EA011230B1 - Optically active carboxamides and use thereof to combat undesirable microorganisms - Google Patents

Abstract

Novel optically active carboxamides of formula (1)wherein R, M and A have the meanings cited in the description.There described several methods for the production of said substances and the use thereof to combat undesirable microorganisms, in addition to novel intermediate products and the production thereof.

Description

This invention relates to new optically active carboxamides, to several methods for their preparation and to their use for combating unwanted microorganisms.

It is known that many carboxamides have fungicidal properties (see, for example, XVO 03/010149, νθ 02/059086, νθ 02/38542, νθ 00/09482, ΌΕ-Α-10229595, EP-A-0591699, EP-A- 0589301 and EP-A-0545099). So known, for example, the racemates of 5-fluoro-1,3-dimethyl-L- [2- (1,3,3-trimethylbutyl) phenyl] -1H-pyrazole-4-carboxamide from νθ 03/010149 and I- [2 - (1,3-dimethylbutyl) phenyl] -2-iodobenzamide from ΌΕ-Α 102 29 595. The effectiveness of these substances is good, but with small expenditures, it is not always sufficient.

In connection with the multilateral requirements for modern pest control products, for example, the magnitude of the effect, duration of action, spectrum of action, spectrum of use, toxicity, the possibility of combining with other biologically active substances, the possibility of combining with excipients used in the preparation of preparations, or with regard to synthesis, and in connection with the possible onset of stability (resistance), it can be argued that the creation of such substances can never be considered rshennym and there is a constant demand for new compounds that, at least on certain aspects of offer advantages with respect to known compounds.

New optically active carboxamides of the formula (I) have been discovered

where B means hydrogen, fluorine, chlorine, methyl, ethyl or trifluoromethyl, M means

M-1

# # #

M-2 M-3 M-4, wherein the bond labeled * is bonded to the amide, while the bond labeled # is linked by an alkyl side chain, B ¹ is hydrogen, fluoro, chloro, methyl or trifluoromethyl,

where B ² means methyl, trifluoromethyl or difluoromethyl, B ³ means hydrogen, fluorine or chlorine or

where B ⁴ means trifluoromethyl, chlorine, bromine or iodine, or A means a radical of the formula (Α3)

where B ⁵ means methyl, trifluoromethyl or difluoromethyl.

The compounds of formula (I) have an 8-configuration [with 8 labeled C-atom in formula (I)].

It was further found that optically active carboxamides of the formula (I) can be obtained if

a) carboxylic acid derivatives of the formula (II)

where A has the meanings given above, and

X ¹ means a halogen or hydroxy group, to be reacted with an amine of the formula (III)

where B and M have the meanings given above,

- 1 011230

if necessary in the presence of a catalyst, if necessary in the presence of a condensing agent, if necessary in the presence of an acid binding agent and, if necessary, in the presence of a diluent, or

b) racemic compounds of the formula (1-rac) ^CH 3

A N (1-wound), n sn _e cn ₃ where I, M and A have the meanings given above, chromatographed on a chiral stationary silica gel phase in the presence of an eluent or a mixture of eluents as a liquid phase or crystallized fractionally with optically active acids to form salts and finally enantiomerically pure or enriched compounds of formula (I) release, or

c) compounds of formula (IV)

where I, M and A have the meanings given above, or the compounds of formula (V)

where I, M and A have the meanings given above, or the mixtures of these two compounds are hydrogenated in the presence of an optically active catalyst, respectively, of a catalyst with optically active ligands.

Finally, it was found that the new optically active carboxamides of formula (I) have very good microbicidal properties and can be used to combat undesirable microorganisms both in plant protection and in material protection.

The new optically active carboxamides of the formula (I) differ from the known carboxamides primarily in their improved action, respectively, reduced consumption, and therefore less environmental impact and less toxicity.

The optically active carboxamides according to this invention are generally described by formula (I). The following are preferred radical values in the formulas above or below. These radical values are true both for the final products of formula (I), and equally for all intermediate products.

I preferably mean hydrogen, methyl or ethyl.

I more preferably mean hydrogen or methyl.

M preferably means M-1.

M, in addition, preferably means M-2.

M, in addition, preferably means M-3.

M, in addition, preferably means M-4.

M more preferably means M-1, wherein I ¹ means hydrogen.

M, in addition, more preferably means M-2, and I means hydrogen.

I ¹ preferably means hydrogen.

I ¹ , in addition, preferably means fluorine, with fluorine more preferably standing in the 4, 5 or 6 position, even more preferably standing in the 4 or 6 position, most preferably standing in the 4 position of the anilide radical [see the above formula (I)].

A preferably means the radical A1.

And more preferably means A1, which means 5-fluoro-1,3-dimethyl-1H-pyrazol-4-yl, 3 trifluoromethyl-1-methyl-1H-pyrazol-4-yl or 3-difluoromethyl-1-methyl-1H- pyrazol-4-yl.

And even more preferably means A1, which means 5-fluoro-1,3-dimethyl-1H-pyrazol-4-yl.

And, in addition, preferably means the radical A2.

And more preferably means A2, which means 2-trifluoromethylphenyl or 2-iodophenyl.

And, in addition, preferably means a radical A3.

A, more preferably, means A3, which means 1,4-dimethylpyrazol-3-yl, 1-methyl-4 trifluoromethylpyrazol-3-yl or 1-methyl-4-difluoromethylpyrazol-3-yl.

And even more preferably means A3, which means 1-methyl-4-trifluoromethylpyrazol-3 yl.

I ² preferably means methyl or trifluoromethyl.

I ³ preferably means hydrogen or fluorine.

I ⁴ preferably means trifluoromethyl or iodine.

- 2 011230

I ⁵ preferably means trifluoromethyl.

The above general or preferred ranges of radicals, respectively explanations, can also be combined with each other, that is, between any areas and preferred areas in any way. They are valid for final products, as well as for starting and intermediate products, respectively.

The named values of the radicals can be combined with each other in any way. In addition, individual values may also occur.

Preferred, more preferred or even more preferred are compounds of formula (I) wherein the substituents have the meanings indicated as preferred, more preferred or even more preferred.

Explanation of methods and intermediates

Method (a)

If 1-methyl-4- (trifluoromethyl) -1H-pyrrole-3carbonyl chloride and {2 - [(18) -1,3,3-trimethylbutyl] phenyl} amine are used as starting materials, then the production method (a) according to this invention can be graphically represented

Derivatives of carboxylic acids used as starting materials in the implementation of the method (a) according to this invention are generally described by formula (II). In this formula (II), radical A has preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (I) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for the radical A. X is preferably chlorine, bromine or hydroxy, more preferably chlorine.

Derivatives of carboxylic acids of the formula (II) are known (see XVO 93/11117, EP-A-0545099, EP-A0589301 and EP-A-0589313).

Amines, also used as starting materials in the implementation of the method (a) according to this invention, are described in General terms by the formula (III). In formula (III), the radicals I and M have preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (I) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

Amines of formula (III) are new compounds.

Amines of formula (Sh-a)

where I has the meanings given above, M ¹ means M-1, get, for example, if

b) in the first stage, the aniline derivative of the formula (VI)

in ¹ (VI), where I ¹ has the meanings given above, are reacted with an alkene of formula (VII) in

CH ₃ sn ₃

(Vii)

H ₃ C where I have the meanings given above, in the presence of a catalyst, if necessary in the presence of a base and, if necessary, in the presence of a diluent, and the alkenaniline of the formula (VIII) thus obtained

- 3 011230 η ₂ ν

(VIII), where I and I ¹ have the meanings given above, are hydrogenated in the second stage, if necessary, in the presence of a diluent and, if necessary, in the presence of a catalyst, and the racemic derivative of aniline thus obtained of the formula (111-a-rac)

n

(111-a-rac) where I and I ¹ have the meaning given above, in the third step they are chromatographed on a chiral stationary silica gel phase in the presence of an eluent or a mixture of eluents as the liquid phase.

Hydrogenation of the compounds of formula (VIII) can be carried out if necessary and in the presence of an optically active catalyst, respectively, in the presence of a catalyst and an optically active ligand, and thereby optically active compounds of the formula (Sh-a) can be obtained.

Compounds of formula (ΙΙΙ-a-rac) can also crystallize fractionally in the presence of optically active acids during the formation of salts, after which enatiomerically pure or enantiomerically enriched compounds of formula (ΙΙΙ-a) can be obtained. In general, all optically active acids are suitable as acids in the formation of diastereomeric salts. An example is: (18) (+) - camphor-10-sulfonic acid, (1H) - (-) - camphor-10-sulfonic acid, 8.8 - (-) - tartaric acid, I, I- (+) - tartaric acid, I-lactic acid, 8-lactic acid or optically active amino acids, preferably natural optically active amino acids.

Used as starting materials in the implementation of the method (b) according to this invention, aniline derivatives are described in General terms by the formula (VI). In this formula (νΙ), the radical I ¹ preferably has the meanings which, in connection with the description of the compounds of the formula (Ι) according to this invention, are indicated as preferred, more preferred, respectively, even more preferred values for of this radical.

Aniline derivatives of the formula (νΙ) are known.

Alkenes, also used as starting materials in the implementation of the method (b) according to this invention, are described in general terms by the formula (νΙΙ). In this formula (νΙΙ), the radical I has preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (Ι) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for this radical.

Alkenes of the formula (νΙΙ) are known or can be obtained by known methods.

Alkenanilines, which in the process (b) according to the invention are obtained as intermediates, are described in general terms by the formula (νΙΙΙ). In this formula (νΙΙΙ), the radicals I and I ¹ have preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (Ι) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

Alkenanilines of the formula (νΙΙΙ) are known and / or can be obtained by known methods.

Amines of the formula (b-b)

sn _e sn ₃ (W-L), where I has the meanings given above, M ² means M-2, M-3 or M-4, you can get, for example, if

e) racemic amines of the formula (b-b-rac)

CH ₃ CH ₃ where I and M ² have the meanings given above, chromatographed on a chiral stationary silica gel phase in the presence of an eluent or

- 4 011230 mixture of eluents as a liquid phase.

Racemic amines of the formula (B-b-rac) are known and / or can be obtained by known methods (see, for example, No. 02/38542, EP-A-1036793 and EP-A-0737682).

Method (b)

The racemic compounds used as starting materials in the implementation of the method (b) according to this invention are described in General terms by the formula (1-rac). In this formula, the radicals B, M and A have preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (I) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

The racemic compounds of formula (1-rac) used in the implementation of method (b) according to this invention are known and can be obtained by known methods (see, for example, No. 0 03/010149, No. 0 02/38542 and ΌΕ-Α-10229595 ) Racemic compounds of formula (1-rac) can be obtained, for example, if derivatives of carboxylic acids of formula (II) are reacted with racemic compounds of formulas (ΙΙΙ-a-rac) or (ΙΙΙ-b-rac) by analogy with method (a) according to this invention.

In the implementation of the method (b) according to this invention work according to methods of preparative chromatography, preferably by methods of liquid chromatography high resolution (GHUR). In this case, a chiral stationary silica gel phase is used. Especially proved to be good for the separation of compounds of the formula (Ι-rac) on both enantiomers of chiracel 0Ό®. This separation material is commercially available. Other stationary phases can also be used as material for chromatography.

If compounds of the formula (Ι-rac) must be separated by fractional crystallization into individual optically active compounds, then all optically active acids are generally suitable for the formation of diastereomeric salts. As an example, mention should be made of: (18) - (+) - camphor-10-sulfonic acid, (1B) - (-) - camphor-10-sulfonic acid, 8.8 - (-) - tartaric acid, B, B- ( +) tartaric acid, B-lactic acid, 8-lactic acid or optically active amino acids, optically active naturally occurring amino acids are preferred.

Method (s)

If Y- [2- (1,3-dimethylbut-1-en-1-yl) phenyl] -5-fluoro-1,3dimethyl-1H-pyrazole-4-carboxamide, hydrogen and one optically active are used as starting materials the catalyst, the implementation of the method (C) according to this invention can be graphically represented in the form of the following diagram:

The compounds used as starting materials in the implementation of the method (C) according to this invention are described in General terms by the formula (Ιν) and (V). In these formulas, the radicals B, M and A preferably have, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (Ι) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

Compounds of formula (Ιν) and (V) (or a mixture of these compounds) are obtained if

D) derivatives of carboxylic acids of the formula (ΙΙ)

where A has the meanings given above, and

X ¹ means a halogen or hydroxy group, is reacted with either an alkenaniline of the formula (νΙΙΙ)

where B and B ¹ have the meanings given above, or with alkenaniline of the formula (ΙΧ)

- 5 011230

where I and I ¹ have the meanings given above, if necessary in the presence of a catalyst, if necessary in the presence of a condensing agent, if necessary in the presence of an acid binding agent, and if necessary in the presence of a diluent, or

d) carboxamides of the formula (X)

where M and A have the meanings given above, and Υ means bromine or iodine, is reacted with an alkene of formula (VII)

ns - '^^ sn, where I has the meanings given above, or with an alkene of the formula (XI) (VII), (XI), where I has the meanings given above, in the presence of a catalyst, if necessary in the presence of a base and if necessary in the presence of a diluent.

Derivatives of carboxylic acids of the formula (II), used as starting materials in the implementation of the method (I) according to this invention, are known and already described in connection with method (a).

Alkenanilines of formula (VIII), also used as starting materials in the implementation of method (I) according to this invention, are known and have already been described above in connection with method (b).

Alkenanilines, alternatively used as starting materials in the implementation of the method (I) according to this invention, are described in General terms by the formula (IX). In this formula (IX), the radicals I and I ¹ have preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (I) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

Alkenanilines of formula (IX) are known and / or can be obtained by known methods.

Carboxamides used as starting materials in the implementation of the method (e) according to this invention are described in General terms by the formula (X). In this formula (X), the radicals M and A have preferably, more preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (I) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

Carboxamides of the formula (X) are known and / or can be obtained by known methods (see \ UO 03/010149).

Alkenes of the formula (VII), also used as starting materials in the implementation of method (e) according to this invention, are known and have already been described in connection with method (b).

Alkenes, alternatively used as starting materials in the implementation of the method (e) according to this invention, are described in General terms by the formula formula (XI). In this formula (XI), the radical I has preferably, respectively, even more preferably those values which, in connection with the description of the compounds of formula (I) according to this invention, have been indicated as preferred, more preferred, respectively, even more preferred values for these radicals.

Alkenes of formula (XI) are known or can be obtained by known methods.

Reaction conditions

As a diluent in the implementation of methods (a) and (I) according to this invention, all inert organic solvents are suitable. These preferably include aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons

- 6 011230 such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or tri-chloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2 diethoxyethane or anisole, or amides, such as Ν, Ν-di- methylformamide, Ν, Ν-dimethylacetamide, Ν methylformanilide, Ν-methyl-pyrrolidone or hexamethylphosphoric triamide.

Methods (a) and (1) according to this invention are carried out, if necessary, in the presence of a suitable acid acceptor. As such, all conventional inorganic or organic bases are suitable. These preferably include hydrides, hydroxides, amides, alcoholates, acetates, carbonates and bicarbonates of alkaline earth and alkali metals, such as, for example, sodium hydride, sodium amide, sodium methylate, sodium ethylate, potassium tert-butylate, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate or ammonium carbonate, as well as tertiary amines such as trimethylamine, triethylamine, tributyl amine, Ν, Ν-dimethyl ilin, Ν, Νdimetilbenzilamin, pyridine, Ν-methylpiperidine, Ν-methylmorpholine, Ν, Ν-dimethylaminopyridine, diazabicyclooctane (lavo), diazabicyclononene (ΌΒΝ) or diazabicycloundecene (ΌΒυ).

Methods (a) and (1) according to this invention are carried out, if necessary, in the presence of a suitable condensing agent. As such, all conventional condensing agents used for such amidation reactions are suitable. Examples include acid halide forming substances such as phosgene, phosphorus tribromide, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride or thionyl chloride; anhydride forming agents such as ethyl chloroformate, methyl chloroformate, isopropyl chloroformate, isobutyl chloroformate or methanesulfonyl chloride; carbodiimides, such as Ν, Ν'-dicyclohexylcarbodiimide (OSS), or other conventional condensing agents, such as phosphorus pentoxide, polyphosphoric acid, Ν, Ν'-carbonyldiimidazole, 2ethoxy-Y-ethoxycarbonyl-1,2-dihydroquinoline (ΕΕΌΡ), triphenyl phosphine / carbon tetrachloride or bromotripyrrolidinophosphonium hexafluorophosphate.

Methods (a) and (1) according to this invention are carried out, if necessary, in the presence of a catalyst. Examples include 4-dimethylaminopyridine, 1-hydroxybenzotriazole or dimethylformamide.

The reaction temperature during the implementation of methods (a) and (1) according to this invention can vary in a wide range. As a rule, operate at a temperature of from 0 to 150 ° C., More preferably at a temperature of from 0 to 80 ° C.

When carrying out the method (a) according to this invention, to obtain 1 mol of the carboxylic acid derivative of the formula (II), 0.2-5 moles are generally taken per mole of the carboxylic acid derivative, more preferably 0.5-2 moles of the aniline derivative of the formula (III).

To implement the method (1) according to this invention for the preparation of compounds of formulas (IV) and (V), 0.2-5 moles are generally taken per mole of the carboxylic acid derivative of the formula (II), more preferably 0.5-2 moles of alkenaniline of the formula ( Viii) or (ix).

In each case, all conventional inert organic solvents, as well as mixtures thereof, or also mixtures thereof with water, are suitable as eluents in the implementation of method (b) according to the invention. If necessary, halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane; dichloromethane, chloroform; alcohols such as methanol, ethanol, propanol; nitriles such as acetonitrile; esters such as methyl or ethyl ester of acetic acid. More preferably, aliphatic hydrocarbons such as hexane or heptane are used, and alcohols such as methanol or propanol, most preferably n-heptane and isopropanol, or mixtures thereof, are used.

The reaction temperature during the implementation of method (b) according to this invention in each case can vary in a wide range. Usually operate at a temperature of from 10 to 60 ° C, more preferably at a temperature of from 10 to 40 ° C, most preferably at room temperature.

In the implementation of the method (b) according to this invention, as a rule, a one percent solution of the racemic compound (Praz) is used for chromatographic separation. However, other concentrations may be used. Processing is carried out in the usual way. Usually they act in such a way that the eluent is substantially distilled off, the solid components are filtered off and dried after washing with n-heptane. The residue, if necessary, is chromatographically purified from possible impurities. In this case, mixtures of n-hexane, respectively, cyclohexane and ethyl acetate, the composition of which is suitable for the corresponding compound to be cleaned, are used as an eluent.

All inert organic solvents are suitable as a diluent in the first stage of the process (b) according to this invention, as well as the method (e) according to this invention. These preferably include nitriles, such as acetonitrile, propionitrile, n- or isobutyronitrile or benzonitrile, or amides, such as Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetamide, Ν

- 7 011230 methylformanilide, Ν-methylpyrrolidone or hexamethylphosphoric triamide.

The first stage of method (b) according to this invention, as well as method (e) according to this invention is carried out, if necessary, in the presence of a suitable acid acceptor. As such, all conventional inorganic or organic bases are suitable. These preferably include hydrides, hydroxides, amides, alcoholates, acetates, carbonates or bicarbonates of alkaline earth and alkali metals, such as, for example, sodium hydride, sodium amide, sodium methylate, sodium ethylate, potassium tert-butylate, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate or ammonium carbonate, as well as tertiary amines such as trimethylamine, triethylamine, tributyl amine, Ν, Ν-dimeti aniline, Ν, Ν-dimethylbenzylamine, pyridine, Ν-methylpiperidine, Ν-methylmorpholine, Ν, Ν-dimethylaminopyridine, diazabicyclooctane (ΌΛΒΟΘ), diazabicyclononene (ΌΒΝ) or diazabicycloundecene (ΌΒυ).

The first stage of method (b) according to this invention, as well as method (e) according to this invention is carried out in the presence of one or more catalysts. Palladium salts and complexes are particularly suitable for this. Palladium chloride, palladium acetate, tetrakis (triphenylphosphine) palladium or bis- (triphenylphosphine) palladium chloride are suitably suitable. The palladium complex can also be created in the reaction mixture when the palladium salt and complex ligand are separately fed into the reaction. As ligands, organophosphorus compounds are preferably meant. Examples include triphenylphosphine, tri-o-tolylphosphine, 2,2'-bis (diphenylphosphino) 1,1'-binaphthyl, dicyclohexylphosinbiphenyl, 1,4-bis (diphenylphosphino) butane, bisdiphenylphosphineferrocene, di (tert-butylphosphino) biphenyl, di- (cyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2'Ν, Ν-dimethylaminobiphenyl, tricyclohexylphosphine, tri-tert-butylphosphine. However, ligands can also be neglected.

The first stage of method (b) according to this invention, as well as method (e) according to this invention, is further carried out, if necessary, in the presence of another (other) metal salt, such as a copper salt, for example copper iodide (1).

The reaction temperature in the implementation of the first stage of method (b) according to this invention, as well as method (e) according to this invention can vary in a wide range. Generally operate at a temperature of from 20 to 180 ° C., More preferably at a temperature of from 50 to 150 ° C.

In the first step of the process (b) according to the present invention, for the production of an alkenaniline of the formula (VIII), 1-5 moles are generally taken per mole of the aniline derivative of the formula (VI), more preferably 1-3 moles of the alkene of the formula (VII).

When carrying out the method (e) according to this invention, for the preparation of compounds of the formula (IV) and (V), 1 mol of carboxamide of the formula (X) is taken, as a rule, from 1 to 5 mol, more preferably from 1 to 3 moles of the alkene of the formula (VII) ) or (XI).

All inert organic solvents are suitable as a diluent in the implementation of method (c) according to this invention, as well as for the second stage (hydrogenation) of method (b) according to this invention. These include preferably aliphatic or alicyclic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane or decalin; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane or 1,2 diethoxyethane; alcohols such as methanol, ethanol, n- or iso-propanol, n-, iso-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, mixtures thereof with water or clear water.

The second stage (hydrogenation) of method (b) according to this invention is carried out in the presence of a catalyst. As such, all catalysts that are commonly used for hydrogenation are suitable. Examples include Raney nickel, palladium, ruthenium or platinum, if necessary, on a solid support such as, for example, activated carbon.

Chiral hydrogenation in the implementation of method (c) according to this invention, as well as in the implementation of method (b) is carried out in the presence of optically active ligands. An example is the combination of (K, K.) - Me-OiRyo8 / KiS1 ₂ ® or (8, §) -Me-OiRyo8 / KiS1 ₂ ® (depending on the desired enantiomer).

Hydrogenation in the second stage of method (b) according to this invention can be carried out not in the presence of hydrogen, but by combining the catalyst with triethylsilane.

The reaction temperature during the implementation of method (c) according to this invention, as well as the second stage of method (b) according to this invention can vary over a wide range. As a rule, they work at a temperature of from 0 to 150 ° C, more preferably at a temperature of from 20 to 100 ° C.

The method (c) according to this invention, as well as the second stage of the method (b) according to this invention is carried out at a hydrogen pressure of from 0.5 to 200 bar, more preferably from 2 to 50 bar, most preferably from 3 to 10 bar.

- 8 011230

In the case of the third stage (b) according to the invention, respectively, according to the method (e) according to the invention, all conventional inert organic solvents, as well as mixtures thereof or, if necessary, mixtures with water, are suitable as eluents. If necessary, halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane; dichloromethane, chloroform; alcohols such as methanol, ethanol, propanol; nitriles such as acetonitrile; esters such as methyl or ethyl ester of acetic acid. More preferably aliphatic hydrocarbons such as hexane or heptane are used, and alcohols such as methanol or propanol, even more preferably n-heptane and isopropanol, or mixtures thereof, are used.

The reaction temperature in the implementation of the third stage of method (b) according to this invention, respectively, of method (e) according to this invention can be varied in a wide range. As a rule, they work at a temperature of from 10 to 60 ° C, more preferably at a temperature of from 10 to 40 ° C, most preferably at room temperature.

When implementing the third step of method (b) according to this invention, respectively, method (e) according to this invention, as a rule, an approximately one percent solution of the racemic compound (β-α-rac), respectively, (III-β-rac) is used for chromatographic separation ) However, other concentrations are also possible. Processing is carried out in the usual way. Usually it is done in such a way that the eluate is distilled off to a large extent, the solid components are filtered off and dried after washing with n-heptane. The residue, if necessary, is purified chromatographically from possible impurities. In this case, mixtures of n-hexane, respectively, cyclohexane and ethyl acetate, which composition is selected in each case for the compound to be purified, are used as eluents.

Unless otherwise specified, all methods according to this invention are typically carried out at normal pressure. However, it is also possible to work under reduced and elevated pressures — generally at pressures from 0.1 to 10 bar.

The substances according to this invention exhibit strong microbicidal activity and can be used to combat undesirable microorganisms, such as fungi and bacteria, in protecting plants and in protecting materials.

Fungicides are used in plant protection to control plasmodioforomycetes (P1akshobyur1yugotuyes1s5). oomycetes (Ooshuss1s5). chitridiomycetes (Syu1pbyushus1ek), cygomycetes (2udoshuss1s5). Ascomycetes (Lksoshusyek), Basidiomycetes (Vak1byushus1ek) and Deuteromycetes (Osschosusjek).

Bactericides are used in plant protection to control pseudomonasaceae (Rkeibosopasaceae), rhizobiaceae (Vychoceceae), enterobacteriosis (Epiloeraceaeaceae), and corynebacteriothecaeae (Sogupeacidaeaceaeaceae).

As an example, but not limited to, we can name some pathogens of fungal or bacterial diseases that fall under the generic concepts listed above:

species of the xanthomonas genus (HapLoshopak), such as, for example, HapLoshopak sashrek ρν. Deafening species of the pseudomonas genus (Rkeiboshopak), such as, for example, Rkeiboshopak kuppdae ρν. 1asigushapk; species of the Erwinia genus (Ertsha), such as, for example, Er \\ 'yia upshtoga;

species of the genus pitium (Ru1ishish), such as, for example, Ruishsh and Shshish;

species of the phytophthora genus (RyuFryYoga), such as, for example, RNuYurYNoga shGek1apk;

species of the genus pseudoperonospore (Rkeiboregopocroga), such as, for example, Rkeiboregopocrooga yishii or Rkeiboregopocroga siepepk;

species of the plasmopara genus (P1akshoraga), such as, for example, P1akshoraga t111co1a;

species of the genus Bremia (Vgesh1a), such as, for example, Vgesh1a 1ac1isae;

species of the genus Peronospore (Regopokrog), such as, for example, Regopokrogrog or R. ак gakkuaye;

species of the genus erisife (Eguyrye), such as, for example, Eguyrye dgashsh;

Species of the genus sphero-library (8ryegoLesa), such as, for example, 8ryego1esa giNdshea;

species of the genus podosphere (Robocryaega), such as, for example, Robocryaega 1eiso1psya;

species of the genus venturia (Uep1ila), such as, for example, UepShpa shaes. | IAK;

species of the genus Pirenophore (Rugeporyoga), such as, for example, Rugeporyoga 1gek or R. Ogashshaa (conidia form: Drexler, syn: helminthosporium);

species of the genus cochliobolus (Sosyuyuoik), such as, for example, Sosyuyuoikik kabtik (conidia form: Drexler, syn: helminthosporium);

species of the genus uromitses (Igoshusek), such as, for example, Igoshusek arrepb1si1a1ik;

species of the genus puccinia (Risschsha), such as, for example, Rhyschsha Hesopbya;

species of the genus sclerotinia (8s1go11sha), such as, for example, 8s1egobsha kskgobogish;

species of the genus tillecium (TSheba), such as, for example, TSheba sapek;

species of the genus Ustilago (Ikshado), such as, for example, Ikshado Piba or Ikshado Atepae;

species of the genus pelicularia (ReshsShapa), such as, for example, Reshsi1apa kakakp;

species of the genus pyricularia (Rupsi lapa), such as, for example, Rupsi lapa oguhae;

- 9 011230 species of the genus Fusaria (Bikatsht), such as, for example, Bicalit sintogit;

species of the genus Botritis (VojuIk), such as, for example, Vojuik stethea;

species of the genus septoria (ZerYula), such as, for example, ZerYula will run;

species of the genus leptosphere (Epococcus aureus), such as, for example, Apocynidae;

species of the genus Tserkospor (Segsokrog), such as, for example, Segsokrog sapeksepk;

species of the genus Alternaria (Ayetpapa), such as, for example, Ayetpapa gakkuaye;

species of the pseudocercosporella genus (Rkeibosetsocrotea 11a), such as, for example, Rkeibosetsocroteia 1gro1ls1yuyek;

species of the genus rhizoctonia (Vykhososha), such as, for example, Vykhosusha koash.

Biologically active substances according to this invention also show a strong strengthening effect on plants. Therefore, they are suitable for mobilizing the plant's own defenses against damage by unwanted microorganisms.

Under the substances that strengthen (form resistance) plants, it is understood in this connection those substances that are able to stimulate the plant's defense system in such a way that treated plants, upon subsequent inoculation with undesirable microorganisms, show good resistance to these microorganisms.

In this case, undesirable microorganisms should be understood as phytopathogenic fungi, bacteria and viruses. Therefore, the substances according to this invention can be used to protect plants for a certain period of time after treatment from damage by these pathogens. The period of time during which protection is achieved generally lasts from 1 to 10 days, preferably from 1 to 7 days after treatment of plants with biologically active substances.

Good tolerance by plants of biologically active substances in concentrations that are necessary for combating plant diseases allows the processing of aboveground parts of plants, plants and seeds and soil.

Moreover, the biologically active substances according to this invention can be used with particularly good success in controlling diseases of cereal plants, for example, species of the genus Puccinia (Risasha), and diseases found in viticulture, horticulture and vegetable growing, such as, for example, species of the genus botritis (Vojuik), species of the genus venturia (UeShila) or species of the genus alternaria (Ajetpapa).

Biologically active substances according to this invention are also suitable for increasing the size of the crop. In addition, they have minimal toxicity and are well tolerated by plants.

Biologically active substances according to this invention can also be used, if necessary, in certain concentrations and expendable amounts as herbicides, to affect plant growth, as well as to control animal pests. They can also be used, if necessary, as intermediates and starting materials for the synthesis of other biologically active substances.

According to this invention, it is possible to treat whole plants or parts of plants. Moreover, a plant is understood to mean all plants and plant populations, such as desirable and undesirable wild and cultivated plants (including naturally occurring cultivated plants). Crop plants can be plants that can be obtained by traditional methods of cultivation and optimization, or by methods of biotechnology and genetic engineering, or a combination of these methods, including transgenic plants and including plant varieties protected and unprotected by law for the protection of varieties. Plant parts should be understood as all the aboveground and underground parts and organs of plants, such as the shoot (shoot), leaf, flower and root, which include, for example, leaves, needles, stems, trunks, flowers, fruits and seeds, as well as roots, tubers, rhizomes. Parts of the plant also include the commercial product of the crop, as well as vegetative and generative propagation material, for example, cuttings, tubers, rhizomes, cuttings and seeds.

The treatment according to this invention of plants or parts of plants with a combination of biologically active substances occurs directly or by affecting their environment, habitat or storage facilities by conventional methods, for example by dipping, spraying, steaming, spraying, dispersing, applying, spraying, and in case material for propagation, especially seeds, by forming single or multi-layer shells on them.

The substances of this invention can be used to protect technical materials from damage or destruction by undesirable microorganisms.

Under technical materials should be understood in this regard, non-living materials that are prepared for use in technology. For example, technical materials that must be protected from microbial alteration or destruction can be adhesives, adhesives, paper and cardboard, textiles, leather, wood, paints and plastics, lubricants, coolants and other materials that may be affected by microorganisms or destroyed by them. As part of the materials to be protected, also parts of production

- 10 011230 installations, for example water cooling circuits, which can be damaged due to the multiplication of microorganisms. In the framework of the present invention, adhesives, adhesives, paper and cardboard, textiles, leather, wood, paints, cutting fluids and heat transferring fluids, especially preferably wood, should be mentioned as technical materials.

As microorganisms that can cause the destruction or alteration of technical materials, mention should be made, for example, of bacteria, fungi, yeast, algae and mucus organisms. Mostly the biologically active substances according to this invention act on fungi, especially mold fungi, staining and wood-destroying fungi (basidiomycetes), as well as on mucus organisms and algae.

It is worth mentioning, for example, the microorganisms of the following genera: alternaria (AIetapa), species such as AIetapa 1epsh8, aspergillus (AkregdShik), species such as AkregdShik shdeg, hetomyum (Sye1ot1it), such species as Syeolosomidae, species such as Soshyryogia! apa, lentinus (BepIpik), species such as BepIpik Idgshik, penicillium (Reshexpus), species such as Reshpicus dlaiisish, polyporus (Poruliidae), species such as Roporogidae ursuosobioge ), of species such as Acereosum rts11ts1ap8, sclerophoma (8c1egoriosha), such as ides such as 8c1egoryut rjuorya, trichoderma (Tisynta), species such as Tisynta utbe, Escherichia (Excepsoa), species such as Excepsoi pseudomonas (Rkeibotopocapophytae, 81) like 81arNu1osossi5 aigeyik.

Biologically active substances, depending on their respective physical and / or chemical properties, can be converted into conventional formulations and preparations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, microcapsules in polymeric substances and shell coatings for coating seed material, as well as formulations for obtaining IBU (ultra-small volume) - cold and warm fog.

These formulations and preparations are prepared by conventional methods, for example, mixing biologically active substances with fillers, i.e. with liquid solvents, pressurized liquefied gases and / or solid fillers, if necessary with the use of surfactants, i.e. emulsifiers and / or dispersants and / or foaming agents. In the case of using water as a filler, for example, organic solvents can be used as an auxiliary solvent. As liquid solvents, mainly suitable are: aromatic compounds such as xylene, toluene, or alkylnaphthalenes, chlorinated aromatic compounds and chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethenes or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffinic hydrocarbons, for example petroleum fractions, alcohols, such as butanol or glycol, also their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl iso-butyl ketone or cyclohexanone, highly polar races voriteli such as dimethylformamide or dimethyl sulphoxide, and also water. By liquefied gaseous fillers or carriers is meant liquids which are gaseous at ordinary temperatures and normal pressure, for example, aerosol working gases, such as halocarbons, as well as butane, propane, nitrogen and carbon dioxide. As solid fillers, for example, natural rock flour, such as kaolin, clay, talc, quartz, chalk, attapulgite, montmorillonite or diatomaceous earth, and synthetic hard rock flour, such as finely divided silicic acid, alumina and silicates, are suitable. As solid fillers for granules are suitable: for example, crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite, dolomite and synthetic granules from inorganic and organic flour, as well as granules from organic materials such as sawdust, coconut shells, corn cobs and tobacco stalks. Suitable emulsifying and / or foaming agents are, for example, nonionic and anionic emulsifiers, such as fatty acid and polyoxyethylene ethers, fatty alcohol and polyoxyethylene ethers, for example alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, as well as protein hydrolysates. Suitable dispersing agents are, for example, lignin sulfate spent solutions and methyl cellulose.

In the formulations and preparations, adhesion improvers, such as carboxymethyl cellulose, natural and synthetic powdery, granular or latex-like polymers, such as gum arabic, polyvinyl alcohol, polyvinyl acetate, and natural phospholipids, such as cephalin and lecithin, and synthetic, can be used. Other additives may be mineral and vegetable oils.

Dyes such as inorganic pigments, for example, iron oxide, oxide can be used.

- 11 011230 titanium, ferrocyanine blue, and organic dyes, such as alizarin, azo and metal phthalocyanine dyes and nutritional microcomponents, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

Formulations and preparations generally contain from 0.1 to 95% by weight of biologically active substances, preferably from 0.5 to 90% by weight.

The biologically active substances according to this invention can be used as such or in their formulations and preparations, as well as in mixtures with known fungicides, bactericides, acaricides, nematicides or insecticides in order, for example, to expand the spectrum of action or prevent the development of resistance. In many cases, a synergistic effect is obtained, i.e. the effectiveness of the mixture is higher than the sum of the efficiencies of the individual components.

The following compounds are suitable as partners for mixtures.

Fungicides

2-phenylphenol; 8-hydroxyquinoline sulfate; acibenzolar-8-methyl; aldimorph; amidoflumet; ampropylphos; ampropylphos-potassium; andoprim; anilazine; azaconazole; azoxystrobin; benalaxyl; benodanil; benomyl; bentiavalicarb-isopropyl; benzamacryl; benzamacryl isobutyl; bilanafos; binapacryl; biphenyl; bitertanol; blasticidin-8; bromukonazole; bupirimate; butiobate; butylamine; calcium polysulfides; capsimycin; captafol; captan; carbendazim; carboxin; carpropamide; carvone; quinomethionate; chlobenthiazone; chlorphenazole; Chloroneb; chlorothalonil; chlozolinate; closilacon; cyazofamide; cyflufenamide; cymoxanil; cyproconazole; cyprodinil; ciprofuram; dagger 6, debacarb; dichlorofluanide; dichlon; dichlorophen; diclocimet; diclomesine; dicloran; dietofencarb; diphenoconazole; diflumetorim; dimethyrimol; dimetomorph; dimoxystrobin; diniconazole; diniconazole-M; dinocap; diphenylamine; dipyrithione; ditalymphos; dithianon; to the bottom; drazoxolone; edifenfos; epoxyconazole; etaboxam; etirimol; etridiazole; famoxadone; fenamidone; fenapanil; fenarimol; fenbuconazole; fenfuram; phenhexamide; phenitropane; phenoxanyl; fenpiclonil; fenpropidin; fenpropimorph; ferbes; fluazinam; flubenzimine; fludioxonil; flumeover; flumorph; fluoromide; fluoxastrobin; fluquinconazole; flurprimidol; flusilazole; flusulfamide; flutolanil; flutriafol; folpet; fosetil-A1, fosetil-sodium; fuberidazole; furalaxyl; furametpir; furcarbanil; furmecyclox; guazatin; hexachlorobenzene; hexaconazole; gimexazole; imazalil; imibenconazole; iminoctadine triacetate; iminoctadine tris (albesil); iodocarb; ipconazole; iprobenfos; iprodione; iprovalicarb; irumamycin; isoprothiolane; isovaledione; kazugamitsin; kresoxim-methyl; mankozeb; maneb; meferimzone; mepanipyrim; Mepronil; metalaxyl; metalaxyl-M; metconazole; metasulfocarb; metfuroxam; metira; metominostrobin; Metsulfovax; mildiomycin; myclobutanil; myclozoline; natamycin; nicobifen; nitrotalizopropyl; noviflumuron; noirimol; Ofurace oryzastrobin; oxadixyl; oxolinic acid; oxpoconazole; oxycarboxine; oxyfentinine; paclobutrazole; pefurazoate; penconazole; pencicuron; fosdifen; phthalide; picoxystrobin; piperaline; polyoxins; polyoxorim; probenazole; chloraz; procymidone; propamocarb; propanosine sodium; propiconazole; propineb; proquinazide; prothioconazole; pyraclostrobin; pyrazophos; pyrifenox; pyrimethanil; pyroquilone; pyroxyfur; pyrrolnitrin; quinconazole; quinoxifene; Quintocene; simeconazole; spiroxamine; sulfur; tebuconazole; teclofthalam; teknazene; tetcyclacis; tetraconazole; thiabendazole; tiziofen; tiflusamide; thiophanate methyl; tiram; thioximide; tolclophos methyl; tolylfluanide; triadimephone; triadimenol; triazbutyl; triazoxide; tricycamide; tricyclazole; tridemorph; trifloxystrobin; triflumisole; triforin; triticonazole; uniconazole; validamycin A; vinclozolin; zineb; ziram; zoxamide; (28) -Y- [2- [4 - [[3- (4-chlorophenyl) -2propinyl] oxy] -3-methoxyphenyl] ethyl] -3-methyl-2 - [(methylsulfonyl) amino] butanamide; 1 - (1-naphthalenyl) -1H-pyrrole-2,5-dione; 2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine; 2-amino-4-methyl-Y-phenyl-5thiazolecarboxamide; 2-chloro-Y- (2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl) -3-pyridinecarboxamide; 3,4,5-trichloro-2,6-pyridinedicarbonitrile; actinovate; cis-1- (4-chlorophenyl) -2- (1H-1,2,4-triazol-1-yl) cycloheptanol; methyl 1- (2,3-dihydro-2,2-dimethyl-1H-inden-1-yl) -1H-imidazole-5-carboxylate; potassium hydrogen carbonate; Y- (6-methoxy-3-pyridinyl) cyclopropanecarboxamide; Y-butyl-8- (1,1-dimethylethyl) -1 oxaspiro [4.5] decan-3-amine; sodium tetratiocarbonate; as well as copper salts and copper preparations, such as Bordeaux fluid; copper hydroxide; copper naphthenate; copper oxychloride; copper sulfate; kufraneb; copper oxide; mancopper; copper oxide.

Bactericides

Bronopol; dichlorophen; nitrapirine; nickel dimethyldithiocarbamate; kasugamycin; octilinone; furancarboxylic acid; oxytetracycline; probenazole; streptomycin; teclofthalam; copper sulfate and other copper compounds.

Insecticides / Acaricides / Nematicides:

1. Inhibitors of acetylcholinesterase (LS11E)

1.1 carbamates (for example, alanicarb, aldicarb, aldoxycarb, allixicarb, aminocarb, azamethiphos, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxyme, butoxycarboxy, carbaryl, ethanofarbenocarbenofenocarbenofenocarbenofarbene , formethanate, furatiocarb, isoprocarb, metham sodium, methiocarb, methomil, metolcarb, oxamyl, pyrimicarb, promecarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb,

- 12 011230

HMS, xylylcarb).

I. 2 Organophosphates (for example, acephate, azamethiphos, azinphos (-methyl, -ethyl), bromofos-ethyl, bromphenvinphos (-methyl), butathiophos, cadusafos, carbofenotion, chloroethoxyphos, chlorphenvinphos, chlormephos, chlorpyrilethyl-(-meth) , coumaphos, cyanofenphos, cyanophos, chlorfenvinphos, demethone-8methyl, demethone-8-methylsulfone, dialiphos, diazinon, dichlorofention, dichlorvos / ΌΌνΡ, dicrotofos, dimethoate, dimethylbenzofosfofof, diulfabenzofosfofof, diulfabenzofosfofof, diulfabenzofosfofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, diofenfosfofofof, dyfofenfosfofofof, diofenfosfofofof, diofenfosfofofof, dyfonfosfofofof, , fenitrotion, fensulfotion, fenthion, flupirazofos, phonophos, formion, phosme ilyan, fostiazate, heptenophos, iodophenphos, iprobenfos, isazophos, isofenfos, isopropyl O-salicylate, isoxathion, malathion, mekarbam, methacryphos, methamidophos, methidation, mevinphos, monocrotofos, oleth-methylmetho-methylethomethone-omethylmethomethone ), fentoate, forate, fosalone, phosphate, phosphamidone, phosphocarb, foxime, pyrimifos (-methyl / ethyl), profenofos, propaphos, propetamphos, prothiophos, protoate, pyraclofos, pyridafention, pyridathion, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos, quinulfofos , temefos, terboufos, tetrachlorvinphos, thiometon, triazofo s, triclorphone, vamidotion).

2. Sodium channel modulators / voltage-dependent sodium channel blockers

2.1 Pyrethroids (e.g. acrinatrin, allethrin (b-cis-trans, b-trans), beta-cyfluthrin, bifentrin, bioallertrin, bioallethrin-8-cyclopentyl isomer, bioethanometrin, biopermetrin, bioresmetrin, chloaportrin, cis-cypermethrin resmetrin, cis-permethrin, clocitrin, cycloprotrin, cyfluthrin, cygalotrin, cypermethrin (alpha, beta, theta, zeta), cifenotrin, ΌΌΤ, deltamethrin, empentrin (1Kizomer), esfenvalerate, etofenprox, fenfrinprin, fenfrinprin, fenfrinprin, fenfrinprin, fenfrinthrin, fenfrinthrin fenvalerate, flucrocytinate, flucytrinate, flufenprox, flumetrin, fluvalinate, fubfenprox, gamma-cygalotrin, imiprotrin, cadetrin, lambda-cygalotrin, metoflutrin, permethrin (cis-, trans-), phenotrin (1K-trans isomer), pralletrin, proflutrin, protrifenbute, pyresmethrin, resmetrin, KP 15525, silafluofen, taut-fluwa teflutrin, tetralletrin, tetramethrin (1K isomer), tralometrin, transfluthrin, ΖΧΙ 8901, pyrethrins (pyrethrum)).

2.2 Oxadiazines (e.g. indoxacarb).

3. Acetylcholine receptor agonists / antagonists

3.1 Chloronicotinyls / neonicotinoids (e.g. acetamipride, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid, thiamethoxam).

3.2 Nicotines, bensultap, cartap.

4. Acetylcholine Receptor Modulators

4.1 Spinosins (e.g. spinosad).

5. OABA (gamma-aminobutyric acid) -controlled chloride channel antagonists

5.1 Cyclodienes organochlorins (e.g. campechlor, chlordane, endosulfan, gamma-HCH, HCH, heptachlor, lindane, methoxychlor).

5.2 Fiproles (e.g., acetoproles, etioproles, fipronil, vanilliproles).

6. Activators of the chloride channel

6.1 Mectins (e.g., abamectin, avermectin, emamectin, emamectin-benzoate, ivermectin, milbemectin, milbemycin).

7. Juvenil hormone mimetic (for example, diophenolane, epophenonane, phenoxycarb, hydroprene, kinoprene, metoprene, pyriproxifene, triprene).

8. Ecdysagonists / Ruptures

8.1 Diacylhydrazines (e.g. chromaphenosides, halophenosides, methoxyphenosides, tebufenosides).

9. Chitin biosynthesis inhibitors

9.1 Benzoylureas (e.g. bistrifluuron, chlorofluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluuron, teflubenzuron), trifl.

9.2 Buprofesin.

9.3 Cypromazines.

10. Oxidative phosphorylation inhibitors, ATP-breakers

10.1 Diafentiuron.

10.2 Organotins (e.g. azocyclotin, cyhexatin, fenbutatin oxide).

II. Oxidative phosphorylation breakers through interruption of the H-proton gradient

11.1 Pyrroles (e.g. chlorfenapyr).

11.2 Dinitrophenols (e.g. binapacryl, dinobuton, dinocap, ΌΝΘΟ).

12. Site-1 electron transfer inhibitors

12.1 Series ΜΕΤΙ (for example, phenazaquin, fenpiroximate, pyrimidiphene, pyridaben, tebufenpyrad, tolfenpyrad).

12.2 Hydramethylnones.

12.3 Dicofol.

13. Site-11-electron transfer inhibitors

13.1 Rotenones.

- 13 011230

14. Inhibitors of site-III-electron transfer

14.1 Acequinocyl, fluacripyrim.

15. Microbial destruction of the membrane of the intestines of insects

Strains VasShik 11shppshchepk1k.

16. Fat synthesis inhibitors

16.1 Tetronic acids (e.g. spirodiclofen, spiromesifen).

16.2 Tetric acids [eg 3- (2,5-dimethylphenyl) -8-methoxy-2-oxo-1-azaspiro [4.5] dec-3-en-4-yl-ethyl carbonate (otherwise: carboxylic acid, 3- (2,5-dimethylphenyl) -8-methoxy-2-oxo-1azaspiro [4.5] dec-3-en-4-yl-ethyl ether, CA8-Ved.-Yo .: 382608-10-8) and carboxylic acid , cis-3 (2,5-dimethylphenyl) -8-methoxy-2-oxo-1-azaspiro [4.5] dec-3-en-4-yl ethyl ether (CA8-Ved.-Yo .: 203313-25 -one)].

17. Carboxamides (for example, flonicamide).

18. Octopaminergic agonists (eg, amitraz).

19. Inhibitors of magnesia-stimulated ATPase (for example, propargite).

20. Phthalamides (for example, N- [1,1-dimethyl-2- (methylsulfonyl) ethyl] -3-iodine-N- [2-methyl-4- [1,2,2,2tetrafluoro-1- (trifluoromethyl) ethyl] phenyl] -1,2-benzene dicarboxamide (CA8-Ved.-Yo: 272451-65-7).

21. Analogues of nereistoxin (for example, thiocyclam hydrooxalate, thiosultap sodium).

22. Biology, hormones or pheromones (for example, azadirachtin, VasShik kres, Veiuye Da kres, codlemone, Mayitus khres, Raesbotusek kres, turinguensin, UegDsSht kres).

23. Biologically active substances with unknown or nonspecific mechanisms of action.

23.1 Carbonating (fumigating) agents (e.g. aluminum phosphide, methyl bromide, sulfuryl fluoride).

23.2 Selective eat-on inhibitors (e.g. cryolites, flonicamide, pymetrozine).

23.3 Tick growth inhibitors (e.g. clofentazine, ethoxazole, hexithiazox).

23.4 Amidoflumet, benclothiaz, benzoximate, biphenazate, bromopropylate, buprofesin, quinomethionate, chlorodimeform, chlorobenzylate, chloropicrin, clotiazoben, cycloprene, dicyclanil, phenoxenone methylene chloride, flubenzin-azimonjenoxymene, flubenzin-azimenoniminone potassium oleate, pyridinyl, sulfulfuramide, tetradiphon, tetrasul, triaratene, verbutin, then the compound 3-methylphenylpropylcarbamate (tsumacide Ζ), the compound 3- (5-chloro-3-pyridinyl) -8- (2,2,2-trifluoroethyl) - 8-azabicyclo [3.2.1] octane-3-carbonite sludge (CA8-Ved.-No. 185982-80-3) and the corresponding 3-endo isomer (CA8-Ved.-No. 185984-60-5) (see νθ 96/37494, νθ 98/25923), as well as preparations that contain insecticidal extracts of plants, nematodes, fungi or viruses.

A mixture with other known biologically active substances, such as herbicides, or with fertilizers and growth regulators, protective substances or chemicals, is also possible.

Moreover, the compounds of formula (I) according to this invention have very good antifungal properties. They have a very wide spectrum of antifungal effects, especially against dermatophytes and sprouting fungi, molds and diphasic fungi (for example, against candida species (Saib1ba), such as Sapba | as well as ErkegtoryUp Dossokit, aspergillus species (AkregdSik), such as AkregdSik shdeg and AkregdSik итt1da1ik, trichophyton species (Tgkoruy! The enumeration of these mushrooms is in no way a limitation of the covered spectrum of mushrooms, but has only an explanatory character.

Biologically active substances can be used as such, in the form of their formulations and preparations or working forms prepared from them, such as ready-to-use solutions, suspensions, powders for spraying, pastes, soluble powders, means for pollination and granules. The application takes place in the usual way, for example by pouring, spraying, spraying, foaming, spreading, etc. Next, you can add a biologically active substance by the method of IIa-Eo \\ - Va1ite (ultra-small volumes) or inject a formulation with a biologically active substance or biologically active substance into the soil. You can also process the seeds of plants.

When using the biologically active substances according to this invention as fungicides, the expendable amounts, depending on the application method, can vary over a wide range. When processing parts of plants, the expendable amounts of the biologically active substance are in the range from 0.1 to 10,000 g / ha, preferably from 10 to 1000 g / ha. In the processing of seed material, the expendable amounts of biologically active substance generally lie in the range from 0.001 to 50 g per 1 kg of seed material, preferably from 0.01 to 10 g per 1 kg of seed material. When processing the soil, the expendable amounts of the biologically active substance are in the range from 0.1 to 10,000 g / ha, preferably from 1 to 5,000 g / ha.

As already mentioned above, according to the present invention, it is possible to treat plants in whole or in part. In a preferred embodiment of the invention, wild-caught or obtained by traditional biological growing methods, such as

- 14 011230 crossing or fusion of protoplasts, plant species and plant varieties, as well as their parts. In another preferred embodiment, transgenic plants and plant varieties are processed that are obtained by genetic engineering, if necessary in combination with traditional methods (genetically modified organisms) and parts thereof. The concept of parts and parts of plants was explained above.

Particularly preferably, according to the invention, plants are processed according to standard commercial quality or cultivars in use. A plant variety is understood to mean plants with new properties (Tyke), which are grown using both traditional growing methods and mutagenesis or recombinant DNA technologies. It can be varieties, breeds, bio and genotypes.

Depending on the species or varieties of plants, their location and growing conditions (soil, climate, growing season, nutrition), superadditive (synergistic) effects may also occur as a result of processing according to this invention. So, for example, it is possible to reduce the amount of consumption, and / or to expand the spectrum of exposure, and / or to increase the efficiency of the substances and means used according to this invention, better plant growth, increased tolerance to dryness or to the content of water and salts in the soil, increased flowering productivity , facilitating harvesting, accelerating ripening, increasing the size of the crop, improved quality and / or increased nutritional value of the crop product, increased storage stability and / or workability that exceed actually the expected effects.

Preferred transgenic plants (obtained using genetic engineering technologies) processed according to this invention are plants or plant varieties that include all plants obtained by genetic engineering modifications of the genetic material, which have given these plants particularly advantageous valuable properties (Ttabk). Examples of such properties are better plant growth, increased tolerance to high or low temperatures, increased tolerance to dryness or to the content of water and salts in the soil, increased flowering productivity, facilitated harvesting, accelerated ripening, increased crop size, improved quality and / or increased nutritional value of the crop product, increased storage stability and / or workability of the crop product. Other and particularly prominent examples of such properties are increased plant protection against animals and microbial pests such as insects, ticks, phytopathogenic fungi, bacteria and / or viruses, as well as increased plant tolerance to certain herbicidal biologically active substances. As an example of transgenic plants, important cultivated plants are mentioned, such as cereals (wheat, rice), corn, soybeans, potatoes, cotton, tobacco, rape, and fruit plants (with fruits such as apples, pears, citruses and grapes), especially corn, soybeans, potatoes, cotton, tobacco and rapeseed. As properties (Tayk), the increased protection of plants from insects, arachnids, nematodes, and gastropods (snails) is especially emphasized with the help of toxins formed in plants, especially those that are produced in plants by means of genetic material from youShik T1shppschep 818 (for example, through genes Cg1A ( a) Sti1A (b), CiuO1A (c), Ciu11A, Ciu111A, Ciu111B2, Ciu9c, Ciu2Ai, CiuSiV and CiuiR, as well as their combinations) (hereinafter Βΐ-plants). As properties (Tyke), the increased resistance of plants to fungi, bacteria, and viruses is also emphasized due to systemic acquired resistance (YauCHsshbsnS Ax. | Shpeg1e ΡοδίδΙοηχ, 8AB), systemin, phytoalexin, eliticoren, and resistance genes and corresponding proteins and toxins. As properties (Tyke), the increased plant tolerance to certain herbicidal biologically active substances, for example, imidazolinones, sulfonylureas, glyphosate or phosphinotricin (for example, the PAT gene), is especially emphasized. Genes that confer the corresponding desired properties (Tyke) in transgenic plants can occur in combination with each other. Examples of plants include corn, cotton, soy and potato varieties sold under the trade names ΥΙΕΕΌ SAKO® (for example, corn, cotton, soy), Kposkoi! ® (for example, corn), 81 atl® (for example, corn), Vo11dagb® (cotton), Shsoyup (cotton) and No. \\ EsaG® (potato). Examples of herbicide-tolerant plants include maize, cotton, and soybean varieties sold under the trade names Coipbir Keabu® (glyphosate tolerance, for example corn, cotton, soybean), Liuu bshk® (tolerance to phosphinotricin, such as rape, 1) (imidazolinone tolerance) and 8T8® (sulfonylurea tolerance, such as corn). As herbicide-resistant plants (usually grown on tolerance to herbicides), mention should be made of varieties that are sold under the name C1eatie1b® (for example, corn). Needless to say, these statements are also valid for varieties that will be developed in the future and will appear in the future on the market of plant varieties with these or new properties developed in the future (Tyke).

Said plants can be particularly preferably treated with compounds of the general formula (I) or mixtures of biologically active substances according to the invention. The preferred ranges indicated above for biologically active substances or mixtures are also valid for

- 15 011230 processing of these plants. Especially preferred is the treatment of plants with compounds or mixtures specifically indicated in this text.

The preparation and use of biologically active substances according to this invention is described in the following examples.

Compounding Examples

Example 1

(+/-) - N- [2- (1,3-dimethylbutyl) phenyl] -5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (200 mg) was dissolved in 25 ml of n-heptane / isopropanol 9: 1 (v / v = volume / volume). In conclusion, the solution is chromatographed using a chiralcell ΘΌ® fractionated silica gel phase [manufacturer: Οαίοοί (Japan), column sizes: 500 mm x 40 mm (inner diameter), particle sizes: 20 μm, flow rate: 40 ml / min] with n- heptane / isopropanol 9: 1 (v / v) as eluent according to the principle of high-performance liquid chromatography (HPLC). To separate the entire amount, 30 ml of a racemate are fed to the column every 30 minutes. The detection of compounds is carried out using a UV detector at a wavelength of 210 nm. After analytical testing for enantiomeric purity, the eluate fractions are respectively collected together, the solvent is distilled off as much as possible under vacuum, the residues are filtered off and dried after washing with n-heptane. The crude product thus obtained was purified on silica gel (solvent: n-hexane / ethyl acetate, 1: 9 1: 4, in each case v / v).

87 mg of Y- {2 - [(18) -1,3-dimethylbutyl] phenyl} -5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide are obtained (melting point 52-54 ° C, specific coefficient rotation [a] _c = +6.7, c = 0.87; methanol, 20 ° C, its value = 99%).

The enantiomeric purity of the carboxamides of formula (I) is determined using analytical GHUR under the following conditions: separating phase: chiralcell ΘΌ® (company Οαίοοί. Japan); 5 μm, column: 250 mm x 4.6 mm (inner diameter), eluting agent: n-heptane / 2-propanol 10: 1, flow rate: 0.5 ml / min, UV detector: 210 nm.

Analogously to example 1, and also in accordance with the instructions of the General description of the method receive are given in table. 1 compounds of formula (I).

Table 1 ₍₁₎ n ⁿ sn ₃ sn _e

Example No. IN m BUT Lodine P (pH 2.3) Specific rotation coefficient [<x] ₀ its meaning 2 SNZ _and x “P 3,55 -5.2 (s = 0.7; CHC1 ₃ ; 20 ° C) 99% 3 n BUT ά 4.10 - 8.8 (s = 0.7; CHC1 ₃ ; 20 ° C) 99%

- 16 011230

Example No. TO m BUT Lodine P (pH 2.3) Specific Rotation Ratio [αίο its purpose 4 n ¥ ά 4.12 - 5.0 (s = 0.9; CHC1 ₃ ; 2C ° C) 97% 5 n ¥ sn ₃ 3.60 + 4.3 (c = 0.3; CHzON; 20 ° C) 95% 6 n ¥ ¥ sn ₃ 3.83 -4.0 (c = 0.5; CHzON; 20 ° C) 99%

Determination of the 1odR values given in the preceding tables and in the examples for the preparation of compounds is carried out in accordance with the instruction EEC-E1gesbue 79/831 Appech ν.Α8 using HPLC (high-performance liquid chromatography) on a phase reversal column (C 18). Temperature: 43 ° C.

The determination is carried out in the acidic region at pH 2.3 with 0.1 percent aqueous phosphoric acid and acetonitrile as eluent; linear gradient from 10% acetonitrile to 90% acetonitrile.

Calibration is carried out using unbranched alkan-2-ones (with 316 carbon atoms) for which 1odP values are known (determination of 1odP values is carried out based on retention times by linear interpolation between two consecutive alkanones).

Lambda max values are determined using UV spectra in the region of 200-400 nm at the maximum of the chromatographic signal.

Application examples

Example A. Robocrbaega test (apple tree) / protective

Solvent: 24.5 parts by weight acetone, 24.5 parts by weight dimethylacetamide.

Emulsifier: 1 part by weight alkyl aryl polyglycol ether.

To prepare a suitable formulation of a biologically active substance, 1 weight is mixed. including biologically active substances with the indicated amounts of solvent and emulsifier and dilute the concentrate with water to the desired concentration.

To test the protective activity, young plants are sprayed with the indicated consumable amounts of a biologically active substance preparation. After drying of the plaque from spraying, the plants are inoculated with an aqueous suspension of spores of the powdery mildew pathogen Robokrbaega 1eiso1ps11a. After this, the plants are placed in a greenhouse at a temperature of about 23 ° C and a relative humidity of about 70%.

10 days after inoculation, an assessment occurs. In this case, 0% means an efficiency that corresponds to the effectiveness of the control, while an efficiency of 100% means that no damage is observed.

- 17 011230

Biologically active substance

Consumable amount of biologically active

Table A. Test for Roboaryaega (apple tree) / protective percentage

Effectiveness in

12.5 98

12.5 28

Example B. Test for 8ryeogyesa (cucumbers) / protective.

Solvent: 24.5 parts by weight acetone, 24.5 parts by weight dimethylacetamide.

Emulsifier: 1 part by weight alkyl aryl polyglycol ether.

To prepare a suitable formulation of a biologically active substance, 1 weight is mixed. including biologically active substances with the indicated amounts of solvent and emulsifier and dilute the concentrate with water to the desired concentration.

To test the protective activity, young plants of cucumbers are sprayed with the indicated consumable amounts of a biologically active substance preparation. After drying of the plaque from spraying, the plants are inoculated with an aqueous suspension of spores of sproutidae yiidtea. After this, the plants are placed in a greenhouse at a temperature of about 23 ° C and a relative humidity of about 70%.

7 days after inoculation, an assessment occurs. In this case, 0% means an efficiency that corresponds to the effectiveness of the control, while an efficiency of 100% means that no damage is observed.

- 18 011230

Table B. Test for 8r11asgo111sea (cucumbers) / protective

- 19 011230

Biologically active substance

According to the invention

Expense quantity Effective biologically nost in active percent substances in g / ha

Experience for comparison:

85

fifteen

According to the invention:

3,125 98

3,125 35

Example C. Test for νοηΐιιπα (apple tree) / protective.

Solvent: 24.5 parts by weight acetone, 24.5 parts by weight dimethylacetamide.

Emulsifier: 1 part by weight alkyl aryl polyglycol ether.

To prepare a suitable formulation of a biologically active substance is mixed 1

- 20 011230 weight. including biologically active substances with the indicated amounts of solvent and emulsifier and dilute the concentrate with water to the desired concentration.

To test the protective activity, young plants are sprayed with the indicated consumable amounts of a biologically active substance preparation. After drying of the plaque from spraying, the plants are inoculated with an aqueous conidia suspension of the apple scab causative agent νοηΐιιπο еци еци и и and left for one day in an incubation booth at a temperature of about 20 ° C and a relative humidity of 100%.

After this, the plants are placed in a greenhouse at a temperature of about 21 ° C and a relative humidity of about 90%.

10 days after inoculation, an assessment occurs. In this case, 0% means an efficiency that corresponds to the effectiveness of the control, while an efficiency of 100% means that no damage is observed.

Table C. Test for νοηΐιιπο (apple tree) / protective

Biologically active substance according to the invention

Consumable amount of biologically active substance in g / ha

Percentage Efficiency

According to the invention:

one hundred

According to the invention:

one hundred

- 21 011230

- 22 011230

Expense active quantity Effective biologically nost in > real estate active percent substances in g / ha

Example Ό. Test for Woogui§ (beans) / protective.

Solvent: 24.5 parts by weight acetone, 24.5 parts by weight dimethylacetamide.

Emulsifier: 1 part by weight alkyl aryl polyglycol ether.

To prepare a suitable formulation of a biologically active substance, 1 weight is mixed. including biologically active substances with the indicated amounts of solvent and emulsifier and dilute the concentrate with water to the desired concentration.

To test the protective activity, young plants are sprayed with the indicated consumable amounts of a biologically active substance preparation. After drying of the plaque from spraying, two small pieces of agar are grown on each leaf, overgrown with B1u05 sshegea. Inoculated plants are placed in a darkened chamber at a temperature of about 20 ° C and a relative humidity of 100%.

2 days after inoculation, the size of the lesion spots on the leaves is evaluated. In this case, 0% means an efficiency that corresponds to the effectiveness of the control, while an efficiency of 100% means that no damage is observed.

- 23 011230

Table Ό. НаοΐΓνΐίδ Test (Beans) / Protective

- 24 011230

Example E. Test for AIetapa (tomato) / protective.

Solvent: 24.5 parts by weight acetone, 24.5 parts by weight dimethylacetamide.

Emulsifier: 1 part by weight alkyl aryl polyglycol ether.

To prepare a suitable formulation of a biologically active substance, 1 weight is mixed. including biologically active substances with the indicated amounts of solvent and emulsifier and dilute the concentrate with water to the desired concentration.

To test the protective activity, young plants are sprayed with the indicated consumable amounts of a biologically active substance preparation. After drying of a raid from spraying races

- 25 011230 tenii are inoculated with an aqueous suspension of AIspapa spores δοϊαηί. Plants are placed in an incubation booth at a temperature of about 20 ° C and a relative humidity of 100%.

3 days after inoculation, an assessment occurs. In this case, 0% means an efficiency that corresponds to the effectiveness of the control, while an efficiency of 100% means that no damage is observed.

Table E. Test for AIgspapa (tomato) / protective

Biologically active substance according to the invention

Consumable amount of biologically active substance in g / ha

Efficiency in percent of the invention:

According to

Claims (8)

CLAIM 1. Optically active carboxamides of formula (I) where K denotes hydrogen, fluorine, chlorine, methyl, ethyl or trifluoromethyl, M means the bond labeled with * is linked to amide, while the bond labeled with # is linked with an alkyl side chain, K ^{* 1} means hydrogen, fluorine, chlorine, methyl or trifluoromethyl, A means a radical of formula (A1) where K ² means methyl, trifluoromethyl or difluoromethyl, K ³ means hydrogen, fluorine or chlorine, or A means a radical of formula (A2) where K ⁴ means trifluoromethyl, chlorine, bromine or iodine, or A means a radical Formula (A3) - 26 011230 where I ⁵ means methyl, trifluoromethyl or difluoromethyl. 2. Optically active carboxamide formula (I) according to claim 1, in which I mean hydrogen, methyl or ethyl, M means M-1 or M-2, I ¹ means hydrogen, fluorine, chlorine, methyl or trifluoromethyl, I ² means methyl or trifluoromethyl, I ³ means hydrogen or fluorine, I ⁴ means trifluoromethyl or iodine, I ⁵ means trifluoromethyl. 3. The method of obtaining optically active carboxamide formula (I) according to claim 1, characterized in that a) carboxylic acid derivatives of the formula (II) o D. _X 1 (II), A 'where A has the meanings given in claim 1, and X ¹ means a halogen or hydroxy group, is reacted with an amine of formula (III) where I and M have the meanings given in claim 1, if necessary in the presence of a catalyst, if necessary in the presence of a condensing agent, if necessary in the presence of an acid binding agent, and if necessary in the presence of a diluent, or B) racemic compounds of the formula (1-rats) where I, M and A have the meanings given in claim 1, are chromatographed on a chiral stationary silica gel phase in the presence of an eluent or mixture of eluents as a liquid phase, or fractionally crystallized with optically active acids with salt formation and, in conclusion, enantiomerically pure or enriched compounds of formula (I) are released, or c) compounds of formula (IV) where I, M and A have the meanings given in paragraph 1, or compounds of the formula (V) where I, M and A have the meanings given in claim 1, or mixtures of both compounds are hydrogenated in the presence of optically active catalyst, respectively, a catalyst with optically active ligands. 4. Means for combating undesirable microorganisms, characterized in that it contains at least one optically active carboxamide of formula (I) according to claim 1, along with fillers and / or surface-active substances. 5. The use of optically active carboxamides of the formula (I) according to claim 1 for the control of undesirable microorganisms. 6. A method of controlling undesirable microorganisms, characterized in that optically active carboxamides of formula (I) according to claim 1 are applied to said microorganisms and / or their habitats. - 27 011230 7. A method of obtaining agents for controlling undesirable microorganisms, characterized in that the optically active carboxamides of formula (I) according to claim 1 are mixed with fillers and / or surface-active substances. 8. Amines of formula (III) (III), where I and M have the meanings given in paragraph 1.