Indian Patents. 220330:"A FUNGICIDAL COMPOSITION"

Title of Invention	"A FUNGICIDAL COMPOSITION"
Abstract	Fungicidal compositions effective in the control of paddy rice diseases, containing as the active ingredients both a compound represented by the general formula (1) or an acid addition salt thereof and at least one member selected from among strobilurin insecticides: (1) wherein R is hydrogen, -COR<1>, -COOR<1> (wherein R<1> is alkyl having 1 to 4 carbon atoms), -COCH2OCH3, or -COCH2OCOCH3.

Full Text	yet. These compounds, however, are expected to have a mechanism of action different from conventional control agents for rice blast, for example, because control effect can also be attained against strains resistant to kasugamycin, organic phosphorus agents and strobilurin compounds and, in addition, fungicidal activity is exhibited without inhibition of biosynthesis of melanin in culture media. Strobilurin fungicidal compounds have been reported to have excellent control effect or high fungicidal activity against a plurality of fungal diseases of paddy rice including rice blast, or various fungal diseases or pathogenic fungi as fungi causative of these diseases that pose cultivation problems of barley and wheat, vegetables, and fruit trees. The excellent control effect of strobilurin compounds and the mechanism of action thereof are described, for example, in Noyaku Handobukku (Agricultural Chemical Handbook) 2001 (published in 2001 by Japan Plant Protection Association), and Ippan Itaku Shiken Seisekisho (General Contract Test Report) (published by Japan Plant Protection Association). Rice blast is the most serious disease involved in paddy rice cultivation. Rice blast is a plant disease induced by parasitism of fungi of the genus Pyricularia which are a kind of mold fungi and belong to deuteromycetes. Up to now, many excellent control agents and methods for rice blast have been reported. In some cases, however, even after the application of such control agents, an outbreak of rice blast takes place under certain meteorological conditions, such as unseasonably cool summer weather and very long rainy seasons, and due to unfavorable cultivation conditions, such as unsatisfactory management of seedlings and fertilizing. For these reasons, the development of control agents having better control effect against rice The present invention relates to a fungicidal composition. [BACKGROUND OF THE INVENTION] Field of the Invention The present invention relates to a fungicidal composition having excellent control effect against diseases of paddy rice, and more particularly to a fungicidal composition having excellent control effect against fungal diseases of paddy rice including rice blast. Related Art WO 01/92231 (International Publication Date: 6 December, 2001) filed by the present applicant discloses compounds, having excellent fungicidal activity of formula 11) or acid addition salts thereof: (Formula Removed) wherein R represents a hydrogen atom; -COR1 or -COOR1, wherein R1 represents an alkyl group having 1 to 4 carbon atoms; -COCH2OCH3; or -COCH2OCOCH3. In this publication, the physicochemical properties of the above compounds and control effect of the above compounds against rice blast are also described. Furthermore, the publication describes that the above compounds are excellent in therapeutic effect against rice blast, as well as in residual activity and prophylactic effect, and that these effects are different from the therapeutic effect of conventional rice blast control agents. The mechanism of action of the compounds represented by formula (1) has not been fully elucidated blast has been desired. Further, a recent increase in the number of farmers with a side job and an increase in the number of aged people engaging in agriculture have led to a demand for the development of a technique that can extend a period during which disease control can be carried out, and can reduce the number of applications and amount of labor. Furthermore, the development of chemical agents, which can exhibit control effect simultaneously against a plurality of diseases, has been desired from the viewpoints of labor saving and a reduction in amount of an agricultural chemical to be applied. [SUMMARY OF THE INVENTION] As a result of evaluation of overall effect of the above-described plurality of activities, duration time of these activities, etc., the present inventors have now found that a mixture composition comprising a compound represented by formula (1) (2,3-dimethyl-6-t-butyl-8-fluoro-4-quinolinol derivative) and at least one compound selected from the group consisting of strobilurin fungicides does not sacrifice the activity of each ingredient and, at the same time, develops synergistic effect and exhibits excellent^ control effect against rice blast. Further, in this connection, it has been found that the above composition has excellent control effect against rice blast, a representative disease of paddy rice, at low dose for a long period of time, when the composition has been applied at proper timing, as well as when the application time has been delayed past the proper timing. The present invention has been made based on such finding. Accordingly, an object of the present invention is to provide a chemical agent which has excellent control effect against diseases of paddy rice and has excellent control effect at low dose for a long period of time (Formula Removed) even when the application time has been delayed from proper application timing. According to an aspect of the present invention, there is provided a fungicidal composition comprising as active ingredients a compound of formula (1) or an acid addition salt thereof: (Formula Removed) wherein R represents a hydrogen atom; -COR1 or -COOR1, wherein R1 represents an alkyl group having 1 to 4 carbon atoms; -COCH2OCH3; or -COCH2OCOCH3, and at least one compound selected from the group consisting of strobilurin fungicides. According to another aspect of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying an effective amount of the above fungicidal composition to an area to be treated. According to a further aspect of the present invention, there is provided use of the above fungicidal composition, for the production of a control agent for a disease of paddy rice. The fungicidal composition according to the present invention comprises a mixture of two compounds different from each other in mechanism of action and fungicidal spectrum. The fungicidal composition according to the present invention has excellent control effect against rice blast, as well as against other fungal diseases of paddy rice, for example, sheath blast, ear burn due to Helminthosporium leaf spot, Cercospora leaf spot or the like, dicoloration of grains of rice caused, for example, by the genus Curvularia and the genus Alternaria, and false smut. According to the fungicidal composition of the present invention, the ingredients in the fungicidal composition act together in a synergistic fashion to provide unexpected and significant control effect. Therefore, according to the fungicidal composition of the present invention, the necessary chemical application rate per area can be reduced. In addition, according to the fungicidal composition of the present invention, excellent control effect can be attained at a lower dose compared with using each ingredient of the composition separately. Further, in this case, the control effect is durable for a long period of time. Therefore, according to the fungicidal composition of the present invention, the necessary number of treatments of plants can be reduced. Further, the total amount of the chemical agent used for a target plant during the cultivation period can be reduced. The fungicidal composition according to the present invention can exhibit excellent control effect when the composition has been applied for control treatment at proper timing, and even when the application time has been delayed past the proper timing. The fungicidal composition according to the present invention can realize simultaneous control against a plurality of diseases and, at the same time, can reduce the risk of the development of resistance of fungi. The fungicidal composition according to the present invention can be expected to greatly contribute to labor-saving in agriculture, environmental protection, and stable food production. [DETAILED DESCRIPTION OF THE INVENTION] Fungicidal composition As described above, the fungicidal composition according to the present invention comprises as active ingredients a compound of formula (1) or an acid addition salt thereof and at least one compound belonging to strobilurin fungicides. The fungicidal composition may be used for the control of diseases of plants, preferably the control of diseases of rice, more preferably the control of diseases of paddy rice. Examples of such diseases include: rice blast; ear burn due to Helminthosporium leaf spot, Cercospora leaf spot or the like; dicoloration of grains of rice caused, for example, by the genus Curvularia and the genus Alternaria; false smut; and sheath blast. More preferably, the fungicidal composition according to the present invention is used for the control of rice blast. In the present invention, "comprising as an active ingredient" means that a carrier suitable for desired formulation may of course be incorporated and, in addition, other chemical agents usable in combination with the compound of the present invention may be incorporated. Here the term "rice" is used to embrace paddy rice and rice grown in dry fields. The term "paddy rice" refers to rice cultivated in paddy fields. Compounds of formula (1) The fungicidal composition according to the present invention includes a compound of formula (1) or an acid addition salt thereof. In formula (1), R represents a hydrogen atom, -COR1, -COOR1, -COCH2OCH3, or -COCH2OCOCH3. In the present invention, R1 represents an alkyl group having 1 to 4 carbon atoms. In the present invention, the alkyl group may be in any of straight chain, branched chain, and cyclic forms. Further, one or more hydrogen atoms on the alkyl group may be optionally substituted by one or more according to the present invention comprises as active ingredients a compound of formula (1) or an acid addition salt thereof and at least one compound belonging to strobilurin insecticides. The fungicidal composition may be used for the control of diseases of plants, preferably the control of diseases of rice, more preferably the control of diseases of paddy rice. Examples of such diseases include: rice blast; ear burn due to Helminthosporium leaf spot, Cercospora leaf spot or the like; dicoloration of grains of rice caused, for example, by the genus Curvularia and the genus Alternaria; false smut; and sheath blast. More preferably, the fungicidal composition according to the present invention is used for the control of rice blast. In the present invention, "comprising as an active ingredient" means that a carrier suitable for desired formulation may of course be incorporated and, in addition, other chemical agents usable in combination with the compound of the present invention may be incorporated. Here the term "rice" is used to embrace paddy rice and rice grown in dry fields. The term "paddy rice" refers to rice cultivated in paddy fields. Compounds of formula (1) The fungicidal composition according to the present invention includes a compound of formula (1) or an acid addition salt thereof. In formula (1), R represents a hydrogen atom, -COR1, -COOR1, -COCH2OCH3, or -COCH2OCOCH3. In the present invention, R1 represents an alkyl group having 1 to 4 carbon atoms. In the present invention, the alkyl group may be in any of straight chain, branched chain, and cyclic forms. Further, one or more hydrogen atoms on the alkyl group may be optionally substituted by one or more substituents which may be the same or different. Specific examples of R1 include methyl, ethyl, n-propyl, isopropyl, and n-butyl. In formula (1) , when R represents a hydrogen atom, the compounds of formula (1) may take a structure of formula (2) which is a tautomer of the compounds of formula (1) . It would be apparent to a person having ordinary skill in the art that the compounds of formula (1) embrace the compounds of formula (2). (Formula Removed) In the present invention, the term "acid addition salt" refers to salts, which are generally usable in the fields of agriculture and gardening, for example, hydrochlorides, nitrates, sulfates, phosphates, and acetates. It should be noted that the compounds of formula (1) may take the form of hydrates or solvates. In the present invention, such hydrates and solvates are also embraced in the compounds of formula (1). Specific examples of compounds of formula (1) include compounds 1 to 11 in working examples which will be described later. Production process of compounds of formula (1) The compounds of formula (1) may be synthesized by any appropriate process regarding the formation of a bond or the introduction of a substituent. For example, a compound of formula (1) can be produced from 4-t-butyl-2-fluoroaniline, which can be synthesized by a conventional method, according to the following scheme. (Scheme Removed) wherein R represents a hydrogen atom, -COR1, -COOR1, COCH2OCH3, or -COCH2OCOCH3 ; R1 represents an alkyl group having 1 to 4 carbon atoms; and R2 represents -R1, -OR1, -CH2OCH3, or -CH2OCOCH3. According to this scheme, a compound of formula (2) is first provided (step (a)), and, if necessary, the compound of formula (2) is then reacted with the compound of formula (3) or (4) in the presence or absence of a base (step (b)) to give the compound of formula (1) . """" The above scheme will be described in more detail. Step (a): A compound of formula (2) is first prepared from 4-t-butyl-2-fluoroaniline and ethyl 2-methyl-acetoacetate, for example, according to J. Am. Chem. Soc. 70, 2402 (1948) and Tetrahedron Lett. 27, 5323 (1986). The compound of formula (2) corresponds to the compound of formula (1) wherein R represents a hydrogen atom. 4-t-Butyl-2-fluoroaniline used herein may be prepared by a conventional method described, for example, in Chem. Abs. 42, 2239 or J. Chem. Soc, Chem. Commun., 1992, 595. Step (b) : Next, when a compound of formula (1) , wherein R represents a group other than a hydrogen atom, is desired, this compound can be produced by reacting the compound of formula (2) with the compound of formula (3) or (4) in the presence or absence of a base. Bases usable herein include, for example, organic amines, such as triethy1amine and pyridine, and inorganic bases, such as sodium carbonate, potassium carbonate, and sodium hydride. The compound of formula (3) or (4) is preferably used in an amount of 1 to 50 equivalents, more preferably 1 to 10 equivalents, based on the compound of formula (2) . The reaction in step (b) may be carried out in the absence of a solvent or in the presence of an organic solvent inert to the reaction, for example, dimethylformamide or tetrahydrofuran, for example, in the temperature range of 0 to 140°C. Strobilurin fungicide In the present invention, the strobilurin fungicides may be any one which is known as a strobilurin fungicide in the art. Strobilurin fungicides are described as fungicides, for example, in Noyaku Handobukku (Agricultural Chemical Handbook) 2001 (published in 2001 by Japan Plant Protection Association) and Noyaku Yoran (Agricultural Chemical Manual) (published in 2001 by Japan Plant Protection Association). A person having ordinary skill in the art could properly select the strobilurin fungicides by making reference to these documents. Specific examples of the strobilurin fungicide usable in the present invention include azoxystrobin, metominostrobin, kresoxim-methyl, trifloxystrobin, orysastrobin, fluoxastrobin, pyraclostrobin, and picoxystrobin. In a preferred embodiment of the present invention, the strobilurin fungicide is selected from azoxystrobin, metominostrobin, and orysastrobin. In a more preferred embodiment of the present invention, the strobilurin fungicide is selected from azoxystrobin and metominostrobin. Other ingredients When the fungicidal composition according to the present invention is actually applied, a composition consisting of the above active ingredients only as such may be used. Alternatively," the composition may be mixed, for example, with suitable carriers or adjuvants for formulations, to prepare any suitable formulation, such as dusts, granules, packs, wettable powders, wettable granules, floables, liquid formulations, microcapsules, or emulsifiable concentrates. This permits the fungicidal composition according to the present invention to be suitably used for appropriate various applications. Formulation may be prepared by a method known in the art as in general agricultural chemicals. Specifically, for example, formulation may be prepared by mixing active ingredients, if necessary, for example, with a solid carrier, a solvent, a surfactant, and other adjuvants. The carrier and the like may be selected according to purposes of use, for example, improvement in properties of formulations, stabilization of active ingredients and an enhancement in effect. Solid carriers usable herein include, for example, clay, talc, calcium carbonate, diatomaceous earth, zeolite, bentonite, acid clay, activated clay, attapulgus clay, vermiculite, pearlite, pumice, white carbon, titanium dioxide, water-soluble salts, wood flour, corn cob, walnut shell, cellulose powder, starch, dextrin, and saccharides. Examples of solvents usable herein include: aromatic solvents such as xylene, C9 alkylbenzenes, C10 alkylbenzenes, alkylnaphthalenes, and high-boiling aromatic hydrocarbons; aliphatic solvents such as n-paraffins, iso-paraffins, and naphthenes; mixed solvents such as solvents produced from kerosene or coal oil; machine oils such as high-boiling aliphatic hydrocarbons; alcohols such as ethanol, isopropanol, and cyclohexanol; polyhydric alcohols such as ethylene glycol, diethylene glycol, propylene glycol, hexylene glycol, polyethylene glycol, and polypropylene glycol; polyhydric alcohol derivatives such as propylene glycol ether; ketones such as cyclohexanone and gamma-butyrolactone; esters such as fatty acid methyl esters (for example, coconut oil fatty acid methyl esters) and dibasic acid methyl esters (for example, succinic acid dimethyl esters, glutamic acid dimethyl esters, and adipic acid dimethyl esters); nitrogen-containing solvents such as N-alkylpyrrolidone; fats and oils such as coconut oils, soybean oils, and rapeseed oils; and water. Examples of surfactants usable herein include sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, sucrose fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid diesters, polyoxyethylene castor oils, polyoxyethylene hydrogenated castor oils, polyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene dialkylphenyl ethers, polyoxyethylene alkylphenyl ether/formalin condensates, polyoxyethylene/polyoxypropylene block polymers, alkylpolyoxyethylene/polyoxypropylene block polymer ethers, alkylphenyl polyoxyethylene/polyoxypropylene block polymer ethers, polyoxyethylene alkylamines, polyoxyethylene fatty acid amides, polyoxyethylene bisphenyl ethers, polyoxyethylene benzylphenyl ethers, polyoxyethylene styrylphenyl ethers, polyoxyethylene ether-type silicones, ester-type silicones, fluorosurfactants or other nonionic surfactants, alkyl sulfates, polyoxyethylene alkyl ether sulfates, polyoxyethylene alkylphenyl ether sulfates, polyoxyethylene benzylphenyl ether sulfates, polyoxyethylene/polyoxypropylene block polymer sulfates, paraffin sulfonates, AOSs, dialkylsulfosuccinates, alkylbenzene sulfonates, naphthalene sulfonates, naphthalene sulfonate/formalin condensates, alkyldiphenyl ether disulfonates, lignin sulfonates, polyoxyethylene alkylphenyl ether sulfonates, polyoxyethylene alkyl ether sulfosuccinic acid half esters, fatty acid salts, N-methyl-fatty acid sarcosinates, resin acid salts, polyoxyethylene alkyl ether phosphates, polyoxyethylene alkylphenyl ether phosphates, polyoxyethylene benzylated phenyl ether phosphates, polyoxyethylene/polyoxypropylene block polymer phosphates, lecithins, alkylphosphates, alkyltrimethylammonium chlorides, methyl/polyoxyethylene alkylammonium chlorides, alkyl N-methyl-pyridinium bromides, alkylmethylated ammonium chlorides, alkylpentamethylpropylenediamine dichlorides, alkyldimethylbenzalkonium chlorides, benzethonium chlorides, dialkyldiaminoethylbetaines, and alkyldimethylbenzylbetaines. Adjuvants usable herein include, for example, isopropyl phosphate, carboxymethylcellulose, PVA, sodium tripolyphosphate, sodium hexametaphosphate, xanthan gum, guar gum, carboxymethylcellulose, sodium benzoate, potassium sorbate, p-hydroxybenzoic esters, 1,2-benzothiazolin-3-one, ethylene glycol, diethylene glycol, propylene glycol, polyvinyl pyrrolidone, urea, hexamethylenetetramine, antioxidants, ultraviolet absorbers, zeolites, quick lime, magnesium oxide, hydrophobic high-boiling solvents, sodium polyacrylate, alginic acid, kraft lignin, methacrylic acid/vinyl pyrrolidone copolymer, glycerin, sorbitol, and water-swellable polymeric compounds. The above carriers, surfactants, dispersants, and adjuvants may be used solely or in a combination of two or more of them selected from the same group or different groups. In the fungicidal composition according to the present invention, the mixing proportion of the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides may be such that the total amount of them (the total amount of the active ingredients) is 0.1 to 90 parts by weight, preferably 1 to 70 parts by weight, based on 100 parts by weight of the fungicidal composition. The total amount of the active ingredients may be properly selected by taking into consideration formulation, application method, service environment, and other conditions of the fungicidal composition. For example, when the fungicidal composition is in a wettable powder form, the total amount of the active ingredients is 5 to 50% by weight, preferably 10 to 30% by weight. On the other hand, when the fungicidal composition is in a dust form, the total amount of the active ingredients is 0.5 to 5.0% by weight, preferably 1.0 to 2.0% by weight. In the fungicidal composition according to the present invention, the mixing ratio between the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides is in the range of 1 : 100 to 100 : 1, preferably in the range of 1 : 20 to 20 : 1. When the fungicidal composition according to the present invention is used, the fungicidal composition as such may be used directly. If necessary, the fungicidal composition may be diluted with a diluting liquid, such as water, followed by treatment, for example, application to an area to be treated, admixing into the area to be treated, application to water surface in the area to be treated, or immersion in the area to be treated. Specific examples of the treatment include application to plant per se (application to stems and leaves), application to raising seedling boxes, application to soil (admixing with soil or application to side stripes) , application to field water (application to water surface or application to regular paddy field), and application to seeds (seed treatment). According to another aspect of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying an effective amount of the fungicidal composition according to the present invention to an area to be treated. The term "area to be treated" refers to an area which should be treated with the fungicidal composition according to the present invention for rice disease control purposes. Examples of such areas include rice plants, raising seedling boxes, soils, field water, and seeds. Preferably, the area to be treated is rice plant, soil, or field water. The amount of the fungicidal composition according to the present invention used may be properly varied depending upon service environment, growth state of object plants, mixing ratio of active ingredients, formulations, application time, application method, and target disease to be controlled. In general, the amount of the fungicidal composition used is 1 to 1,500 g, preferably 10 to 150 g, per 10 ares in terms of the total amount of the active ingredients. For example, when the fungicidal composition is applied to a rice plant, the amount of the fungicidal composition used is 5 to 500 g, preferably 10 to 100 g, per 10 ares in terms of the total amount of the active ingredients. The fungicidal composition according to the present invention may be used as a mixture, for example, with other fungicides, insecticides, miticides, herbicides, plant growth-regulating agents, or fertilizers. In general, the fungicidal composition according to the present invention is previously formed into a desired formulation in the above-described manner. Alternatively, a method may be adopted wherein a formulation comprising one of the active ingredients in the composition, that is, one of the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides, and a formulation comprising the other active ingredient are previously prepared and, in use, these formulations are mixed together on site. Thus, according to another aspect of the present invention, there is provided a combination comprising a compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides. In a preferred embodiment, in the above combination, the compound of formula (1) or an acid addition salt thereof is provided as a first composition comprising the compound of formula (1) or an acid addition salt thereof as an active ingredient, and the at least one compound selected from the group consisting of strobilurin fungicides is provided as a second composition comprising the at least one compound as an active ingredient. In this case, as with the above-described fungicidal composition, the first composition and the second composition may be in any formulation form which has been prepared by additionally using suitable carrier or adjuvant. This combination may be provided in such a form as a chemical set. According to another aspect of the present invention, there is provided use of the above combination for the production of a control agent for a disease of paddy rice. The "control agent for a disease of paddy rice" comprises the fungicidal composition according to the present invention. According to still another aspect of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides to an area to be treated either simultaneously or separately. In this method, "simultaneous" application embraces such an embodiment that the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides are pre-mixed together to prepare a mixture which is then applied to the target area. "Separate" application embraces such an embodiment that, without pre-mixing of the compound of formula (1) or an acid addition salt thereof with a at least one compound selected from the group consisting of strobilurin fungicides, the compound of formula (1) or an acid addition salt thereof is applied either earlier or later than the other ingredient. In a further preferred embodiment of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying (A) a first composition comprising a compound of formula (1) or an acid addition salt thereof as an active ingredient, and (B) a second composition comprising at least one compound selected from the group consisting of strobilurin fungicides as an active ingredient, to an area to be treated. [EXAMPLES] The following examples further illustrate the present invention, but are not intended to limit it. Production of compounds of formula (1) Compounds of formula (1) having substituents indicated in Table 1 below (compounds 1 to 11) were prepared. Table 1 (Table Removed) Compounds 1 to 11 were prepared according to the following procedure. Production of 4-t-butyl-2-fluoroaniline SELECTFLUOR (manufactured by Aldrich Chemical Company Inc.) (l-chloro-methyl-4-fluoro-l,4-diazoniabicyclo[2,2,2]octane-bis-tetrafluoroborate) (15 g) was added to acetonitrile (200 ml) , and the mixture was heated at 70°C for 30 min to dissolve SELECTFLUOR in acetonitrile. The reaction solution thus obtained was cooled to 60°C, and 4-t-butyl-acetanilide (5.7 g) was added to the cooled reaction solution. The mixture was stirred at 100°C for one hr, and the reaction solution was then allowed to stand for cooling. The cooled reaction solution was then added to water (200 ml), followed by extraction with ethyl acetate (100 ml, twice). The ethyl acetate layer was washed with saturated brine and was dried over anhydrous sodium sulfate, and the solvent was then removed by distillation under the reduced pressure. The crude product thus obtained was purified by chromatography on silica gel (Wako Gel C-200 manufactured by Wako Pure Chemical Industries, Ltd., elution solvent: n-hexane-ethyl acetate (10 : 1)) to give 4-t-butyl-2-fluoro-acetanilide (3.06 g). This 4-t-butyl-2-fluoro-acetanilide (3.67 g) was added to a mixed solution composed of ethanol (30 ml) and concentrated hydrochloric acid (15 ml) , and the mixture was stirred at 95°C for 2 hr. The reaction solution was allowed to stand for cooling, and the cooled reaction solution was then poured into water, followed by neutralization with a saturated aqueous sodium hydrogencarbonate solution and extraction with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure to give 4-t-butyl-2-fluoroaniline (3.49 g) . 1H-NMR data on this compound in deutro-chloroform were as shown below. 8 (ppm): 7.01 (1H, dd), 6.95 (1H, dd), 6.73 (1H, m), 1.28 (9H, s) Compound 1: 2,3-Dimethyl-6-t-butyl-8-fluoro-4- hydroxyquinoline 4-t-Butyl-2-fluoroaniline (4.79 g) prepared according to the above process and ethyl 2-methyl-acetoacetate (4.96 g) were refluxed in toluene (60 ml) in the presence of trifluoroboron etherate (0.3 ml) for 3 hr to prepare a reaction solution. The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The reaction product was refluxed in diphenyl ether (80 ml) for one hr and was allowed to stand for cooling. The precipitated product was then collected by filtration under the reduced pressure to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-hydroxyquinoline (compound 1, 1.66 g) . 1H-NMR data on this compound in deutro-DMSO (dimethyl sulfoxide) were as shown below. 5 (ppm): 11.27 (1H, br.s), 7.83 (1H, s), 7.59 (1H, br.d), 2.41 (3H, s), 1.96 (3H, s), 1.31 (9H, s) Compound 2: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-acetyl-quinoline The compound 1 (50 mg) was stirred in acetic anhydride (3 ml) at 120°C for 3 hr to prepare a reaction solution. Acetic anhydride was removed from the reaction solution by distillation under the reduced pressure. The residue was dissolved in ethyl acetate. The solution was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate, and the solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (5 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-acetylquinoline (compound 2, 35.7 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.43 (1H, dd), 7.37 (1H, d), 2.78 (3H, s), 2.51 (3H, s), 2.26 (3H, s), 1.38 (9H, s) Compound 3: 2,3-Dimethyl-6-t-butyl-8-fluoro-4- propionylquinoline In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, propionyl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-propionylquinoline (compound 3, 21 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.42 (1H, dd), 7.36 (1H, d), 2.81 (2H, q), 2.75 (3H, s), 2.25 (3H, s), 1.43 (3H, t), 1.37 (9H, s) Compound 4: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-butyryl-quinoline In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, butyryl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-butyrylquinoline (compound 4, 64 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.43 (1H, dd), 7.37 (1H, d), 2.76 (2H, t), 2.75 (3H, s) , 2.25 (3H, s) , 1.94 (2H, m) , 1.37 (9H, s) , 1.15 (3H, t) Compound 5: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-valeryl-quinoline In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, valeryl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3- dimethyl-6-t-butyl-8-fluoro-4-valerylquinoline (compound 5, 120 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. 6 (ppm): 7.42 (1H, dd), 7.37 (1H, d), 2.78 (2H, t), 2.75 (3H, s) , 2.25 (3H, s) , 1.89 (2H, m) , 1.56 (2H, m) , 1.37 (9H, s), 1.03 (3H, t) Compound 6: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-methoxy-carbonylquinoline In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, methyl chloroformate (200 \|il) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-buty1-8-f1uoro-4-methoxycarbony1-quinoline (compound 6, 100 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.45 (1H, br.s), 7.43 (1H, dd), 4.00 (3H, s), 2.76 (3H, s), 2.31 (3H, s), 1.38 (9H, s) Compound 7: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-ethoxy-carbonylquinoline In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (60 mg) . The compound 1 (200 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, ethyl chloroformate (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-ethoxycarbonyl-quinoline (compound 7, 220 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. 5 (ppm): 7.45 (1H, br.s), 7.43 (1H, dd), 4.40 (2H, q, J = 6.7 Hz), 2.32 (3H, s), 2.04 (3H, s), 1.44 (3H, t), 1.38 (9H, s) Compound 8: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-n-propoxy-carbonylquinoline In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, n-propyl chloroformate (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-n-propoxycarbonyl-quinoline (compound 8, 96 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.45 (1H, br.s), 7.43 (1H, dd), 4.35 (2H, t, J = 6.7 Hz), 2.75 (3H, s), 2.31 (3H, s) , 1.82 (2H, m), 1.38 (9H, s), 1.04 (3H, t) Compound 9: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-n-butoxy-carbonylquinoline In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (60 mg) . The compound 1 (200 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, n-butyl chloroformate (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-n-butoxycarbonyl-quinoline (compound 9, 142 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.45 (1H, d), 7.43 (1H, dd), 4.35 (2H, t), 2.75 (3H, s) , 2.32 (3H, s) , 1.77 (2H, m) , 1.48 (2H, m) , 1.38 (9H, s), 0.99 (3H, t) Compound 10: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-methoxy-acetylquinoline In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (165 mg) . The compound 1 (680 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, methoxyacetyl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-methoxyacetylquinoline (compound 10, 390 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. 8 (ppm): 7.42 (1H, dd), 7.35 (1H, d), 4.51 (2H, s), 3.62 (3H, s), 2.75 (3H, s), 2.26 (3H, s), 1.37 (9H, s) Compound 11: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-acetoxy-acetylquinoline In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (44 mg) . The compound 1 (200 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, acetoxyacetyl chloride (100 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-acetoxyacetylquinoline (compound 11, 140 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below. δ (ppm): 7.43 (1H, dd), 7.42 (1H, br.s), 5.02 (2H, s), 2.75 (3H, s), 2.27 (3H, s), 2.23 (3H, s), 1.40 (9H, s) Preparation Examples Preparation Example 1: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder. Compound 2 20 pts.wt. Azoxystrobin 20 pts.wt. Diatomaceous earth 28 pts.wt. White carbon (tradename; manufactured by Shionogi & Co. , LTD.) 13 pts.wt. Polyoxyethylene lauryl ether 12 pts.wt. Calcium lignin sulfonate 7 pts.wt. Preparation Example 2: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder. Compound 2 15 pts.wt. Azoxystrobin 5 pts.wt. Diatomaceous earth 47 pts.wt. Clay 10 pts.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 10 pts.wt. Polyoxyethylene lauryl ether 8 pts.wt. Calcium lignin sulfonate 5 pts.wt. Preparation Example 3: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder. Compound 2 20 pts.wt. Azoxystrobin 10 pts.wt. Diatomaceous earth 42 pts.wt. Clay 5 pts.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 10 pts.wt. Polyoxyethylene lauryl ether 8 pts.wt. Calcium lignin sulfonate 5 pts.wt. Preparation Example 4: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder. Compound 2 20 pts.wt. Metominostrobin 20 pts.wt. Diatomaceous earth 37 pts.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 10 pts.wt. Polyoxyethylene lauryl ether 8 pts.wt. Calcium lignin sulfonate 5 pts.wt. Preparation Example 5: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder. Compound 2 15 pts.wt. Metominostrobin 5 pts.wt. Diatomaceous earth 47 pts.wt. Clay 10 pts.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 10 pts.wt. Polyoxyethylene lauryl ether 8 pts.wt. Calcium lignin sulfonate 5 pts.wt. Preparation Example 6: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder. Compound 2 20 pts.wt. Metominostrobin 10 pts.wt. Diatomaceous earth 42 pts.wt. Clay 5 pts.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 10 pts.wt. Polyoxyethylene lauryl ether 8 pts.wt. Calcium lignin sulfonate 5 pts.wt. Preparation Example 7: Dust The following ingredients were homogeneously ground to prepare dust. Compound 2 1.2 pts . wt. Azoxystrobin 0.5 pt.wt. Clay 97.1 pts.wt. Calcium carbonate 0.5 pt.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 0.2 pt.wt. Driless A (tradename; manufactured by SANKYO CO., LTD.) 0.5 pt.wt. Preparation Example 8; Dust The following ingredients were homogeneously ground to prepare dust. Compound 2 1 pt.wt. Azoxystrobin 0.5 pt.wt. Clay 97.1 pts.wt. Calcium carbonate 0.5 pt.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 0.4 pt.wt. Driless A (tradename; manufactured by SANKYO CO., LTD.) 0.5 pt.wt. Preparation Example 9: Dust The following ingredients were homogeneously ground to prepare dust. Compound 2 1.2 pts . wt. Metominostrobin 0.5 pt.wt. Clay 97.1 pts.wt. Calcium carbonate 0.5 pt.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 0.2 pt.wt. Driless A (tradename; manufactured by SANKYO CO. , LTD.) 0 .5 pt. wt. Preparation Example 10: Dust The following ingredients were homogeneously ground to prepare dust. Compound 2 1 pt.wt. Metominostrobin 0.5 pt.wt. Clay 97.1 pts.wt. Calcium carbonate 0.5 pt.wt. White carbon (tradename; manufactured by Shionogi & Co., LTD.) 0.4 pt.wt. Driless A (tradename; manufactured by SANKYO CO., LTD.) 0.5 pt.wt. Evaluation tests Test A: Control effect against rice blast by application before spread of rice blast (test in suitable timing for control) A potting compost was placed in a plastic vat (about 30 cm x 50 cm) , and seed rice (variety: Koshihikari) after forcing of germination was inoculated into the vat, followed by dense planting cultivation. This rice was used for the test. The rice was raised for about 2 weeks in a glass greenhouse under conditions of 25°C in the daytime and 20°C in the night-time. At the time when the rice was grown to a three or four leaf stage, diseased leaves, which had been previously inoculated with rice blast fungi (race 037) and had developed rice blast, were placed on the densely planted rice, followed by standing under humidified conditions for inoculation of rice blast fungi for 24 hr. The rice plant was then again returned to within the glass greenhouse. Seven or eight days after that, the presence of lesions was observed, followed by first chemical application. In this case, a test chemical liquid was diluted with a 10% aqueous acetone solution (with 5,000-fold diluted Neoesterin (tradename; manufactured by KUMIAI CHEMICAL INDUSTRY CO., LTD.) as a spreader added thereto) to predetermined concentrations. Each of the test chemical liquids thus prepared was applied in an amount of 15 ml per vat by means of a spray gun. When second chemical application is carried out, six or seven days after the first chemical application, the second chemical application was carried out in the same manner as in the first chemical application. After the chemical application, the rice was controlled in the glass greenhouse. During this period, at one to two days intervals, the rice was placed under humidified conditions for 24 hr to accelerate the development and spread of rice blast. Ten days after the final chemical application, for 40 plants per vat, the lesion area of the surface of a blade located one leaf below the uppermost leaf was observed, and the percentage lesion area in the treated plot was determined. The percentage lesion area in the nontreated plot was also determined in the same manner as in the treated plot. For each test chemical agent, the protective value was determined from the results obtained on the treated plot and the results obtained on the nontreated plot by the following equation. Protective value = [1 - (percentage lesion area in treated plot/percentage lesion area in nontreated plot)] x 100 The prophylactic effect and residual effect of the test chemical agent can be determined by a method in which, after the elapse of predetermined days after the treatment with the chemical agent, observation is made on whether or not the percentage lesion area is increased. Accordingly, the prophylactic effect and residual effect were determined based on whether or not the final protective value was increased. The test was carried out for each group consisting of chemical agents indicated in Tables Al to A3 below. The chemical application was carried out once or twice. The results were as shown in Tables Al to A3. Table Al; Double application test (Table Removed) Table A2: Single application test (Table Removed) Table A3: Single application test (Table Removed) Test B: Control effect against rice blast by application after spread of rice blast (application delay test) A potting compost was placed in a plastic vat (about 30 cm x 50 cm) , and seed rice (variety: Koshihikari) after forcing of germination was inoculated into the vat, followed by dense planting cultivation. This rice was used for the test. The rice was raised for about 2 weeks in a glass greenhouse under conditions of 25°C in the daytime and 20°C in the night-time. At the time when the rice was grown to a three or four leaf stage, diseased leaves, which had been previously inoculated with rice blast fungi (race 037) and had developed rice blast, were placed on the densely planted rice, followed by standing under humidified conditions for inoculation of rice blast fungi for 24 hr. The rice plant was then again returned to within the glass greenhouse. Seven or eight days after that, the presence of lesions was observed. Thereafter, the rice was again placed under humidified conditions for 24 hr to accelerate the second infection and to spread rice blast in the vat. After the elapse of about three or four days after the acceleration of the spread of rice blast, very small secondary lesion was confirmed, followed by the first chemical application. The other test conditions, for example, test chemical liquid conditions, application method, application intervals, rice blast development and control method after the initiation of the application, calculation of percentage lesion area, and calculation of protective value, were the same as those in test A. When the second chemical application was carried out, the chemical application intervals were the same as those in test A. The test was carried out for each group consisting of chemical agents indicated in Tables Bl to B4 below. The results were as shown in Tables Bl to B4. Table Bl: Double application test (Table Removed) Table B2; Single application test (Table Removed) Table B3: Single application test (Table Removed) Table B4; Single application test (Table Removed) WE CLAIM: 1. A fungicidal composition for use in the control of a disease of paddy rice, comprising as active ingredients a 2,3-dimethyl-6-t-butyl-8-fluoro-4-quinolinol derivative of formula (1) or an acid addition salt thereof; (Formula Removed) wherein R represents a hydrogen atom; -COR1 or -COOR1, wherein R1 represents an alkyl group having 1 to 4 carbon atoms; -COCH2OCH3; or -COCH2OCOCH3, and at least one compound selected from the group consisting of strobilurin fungicides wherein the mixing ratio between the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides is in the range of from 2 : 50 to 50 : 2. 2. The fungicidal composition as claimed in claim 1, wherein the compound belonging to the strobilurin fungicide is selected from azoxystrobin and metominostrobin.

Full Text

yet. These compounds, however, are expected to have a mechanism of action different from conventional control agents for rice blast, for example, because control effect can also be attained against strains resistant to kasugamycin, organic phosphorus agents and strobilurin compounds and, in addition, fungicidal activity is exhibited without inhibition of biosynthesis of melanin in culture media.
Strobilurin fungicidal compounds have been reported to have excellent control effect or high fungicidal activity against a plurality of fungal diseases of paddy rice including rice blast, or various fungal diseases or pathogenic fungi as fungi causative of these diseases that pose cultivation problems of barley and wheat, vegetables, and fruit trees. The excellent control effect of strobilurin compounds and the mechanism of action thereof are described, for example, in Noyaku Handobukku (Agricultural Chemical Handbook) 2001 (published in 2001 by Japan Plant Protection Association), and Ippan Itaku Shiken Seisekisho (General Contract Test Report) (published by Japan Plant Protection Association).
Rice blast is the most serious disease involved in paddy rice cultivation. Rice blast is a plant disease induced by parasitism of fungi of the genus Pyricularia which are a kind of mold fungi and belong to deuteromycetes. Up to now, many excellent control agents and methods for rice blast have been reported.
In some cases, however, even after the application of such control agents, an outbreak of rice blast takes place under certain meteorological conditions, such as unseasonably cool summer weather and very long rainy seasons, and due to unfavorable cultivation conditions, such as unsatisfactory management of seedlings and fertilizing. For these reasons, the development of control agents having better control effect against rice
The present invention relates to a fungicidal composition.
[BACKGROUND OF THE INVENTION] Field of the Invention
The present invention relates to a fungicidal composition having excellent control effect against diseases of paddy rice, and more particularly to a fungicidal composition having excellent control effect against fungal diseases of paddy rice including rice blast. Related Art
WO 01/92231 (International Publication Date: 6 December, 2001) filed by the present applicant discloses compounds, having excellent fungicidal activity of formula 11) or acid addition salts thereof:
(Formula Removed)
wherein
R represents a hydrogen atom; -COR1 or -COOR1, wherein R1 represents an alkyl group having 1 to 4 carbon atoms; -COCH2OCH3; or -COCH2OCOCH3. In this publication, the physicochemical properties of the above compounds and control effect of the above compounds against rice blast are also described. Furthermore, the publication describes that the above compounds are excellent in therapeutic effect against rice blast, as well as in residual activity and prophylactic effect, and that these effects are different from the therapeutic effect of conventional rice blast control agents.
The mechanism of action of the compounds represented by formula (1) has not been fully elucidated
blast has been desired. Further, a recent increase in the number of farmers with a side job and an increase in the number of aged people engaging in agriculture have led to a demand for the development of a technique that can extend a period during which disease control can be carried out, and can reduce the number of applications and amount of labor. Furthermore, the development of chemical agents, which can exhibit control effect simultaneously against a plurality of diseases, has been desired from the viewpoints of labor saving and a reduction in amount of an agricultural chemical to be applied.
[SUMMARY OF THE INVENTION]
As a result of evaluation of overall effect of the above-described plurality of activities, duration time of these activities, etc., the present inventors have now found that a mixture composition comprising a compound represented by formula (1) (2,3-dimethyl-6-t-butyl-8-fluoro-4-quinolinol derivative) and at least one compound selected from the group consisting of strobilurin fungicides does not sacrifice the activity of each ingredient and, at the same time, develops synergistic effect and exhibits excellent^ control effect against rice blast. Further, in this connection, it has been found that the above composition has excellent control effect against rice blast, a representative disease of paddy rice, at low dose for a long period of time, when the composition has been applied at proper timing, as well as when the application time has been delayed past the proper timing. The present invention has been made based on such finding.
Accordingly, an object of the present invention is to provide a chemical agent which has excellent control effect against diseases of paddy rice and has excellent control effect at low dose for a long period of time
(Formula Removed)
even when the application time has been delayed from proper application timing.
According to an aspect of the present invention, there is provided a fungicidal composition comprising as active ingredients
a compound of formula (1) or an acid addition salt thereof:
(Formula Removed)
wherein
R represents a hydrogen atom; -COR1 or -COOR1, wherein R1 represents an alkyl group having 1 to 4 carbon atoms; -COCH2OCH3; or -COCH2OCOCH3, and
at least one compound selected from the group consisting of strobilurin fungicides.
According to another aspect of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying an effective amount of the above fungicidal composition to an area to be treated.
According to a further aspect of the present invention, there is provided use of the above fungicidal composition, for the production of a control agent for a disease of paddy rice.
The fungicidal composition according to the present invention comprises a mixture of two compounds different from each other in mechanism of action and fungicidal spectrum. The fungicidal composition according to the present invention has excellent control effect against rice blast, as well as against other fungal diseases of paddy rice, for example, sheath blast, ear burn due to Helminthosporium leaf spot, Cercospora leaf spot or the
like, dicoloration of grains of rice caused, for example, by the genus Curvularia and the genus Alternaria, and false smut. According to the fungicidal composition of the present invention, the ingredients in the fungicidal composition act together in a synergistic fashion to provide unexpected and significant control effect. Therefore, according to the fungicidal composition of the present invention, the necessary chemical application rate per area can be reduced. In addition, according to the fungicidal composition of the present invention, excellent control effect can be attained at a lower dose compared with using each ingredient of the composition separately. Further, in this case, the control effect is durable for a long period of time. Therefore, according to the fungicidal composition of the present invention, the necessary number of treatments of plants can be reduced. Further, the total amount of the chemical agent used for a target plant during the cultivation period can be reduced. The fungicidal composition according to the present invention can exhibit excellent control effect when the composition has been applied for control treatment at proper timing, and even when the application time has been delayed past the proper timing. The fungicidal composition according to the present invention can realize simultaneous control against a plurality of diseases and, at the same time, can reduce the risk of the development of resistance of fungi. The fungicidal composition according to the present invention can be expected to greatly contribute to labor-saving in agriculture, environmental protection, and stable food production.
[DETAILED DESCRIPTION OF THE INVENTION] Fungicidal composition
As described above, the fungicidal composition
according to the present invention comprises as active ingredients a compound of formula (1) or an acid addition salt thereof and at least one compound belonging to strobilurin fungicides.
The fungicidal composition may be used for the control of diseases of plants, preferably the control of diseases of rice, more preferably the control of diseases of paddy rice. Examples of such diseases include: rice blast; ear burn due to Helminthosporium leaf spot, Cercospora leaf spot or the like; dicoloration of grains of rice caused, for example, by the genus Curvularia and the genus Alternaria; false smut; and sheath blast. More preferably, the fungicidal composition according to the present invention is used for the control of rice blast.
In the present invention, "comprising as an active ingredient" means that a carrier suitable for desired formulation may of course be incorporated and, in addition, other chemical agents usable in combination with the compound of the present invention may be incorporated.
Here the term "rice" is used to embrace paddy rice and rice grown in dry fields. The term "paddy rice" refers to rice cultivated in paddy fields.
Compounds of formula (1)
The fungicidal composition according to the present invention includes a compound of formula (1) or an acid addition salt thereof.
In formula (1), R represents a hydrogen atom, -COR1, -COOR1, -COCH2OCH3, or -COCH2OCOCH3. In the present invention, R1 represents an alkyl group having 1 to 4 carbon atoms. In the present invention, the alkyl group may be in any of straight chain, branched chain, and cyclic forms. Further, one or more hydrogen atoms on the alkyl group may be optionally substituted by one or more
according to the present invention comprises as active ingredients a compound of formula (1) or an acid addition salt thereof and at least one compound belonging to strobilurin insecticides.
The fungicidal composition may be used for the control of diseases of plants, preferably the control of diseases of rice, more preferably the control of diseases of paddy rice. Examples of such diseases include: rice blast; ear burn due to Helminthosporium leaf spot, Cercospora leaf spot or the like; dicoloration of grains of rice caused, for example, by the genus Curvularia and the genus Alternaria; false smut; and sheath blast. More preferably, the fungicidal composition according to the present invention is used for the control of rice blast.
In the present invention, "comprising as an active ingredient" means that a carrier suitable for desired formulation may of course be incorporated and, in addition, other chemical agents usable in combination with the compound of the present invention may be incorporated.
Here the term "rice" is used to embrace paddy rice and rice grown in dry fields. The term "paddy rice" refers to rice cultivated in paddy fields.
Compounds of formula (1)
The fungicidal composition according to the present invention includes a compound of formula (1) or an acid addition salt thereof.
In formula (1), R represents a hydrogen atom, -COR1, -COOR1, -COCH2OCH3, or -COCH2OCOCH3. In the present invention, R1 represents an alkyl group having 1 to 4 carbon atoms. In the present invention, the alkyl group may be in any of straight chain, branched chain, and cyclic forms. Further, one or more hydrogen atoms on the alkyl group may be optionally substituted by one or more
substituents which may be the same or different. Specific examples of R1 include methyl, ethyl, n-propyl, isopropyl, and n-butyl.
In formula (1) , when R represents a hydrogen atom, the compounds of formula (1) may take a structure of formula (2) which is a tautomer of the compounds of formula (1) . It would be apparent to a person having ordinary skill in the art that the compounds of formula (1) embrace the compounds of formula (2).
(Formula Removed)
In the present invention, the term "acid addition salt" refers to salts, which are generally usable in the fields of agriculture and gardening, for example, hydrochlorides, nitrates, sulfates, phosphates, and acetates.
It should be noted that the compounds of formula (1) may take the form of hydrates or solvates. In the present invention, such hydrates and solvates are also embraced in the compounds of formula (1).
Specific examples of compounds of formula (1) include compounds 1 to 11 in working examples which will be described later.
Production process of compounds of formula (1)
The compounds of formula (1) may be synthesized by
any appropriate process regarding the formation of a
bond or the introduction of a substituent.
For example, a compound of formula (1) can be
produced from 4-t-butyl-2-fluoroaniline, which can be
synthesized by a conventional method, according to the following scheme.
(Scheme Removed)
wherein
R represents a hydrogen atom, -COR1, -COOR1, COCH2OCH3, or -COCH2OCOCH3 ;
R1 represents an alkyl group having 1 to 4 carbon atoms; and
R2 represents -R1, -OR1, -CH2OCH3, or -CH2OCOCH3.
According to this scheme, a compound of formula (2) is first provided (step (a)), and, if necessary, the compound of formula (2) is then reacted with the compound of formula (3) or (4) in the presence or absence of a base (step (b)) to give the compound of formula (1) . """"
The above scheme will be described in more detail.

Step (a):
A compound of formula (2) is first prepared from 4-t-butyl-2-fluoroaniline and ethyl 2-methyl-acetoacetate, for example, according to J. Am. Chem. Soc. 70, 2402 (1948) and Tetrahedron Lett. 27, 5323 (1986). The compound of formula (2) corresponds to the compound of formula (1) wherein R represents a hydrogen atom. 4-t-Butyl-2-fluoroaniline used herein may be prepared by a conventional method described, for example, in Chem. Abs. 42, 2239 or J. Chem. Soc, Chem. Commun., 1992, 595.
Step (b) :
Next, when a compound of formula (1) , wherein R represents a group other than a hydrogen atom, is desired, this compound can be produced by reacting the compound of formula (2) with the compound of formula (3) or (4) in the presence or absence of a base.
Bases usable herein include, for example, organic amines, such as triethy1amine and pyridine, and inorganic bases, such as sodium carbonate, potassium carbonate, and sodium hydride. The compound of formula (3) or (4) is preferably used in an amount of 1 to 50 equivalents, more preferably 1 to 10 equivalents, based on the compound of formula (2) . The reaction in step (b) may be carried out in the absence of a solvent or in the presence of an organic solvent inert to the reaction, for example, dimethylformamide or tetrahydrofuran, for example, in the temperature range of 0 to 140°C.
Strobilurin fungicide
In the present invention, the strobilurin fungicides may be any one which is known as a strobilurin fungicide in the art. Strobilurin fungicides are described as fungicides, for example, in Noyaku Handobukku (Agricultural Chemical Handbook) 2001 (published in 2001 by Japan Plant Protection Association) and Noyaku Yoran (Agricultural Chemical
Manual) (published in 2001 by Japan Plant Protection Association). A person having ordinary skill in the art could properly select the strobilurin fungicides by making reference to these documents.
Specific examples of the strobilurin fungicide usable in the present invention include azoxystrobin, metominostrobin, kresoxim-methyl, trifloxystrobin, orysastrobin, fluoxastrobin, pyraclostrobin, and picoxystrobin.
In a preferred embodiment of the present invention, the strobilurin fungicide is selected from azoxystrobin, metominostrobin, and orysastrobin.
In a more preferred embodiment of the present invention, the strobilurin fungicide is selected from azoxystrobin and metominostrobin.
Other ingredients
When the fungicidal composition according to the present invention is actually applied, a composition consisting of the above active ingredients only as such may be used. Alternatively," the composition may be mixed, for example, with suitable carriers or adjuvants for formulations, to prepare any suitable formulation, such as dusts, granules, packs, wettable powders, wettable granules, floables, liquid formulations, microcapsules, or emulsifiable concentrates. This permits the fungicidal composition according to the present invention to be suitably used for appropriate various applications.
Formulation may be prepared by a method known in the art as in general agricultural chemicals. Specifically, for example, formulation may be prepared by mixing active ingredients, if necessary, for example, with a solid carrier, a solvent, a surfactant, and other adjuvants. The carrier and the like may be selected according to purposes of use, for example, improvement
in properties of formulations, stabilization of active ingredients and an enhancement in effect.
Solid carriers usable herein include, for example, clay, talc, calcium carbonate, diatomaceous earth, zeolite, bentonite, acid clay, activated clay, attapulgus clay, vermiculite, pearlite, pumice, white carbon, titanium dioxide, water-soluble salts, wood flour, corn cob, walnut shell, cellulose powder, starch, dextrin, and saccharides.
Examples of solvents usable herein include: aromatic solvents such as xylene, C9 alkylbenzenes, C10 alkylbenzenes, alkylnaphthalenes, and high-boiling aromatic hydrocarbons; aliphatic solvents such as n-paraffins, iso-paraffins, and naphthenes; mixed solvents such as solvents produced from kerosene or coal oil; machine oils such as high-boiling aliphatic hydrocarbons; alcohols such as ethanol, isopropanol, and cyclohexanol; polyhydric alcohols such as ethylene glycol, diethylene glycol, propylene glycol, hexylene glycol, polyethylene glycol, and polypropylene glycol; polyhydric alcohol derivatives such as propylene glycol ether; ketones such as cyclohexanone and gamma-butyrolactone; esters such as fatty acid methyl esters (for example, coconut oil fatty acid methyl esters) and dibasic acid methyl esters (for example, succinic acid dimethyl esters, glutamic acid dimethyl esters, and adipic acid dimethyl esters); nitrogen-containing solvents such as N-alkylpyrrolidone; fats and oils such as coconut oils, soybean oils, and rapeseed oils; and water.
Examples of surfactants usable herein include sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, sucrose fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid diesters, polyoxyethylene castor oils, polyoxyethylene
hydrogenated castor oils, polyoxyethylene alkyl ethers,
polyoxyethylene alkylphenyl ethers, polyoxyethylene
dialkylphenyl ethers, polyoxyethylene alkylphenyl
ether/formalin condensates,
polyoxyethylene/polyoxypropylene block polymers,
alkylpolyoxyethylene/polyoxypropylene block polymer
ethers, alkylphenyl polyoxyethylene/polyoxypropylene
block polymer ethers, polyoxyethylene alkylamines,
polyoxyethylene fatty acid amides, polyoxyethylene
bisphenyl ethers, polyoxyethylene benzylphenyl ethers,
polyoxyethylene styrylphenyl ethers, polyoxyethylene
ether-type silicones, ester-type silicones,
fluorosurfactants or other nonionic surfactants, alkyl
sulfates, polyoxyethylene alkyl ether sulfates,
polyoxyethylene alkylphenyl ether sulfates,
polyoxyethylene benzylphenyl ether sulfates,
polyoxyethylene/polyoxypropylene block polymer sulfates,
paraffin sulfonates, AOSs, dialkylsulfosuccinates,
alkylbenzene sulfonates, naphthalene sulfonates,
naphthalene sulfonate/formalin condensates,
alkyldiphenyl ether disulfonates, lignin sulfonates,
polyoxyethylene alkylphenyl ether sulfonates,
polyoxyethylene alkyl ether sulfosuccinic acid half
esters, fatty acid salts, N-methyl-fatty acid
sarcosinates, resin acid salts, polyoxyethylene alkyl
ether phosphates, polyoxyethylene alkylphenyl ether
phosphates, polyoxyethylene benzylated phenyl ether
phosphates, polyoxyethylene/polyoxypropylene block
polymer phosphates, lecithins, alkylphosphates,
alkyltrimethylammonium chlorides, methyl/polyoxyethylene
alkylammonium chlorides, alkyl N-methyl-pyridinium
bromides, alkylmethylated ammonium chlorides,
alkylpentamethylpropylenediamine dichlorides,
alkyldimethylbenzalkonium chlorides, benzethonium chlorides, dialkyldiaminoethylbetaines, and alkyldimethylbenzylbetaines.
Adjuvants usable herein include, for example, isopropyl phosphate, carboxymethylcellulose, PVA, sodium tripolyphosphate, sodium hexametaphosphate, xanthan gum, guar gum, carboxymethylcellulose, sodium benzoate, potassium sorbate, p-hydroxybenzoic esters, 1,2-benzothiazolin-3-one, ethylene glycol, diethylene glycol, propylene glycol, polyvinyl pyrrolidone, urea, hexamethylenetetramine, antioxidants, ultraviolet absorbers, zeolites, quick lime, magnesium oxide, hydrophobic high-boiling solvents, sodium polyacrylate, alginic acid, kraft lignin, methacrylic acid/vinyl pyrrolidone copolymer, glycerin, sorbitol, and water-swellable polymeric compounds.
The above carriers, surfactants, dispersants, and adjuvants may be used solely or in a combination of two or more of them selected from the same group or different groups.
In the fungicidal composition according to the present invention, the mixing proportion of the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides may be such that the total amount of them (the total amount of the active ingredients) is 0.1 to 90 parts by weight, preferably 1 to 70 parts by weight, based on 100 parts by weight of the fungicidal composition.
The total amount of the active ingredients may be properly selected by taking into consideration formulation, application method, service environment, and other conditions of the fungicidal composition. For example, when the fungicidal composition is in a wettable powder form, the total amount of the active ingredients is 5 to 50% by weight, preferably 10 to 30% by weight. On the other hand, when the fungicidal composition is in a dust form, the total amount of the
active ingredients is 0.5 to 5.0% by weight, preferably 1.0 to 2.0% by weight.
In the fungicidal composition according to the present invention, the mixing ratio between the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides is in the range of 1 : 100 to 100 : 1, preferably in the range of 1 : 20 to 20 : 1.
When the fungicidal composition according to the present invention is used, the fungicidal composition as such may be used directly. If necessary, the fungicidal composition may be diluted with a diluting liquid, such as water, followed by treatment, for example, application to an area to be treated, admixing into the area to be treated, application to water surface in the area to be treated, or immersion in the area to be treated. Specific examples of the treatment include application to plant per se (application to stems and leaves), application to raising seedling boxes, application to soil (admixing with soil or application to side stripes) , application to field water (application to water surface or application to regular paddy field), and application to seeds (seed treatment).
According to another aspect of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying an effective amount of the fungicidal composition according to the present invention to an area to be treated. The term "area to be treated" refers to an area which should be treated with the fungicidal composition according to the present invention for rice disease control purposes. Examples of such areas include rice plants, raising seedling boxes, soils, field water, and seeds. Preferably, the area to be treated is rice plant, soil, or field water.
The amount of the fungicidal composition according
to the present invention used may be properly varied depending upon service environment, growth state of object plants, mixing ratio of active ingredients, formulations, application time, application method, and target disease to be controlled. In general, the amount of the fungicidal composition used is 1 to 1,500 g, preferably 10 to 150 g, per 10 ares in terms of the total amount of the active ingredients. For example, when the fungicidal composition is applied to a rice plant, the amount of the fungicidal composition used is 5 to 500 g, preferably 10 to 100 g, per 10 ares in terms of the total amount of the active ingredients.
The fungicidal composition according to the present invention may be used as a mixture, for example, with other fungicides, insecticides, miticides, herbicides, plant growth-regulating agents, or fertilizers.
In general, the fungicidal composition according to the present invention is previously formed into a desired formulation in the above-described manner. Alternatively, a method may be adopted wherein a formulation comprising one of the active ingredients in the composition, that is, one of the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides, and a formulation comprising the other active ingredient are previously prepared and, in use, these formulations are mixed together on site.
Thus, according to another aspect of the present invention, there is provided a combination comprising a compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides.
In a preferred embodiment, in the above combination, the compound of formula (1) or an acid addition salt thereof is provided as a first composition comprising the compound of formula (1) or an acid addition salt
thereof as an active ingredient, and the at least one compound selected from the group consisting of strobilurin fungicides is provided as a second composition comprising the at least one compound as an active ingredient. In this case, as with the above-described fungicidal composition, the first composition and the second composition may be in any formulation form which has been prepared by additionally using suitable carrier or adjuvant. This combination may be provided in such a form as a chemical set.
According to another aspect of the present invention, there is provided use of the above combination for the production of a control agent for a disease of paddy rice. The "control agent for a disease of paddy rice" comprises the fungicidal composition according to the present invention.
According to still another aspect of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides to an area to be treated either simultaneously or separately.
In this method, "simultaneous" application embraces such an embodiment that the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides are pre-mixed together to prepare a mixture which is then applied to the target area. "Separate" application embraces such an embodiment that, without pre-mixing of the compound of formula (1) or an acid addition salt thereof with a at least one compound selected from the group consisting of strobilurin fungicides, the compound of formula (1) or an acid addition salt thereof is applied either earlier or later than the other ingredient.
In a further preferred embodiment of the present invention, there is provided a method for controlling a disease of rice, comprising the step of applying
(A) a first composition comprising a compound of formula (1) or an acid addition salt thereof as an active ingredient, and
(B) a second composition comprising at least one compound selected from the group consisting of strobilurin fungicides as an active ingredient,
to an area to be treated.
[EXAMPLES]
The following examples further illustrate the present invention, but are not intended to limit it. Production of compounds of formula (1)
Compounds of formula (1) having substituents indicated in Table 1 below (compounds 1 to 11) were prepared.
Table 1

(Table Removed)
Compounds 1 to 11 were prepared according to the
following procedure.
Production of 4-t-butyl-2-fluoroaniline SELECTFLUOR (manufactured by Aldrich Chemical Company Inc.) (l-chloro-methyl-4-fluoro-l,4-diazoniabicyclo[2,2,2]octane-bis-tetrafluoroborate) (15 g) was added to acetonitrile (200 ml) , and the mixture was heated at 70°C for 30 min to dissolve SELECTFLUOR in acetonitrile. The reaction solution thus obtained was cooled to 60°C, and 4-t-butyl-acetanilide (5.7 g) was added to the cooled reaction solution. The mixture was stirred at 100°C for one hr, and the reaction solution was then allowed to stand for cooling. The cooled reaction solution was then added to water (200 ml), followed by extraction with ethyl acetate (100 ml, twice). The ethyl acetate layer was washed with saturated brine and was dried over anhydrous sodium sulfate, and the solvent was then removed by distillation under the reduced pressure. The crude product thus obtained was purified by chromatography on silica gel (Wako Gel C-200 manufactured by Wako Pure Chemical Industries, Ltd., elution solvent: n-hexane-ethyl acetate (10 : 1)) to give 4-t-butyl-2-fluoro-acetanilide (3.06 g). This 4-t-butyl-2-fluoro-acetanilide (3.67 g) was added to a mixed solution composed of ethanol (30 ml) and concentrated hydrochloric acid (15 ml) , and the mixture was stirred at 95°C for 2 hr. The reaction solution was allowed to stand for cooling, and the cooled reaction solution was then poured into water, followed by neutralization with a saturated aqueous sodium hydrogencarbonate solution and extraction with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure
to give 4-t-butyl-2-fluoroaniline (3.49 g) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
8 (ppm): 7.01 (1H, dd), 6.95 (1H, dd), 6.73 (1H, m), 1.28 (9H, s)
Compound 1: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-
hydroxyquinoline
4-t-Butyl-2-fluoroaniline (4.79 g) prepared according to the above process and ethyl 2-methyl-acetoacetate (4.96 g) were refluxed in toluene (60 ml) in the presence of trifluoroboron etherate (0.3 ml) for 3 hr to prepare a reaction solution. The reaction solution thus obtained was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The reaction product was refluxed in diphenyl ether (80 ml) for one hr and was allowed to stand for cooling. The precipitated product was then collected by filtration under the reduced pressure to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-hydroxyquinoline (compound 1, 1.66 g) . 1H-NMR data on this compound in deutro-DMSO (dimethyl sulfoxide) were as shown below.
5 (ppm): 11.27 (1H, br.s), 7.83 (1H, s), 7.59 (1H, br.d), 2.41 (3H, s), 1.96 (3H, s), 1.31 (9H, s)
Compound 2: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-acetyl-quinoline
The compound 1 (50 mg) was stirred in acetic anhydride (3 ml) at 120°C for 3 hr to prepare a reaction solution. Acetic anhydride was removed from the reaction solution by distillation under the reduced pressure. The residue was dissolved in ethyl acetate. The solution was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over
anhydrous sodium sulfate, and the solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (5 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-acetylquinoline (compound 2, 35.7 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.43 (1H, dd), 7.37 (1H, d), 2.78 (3H, s), 2.51 (3H, s), 2.26 (3H, s), 1.38 (9H, s)
Compound 3: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-
propionylquinoline
In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, propionyl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-propionylquinoline (compound 3, 21 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.42 (1H, dd), 7.36 (1H, d), 2.81 (2H, q), 2.75 (3H, s), 2.25 (3H, s), 1.43 (3H, t), 1.37 (9H, s)
Compound 4: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-butyryl-quinoline
In tetrahydrofuran (3 ml) was suspended 60% sodium
hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, butyryl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-butyrylquinoline (compound 4, 64 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.43 (1H, dd), 7.37 (1H, d), 2.76 (2H, t), 2.75 (3H, s) , 2.25 (3H, s) , 1.94 (2H, m) , 1.37 (9H, s) , 1.15 (3H, t)
Compound 5: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-valeryl-quinoline
In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, valeryl chloride (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-
dimethyl-6-t-butyl-8-fluoro-4-valerylquinoline (compound 5, 120 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
6 (ppm): 7.42 (1H, dd), 7.37 (1H, d), 2.78 (2H, t), 2.75 (3H, s) , 2.25 (3H, s) , 1.89 (2H, m) , 1.56 (2H, m) , 1.37 (9H, s), 1.03 (3H, t)
Compound 6: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-methoxy-carbonylquinoline
In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, methyl chloroformate (200 |il) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-buty1-8-f1uoro-4-methoxycarbony1-quinoline (compound 6, 100 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.45 (1H, br.s), 7.43 (1H, dd), 4.00 (3H, s), 2.76 (3H, s), 2.31 (3H, s), 1.38 (9H, s)
Compound 7: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-ethoxy-carbonylquinoline
In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (60 mg) . The compound 1 (200 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, ethyl chloroformate (200 µl) was added thereto, and the mixture was stirred for 3
hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-ethoxycarbonyl-quinoline (compound 7, 220 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
5 (ppm): 7.45 (1H, br.s), 7.43 (1H, dd), 4.40 (2H, q, J = 6.7 Hz), 2.32 (3H, s), 2.04 (3H, s), 1.44 (3H, t), 1.38 (9H, s)
Compound 8: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-n-propoxy-carbonylquinoline
In tetrahydrofuran (3 ml) was suspended 60% sodium hydride (20 mg) . The compound 1 (124 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, n-propyl chloroformate (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-n-propoxycarbonyl-quinoline (compound 8, 96 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.45 (1H, br.s), 7.43 (1H, dd), 4.35 (2H,
t, J = 6.7 Hz), 2.75 (3H, s), 2.31 (3H, s) , 1.82 (2H, m), 1.38 (9H, s), 1.04 (3H, t)
Compound 9: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-n-butoxy-carbonylquinoline
In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (60 mg) . The compound 1 (200 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, n-butyl chloroformate (200 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-n-butoxycarbonyl-quinoline (compound 9, 142 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.45 (1H, d), 7.43 (1H, dd), 4.35 (2H, t), 2.75 (3H, s) , 2.32 (3H, s) , 1.77 (2H, m) , 1.48 (2H, m) , 1.38 (9H, s), 0.99 (3H, t)
Compound 10: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-methoxy-acetylquinoline
In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (165 mg) . The compound 1 (680 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, methoxyacetyl chloride (200
µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a
saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-methoxyacetylquinoline (compound 10, 390 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
8 (ppm): 7.42 (1H, dd), 7.35 (1H, d), 4.51 (2H, s), 3.62 (3H, s), 2.75 (3H, s), 2.26 (3H, s), 1.37 (9H, s)
Compound 11: 2,3-Dimethyl-6-t-butyl-8-fluoro-4-acetoxy-acetylquinoline
In tetrahydrofuran (10 ml) was suspended 60% sodium hydride (44 mg) . The compound 1 (200 mg) was added to the suspension under ice cooling, and the mixture was stirred for 30 min. Further, acetoxyacetyl chloride (100 µl) was added thereto, and the mixture was stirred for 3 hr. The reaction solution thus obtained was poured into ice water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under the reduced pressure. The crude product was purified by chromatography on silica gel (Wako Gel C-200, elution solvent: n-hexane-ethyl acetate (3 : 1)) to give 2,3-dimethyl-6-t-butyl-8-fluoro-4-acetoxyacetylquinoline (compound 11, 140 mg) . 1H-NMR data on this compound in deutro-chloroform were as shown below.
δ (ppm): 7.43 (1H, dd), 7.42 (1H, br.s), 5.02 (2H, s), 2.75 (3H, s), 2.27 (3H, s), 2.23 (3H, s), 1.40 (9H, s)
Preparation Examples
Preparation Example 1: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder.
Compound 2 20 pts.wt.
Azoxystrobin 20 pts.wt.
Diatomaceous earth 28 pts.wt.
White carbon (tradename; manufactured
by Shionogi & Co. , LTD.) 13 pts.wt.
Polyoxyethylene lauryl ether 12 pts.wt.
Calcium lignin sulfonate 7 pts.wt.
Preparation Example 2: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder.
Compound 2 15 pts.wt.
Azoxystrobin 5 pts.wt.
Diatomaceous earth 47 pts.wt.
Clay 10 pts.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 10 pts.wt.
Polyoxyethylene lauryl ether 8 pts.wt.
Calcium lignin sulfonate 5 pts.wt.
Preparation Example 3: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder.
Compound 2 20 pts.wt.
Azoxystrobin 10 pts.wt.
Diatomaceous earth 42 pts.wt.
Clay 5 pts.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 10 pts.wt.
Polyoxyethylene lauryl ether 8 pts.wt.
Calcium lignin sulfonate 5 pts.wt.
Preparation Example 4: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder.
Compound 2 20 pts.wt.
Metominostrobin 20 pts.wt.
Diatomaceous earth 37 pts.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 10 pts.wt.
Polyoxyethylene lauryl ether 8 pts.wt.
Calcium lignin sulfonate 5 pts.wt.
Preparation Example 5: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder.
Compound 2 15 pts.wt.
Metominostrobin 5 pts.wt.
Diatomaceous earth 47 pts.wt.
Clay 10 pts.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 10 pts.wt.
Polyoxyethylene lauryl ether 8 pts.wt.
Calcium lignin sulfonate 5 pts.wt.
Preparation Example 6: Wettable powder The following ingredients were homogeneously ground to prepare wettable powder.
Compound 2 20 pts.wt.
Metominostrobin 10 pts.wt.
Diatomaceous earth 42 pts.wt.
Clay 5 pts.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 10 pts.wt.
Polyoxyethylene lauryl ether 8 pts.wt.
Calcium lignin sulfonate 5 pts.wt.
Preparation Example 7: Dust
The following ingredients were homogeneously ground to prepare dust.
Compound 2 1.2 pts . wt.
Azoxystrobin 0.5 pt.wt.
Clay 97.1 pts.wt.
Calcium carbonate 0.5 pt.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 0.2 pt.wt.
Driless A (tradename; manufactured
by SANKYO CO., LTD.) 0.5 pt.wt.
Preparation Example 8; Dust
The following ingredients were homogeneously ground to prepare dust.
Compound 2 1 pt.wt.
Azoxystrobin 0.5 pt.wt.
Clay 97.1 pts.wt.
Calcium carbonate 0.5 pt.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 0.4 pt.wt.
Driless A (tradename; manufactured
by SANKYO CO., LTD.) 0.5 pt.wt.
Preparation Example 9: Dust
The following ingredients were homogeneously ground to prepare dust.
Compound 2 1.2 pts . wt.
Metominostrobin 0.5 pt.wt.
Clay 97.1 pts.wt.
Calcium carbonate 0.5 pt.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 0.2 pt.wt.
Driless A (tradename; manufactured
by SANKYO CO. , LTD.) 0 .5 pt. wt.
Preparation Example 10: Dust
The following ingredients were homogeneously ground to prepare dust.
Compound 2 1 pt.wt.
Metominostrobin 0.5 pt.wt.
Clay 97.1 pts.wt.
Calcium carbonate 0.5 pt.wt.
White carbon (tradename; manufactured
by Shionogi & Co., LTD.) 0.4 pt.wt.
Driless A (tradename; manufactured
by SANKYO CO., LTD.) 0.5 pt.wt.
Evaluation tests
Test A: Control effect against rice blast by
application before spread of rice blast (test in
suitable timing for control)
A potting compost was placed in a plastic vat (about 30 cm x 50 cm) , and seed rice (variety: Koshihikari) after forcing of germination was inoculated into the vat, followed by dense planting cultivation. This rice was used for the test.
The rice was raised for about 2 weeks in a glass greenhouse under conditions of 25°C in the daytime and 20°C in the night-time. At the time when the rice was grown to a three or four leaf stage, diseased leaves, which had been previously inoculated with rice blast fungi (race 037) and had developed rice blast, were placed on the densely planted rice, followed by standing under humidified conditions for inoculation of rice blast fungi for 24 hr. The rice plant was then again returned to within the glass greenhouse. Seven or eight days after that, the presence of lesions was observed, followed by first chemical application. In this case, a test chemical liquid was diluted with a 10% aqueous acetone solution (with 5,000-fold diluted Neoesterin
(tradename; manufactured by KUMIAI CHEMICAL INDUSTRY CO., LTD.) as a spreader added thereto) to predetermined concentrations. Each of the test chemical liquids thus prepared was applied in an amount of 15 ml per vat by means of a spray gun. When second chemical application is carried out, six or seven days after the first chemical application, the second chemical application was carried out in the same manner as in the first chemical application.
After the chemical application, the rice was controlled in the glass greenhouse. During this period, at one to two days intervals, the rice was placed under humidified conditions for 24 hr to accelerate the development and spread of rice blast.
Ten days after the final chemical application, for 40 plants per vat, the lesion area of the surface of a blade located one leaf below the uppermost leaf was observed, and the percentage lesion area in the treated plot was determined. The percentage lesion area in the nontreated plot was also determined in the same manner as in the treated plot. For each test chemical agent, the protective value was determined from the results obtained on the treated plot and the results obtained on the nontreated plot by the following equation.
Protective value = [1 - (percentage lesion area in treated plot/percentage lesion area in nontreated plot)] x 100
The prophylactic effect and residual effect of the test chemical agent can be determined by a method in which, after the elapse of predetermined days after the treatment with the chemical agent, observation is made on whether or not the percentage lesion area is increased. Accordingly, the prophylactic effect and residual effect were determined based on whether or not the final protective value was increased.
The test was carried out for each group consisting
of chemical agents indicated in Tables Al to A3 below. The chemical application was carried out once or twice. The results were as shown in Tables Al to A3.
Table Al; Double application test
(Table Removed)
Table A2: Single application test
(Table Removed)
Table A3: Single application test
(Table Removed)
Test B: Control effect against rice blast by
application after spread of rice blast (application
delay test)
A potting compost was placed in a plastic vat (about 30 cm x 50 cm) , and seed rice (variety: Koshihikari) after forcing of germination was inoculated into the vat, followed by dense planting cultivation. This rice was used for the test.
The rice was raised for about 2 weeks in a glass greenhouse under conditions of 25°C in the daytime and 20°C in the night-time. At the time when the rice was grown to a three or four leaf stage, diseased leaves, which had been previously inoculated with rice blast fungi (race 037) and had developed rice blast, were placed on the densely planted rice, followed by standing under humidified conditions for inoculation of rice blast fungi for 24 hr. The rice plant was then again returned to within the glass greenhouse. Seven or eight days after that, the presence of lesions was observed. Thereafter, the rice was again placed under humidified conditions for 24 hr to accelerate the second infection and to spread rice blast in the vat. After the elapse of about three or four days after the acceleration of the spread of rice blast, very small secondary lesion was confirmed, followed by the first chemical application.
The other test conditions, for example, test chemical liquid conditions, application method, application intervals, rice blast development and control method after the initiation of the application, calculation of percentage lesion area, and calculation of protective value, were the same as those in test A. When the second chemical application was carried out, the chemical application intervals were the same as those in test A.
The test was carried out for each group consisting of chemical agents indicated in Tables Bl to B4 below.
The results were as shown in Tables Bl to B4.
Table Bl: Double application test
(Table Removed)
Table B2; Single application test
(Table Removed)
Table B3: Single application test
(Table Removed)
Table B4; Single application test
(Table Removed)

WE CLAIM:
1. A fungicidal composition for use in the control of a disease of paddy rice, comprising as active ingredients a 2,3-dimethyl-6-t-butyl-8-fluoro-4-quinolinol derivative of formula (1) or an acid addition salt thereof;
(Formula Removed)
wherein
R represents a hydrogen atom; -COR1 or -COOR1, wherein R1 represents an alkyl group having 1 to 4 carbon atoms; -COCH2OCH3; or -COCH2OCOCH3, and
at least one compound selected from the group consisting of strobilurin fungicides
wherein the mixing ratio between the compound of formula (1) or an acid addition salt thereof and at least one compound selected from the group consisting of strobilurin fungicides is in the range of from 2 : 50 to 50 : 2.
2. The fungicidal composition as claimed in claim 1, wherein the compound belonging to the strobilurin fungicide is selected from azoxystrobin and metominostrobin.

Documents:

1548-delnp-2005-abstract.pdf

1548-delnp-2005-claims.pdf

1548-delnp-2005-complete specification (granted).pdf

1548-DELNP-2005-Correspondence Others-(12-12-2011).pdf

1548-delnp-2005-Correspondence Others-(30-12-2011).pdf

1548-delnp-2005-correspondence-others-(23-03-2010).pdf

1548-delnp-2005-correspondence-others.pdf

1548-delnp-2005-correspondence-po.pdf

1548-delnp-2005-description (complete).pdf

1548-delnp-2005-drawings.pdf

1548-delnp-2005-form-1.pdf

1548-delnp-2005-form-13-(23-03-2010).pdf

1548-delnp-2005-form-18.pdf

1548-delnp-2005-form-2.pdf

1548-delnp-2005-form-3.pdf

1548-delnp-2005-form-5.pdf

1548-DELNP-2005-GPA-(12-12-2011).pdf

1548-delnp-2005-gpa.pdf

1548-delnp-2005-pct-210.pdf

1548-delnp-2005-pct-304.pdf

1548-delnp-2005-pct-332.pdf

1548-delnp-2005-pct-338.pdf

1548-delnp-2005-pct-409.pdf

1548-delnp-2005-petition-137.pdf

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Patent Number

220330

Indian Patent Application Number

1548/DELNP/2005

PG Journal Number

30/2008

Publication Date

25-Jul-2008

Grant Date

23-May-2008

Date of Filing

15-Apr-2005

Name of Patentee

MEIJI SEIKA KAISHA, LTD.

Applicant Address

4-16, KYOBASHI 2-CHOME, CHUO-KU, TOKYO-TO, JAPAN

Inventors:

#	Inventor's Name	Inventor's Address
1	MAKOTO MATSUMURA	760 MOROOKA-CHO, KOUHOKU-KU, YOKOHAMA-SHI, KANAGAWA-KEN, JAPAN
2	MAKOTO MATSUMURA	760 MOROOKA-CHO, KOUHOKU-KU, YOKOHAMA-SHI, KANAGAWA-KEN, JAPAN

PCT International Classification Number

A01N 43/42

PCT International Application Number

PCT/JP2003/013850

PCT International Filing date

2003-10-29

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2002-315503	2002-10-30	Japan