CS208456B2 - Fungicide means and method of making the active substances - Google Patents

Abstract

1. A-zolyl-1-fluorophenoxy-butane derivatives of the general formula see diagramm : EP0009707,P10,F1 in which A represents a keto group or a CH(OH) group, B represents a nitrogen atom or a CH group and Y represents chlorine or bromine, and their physiologically acceptable salts.

Description

The invention relates to novel 1-azolyl-1-fluoroenoxybutane derivatives, to a process for their preparation and to their use as fungicides.

It is already known, ie derivatives of 1-jzo0yl chlopetloxybutanu-1, such as 4-chlH'-1- (4-chlorophenoxy-3,3-L dimettyl-1- (1-yl) and - (imda? _JC ^ l ^^^ l-ll.Уbu1 N ^ 2 ^ and 4-lн bгoIm1 - ((4Chhooreeoly) _-3> Зз _d-l ^ mt Thl-1- (imidazol-1-yl) butan-2 They exhibit good fungicidal properties (see DOS Nos. 26 32 602 and DOS 26 32 603) However, the good effect of these substances, in particular when applied in lower quantities and concentrations, is not entirely satisfactory.

We have found novel derivatives of 1-halogenated-1-azzOyl fUl0feoloxybutaou _s formula I

(I) in which

A represents a ketOcapsule or a group CH (OH),

B represents a nitrogen atom or a CH group

Y is a halogen atom, and a physiologically tolerable salt thereof.

These compounds have potent fungicidal properties.

Those compounds of formula I wherein A is CH (OH) contain two asymmetric carbon atoms and may therefore exist in the form of two geometric isomers (erythroe threo form), which may result in different proportions in their preparation. In both these cases, the compounds exist in the form of optical isomers. All isomers of the compounds of the invention are within the scope of the invention.

The halogenated 1-azolyl-1-fluorophenoxybutane derivatives of formula (I) above are obtained by reacting a bromoetherketone of formula (II)

O-CH-CO I Br

CH,

^13- c-ch ₂ y

CH ₃ in which

Y is as defined above, reacted with an azoler of formula III θ = Ί н - |

VZN (II) (III) wherein

In the presence of an acid binding agent and in the presence of a diluent, the abovementioned ketoderivative is reduced in a manner known per se by complex borohydrides, optionally in the presence of a diluent.

Furthermore, the halogenated 1-azolyl-1-fluorophenoxybutane derivatives obtained by the process of the invention can be converted into salts by reaction with acids.

Surprisingly, the active compounds according to the invention show considerably higher fungicidal activity, in particular against various powdery mildew species, than the known 1-azolyl-1-chlorophenoxybutane derivatives, such as 4-chloro-1- (4-chlorophenoxy) -3,3- dimethyl-1- (1,2,4-triazole- (imidazol-1-yl) butan-2-one and 4-bromo-1- (4-chlorophenoxy) -3,3-dimethyl-1- (imidazol-1) The compounds of the present invention are an enrichment of the prior art.

Among the compounds of formula (I) according to the invention, those in which Y represents a chlorine or bromine atom and A and V are as defined above are preferred.

If 1-bromo-4-chloro-3,3-dimethyl-1- (4-fluorophenoxy) butan-2-one and 1,2,4-triazole are used as starting materials, the reaction according to the invention can be described as follows: reaction scheme:

Even ^Нз O ^{+ H} / ^{B8 'of}

-O-CH-CO-C-CHoCl

II ²

Br CH ₃

-HBr

<f ^H 3

O-CH-CO-C-CH, Cl

I i ²

CH ₃

When used as a starting material 4-chloro-3 _J 3-dimethyl-1- (4-fluorophenoxy) -1- (1,2,4-triazol-1-yl) -butan-2-one and sodium borohydride are the the reaction sequence according to the invention can be described by the following reaction scheme:

F

CH ₃ I ³

O-CHI

CO-C-CHXI I ^Z CH ₃

The bromether ketones used as starting materials are generally defined by the above formula II. In this formula, Y is preferably a chlorine or bromine atom.

Bromether ketones of formula II are not yet known, but can be obtained in a known manner, for example by reacting fluorophenol with a bromoketone of formula IV? ^H 3 Br-CH ₂ -CO-C-CH ₂ Y (IV) wherein f is as defined above

The remaining active hydrogen atom is then replaced in a conventional manner by 2a bromine (see also examples).

Examples of starting materials of the formula II are:

1-Bromo-4-chloro- (4-fluorophenoxy) -3,3-dimethylbutan-2-one

1,4-dibromo- (4-fluorophenoxy) -3,3-dimethylbutan-2-ene.

Suitable salts of the compounds of the formula I are salts with physiologically compatible acids, which preferably include hydrohalic acids, such as hydrochloric and hydrobromic acids, in particular hydrochloric acid, furthermore phosphoric acid, nitric acid, mono- and dibasic carboxylic and hydroxycarboxylic acids, such as for example, acetic acid, citric acid, sorbic acid, lactic acid, and 1,5-naphthalenedisulfonic acid.

Suitable diluents for use in the process according to the invention are preferably inert organic solvents, which preferably include ketones such as diethyl ketone and in particular acetone and methyl ethyl ketone, nitrile such as propionitrile and especially acetonitrile, alcohols such as ethanol or isopropanol, ethers such as tetrahydrofuran or dioxane, aromatic hydrocarbons such as toluene, 1,3-dichlorobenzene and benzene, formamides such as especially dimethylformamide, and halogenated hydrocarbons such as inethylene chloride, carbon tetrachloride or chloroform.

The reaction is carried out in the presence of an acid binding agent. All conventional inorganic or organic acid acceptors, such as alkali metal carbonates, such as sodium carbonate, potassium carbonate and sodium bicarbonate, or tertiary alkylamines, cycloalkylamines or aralkylamines such as triethylamine, N, N-dimethylcyclohexylamine, dicyclohexylmethylamine and Ν, may be used. Ν-dimethylbenzylamine, followed by pyridine and diazabicyclooctane. An appropriate excess of the starting azole of formula III is preferably used as the acid acceptor.

The reaction temperatures of the process of the invention can be varied within wide limits. In general, the reaction is carried out at a temperature between about 0 ° C to 150 ° C, preferably at 60 ° C to 120 ° C.

In the process according to the invention, preferably 1 to 2 moles of azole and 1 to 2 moles of acid binding agent are used per mole of the compound of the formula (III). To isolate the compounds of formula (I), the solvent is distilled off, the residue is taken up in an organic solvent and the solution is washed with water. The organic phase is dried over sodium sulphate, freed from solvent by evaporation in vacuo and the crystals are purified by disinfection or recrystallization.

Suitable diluents for the reduction according to the invention are polar organic solvents which belong 'preferably alcohols such _meShanol> ethanol, butanol and II, isopropanol, and ethers, such as diethyl ether or TSTR ^^ ^ yer1furan. The reduction is generally carried out at a temperature of 0 to 30 ° C, preferably at a temperature of 0 to 20 ° C. In this case, 1 mol of borohydride, such as sodium borohydride or alcohol, is used per mole of the corresponding ketoderivative. To isolate the compounds of formula (I), the residue is taken up, for example with dilute hydrochloric acid, the solution is rendered alkaline and extracted with an organic solvent, or only water is added to the residue and the mixture is shaken with an organic solvent. Further processing is then carried out in the usual manner.

The active compounds according to the invention show a strong microbicidal action and can be used in practice to combat undesirable microorganisms. The active compounds described can be used as plant protection agents.

Fungicides are used in plant protection to combat fungi in the classes PlasmodiophorommccSes, Oooyccees, ChhCгieiomycctes, Zygommccees, Ascommccees, Basidiomycctes and DeuteromècSes.

Since the active substances are well tolerated at the concentrations used to control plant diseases, they can be used to treat above-ground parts of plants, seedlings, seeds and soil.

As plant protection agents, the active compounds according to the invention can be used with particular good results in combating Erysiphe species. It is advantageous that the active compounds according to the invention not only have a protective effect but are also systemically active. This efficacy makes it possible to protect the plants against fungal attack by delivering the active substance to the above-ground parts of the plants through the soil and the root system or through the seeds.

The active compounds can be converted into the customary formulations such as solutions, emulsions, suspensions, powders, foams, pastes, granulates, aerosols, natural and synthetic substances impregnated with the active compounds, small particles coated with polymeric substances and seed coatings, flammable additives such as smoke cartridges, smoke jars, smoke spirals and the like, as well as compositions in the form of concentrates of the active substance for cold or hot mist dispersion.

These compositions are prepared in known manner, for example by mixing the active ingredient with fillers, i.e. liquid solvents, with liquefied gases under pressure and / or solid and carrier substances, optionally using surfactants, i.e. emulsifiers and / or dispersants and / or cross-linking agents. reagents. If water is used as a filler, it is also possible to use, for example, organic solvents as co-solvents.

Substantially suitable liquid solvents are aromatics or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chlorides or meethylene enodides, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example petroleum fractions, alcohols, such as butanol or glycol, and their ethers and esters, ketones, such as acetone, MES hC ^ ^β 'thylket1n, meShhCit1iutclketon or cyclohexanone, strongly polar budget ^ ^ now, as dimethylfomamide and

20845β dimethylsulfoxide as well as water. Liquefied gaseous fillers or carriers are liquids which are gaseous at normal temperature and pressure, for example aerosol propellants such as halogenated hydrocarbons, as well as butane, propane, nitrogen and carbon dioxide.

Suitable solid carriers are: natural stone meal, such as kaolins, slumina, talc, chalk, quartz, stpspulgite, montmorillonite or silica, and synthetic stone meal, such as highly dispersed kernic acid, alumina with silicates. Suitable solid carriers for the preparation of granulites are crushed and fractionated natural stone materials such as limestone, marble, pumice, εβρίοϋΊ and dolomite, as well as synthetic granules from inorganic with organic flours and organic granules from organic granules. , such as sawdust, coconut shells, corn sticks with tobacco stems.

As emulsifiers' nrbo / foam-forming agents there UVSH nonionic with anionic rmmlgátory like after l ^ l ^ xy-biphenylcarbonitrile smears mostných acids, poly-alcohols etlhflrnethery mostných example _{slkylsrylpilyilykoietler>} slkylsllfitl'ty, slkylsuuféty, with protein hydrolysates, with a dispersants such as lignin, sulfide waste liquors with oerthrlcellulose.

The compositions of the invention may contain adhesives such as sodium methylcellulose, natural with synthetic powdered, granular or lexxic polymers such as gum arabic, polyvinyl alcohol with water-lacquate poles.

Further, these compositions may contain coloring agents such as inorganic pigments, for example iron oxide, titanium dioxide with fractionated blue, organic coloring agents such as mucosal dyes with metallic azo-fluxes, as well as trace elements, crumbs, crumbs, manganese, cobalt, molybdenum with zinc.

The substrates generally contain 0.1 to 95% by weight. preferably 0.5 to 90% by weight of the active ingredient can be used.

The active compounds according to the invention can be present in the formulations in admixture with other known active compounds, such as fungicides, insecticides, scaricides, neo-isocides, herbicides, avian antiseptics, growth agents, plant nutrients with soil improvers.

The active compounds according to the invention can be applied as such, in the form of concentrates or by further dilution of the application forms prepared therefrom, such as ready-to-use solutions, suspensions, suspensions, powders, granules pastes. The application is carried out in a conventional manner, for example by watering, dipping, spraying, fogging, evaporating, injecting, anointing, dusting, tossing, dry pickling, wetting, wetting or slurrying, or incrustation.

When the active ingredients are used for the treatment of the above-mentioned parts of plants, their concentrations in the applied compositions can be varied within a wide range. These concentrations generally lie between 1 and 0.000% by weight, preferably between 0.5 and 0.001% by weight.

In the treatment of seed, from 0.001 to 50 g, preferably from 0 to 10 g, of active compound are generally required per kilogram of seed. .

In the treatment of the soil, depending on the type of effect, the concentration of active compound is from 0.00001 to 0.1% by weight, preferably from 0.0001 to 0.02% by weight.

Example A

Test for Erysiphe graminis var. hordei (fusariosis) - treatment of plant shoots (mycosis destroying the leaves) - protective effect

To prepare a suitable active agent, 0.25 parts by weight of the active compound are mixed in 25 parts by weight of dimethylformamide and 0.06 parts by weight of the slkylaryl polyglycol ether as emulsifier, and 975 parts by weight of water are added. The resulting concentrate is then diluted with water to the desired final concentration.

To determine the protective effect, young barley plants (a single leaf stage species) are wetted with a pre-treatment proetnddker and, after drying, sprayed with spores of Erysiphe graminis var. Hordei.

After six days of growing the plants at a temperature of 21-22 ° C and 80-90% air humidity, the extent of the disease on the plants is evaluated. The degree of infestation is expressed as the percentage of infestation of the untreated control plants, with 0% indicating no infestation and 100% the same infestation as the untreated control plants. The lower the degree of attack, the more effective the test substance is.

Active substances, concentration of active substances in spraying and degree of attack are given in the following table:

Table A test for Erysiphe graminis (treatment of plant shoots) - Prtctive effect Active substance Infestation concentration in% napaCl

% SO3H of active ingredient in spray% wt.

0.00025 days of treated control plants

100 (known)

(known)

0.00025

37.5 _SO3 H

Cl

SO3H

0.00025

50.0 (known) active substance

F

CH, i *

O-CH-CO-C-CH, Cl

II ²

SO ₃ H concentration of the active substance in the spraying% wt.

0.00? · 5 infections in% of untreated control plants

10.0

Ex. D. B

Test for systemic action on powdery mildew (Erysiphe grami ^ is var. Hordei) - fungal disease of shoots

The active ingredient is used in the form of powdered seed dressings. This mordant is prepared by mixing the respective active ingredient with equal parts by weight of talc. and diatomaceous earth to a finely divided powder mixture containing the active ingredient in the desired concentration.

The barley seed is treated by shaking with pre-dressing in a closed glass container. The seed is then sown (3 x 12 grains) 2 cm deep into pots containing a mixture of one volume of standard peat soil and one volume of quartz sand. Germination and emergence of plants takes place under favorable conditions in the greenhouse. 7 days after planting, when the barley plants unfold their first leaf, they are dusted with fresh spores of Erysiphe graminis var. hordei and further cultured at temperatures of 21 to 22 ° C and 80 to 90% relative humidity of the air under intense light illumination daily. Typical powdery mildew spots are formed on the leaves of the plants within 6 days.

The degree of infestation is expressed as the percentage of infestations of the treated conspicuous plants, with 0% representing no infestation and 100% the same infestation as for non-green control plants. The more active the active substance, the lower the extent of the disease.

The active compounds, the active compound concentrations in the compositions, the consumption of the solvents and the percentage of the extent of the disease are given in the following table;

T a be 1 k a. B test for Erysiphe graminis var. hordei - systemic effect active substance

Cl

OH CH,

I 1 J

O-CH-CH-C-CH, Br

II ² concentration of active substance in cider (% w / w) Solvent consumption (g / kg seed) Spinning in% of infestation of untreated control plants

50.0 (known)

F

OH CH,

I I *

O-CH-CH-C-CH, Br I ^from CH ₃

3 '2,5

The preparation of the active compounds according to the invention is illustrated by the following non-limiting examples.

Peak 1 and cli

SO ₃ H g (0.177 mol) of 1-bromo-4-chloro-3,3'-dimethyl-1- (4-fluorophenoxy) butan-2-one is dissolved in 600 ml of absolute acetooiiril, 24.2 g (0.35 g) is added. mol) of 1,2,4-triazole and the mixture was refluxed for 6 hours. The solvent is distilled off in a water pump vacuum, the residue is taken up in 700 ml of meethlene chloride, the organic phase is extracted twice with 1.5 l of water each time and dried over sodium sulphate. The foam was removed in a water pump vacuum and the oily residue was taken up in 200 ml of acetone. 18 g (0.1 mol) of 1,5-naphthalenedisuironic acid dissolved in 100 ml of acetone are added to the solution and the precipitate formed is filtered off with suction.

47 g (55.7% of theory) of 4-chloro-3,3-dimethyl-hhl-11 (4-fluoro-oxo) -1- (1,2,4-4,44-azol-4-yl) -butane-424-n-4,5-nartalleditulrunate of melting point 200 DEG are obtained. C. »

Preparation of the starting material

CH ₃ .

F-O 2 -O-CH-CO-C-CH ₂ Cl

Br CH ₃

To a solution of 56 g (0.5 mol) of p-fluorophenyl and 85 g of potassium carbonate in 700 ml of acetone was added dropwise 100.2 g (0.617 mol) of 1,44-dichloro-3,4-dimethylbutane-24 -UN. The mixture was stirred at reflux for 6 hours, sucked off well and the solvent was distilled off. 101.5 g (63% of theory) of crude 4-chloro-43,34-dimethyl-4 (44-fluorophenoxy) -autan-44-one are obtained, which is dissolved in 600 ml of meethyenchloride θ and 66.3 g (0.415 mol) of bromine are added dropwise at room temperature. to blend the mixture. The reaction mixture is stirred for a further 30 minutes, then the solvent is removed in a water-jet vacuum and 100 ml of pentane are added to the residue, the residue crystallizes. 114 g (85% of theory) of 1-bromo-4- (4H, 4'-benzo-1- (4-fluorophenoxy) autan-4-one), m.p. 74 DEG C., are obtained.

'ch,

I ''

C 1 CH 2 -CO-C-CH 2 Cl

AND

CH ₃

050 g (7.8 mol) of 78% 4-chloro-3,3-dimethylautan-2-one are dissolved in 6 liters of methylene chloride and - 450 g of chlorine are introduced into the solution at 10 to 11 ° C over 6 hours. . The reaction mixture is stirred for a further 30 minutes, then excess hydrogen chloride is purged with nitrogen and the mixture is distilled through a 60 cm packed column. There are obtained 832 g (63% of theory) of 1,4-dichloro-3,3-dimethyl-buten-2-ene having a boiling point of 50-54 ° C / 13.3 Pa and a purity of 75%.

Example 2

To a solution of 25 g (0.053 mol) of 4-chloro-3,3-dimethyl-1 '(4-fluorophenoxy) -1- (1,2,4-triazol-1'-yl) butan-2-one nephthalenedisulfonate. (Example 1) 4.75 g (0.12 mol) of sodium borohydride were added in portions of 400 ml of methanol in portions, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was stirred at room temperature for 2 hours, then distilled off the solvent in half the volume in a water-jet vacuum, and evaporated to 400 ml of saturated sodium bicarbonate solution. The mixture was extracted with 300 ml of methylene chloride and the organic phase was separated, washed twice with 100 ml of water each time, dried over sodium sulfate and the solvent was removed by evaporation. 9.1 g (36.4% ttorite) of 4-chloro-3,3-imidazole-1- (4-fluorophosphorus) - (1- (1,2 _J 4-triazyl-11-yl) bitane) are obtained. M.p. 87-90 ° C.

In an analogous manner, the following compounds of Example A are prepared

F

CH ₃

I melting point (° C)

3 WHAT N Br 180 (x 1/2 NDS) 4 CHOH N Br 100 ALIGN! 5 WHAT CH Br 241 (x 1/2 NDS) 6 what CH Cl 254 (x 1/2 NDS) 7 CHOH CH Br 116 8 CHOH CH CL 115

Legend: NDS = 1,5-oaftaltniisiffonic acid.

Claims (2)

1. A fungicidal breast, containing as an active ingredient an altspon jtdtn derivative of 1-azolyl-1 &apos; A is C or CH (OH), B is N or CH and Ϊ denotes a salt of lΘlsgtni, or a physiologically salt thereof. 2. A process for the preparation of the active substances according to claim 1, characterized in that the brsmetherketso of formula II, O-CH-CO-C-CH ₉ y I 1 Br in which Y is as defined above, (II) reacted with an azole of formula III HN П \ = ^N (III) in which · Has the above-mentioned effluent, in the presence of an acid-binding agent and in the presence of a diluent, whereupon any ketoderivative obtained in a manner known per se is reduced by complex borohydrides, optionally in the presence of a diluent, and .