MXPA96004347A - Acid derivatives 2- (4-pirazolylioxi-pirimidin-5-il) acet - Google Patents

Abstract

This invention relates to novel 2- (4-pyrazolyloxy-pyrimidin-5-yl) acetic derivatives of the formula (I), wherein, R 1 is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms of carbon, alkylthio of 1 to 4 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or dialkylamino of 1 to 4 carbon atoms, is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, or dialkylamino of 1 to 4 carbon atoms, is hydrogen or methyl, is aryl, arylalkyl of 1 to 4 carbon atoms, heteroaryl, or heteroarylalkyl of 1 to 4 carbon atoms, wherein each of the aromatic rings may be optionally substituted, and is CH or nitrogen, the use of such compounds for the control of phytopathogens, compositions for facilitating such use, and the preparation of the compounds of the formula (

Description

DERIVATIVES OF. ACID 2- P ftAZOIILOXI- PIRIMIDIN-5-IL) ACETIC This in. andon refers to novel 2- (4-pyrazyl) -l yloxy-pyrimidin-5-yl) acetic acid derivatives, the synthesis thereof and the use of the compounds for the control of phytopathogens. It has now been found that the compounds of the formula I wherein R 1 is hydrogen, alkyl of 1 to carbon atoms, alkoxy of 1 to carbon atoms, alkylthio of 1 to carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or dialkylamino of 1 to 4 carbon atoms, is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to carbon atoms, alkylation: 23Q «7 thio of 1 to? carbon atoms, or dialkylamino of 1 to 4 carbon atoms, R is hydrogen or methyl, R is aryl, arylalkyl of 1-4 carbons- 4-bond, heteroaryl, or heteroarylalkyl of 1 to 4 carbon atoms, wherein each of the aromatic rings can be optionally substituted; and X is CH or nitrogen; they are surprisingly effective against phytopathogens. In the definitions of the radicals of the formula I, alkyl is understood to embrace straight or branched chain alkyl groups. For example, alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertiary butyl or secondary butyl. For example, alkoxy embraces methoxy, ethoxy, n-propoxy, isopropoxy, n-butyloxy, isobutyloxy, tertiary butyloxy or secondary butyloxy. Alkylthio means petthylthio, ethylthio, isopro-pylthio, propylthio, n-butylthio, isobutylthio, tertiary butylthio or secondary butylthio. Cycloalkyl means, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Dialkylamino means, for example, dimethylamino, diethylamino, dipropylamino, ethylmethylamino, ethyl-propylamino, methylbutylamino, ethylpropylamino, or ethylbutoylamino. Aryl represents aromatic hydrocarbon radicals, for example phenyl or naphthyl, with phenyl being preferred. The aryl radical can also be optionally substituted. Heteroaryl represents cyclic alkyl rings of 5 or 5 aromatic members comprising one, two or three ring atoms selected from nitrogen, oxygen and sulfur, which may also be in condensed form with another heteroaryl radical or aryl radical. Heteroaryl is bonded to the oxygen bridge through a carbon atom of the ring member. The heteroaryl may also be optionally substituted. Examples for heteroaryl are pyridyl, pyrimidinyl, thienyl, oxazolyl, oxadiazolyl, triazolyl, thiadiazolyl, furyl, isoxazolyl, thiazolyl, i idazolyl, pyridazinyl, quinolinyl, quinazolinyl, benzothienyl, benzofuryl, benzimidazolyl, pyrazolyl, benzothiazolyl, benzoxazolyl, and the like. Preferably arylalkyl means phenylalkyl such as benzyl, phenylethyl, phenylpropyl, or 1-phenyl-ethyl. The aryl radical can also be optionally substituted. "Heteroarylalkyl" means an aromatic 5- or 6-membered cyclic radical comprising one, two or three ring atoms selected from nitrogen, oxygen and sulfur, which are bonded to the oxygen bridge through an alkylene group, similar to ~~~ * -CH2-CH - - i -o -CH (CH ^) -. The heteroaryl radical is linked to the alkylene group through a carbon atom of the ring member. Examples for heteroarylalkyl are thienylmethyl, thienylethyl, fylmethyl, pyridyl ethyl, pyrrhasyl ethyl and the like. The pyrazolyl ring can be bonded to the oxygen bridge via position 3 or 4. However, 3-pyrazolyl is preferred. In the radicals they are combined of other diverse definitions, each one of the definitions has the given meanings for the partial definition of separated way. The above aryl and heteroaryl radicals can also be substituted. Where the aryl or heteroaryl is substituted, it is preferably substituted by one, two or three radicals selected from the group comprising halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms, haloalkoxy of 1 to 4 carbon atoms, acyl of 2 to 8 carbon atoms, benzoyl, alkylthio of 1 to 4 carbon atoms, cyano, phenyl, phenoxy, nitro, or a group -C (CH-) = N-0-alkyl of 1 to 4 carbon atoms. Halogen means fluorine, chlorine, bromine and iodine, with the fluorine and chlorine that are preferred. Haloalkyl means straight or branched chain alkyl groups, which are mono- to perhalogenated with lower alkyl straight chain, the preferred alkyl and perhalogenated fluorine being straight chain lower alkyl, the alkyl being preferred and with fluorine and chlorine, being the preferred halogens. Examples of trifluoromethyl, difluoromethyl, 2,2,2-tri-fluoroethyl or 2, 2, 3,, 3-pentafluoropropyl. Haloalcaxi wants to desy alkoxy groups, which are mono- to perhaloge-nados. Examples are difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or 1,1, 2,4-tetrafluoroethoxy. Examples of acyl are acetyl, propionyl, butyroyl, isopropyl-nyl, hexanoyl or octanoyl. Preferred subgroups of compounds of the formula I or those in which either a) R., is methyl, ethyl or cyclopropyl; or b) R2 is methyl or methoxy; or c) the pyrazole ring is bonded to the oxygen bridge in the 3-position (or d) R, is chlorophenyl, dichlorophenyl, fluorophenyl, methyl-chlorophenyl, trifluoromethylphenyl, trifluoromethyl-chlorophenyl, difluoro-ethoxyphenyl, trifluoromethoxyphenyl, methylphenyl, or dimethylphenyl. A preferred, additional subgroup is where R1 and R? they are methyl, and R, is chlorophenyl, dichlorophenyl, fluorophenyl, methyl-chlorophenyl, trifluoromethylphenyl, trifluoromethyl-chlorophenyl, difluoromethoxyphenyl, tri-fluoromethoxyphenyl, methylphenyl, or dimethylphenyl. Among this subgroup, those compounds where X is CH are preferred. Compounds Individual, preferred of formula I are: 2- [2,4-dimethyl-6- (1- (3-trifluoromethyl-phenyl) -1H) -pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methacrylate; 2- [2,. Dimethyl-6- (1 - (3, 5-dimethylphenyl) -TH-pyrazol-5-yloxy) -pyrimidin-5-yl] -3-methoxyacrylate; Methyl 2- [2,4-dimethyl-6- (1- (5-chloro-2-methylphenyl) -1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxyacrylate; Y 2- [2-Methyl-4-methoxy-6- (1 - (5-chloro-2-methylphenyl) -1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methacrylate .

The double bond of the acrylic acid structure in the compounds of the formula I can be in the E or Z form. In this document, the E and Z forms are identified where specifically implied. In all other cases, mixtures of the two isomers are proposed. Where the E and Z isomers are obtained during synthesis, they can be separated by known techniques, such as crystallization, chromatography or distillation. In the preparation methods described, forms are preferably obtained Compounds of the formula I can be obtained by the 0-methylation of a compound of the formula II where R .., R2 > R »R 7 X are as defined above. The 0-methylation (II-I) can be carried out in a manner known per se during the preparation of 3-methoxyacrylates using conventional methylating agents. Examples of suitable methylation agents include methyl iodide and dimethyl sulfate. O-methylation is conveniently carried out in the presence of a base. The reaction temperature is conveniently in the range of 0 ° C to the boiling point of the reaction mixture, for example, at about room temperature. Inert solvents can be used where desired. Examples of suitable bases include alkali metal hydrides such as sodium hydride, alkali metal alcoholates such as sodium methylate or alkali metal carbonates. Examples of suitable inert solvents include aromatic hydrocarbons such as benzene and toluene; ethers such as diethyl ether, tetrahydrofuran and 1,2-dimethoxyethane; polar solvents such as dimethylformamide, dimethyl sulfoxide, alcohols such as methanol; acetone or a mixture comprising two or more of them. The desired final product is isolated and purified according to known techniques, for example by evaporation of the solvent, chromatography and crystallization. The compounds of the formula I are only slightly basic in nature. These can form salts with sufficiently strong acids such as HCl and HBr. The compounds of the formula II, wherein X is CH, can be obtained by the reaction of compounds of the formula III where R .., Rj > Ro and R are as defined above and alkyl is alkyl of 1 to 10 carbon atoms, with a formylating agent, for example N, N-diformyl-ethylamine or methyl formate in the presence of a base. This reaction is essentially a Claisen reaction and can be carried out under the conditions known for such a reaction. The reaction (III - * II) can be carried out in an inert solvent. Examples of suitable solvents are as described for the 0-methylation of the compounds of the formula II. Examples of suitable bases are thus typically agitated for a Claisen reaction such as alkali metal alcoholates, for example, sodium methylate; alkaline metal hydrides, for example sodium hydride; and lithium amides or sodium amides, for example lithium diethylamide. The reaction temperature can vary within wide ranges, for example from 0 ° C to the boiling point of, la. reaction mixture and is preferably almost at room temperature. In an alternative procedure, the compounds of the formula II can also be obtained by reacting the compounds of the formula III with a 1: 1 adduct of dimethylformamide and dimethyl sulfate in the presence of a strong base, such as t-BuOK and hydrolyze the intermediate obtained from the Illa formula where R .., R? and they are as defined above. This reaction variant is preferably carried out in an inert solvent at a temperature between -70 ° C to -30 ° C, preferably -60 ° C to -4-0 ° C. Suitable solvents are ethers such as tetrahydrofuran, dioxane, diethyl ether or glime. Suitable bases are, for example, alkaline alcohols such as t-BuOK; or alkali hydrides such as NaH, KH. The passage of hydrolysis is typically done in a two-fascia system, by adding water, and at a temperature of 0 ° C to + 4-0 ° C, pre-eminently at room temperature. The compound of Formula II wherein X is nitrogen can be obtained by reacting the compounds of formula III with an alkyl nitrite in the presence of a base, optionally in the presence of an inert solvent. In a variant of this process, the compounds of the Formula II wherein X is N, can also be obtained by reacting a compound of the formula III with an alkyl nitrite in the presence of hydrochloric acid, optionally in an inert solvent. The reaction temperature will conveniently be in the range of -4-0 ° C to 3 ° C for example, at about -20 ° C to 0 ° C. Inert solvents can be used where desired. Examples of suitable bases include alkali metal hydrides such as sodium hydride and alkali metal alcoholates such as potassium tert-butylate. Examples of suitable inert solvents include aromatic hydrocarbons such as benzene and toluene; ethers such as diethyl ether tetrahydrofuran and, 2-dimethoxyethane; polar solvents such as dimethylformamide, dimethyl sulfoxide, alcohols such as tert-butanol; or a mixture comprising two or more thereof.

In a reactor of the two-step process (III - * II - »I), the compounds of the formula I can be obtained by a reaction in a single container of the compounds of the formula III, without the isolation and purification of the intermediate compounds of the formula II. The acetic acid esters of the formula III can be obtained from the compounds of the formula IV RG -CH2- COOCH3 (IV) Cl wherein R- and R2 are as defined above, by reacting with a hydroxy-pyrazole of formulas V or VI where R-, and R, are as defined previously - in the presence 3 4 of a base and an inert solvent. The proper bases and solvents are as for (II - »I). The compounds of formula IV wherein R is hydrogen, alkyl, alkoxy, or dialkylamino are known from European patent application No. 634 495 and European patent application No. 667 343. The compounds of formula IV, wherein R2 is alkylthio, can be obtained by reacting a compound of the formula VII (vp) wherein R .. is as defined above with a mercaptan of the formula VIII H-S-R2 (V? D wherein R2 is as defined above, in the presence of a base. This reaction is preferably carried out in an inert solvent such as an ether, for example glyme (dimethoxyethane). Suitable bases are U-hydride-sodium, sodium methylate or the like. In a preferred variant, the base is reacted with the mercaptan first, to give the sodium salt, which can then be reacted with the compound of the formula VII without the presence of a base. Alternatively, the intermediates of the formula III can be obtained, wherein R 2 is alkoxy of 1 to 4 carbon atoms or dialkylamino of 1 to 4 carbon atoms by reacting the dichloropyrimidinyl acetic esters of starting material of the formula VII with a hydroxypyrazole of the formulas V or VI first, and by reacting the intermediates obtained from the formula IX wherein R-, R and R¿ are as defined above, with a compound of formula X H-R, (X) where R? is alkyloxy of 1 to 4 carbon atoms or dialkylamino of 1 to 4 carbon atoms, in the presence of a base The reaction conditions for this variant of the synthesis (VII + V / VI? IX + X? III ) are similar to those given for the reaction of VII with VIII The intermediaries of formulas II, III and IX have been developed in a special manner for the synthesis of compounds of formula I. Therefore, they constitute a part of the present invention. The starting materials of formulas IV, V, VI, VII and VIII are known, or can be prepared in analogy to known processes. The compounds of the formula V, wherein R, is aryl or heteroaryl, each optionally substituted, can be obtained preferably by the use of a new oxidation process, which has been developed especially for the synthesis of the compounds of the formula I. Therefore, it is part of the present invention. The novel oxidation process for preparing the compounds of the formula V, wherein R, is aryl or heteroaryl, each optionally substituted, comprises oxidizing the aryl- or heteroaryl-pyridine mother-of-formula XI wherein R is aryl or heteroaryl, each optionally substituted, with an oxidizing agent, prepared in situ from H2O2 and a catalyst. The oxidation step (XI -> V) is preferably carried out in an inert solvent, such as formic acid or acetic acid, at low temperatures. Preferably, the exothermic oxidation process is controlled by cooling, or by controlled addition of the oxidizing agent. The temperatures are preferably maintained below + 50 ° C, especially in the range from 0 ° C to + 30 ° C. Suitable oxidizing agents are H2O2 in the presence of oxidation catalysts. Suitable oxidation catalysts are vanadyl acetylacetonate, copper (II) acetylacetonate, manganese oxide (Mn? 2) > selenium oxide (Se? 2) »nickel oxide (IO2), and the like. The compounds of the formula I are effective against phytopathogens, including phytopathogenic fungi. Its advantageous fungicidal activity is established by in vivo tests with test concentrations of 0.1 to 500 mg i. . / I, against Uromyces appendiculatus in climbing bean, against Puccinia triticina in wheat, against Sphaerotheca fuliginea in cucumber, against Erysiphe gra inis in wheat and barley, against Podosphaera leucotricha in apple, against Uncinula necator in grapevine, against Leptosphaeria nodorum in wheat, against Cochlio-bolus sativus and Pyrenophora graminea in barley, against Venturia inaequalis in apple, against Phytophthora infestans in tomato and against Plasmopara viticola in grapevine. Many of the compounds of the formula I have an excellent tolerance in the plant and a systemic action. Therefore, the compounds of the invention are indicated for the treatment of plants, seeds and soil, to combat phytopathogenic fungi, for example 3asidiomycetes of the order Uredinales (molds) such as Puccinia spp, Hemileia spp, Uromyces spp; and Ascomycetes of the order Erysiphales (powdery mildew) such as. Erysiphe ssp. Podosphaera spp, Uncinula spp, Sphaerotheca spp; as well as Cochliobolus; Pyrenophora spp; Venturia ssp; Mycosphaerella spp; Leptosphaeria; Deutero ycetes such as Pyricularia, Pellicularia (Corticium), Botrytis; and Oomycetes such as Phytophthora spp, Plasmopara spp. The compounds of formula I are particularly effective against mold and mildew, fungi pyrenophora and leptosphaeria, in particular against pathogens of monocotyledonous plants such as cereals, including wheat-and barley.The amount of the compound of the invention to be applied, will depend on various factors such as the compound used, the subject of treatment (plants, soil, seeds), the type of treatment (for example, sprinkling, sprinkling, seed treatment), the purpose of the treatment (prophylactic or therapeutic) ), the type of fungi to be treated and the application time In general, satisfactory results are obtained, the compounds of the invention are applied in an amount of about 0.01 to 2.0, preferably about 0.02 to 1 kg. / ha, in the case of a plant or soil treatment, for example 0.04 to 0.500 kg of active ingredient (ai) per ha in extensive crops such as cereals, or concentrations of 4 to -50 g of i. to. per hl in crops, such as fruits, vines and vegetables (in an application volume of 300 to 1000 1 / ha - depending on the size or volume of the crop leaf - which is equivalent to an application rate of approximately 30- 500 g / ha). The treatment can be repeated, if desired, for example, in intervals of 8 to 30 days. Where the solvents of the invention are used for the treatment of seeds, in general, satisfactory results are obtained, if the blankets are used in an amount of about 0.05 to 0.5, preferably about 0.1 to 0.3 g / kg of seeds. The term "land" as used herein, is proposed to encompass any conventional growth medium, either natural or artificial. The compounds of the invention can be used in a large number of crops, such as soybeans, coffee beans, ornamentals (pelargonium, roses), vegetables (for example pea, cucumber, celery, tomato and bean plants), beets, sugarcane, cotton, flax, corn (corn), vineyards, pommel or fruit of fruit pip and stone (for example, apple, pears, prunes) and in cereals (for example, wheat, oats, barley, rice) . The invention also provides fungicidal compositions, which comprise as a fungicide, a compound of formula I in association with an agriculturally acceptable diluent (diluent below). These are obtained in a conventional manner, for example by mixing a compound of the invention with a diluent and optionally additional ingredients, such as surfactants. The term "diluents" as used herein means a liquid or solid material, acceptable in agriculture, which can be added to the active agent to bring it in an easier or better application, respectively, to dilute the active agent to a resistance of activity that can be used or desired. Examples of such diluents are talc, kaolin, diatomaceous earth, xylene or water. In particular, the formulations used in the form of condensation dispersants such as dispersible in water or wettable powders, may contain surfactants such as wetting and dispersing agents, for example, the condensation product of formaldehyde with naphthalene sulfonate, an alkylarylsulfonate, an sulfonate - of lignin, a fatty alkyl sulfate, an ethoxylated alkylphenol and an ethoxylated fatty alcohol. In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% of surfactant acceptable in agriculture and from 10 to 99.99% diluent (s). Concentrated forms of composition, for example emulsion concentrates, generally contain from about 2 to 90%, preferably from 5 to 70% by weight of active agent. The application forms of the formulation generally contain from 0.0005 to 10% by weight of a compound of the invention as the active agent, the typical spray suspensions, for example, can contain from 0.0005 to 0.05, for example 0.0001, 0.002 or 0.005% by weight of active agent. In addition to the usual diluents and surfactants, the compositions of the invention may comprise additional additives for special purposes, for example stabilizers, deactivators (for solid formulations or carriers with an active surface), agents for improving adhesion to plants, inhibitors of corrosion, antifoaming agents and dyes. In addition, additional fungicides with similar or complementary fungicidal activity, for example sulfur, chlorota-lonyl, euparene; a guanidine fungicide such as guazatine; dithiocarbamates such as mancozeb, maneb, zineb, propineb; sulfenylphthalimides of trichloromethane and the like such as somo saptan, captafol and folpet; .benzimidazoles such as carbendazim, benomyl; azoles such as ciproconazole, flusilazole, flutriafol, hexa-sonazole, propiconazole, tebuconazole, epoxiconazole, triti-conazole, prochloraz; Morpholines such as phenpropimorph, phenpropidine, or other beneficially acting materials, such osmoximoxanil, oxadixyl, metalaxyl, or insecticides may be present in the formulations. Examples of fungicidal formulations of the plant are as follows: to. Formulation in Wettable Powder parts of a compound of formula I are mixed and ground with 4 parts of fine silica, synthetic, 3 parts of sodium lauryl sulfate, 7 parts of sodium lignin sulfonate and 66 parts of finely divided kaolin and 10 parts of earth diatomaceous until the average particle size is about 5 microns. The resulting wettable powder is diluted with water before using a spray liquor, which can be applied by foliar spray as well as by application to the root by flooding. b. Granules 94"5 parts by weight of quartz sand in a drum mixer, 0.5 parts by weight of a binder (surfactant or nonionic surfactant) are sprayed and mixed thoroughly. Then 5 parts by weight of a compound of the invention of the formula I are added and the complete mixing is continued to obtain a granular formulation is a particle size in the range of 0. 3 to 0.7 mm (where required, the granules can be dried by the addition of 1 to 5% by weight of talc). The granules can be applied by incorporation into the soil adjacent to the plants to be treated. c. Emulsion concentrate 1 0 parts by weight of a compound of the formula I are mixed with 10 parts by weight of an emulsifier and 80 parts by weight of xylene. The concentrate obtained in this way is diluted with water to form an emulsion of the desired concentration, before application. d. Seed treatment . 45 parts of a compound of the formula I are mixed with 1.5 parts of ethylene oxide adduct of diamnyl phenoldecaglycol ether, 2 parts of extra-light oil, 51 parts of talcum fine and 0.5 parts of dyeing roltonin B. The mixture is milled in a counterplex mill at 10,000 rpm until an average particle size of less than one is obtained. 20 microwaves The resulting dry powder has good adhesion and can be applied to the seeds, for example by mixing for 2 to 5 minutes in a slowly rotating container. The following examples further illustrate the present invention. All temperatures are in centigrade.

Example 1: 2- [2,4-Dimethyl-6- (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methacrylate a) 2- [2,4-dimethyl-6- (1-f-enyl-1H-pyrazol-3-yloxy) -pyrimid-5-yl] -acetic acid methyl ester A mixture of methyl (4-chloro-2,6-dimethyl-5-pyrimidinyl) -acetate (5.0 g, 23 mmol), 1-phenyl-1 H-pyrazole-3 is heated at + 120 ° C. -on (3.73 g, 23 mmol), potassium carbonate (5.5 g, 40 mmol) in dimethylformamide (30 ml), for 2 hours. addition of water, extraction with ether and drying give intermediate methyl 2- [2,4-dimethyl-6- (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetate. like a yellow oil. 1 H-NMR (CDC13): 7.86 (d, 1H), 7.67-7.20 (m, 5H); 6.32 (d, 2H); 3.80 (s, 2H); 3.70 (s, 3H); 2.57 (s, 3H); 2.36 (s, 3H). b) methyl 2- [2,4-dimethyl-6- (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetate intermediate (6.8 g, 20 mmol), NaH (0.8 g, of an 80% suspension in oil, 25 mmol) and N, N-diformylmethylamine (5 ml) in dimethylformamide (40 ml) is stirred at 45 ° C for two hours. Dimethyl sulfate (2.4 ml, 25 mmol) is added at room temperature and stirring is continued for a further two hours. Dilution with ether, washing with brine, drying and chromatography on silica gel (eluent: ethyl acetate / hexane 1: 1) give 2- [2,4-dimethyl-6- (1-phenyl-1H- methyl pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxyacrylate as a colorless oil. 1 H NMR (CDC13): 7.86 .. (d, ÍH); 7.6 * 3 (s, 1H); 7.67-7.20 (m, 5H); 6.32 (d, 1H); 3-88 (s, 3H); 3.70 (s, 3H); 2.57 (s, 3H); 2.36 (s, 3H).

Example 2 2-Methoximino- [2-methyl-4-dimethylamino-6- (l-phenyl-1 H -py-zol-3-yloxy) -pyrimidin-5-yl] -methyl ester a) 2- [2-Methyl-4-dimethylamino-6- (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetic acid methyl ester A mixture of (4,6-dichloro-2-yl-pyrimidin-5-yl) -methyl ester (5.43 g, 23 mmol), 1-phenyl-1 H- is heated to + 120 ° C. pyrazole-3-on (3.73 g, 23 mmol) and potassium carbonate (5.5 g, 40 mmol) in dimethylformamide (30 ml), for 30 minutes. The addition of dimethylamine (10 ml of a 25% aqueous solution) at room temperature, stirring for 20 hours and the preparation give 2- [2-methyl-4-dimethylamino-6- (1-phenyl-1H-pyrazole Methyl-3-yloxy) -pyrimidin-5-yl] -acetate as an oil. b) 2-Hydroximino-2- [2-methyl-4-dimethylamino-6- (1-phenyl-1 H -pyrazol-3-yloxy) -pyrimidin-5-yl] -acetic acid methyl ester A solution of methyl 2- [2-methyl-4-dimethyl-amino-6- (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetate (8.0 g, 22 mmol) is added. ) in dimethoxyethane (20 ml), to a solution of t-BuOK (7.3 g, 65 mmol) and t-BuONO (8 ml) in dimethoxyethane (80 ml) at -40 ° C.

After stirring for 30 minutes, the mixture is rapidly cooled with ammonium slurry (aqueous solution, 75 ml). The mixture is stirred for two hours. Extraction with ether, drying and chromatography on silica gel (eluent: ethyl acetate / hexane 1: 1) give 2-hydroxyimino-2- [2-methyl-4-dimethylamino-6- (1-phenyl- Crystalline methyl 1H-pyrazol-3-yloxy) -pyrimidin-5-yl-acetate. c) 2-Hydroxymino-2- [2-ethyl-4-dimethylamino-6- (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -methyl ester (3.5 g, 8.8 mmoles) to a suspension of NaH (0.3 g, 10 mmol) in dimethylformamide (30 ml) and dimethyl sulfate (0.9 ml, 9.7 mmol). The mixture is stirred at room temperature for 2 hours. Dilution with ether, washing with brine, drying and chromatography on silica gel (eluent: ethyl acetate / hexane 1: 1) give 2-methoximino-2- [2-methyl-4-dimethylamino-6] - (1-phenyl-1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetic acid methyl ester. 1 H-NMR (CDC13): 7.82 (d, 1H); 7.67-7.20 (m, 5H); 6.22 (d, 2H); 4.06 (s, 3H); 3.88 (s, 3H); 3.03 (s, 6H); 2.41 (s, 3H).

Employ 2-22,4-Dimethyl- (1- (2,6-dichlorobenzyl) -1 H -pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methyl acrylate a) 2- [2,4-Dimethyl-6- (1- (2,6-dichlorobenzyl) -1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetic acid methyl ester A mixture of methyl (2,4-dimethyl-6-chloro-5-pyrimidinyl) -acetate (0.5 g, 23 min), 1- (2,6-dichlorobenzyl) - is heated to + 130 ° C. -pyrazol-3-on (5.80 g, 23 mmol) and potassium carbonate. (10.0 g, 70 mmol) in dimethylformamide (30 ml), for 2 hours. The addition of water, extraction with ether and drying give 2- [2,4-dimethyl-6- (1- (2,6-dichlorobenzyl) -1H-pyrazol-3-yl-oxy) -pyrimidine-5 -yl] -methyl intermediate as a yellow oil. b) Methyl 2- [2,4-dimethyl-6- (1- (2,6-dichlorobenzyl) -1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -acetic acid intermediate (9.6 g, 23 mmoles) is dissolved in dimethylformamide (20 ml) and added at + 30 ° C to a suspension of NaH (1.3 g, of an 80% suspension in oil, 4 mmole) and N, N-diformylmethylamine (10 ml) in dimethylformamide (40 ml). The reaction mixture is stirred for 2 hours at + 45 ° C. Dimethyl sulfate (2.4 ml, 25 mmol) is added at room temperature with cooling and stirring is continued for two additional hours. Dilution with ether, washing with brine, drying and chromatography on silica gel (eluent: ethyl acetate / hexane 3: 1) give 2- [2,4-dimethyl-6- (1 - (2.6 methyl-dichloro-benzyl) -1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxyacrylate as a colorless oil (4.8 g). 1 H NMR (CDC13): 7.59 (s, 1H); 7.39-7.23 (m, 3H); 7.19 (d, 1H); 6.04 (d, ÍH); 5.54 (s, 2H); 3.83 (s, 3H); 3.67 (s, 3H); 2.53 (s, 3H); 2 .33 (a, 3H).

Example 4 2- [2,4-Dimethyl-6- (1- (2-methylphenyl) -1H-pyrazol-4-yloxy) 'pyrimidin-5-yl] -3-methoxy-methacrylate a) 2- [2,4-Dimethyl-6- (1- (2-methylphenyl) -1H-pyrazol-4-yl-oxy) -pyrimidin-5-yl] -acetic acid methyl ester A mixture of methyl (4-chloro-2,6-dimethyl-5-pyrimidinyl) -acetate (4.6 g, 21 mmol), 1- (2-methylphenyl) -1 H-pyrazole is heated to + 120 ° C. ol-4-on (4.1 g, 23 mmol) and potassium sarbonate (6.4 g, 46 mmol) in dimethylformamide (50 ml), for 2 hours. Addition of water, extraction of ether and drying give 2- [2,4-dimethyl-6- (1 - (2-methylphenyl) -1H-pyrazol-4-yloxy) -pyrimidin-5-yl] - intermediate methyl acetate as an oil. NMR-H (CDC13): 7.23-7.96 (m, 6H); 3-78 (s, 2H); 3.73 (s, 3H); 2.58 (s, 3H); 2.47 (s, 3H); 2.29 (s, 3H). b) 2- [2,4-Dimethyl-6- (1- (2-methylphenyl) -1H-pyrazol-4-yloxy) -pyrimidin-5-yl] -methyl methyl ester intermediate (6.0 g, 17 mmol), sodium hydride (0.9 g, 37 mmol) and N, N-diformylmethylamine (6 ml) in a mixture of dimethyl formamide (20 ml) and 1,2-diaethoxyethane (20 iri.) Is stirred at 45CC for 3 hours. Methyl iodide (4.2 g, 30 mmol) is added at room temperature and the stirring is continued for an additional 16 hours. Dilution with ether, washing with brine, drying and chromatography on silica gel (eluent: ethyl acetate / hexane 3: 7) give 2- [2,4-dimethyl-6- (1 - (2 methyl-methylphenyl) -1H-pyrazol-4-yloxy) -pyrimidin-5-yl] -3-methoxyacrylate as a colorless oil. NMR-1H (CDC13): 7.26-7.95 (m, 6H); 3.90 (s, 3H); 3.74 (s, 3H); 2.59 (s, 3H); 2.38 (s, 3H); 2.33 (s, 3H).

Example 5 1- (2,5-Dichlorophenyl) -2-pyrazolone a) 1 - (2,5-Dichlorophenyl) -3-pyrazolidone Refluxing hydrochloride of 2,5-dichloropropylhydrazine (240 g, 1.1 mol) and acrylamide (100 g, 1.4 mol) in a solution of sodium (56 g, 2.4 mol) in ethanol (1000 ml) and toluene are heated to reflux. 1000 ml) for 3 hours. Evaporation of the solvents, acidification with acetic acid, dilution with water, filtration and drying (high vacuum, + 100 ° C) give 1 - (2, -dichlorophene) -3-pyrazolidone. b) Hydrogen peroxide (30% solution in water, 120 ml) is slowly added to a stirred suspension well of 1- (2,5-dichlorophenyl) -3-pyrazolidone (200 g, 0.86 mol) and sodium dioxide. , selenium (3-0"-g) in acetic acid (1000 ml) The temperature is reduced by cooling to not exseder + 50 ° C. After stirring at this temperature for 1 hour, add crushed ice and water The product is filtered and dried to produce 1- (2,5-dislorophenyl) -3-pyrazolone, mp 201-202 ° C.

Example 6 1 - . 1-Phenyl-3-pyrazolidone Phenylhydrazine (10.8 g, 0.1 mole) and acrylamide (7.8 g, 0.11 mole), powdered potassium hydroxide (12.5 g, 0.22) and a catalytic amount of tetrabutylammonium bromide were re fl uxed for 30 minutes. The presipitated filter and wash are toluene. The sold crystalline dissolves in water. Assyri fi cation with acetic acid, filtration and drying give 1-phenyl-3-pyrazolidone. The compounds of the following tables are obtained analogously: Table 1 Table 2 3. CH, CH, 1 -naphthyl 7.52-8.1 L (m, 9H); 3.93 (s, 3H); 3.77 (s, 3H); 2.62 (s, 3H); 2.39 (s, 3H).

Table Table 5 .a 6 Table 7 : abla -a¿-L =.

Cabla 10 Table 11 - 7 or - Table 12 Example A: Astividad shows the Pulverulent Rust Sphaerothesa fuliginea: Cucumis sativus (cucumber), 7 days old (cotyledon stage) plants are sprayed until they are almost spilled, they are a suspension that is 63 mg / 1 of active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inoculated with a spore suspension containing 1x105 / ml conidium freshly collected from Sphaerotheca_fuliginea and then incubated in the greenhouse for 7 days at + 24 ° C and 60% r.h.

The effectiveness of the test compounds is determined by comparing the degree of fungal attack with that of test plans and inoculated similarly, untreated. In this test, the compounds 1.03, 1.06, 1.09, 1.10, 1.12, 1.13, 1.38, 1.39, 1.40, 1.41, 1.43, 1.44, 1.45, 1.48, 1.51, 1.64, 1.65, 1.66, 1.67, 1.68, 1.69, 1.70, 1.71, 1.73, 1.74, 1.75, 1.76, 1.78, 1.79, 1.80, 1.81, 1.83, 1.86, 1.88, 1.89, 1.90, 1.92, 1.93, 1.94, 1.95, 1.96, 1.97, 1.98, 3.01, 3.02, 3.03, 3.04, 3.07, 3.08 3.15, 3.16, 3-31, 3.35, 3.36, 3-37, 3.39, 3.40, 3.41 showed an efisasia of more than 90%. Similar methods are used to test the compounds for the following pathogens: Podosphaera leusotrisha in apple, Erysiphe gra inis in wheat and barley (dry inoculation), Unsinula nesator in grape.

Example B: Astivity against Maha, Caatra í rapa, Pyrsmphara Lep > tosphaeria Uromyces appendiculatus: Plants of Phaseolus vulgaris (climbing frijol), 14 days old (2-leaf stage), were added to the plants and spilled with a suspension that "contains 63 mg / 1 of the active ingredient." The deposit is then allowed to dry. One day later, the treated plants are inoculated with a spore suspension containing 1 x 10 / ml of freshly chopped spores of Uromyces-appendicu-latus.Incubation is carried out for 3 days in a high humidity compartment at + 23 ° C. and> 95 hr and then for 10 days at + 24 ° C and 60% rh The effectiveness of the compounds is determined by comparing the degree of fungal attack with that of verifying plants similarly inoculated, untreated. this test, the 1.01 compounds, 1.02, 1.03, 1.04, 1.06, 1.08, 1.09, 1.10, 1.11, 1.12, 1.13, 1.17, 1.37, 1.38, 1.39, 1.40, 1.41, 1.43, 1.44, 1-45, 1-48, 1.51, 1.64, 1.65 , 1.66, 1.67, 1.68, 1.69, 1.70, 1.71, 1.73, 1.74, 1-75, 1.76, 1.77, 1.78, 1.79, 1.80, 1.81, 1.83, 1.84, 1.86, 1.88, 1.89, 1.90, 1.92, 1.93, 1.94 , 1.95, 1.96, 1.97, 1.98, 1.99, 3.01, 3.02, 3.03, 3.04, 3.06, 3.07, 3.08, 3.09, 3.15, 3.16, 3.25, 3.31, 3-33, '3.35, 3.37, 3.38, 3- 39, 3.40 and 3.41 showed an efficacy of at least 90%. Similar methods are used to test the compounds against the following pathogens: Puccinia triticina in wheat (plants 10 days old) Pyrenophora grass in barley, Leptosphaeria nodorum. in wheat, Centuria inaequalis in apple (plants 21 days old; the spore suspension contains 1% malt).

Example C: Gentle Mold Activity Plants of Lycopersicon esculentum (tomato) with 6 leaves are sprayed, until almost spilling with a rosé suspension containing 63 mg / 1 of the active ingredient. The deposit is then allowed to dry. One day later. the treated plants are inoculated with a spore suspension containing 1 x 10 / ml of freshly cholerae sporangia of Phytophthora infestans and then are incubated for 7 days in a high humidity compartment at + 18 ° C and > 95% of h.r. The effectiveness of the test suites is determined by comparing the degree of fungal attack with that of verification plants similarly inoculated, untreated. In this test, the compounds 1.02, 1. 03, 1.04, 1.06, 1.09, 1.10, 1.12, 1.17, 1.37, 1.38, 1.40, 1.41, 1.51, 1.65, 1.67, 1.69, 1.71, 1.73, 1.76, 1.78, 1.93, 1.95, 1.96, 1.97, 1.98, 3.01, 3.05, 3.06, 3.09, 3.40 and 3.41 showed efficacy of at least 90%. A similar method is used to test the compounds against Plasmopara viticola en vid.

Example D: Activity after Seed Treatment The compounds of the invention can also be used for seed treatment. The advantageous funcigida astivity is established by in vitro test with the following pathogens: Pyrenophora graminea, Ustilago nuda, Gerlachia nivalis, Leptoshpaeria nodorum. Wheat seeds are inoculated in autoclave with spores or mycelium of the pathogens and coated with different concentrations of the test compounds that result in doses of 50 g. i.a./100 kg of seeds. The treated seeds were then sesolocan on agar plates and the pathogens were allowed to grow for 3 - 8 days at + 24 ° C in the dark. The eficasia of the test compounds is determined by comparing the degree of fungal growth that springs from the inoculated seeds treated and untreated. To evaluate the tolerance of the sultivo plant of the compounds, healthy seeds of wheat and barley are coated with the doses mentioned above. The seeds are then allowed to germinate in petri dishes on moist filter paper in high humidity at + 18 ° C for 10 days. Damage to the plant is recorded, comparing the yield of treated and untreated nursery plants. In this test, the compounds of the formula I show an efficacy of at least 90% against Pyrenophora grass.

It is noted that in relation to this date, the best method conosido by the solisitante to carry out the aforementioned invention, is the one that is clear from the present description of the invention.

Having described the invention as above, the following are claimed as property:

Claims (16)

1 . Compue s to the formula I characterized in that R. is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, alkylthio of 1 to 4 carbon atoms, or dialkylamino of 1 to 4 carbon atoms, R ~ is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or dialkylamide of 1 to 4 carbon atoms, R is hydrogen or methyl, R, is aryl, arylalkyl of 1 to 4 carbon atoms, 4 heteroaryl, or heteroarylalkyl of 1 to 4 carbon atoms, wherein each of the aromatic rings may be optionally substituted; and X is CH or nitrogen.

2. A compound according to claim 1, characterized in that the aromatic rings in R 4 are optionally substituted by one, two or three radicals selected from the group comprising halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4. carbon atoms, haloalkyl - of 1 to 4 carbon atoms, haloalkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, phenyl, phenoxy, nitro or a group -C (CH) = N- 0-alkyl of 1 to 4 carbon atoms.

3. A compound according to claim 1 or 2, characterized in that R. i is methyl, ethyl or cyclopropyl.

4. A compound according to claim 1 or 2, characterized in that R? It is methyl or methoxy.

5. A compound according to claims 2 or 2, characterized in that the pyrazole ring is bonded to the oxygen bridge n'the 3 or 4 position.

6. A compound according to claim 1 or 2, characterized in that R is chloro-phenyl, dichlorophenyl, fluo ofenyl, methyl-chlorophenyl, trifluoromethylphenyl, trifluoro-ethyl-slorophenyl, difluo-romethoxyphenyl, trifluoromethoxyphenyl, methylphenyl, or dimethylphenyl.

7. A structure of soundness is claim 1, characterized in that R-j and R2 are methyl, R is chlorophenyl, dichlorophenyl, fluorophenyl, methyl-slorophenyl, trifluoromethylphenyl, trifluoromethyl-chloropropyl, difluoromethoxyphenyl, trifluoromethoxyphenyl, methylphenyl or dimethylphenyl.

8. A compound according to claim 7, characterized in that X is CH.

9. A compound according to claim 1, characterized in that it is selected from the group comprising 2- [2,4-dimethyl-6- (- (3-trifluoromethylphenyl) -1H-pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methacrylate; 2- [2,4-Dimethyl-6- (1- (3, 5-dimethylphenyl) -1H-pyrazol-4-yloxy) -pyrimidin-5-yl] -3-methoxyacrylate methyl; 2- [2, 4-dimethyl-6- (1 - (5-chloro-2-methyl-methyl) -1 H -pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methacrylate; Y 2- [2-Methyl-4-methoxy-6- (1 - (5-chloro-2-methylphenyl) -1 H-pyrazol-3-yloxy) -pyrimidin-5-yl] -3-methoxy-methacrylate .

10. Method for combating phytopathogenic fungi, characterized in that it comprises applying to fungi or their habitat, an antifungally effective amount of a compound of formula I, according to claim 1.

11. Fungiidase composition characterized in that it comprises a compound of formula I set forth in claim 1 and a diluent acceptable in agriculture.

12. A process for preparing a compound of the formula I according to claim 1, characterized in that the 0-methylation of a compound of the formula II wherein R, R, R, R, and X are as defined in claim 1.

13. Compounds of formula II ^ characterized in that R, R, R, R and X are somo s and define for formula I in claim 1.

14- Compounds of formula III characterized in that R., R, R, R ^ on as defined for claim 1.

15. -Compounds of formula IX characterized in that R-j, R3 and ^ are as defined for Ca formula I in claim 1.

16. A preparation for the preparation of the compounds of the formula V characterized in that R is aryl or heteroaryl each optionally substituted as defined in claim 1, the process is interfaced because it comprises oxidizing an aryl- or heteroarylpyrazolidone of the formula ?? NH or =? R < (XI) wherein R is aryl or heteroaryl, each optionally substituted with an oxidizing agent, prepared in situ from ^ 2 ^ 2 and a catalyst. SUMMARY OF THE INVENTION This invention relates to novel 2- (4-urazolyloxy-pyridin-5-yl) acetic acid derivatives of the formula I where R1 is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or dialkylamino of 1 to 4 atoms of sarbon, is hydrogen, alkyl of 1 to 4 atoms of sarbon, alsoxi of 1 to 4 atoms of sarbon, alkylthio of 1 to 4 carbon atoms, or dialkylamino of 1 to 4 carbon atoms, R3 is hydrogen or methyl, is aryl, arylalkyl from 1 to 4 carbon R4 atoms, heteroaryl, or heteroarylalkyl of 1 to 4 carbon atoms, wherein each of the aromatic rings may be optionally substituted; and X is CH or nitrogen; the use of such compounds for the control of phytopathogens, compositions for facilitating such use, and the preparation of the compounds of the formula I.