Benzamidoxim derivatives, intermediate products and methods for preparing and using them as fungicides

ES 2 188 016 T3

DESCRIPTION

Derivative of benzamidoxime, intermediate products and procedure for its production and its use as fungicides.

The present invention relates to new derivatives of benzamidoxime, to processes and intermediate products for their preparation, and to their use as fungicides.

However, JP-A 09/235262 and JP-A 02/006453 describe derivatives of benzamidoxime with fungicidal efficacy, which are not completely satisfactory, however, especially in low application amounts. EP-A-0624567 discloses new 3-fluorophenol derivatives.

Therefore, it was the task of the present invention to make available new benzamidoxime derivatives with improved action, especially also in low application amounts.

Surprisingly, benzamidoxime derivatives of formula I have now been discovered

<img file="ES2188016T3_D0001.tif" />

the substituents having the following meanings:

R¹ hydrogenic or fluorine;

R² alkyl with 1 to 4 carbon atoms, which may be substituted by cyano, halogenated alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms-alkyl with 1 to 4 carbon atoms, alkenyl with 3 to 6 carbon atoms carbon, halogenated alkenyl with 3 to 6 carbon atoms, alkynyl with 3 to 6 carbon atoms, cycloalkyl with 3 to 8 carbon atoms-alkyl with 1 to 4 carbon atoms;

R³ means phenyl-alkyl with 1 to 6 carbon atoms, which can carry on the phenyl ring one or more substituents selected from the group consisting of halogen, alkyl with 1 to 4 carbon atoms, halogenated alkyl with 1 to 4 carbon atoms of carbon, alkoxy with 1 to 4 carbon atoms or halogenated alkoxy with 1 to 4 carbon atoms, or thienyl-alkyl with 1 to 4 carbon atoms, which can carry on the thienyl ring one or more substituents selected from the group consisting of halogen, alkyl with 1 to 4 carbon atoms, halogenated alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms or alkoxy halogenated with 1 to 4 carbon atoms, or pyrazole-alkyl with 1 to 4 carbon atoms, which can carry one or more substituents selected from the group consisting of halogen on the pyrazole ring, alkyl with 1 to 4 carbon atoms, halogenated alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms or halogenated alkoxy with 1 to 4 carbon atoms.

In the definition of the substituents R¹ aR³, the concepts indicated as a collective concept represent a group of compounds.

Halogen represents respectively fluorine, bromine, chlorine or iodine, especially fluorine or chlorine.

They also represent, by way of example:

- alkyl with 1 to 4 carbon atoms: methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl,

2-methylpropyl or 1,1-dimethylethyl, especially ethyl;

- halogenated alkyl with 1 to 4 carbon atoms: an alkyl radical with 1 to 4 carbon atoms as indicated above, which may be partially or completely substituted by fluorine, chlorine, bromine and / or iodine, for example trichloromethyl, trifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl,

2,2-Difluoroethyl, 2,2,2-trifluoroethyl, 2,2,, 2-trichloroethyl, 2-fluoropropyl, 3-fluoropropyl, 2-chloropropyl or

3-chloropropyl, especially 2-fluoroethyl or 2-chloroethyl;

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- cyano-C 1 -C 4 -alkyl: cyanomethyl, 1-cyano-1-ethyl, 2-cyano-1-ethyl, 1-cyano-1-propyl, 2-cyano-1-propyl, 3-cyano-1- propyl, 1-cyano-2-propyl or 2-cyano-2-propyl, especially cyanomethyl or 2-cyanoethyl;

- alkoxy with 1 to 4 carbon atoms: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy, especially methoxy or ethoxy;

C 1-4 alkoxy-C 1-4 alkyl: C 1-4 alkyl substituted by C 1-4 alkoxy as mentioned above, i.e., for example methoxymethyl, ethoxymethyl , n-propoxymethyl, (1-methylethoxy) methyl, n-butoxymethyl, (1-methylpropoxy) methyl, (2-methylpropoxy) methyl, (1,1-dimethylethoxy) methyl, 2- (methoxy) ethyl or 2- (ethoxy) ) ethyl, especially methoxymethyl or 2-methoxyethyl;

- alkenyl with 3 to 6 carbon atoms: for example prop-2-en-1-yl, n-buten-4-yl, 1-methyl-prop-2en-1-yl, 2-methyl-prop-2- en-1-yl or 2-buten-1-yl, especially prop-2-en-1-yl;

- halogenated alkenyl with 3 to 6 carbon atoms: alkenyl with 3 to 6 carbon atoms as mentioned above, which is partially or completely substituted by fluorine, chlorine and / or bromine, for example 2-chloroalyl, 3-chloroalyl, 2 , 3-dichloroallyl or 3,3-dichloroallyl, especially 2-chloroallyl;

- alkynyl with 3 to 6 carbon atoms: for example prop-1-yn-1-yl, prop-2-yn-1-yl, n-but-1-y-1-yl, n-but-1- yn-3-yl, n-but-1-yn-4-yl or n-but-2-yn-1-yl, especially prop-2-yn-1-yl;

- cycloalkyl with 3 to 8 carbon atoms-alkyl with 1 to 4 carbon atoms: for example cyclopropylmethyl, cyclobutylmethyl, cyclopentyl-methyl, cyclohexylmethyl, (cyclopropyl) -ethyl, 1 (cyclobutyl) -ethyl, 1- (cyclopentyl) - ethyl, 1- (cyclohexyl) -ethyl, 1- (cycloheptyl) -ethyl, 1- (cyclooctyl) -ethyl, 2 (cyclopropyl) -ethyl or 2- (cyclobutyl) -ethyl, especially cyclopentyl-methyl;

- phenyl-alkyl with 1 to 6 carbon atoms: for example benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenyl-1-propyl, 2-phenyl-1-propyl, 3-phenyl-1-propyl, especially benzyl or 2-phenylethyl;

thienyl-alkyl with 1 to 4 carbon atoms: for example 2-thienylmethyl, 3-thienylmethyl or 2-thienylethyl;

pyrazole alkyl with 1 to 4 carbon atoms: for example 1-pyrazolylmethyl, 2-pyrazolylmethyl, 3-pyrazolylmethyl or 2-pyrazolylmethyl.

As a general rule, compounds in which the substituent R² represents cyclopropylmethyl and the substituent R³ represents benzyl, which has on the phenyl ring one to three substituents selected from the group mentioned above, in particular 1 to 3 substituents selected from fluorine, chlorine, methyl, methoxy or trifluoromethyl.

Compounds of formula I in which R¹ aR³ have the meanings indicated in Table 1 below, they are especially preferred.

TABLE 1

<td>No.</td><td>R¹</td><td>R²</td><td>R³</td><td>mp ° C</td>

<td>I.1</td><td>H</td><td>C2H5</td><td>C6H5-CH2</td><td>Oil</td>

<td>I.2</td><td>H</td><td>C2H5</td><td>4-CH₃OC₆H₄-CH₂</td><td>Oil</td>

<td>I.3</td><td>H</td><td>CH₂-CH = CH₂</td><td>C6H5-CH2</td><td>Oil</td>

<td>I.4</td><td>H</td><td>CH₂-C CH</td><td>C6H5-CH2</td><td>Oil</td>

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TABLE 1 (continued)

<td>No.</td><td>R¹</td><td>R²</td><td>R³</td><td>mp ° C</td>

<td>I.5</td><td>H</td><td>CIH-C CH</td><td>4-CH₃OC₆H₄-CH₂</td><td>Oil</td>

<td>I.6</td><td>H</td><td>cPr</td><td>C6H5-CH2</td><td></td>

<td>I.7</td><td>H</td><td>cPr</td><td>4-FC₆H₄-CH₂</td><td> 75-77</td>

<td>I.8</td><td>H</td><td>cPr</td><td>4-Cl-C₆H₄-CH₂</td><td> 81-83</td>

<td>I.9</td><td>H</td><td>cPr</td><td>4-CH₃OC₆H₄-CH₂</td><td> 57-59</td>

<td>I.10</td><td>H</td><td>cPr</td><td>4-CF₃-C₆H₄-CH₂</td><td></td>

<td>I.11</td><td>H</td><td>cPr</td><td>2-thienylmethyl</td><td>Oil</td>

<td>I.2</td><td>H</td><td>cPr</td><td>3-thienylmethyl</td><td>Oil</td>

<td>I.13</td><td>H</td><td>cPr</td><td>Pyrazolyl-1-methyl</td><td></td>

<td>I.14</td><td>H</td><td>cPr</td><td>4-CH₃-C₆H₄-CH₂</td><td></td>

<td>I.15</td><td>5-F</td><td>CH₂-CH = CH₂</td><td>C6H5-CH2</td><td></td>

<td>I.16</td><td>5-F</td><td>ch₂-ch = ch₂</td><td>4-CH₃-C₆H₄-CH₂</td><td></td>

<td>I.17</td><td>5-F</td><td>CIH-C CH</td><td>C6H5-CH2</td><td></td>

<td>I.18</td><td>5-F</td><td>CIH-C CH</td><td>4-CH₃OC₆H₄-CH₂</td><td></td>

<td>I.19</td><td>5-F</td><td>cPr</td><td>C6H5-CH2</td><td> 62-65</td>

<td>No.</td><td>R¹</td><td>R²</td><td>R³</td><td>mp ° C</td>

<td>I.20</td><td>5-F</td><td>cPr</td><td>4-FC₆H₄-CH₂</td><td> 64-67</td>

<td>I.21</td><td>5-F</td><td>cPr</td><td>4-Cl-C₆H₄-CH₂</td><td> 72-75</td>

<td>I.22</td><td>5-F</td><td>cPr</td><td>4-CH₃-C₆H₄-CH₂</td><td> 74-76</td>

<td>I.23</td><td>5-F</td><td>cPr</td><td>4-CH₃OC₆H₄-CH₂</td><td> 79-81</td>

<td>I.24</td><td>5-F</td><td>cPr</td><td>4-CF₃-C₆H₄-CH₂</td><td></td>

<td>I.25</td><td>4-F</td><td>cPr</td><td>C6H5-CH2</td><td></td>

<td>I.26</td><td>4-F</td><td>cPr</td><td>4-CH₃OC₆H₄-CH₂</td><td></td>

<td>I.27</td><td>H</td><td>cPr</td><td>4-CH₃-C₆H₄-CH₂</td><td> 69-71</td>

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TABLE 1 (continued)

<td>No.</td><td>R¹</td><td>R²</td><td>R³</td><td>mp ° C</td>

<td>I.28</td><td>H</td><td>CIH-C CH</td><td>4-FC₆H₄-CH₂</td><td> 74-76</td>

<td>I.29</td><td>H</td><td>C2H5</td><td>4-FC₆H₄-CH₂</td><td>Oil</td>

<td>I.30</td><td>H</td><td>CH₂-CH = CH₂</td><td>4-FC₆H₄-CH₂</td><td>Oil</td>

<td>I.31</td><td>H</td><td>ch₂-ch = ch₂</td><td>4-CH₃OC₆H₄-CH₂</td><td>Oil</td>

<td>I.32</td><td>H</td><td>CH2-CH (CH3) 2</td><td>C6H5-CH2</td><td> 65-67</td>

<td>I.33</td><td>H</td><td>CH2-C (CH3) = CH2</td><td>C6H5-CH2</td><td>Oil</td>

cPr represents cyclopropylmethyl in the table above.

The benzamidoxime derivatives of the formula I according to the invention are obtained according to the procedure according to the invention by dissociation of fluorinated benzonitrile ethers of the formula II, reaction of the benzonitriles obtained III with halogenated alkanes CHF2Hal, such as CHF2Cl, in a basic medium (preferably in the presence of an alkali metal hydroxide (to give IV benzonitriles, and subsequent reaction of IV with hydroxylamine or its salts in aqueous solution, preferably in water or water / alkanol mixtures, optionally in the presence of a base to give the benzamidoximes of the formula V, which are then alkylated in a manner known per se to give the pre-products VI.

The benzamidoximes VI can then be acylated in a manner known per se with the corresponding acid halides, preferably the corresponding acid chlorides, by heating in inert solvents (preferably at temperatures in the range 20 to 100 ° C).

Suitable inert solvents are especially hydrocarbons or ethers, particularly preferably aromatic hydrocarbons, such as toluene or xylene, to name just two examples.

(See Formula on next page)

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<img file="ES2188016T3_D0002.tif" />

The intermediate products of formula III indicated in the previous reaction scheme, in which R¹ represents fluorine, and the intermediates of formulas IV, V and VI are new and constitute a further object of the invention.

The obtaining of these new intermediates with a difluoro substitution can be carried out starting from 2,3-difluoro-6-methoxybenzoaldehyde (which can be obtained, for example, according to the procedure of example 27 of WO 97/03071) according to to the variants described in example 2 up to compound stage IV. The subsequent steps for obtaining the corresponding compounds V and VI are known per se to the skilled person.

The preferred compounds of formulas IV, V and VI are those in which R¹ yR² (compounds VI) have the meanings cited above for compounds of the formula I.

The preferred compounds of formula IV are the compounds indicated in the following table 2:

(See TABLES on the next page)

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<td>No.</td><td>R¹</td><td>mp [° C], NMR (CDCl₃) ppm</td>

<td>II.1</td><td>H</td><td>6.7 t (1H); 7.05-7.2 m (2H); 7.55-7.7m (1H)</td>

<td>II.2</td><td>5-F</td><td>6.65 t (1H); 7.05-7.2 m (1H); 7.4-7.5m (1H)</td>

<td>II.3</td><td>4-F</td><td></td>

The preferred compounds of formula V are listed in Table 3.

<td>No.</td><td>R¹</td><td>mp [° C], NMR (CDCl₃) ppm</td>

<td>III.1</td><td>H</td><td>5.9 s (2H); 7.0-7.2 m (2H); 7.15 t (1H); 7.4-7.55 m (1H)</td>

<td>III.2</td><td>5-F</td><td>4.9 s (2H); 6.5 t (1H); 6.95-7.05 m (1H); 7.15-7.3 m (1H); 8.0 s (1H)</td>

<td>III.3</td><td>4-F</td><td></td>

Some preferred compounds of formula VI are listed in Table 4 below.

<td>No.</td><td>R¹</td><td>R²</td><td>mp [◦C], NMR (CDCl₃) ppm</td>

<td>IV.1</td><td>H</td><td>C2H5</td><td></td>

<td>IV.2</td><td>H</td><td>CH₂-CH = CH₂</td><td></td>

<td>IV.3</td><td>H</td><td>CH₂-C CH</td><td></td>

<td>IV.4</td><td>H</td><td>c-Pr</td><td>0.3 m (2H); 0.55m (2H); 1.2 m (1H); 3.9 d (2H); 4.85 s, br (2H); 6.6 t (1H); 6.85-7.1 m (2H); 7.35-7.45 m (1H)</td>

<td>IV.5</td><td>5-F</td><td>C2H5</td><td></td>

<td>IV.6</td><td>5-F</td><td>CH₂-CH = CH₂</td><td></td>

<td>IV.7</td><td>5-F</td><td>CH₂-C CH</td><td></td>

<td>IV.8</td><td>5-F</td><td>c-Pr</td><td>0.3 m (2H); 0.55m (2H); 1.2 m (1H); 3.85 d (2H); 4.9 s, br (2H); 6.55 t (1H); 7.0-7.1 m (2H); 7.15-7.2 m (1H)</td>

Compounds I are distinguished by an extraordinary action against a wide spectrum of phytopathogenic fungi, especially the class of ascomycetes, deuteromycetes, phycomycetes and basidiomycetes. In part they have systemic efficacy, and can therefore also be used as insecticides for leaves and soil.

Plants are usually sprayed or dusted with the active ingredients, or the seeds of plants are treated with the active ingredients.

The formulations are obtained in a manner known per se, for example by diluting the active principle with solvents and / or carrier substances, if desired using emulsifying and dispersing agents, it is also possible to use other organic solvents as auxiliary solvents in the case of water. as a diluent. For this purpose, essentially auxiliary substances are considered: solvents, such as aromatic compounds (for example xylene), chlorinated aromatic compounds (for example chlorobenzenes), paraffins (for example mineral oil fractions), alcohols (for example

ES 2 188 016 T3 methanol, butanol), ketones (for example cyclohexanone), amines (for example ethanolamine, dimethylformamide) and water; carrier substances, such as natural mineral flours (for example kaolins, aluminum oxides, talc, chalk), and synthetic mineral flours (for example highly dispersed silicic acid, silicates); emulsifying agents, such as non-ionogenic and anioonic emulsifiers (for example polyoxyethylene fatty alcohol ethers, alkyl sulphonates and aryl sulphonates), and dispersing agents, such as sulphite leaching of lignin and methyl cellulose.

The alkaline, alkaline and ammonium salts of aromatic sulfoonic acids, for example lignin-, phenol-, naphthalene- and dibutylnaphthalinsulphonic acids, as well as fatty acids, alkyl and alkylaryl sulphonates, alkyl and lauryl sulphates, fatty alcohol, as well as salts of sulfated hexa-, hepta and octadecanols, as well as of fatty alcohol glycol ether, condensation products of sulphonated naphthalene and its derivatives with formaldehoide, condensation products of naphthalene, or of naphthalene sulphonic acid, with phenol and formaldehoide, polyoxyethylenectylphenol ether, isooctyl-, octyl- or nonylphenol ethoxylate, alcohol polyglycol eutylphenyl, condensed alcohol polyglycholethyl ether fatty alcohol-ethylene oxide, ethoxylated castor oil, polyoxyethylene alkyl ether or polyoxypropylene, Laoric alcohol polyglycoleteracetate, sorbitol osters, lignin sulphite leaching or methylcellulose.

Powders, dispersing and dusting agents can be obtained by mixing or grinding the active substances together with a solid carrier substance.

Granules, for example coating, impregnated or homogeneous granules, are usually obtained by binding the active ingredients to solid carrier substances. Solid carrier substances are mineral earths, such as silica gel, siloic acids, siloic gels, silicates, talc, kaolin, attaclay, limestone, lime, chalk, bol, loess, clay, dolomite, diatomaceous earth, calcium sulfate and magnesium, magnesium oxide, ground synthetic materials, fertilizing agents, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas and vegetable products, such as cereal flour, tree bark flour, wood and walnut shells, cellulose powder or other solid support substances.

Examples of such preparations are:

I. a solution consisting of 90 parts by weight of a compound I according to the invention and 10 parts by weight of N-methyl-2-pyrrolidone, which is suitable for application in the form of ultrafine drops;

II. a mixture consisting of 10 parts by weight of a compound I according to the invention, 70 parts of xylene, 10 parts by weight of addition product from 8 to 10 moles of ethylene oxide in 1 mole of oleic acid N-monoethanolamide, 5 parts in weight of calcium salt of dodecylbenzenesulfonic acid, 5 parts by weight of product of addition of 40 moles of ethylene oxide in 1 mole of castor oil; a dispersion is obtained by fine distribution of the solution in water;

III. an aqueous dispersion consisting of 10 parts by weight of a compound I according to the invention, 40 parts by weight of cyclohexanone, 30 parts by weight of iso-butanol, 20 parts by weight of product of addition of 40 moles of ethylene oxide in 1 mol of castor oil;

IV. an aqueous dispersion consisting of 10 parts by weight of a compound I according to the invention, 25 parts by weight of cyclohexanol, 55 parts by weight of a fraction of mineral oil boiling point 210 to 280 ° C, and 10 parts by weight of product of addition of 40 moles of ethylene oxide in 1 mole of castor oil;

V. a mixture, ground in a hammer mill, consisting of 80 parts by weight, preferably of a solid compound I according to the invention, 3 parts by weight of sodium salt of di-isobutylnaphthalene-2-sulfoonic acid, 10 parts by weight sodium salt of a ligninsulfonic acid from a sulphite leaching of lignin and 7 parts by weight of powdered silica gel; a spray mixture is obtained by fine distribution of the mixture in water;

SAW. an intimate mixture consisting of 3 parts by weight of a compound I according to the invention and 97 parts by weight of finely divided kaolin; This dusting agent contains 3% by weight of active principle;

VII. an intimate mixture consisting of 30 parts by weight of a compound I according to the invention, 62 parts by weight of powdered silica gel and 8 parts by weight of paraffin oil, which was sprayed on the surface of this silica gel; This preparation provides good adherence to the active principle;

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VIII. a stable aqueous dispersion consisting of 40 parts by weight of a compound I according to the invention, 10 parts by weight of sodium salt of a phenolsulfanic acid-urea-formaldehyde condensate, 2 parts by weight of silica gel and 48 parts by weight of water, which can be further diluted;

IX. a stable oleaginous dispersion consisting of 20 parts by weight of a compound I according to the invention, 2 parts by weight of calcium salt of dodecylbenzenesulfáonic acid, 8 parts by weight of polyglycolether of fatty alcohol, 20 parts by weight of sodium salt of a condensate of phenolsulfáonic acid-urea-formaldehyde, and 50 parts by weight of a paraphanic mineral oil.

The new compounds are distinguished by an extraordinary action against a wide spectrum of phytopathogenic fungi, especially the class of ascomycetes, deuteromycetes, phycomycetes and basidiomycetes. In part they have systemic efficacy, and can therefore also be used as insecticides for leaves and soil.

They have special significance for combating a plurality of fungi in various crop plants, such as wheat, rye, barley, oats, rice, corn, grass, cotton, soy, coffee, sugar cane, vine, fruit and ornamental plants, and vegetables, such as cucumbers, broad beans and cucurbits, as well as in the seeds of these plants.

The compounds are applied by treating the fungi or the seeds, plants, materials or soils to be protected against fungal attack, with a fungicidally effective amount of active ingredients.

The application is carried out before or after the infection of the materials, plants or seeds due to fungi.

The new compounds are especially suitable for combating the following plant diseases:

Erysiphe graminis (powdery mildew) in cereals, Erysiphe cichoracearum and Spaerotheca fuliginea in cucurbitaceae, Podosphaera leucotricha in apples, Uncinula necator in vine, types of Puccinia in cereals, types of Rhizoctonia in cotton and grass, types of Ustilago in cereals and sugar cane, Venturia inaequalis (rona) on apples, Helminthosporium types on cereals, Septoria nodorum on wheat, Botrytis cinerea (gray mold) on strawberries, vine, ornamental plants and vegetables, Cercospora arachidicola in peanuts, Pseudocercosporella herpotrichoides in wheat and barley, Pyricularia oryzae in rice, Phytophthora infestans in potatoes and tomatoes, types of Fusarium and Verticillium in various plants, Plasmopara viticola in vine, types of Alternaria in vegetables and fruits.

The new compounds can also be used in the protection of materials (protection of wood), for example against Paecilomyces variotii.

The fungicidal agents generally contain between 0.1 and 95, preferably between 0.5 and 90% by weight of active principle.

The amounts of application are located, depending on the type of desired effect, between 0.025 and 2, preferably 0.1 and 1 kg of active ingredient per ha.

In the case of seed treatment, amounts of active principle of 0.001 to 50 g, preferably 0.01 to 10 g, are generally required per kilogram of seeds.

The agents according to the invention can be presented in the form of application as fungicides also together with other active principles, for example with herbicides, insecticides, growth regulators, fungicides, or also with fertilizing agents.

In the case of mixing with fungicides, in many cases an extension of the spectrum of fungicidal action is obtained.

The following list of fungicides, with which the compounds can be applied together according to the invention, will explain but not limit the possibilities of combination:

sulfur, dithiocarbamates and their derivatives, such as iron dimethyldithiocarbamate, zinc dimethyldithiocarbamate, zinc ethylenebisdithiocarbamate, manganese ethylenebisdithiocarbamate, zinc-manganese-ethylenediamine-bisdithiocarbamate , N-ammonium-zinc ethylene bisdithiocarbamate, zinc N-ammonium ecarbamate (N-ethylene-dithiocarbamate) complex, , ammonia complex of zinc (N, N'-propylene-bis-dithiocarbamate), (N, N'9

ES 2 188 016 T3 zinc propylene bis-dithiocarbamate), N, N'-polypropylene bis (thiocarbamoyl) disulfide;

nitro derivatives, such as dinitro - (1-methylheptyl) -phenylcrotonate, 2-sec-butyl-4,6-dinitrophenyl-3,3-dimethylacrylate, 2-sec-butyl-4,6-dinitrophenyl-isopropylcarbonate, 5-nitro-isophthalate di-isopropyl;

Heterocolic substances, such as 2-heptadecyl-2-imidazoline acetate, 2,4-dichloro-6 - (o-chloroanilino) -s-triazine, O, O-diethyl-phthalimidophosphonothioate, 5-amino-1 - [bis - ( dimethylamino) -phosphinyl)] 3-phenyl-1,2,4-triazole, 2,3-dicyano-1,4-dithioanthraquinone, 2-thio-1,3-dithiolo [4,5-b] quinoxaline,

- (Buty-carbamoyl-2-benzimidazole) -methyl carbamate, 2-methoxycarbonylamino-benzimidazole,

- (furyl - (2)) - benzimidazole, 2 - (thiazolyl - (4)) - benzimidazole, N - (1,1,2,2-tetrachlorethylthio) -tetrahydrophthalimide, N-trichloromethyl-thio-tetrahydrophthalimide, N-trichloromethylthio - phthalimide;

N-dichlorofluoromethylthio-N ', N' -dimethyl-N-phenyl-sulfuric acid diamide, 5-ethoxy-3-trichloro-methyl-1,2,3-thiadiazole, 2-rhodanmethylthiobenzothiazole, 1,4-dichloro-2 , 5-dimethoxy-benzene,

4- (2-chlorophenylhydrazono) -3-methyl-5-isoxazolone, 2-thio-1-pyridine oxide, 8-hydroxyquinoline, or its copper salt, 2,3-dihydro-5-carboxanilido-6-methyl - 1,4-oxathine, 4,4-dioxide

2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathine, 2-methyl-5,6-dihydro-4H pyran-2-carboxolic acid anilide, 2-methyl-furan-3- acid anilide Carboxolic, 2,5-dimethyl acid anilide

- furan-3-carboxylic acid, 2,4,5-trimethyl-furan-3-carboxylic acid anilide, 2,5-dimethyl-furan-3-carboxylic acid cyclohexylamide, N-cyclohexyl-N-methoxy-acid amide 2,5-dimethyl-furan-3-carboxolic, 2-methyl-benzoic acid anilide, 2-iodo-benzoic acid anilide,

N-formyl-N-morpholine 2,2,2-trichloroethylacetal, piperazin-1,4-diylbis - (1 - (2,2,2-trichloroethyl) -formamide, 1 - (3,4-dichloroanilino) - 1-formylamino-2,2,2-trichloroethane, 2,6-dimethyl N-tridecyl-morpholine, or its salts, 2,6-dimethyl-N-cyclododecylmorpholine, or its salts, N - [3 - (p - tert-butylphenyl) -2-methylpropyl] -cis-2,6-dimethyl-morpholine, N - [3 - (p-tert-butylphenyl) -2-methyl-propyl] -piperidine, 1 - [2 - (2,4-dichlorophenyl) -4-ethyl-1,3-dioxolan-2-yl-ethyl] -1H 1,2,4-triazole, 1 - [2 - (2,4-dichlorophenyl) - 4-n-propyl-1,3-dioxolan-2-yl-ethyl] -1H-1,2,4-triazole, N - (n-propyl) -N - (2,4,6-tri-chlorophenoxyethyl ) - N'-imidazol-yl-urea, 1 - (4-chlorophenoxy) -3,3-dimethyl-1 - (1H-1,2,4-triazol-1-yl) -2-butanone, (2 - chlorophenyl) - (4-chlorophenyl) -5-pyrimidine-methanol,

5- butyl-2-dimethylamino-4-hydroxy-6-methyl-pyrimidine, bis - (p-chlorophenyl) -3-pyridinemethanol, 1,2bis - (3-ethoxycarbonyl-2-thioureido-benzene, 1,2-bis - (3-methoxycarbonyl-2-thioureido) -benzene, [2 - (4-chloro-phenyl) ethyl] - (1,1-dimethylethyl) -1H-1,2,4-triazole-1-ethanol, 1 - [3 - (2-chlorophenyl) -1 (4-fluoro-phenyl) oxiran-2-yl-methyl] -1H-1,2,4-triazole, as well as various fungicides, such as dodecylguanidine acetate, 3 - [3 - (3,5-dimethyl-2-oxycyclohexyl) -2-hydroxyethyl] -glutarimide, hexachlorobenzene, DL-methyl-N - [2,6-dimethyl-phenyl) -N-furoyl (2) -alaninate, DL-N - (2,6-dimethyl-phenyl) -N - (2'-methoxyacetyl) -methyl alaninate, N - (2,6-dimethylphenyl) -N-chloroacetyl-D, L-2-aminobutyrolactone, DL- Methyl N - (2,6-dimethyl-phenyl) -N - (phenylacetyl) -alaninate, 5-methyl-5-vinyl-3 - (3,5-dichlorophenyl) -2,4-dioxo-1,3 - oxazolidine, 3 - (3,5-dichlorophenyl) -5-methyl-5-methoxymethyl-1,3-oxazolidine-2,4-dione, 3- (3,5-dichlorophenyl) -1-isopropylcarbamoylhydantoon, acid imide N - (3 , 5-dichlorophenyl) -1,2-dimethylcyclopropan-1,2-dicarboxylic,

- cyano - [N - (ethylaminocarbonyl) -2-methoxyimino] -acetamide, 1 - [2 - (2,4-dichlorophenyl) -pentyl] -1H-1,2,4-triazole, alcohol 2,4-difluoro- α - (1H-1,2,4-triazolyl-1-methyl) -benzohydrolic, N - (3-chloro-2,6-dinitro-4-trifluoromethyl-phenyl) -5-trifluoromethyl-3-chloro-2 - aminopyridine, 1 - ((bis - (4-fluorophenyl) -methylsilyl) -methyl) -1H-1,2,4-triazole;

strobirulins, such as methyl-E-methoxyimino - [α - (o-tolyloxy) -o-tolyl] acetate, methyl-E-2 - {2 [6 - (2-cyanophenoxy) pyrimidin-4-yloxy] phenyl} -3 - methoxyacrylate, methyl-E-methoxy-imino - [α - (2,5-dimethyloxy) -o-tolyl] acetamide;

anilino-pyrimidines, such as N - (4,6-dimethylpyrimidin-2-yl) aniline, N - [4-methyl-6 - (1-propynyl) pyrimidin-2-yl] aniline, N - (4-methyl-6 - cyclopropyl-pyrimidin-2-yl) aniline;

phenylpyrroles, such as 4- (2,2-difluoro-1,3-benzodioxol-4-yl) -pyrrole-3-carbonitrile; cinnamic acid amides, such as 3- (4-chlorophenyl) -3- (3,4-dimethoxyphenyl) -acrylic acid morpholide.

Example 1

a) 6-fluoro-2-hydroxybenzonitrile

7.8 g of 2-methoxy-6-fluorobenzonitrile and 18.0 g of pyridine hydrochloride were heated for 5 hours at 195 ° C

ES 2 188 016 T3 under dry nitrogen. After cooling, the load was distributed between 50 ml of water and 50 ml of tert-butylmethylether, and then the organic phase was extracted with 40 ml of 2n NaOH. The alkaline extract was adjusted to pH 5, and then extracted twice with 40 ml of tert-butylmethylether respectively. After evaporation of the solvent, 4.7 g of the desired product was obtained as an oil (HPLC: 93%). NMR (DMSO) ppm: 6.8-6.95 m (2H); 7.5-7.6 m (1H); 11.8 s, br (1H).

b) 2-Difluoromethoxy-6-fluorobenzonitrile

In a mixture of 10.0 g of 2-hydroxy-6-fluorobenzonitrile, 50 ml of 1,2-dimethoxyethane and 25 ml of NaOH (33%), 6.3 g of chlorodifluoromethane ( in this case, the reflux condenser was cooled with dry ice) and subsequently stirred for 1 hour at 70-75 C. After cooling, the batch was diluted with 300 ml of water and extracted three times with 150 ml of tertiary. butylmethyl ether respectively. After evaporation of the solvent, 6.5 g of the desired product was obtained as an oil. NMR (CDCl3) ppm: 6.7 t (1H), 7.05-7.20m (2H), 7.55-7.70m (1H).

c) 2-Difluoromethoxy-6-fluorobenzamidoxime

A mixture of 6.4 g of 2-difluoromethoxy-6-fluorobenzonitrile and 3.1 g of hydroxylamine hydrochloride, 2.6 g of sodium carbonate, 7 ml of water and 35 ml of ethanol was stirred for 20 hours at 75 ° C.

After evaporation of the solvent, the residue was distributed between 40 ml of 2n HCl and 20 ml of ethyl acetate. After separation of the HCl phase, neutralization to pH 7 and triple extraction with 40 ml of tert-butylmethyl ether respectively, the solvent was evaporated. 6.0 g of the desired product was obtained. NMR (DMSO) ppm: 5.9 s (2H); 7.0-7.2 m (2H); 7.15 t (1H); 7.4-7.44 m (1H); 9.5 s (1H).

d) 2-Difluoromethoxy-6-fluorobenzamido- [O-cyclopropylmethyl] -oxime

To a solution of 3.0 g of 2-difluoromethoxy-6-fluorobenzamidoxime in 30 ml of dimethylformamide (DMF) at 0 to 5 ° C 0.4 g of 80% sodium hydride were added, and the mixture was stirred for 3 hours. temperature. 1.8 g of bromocyclopropylmethane were then added at the same temperature, and the mixture was subsequently stirred for 2 hours to 5^°C and overnight at room temperature. The batch was stirred into 300 ml of water, and extracted three times with 70 ml of cyclohexane respectively. After evaporation of the cyclohexane, 1.9 g of the desired product were obtained.

NMR (CDCl3) ppm: 0.3m (2H), 0.55m (2H), 1.2m (1H), 3.9d (2H), 4.85s, br (2H), 6.6t (1H); 6.85-7.1 m (2H); 7.35-7.45m (1H).

e) N-phenylacetyl-2-difluoromethoxy-6-fluorobenzamido - [O-cyclopropylmethyl] -oxime (compound I.6 of table 1)

1.9 g of the 2-difluoromethoxy-6-fluorobenzamido- [O-cyclopropyl-methyl] -oxime obtained according to step d) and 1.5 g of phenylacetic acid chloride were heated with 40 ml of toluene for 20 hours at reflux. After cooling, 40 ml of water were added and the pH was adjusted to 11. From the toluene phase, after evaporation of the solvent and subsequent column chromatography on silica gel with a 99: 1 mixture of cyclohexane and ethyl acetate as eluent, 1.6 g of the desired product with one point 58-60 meltdown^°C.

NMR (CDCl3) ppm: 0.2m (2H), 0.50m (2H), 1.0m (1H), 3.9d (2H), 6.4t (1H), 6.85-7.0m (2H ): 7.2-7.5m (6H); 8.5 s (1H).

N-phenylacetyl-2-difluoromethoxy-6-fluorobenzamido- [O-allylmethyl] -oxime (compound I.3 of table 1) was obtained anaologously as oil.

ES 2 188 016 T3

Example 2

Obtaining 2-hydroxy-5,6-difluorobenzonitrile

a) Obtaining 2-methoxy-5,6-difluorobenzaldehydoxime

A mixture of 16.0 g of hydroxylamine hydrochloride, 18.9 g of sodium acetate and 110 ml of 90% aqueous methanol was dropped under stirring at 20-25 ° C a solution of 29.4 g of 2-methoxy- 5,6-difluorobenzaldehyde (according to example 27 of WO 97/03071). After 16 hours of stirring, after evaporation of methanol, kneading with 250 ml of water, washing and drying, 28.3 g of the desired product were obtained with a melting point of 199-201 C.

b) Obtaining 2-methoxy-5,6-difluorobenzonitrile

20 drops of dimethylformamide were added to a suspension of 18.7 g of the product obtained according to

a) in 100 ml of toluene, and 16.6 g of thionyl chloride were added, ensuring that the temperature did not rise above 30 C. After 4 hours of stirring at 30 C, evaporation of toluene and thionyl chloride in In vacuo, 16.5 g of the desired product was isolated as an oil. NMR (CDCl3) ppm:

3.9 s (3H), 6.65-6.75m (1H), 7.3-7.45m (1H).

c) Obtaining 2-hydroxy-5,6-difluorobenzonitrile

To a solution of 23.0 g of the product obtained according to b) in 70 ml of toluene at 50 ° C, under stirring, 21.7 g of AlCl3 were added in portions. Once the addition had ended, it was heated under reflux for 2 hours. After cooling, the reaction mixture was poured into 350 ml of water, and brought to a pH value of 1 with 2n HCl. The crude product thus obtained was extracted with tert-butylmethylether (2 x 100 ml), and purified by dissolution in 2n NaOH (2 x 80 ml) and acidified from the alkaline phase with 2n HCl to pH 5. After extraction with tert-butylmethyl ether (2 x 80 ml), dried and evaporation of solvent, were isolated

19.9 g of the desired product as an oil. NMR (CDCl3) ppm: 6.45 s, br (1H); 6.7-6.8 m (1H); 7.25-7.4 m (1H).

Example 3

Efficacy against mildew of wheat

Wheat sprouts leaves of the "Frühgold" species grown in pots with an aqueous preparation of active principle, which was made from a mother solution consisting of 10% of active principle, 63% of cyclohexanone and a 27% emulsifying agent, and 24 hours after drying the spray layer was dusted with spores of wheat mildew (Erysiphe graminis f. Sp. Tritici). The test plants were then placed in the greenhouse at temperatures between 20 and 22 ° C, and at 75 to 80% relative air humidity. After 7 days, the mildew development measure was determined visually in percentage of total leaf surface.

The plants treated with the active principles I.3, I.6, I.7, I.8, I.9, I.11, I.12 and I.27 of table 1 with aqueous preparation of active principle that contained 63 ppm did not show any attack, while the untreated plants were 80% attacked.

Example 4

Efficacy against mildew of wheat

Wheat sprouts leaves of the "Fruühgold" species grown in pots with an aqueous preparation of active principle, which was made from a mother solution consisting of 10% of active principle, 63% of cyclohexanone and a 27% emulsifying agent, and 24 hours after drying the spray layer was dusted with spores of wheat mildew (Erysiphe graminis f. Sp. Tritici). The test plants were then placed in the greenhouse at temperatures between 20 and 22^°C, and 75 to 80% relative humidity of the air. After 7 days, the measurement of mildew development was visually determined in percentage of total leaf surface.

The plants treated with the active principles II.1 and II.3 of table 2 did not show any attack, while the untreated plants were 80% attacked.