence or absence of a base to produce a mercaptan salt represented by the general formula [3] in the reaction system and then reacting the mercaptan salt [3] with a halogen derivative represented by the general formula [4] without isolating the mercaptan salt [3] {optionally, a radical generator [e.g. Rongalit (trade name), CH2(OH)SO2Na.2H2O] may be added}.
The reaction temperature in each reaction is any temperature ranging from 0° C. to the reflux temperature in reaction system, preferably a temperature range of 0° C. to 100° C. The reaction time is 0.5 to 24 hours although it differs depending upon the compounds used.
With respect to the amounts of the reagents used in the reactions, the amounts of the compound represented by the general formula [2] and the compound represented by the general formula [4] are each 1 to 3 equivalents relative to 1 equivalent of the compound represented by the general formula [1]; and when a base is used, the amount of the base is 0.5 to 3 equivalents.
As the solvent used, there can be mentioned, for example, ethers such as dioxane, tetrahydrofuran (THF) and the like; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidinone and the like; sulfur compounds such as dimethyl sulfoxide, (DMSO), sulfolane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol and the like; ketones such as acetone, 2-butanone and the like; nitriles such as acetonitrile and the like; water; and mixtures thereof.
As the base used, there can be mentioned, for example, metal hydrides such as sodium hydride and the like; alkali metal amides such as sodium amide, lithium diisopropylamide and the like; organic bases such as pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene and the like; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like; alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal bicarbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and the like (inorganic bases); and metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tertbutoxide and the like.
(Step 2)
A sulfoxide derivative represented by the general formula [6] can be produced by reacting the sulfide derivative represented by the general formula [5] with an oxidizing agent in an appropriate solvent in the presence or absence of a catalyst.
The reaction temperature is any temperature ranging from 0° C. to the reflux temperature in reaction system, preferably a temperature range of 0° C. to 60° C. The reaction time is 1 to 72 hours although it differs depending upon the compounds used.
With respect to the amounts of the reagents used in the reaction, the amount of the oxidizing agent is 1 to 3 equivalents relative to 1 equivalent of the compound represented by the general formula [5] and, when the catalyst is used, the amount of the catalyst is 0.01 to 0.5 equivalent.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; ethers such as dioxane, tetrahydrofuran (THF), dimethoxyethane, diethyl ether and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidinone and the like; alcohols such as methanol ethanol, propanol, isopropanol, butanol, tert-butanol and the like; ketones such as acetone, 2-butanone and the like; nitrites such as acetonitrile and the like; acetic acid; water; and mixtures thereof.
As the oxidizing agent used, there can be mentioned, for example, organic peroxides such as m-chloroperbenzoic acid, hydrogen peroxide, performic acid, peracetic acid and the like; and inorganic peroxides such as potassium permanganate, sodium periodate and the like.
As the catalyst used, there can be mentioned, for example, metal catalysts such as sodium tungstate and the like.
(Step 3)
A sulfone derivative represented by the general formula [7] can be produced by reacting the sulfoxide derivative represented by the general formula [6] with an oxidizing agent in an appropriate solvent in the presence or absence of a catalyst.
The reaction temperature is any temperature ranging from 0° C. to the reflux temperature in reaction system, preferably a temperature range of 0° C. to 60° C. The reaction time is 1 to 72 hours although it differs depending upon the compounds used.
With respect to the amounts of the reagents used in the reaction, the amount of the oxidizing agent is 1 to 3 equivalents relative to 1 equivalent of the compound represented by the general formula [6] and, when the catalyst is used, the amount of the catalyst is 0.01 to 0.5 equivalent.
The solvent, oxidizing agent and catalyst used can be the same as used in the step 2.
(Step 4)
The sulfone derivative represented by the general formula [7] can also be produced by reacting the sulfide derivative represented by the general formula [5] with an oxidizing agent of an appropriate amount in an appropriate solvent in the presence or absence of a catalyst, without isolating the sulfoxide derivative represented by the general formula [6].
The reaction temperature is any temperature ranging from 0° C. to the reflux temperature in reaction system, preferably a temperature range of 0° C. to 60° C. The reaction time is 1 to 72 hours although it differs depending upon the compounds used.
With respect to the amounts of the reagents used in the reaction, the amount of the oxidizing agent is 1 to 3 equivalents relative to 1 equivalent of the compound represented by the general formula [5] and, when the catalyst is used, the amount of the catalyst is 0.01 to 0.5 equivalent.
The solvent, oxidizing agent and catalyst used can be the same as used in the step 2.
(Step 5)
The sulfide derivative represented by the general formula [5] can also be produced by reacting a compound represented by the general formula [8] with a mercaptan derivative represented by the general formula [9] in a solvent or in the absence of a solvent (preferably in an appropriate solvent) in the presence of a base.
The reaction temperature is any temperature ranging from 0° C. to the reflux temperature in reaction system, preferably a temperature range of 0° C. to 100° C. The reaction time is 0.5 to 24 hours although it differs depending upon the compounds used.
With respect to the amounts of the reagents used in the reaction, the amount of the compound represented by the general formula [9] is 1 to 3 equivalents relative to 1 equivalent of the compound represented by the general formula [8] and the amount of the base is 0.5 to 3 equivalents.
As the solvent used, there can be mentioned, for example, ethers such as diethyl ether, dimethoxyethane, dioxane, tetrahydrofuran (THF) and the like; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidinone and the like; sulfur compounds such as dimethyl sulfoxide, (DMSO), sulfolane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol and the like; ketones such as acetone, 2-butanone and the like; nitriles such as acetonitrile and the like; water; and mixtures thereof.
As the base used, there can be mentioned, for example, metal hydrides such as sodium hydride and the like; alkali metal amides such as sodium amide, lithium diisopropylamide and the like; organic bases such as pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene and the like; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like; alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal bicarbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and the like (inorganic bases); and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like.
Of the compounds represented by general formula [8], those wherein L is a halogen atom, i.e. a compound represented by the general formula [12] and a compound represented by the general formula [13] can be produced by the following method.
(Step 6)
wherein X1, R1, R2, R3 and R4 have the same meanings as given above.
The isoxazoline compounds represented by the general formulas [12] and [13] can be produced by reacting an olefin derivative represented by the general formula [10] with an oxime derivative represented by the general formula [11] in a solvent or in the absence of a solvent (preferably in an appropriate solvent) in the presence of a base. As necessary, the compounds of the general formula [12] and [13] are separated from each other and purified. However, when both R3 and R4 are a hydrogen atom, the isoxazoline compound represented by the general formula [12] is obtained predominantly.
The reaction temperature is any temperature ranging from 0° C. to the reflux temperature in reaction system, preferably a temperature range of 0° C. to 80° C. The reaction time is 0.5 hour to 2 weeks although it differs depending upon the compounds used.
With respect to the amounts of the reagents used in the reaction, the amount of the compound represented by the general formula [10] is 1 to 3 equivalents relative to 1 equivalent of the compound represented by the general formula [11].
As the solvent used, there can be mentioned, for example, ethers such as ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethyl ether, dioxane, tetrahydrofuran and the like; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like, esters such as ethyl acetate, butyl acetate and the like; water; and mixtures thereof.
As the base used, there can be mentioned, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like; alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal bicarbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and the like; alkali metal acetates such as sodium acetate, potassium acetate and the like; alkali metal fluorides such as sodium fluoride, potassium fluoride and the like; and organic bases such as pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene and the like.
Incidentally, the compound represented by the general formula [10] used in the above production process as an intermediate may be a commercial product or can be produced by a known reaction such as the Witting reaction or the like. The compound represented by the general formula [11] can be produced by, for example, the method described in Liebigs Annalen der Chemie, 985 (1989).
The compound represented by the general formula [1] can be produced from the previously shown compound represented by the general formula [12] by the following methods.
(Step 7 to Step 10)
wherein X1, R1, R2, R3, R4 and R7 have the same meanings as given above.
A compound represented by the general formula [15] can be produced based on the method shown in the step 5 (step 7); a compound represented by the general formula [16] can be produced based on the method shown in the step 2 (step 8) ; the compound represented by the general formula [1] can be produced from the compound of the general formula [15] based on the method shown in the step 4 (step 10), or from the compound of the general formula [16] based on the method shown in the step 3 (step 9). The solvent, base, oxidizing agent and catalyst used can be the same as used in the step 2, the step 3, the step 4 or the step 5.
Of the compounds represented by the general formula [4], a compound represented by the general formula [21] can be produced by the methods shown below.
(Steps 11 and 12)
wherein R5, X1 and Y have the same meanings as given above; and R8 is an alkyl group.
(Step 11)
A compound represented by the general formula [20] can be produced by reacting a compound of the general formula [17], [18] or [19] with a reducing agent in a solvent.
This reaction is conducted ordinarily at a temperature of −60 to 150° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used, the amount of the reducing agent is desired to be 0.5 to 2 equivalents per 1 equivalent of the compound of the general formula [17], [18] or [19], but it can be varied appropriately depending upon the conditions of the reaction.
As the reducing agent, there can be mentioned, in production of the compound of the general formula [20] from the compound of the general formula [17], metal hydrides such as diisobutyl aluminum hydride and the like; metal-hydrogen complex compounds such as sodium borohydride, lithium aluminum hydride and the like; and so forth. In production of the compound of the general formula [20] from the compound of the general formula [18] or [19], there can be mentioned, for example, metal hydrides such as diisobutyl aluminum hydride and the like; metal-hydrogen complex compounds such as sodium borohydride, lithium aluminum hydride and the like; and diborane.
As the solvent used, there can be mentioned, for example, ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; aromatic hydrocarbons such as benzene, toluene and the like; and alcohols such as methanol, ethanol and the like.
(Step 12)
A compound represented by the general formula [21] can be produced by reacting the compound of the general formula [20] with a halogenating agent in a solvent.
This reaction is conducted ordinarily at −50 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used, the amount of the halogenating agent is desired to be 1 to 3 equivalents per 1 equivalent of the compound of the general formula [20] but it can be varied appropriately depending upon the conditions of the reaction.
As the halogenating agent used, there can be mentioned, for example, hydrogen chloride, hydrogen bromide, phosphorus trichloride, phosphorus tribromide, and thionyl chloride.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloroethane, carbon tetrachloride and the like; acids such as acetic acid and the like; and ethers such as tetrahydrofuran and the like.
The compound represented by the general formula [4] can be produced by the following method.
wherein R5, R6, X1 and Y have the same meanings as given above.
(Step 13)
The compound represented by the general formula [4] can be produced by reacting a compound represented by the general formula [22] with a halogenating agent in a solvent in the presence or absence of a catalyst. In this step, the reaction may be conducted under light irradiation.
This reaction is conducted ordinarily at 30 to 150° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used, the amount of the halogenating agent is desired to be 1 to 10 equivalents per 1 equivalent of the compound of the general formula [22] but it can be varied appropriately depending upon the conditions of the reaction. The amount of the catalyst is 0.01 to 0.5 equivalent.
As the halogenating agent used, there can be mentioned, for example, halogens such as bromine, chlorine and the like; N-halosuccinimides such as N-bromosuccinimide and the like; and pyridine salts such as pyridinium perbromide and the like.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; and carboxylic acids such as formic acid, acetic acid and the like.
As the catalyst used, there can be mentioned, for example, benzoyl peroxide, α,α-azobisisobutyronitrile, and mixtures thereof.
Of the compounds represented by the general formula [4], a compound represented by the general formula [24] can be produced by the following method.
wherein X1 and Y have the same meanings as given above.
(Step 14)
The compound represented by the general formula [24] can be produced by reacting a compound represented by the general formula [23] with a hydrogen halide and formaldehyde or paraformaldehyde in a solvent in the presence or absence of a Lewis acid, based on the method described in Org. Synth., III, 557 (1955) or J. Am. Chem. Soc., 72, 2216 (1950), or by reacting the compound represented by the general formula [23] with a halogenomethyl ether in a solvent in the presence of a Lewis acid, based on the method described in J. Am. Chem. Soc., 97, 6155 (1975).
This reaction is conducted ordinarily at −40 to 150° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used, it is desired that the amount of the hydrogen halide is 1 to 2 equivalents, the amount of formaldehyde or paraformaldehyde is 1 to 2 equivalents, the amount of the Lewis acid is 1 to 2 equivalents, and the amount of the halogenomethyl ether is 1 to 2 equivalents, all relative to 1 equivalent of the compound of the general formula [23]. However, these amounts can be varied appropriately depending upon the conditions of the reaction.
As the Lewis acid used, there can be mentioned, for example, titanium tetrachloride, zinc chloride, aluminum chloride and zinc bromide.
As the hydrogen halide used, there can be mentioned hydrogen chloride, hydrogen bromide and hydrogen iodide.
As the solvent used, there can be mentioned, for example, halogenating hydrocarbons such as dichloroethane, carbon tetrachloride, chloroform and the like; aliphatic hydrocarbons such as hexane, heptane and the like; ethers such as dioxane, tetrahydrofuran and the like; carboxylic acids such as acetic acid and the like; carbon disulfide; and mixtures thereof.
Of the compounds represented by the general formula [19], a compound represented by the general formula [25] can be produced by the following method.
wherein Y has the same meaning as given above.
(Step 15)
The compound represented by the general formula [25] can be produced by reacting the compound of the general formula [23] with N,N-dimethylformamide (DMF) in a solvent or in the absence of a solvent in the presence of phosphoryl chloride, phosgene or thionyl chloride, based on the method described in Org. Synth., IV, 831 (1963) [Vilsmeier method], or by reacting the compound of the general formula [23] with a dihalogenomethyl ether in a solvent in the presence of a Lewis acid, followed by hydrolysis, based on the method described in Chem. Ber., 93, 88 (1960).
This reaction is conducted ordinarily at −40 to 150° C. for 10 minutes to 24 hours.
With respect to the amounts of reagents used in the reaction, it is desired that the amount of phosphoryl chloride, phosgene or thionyl chloride is 1 to 2 equivalents, the amount of N,N-dimethylformamide is 1 to 2 equivalents, the amount of Lewis acid is 1 to 2 equivalents, and the amount of dihalogenomethyl ether is 1 to 2 equivalents, all relative to 1 equivalent of the compound of the general formula [23]; however, these amounts can be varied appropriately depending upon the conditions of the reaction.
As the Lewis acid used, there can be mentioned, for example, titanium tetrachloride, tin tetrachloride, zinc chloride, aluminum chloride and zinc bromide.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chloroform and the like; aliphatic hydrocarbons such as hexane, heptane and the like; ethers such as dioxane, tetrahydrofuran and the like; carboxylic acids such as acetic acid and the like; amides such as N,N-dimethylformamide and the like; sulfur compound such as carbon disulfide and the like; and mixtures thereof.
The compound represented by the general formula [17], [18] or [19] can be produced by the following method.
wherein X2 is a chlorine atom, a bromine atom or an iodine atom; and R5, R6 and Y have the same meanings as given above.
(Steps 16 and 17)
The compound represented by the general formula [17], [18] or [19] can be produced by reacting a compound represented by the general formula [26] with a magnesium reagent in a solvent or in the absence of a solvent based on the method described in J. Org. Chem., 65, 4618 (2000), to obtain a compound of the general formula [27] and reacting the compound of the general formula [27] with an electrophilic reagent, or by reacting the compound of the general formula [26] with a lithium reagent based on the method described in Synth. Commum., 24(2), 253 (1994) to obtain a compound of the general formula [28] and reacting the compound of the general formula [28] with an electrophilic reagent.
This reaction is conducted ordinarily at −100 to 150° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, it is desired that the amount of the magnesium reagent is 1 to 5 equivalents, the amount of the electrophilic reagent is 1 to 5 equivalents, or the amount of the lithium reagent is 1 to 5 equivalents and the amount of the electrophilic reagent is 1 to 5 equivalents, all relative to 1 equivalent of the compound of the general formula [26]; however, these amounts can be varied appropriately depending upon the conditions of the reaction.
As the magnesium reagent used, there can be mentioned, for example, metallic magnesium, isopropyl magnesium bromide and diisopropyl magnesium and the like.
As the lithium reagent used, there can be mentioned, for example, n-butyl lithium and n-hexyl lithium and the like.
As the electrophilic reagent used, there can be mentioned, for example, esters such as ethyl formate, ethyl cyanoformate, ethyl acetate and the like; acid halides such as acetyl chloride, methyl chloroformate and the like; amides such as N,N-dimethylformamide and the like; and carbon dioxide.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chloroform and the like; aliphatic hydrocarbons such as hexane, pentane and the like; ethers such as dioxane, tetrahydrofuran and the like; and mixtures thereof.
A compound represented by the general formula [31] can be produced by the following method.
wherein Y has the same meaning as given above; R9 is a hydrogen atom, an alkyl group, an acyl group or an alkoxycarbonyl group; R10 is an alkyl group, a haloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkoxycarbonylalkyl group, an optionally substituted benzyl group, an optionally substituted heterocyclic alkyl group, alkenyl group, an alkynyl group, an alkylsulfonyl group, a haloalkylsulfonyl group, an optionally substituted aromatic heterocyclic group, an optionally substituted phenylsulfonyl group, an acyl group, a haloalkylcarbonyl group, an optionally substituted benzylcarbonyl group or an optionally substituted benzoyl group; and L1 is an eliminatable group such as halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 alkylsulfonyl group, optionally substituted benzylsulfonyl group, optionally substituted phenylsulfonyloxy group, optionally substituted benzylsulfonyloxy group or the like; when R10 is a haloalkyl group, L1 is an eliminatable group having a reactivity higher than that of the halogen atom which remains after haloalkylation and, when R10 is, for example, a CHF2 group, L1 is a chlorine atom or a bromine atom and, when R10 is a CH2CF3 group, L1 is a chlorine atom, a bromine atom, an iodine atom, a p-toluenesulfonyloxy group, a methylsulfonyloxy group, a trifluoromethylsulfonyloxy group or the like.
(Step 18)
The compound represented by the general formula [31] can be produced by reacting a compound represented by the general formula [29] with a compound represented by the general formula [30] in a solvent in the presence of a base.
This reaction is conducted ordinarily at 0 to 120° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the compound represented by the general formula [30] is 1 to 20 equivalents and the amount of the base is 1 to 3 equivalents, all relative to 1 equivalent of the compound represented by the general formula [29].
As the base used, there can be mentioned, for example, alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like; alkali metal hydrides such as potassium hydride, sodium hydride and the like; alkali metal alkoxides such as sodium ethoxide, sodium methoxide and the like; and organic bases such as 1,8-diazabicyclo[5.4.0]-7-undecene and the like.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as chloroform, dichloroethane and the like; ethers such as diethyl ether, tetrahydrofuran and the like; aromatic hydrocarbons such as benzene, toluene and the like; aliphatic hydrocarbons such as hexane, heptane and the like; ketones such as acetone, methyl isobutyl ketone and the like; esters such as ethyl acetate and the like; amides such as N-methylpyrrolidone, N,N-dimethylformamide and the like; sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; acetonitrile; and mixtures thereof.
A compound represented by the general formula [34] can be produced by the following method.
wherein L1, α, β and γ have the same meanings as given above; and R11 is an alkyl group, an alkyl group mono-substituted with a group selected from the substituent group β, a haloalkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an alkylsulfinyl group, an alkylsulfonyl group, an alkylsulfonyl group mono-substituted with a group selected from the substituent group γ, a haloalkylsulfonyl group, an optionally substituted phenyl group, an optionally substituted aromatic heterocyclic group, an optionally substituted phenylsulfonyl group, an optionally substituted aromatic heterosulfonyl group, an acyl group, a haloalkylcarbonyl group, an optionally substituted benzylcarbonyl group, an optionally substituted benzoyl group, an alkoxycarbonyl group, an optionally substituted benzyloxycarbonyl group, an optionally substituted phenoxycarbonyl group or a carbamoyl group (its nitrogen atom may be substituted with same or different alkyl groups or an optionally substituted phenyl group; and the carbon atoms of the pyrazole ring may be substituted with 1 to 2 same or different groups selected from the substituent group α.
(Step 19)
The compound represented by the general formula [34] can be produced by reacting a compound represented by the general formula [32] with a compound represented by the general formula [33] in a solvent in the presence of a base.
This reaction is conducted ordinarily at 0 to 120° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the compound [33] is 1 to 20 equivalents and the amount of the base is 1 to 3 equivalents, all relative to 1 equivalent of the compound represented by the general formula [32].
As the base and solvent used, there can be mentioned, for example, the same substances as used in the step 18.
As the method for introducing a trifluoromethyl group into Y, there can be mentioned, for example, the methods described in J. Chem. Soc. Perkin Trans. 1, 8, 2293-2299 (1990), J. Fluorine Chem., 50(3), 411-426 (1990), J. Chem. Soc. Chem. Commun., 18, 1389-1391 (1993), J. Chem. Soc. Chem. Commun., 1, 53-54 (1992), Chem. Lett., 1719-1720 (1981), Chem. Pharm. Bull., 38(9), 2446-2458 (1990), J. Chem. Soc. Perkin. Trans. 1, 921-926 (1988), Hetercycles, 37(2), 775-782 (1994), Tetrahedron Lett., 30(16), 2133-2136 (1989), J. Chem. Soc. Perkin Trans. 1, 2755-2761 (1980), Hetercycles, 22(1), 117-124 (1984), Eur. J. Med. Chem. Chim. Ther., 24, 249-258 (1989), Acta Chem. Scand. Ser. B, 38(6), 505-508 (1984), J. Fluorine Chem., 21, 495-514 (1982), J. Chem. Soc. Chem. Commun., 10, 638-639 (1988), J. Fluorine Chem., 67(1), 5-6 (1994), J. Heterocycl. Chem., 31(6), 1413-1416 (1994), Chem. Heterocycl. Compd., 30(5), 576-578 (1994), F. Fluorine Chem., 78(2), 177-182 (1996), J. Heterocycl. Chem., 34(2) 551-556 (1997), Tetrahedron, 55(52), 15067-15070 (1999), and Synthesis, 11, 932-933 (1980); and methods similar thereto.
The compounds represented by the general formulas [4], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [29] and [31] can be produced by the methods described, when Y is a pyrrolyl group, in Methoden der Organischen Chemie, E6a, 556-798 (1994); when Y is a pyrazolyl group, in Methoden der Organischen Chemie, E8b, 399-763 (1994) or JP-A-2000-219679; when Y is an isothiazolyl group, in Methoden der Organischen Chemie, E8a, 668-798 (1993); when Y is an oxazolyl group, in Methoden der Organischen Chemie, E8a, 891-1019 (1993); when Y is an imidazolyl group, in Methoden der Organischen Chemie, E8c, 1-215 (1994); when Y is a pyridazinyl group, in Methoden der Organischen Chemie, E9a, 557-682 (1997); when Y is a pyrimidinyl group, in Methoden der Organischen Chemie, E9b/1, 1-249 (1998); when Y is a pyrazinyl group, in Methoden der Organischen Chemie, E9b/1, 250-372 (1998); when Y is a triazinyl group, in Methoden der Organischen Chemie, E9c, 530-796 (1998); when Y is a triazolyl group, in Methoden der Organischen Chemie, E8d, 305-405, 479-598 (1994); when Y is an oxadiazolyl group, in Methoden der Organischen Chemie, E8c, 397-818 (1994); when Y is a benzothienyl group, in Methoden der Organischen Chemie, E6b1, 217-322 (1994); when Y is an indolyl group, in Methoden der Organischen Chemie, E6b1, 546-848 (1994), Methoden der Organischen Chemie, E6b2, 849-1336 (1994), or Unexamined International Patent Publication No. WO 97/42188; when Y is a benzoxazolyl group, in Methoden der Organischen Chemie, E8a, 1020-1194 (1993); when Y is a benzoimidazolyl group, in Methoden der Organischen Chemie, E8c, 216-391 (1994); when Y is a benzoisoxazolyl group, in Methoden der Organischen Chemie, E8a, 226-348 (1993); when Y is a benzoisothiazolyl group, in Methoden der Organischen Chemie, E8a, 799-852 (1993); when Y is an indazolyl group, in Methoden der Organischen Chemie, E8b, 764-864 (1994); when Y is a quinolyl group, in Methoden der Organischen Chemie, E7a, 290-570 (1991); when Y is an isoquinolyl group, in Methoden der Organischen Chemie, E7a, 571-758 (1991); when Y is a phthalazinyl group, in Methoden der Organischen Chemie, E9a, 744-789 (1997); when Y is a quinoxalinyl group, in Methoden der Organischen Chemie, E9b/2, 93-265 (1998); when Y is a quinazolinyl group, in Methoden der Organischen Chemie, E9b/2, 1-192 (1998); when Y is a cinnolinyl group, in Methoden der Organischen Chemie, E9a, 683-743 (1997); and when Y is a benzotriazolyl group, in Methoden der Organischen Chemie, E8d, 406-478 (1994); or by methods similar thereto.
[Production Process 2]
wherein R1, R2, R3, R4, R5, R6 and α have the same meanings as given above; and the carbon atoms of the pyrazole ring may be substituted with 1 to 2 same or different groups selected from the substituent group α.
(Step 20)
A compound of the present invention represented by the general formula [36] can be produced by reacting a compound of the present invention represented by the general formula [35] (which can be produced by the production process 1) with an acid in a solvent.
This reaction is conducted ordinarily at 0 to 120° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the acid is desired to be 1 to 10 equivalents per 1 equivalent of the present compound represented by the general formula [35], but can be varied appropriately depending upon the conditions of the reaction.
As the acid used, there can be mentioned, for example, hydrochloric acid, hydrobromic acid and trifluoroacetic acid.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidinone and the like; sulfur compounds such as dimethyl sulfoxide (DMSO), sulfolane and the like; carboxylic acids such as formic acid, acetic acid and the like; and water.
[Production Process 3]
wherein R1, R2, R3, R4, R5, R6, R11 and α have the same meanings as given above; and the carbon atoms of the pyrazole ring may be substituted with 1 to 2 same or different groups selected from the substituent group α.
(Step 21)
A compound of the present invention represented by the general formula [38] can be produced by reacting a compound of the present invention represented by the general formula [36] (which can be produced by the production process 2) with the compound represented by the general formula [33] in a solvent in the presence of a base.
With respect to the amounts of the reagents used in the reaction, the amount of the compound represented by the general formula [33] is 1 to 3 equivalents and the amount of the base is 1 to 3 equivalents, all relative to 1 equivalent of the compound represented by the general formula [36].
As the solvent used, there can be mentioned, for example, ethers such as dioxane, tetrahydrofuran (THF) and the like; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidinone and the like; sulfur compounds such as dimethyl sulfoxide (DMSO), sulfolane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol and the like; ketones such as acetone, 2-butanone and the like; nitriles such as acetonitrile and the like; water; and mixtures thereof.
As the base used, there can be mentioned, for example, metal hydrides such as sodium hydride and the like; alkali metal amides such as sodium amide, lithium diisopropylamide and the like; organic bases such as pyridine, triethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene and the like; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like; alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkali metal bicarbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and the like; and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like.
[Production Process 4]
wherein R1, R2, R3, R4, R5, R6 and R10 have the same meanings as given above; R12 is a trifluoromethyl group, a difluoromethyl group or a difluoromethoxy group; X3 is a chlorine atom or a fluorine atom; R13 is an alkyl group, a haloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkenyl group, an alkynyl group, an optionally substituted phenyl group, an optionally substituted aromatic heterocyclic group, an alkoxycarbonylalkyl group, an optionally substituted heteroalkyl group or an optionally substituted benzyl group; R14 is an alkyl group, a haloalkyl group, an optionally substituted phenyl group, an optionally substituted aromatic heterocyclic group, an alkoxycarbonylalkyl group or an optionally substituted benzyl group; R15 and R16 may be the same or different and are each a hydrogen atom, an alkyl group, an optionally substituted phenyl group, an acyl group, a haloalkylcarbonyl group, an optionally substituted benzylcarbonyl group, an optionally substituted benzoyl group, an alkylsulfonyl group, a haloalkylsulfonyl group, an optionally substituted benzylsulfonyl group or an optionally substituted phenylsulfonyl group; and Z1 is a sulfur atom or N—R17 (R17 is a hydrogen atom or R10).
A compound of the present invention represented by the general formula [41], the general formula [43] or the general formula [45] can be produced by reacting a compound of the present invention represented by the general formula [39] with a compound represented by the general formula [40] (step 22), the general formula [42] (step 23) or the general formula [44] (step 24) in the absence or presence of a solvent and, as necessary, in the presence of a base.
This reaction is conducted ordinarily at 20 to 200° C., preferably at 30 to 180° C. for 10 minutes to 48 hours, under pressure if necessary.
With respect to the amounts of the reagents used in the reaction, the amount of the compound represented by the general formula [40], the general formula [42] or the general formula [44] is 1 to 20 equivalents per 1 equivalent of the compound of the present invention represented by the general formula [39].
As the base used, there can be mentioned, for example, inorganic bases such as potassium carbonate, sodium hydroxide, potassium hydride, sodium hydride and the like; alkali metal alkoxides such as sodium ethoxide, sodium methoxide and the like; and organic bases such as 1,8-diazabicyclo[5.4.0]-7-undecene and the like.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as chloroform and the like; ethers such as diethyl ether, tetrahydrofuran and the like; aromatic hydrocarbons such as benzene, toluene and the like; aliphatic hydrocarbons such as hexane, heptane and the like; ketones such as acetone, methyl isobutyl ketone and the like; esters such as ethyl acetate and the like; amides such as N-methylpyrrolidone, N,N-dimethylformamide and the like; sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; nitriles such as acetonitrile and the like; and mixtures thereof.
[Production Process 5]
wherein R1, R2, R3, R4, R5, R6, R12, R13 and Z1 have the same meanings as given above.
(Step 25)
A compound of the present invention represented by the general formula [47] can be produced by reacting the present invention compound represented by the general formula [41] with an acid in a solvent.
This reaction is conducted ordinarily at 0 to 120° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the acid is desirably 1 to 10 equivalents per 1 equivalent of the present invention compound represented by the general formula [41] but can be varied appropriately depending upon the conditions of the reaction.
As the acid and solvent used, there can be mentioned the same substances as used in the production process 2.
[Production Process 6]
wherein Y, R1, R2, R3, R4, R5, R6, R10, L1 and α have the same meanings as given above; and Y may be substituted with 1 to 5 same or different groups selected from the substituent group α.
(Step 26)
A compound of the present invention represented by the general formula [49] can be produced by reacting a compound of the present invention represented by the general formula [48] with the compound represented by the general formula [30] in a solvent in the presence of a base.
This reaction is conducted ordinarily at 0 to 150° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the base is desirably 1 to 1.2 equivalents per 1 equivalent of the present invention compound represented by the general formula [48] but can be varied appropriately depending upon the conditions of the reaction.
As the base and solvent used, there can be mentioned the same substances as used in the production process 3.
[Production Process 7]
wherein Y, R1, R2, R3, R4, R5, R6 and α have the same meanings as given above; R18 is an alkyl group, an optionally substituted benzyl group or an optionally substituted phenyl group; and Y may be substituted with 1 to 5 same or different groups selected from the substituent group α.
(Step 27)
A compound of the present invention represented by the general formula [51] can be produced by hydrolyzing a compound of the present invention represented by the general formula [50] in water or a water/solvent mixture in the presence or absence of a base.
This reaction is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the base, when used, is desirably 1 to 2 equivalents per 1 equivalent of the present invention compound represented by the general formula [50] but can be varied appropriately depending upon the conditions of the reaction.
As the base used, there can be mentioned, for example, inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide and the like; and organic bases such as 1,8-diazabicyclo[5.4.0]-7-undecene and the like.
As the solvent to be mixed with water, there can be mentioned, for example, alcohols such as methanol, ethanol and the like; ethers such as tetrahydrofuran and the like; ketones such as acetone, methyl isobutyl ketone and the like; amides such as N,N-dimethylformamide and the like; sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; nitriles such as acetonitrile and the like; and mixtures thereof.
[Production Process 8]
wherein Y, R1, R2, R3, R4, R5, R6 and α have the same meanings as given above; R19 is a hydrogen atom or an alkyl group; R20 is an alkyl group; and Y may be substituted with 1 to 5 same or different groups selected from the substituent group α.
(Step 28)
A compound of the present invention represented by the general formula [54] can be produced by reacting a compound of the present invention represented by the general formula [52] with a compound represented by the general formula [53] in a solvent in the presence of a base.
This reaction is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, it is desired that the amount of the compound represented by the general formula [53] is 1 to 5 equivalents and the amount of the base is 1 to 10 equivalents, all relative to 1 equivalent of the compound of the present invention represented by the general formula [52], but these amounts may be varied appropriately depending upon the conditions of the reaction.
As the base used, there can be mentioned, for example, metal carbonates such as potassium carbonate, sodium carbonate and the like; metal acetates such as potassium acetate, sodium acetate and the like; and organic bases such as triethylamine, dimethylamine, 1,8-diazabicyclo[5.4.0]-7-undecene and the like.
As the salt of NH2OR20 used, there can be mentioned NH2OR20 hydrochloride, NH2OR20 sulfate, etc.
As the solvent used, there can be mentioned, for example, alcohols such as methanol, ethanol and the like; ethers such as tetrahydrofuran and the like; amides such as N,N-dimethylformamide and the like; water; and mixtures thereof.
[Production Process 9]
wherein Y, R1, R2, R3, R4, R5, R6 and α have the same meanings as given above; R21 and R22 are each a hydrogen atom or an alkyl group; and Y may be substituted with 1 to 5 same or different groups selected from the substituent group α.
(Steps 29 and 30)
A compound of the present invention represented by the general formula [58] can be produced by reacting the present invention compound represented by the general formula [51] with a halogenating agent in the presence or absence of a solvent to produce a compound of the present invention represented by the general formula [56] (step 29) and then reacting the compound represented by the general formula [56] with a compound represented by the general formula [57] in the presence or absence of a solvent (step 30).
The reaction of the step 29 is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the regents used in the reaction, the amount of the halogenating agent is desired to be 1 to 100 equivalents per 1 equivalent of the present invention compound represented by the general formula [51], but may be varied appropriately depending upon the conditions of the reaction.
As the halogenating agent used, there can be mentioned, for example, thionyl chloride, oxalyl chloride, etc.
As the solvent used, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform and the like; ethers such as diethyl ether, tetrahydrofuran and the like; and aromatic hydrocarbons such as benzene, toluene and the like.
The reaction of the step 30 is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the regents used in the reaction, the amount of the compound represented by the general formula [57] is desired to be 2 to 100 equivalents per 1 equivalent of the present invention compound represented by the general formula [56], but may be varied appropriately depending upon the conditions of the reaction.
As the solvent used, there can be mentioned, for example, the same solvents as used in the step 29.
[Production Process 10]
wherein Z1, R1, R2, R3, R4, R5, R6, R12 and X3 have the same meanings as given above.
A compound of the present invention represented by the general formula [60] can be produced by reacting the present invention compound represented by the general formula [39] with a compound represented by the general formula [59] in a solvent.
This reaction is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the regents used in the reaction, the amount of the compound represented by the general formula [59] is desired to be 1 to 2 equivalents per 1 equivalent of the present invention compound represented by the general formula [39], but may be varied appropriately depending upon the conditions of the reaction.
As the solvent used, there can be mentioned, for example, ethers such as dioxane, tetrahydrofuran and the like; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide, N-methyl-2-pyrrolidinone and the like; sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; ketones such as acetone, 2-butanone and the like; nitriles such as acetonitrile and the like; water; and mixtures thereof.
[Production Process 11]
wherein Y, R1, R2, R3, R4, R5, R6 and α have the same meanings as given above; R23 is an alkyl group, a haloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkenyl group, an alkynyl group, an alkoxycarbonylalkyl group, an optionally substituted heteroalkyl group or an optionally substituted benzyl group; and Y may be substituted with 1 to 5 same or different groups selected from the substituent group α.
(Step 32)
A compound of the present invention represented by the general formula [62] can be produced by a known method (Synthesis, 1981, 1-28) of reacting the present invention compound represented by the general formula [48] with a compound represented by the general formula [61] in the presence of an azo compound and triphenylphosphine.
This reaction is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, it is desired that the amount of the compound represented by the general formula [61] is 1 to 1.5 equivalents, the amount of the azo compound is 1 to 1.5 equivalents and the amount of triphenylphosphine is 1 to 1.5 equivalents, all relative to 1 equivalent of the present invention compound represented by the general formula [48], but these amounts can be varied appropriately depending upon the conditions of the reaction.
As the solvent used, there can be mentioned, for example, ethers such as dioxane, tetrahydrofuran and the like; halogenated hydrocarbons such as dichloroethane, carbon tetrachloride, chlorobenzene, dichlorobenzene and the like; amides such as N,N-dimethylacetamide, N,N-dimethylformamide, N-methyl-2-pyrrolidinone and the like; sulfur compounds such as dimethyl sulfoxide, sulfolane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; nitriles such as acetonitrile and the like; and mixtures thereof.
As the azo compound used, there can be mentioned, for example, diethyl azodicarboxylate and diisopropyl azodicarboxylate.
[Production Process 12]
wherein X3, n, R1, R2, R3, R4, R5, R6, R10 and α have the same meanings as given above; Z2 is an oxygen atom, a sulfur atom or N—R17; R17 is a hydrogen atom or R10, m is an integer of 1 to 4; and the carbon atom at the 3-position of the pyrazole ring may be substituted with a group selected from the substituent group α.
(Step 33)
A compound of the present invention represented by the general formula [64] can be produced by reacting a compound of the present invention represented by the general formula [63] in a solvent in the presence of a base.
This reaction is conducted ordinarily at 0 to 100° C. for 10 minutes to 24 hours.
With respect to the amounts of the reagents used in the reaction, the amount of the base is desirably 1 to 3 equivalents per 1 equivalent of the present invention compound represented by the general formula [63], but may be varied appropriately depending upon the conditions of the reaction.
As the base and solvent used, there can be mentioned the same bases and solvents as used in the production process 3.
Next, the process for production of the present invention compound, the method for formulation of the present invention herbicide, and the application of the present herbicide are described specifically by way of examples. Incidentally, description is also made on the process for production of an intermediate for the present invention compound.
1.2 g (15.0 mmoles) of sodium hydrosulfide hydrate (purity: 70%) was added into a solution of 2.1 g (10.0 mmoles) of 5-chloromethyl-5-methyl-3-methylsulfonyl-2-isoxazoline dissolved in 20 ml of N,N-dimethylformamide. The mixture was stirred for 2 hours. Then, there were added 2.1 g (15.0 mmoles) of anhydrous potassium carbonate, 2.3 g (15.0 mmoles) of Rongalit and 2.8 g (10.0 mmoles) of 4-bromomethyl-5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole. The mixture was stirred at room temperature for 2 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution, followed by drying over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 3.3 g (yield: 100.0%) of 3-(5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline.
4.3 g (25.0 mmoles) of m-chloroperbenzoic acid (70%) was added, with ice-cooling, into a solution of 3.3 g (10.0 mmoles) of 3-(5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline dissolved in 20 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride ride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with hexane to obtain 2.8 g (yield: 76.0%) of a white powder (melting point: 114 to 116° C.) of 3-(5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-chloromethyl-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.63 (2H, s), 3.96 (3H, s), 3.62 (2H, q), 3.32 (2H, ABq, J=13.4, Δν=164.1 Hz), 1.63 (3H, s)
Into a solution of 24.2 g (70.9 mmoles) of (1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methane-thiol dissolved in 20 ml of N,N-dimethylformamide were added 11.8 g (85.0 mmoles) of anhydrous potassium carbonate and 20 ml of a N,N-dimethylformamide solution containing 2.1 g (10.0 mmoles) of 5-chloromethyl-5-methyl-3-methylsulfonyl-2-isoxazoline. The mixture was stirred overnight to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and then dried over anhydrous magnesium sulfate. The resulting solution was filtered and the filtrate was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 23.1 g (yield: 80.5%) of a colorless viscous liquid (nD20=1.5051) of 3-(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.24 (2H, s), 3.55 (2H, q), 3.02 (2H, ABq, J=16.7, Δν=110.5 Hz), 1.71 (9H, s), 1.57 (3H, s)
Into 100 ml of an acetic acid solution of 25% hydrobromic acid was added 22.0 g (54.4 mmoles) of 3-(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline. The mixture was stirred at room temperature for 2 hours and at 40° C. for 1 hour to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and then dried over anhydrous magnesium sulfate. The resulting solution was filtered and the filtrate was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with hexane to obtain 17.7 g (yield: 93.7%) of a milky white powder (melting point: 105 to 107° C.) of 3-(5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.26 (2H, s), 3.56 (2H, q), 3.03 (2H, ABq, J=16.7, Δν=111.8 Hz), 1.56 (3H, s)
0.6 g (4.3 mmoles) of anhydrous potassium carbonate and 0.74 g (4.7 mmoles) of ethyl iodide were added into a solution of 1.5 g (4.3 mmoles) of 3-(5-chlorotrifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline dissolved in 25 ml of N,N-dimethylformamide. The mixture was stirred at room temperature for 5 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with an aqueous citric acid solution and a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was filtered and the filtrate was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 0.91 g (yield: 56.0%) of 3-(1-ethyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline and 0.45 g (yield: 28.0%) of 3-(1-ethyl-3-chloro-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazline.
1.31 g (5.3 mmoles) of m-chloroperbenzoic acid (70%) was added, with ice-cooling, into a solution of 0.91 g (2.4 mmoles) of 3-(1-ethyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline dissolved in 40 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with diisopropyl ether to obtain 0.81 g (yield: 82.0%) of a white powder (melting point: 123 to 124° C.) of 3-(1-ethyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-chloromethyl-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.64 (2H, s), 4.29 (2H, q), 3.62 (2H, q), 3.30 (2H, ABq, J=17.8, Δν=125.6 Hz), 1.55-1.50 (6H, m)
3.4 g (42.3 mmoles) of sodium hydrosulfide hydrate (purity: 70%) was added into a solution of 4.6 g (21.6 mmoles) of 3-methylsulfonyl-5-chloromethyl-5-methyl-2-isoxazoline dissolved in 70 ml of DMF. The mixture was stirred for 2 hours. Then, there were added 3.0 g (21.6 mmoles) of potassium carbonate, 3.3 g (21.6 mmoles) of Rongalit and 5-bromomethyl-4-ethoxy-6-trifluoromethylpyrimidine. The mixture was stirred at room temperature for 21 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution, followed by drying over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (solvent system: hexane-ethyl acetate) to obtain 1.9 g (yield: 30.3%) of 3-(4-ethoxy-6-trifluoromethylpyrimidin-5-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 8.78 (1H, s), 4.57 (2H, q), 4.45 (2H, s), 3.57 (2H, q), 3.03 (2H, ABq, J=16.8, Δν=114.3 Hz), 1.58 (3H, s), 1.45 (3H, t)
3.2 g (12.9 mmoles) of m-chloroperbenzoic acid (70%) was added, with ice-cooling, into a solution of 1.9 g (5.1 mmoles) of 3-(4-ethoxy-6-trifluoromethylpyrimidin-5-ylmethylthio)-5-chloromethyl-5-methyl-2-isoxazoline dissolved in 30 ml of chloroform. The mixture was stirred at room temperature for 5 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, an aqueous sodium hydrogencarbonate solution, and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with hexane to obtain 1.8 g (yield: 87.7%) of white crystals (melting point: 76.0 to 78.0° C.) of 3-(4-ethoxy-6-trifluoromethylpyrimidin-5-ylmethylsulfonyl)-5-chloromethyl-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 8.87 (1H, s), 5.03 (2H, s), 4.59 (2H, q), 3.64 (2H, q), 3.33 (2H, ABq, J=17.7, Δν=125.9 Hz), 1.64 (3H, s), 1.46 (3H, t)
6.9 g (85.8 mmoles) of sodium hydrosulfide hydrate (purity: 70%) was added, at room temperature, into a solution of 9.1 g (42.9 mmoles) of 5-chloromethyl-5-methyl-3-methylsulfonyl-2-isoxazoline dissolved in 50 ml of N,N-dimethylformamide. The mixture was stirred for 2 hours. Then, there were added 5.9 g (42.9 mmoles) of anhydrous potassium carbonate, 6.6 g (42.9 mmoles) of Rongalit and the crude product of 4-bromomethyl-1-ethyl-5-fluoro-3-trifluoromehtyl-1H-pyrazole (equivalent to 42.9 mmoles) obtained in Reference Example 20. The mixture was stirred at room temperature for 30 minutes to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 10.3 g (yield: 66.9%) of 5-chloromethyl-3-(1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyraz-ol-4-ylmethylthio)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.15-4.08 (4H, m), 3.54 (2H, q), 3.01 (2H, ABq, J=16.7, Δν=110.8 Hz), 1.55 (3H, s), 1.47 (3H, t)
1.23 g (5.0 mmoles) of m-chloroperbenzoic acid (purity: 70%) was added, with ice-cooling, into a solution of 0.72 g (2.0 mmoles) of 5-chloromethyl-3-(1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with n-hexane to obtain 0.64 g (yield: 82.1%) of a white powder (melting point: 73 to 75° C.) of 5-chloromethyl-3-(1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.56 (2H, s), 4.17 (2H, q), 3.61 (2H, q), 3.31 (2H, ABq, J=17.8, Δν=123.6 Hz), 1.58 (3H, s), 1.50 (3H, t)
4.3 g (22.5 mmoles) of sodium methoxide (in the form of a 28% methanol solution) was added, at room temperature, into a solution of 5.4 g (15.0 mmoles) of 5-chloromethyl-3-(1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 30 ml of methanol. The mixture was heated for refluxing for 8 hours, to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 3.3 g (yield: 59.1%) of 5-chloromethyl-3-(1-ethyl-5-methoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-meth-yl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.26 (2H, s), 4.06 (5H, m), 3.55 (2H, q), 3.02 (2H, ABq, J=16.9, Δν=110.5 Hz), 1.56 (3H, s), 1.41 (3H, t)
1.24 g (5.0 mmoles) of m-chloroperbenzoic acid (purity: 70%) was added, with ice-cooling, into a solution of 0.74 g (2.0 mmoles) of 5-chloromethyl-3-(1-ethyl-5-methoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with n-hexane to obtain 0.72 g (yield: 89.2%) of a white powder (melting point: 139 to 140° C.) of 5-chloromethyl-3-(1-ethyl-5-methoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.60 (2H, s), 4.13-4.06 (5H, m), 3.30 (2H, ABq, J=17.8, Δν=122.8 Hz), 1.58 (3H, s), 1.46 (3H, t)
4.21 g (9.0 mmoles) of sodium methyl thioalcoholate (in the form of a 15% aqueous solution) was added, at room temperature, into a solution of 1.08 g (3.0 mmoles) of 5-chloromethyl-3-(1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of N,N-dimethylformamide. The mixture was stirred at room temperature overnight to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein to obtain a crude product of 5-chloromethyl-3-(1-ethyl-5-methylthio-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline.
3.74 g (15.0 mmoles) of m-chloroperbenzoic acid (purity: 70%) was added, with ice-cooling, into a solution of a crude product of 5-chloromethyl-3-(1-ethyl-5-methylthio-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline (equivalent to 3.0 mmoles) dissolved in 30 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with n-hexane to obtain 1.15 g (yield: 84.8%) of a white powder (melting point: 113 to 114° C.) of 5-chloromethyl-3-(1-ethyl-5-methylsulfonyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 5.08 (2H, bR), 4.60 (2H, q), 3.64 (2H, q), 3.41 (3H, s), 3.36 (2H, ABq, J=17.5, Δν=163.1 Hz), 1.65 (3H, s), 1.60 (3H, t)
0.30 g (6.0 mmoles) of sodium cyanide was added, at room temperature, into a solution of 1.08 g (3.0 mmoles) of 5-chloromethyl-3-(1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of N,N-dimethylformamide. The mixture was stirred at 50° C. for 10 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 1.10 g (yield: quantitative) of 5-chloromethyl-3-(5-cyano-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline.
1.85 g (7.5 mmoles) of m-chloroperbenzoic acid (purity: 70%) was added, with ice-cooling, into a solution of 1.10 g (3.0 mmoles) of 5-chloromethyl-3-(5-cyano-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 20 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with n-hexane to obtain 1.15 g (yield: 84.8%) of a white powder (melting point: 76 to 78° C.) of 5-chloromethyl-3-(5-cyano-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.73 (2H, s), 4.45 (2H, q), 3.62 (2H, q), 3.35 (2H, ABq, J=17.6, Δν=129.6 Hz), 1.59-1.46 (6H, m)
10 ml of boron tribromide (2 M/liter of dichloromethane solution, 20.2 mmoles) was added, at −60° C., into a solution of 2.5 g (6.7 mmoles) of 5-chloromethyl-3-(1-ethyl-5-methoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-meth-yl-2-isoxazoline dissolved in 30 ml of dichloromethane. The mixture was stirred at room temperature overnight to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into ice water and extraction with chloroform was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 1.6 g (yield: 66.7%) of 5-chloromethyl-3-(1-ethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline.
0.3 g (5.4 mmoles) of ethanol and 1.4 g (5.4 mmoles) of triphenylphosphine were added, at room temperature, into a solution of 1.6 g (4.5 mmoles) of 5-chloromethyl-3-(1-ethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-meth-yl-2-isoxazoline dissolved in 20 ml of tetrahydrofuran. Thereto was added, with ice-cooling, 1.1 g (5.4 mmoles) of diisopropyl azodicarboxylate. The mixture was stirred for 1 hour to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 1.5 g (yield: 86.8%) of 5-chloromethyl-3-(5-ethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline.
2.4 g (9.7 mmoles) of m-chloroperbenzoic acid (purity: 70%) was added, with ice-cooling, into a solution of 1.5 g (3.9 mmoles) of 5-chloromethyl-3-(5-ethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with diisopropyl ether to obtain 0.71 g (yield: 43.8%) of a white powder (melting point: 67 to 69° C.) of 5-chloromethyl-3-(5-ethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.58 (2H, s), 4.32 (2H, q), 4.09 (2H, q), 3.61 (2H, q), 3.28 (2H, ABq, J=17.8, Δν=121.7 Hz), 1.62 (3H, s), 1.48-1.43 (6H, m)
6.4 g (80.0 mmoles) of sodium hydrosulfide hydrate (purity: 70%) was added, at room temperature, into a solution of 8.5 g (40.0 mmoles) of 5-chloromethyl-5-methyl-3-methylsulfonyl-2-isoxazoline dissolved in 40 ml of N,N-dimethylformamide. The mixture was stirred for 1 hour. Then, there were added, with ice-cooling, 6.6 g (48.0 mmoles) of anhydrous potassium carbonate, 7.4 g (48.0 mmoles) of Rongalit and 10.4 g (40.0 mmoles) of 4-bromomethyl-5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole. The mixture was stirred with ice-cooling for 30 minutes, to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 11.8 g (yield: 85.5%) of a light yellow viscous liquid (refractive index: nD20=1.4974) of 5-chloromethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-iso-xazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.15 (2H, s), 3.80 (3H, s), 3.54 (2H, q), 3.01 (2H, ABq, J=16.8, Δν=147.8 Hz), 1.53 (3H, s)
0.9 g (4.4 mmoles) of sodium methoxide (in the form of a 28% methanol solution) was added, at room temperature, into a solution of 1.0 g (2.9 mmoles) of 5-chloromethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of methanol. The mixture was heated for refluxing for 5 hours, to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order, and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 3.3 g (yield: quantitative) of 5-chloromethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmeth-ylthio)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.26 (2H, s), 4.06 (3H, s), 3.72 (3H, s), 3.55 (2H, q), 3.02 (2H, ABq, J=16.7, Δν=111.0 Hz), 1.56 (3H, s)
28.0 ml of boron tribromide (2 M/liter of a dichloromethane solution, 55.9 mmoles) was added, at 0° C., into a solution of 10.0 g (28.0 mmoles) of 5-chloromethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-meth-yl-2-isoxazoline dissolved in 30 ml of dichloromethane. The mixture was stirred at room temperature for 30 minutes to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into ice water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order, and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with n-hexane to obtain 8.4 g (yield: 87.2%) of a light pink powder (melting point: 111 to 112° C.) of 5-chloromethyl-3-(5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-iso-xazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.01 (2H, s), 3.69 (3H, s), 3.55 (2H, q), 3.09 (2H, ABq, J=17.0, Δν=114.4 Hz), 1.56 (3H, s)
0.5 g (3.5 mmoles) of anhydrous potassium carbonate was added, at room temperature, into a solution of 1.0 g (2.9 mmoles) of 5-chloromethyl-3-(5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline dissolved in 10 ml of N,N-dimethylformamide. Thereto was added, at room temperature, 0.6 g (3.5 mmoles) of isopropyl iodide. The mixture was stirred for 30 minutes to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order, and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 0.5 g (yield: 45.0%) of 5-chloromethyl-3-(1-methyl-5-isopropoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxazoline.
0.65 g (2.64 mmoles) of m-chloroperbenzoic acid (purity: 70%) was added, with ice-cooling, into a solution of 0.5 g (1.2 mmoles) of 5-chloromethyl-3-(1-methyl-5-isopropoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5-methyl-2-isoxa-zoline dissolved in 10 ml of chloroform. The mixture was stirred at room temperature for 20 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogensulfite solution, water, an aqueous sodium hydrogencarbonate solution, water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The resulting crystals were washed with diisopropyl ether to obtain 0.49 g (yield: 90.0%) of a light yellow viscous liquid of 5-chloromethyl-3-(1-methyl-5-isopropoxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5-methyl-2-isoxazoline.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.64 (1H, s), 4.51 (2H, s), 3.76 (3H, s), 3.61 (2H, q), 3.24 (2H, ABq, J=17.8, Δν=116.9 Hz), 1.61 (3H, s), 1.40 (6H, d)
The compounds produced based on the methods of Examples 1 to 24 are shown in Tables 58 to 60.
23.0 g (0.5 M) of monomethylhydrazine and 5 ml of concentrated hydrochloric acid were added into a solution of 92.1 g (0.5 M) of ethyl trifluoroacetoacetate dissolved in 500 ml of ethanol. The mixture was heated and refluxed for 2 days to give rise to a reaction. After the completion of the reaction, the reaction mixture was subjected to reduced pressure distillation to remove the most part of the solvent contained therein. The residue was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting material was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was washed with n-hexane to obtain 60.0 g (yield: 72.2%) of a white powder of 1-methyl-3-trifluoromethyl-1H-pyrazol-5-ol.
360 g (2.31 M) of phosphorus oxychloride was added to 60.0 g (0.76 M) of N,N-dimethylformamide with ice-cooling. Thereto was added, at room temperature, 64.0 g (0.385 M) of 1-methyl-3-trifluoromethyl-1H-pyrazol-5-ol. The mixture was heated and refluxed for 1 hour to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water with ice-cooling, and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogencarbonate solution and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate mixed solvent) to obtain 60.4 g (yield: 73.4%) of white crystals of 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde.
1H-NMR [CDCl3/TMS, δ (ppm)]: 9.96 (1H, d), 3.96 (3H, s)
A solution of 10.0 g (47.0 mmoles) of 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde dissolved in 100 ml of methanol was cooled to 0° C. Thereto was gradually added 2.1 g (56.5 mmoles) of sodium borohydride. The mixture was stirred at room temperature for 2 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 8.3 g (yield: 82.2%) of (5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.
A solution of 8.3 g (38.7 mmoles) of (5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol dissolved in 100 ml of diethyl ether was cooled to −10° C. Thereto was added 12.6 g (46.4 mmoles) of phosphorus tribromide. The mixture was stirred at room temperature for 1 hour to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into ice water and extraction with diethyl ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 10.7 g (yield: 99.9%) of 4-bromomethyl-5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole.
373.8 g (3.0 M) of tert-butylhydrazine hydrochloride and 50 ml of concentrated hydrochloric acid were added to a solution of 552.3 g (3.0 M) of ethyl trifluoroacetoacetate dissolved in 1,500 ml of ethanol. The mixture was heated and refluxed for 2 days to give rise to a reaction. After the completion of the reaction, the reaction mixture was subjected to reduced pressure distillation to remove the most part of the solvent contained therein. The residue was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was washed with n-hexane to obtain 369.0 g (yield: 59.1%) of a white powder of 1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-ol.
462.0 g (3.0 M) of phosphorus oxychloride was added to 87.7 g (1.2 M) of N,N-dimethylformamide with ice-cooling. Thereto was added, at room temperature, 208.2 g (1.0 M) of 1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-ol. The mixture was heated and refluxed for 10 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with water, a 5% aqueous sodium hydroxide solution and water in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate mixed solvent) to obtain 131.5 g (yield: 21.7%) of white crystals of 1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde.
1H-NMR [CDCl3/TMS, δ (ppm)]: 9.97 (1H, d), 1.76 (9H, s)
A solution of 39.9 g (156.9 mmoles) of 1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde dissolved in 300 ml of methanol was cooled to 0° C. Thereto was gradually added 6.5 g (172.6 mmoles) of sodium borohydride. The mixture was stirred at room temperature for 3 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 37.7 g (yield: 93.6%) of (1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.
1H-NMR [CDCl3/TMS, δ (ppm)]: 4.60 (2H, d), 1.72 (9H, s), 1.58 (1H, t)
A solution of 9.2 g (35.7 mmoles) of (1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol dissolved in 100 ml of diethyl ether was cooled to −10° C. Thereto was added 11.6 g (42.9 mmoles) of phosphorus tribromide. The mixture was stirred at room temperature overnight to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into ice water and extraction with diethyl ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 10.0 g (yield: 87.3%) of 4-bromomethyl-1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyra-zole.
43.5 g (136.1 mmoles) of 4-bromomethyl-1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole was added to 300 ml of a N,N-dimethylformamide solution containing 21.8 g (272.2 mmoles) of sodium hydrosulfide hydrate (purity: 70%). The mixture was stirred at room temperature overnight to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into ice water and extraction with diethyl ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 32.3 g (yield: 87.0%) of (1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-metha-nethiol.
1H-NMR [CDCl3/TMS, δ (ppm)]: 3.65 (2H, d), 1.90 (1H, t), 1.70 (9H, s)
77.5 g (945.0 mmoles) of anhydrous sodium acetate was added, at room temperature, into a solution of 49.2 g (300.0 mmoles) of 4-hydroxy-6-trifluoromethylpyrimidine dissolved in 600 ml of acetic acid. Thereto was gradually added, at 45° C., 50.3 g (315 mmoles) of bromine. The mixture was stirred at the same temperature for 3 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was washed with n-hexane to obtain 38.9 g (yield: 53.4%) of 5-bromo-4-hydroxy-6-trifluoromethylpyrimidine.
24.3 g (100.0 mmoles) of 5-bromo-4-hydroxy-6-trifluoromethylpyrimidine was suspended in 18.5 g (120.0 mmoles) of phosphorus oxychloride. The suspension was stirred at 100° C. for 2 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was gradually poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 21.5 g (yield: 82.4%) of 5-bromo-4-chloro-6-trifluoromethylpyrimidine.
0.94 g (13.77 mmoles) of sodium ethoxide was added at room temperature into a solution of 3.00 g (11.48 mmoles) of 5-bromo-4-chloro-trifluoromethylpyrimidine dissolved in 50 ml of ethanol. The mixture was stirred to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was poured into water and extraction with chloroform was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 2.44 g (yield: 82.9%) of 5-bromo-4-ethoxy-6-trifluoromethylpyrimidine.
A solution of 5.76 g (21.3 mmoles) of 5-bromo-4-ethoxy-6-trifluoromethylpyrimidine dissolved in 250 ml of tetrahydrofuran was cooled to −78° C. Thereinto was dropwise added 22.6 ml of a 1.6 M hexane solution containing 36.1 mM of n-butyl lithium. The mixture was stirred for 40 minutes. Thereto was added 2.7 g (45.1 mmoles) of methyl formate. The mixture was stirred for 1.5 hours to give rise to a reaction. After the completion of the reaction, an aqueous ammonium chloride solution was added and extraction with ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate mixed solvent) to obtain 3.82 g (yield: 81.6%) of 4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde.
1H-NMR [CDCl3/TMS, δ (ppm)]: 10.41 (1H, s), 8.95 (1H, s), 4.63 (2H, q), 1.48 (3H, t)
A solution of 3.82 g (17.2 mmoles) of 4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde dissolved in 50 ml of methanol was added, with ice-cooling, into a solution of 1.7 g (45.7 mmoles) of sodium borohydride dissolved in 50 ml of methanol. The mixture was stirred at 0° C. for 1 hour to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 3.77 g (yield: 97.8%) of (4-ethoxy-6-trifluoromethylpyrimidin-5-yl)-methanol.
1H-NMR [CDCl3/TMS, δ (ppm)]: 8.80 (1H, s), 4.81 (2H, s), 4.59 (2H, q), 2.28 (1H, bR), 1.48 (3H, t)
A solution of 3.77 g (17.0 mmoles) of (4-ethoxy-6-trifluoromethylpyrimidin-5-yl)-methanol dissolved in 50 ml of ether was cooled to 0° C. Thereto was added 2.0 g (7.2 mmoles) of phosphorus tribromide. The mixture was stirred at room temperature for 1 hour. The resulting salt was dissolved in methanol and the solution was stirred for 1 hour to give rise to a reaction. The reaction mixture was poured into water and extraction with ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain a crude product of 5-bromomethyl-4-ethoxy-6-trifluoromethylpyrimidine.
1H-NMR [CDCl3/TMS, δ (ppm)]: 8.79 (1H, s), 4.61 (2H, q), 4.55 (2H, s), 1.49 (3H, t)
Into a solution of 55.2 g (300.0 mmoles) of ethyl trifluoroacetoacetate dissolved in 300 ml of ethanol were added 18.0 g (300.0 mmoles) of monoethylhyrazine and 5 ml of concentrated hydrochloric acid. The mixture was heated and refluxed for 2 days to give rise a reaction. After the completion of the reaction, the reaction mixture was subjected to reduced pressure distillation to remove the most part of the solvent contained therein. The residue was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was washed with n-hexane to obtain 35.5 g (yield: 65.7%) of a white powder of 1-ethyl-3-trifluoromethyl-1H-pyrazol-5-ol.
91.1 g (591.2 mmoles) of phosphorus oxychloride was added to 18.0 g (246.3 mmoles) of N,N-dimethylformamide with ice-cooling. Thereto was added, at room temperature, 35.5 g (197.1 mmoles) of 1-ethyl-3-trifluoromethyl-1H-pyrazol-5-ol. The mixture was heated and refluxed for 3 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water with ice-cooling, and extraction with chloroform was conducted. The resulting organic layer was washed with an aqueous sodium hydrogencarbonate solution and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain a crude product of 5-chloro-1-ethyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde.
34.3 g (591.3 mmoles) of potassium fluoride (a spray-dried product) was added, at room temperature, into a solution of a crude product of 5-chloro-1-ethyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde (equivalent to 197.1 mmoles) dissolved in 100 ml of dimethyl sulfoxide. The mixture was stirred at 100° C. for 3 days to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution in this order and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography to obtain 11.1 g (yield: 26.8%) of 1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde.
1H-NMR [CDCl3/TMS, δ (ppm)]: 9.86 (1H, d), 4.19 (2H, q), 1.52 (3H, t)
A solution of 11.1 g (52.8 mmoles) of 1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde dissolved in 50 ml of methanol was cooled to 0° C. Thereto was gradually added 2.1 g (55.5 mmoles) of sodium borohydride. The mixture was stirred at room temperature for 3 hours to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water and extraction with diethyl ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 9.1 g (yield: 81.3%) of (1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.
A solution of 9.1 g (42.9 mmoles) of (1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol dissolved in 100 ml of diethyl ether was cooled to −10° C. Thereto was added 12.2 g (45.0 mmoles) of phosphorus tribromide. The mixture was stirred at room temperature overnight to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into ice water and extraction with diethyl ether was conducted. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain a crude product of 4-bromomethyl-1-ethyl-5-fluoro-3-trifluoromethyl-1H-pyrazole.
42.0 g (711.9 mmoles) of potassium fluoride was added into a solution of 60.4 g (282.7 mmoles) of 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde dissolved in 700 ml of dimethyl sulfoxide. The mixture was stirred at 120 to 140° C. for 5 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate mixed solvent) to obtain 36.8 g (yield: 66.0%) of 5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-.
A solution of 36.8 g (187.6 mmoles) of 5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde dissolved in 200 ml of methanol was added, with ice-cooling, into a solution of 3.9 g (102.6 mmoles) of sodium borohydride dissolved in 500 ml of methanol. The mixture was stirred at 0° C. for 30 minutes to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was poured into water and extraction with ethyl acetate was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 35.4 g (yield: 95.4%) of (5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.
A solution of 35.4 g (178.7 mmoles) of 5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde dissolved in 500 ml of diethyl ether was cooled to −30° C. Thereto was added 54.0 g (199.5 mmoles) of phosphorus tribromide. The mixture was stirred at room temperature for 12 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was poured into water and extraction with diethyl ether was conducted. The resulting organic layer was washed with water and an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to reduced pressure distillation to remove the solvent contained therein, to obtain 31.4 g (yield: 80.8%) of 4-bromomethyl-5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole.
The herbicide of the present invention contains, as an active ingredient, an isoxazoline derivative represented by the general formula [I].
In using the compound of the present invention as a herbicide, the present compound may be used by itself. It can also be used in the form of a powder, a wettable powder, an emulsion, a flowable agent, fine granules, granules, etc. by mixing with a carrier, a surfactant, a dispersing agent, an auxiliary agent, etc. all generally used in herbicide production.
As the carrier used in herbicide production, there can be mentioned, for example, solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, calcium carbonate, slaked lime, siliceous sand, ammonium sulfate, urea and the like; and liquid carriers such as isopropyl alcohol, xylene, cyclohexane, methylnaphthalene and the like.
As the surfactant and the dispersing agent, there can be mentioned, for example, metal salts of alkylbenzenesulfonic acids, metal salts of dinaphthylmethanedisulfonic acid, salts of alcohol sulfates, alkylarylsulfonic acid salts, ligninsulfonic acid salts, polyoxyethylene glycol ether, polyoxyethylene alkyl aryl ethers, monoalkylates of polyoxyethylene sorbitan and the like. As the auxiliary agent, there can be mentioned, for example, carboxymethyl cellulose, polyethylene glycol and gum arabic. The present herbicide, when used, is diluted to an appropriate concentration and sprayed or applied directly.
The herbicide of the present invention can be used by post-emergence application, pre-emergence application or water surface application, etc. The amount of the active ingredient used is determined appropriately so as to meet the application purpose. When the present compound is made into a powder or granules, the amount is appropriately determined in a range of 0.01 to 10% by weight, preferably 0.05 to 5% by weight. When the present compound is made into an emulsion or a wettable powder, the amount is appropriately determined in a range of 1 to 50% by weight, preferably 5 to 30% by weight. When the present compound is made into a flowable agent, the amount is appropriately determined in a range of 1 to 40% by weight, preferably 5 to 30% by weight.
The amount of the present herbicide used varies depending upon the kind of the compound used, the target weed, the tendency of weed emergence, the environmental conditions, the form of the herbicide used, etc. When the present herbicide is used per se as in the case of a powder or granules, the amount is appropriately selected in a range of 1 g to 50 kg, preferably 10 g to 10 kg per 1 hectare in terms of the active ingredient. When the present herbicide is used in a liquid form as in the case of an emulsion, a wettable powder or a flowable agent, the amount is appropriately selected in a range of 0.1 to 50,000 ppm, preferably 10 to 10,000 ppm.
The compound of the present invention may be mixed as necessary with an insecticide, a fungicide, other herbicide, a plant growth-regulating agent, a fertilizer, etc.
Next, herbicide formulation from the present compound is described specifically by showing typical examples of herbicide formulation. The kinds of compounds and additives and their compounding ratios are not restricted to those shown below and can be varied widely. In the following description, “parts” refer to parts by weight.
(Formulation 1) Wettable Powder
10 parts of a present invention compound No. 2 were mixed with 0.5 part of polyoxyethylene octylphenyl ether, 0.5 part of a sodium salt of a β-naphthalenesulfonic acid-formalin condensate, 20 parts of diatomaceous earth and 69 parts of clay. The mixture was ground to obtain a wettable powder.
(Formulation 2) Flowable Agent
20 parts of a coarsely ground present invention compound No. 2 were dispersed in 69 parts of water. Thereto were added 4 parts of a sulfate of a polyoxyethylene styrenated phenyl ether, 7 parts of ethylene glycol and 200 ppm, relative to the herbicide produced, of Silicone AF-118N (a product of Asahi Chemical Industry, Co. Ltd.). The resulting mixture was stirred for 30 minutes using a high-speed stirrer and then ground using a wet grinder to obtain a flowable agent.
(Formulation 3) Emulsion
To 30 parts of a present invention compound No. 2 were added 60 parts of an equal volume mixture of xylene and isophorone and 10 parts of a surfactant mixture of a polyoxyethylene sorbitan alkylate, a polyoxyethylene alkylaryl polymer and an alkylaryl sulfonate. The resulting mixture was stirred sufficiently to obtain an emulsion.
Formulation 4) Granules
10 parts of water was added to 10 parts of a present invention compound No. 2, 80 parts of an extender which was a 1:3 mixture of talc and bentonite, 5 parts of white carbon and 5 parts of a surfactant mixture of a polyoxyethylene sorbitan alkylate, a polyoxyethylene alkylaryl polymer and an alkylaryl sulfonate. The resulting mixture was kneaded sufficiently to form a paste. The paste was extruded through the eyes (diameter: 0.7 mm) of a sieve. The extrudate was dried and cut into a length of 0.5 to 1 mm to obtain granules.
Next, Application Examples of the present herbicide are described to show the effect of the present compound.
A paddy field soil was filled in a plastic pot of 100 cm2 and subjected to puddling. Then, seeds of Echinochloa oryzicola Vasing. and Monochoria vaginalis (Murm. f.) Presl var. plantaginea (Roxb.) Solms-Laub. were sowed and water was filled in a depth of 3 cm. Next day, wettable powders produced in accordance with the Formulation 1 were diluted with water and dropped on the water surface. The application amount of each wettable powder was 1,000 g per 1 hectare in terms of the active ingredient. Then, breeding was made in a greenhouse, and the herbicidal effect of each wettable powder was examined at the 21st day from the treatment in accordance with the standard shown in Table 61. The results are shown in Table 62.
Monochoria vaginalis
Echinochloa
oryzicola
An upland field soil was filled in a plastic pot of 80 cm2. Seeds of Echinochloa crus-galli (L.) Beauv. var. crus-galli and Setaria viridis (L.) Beauv. were sowed, followed by covering with the same soil. Wettable powders produced in accordance with the Formulation 1 were diluted with water and sprayed uniformly on the soil surface using a small sprayer, in an amount of 1,000 liters per 1 hectare so that the amount of each active ingredient became 1,000 g per 1 hectare. Then, breeding was made in a greenhouse, and the herbicidal effect of each wettable powder was examined at the 21st day from the treatment in accordance with the standard shown in Table 61. The results are shown in Table 63.
Echinochloa
crus-galli
Setaria viridis
crus-galli
A sand was filled in a plastic pot of 80 cm2. Seeds of Echinochloa crus-galli (L.) Beauv. var. crus-galli and Setaria viridis (L.) Beauv. were sowed. Breeding was made in a greenhouse for 2 weeks. Wettable powders produced in accordance with the Formulation 1 were diluted with water and sprayed on the whole foliage of plants from above the plants using a small sprayer in an amount of 1,000 liters per 1 hectare so that the amount of each active ingredient became 1,000 g per 1 hectare. Then, breeding was made in the greenhouse, and the herbicidal effect of each wettable powder was examined at the 14th day from the treatment in accordance with the standard shown in Table 61. The results are shown in Table 64.
Echinochloa crus-galli
Setaria viridis
crus-galli
The compound represented by the general formula [I] according to the present invention shows an excellent herbicidal effect over a wide period from before germination to growth, to various weeds causing problems in upland fields, for example, broadleaf weeds [e.g. Polygonum lapathifolium L. subsp. nodosum (Pers.) Kitam., Amaranthus viridis L., Chenopodium album L., Stellaria media (L.) Villars, Abutilon theophrasti Medik., Sida spinosa, Sesbaria exaltata, Ipomoea spp. and Xanthium strumarium L.], perennial or annual cyperaceous weeds [e.g. Cyperus rotundus L., Cyperus esculentus, Kyllinga brevifolia Rottb. subsp. leiolepis (Fraxch. et Savat.) T. Koyama, Cyperus microiria Steud., and Cyperus iria L.], and Granineous weeds [e.g. Echinochloa crus-galli (L.) Beauv. var. crus-galli, Digitaria ciliaris (Retz.) Koeler, Setaria viridis (L.) Beauv., Poa annua L., Sorghum halepense (L.) Pers., Alopecurus aequalis Sobol. var. amurensis (Komar.) Ohwi, and Avena fatua L.]. Further, the present compound shows a herbicidal effect also to weeds emerging in paddy fields, i.e. annual weeds [e.g. Echinochloa oryzicola Vasing., Cyperus difformis L., and Monochoria vaginalis (Burm. f.) Presl. var. plantaginea (Roxb.) Solms-Laub.] and perennial weeds [e.g. Sagittaria trifolia L., Sagittaria pygmaea Miq., Cyperus serotinus Rottb., Eleocharis kuroguwai Ohwi, Scirpus juncoides Roxb. subsp. hotarui (Ohwi) T. Koyama and Alisma canaliculatum].
The herbicide of the present invention has high safety to crops, particularly to rice, wheat, barley, corn, grain sorghum, soybean, cotton, sugar beat, etc.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2001-187679 | Jun 2001 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP02/06183 | 6/20/2002 | WO | 00 | 6/12/2004 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO03/000686 | 1/3/2003 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 7238689 | Nakatani et al. | Jul 2007 | B2 |
| Number | Date | Country |
|---|---|---|
| 1 203 768 | Sep 2000 | EP |
| 1 364 946 | Nov 2003 | EP |
| 5-105672 | Apr 1993 | JP |
| 05-105672 | Apr 1993 | JP |
| 9-328483 | Dec 1997 | JP |
| 09-328483 | Dec 1997 | JP |
| 03010165 | Feb 2003 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20040259734 A1 | Dec 2004 | US |
