DE4320498A1 - Azolylmethylspiro[2,4]heptanols - Google Patents

Abstract

There are described novel azolylmethylspiro[2,4]heptanols, a process for their preparation, and their use as fungicides in the protection of materials.

Description

The present invention relates to new azolylmethylspiro- [2,4] -heptanols, a ver drive to their manufacture and their use as fungicides in material protection.

It is known from EP 378.953 that compounds of the type

have a fungicidal effect in crop protection.

In some cases, however, the effect of these substances leaves at low application rates to be desired.

New azolylmethylspiro- [2,4] -heptanols of the formula (I)

in which
R¹, R², R³, R⁴ independently of one another for hydrogen, C₁-C₆-alkyl, alkenyl or halogen, and
R⁵ represents phenyl, furyl, thienyl, optionally substituted by 1 to 4 groups of halogen, C₁-C₆-alkyl, alkoxy, thioalkaryl, alkenyl or haloalkyl or haloalkoxy,
X for CH or N
stands,
as well as their acid addition salts and metal salt complexes
found.

Depending on the substitution on the cyclopropyl ring, various Enantiomers / diastereomers occur. Also on the R⁵-cyclopentane ring Double bond two isomers (cis, trans) occur. The present invention relates to both the individual isomers and their mixtures.

The following substituent meanings are preferred in the application:

Alkyl: methyl, ethyl, propyl, isopropyl, n-, i-, s-, t-butyl, n-pentyl, n-hexyl and their branched isomers,
Alkenyl: exo-methylene, allyl, vinyl, butenyl each bound in the 1- or 2- or 3- position,
Alkoxy: C₁-C₄-alkoxy such as methoxy, ethoxy, n-, i-propyloxy, n-, i-, s-, t-butyloxy,
Halogen: F, Cl, Br, I,
Haloalkyl, haloalkoxy: CF₃, CF₂CF₃, O-CF₃,

Preferred among the compounds of formula (I) are those in which
R¹, R², R³, R⁴ independently of one another for hydrogen, methyl, fluorine or chlorine,
R⁵ represents phenyl, thienyl or furyl, which are optionally substituted by 1 to 3 groups such as halogen, C₁-C₃-alkyl, alkoxy, haloalkyl or haloalkoxy, and
X represents CH or N.

Compounds of the formula (I) in which
R¹, R², R³, R⁴ independently of one another represent hydrogen, methyl or fluorine, but in which at least two radicals are hydrogen,
R⁵ represents phenyl, furyl, thienyl, 4-chlorothienyl, or phenyl substituted by 1 to 2 chlorine, fluorine, CF₃ or O-CF₃ groups.

It was also found that the new compounds of the formula (I) are obtained if

• 1) compounds of the formula (II) in a diluent and in the presence of a base with compounds of the formula (III) R⁵-CHO (III),
• 2) the intermediate of formula (IV) thus obtained then reacted with trimethylsulfonium iodide in the presence of a base, if appropriate in a diluent,
• 3) the intermediate of formula (V) thus obtained ultimately with a compound of formula (VI) optionally added in the presence of a diluent.

By hydrogenation following these reaction steps under metal catalysis with z. B. Pd, PT or Ni, the compounds of the invention can also in the the fungicides known from EP-267 778 are transferred.

The method according to the invention can therefore also be used to produce compounds of the formula (Ib)

be used.

Another subject of the registration are the new intermediates of Formulas (IV) and (V).

Those used as starting compounds for the process according to the invention Spiro- [2,4] -heptan-4-ones are known or can be produced by known methods (Jarowickii, Monthly Bulletin Chemistry 115, 605 (1984).

Inert are used as diluents for carrying out the above processes organic solvents in question. Aliphatic, alicyc are preferably usable lical or aromatic, optionally halogenated hydrocarbons, as in for example gasoline, benzene, toluene, xylene, chlorobenzene, petroleum ether, hexane, Cyclohexane, dichloromethane, chloroform, carbon tetrachloride, ethers such as diethyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl or diethyl ether, Ke clays, such as acetone or butanone, nitriles, such as acetonitrile or propionitrile, amides, such as Dimethylformamide, dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or Hexamethylphosphorsäuretriamid, esters such as ethyl acetate, sulfoxides such Dimethyl sulfoxide or alcohols, such as methanol, ethanol, propanol, butanol, Methoxyethanol or ethoxyethanol.  

The above process is optionally more suitable, usually in the presence of usable inorganic and organic bases performed. Preferably alkali metal hydrides, hydroxides, amides, alcoholates, carbonates or are used -hydrogen carbonates, such as sodium hydride, sodium amide, sodium hydroxide, sodium methylate, sodium ethylate, potassium t-butoxide, sodium carbonate or Sodium hydrogen carbonate or also tertiary amines, such as triethylamine, N, N-dimethylaniline, pyridine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclonones (DBN) or diazabicycloundecene (DBU).

The reaction temperatures can be carried out in carrying out the above processes in can be varied over a wide range. Generally one works at Temperatures between 0 ° C and 200 ° C, preferably at temperatures between 60 ° C and 150 ° C.

When carrying out the above procedures, one generally works under Normal pressure. It is also possible, however, under increased or reduced pressure to work.

To carry out the above process, the compound is used per mole of compound Formula (II) or (IV) in general 1.0 to 5.0 mol, preferably 1.0 to 1.2 mol on compound of the formula (III) or trimethylsulfonium iodide and 0.01 to 1.0 or 1.0 to 5.0 moles of base.

Carrying out the reaction, working up and isolating the reaction products takes place according to generally accepted methods (see also the production examples).

The active compounds according to the invention have a strong microbicidal action and can be used to combat unwanted microorganisms become. The active ingredients are used to protect technical materials against infestation and destruction by unwanted microorganisms.

In the present context, technical materials include non-living ones Understand materials that have been prepared for use in engineering are. For example, technical materials made by the invention  Active substances are to be protected against microbial change or destruction, Adhesives, glue, paper and cardboard, textiles, leather, wood, paints and Plastic items, coolants and other materials may be those of Microorganisms can be attacked or decomposed. As part of the Protective materials are also parts of production facilities, for example Cooling water circuits, called, which affect by multiplication of microorganisms can be pregnant. In the context of the present invention are considered technical Materials preferably adhesives, glues, papers and boxes, leather, wood, Paints, cooling lubricants and heat transfer liquids called particularly preferably wood.

As microorganisms that break down or change the technical Materials such as bacteria, fungi, yeasts, algae and Called slime organisms. Preferably, the ver act reversible active ingredients against fungi, in particular mold, wood-staining and wood-destroying fungi (Basidiomycetes) and against slime organisms and algae.

For example, microorganisms of the following genera may be mentioned:

Alternaria, such as Alternaria tenuis,
Aspergillus, such as Aspergillus niger,
Chaetomium, like Chaetomium globosum,
Coniophora, such as Coniophora puetana,
Lentinus, such as Lentinus tigrinus,
Penicillium, such as Penicillium glaucum,
Polyporus, such as Polyporus versicolor,
Aureobasidium, such as Aureobasidium pullulans,
Sclerophoma, such as Sclerophoma pityophila,
Trichoderma, like Trichoderma viride,
Escherichia, such as Escherichia coli,
Pseudomonas, such as Pseudomonas aeruginosa,
Staphylococcus, such as Staphylococcus aureus.

The active ingredients can depend on their respective physical and / or chemical properties are converted into conventional formulations, such as solutions genes, emulsions, suspensions, powders, foams, pastes, granules, aerosols and Fine encapsulation in polymeric substances.

These formulations are prepared in a known manner, e.g. B. by mixing of the active ingredients are under pressure with extenders, i.e. liquid solvents the liquefied gases and / or solid carriers, if necessary with use formation of surface-active agents, i.e. emulsifiers and / or dispersants and / or foam-generating agents. In case of using water as Extenders can e.g. B. also ver organic solvents as auxiliary solvents be applied. The following are essentially suitable as liquid solvents: aroma ten such as xylene, toluene, alkylnaphthalenes, chlorinated aromatics or chlorinated aliphati cal hydrocarbons, such as chlorobenzenes, chlorethylenes, or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, e.g. B. 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 tel, such as dimethylformamide or dimethyl sulfoxide, and water; with liquefied gaseous extenders or carriers are meant such liquids, wel che are gaseous at normal temperature and pressure, e.g. B. Aerosol Propellants, such as halogenated hydrocarbons, butane, propane, nitrogen and Koh lena dioxide; as solid carriers come into question: B. natural stone powder, such as Kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or Diatomaceous earth and synthetic rock powder, such as highly disperse silica, aluminum minium oxide and silicates; as solid carriers for granules come into question: z. B. broken and fractionated natural rocks such as calcite, marble, pumice, sepiolite, Dolomite and synthetic granules from inorganic and organic flours as well as granules of organic material such as sawdust, coconut shells, corn pistons and tobacco stems; come as emulsifying and / or foam-generating agents in question: e.g. B. non-ionic and anionic emulsifiers, such as polyoxyethylene fat acid esters, polyoxyethylene fatty alcohol ethers, e.g. B. alkylaryl polyglycol ether, alkyl  sulfonates, alkyl sulfates, aryl sulfonates and protein hydrolyzates; as a dispersant come into question: z. B. Ligninsulfitablaugen and methyl cellulose.

Adhesives such as carboxymethyl cellulose, natural, can be used in the formulations and synthetic, powdery, granular or latex-shaped polymers are used, such as gum arabic, polyvinyl alcohol, polyvinyl acetate, and natural phospholi pide, such as cephalins and lecithins and synthetic phospholipids. Other additives can be mineral and vegetable oils.

Dyes such as inorganic pigments, e.g. B. iron oxide, titanium oxide, ferrocy blue and organic dyes such as alizarin, azo and metal phthalocyanine substances and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, Molybdenum and zinc can be used.

The formulations generally contain between 0.1 and 95 percent by weight Active ingredient, preferably between 0.5 and 90%.

The application concentrations of the active ingredients to be used according to the invention depend on the type and occurrence of the microorgan to be controlled and the composition of the material to be protected. The optimal one Amount used can be determined by driving. In general, the Application concentrations in the range of 0.001 to 5 wt .-%, preferably from 0.05 to 1.0 wt .-%, based on the material to be protected.

The effectiveness and the spectrum of action of those which can be used according to the invention Active substances or the agents, concentrates or from them in general Formulations can be increased if necessary further antimicrobial active compounds, fungicides, bactericides, herbicides, insecticides or others Active substances to enlarge the spectrum of effects or to achieve special ones Effects such as B. additional protection against insects. This Mixtures can have a broader spectrum of activity than the invention appropriate connections.  

In many cases, synergistic effects are obtained, i. H. the effectiveness of Mixing is greater than the effectiveness of the individual components. Particularly cheap Mix partners are e.g. B. the following connections:

Sulfenamides such as dichlorfluanid (Euparen), tolylfluanid (Methyleuparen), Folpet, Fluorfolpet;
Benzimidazoles such as Carbendazim (MBC)), Benomyl, Fuberidazole, Thiabendazole or their salts;
Thiocyanates such as thiocyanatomethylthiobenzothiazole (TCMTB), methylene bisthio cyanate (MBT);
quaternary ammonium compounds such as benzyldimethyltetradecylammonium chloride, benzyldimethyldodecylammonium chloride, dodecyldimethylammonium chloride;
Morpholine derivatives such as C₁₁-C₁₄-4-alkyl-2,6-dimethyl-morpholine homologue (tride morph), (±) -cis-4- [3- (tert-butylphenyl) -2-methylpropyl] -2,6-dimethylmorphol -in (fenpropimorph), falimorph;
Phenols such as o-phenylphenol, tribromophenol, tetrachlorophenol, pentachlorophenol, 3-methyl-4-chlorophenol, dichlorophen, chlorophen or their salts;
Azoles such as triadimefon, triadimenol, bitertanol, tebuconazole, propiconazole, azaconazole, hexaconazole, prochloraz, cyproconazole, 1- (2-chlorophenyl) -2- (1-chlorocyclopropyl) -3- (1,2,4-triazol-1-yl ) -propan-2-ol and 1 - (2-chlorophenyl) -2- (1,2,4-triazol-1-yl-methyl) -3,3-dimethyl-butan-2-ol.

Iodopropargyl derivatives such as iodopropargyl butyl carbamate (IPBC), chlorophenyl formal, phenyl carbamate, hexyl carbamate, cyclohexyl carbamate, iodopropargyloxyethyl phenyl carbamate;
Iodine derivatives such as diiodomethyl-p.arylsulfones e.g. B. Diiodomethyl-p-tolyl sulfone;
Bromine derivatives such as bromopol;
Isothiazolines such as N-methylisothiazolin-3-one, 5-chloro-N-methylisothiazolin-3-one, 4,5-dichloro-N-octylisothiazolin-3-one, N-octylisothiazolin-3-one (octilinones);
Benzisothiazolinones, cydopentene isothiazolines;
Pyridines such as 1-hydroxy-2-pyridinthione (and their Na, Fe, Mn, Zn salts), tetrachloro-4-methylsulphonyl-pyridine;
Metal soaps such as tin, copper, zinc naphthenate, octoate, -2-ethylhexanoate, oleate, phosphate, benzoate, oxides such as TBTO, Cu₂O, CuO, ZnO;
Organic tin compounds such as tributyltin naphthenate and tributyltin oxide;
Dialkyldithiocarbamates such as Na and Zn salts of dialkyldithiocarbamates, tetrams thyltiuramidisulfid (TMTD);
Nitriles such as 2,4,5,6-tetrachloroisophthalonitrile (chlorothalonil) and other microbicides with activated halogen groups such as Cl-Ac, MCA, tectamer, bromopol, bromidox;
Benzothiazoles such as 2-mercaptobenzothiazoles; says Dazomet;
Quinolines such as 8-hydroxyquinoline;
Formaldehyde-releasing compounds such as benzyl alcohol mono (poly) hemiformal, oxazolidines, hexahydro-s-triazines, N-methylolchloroacetamide;
Tris-N- (cyclohexyldiazeniumdioxy) aluminum, N- (cyclohexyldiazeniumdioxy) tri-butyltin or K. salts, bis- (N-cyclohexyl) diazinium (-dioxy-copper or aluminum).

The following are preferably added as insecticides:

Phosphoric acid esters such as azinphos-ethyl, azinphos-methyl, 1- (4-chlorophenyl) -4- (O- ethyl, S-propyl) phosphoryloxypyrazole (TIA-230), chlorpyrifos, Coumaphos, Demeton, Demeton-S-methyl, Diazinon, Dichlorvos, Dimethoate, Ethoprophos, Etrimfos, Fenitrothion, Fention, Heptenophos, Parathion, Parathion-methyl,  Phosalones, Phoxim, Pirimiphos-ethyl, Pirimiphos-methyl, Profenofos, Prothiofos, Sulprofos, Triazophos and Trichlorphon.

Carbamates such as aldicarb, bendiocarb, BPMC (2- (1-methylpropyl) phenylmethyl carbamate), butocarboxime, butoxycarboxime, carbaryl, carbofuran, carbosulfan, Cloethocarb, Isoprocarb, Methomyl, Oxamyl, Pirimicarb, Promecarb, Propoxur and Thiodicarb.

Pyrethroids such as allethrin, alphamethrin, bioresmethrin, byfenthrin (FMC 54 800), Cycloprothrin, cyfluthrin, decamethrione, cyhalothrin, cypermethrin, deltamethrin, Alpha-cyano-3-phenyl-2-methylbenzyl-2,2-dimethyl-3- (2-chloro-2-trifluoromethylvinyl) cyclopropanecarboxylate, fenpropathrin, fenfluthrin, fenvalerate, flucythrinate, flu methrin, fluvalinate, permethrin and resmethrin; Nitroimines and nitroimides such as 1- [(6-Chloro-3-pyridinyl) methyl] -4,5-dihydro-N-nitro-1H-imidazol-2-ami-n (imidaclo prid).

Organosilicon compounds, preferably dimethyl (phenyl) silylmethyl-3-phenoxy benzyl ethers such as B. Dimethyl (4-ethoxyphenyl) silylmethyl-3-phenoxybenzyl ether or dimethyl (phenyl) silylmethyl-2-phenoxy-6-pyridylmethyl ether such as e.g. B. Tue. methyl- (2-ethoxyphenyl) silylmethyl-2-phenoxy-6-pyridylmethyl ether or (phenyl) [3- (3-phenoxyphenyl) propyl] dimethyl) silanes such as e.g. B. (4-ethoxyphenyl) - [3 (4-fluoro- 3-phenoxyyphenyl) propyl] dimethylsilane.

Algicides, molluscicides, active substances against are considered as other active substances "sea animals" referring to e.g. B. Settling floor paints.

The production of active ingredients and their use according to the invention illustrated by the following examples.

Manufacturing examples example 1

5.0 g (110.1 mmol) spiro- [2,4] -heptan-4-one and 6.4 g (140.6 mmol) 4- Chlorobenzaldehyde is stirred with 0.1 g of NaOH in 50 ml of methanol for 50 hours and then suctioned off. 9.5 g (90%) of 5- (4-chlorobenzylidene) -spiro- [2,4] - are obtained. heptanon-4-one with melting point 89-90 ° C.

4.81 g (0.02 mol) of 5- (4-chlorobenzylidene) -spiro- [2,4] -heptan-4-one are dissolved in 42 ml Dissolved THF and a solution of 1 g (0.025 mol) sodium hydride (60% in Mineral oil) in 20 ml DMSO and 4.64 g (0.023 mol) trimethylsulfonium iodide in 33 ml DMSO added at -10 ° C and stirred at 25 ° C for 12 h. After extraction with H₂O / CHCl₃ gives 6.50 g of the compound

from which
5.0 g (0.02 mol) are reacted with 1.54 g (0.022 mol) of triazole in 100 ml of DMF in 5 h at 90 ° C. 0.4 g (6%) is obtained after column chromatography with toluene as the eluent

The compound is characterized by its NMR spectrum.  

The following compounds of the formula (I) or the corresponding intermediates of the formulas (IV) are obtained in a corresponding manner and in accordance with the general information on the preparation,
in which Me stands for methyl and Ph for phenyl:

Table 1

Application example

A. To demonstrate the effectiveness against fungi, the minimal inhibitory Concentration (MIC) of the compound I according to the invention determined.

An agar made using malt extract was used with Active substances according to the invention in concentrations of 0.1 mg / l to 5000 mg / l transferred. After solidification, the agar was contaminated with pure cultures of the test organisms listed in Table 1.

After storage for 2 weeks at 28 ° C and 60 to 70% relative humidity the MIC was determined. MIC is the lowest concentration of active ingredient where there is no growth due to the microbe species used, it is in given in Table 2 below.

Table 2

Comparison of the MIC values (mg / l) of compound I according to the invention with compound II

Claims (8)

1. Azolylmethylspiro- [2,4] -heptanols of the formula (I) in which
R¹, R², R³, R⁴ independently of one another for hydrogen C₁-C₆-alkyl, alkenyl or halogen, and
R⁵ represents phenyl, furyl, thienyl, optionally substituted by 1 to 4 groups of halogen, C₁-C₆alkyl, alkoxy, thioalkaryl, alkenyl or haloalkyl or haloalkoxy,
X for CH or N
stands,
as well as their acid addition salts and metal salt complexes. 2. Compounds of formula (I) according to claim 1, in which
Alkyl represents methyl, ethyl, propyl, isopropyl, n-, i-, s-, t-butyl, n-pentyl, n-hexyl and their branched isomers,
Alkenyl for exo-methylene, allyl, vinyl, butenyl is in each case bound in the 1- or 2- or 3- position,
Alkoxy is C₁-C₄alkoxy such as methoxy, ethoxy, n-, i-propyloxy, n-, i-, s-, t-butyloxy,
Halogen represents F, Cl, Br, I and
Haloalkyl or haloalkoxy for CF₃ CF₂CF₃, O-CF₃, stands. 3. Compounds of formula (I) according to claim 1, in which
R¹, R², R³, R⁴ independently of one another for hydrogen methyl, fluorine or chlorine
R⁵ represents phenyl, thienyl or furyl, which are optionally substituted by 1 to 3 groups such as halogen, C₁-C₃-alkyl, alkoxy, haloalkyl or haloalkoxy, and
X represents CH or N. 4. Compounds of formula (I) according to claim 1, in which
R¹, R², R³, R⁴ independently of one another represent hydrogen, methyl or fluorine, but in which at least two radicals are hydrogen,
R⁵ represents phenyl, furyl, thienyl, 4-chlorothienyl, or phenyl substituted by 1 to 2 chlorine, fluorine, CF₃ or O-CF₃ groups. 5. Process for the protection of technical materials, characterized in that that these materials with compounds of formula (I) according to claim 1 treated or mixed. 6. Material protection agent containing at least one compound of the formula (I) according to claim 1.   7. Use of compounds of formula (I) according to claim 1 for protection of technical materials. 8. A process for the preparation of compounds of formula (I) according to claim 1, characterized in that

• 1) compounds of the formula (II) reacted in a diluent and in the presence of a base with compounds of the formula (III) R⁵-CHO (III),
• 2) the intermediate of formula (IV) thus obtained then reacted with trimethylsulfonium iodide in the presence of a base, if appropriate in a diluent,
• 3) the intermediate of formula (V) thus obtained ultimately with a compound of formula (VI) optionally added in the presence of a diluent.