CS243477B2 - Plants' fungi diseases subdueing agent method of efficient substances production - Google Patents

Description

(54) A composition for combating fungal diseases of plants and a method for producing active substances

A composition for controlling fungal diseases of plants, characterized in that it contains a compound of the formula I as active ingredient.

CH ₃ - C - R ₇ ³ I (CH ₂ ) n / I /

x ₂ in ₂ x 7 ^X 1 n active compounds in which hydrogen or chlorine is represented by hydrogen or methyl, and X _is independently chlorine or bromine and is a number of 0 or 1.

Hereinafter, a method of making these is to be described.

The invention discloses novel and -aubetenyl-.alpha.-cyclopropylelkyl-1H-1H-triazole-1-ethenols in which the cyclopiopropyl residue is halogenated (hereinafter the compounds of the present invention), a process for the preparation of these compounds according to the invention - and their use as fungicides.

As used herein, α-carbon refers to the carbon atom of an ethinol moiety which is not bonded to a phenyl group, a hydroxyl group, or a phenyl group.

The compounds of the invention correspond to the general formula I in which:

/ I / «2 * ^X 7 H - X2 and znamená.atom hydrogen or chlorine, represents hydrogen or a methyl ekupinu, independently Aobe znamernaí modes chlorine or bromine atom, and is an integer equal to 0 or 1.

The hydrocyl group of the compounds of the invention may be etherified or esterified.

When the hydroxyl group of the compounds of the present invention is ethoxylated, such ethers are, for example, alkyl ethers having 1 to 5 carbon atoms in the alkyl moiety, alkenyl ethers having 3. C 5- alk 5-, alk alk alk alk alk alk alk. Esters of the compounds of the invention are, for example, esters derived from aliphatic carboxylic acids, such as acetic acid.

The compounds of the invention contain one or more chiral centers. These compounds are generally obtained in the form of racemic mixtures or mixtures of diastereomers. These and other mixtures may, _of course, be separated, either wholly or in part, into individual components or desired mixtures of isomers. This separation is carried out by methods known per se

In accordance with the invention, the compounds of formula (I) are reacted by reacting a compound of formula (II)

(II) wherein M represents a hydrogen atom, a metal atom, or a group of formula III with a compound of formula III

СН _О

Ο-Ο (ΟΗ ₃₎ Ηγ- (ΟΗ _{2) η -ΟΗ}

wherein each general symbol is as defined above.

SUMMARY OF THE INVENTION The present invention provides a composition for combating fungal diseases of plants, characterized in that the active ingredient comprises a compound of the formula I and an agriculturally useful diluent. The present invention also relates to a process for the preparation of these active ingredients as described above.

When M in formula II is hydrogen, the reaction is preferably carried out in the presence of a base.

Compounds of the invention may be obtained in free base form, in the form of a centerline (in the form of acid addition Sou acid, nappíklad ^{hydroxypropoxy} oochoridu, or as alcoholate e.g. přísněného sodium ethoxide), and in the form of a metal complex, for example a complex with copper or zinc, which contains, as anions, a chloride, sulfate or nitrate anion.

Acid addition salts, elkoxides and metal complexes can be obtained from the free free compounds in a conventional manner and vice versa.

The process according to the invention can be carried out, for example, by reacting a compound of formula III with an azole of formula II as such (M = hydrogen) or in the form of a salt (M = metal), preferably an alkali metal salt, e.g. in a reaction inert solvent such as dimethyl amide, at a temperature between room temperature and the reflux temperature of the reaction mixture, or with an azole of formula II in which M is a triackylsilyl group, such as trimethyltilyl, in a reaction inert solvent. reaction conditions in nappíklad -dimethylformamide, in příloínoot even katalytckkého ínnlsSví base such as sodium hydride, suitably from zátařevj ^preferably záhfavu 70 and ^from 9 ° C.

The compounds of the invention can be isolated and purified from the reaction mixture by methods known per se.

Compounds of formula (III) may be obtained

(a) reaction of the topping halohydrins with a base; or

b) reaction of the corresponding ketones of formula IV

Cl

in which / IV /

(IN)

L is 0 or 1,

X represents a halogen methylallyl radical and

Н ^ З means allylol group,

wherein in the presence of a base (alkali metal hydride or hydroxide) using known methods or methods analogous to known methods. When R ^ represents an alkyl group having 8-18 carbon ulh.íku ₉ particular direct alkylC ^ ou group having 8-18 carbon atoms, for example n-dld · cyloolu, the compound of formula V also function as a phase transfer catalyst.

Compounds of the formula IV can also be obtained by methods, for example by addition grouping »CXjX _2» wherein Xj and x maai as hereinbefore defined,. to a compound of formula VI

• ₇ _

0-0 (CH ₃ ) R '- (CH ₂ ) ⁿ -CH ₂ CH ₂ (VI) in which the individual symbols have the meanings given above, or from compounds of formula VII

(VII) in which

R _2, R y and £ maai abovementioned meaning and represents hydrogen or a protecting group hydrootylOTé function (e.g. tetrahydropyran <> pyranyllvlu group) on the double bond and e n ^; first passing eduje group "CX ^ Xg (wherein X ^ and X g are above meanings »then alkotoHcká ^f ^ ce un ^{to (p} o pHpadném cleaving the protecting CI ^for UPIN) oxidizes no keto group. N-di ne - group CX ^ X _2, and oxidation is carried out by known methods.

Carbenes of formula »CX ^ X ₂ can be obtained e.g.

(a) cleavage of helium hydrogen from trihalogel using an alkali metal hydroxide (for example, under conditions of phase transfer reaction); or

b) thermal disintegration (decarbooylation) of a triheleacetate, for example, netri-trihaloacetate or lithium-trihaloacetate, at a temperature of 80 to 120 ° C (for example in solvent mixtures containing a diethyl ether or diethylene glycol dimethyl ether), or

c) thermal des integration of a compound of formula

C ₆ H ₅ HgCX 3 in which

X is halogen, for example in benzene at reflux.

For example, starting materials of formula VI in which n - is 1 are obtained by alkylation of acetophenone with an alkyl halide, and those compounds of formula VI in which n has a value of 0 and 80 are hydrogen are obtained, for example, by reaction of a Qrignaxd compound of allyo type. with optionally substituted benzyl aldehyde.

If the preparation of certain starting materials is not described, these compounds are either known or can be prepared according to the procedures described herein or known, respectively. procedures analogous to those described herein or known.

The compounds of the invention exhibit interesting biological, in particular aotimycotic, properties and can therefore be used as medicaments in the treatment of fungal diseases in humans and other animals. Antimycotic activity can be demonstrated in vitro assays, e.g., in vitro stem ^ avenge zřeSovací for ^{row y} for ad spirited genera and ^d ^ ruhy вдсе such as yeast, fungi and dermaaolyty while pouužvaaí concentration from about 0.05 - 50 / ug / ml, as well as in vivo assays, for example, a thrombotic effect test wherein orally dosages of about 10 to 100 mg / kg body weight per ml, which are intrevaginally infested with Candida albicans, are administered.

The dosages applied for the above purposes vary widely in the compound used, the mode of administration and not the desired result. In general, however, consistent results are obtained when a daily dose of from 1 to 100 mg / kg body weight is administered, which total daily dose is conveniently administered in divided doses of two to four times a day or in a pump. For larger mammals, the dosage range will vary from about 70 to about 2000 mg, with oral dosage forms containing, for example, from about 17.5 to about 1000 mg of active ingredient.

The compounds of the invention may be mixed with conventional pharmaceutically (or veterinarily) viable carriers and optionally with longer excipients. The disclosed compounds may be administered in inertly administrable unit dosage forms, such as tablets or capsules, or alternatively may be administered topically in the form customary for such administration, such as in the form of a massi or cream, or parenterally. The concentration of the active ingredient in these compositions will in general depend on the axis of the compound used, the desired result treated, and the nature of the dosage form from below. In general, however, the results are obtained when the topically active forms of the active ingredient are contained in the active ingredient, for example from 0.05 to 5%, in particular from 0.1 to 1% by weight.

The compounds of the invention may be used analogously to known standard compounds, for example ketoconazole.

Relevant Deno dose of the compound according to the invention the axes a number of factors, for example the ^t axis relative effective. relative iooost ^ ^b YLA zjišfovéna for example, 2- (4-еhllrfenyC) -4- (2,2-diеhllrесkllprlpyC) -3,3-dimethyl-1- (1 H-1 ^^ - trias! -) -yl) butane -2-ol of the vaginal ejanlidiasis model, wherein healing was found after oral administration of a dose of 4 x 12.5 m ^ kg body humor. Thus, the compounds of the present invention may be used in doses analogous to those used for cyclolzole.

The compounds of the invention may also be used as fungicides to combat phytotest in vivo, at about 8% to about 0.05% against other fungi, geraniums, pathogenic fungi. The beneficial fungicidal efficacy of these substances is demonstrated by the test substances used at concentrations of about 0.000 Uromyces appendiculatus (bean rust) on climbing beans, against scabs (such as Homileia and Puccinia) on coffee, looking, and against Erysiphe cichoracearum ) on cucumbers and against other powdery mildew-inducing fungi (eg Erysiphe graminis f. sp · tritlel, Eosphiphe graminis f. sp · hordei, Podosphaera leucotricha, Uncinula necator) on wheat, barley, apple and grapevine · Longer interesting efficacy was observed in vitro against Ustilago maydis (corn fawn) at test compound concentrations from 0.8 to 200 ppm, and in vivo against Rhizoctonia soleni (potato root) at test compound concentrations from about 10 to 160 ppm (calculated on substrate volume) These tests also show good tolerability For the treatment of plants, seeds and soil for the control of phytopathogenic fungi, for example fungi of the classes Basidiomycetes, Ascomycetes and Deuteromycetes, in particular basidiomycetes of the order Uredinales (rust), such as Puccinia spec. Hemileia spec., Uromyces spec., Bcomiphales ascomycetes, such as Erysiphe spec., Podosphaera spec., And Unclnula spec., As well as fungi of the genera Phoma, Rhizoctonia and Helminthosporium.

The following overview gives specific test results for the efficacy of representative compounds of Examples 2.2 and 2.3 against a number of phytopathogenic fungi. These results are reported in E £ 90 values, which are the active compound concentrations in mg / liter that cause 90% fungal destruction. The corresponding values for the modern fungicide propiconazole, which is 1- [2- (2,4-dichlorophonyl) -4-propyl-1,3-dioxolen-2-ylmethyl] -1H-1,2,4, are also given. -triazole (see, for example, The Pesticide Manual, 7th edition, p. 468).

sponge / plant- example 2.2 --- RT53— example 2.3 propiconazole Erysiphe / cucumber 3 2 6 Erysiphe / pŠonice 6 4 8 Podosphaera / Apple tree 9 4 8 Uncinula / grapevine 9 3 9 Uromycos / beans 1 2 10 Puccinia trit./wheat 3 11 27 Mar:

In particular, the above-mentioned overview shows a particularly pronounced anti-rust effect (Uroщусеэ, Puccinia) ·

The amount of the compound to be administered depends on a number of factors, such as the compound used, the subject of treatment (plant, soil, seeds), the type of treatment (e.g. dressing, trowel, spray, dusting, pickling), not the purpose of the treatment (prophylactic or therapeutic treatment) ), the type of fungi being treated and the time of application.

In general, satisfactory results are obtained when the compounds of the invention are applied in an amount of about 0.005 to 2.0, preferably about 0.01 to 1 kg / ha in the case of a plant or soil treatment. for example, at intervals of 8 to 30 days. When using the compounds of the present invention for seed treatment, satisfactory results are generally obtained when the compounds are used in an amount of about 0.05 to 0.5, preferably about 0.1 to 0.3 g / kg seed.

The term soil ** includes all common growth environments, whether natural or artificial.

Ί

The compounds of the present invention can be used in a variety of useful plants such as soybean, kevizkra, ornamental plants (e.g. ^, elargonia or roses), vegetables (e.g., peas, cucumbers, celery, tomato, bob and fazoo), sugar beet, cane , avian, flax, maize, grapevine, pome fruit and stone fruit (for example, apple, pear, évestfy), and in particular suitable for use in cereals (for example, pdernd, oat or barley), especially wheat.

The aforementioned fungicidal compositions of the invention are obtained in a conventional manner, for example by mixing a compound of the invention with a diluent and optionally other additives, such as surfactants.

As used herein, the term diluent refers to a liquid or solid, agriculturally useful material which can be added to the active ingredient to convert it into an easier or more easily administrable form. to dilute the active ingredient to a usable or desired concentration. Examples of such diluents include carbon black, silica, xylene or water. .

In particular, compositions used in the form of a spray coating, such as water-dispersible concentrates or wetting powders, may contain surface-active agents such as wetting and dispersing agents, for example, condensation products of phthalene and naphthalene sulfonate, alkyl acrylate, lignite, ethoxylated fatty alcohols, ethoxylated fatty alcohols. and ethoxylated fatty alcohols.

The aforementioned compositions generally comprise from 0.01% to 90% by weight of the active ingredient, from 0% to 20% of a fungicidal surfactant, and from 10% to 99.99% of the diluent (s). Concentrated forms of the compositions, for example, emulsion filters, generally contain from about 2 to 90%, preferably between 5 and 70%, of the active ingredient. Dosage forms generally comprise from 0.0005% to 10% of the tamonoidic compounds of the invention as active ingredient. Typical spray suspensions may contain, for example, from 0.0005 to 0.05, preferably from 0.001 to 0.02%, by weight of the active ingredient.

In addition to conventional diluents and surfactants, the compositions of the invention may contain other ingredients for special purposes, such as stabilizers, activators (for solid formulations on active surface carriers), plant adhesion promoters, corrosion inhibitors, anti-foaming agents and coloring agents. . In addition, longer fungicides with similar or phloemolemic fungicidal efficacy, or other beneficial effects, such as insecticides, may be present in these compositions.

Examples of preparation of the fungicidal plant protection products according to the invention are given in the following.

a) Compressible powder of parts of the compound of the invention is mixed and milled with 25 parts of fine synthetic silica, 2 parts of triturated silica, 3 parts of silicon-lignin, respectively. and 45 parts finely divided kaolin until the mean dimension is about 5 / m.

The loose readable powder is diluted with water prior to use to form a spray formulation which can be applied by spraying on the leaf as well as by root dressing.

b) GramHat

Onto 94.5 parts of quartz quartz sand was sprayed in a drum mixer with 0.5 parts of mono-hydrophobic (non-ionic teMide), the mixture was thoroughly mixed, then parts of the quartz compound were added. according to the invention and vigorous stirring is continued until the granular composition has a particle size of 0.3 to 0.7 mm. This granulate can be applied by incorporation into the soil around the treated plants.

c) An expanded concentrate of parts of the mono-compound of the present invention is mixed with 10 parts of the mono-mineral eulator and 65 parts of the mono-mineral xylene. and the concentrate is diluted with water to the desired concentration.

d) The seed dressing of the parts of the compound of the invention is mixed with 1.5 parts of ethylenoxide-based diemolphenol-decahydro-ether, 2 parts of spindle oil, 51 parts of ground pulverized residue and 0.5 parts of dyestuff rhodin B in a disintegrator at 10,000 rpm, until the average particle size is ueent than 20 µu «An angry-dry powder formulation provides good adhesion and can be applied to the seed, for example, two to five minutes in a spinning vessel only.

The invention is illustrated by the following examples, but the scope of the invention is not reduced in any desiccant.

Filnal Compounds.

He did

2- (4-chlorophenyl) -4- (2,2-dichlorocyclopropyl) -3,3-diethyl-1- (1H-1,2,4-triazol-1-yl) butan-2-ol

a) To a solution of 3.0 g of 1- (4-chlorophenyl) -3- (2,2-dichlorocoroethyl) -2,2-dimethylthroro-1-one in 30 ml of anhydrous toluene is added 5.1 g of dry toluene at room temperature. dodecyl-dioethylsulphonone, ethyl acetate, sodium sulfate, dried for 15 minutes, powdered potassium hydroxide (1.1 g) was added to the suspension, and dried at 35 ° C for 2 hours. The organic extracts are successively washed three times with water and then with saturated aqueous sodium chloride solution, dried over magnesium sulphate and removed in vacuo. The residue is a colorless oil consisting of 50 ml of water. % 2- (4-chlorophenyl) -2- [2- (2'-dichlorocyclopropyl) -1,1-diretyl] oxirene and 50% dodecylmethyllide;

b) Crude oxirane from the previous reaction was dropped dropwise to dryness in 10 g

1,2,4-triazole and 3.7 g of potassium carbonate in 200 µl of dry diethyl ether, which had been previously heated to 90 ° C, and the resulting drying was maintained for 1 hour while maintaining the temperature at 90 ° C.

After cooling, the reaction drier is poured onto ice and extracted with dichloroethane. and ethyl acetate (initially in a 9: 1 and then 1: 1) and then with ethyl acetate as eluent, and the product was then crystallized from ethyl acetate / hexane to give the title compound as colorless crystals of temperature. melting point 117 to 123 ° C (diasterecueire drying) ·

Example 2

In analogy to Example 1, the reaction of the corresponding azole with the corresponding oxirane gives the following compounds corresponding to the formula Ia.

Cl

example number r ₂ ^(A > ^O x, / x ₂ characterization 2.1 H C (CH 3) ₂ Cl / Cl ^Rf = ^0, 24 ^{/ IA-cx)} 2.2 H C (CH 3) 2 -CH ₂ Br / Br B _f ^»0, 30 ^/ ^ ^{x IAC)} 2.3 H CHCCH3) -CHg Cl / Cl Rf 0.28 / JAc ^{b) * * e)} O * ⁰ 1.559 8

Legend Mixture of di-paste-methyl-AEc = ethyl acetate ¹ mixture of isomers

Intermediates

Example 3

1- (4-chlorophenyl) -3- (2,2-dichlorophenyl) -2,2 ^ 100 ^^^^ 0-) -oo

a) To a solution of 28 g of powdered potassium hydroxide in 500 ml of toluene over zs minutes stirring at místooosi added 45.6 g of 4-PSK chllrftoсlitlPpoopсlketoou retsbbuCyeamonjumbrlmidu 8.1 g, the temperature inside of the reaction mixture will oe 3 ⁰ ° ^{C. P} by stirring for two hours ^p ^ s ^^ místooosi for instance ^also APE altylchlorádu 28 ^.mu.g in 100 ml toluene the reaction mixture is stirred over at OOC Mehta, PSK was poured into ice-water, extracted with ether. The combined organic extracts were washed successively with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated. Frakčoí deestlací crude residue afforded 1 - (4-еhlorftoсl) - ^2> 2-dmttс1ptnt ^4-eo-l-f oo in OIM ^e ^ o ^ zbarvého oil plo ^ bp 95 ° C / 53 Ps.

b) To a solution of 64 g of 1- (4-еh1orftnс1) -2 _l 2diimttyPptot 4'een-1-one in 500 ml ^{of p} chloroUcimu with RL at 0 ° C was slowly PMDA 50 ^{g of a} 50% aqueous solution of tyfroxičlu stáného к t ^Star Smee it over 15 minutes was added portionwise 5 g · trttCybtonсyaamooiumchhoridu after complete addition the reaction mixture was stirred for 8 fits at room temperature. The reaction mixture is poured over ice, extracted with dichloromethane, the combined organic extracts are washed with water and, after drying over magnesium, evaporated in vacuo. The pure title compound was prepared by chromatography on silica with hexane containing 1 to 3% as eluent. The product has an Rf = 0.23 (thin-layer plates ^ Hka ^ lu, 96: 4 hexane as solvent system) ·

AND

In analogy to Example 3 (b), the reaction of the dihalocarbenes and the corresponding unsaturated compounds of formula (VI) gives the following products of formula (IV) wherein the chlorine atom occupies the 4-position on the phenyl moiety.

Claims (2)

SUBJECT OF THE INVENTION A composition for combating fungal diseases of plants, characterized in that it comprises an agriculturally useful diluent and, as active substance, a compound of the general formula I in which: R _o represents a hydrogen or chlorine atom, 2 i R represents a hydrogen atom or a methyl group, R and X ₂ each independently represent a hydrogen, chlorine or bromine д is an integer equal to 0 or 1. 2. A process for the preparation of the active compounds of the formula I as claimed in claim 1, which comprises: M represents a hydrogen atom, a metal or a trialkylsilyl group, reacting at a temperature ranging from room temperature to reflux in a reaction-inert solvent and reacting with a compound of formula III (III): R _2> Ηγ, Xj, X ₂ and ja have the meaning as in point 1.