WO1999026474A1

WO1999026474A1 - Utilization of cyclodextrin complexes for the application of agrochemical active substances

Info

Publication number: WO1999026474A1
Application number: PCT/EP1998/007199
Authority: WO
Inventors: Günter WULFF; Andreas Steinert; Wolfram Andersch; Klaus Stenzel; Jürgen HÖLTERS; Uwe Priesnitz
Original assignee: Bayer Aktiengesellschaft
Priority date: 1997-11-21
Filing date: 1998-11-11
Publication date: 1999-06-03
Also published as: DE19751631A1; AU1668699A

Abstract

The invention relates to inclusion complexes comprised of A) modified cyclodextrins of formula (I) in which n represents 1, 2, or 3 and R?1, R2, and R3¿ represent hydrogen, methyl, 2-hydroxypropyl or acetyl, whereby at least 5 % of the radicals R1, R2, and/or R3 do not represent hydrogen, and B) active substances with fungicidal, bactericidal, insecticidal, acaracidal or nematicidal properties. The inventive inclusion complexes can be used for the application of said agrochemical active substances in the sap flow of plants or over the roots of plants.

Description

Use of cyclodextrin complexes for the application of agrochemical active ingredients

The present invention relates to the use of inclusion complexes of modified cyclodextrins and certain agrochemical active substances for the application of these active substances into the sap flow of plants or via the roots of the plants.

It has already become known that numerous complexes of cyclodextrins or modified cyclodextrins and agrochemical active ingredients can be used to apply the agrochemical active ingredients to the surface of the plants and / or their habitat (cf. JP-A 61-137 804, JP-A 61-137 803 and "Comprehensive Supramolecular Chemistry", Volume 3. Pergamon, Elsevier Science Ltd .. Tarrytown, NY, 1996, pages 503 to 514). The effectiveness of these preparations is, however, not always satisfactory.

It has now been found that inclusion complexes consist of

A) modified cyclodextrins of the formula

in which

n stands for 1, 2 or 3 and

R ¹ , R ² and R ^{3 are} hydrogen, methyl, 2-hydroxypropyl or acetyl, but at least 5% of the radicals R ¹ , R ² and / or R ^{3 are} not hydrogen,

and

B) Active ingredients with fungicidal, bactericidal, insecticidal. acaricidal or nematicidal properties

can be used very well for the application of these agrochemical active ingredients in the sap flow of plants or via the roots of the plants.

Surprisingly, the inclusion complexes which can be used according to the invention show a substantially better activity when applied to the sap flow of plants or via the roots of plants than when applying corresponding preparations to the surface of the plants and / or their habitat.

The substances which can be used according to the invention are inclusion complexes of modified cyclodextrins of the formula (I) and certain agrochemical active substances. These are understood to mean substances in which the agrochemical active substances are enclosed in cavities of the modified cyclodextrins of the formula (I).

The modified cyclodextrins contained in the inclusion complexes which can be used according to the invention are defined by the formula (I). In these cyclodextrins is the degree of substitution, that is the proportion of those groups in which R ¹ , R ² and

R ³ are different from hydrogen, between 5 and 100%. Modified Fected cyclodextrins of formula (I) in which the degree of substitution is between 10 and 70%. Modified cyclodextrins of the formula (I) in which the degree of substitution is between 15 and 60% are particularly preferred.

The following substances may be mentioned as examples of modified cyclodextrins of the formula (I).

Modified cyclodextrin of formula (I), in which

n stands for 2 and

60% of the radicals R ¹ , R ² and R ^{3 are} methyl.

Modified cyclodextrin of formula (I), in which

n stands for 1 and

60% of the radicals R ¹ , R ² and R ^{3 are} methyl.

Modified cyclodextrin of formula (I), in which

n stands for 3 and

60% of the radicals R ¹ , R ² and R ^{3 are} methyl.

Modified cyclodextrin of formula (I), in which

n stands for 2 and

27% of the radicals R ¹ , R ² and R ^{3 represent} 2-hydroxypropyl.

Modified cyclodextrin of formula (I), in which

n stands for 2 and

33% of the radicals R ¹ , R ² and R ^{3 are} acetyl. The modified cyclodextrins of the formula (I) are known or can be prepared by known methods (cf. “Comprehensive Supramolecular Chemistry”, Volume 3, Pergamon, Elsevier Science Ltd., Tarrytown, NY, 1996, pages 503 to 514).

The inclusion complexes which can be used according to the invention contain one or more active ingredients with fungicidal, bactericidal, insecticidal, acaricidal or nematicidal properties.

Examples of fungicides are:

2-aminobutane; 2-anilino-4-methyl-6-cyclopropyl-pyrimidine; 2 ', 6'-dibromo-2-methyl-4 ^, -trifluoromethoxy-4'-trifluoromethyl-1,3-thiazole-5-carboxanilide; 2,6-dichloro-N- (4-trifluoromethylbenzyl) benzamide; (E) -2-methoximino-N-methyl-2- (2-phenoxyphenyl) acetamide; 8-hydroxyquinoline sulfate; Methyl- (E) -2- {2- [6- (2-cyanophenoxy) ~ pyrimidin-4-yloxy] phenyl} -3-methoxyacrylate; Methyl (E) methoximino [alpha- (o-tolyloxy) -o-tolyl] acetate; 2-phenylphenol (OPP), aldimorph, ampropylfos, anilazine,

Azaconazole, Benalaxyl, Benodanil, Benomyl, Binapacryl, Bion, Biphenyl, Bitertanol,

Blasticidin-S, bromuconazole, bupirimate, buthiobate.

Calcium polysulfide, captafol, captan, carbendazim, carboxin, quinomethionate

(Quinomethionate), chloroneb, chloropicrin, chlorothalonil, chlozolinate, cufraneb,

Cymoxanil, cyproconazole, cyprofuram, dichlorophene, diclobutrazole, dichlofluanid, diclomezin. Dicloran, Diethofencarb,

Difenoconazole, dimethirimol, dimethomorph, diniconazole, dinocap, diphenylamine,

Dipyrithion, Ditalimfos, Dithianon, Dodine, Drazoxolon,

Edifenphos, epoxyconazole, ethirimol, etridiazole,

Fenarimol, Fenbuconazole, Fenfuram, Fenitropan, Fenpiclonil, Fenpropidin, Fenpropimorph. Fentin acetate, fentin hydroxide, ferbam, ferim zone, fluazinam, fludioxonil, Fluoromide, Fluquinconazole, Flusilazole, Flusulfamide, Flutolanil, Flutriafol, Folet, Fosetyl-Aluminum, Fthalide, Fuberidazol, Furalaxyl, Furmecyclox,

Guazatine,

Hexachlorobenzene, hexaconazole, hymexazole, imazalil, imibenconazole, iminoctadine, Iprobefos (IBP), iprodione, isoprothiolan,

Kasugamycin, copper preparations such as: copper hydroxide, copper naphthenate, copper oxychloride, copper sulfate, copper oxide, oxine copper and Bordeaux mixture, Mancopper, Mancozeb, Maneb, Mepanipyrim, Mepronil, Metalaxvl, Metconazole, Methasulfocarb, Methfuroxam, Metaxam, Metiram, Mets Myclobutanil, nickel dimethyldithiocarbamate, nitrothal isopropyl, nuarimol,

Ofurace. Oxadixyl, oxamocarb, oxycarboxin,

Pefurazoate, penconazole. Pencycuron, Phosdiphen. Pimaricin, Piperalin, Polyoxin, Probenazol, Prochloraz, Procymidon, Propamocarb, Propiconazole, Propineb, Pyrazophos, Pyrifenox, Pyrimethanil, Pyroquilon, Quintozen (PCNB),

Sulfur and sulfur preparations,

Tebuconazole, Tecloftalam, Technazen, Tetraconazole, Thiabendazole, Thicyofen, Thiophanat-methyl, Thiram, Tolclophos-methyl, Tolylfluanid, Triadimefon, Triadimenol, Triazoxid, Trichlamid, Tricyclazol, Tridemorph, Trifluminclizol, Trifluminozolin, Trifluminozolin, Trifluminozolin, Trifluminozolin, Trifluminozolin, Trifluminozolin, Trifluminozolin, Trifluminozolin, Trifluminozoline, Trifluminozolin, Trifluminozolin, Trifluminozoline, Trifluminozoline, Trifluminozoline, Trifluminozoline, Trifluminozoline, Trifluminozoline, Trifluminozoline, Trifluminozoline, Trifluminclitone

Zineb, Ziram,

8-tert-butyl-2- (N-ethyl-Nn-propyl-amino) -methyl-l, 4-dioxa-spiro- [4,5] decane, N- (R) - (1 - (4- Chlorpheny l) -ethyl) -2,2-dichloro-1-ethyl-3t-methyl-1 r-cyclopropanecarboxamide (mixture of diastereomers or individual isomers). [2-methyl-l - [[[[1- (4-methylphenyl) ethyl] amino] carbonyl] propyl] carbamic acid -

1-methylethyl ester

1-methyl-cyclohexyl-1-carboxylic acid- (2,3-dichloro-4-hydroxy) -anilide, 2- [2- (1-chloro-cyclopropyl) -3 - (2-chlorophenyl) -2-hydroxypropyl] - 2,4-dihydro- [1, 2.4] - triazole-3-thione and l- (3,5-dimethyl-isoxazole-4-sulfonyl) -2-chloro-6,6-difluoro- [1,3] - dioxolo- [4,5-f] - benzimidazole. Examples of bactericides are:

Bronopol, dichlorophene, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furan carboxylic acid, oxytetracycline, probenazole, streptomycin, teclofalam, copper sulfate and other copper preparations.

Examples of insecticides, acaricides and nematicides are:

Abamectin, Acephat, Acrinathrin, Alanycarb, Aldicarb, Alphamethrin, Amitraz,

Avermectin, AZ 60541, Azadirachtin, Azinphos A, Azinphos M, Azocyclotin, Bacillus thuringiensis, 4-Bromo-2- (4-chlorophenyl) -l- (ethoxymethyl) -5- (trifluoromethyl) -lH-pyrrole-3- carbonitrile, bendiocarb, benfuracarb, bensultap, betacyfluthrm, bifenthrin. BPMC, Brofenprox, Bromophos A, Bufencarb, Bupro fezin, Butocarboxin. Butyl pyridaben,

Cadusafos, Carbaryl, Carbofuran, Carbophenothion, Carbosulfan, Cartap, Chloethocarb, Chloretoxyfos, Chlorfenvinphos, Chlorfluazuron, Chlormephos, N - [(6-Chloro ~ 3-pyridinyl) -methyl] -N'-cyano-N-methyl-ethanimidamide , Chlorpyrifos, chlorpyrifos M, cis-resmethrin, clocythrin, clofentezin, cyanophos, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, cyromazine,

Deltamethrin, Demeton-M, Demeton-S, Demeton-S-methyl, Diafenthiuron, Diazinone, Dichlofenthion, Dichlorvos, Dicliphos, Dicrotophos, Diethion, Diflubenzuron,

Dimethoate,

Dimethylvinphos, Dioxathion, Disulfoton, Edifenphos, Emamectin, Esfenvalerat, Ethiofencarb, Ethion, Ethofenprox, Ethoprophos, Etrimphos,

Fenamiphos, Fenazaquin, Fenbutatinoxid, Fenitrothion, Fenobucarb, Fenothiocarb, Fenoxycarb, Fenpropathrin, Fenpyrad, Fenpyroximat, Fenthion. Fenvalerate, Fipronil, Fluazinam, Fluazuron, Flucycloxuron, Flucythrinat, Flufenoxuron, Flufenprox, Fluvalinate, Fonophos, Formothion, Fosthiazat, Fubfenprox, Furathiocarb,

HCH, heptenophos, hexaflumuron, hexythiazox, Imidacloprid, Iprobefos, Isazophos, Isofenphos, Isoprocarb, Isoxathion, Ivermectin,

Lambda cyhalothrin, lufenuron,

Malathion, Mecarbam, Mevinphos, Mesulfenphos, Metaldehyde, Methacrifos, Methamidophos, Methidathion, Methiocarb, Methomyl, Metolcarb, Milbemectin, Monocrotophos. Moxidectin,

Naled, NC 184, Nitenpyram,

Omethoate, Oxamyl, Oxydemethon M, Oxydeprofos,

Parathion A, Parathion M, Permethrin, Phenthoat, Phorat, Phosalon, Phosmet, Phosphamidon, Phoxim, Pirimicarb, Pirimiphos M, Pirimiphos A, Profenophos, Prome- carb, Propaphos, Propoxur, Prothiophos, Prothoat, Pymophroos, Pyrachl

Pyridaphenthion, Pyresmethrin, Pyrethrum, Pyridaben. Pyrimidifen, pyriproxifen.

Quinalphos,

Salithion. Sebufos, Silafluofen, Sulfotep, Sulprofos,

Tebufenozide, Tebufenpyrad, Tebupirimiphos, Teflubenzuron, Tefluthrin, Temefos, Terbam, Terbufos, Tetrachlorvinphos, Thiafenox, Thiodicarb, Thiofanox,

Thiomethon, Thionazin, Thuringiensin, Tralomethrin, Transfluthrin, Triarathen,

Triazophos, Triazuron, Trichlorfon, Triflumuron, Trimethacarb.

Vamidothione, XMC, xylylcarb, zetamethrin.

In the inclusion complexes which can be used according to the invention, the proportion of

Active ingredients with fungicidal, bactericidal, insecticidal. acaricidal or nematicidal properties can be varied within a wide range. In general, between 0.05 and 1 mol, preferably between 0.3 and 1 mol, of one or more of these agrochemical active substances are contained per mole of cyclodextrin of the formula (I).

The inclusion complexes which can be used according to the invention are known or can be prepared by known methods (cf. "Comprehensive Supramolecular Chemistry", Volume 3, Pergamon, Elsevier Science Ltd., Tarrytown, NY 1996, pages 503 to 514). The inclusion complexes which can be used according to the invention are thus obtained by

modified cyclodextrins of formula (I)

- With active ingredients with fungicidal, bactericidal, insecticidal, acaricidal or nematicidal properties

in the presence of water and / or a water-miscible organic diluent, such as methanol, ethanol or acetone, at temperatures between 20 ° C and 100 ° C.

The inclusion complexes which can be used according to the invention are very well suited for the application of the agrochemical active substances mentioned in the sap flow of plants or via the roots of the plants. They can therefore be used as fungicides depending on the agrochemical active ingredients they contain. Bactericides, insecticides.

Acaricides or nematicides are used.

The inclusion complexes which can be used according to the invention can be converted into all formulations which are suitable for application into the sap flow of plants or via the roots of plants. Such formulations are e.g.

Solutions, emulsions. Suspensions or molded articles.

These formulations are prepared in a known manner. e.g. by mixing the inclusion complexes with extenders, that is to say liquid solvents and / or materials forming moldings, if appropriate using surface-active agents, that is to say emulsifiers and / or dispersants. If water is used as an extender, e.g. organic solvents can also be used as auxiliary solvents. The following are essentially suitable as liquid solvents: aromatics. such as xylene, toluene or alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons, such as chlorobenzenes,

Chloroethylene or methylene chloride, aliphatic hydrocarbons, such as cyclo- hexane or paraffins, eg petroleum fractions. Alcohols, such as butanol or glycol, and their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide and dimethyl sulfoxide, and water. Examples of suitable emulsifiers are nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates. Aryl sulfonates and protein hydrolyzates. Possible dispersants are, for example, lignin sulfite liquor and methyl cellulose.

Materials forming moldings can e.g. natural or synthetic

Polymers are used, which are optionally biodegradable.

The formulations generally contain between 0.1 and 95% by weight of inclusion complexes, preferably between 0.5 and 90% by weight.

The inclusion complexes which can be used according to the invention can be used as such, in the form of their formulations or in the use forms prepared therefrom, such as ready-to-use solutions, emulsions or suspensions. The application is done in the usual way, e.g. by injection or other introduction into the sap flow of plants or into the root area of plants.

The inclusion complexes which can be used according to the invention can preferably be used for the treatment of individual plants, for example trees. For this purpose, they are preferably introduced in the form of solutions, emulsions or suspensions, for example by injection into the sap flow of plants. They can also be in the form of suitable moldings, such as rods. Tablets. Foils, tile. Tissues, strips, pins or hollow nails are introduced into the sap flow of the plants. For this purpose, the molded bodies are either introduced into appropriately produced cavities in the plant or simply pressed, pressed or punched into the plant tissue. They can also be pushed under carefully loosened bark or parts of plants, the bark or parts of plants then serving again for covering. The application rate of the inclusion complexes which can be used according to the invention can be varied within a relatively wide range. It depends on the respective agrochemical substances and their content in the inclusion complexes.

The invention is illustrated by the following examples.

Manufacturing examples

example 1

A solution of 15.0 g of cyclodextrin of the formula (I) in which

n stands for 2 and

60% of the radicals R ¹ , R ² and R ^{3 represent} methyl,

in 10 ml of water is added with gentle heating and stirring with 5.0 g of bitertanol. The resulting mixture is first heated under reflux for 5 minutes, then slowly cooled to room temperature with stirring and then stirred for a further 96 hours at room temperature. The reaction mixture is then diluted with 10 ml of water and filtered. The filtrate is freeze-dried. In this way, 15.5 g of an inclusion complex of the above-mentioned modified cyclodextrin and bitertanol are obtained. The bitertanol content in this product is 13.3% by weight.

Example 2

A solution of 15.0 g of cyclodextrin of the formula (I) in which

n stands for 2 and

27% of the radicals R ¹ , R ² and R ^{3 represent} 2-hydroxypropyl.

in 30 ml of water is heated to 60 ° C. with stirring and then a solution of 6.0 g of propoxur in 30 ml of methanol is added at this temperature with vigorous stirring. The resulting mixture is first heated under reflux, then slowly cooled to room temperature with stirring and then shaken for a further 96 hours. The reaction mixture is then filtered and the filtrate is freeze-dried. In this way, 16.0 g of an inclusion complex are obtained from the above-mentioned modified cyclodextrin and propoxur. The content of propoxur in this product is 6.5% by weight.

Example 3

A solution of 10.3 g of cyclodextrin of the formula (I) in which

n stands for 2 and

60% of the radicals R ¹ , R ² and R ^{3 represent} methyl,

in 20 ml of ethanol, a solution of 4.0 g of transfluthrin in 10 ml of ethanol is added with stirring at room temperature. The resulting mixture is first heated under reflux for 5 minutes, then slowly cooled to room temperature with stirring and then left open for 4 days so that the ethanol evaporates. The remaining product is taken up in 50 ml of water. The resulting mixture is concentrated to half its volume under reduced pressure and then filtered. The filtrate is freeze-dried. In this way, 9.5 g of an inclusion complex of the above-mentioned modified cyclodextrin and transfluthrin are obtained. The content of transfluthrin in this product is 3.8% by weight.

Example 4

A solution of 15.1 g of cyclodextrin of the formula (I) in which

n stands for 2 and

33% of the radicals R ¹ , R ² and R ^{3 represent} acetyl,

5.6 g of the fungicidal active ingredient l-methyl-cyclohexyl-l-carboxylic acid (2,3-dichloro-4-hydroxy) anilide are added to 15 ml of water with stirring at room temperature. The resulting mixture is initially mixed at room temperature for 20 minutes. stirred vigorously, then heated under reflux for 5 minutes and then cooled to room temperature within 16 hours with stirring. The reaction mixture is then filtered and the filtrate is freeze-dried. In this way, 13.3 g of an inclusion complex of the above-mentioned modified cyclodextrin and the above-mentioned fungicidal active ingredient are obtained. The active substance content in this product is 7.4% by weight.

Example 5

A solution of 15.9 g of cyclodextrin of the formula (I) in which

n stands for 2 and

60% of the radicals R ¹ , R ² and R ^{3 represent} methyl,

in 20 ml of ethanol with stirring at room temperature with a solution of 7.0 g

Beta-cyfluthrin in 10 ml of ethanol. The resulting mixture is first refluxed for 5 minutes, then slowly cooled to room temperature with stirring and then very slowly mixed with water at room temperature. After a highly cloudy mixture has formed, the diluent is removed under reduced pressure. The residue is in 20 ml

Water added. The resulting mixture is filtered. The filtrate is freeze-dried. In this way, 15.0 g of an inclusion complex of the above-mentioned modified cyclodextrin and beta-cyfluthrin are obtained. The beta-cyfluthrin content in this product is 4.0% by weight.

Example 6

A solution of 15.8 g of cyclodextrin of formula (I). in which

n stands for 2 and

60% of the radicals R ¹ , R ² and R ^{3 represent} methyl, 5.5 g of transfluthrin are added to 10 ml of water with stirring at room temperature. The resulting mixture is treated in an ultrasonic bath at 30 ° C. for 10 minutes without stirring. The reaction mixture is then filtered. The filtrate is freeze-dried. In this way, 1 1.5 g of an inclusion complex of the above-mentioned modified cyclodextrin and transfluthrin are obtained. The content of transfluthrin in this product is 4.3% by weight.

Usage example

Drug uptake test

To prove the systemic absorption of active ingredient in plant tissue

Complexed drug preparation or non-complexed, commercially available drug formulation

dissolved in water in the desired amount.

The solutions thus produced are placed in preparation vials into which the leaves of maize plants are placed in such a way that only the cut surfaces come into contact with the active ingredient solution.

After 3 days of incubation at a temperature of 20 ° C, the leaves are cut off above the wetting surface and subjected to a bioassay. For this purpose, the leaves are placed in Petri dishes on moist filter paper and fed to 10 larvae of Spodoptera frugiperda in the L3 stage. After 7 days, the systemic absorption of active ingredient is determined on the basis of the feeding activity of the larvae and rated in% according to Abbott. Here means 0% that no active ingredient was ingested and the leaves were completely eaten and

100% that active ingredient was absorbed and the leaves remained intact compared to an untreated control.

Active substance preparations, active substance concentrations and test results are shown in the following table.

Claims

claims

1. Use of inclusion complexes

A) modified cyclodextrins of the formula

in which

n stands for 1, 2 or 3 and

and

B) Active ingredients with fungicidal, bactericidal, insecticidal, acaricidal or nematicidal properties for the application of these agrochemical active ingredients in the sap flow of plants or via the roots of plants.

2. Use according to claim 1, characterized in that inclusion complexes of modified cyclodextrins of the formula (I) are used, in which

n, R ¹ , R ² and R ^{3 have} the meaning given above,

wherein between 10 and 70% of the radicals R ¹ , R ² and / or R ^{3 are} not hydrogen.