DE4142458A1 - FUNGICIDE COMPOUNDS - Google Patents

Description

The invention relates to pyridylthiazole derivatives which are useful as fungicides, to processes for their preparation, fungicidal compositions that are the same and methods of using the same for Fighting fungi, especially fungal infections on plants.

2-aryl-6-heteroarylpyridine derivatives are described in EP-A2- 04 51 585 described.

According to the invention, compounds of the general Formula (I) wherein R¹ is R², R²O or R²R³R⁴C, R² is Phenyl is optionally substituted by halogen (especially Chlorine or fluorine), C₁-₄-alkyl or C₁-₄-alkoxy substituted and R³ and R⁴ are independently hydrogen or methyl stand; and the acid addition salts and metal complexes thereof proposed.

According to a preferred embodiment, the invention relates Compounds of general formula (I) wherein R¹ is for R², R²O or R²R³R⁴C, R² is phenyl optionally by halogen (especially chlorine), C₁-₄-alkyl (especially methyl) or C₁-alkoxy (especially methoxy) is substituted, and R³ and R⁴ are independently hydrogen or methyl; and the acid addition salts and metal complexes from that.

The alkyl groups and the alkyl portions of the alkoxy groups contain 1 to 4 carbon atoms and are in even or branched chains. Examples are methyl, Ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

Halogens are z. As fluorine, chlorine and bromine.

The acid addition salts of the compounds of the invention  are z. As salts with inorganic or organic acids, such as Hydrochloric acid, nitric acid, sulfuric acid, acetic acid, 4-toluenesulfonic acid and oxalic acid.

The metal complexes of the compounds of the invention are z. B. complexes with copper, zinc or manganese cations.

According to a further embodiment, the invention relates Compounds of formula (I) wherein R¹ is R²O or R²R³R⁴C R² is phenyl optionally substituted by halogen (especially chlorine or fluorine), C₁-₄-alkyl (especially Methyl or tert-butyl) or C₁-alkoxy (in particular Methoxy), and R³ and R⁴ are independently hydrogen or methyl; and the acid addition salts and Metal complexes thereof.

According to a further embodiment, the invention relates Compounds of formula (I) wherein R¹ is R²R³R⁴C, R² is phenyl, optionally substituted by halogen (especially Chlorine or fluorine), C₁-4-alkyl (especially methyl or tert-butyl) or C₁-alkoxy (in particular methoxy) is substituted, and R³ and R⁴ are independently hydrogen or methyl.

It is preferred that R³ and R⁴ are both hydrogen stand.  

Examples of compounds of the formula (I) according to the invention can be found in Tables I (for compounds of formula (Ia)), II (for compounds of formula (Ib)), and III (for Compounds of the formula (Ic)).

Table I

Table II

Table III

table IV Selected proton NMR data

Table IV shows selected proton NMR data for some Compounds of Tables I, II and III which are incorporated herein characterized as oils or gums. The chemical shifts are measured in ppm from tetramethylsilane, and Deuterochloroform was used throughout as a solvent. The following abbreviations are used:

s = singlet
dd = double doublet
dt = double triplet
m = multiplet
d = doublet
t = triplet
q = quartet
bd = wide doublet

Compounds of the general formula (I) can be prepared in this way as shown in Scheme 1. In Scheme 1 R¹ has the above definition throughout.

Thus, compounds of general formula (I) wherein R¹ is R²O and R² has the meaning given above, be prepared by making a connection of the formula (II) with a compound of the general formula R²OH, wherein R² has the meaning given above, in Presence of a suitable base (such as potassium carbonate) and a suitable copper (I) salt such as. B. Copper (I) - chloride) in a suitable solvent (such as dimethylformamide) at a suitable temperature.

Compounds of general formula (I) wherein R¹ is for  R²R³R⁴C and R², R³ and R⁴ are as defined above have (but R² is phenyl, the not optionally substituted by bromine or iodine), can be prepared by making a connection of the formula (II) with a compound R²R³R⁴CH coupling. The Coupling reaction can be carried out by that the compound R²R³R⁴CH with n-butyllithium and then with Treated with zinc chloride and then tetrakis (triphenylphosphine) palladium ° with the compound of the formula (II) admits. The reaction is at a suitable temperature executed.

Alternatively, compounds of formula (I) wherein R1 is for R²R³R⁴C and R², R³ and R⁴ are as defined above own, be prepared by that one Compound R²R³R⁴CHal, wherein Hal represents a suitable halogen atom (Chlorine, bromine or iodine), with magnesium in one suitable solvents (such as tetrahydrofuran or Diethyl ether) to give a Grignard reagent R²R³R⁴CMgHal manufacture. The Grignard Regenz is then treated with zinc chloride implemented, and the product thus formed is connected of the formula (II) in the presence of tetrakis (triphenylphosphine) palladium ° implemented.

A compound of the general formula (I) wherein R¹ is R² and R² has the meaning given above, can be prepared by making a compound of Formula (II) with a compound R²Hal, wherein R² is the above has stated requirement and Hal for a suitable Halogen atom (chlorine, bromine or iodine), but the more reactive is than any other halogen substituent that may be is present at R². The reactivity is in the order of iodine is greater than bromine greater than chlorine greater as fluorine. The coupling reaction can be carried out thereby be that the compound R²Hal with n-butyllithium and then treated with zinc chloride and then tetrakis (triphenylphosphine) palladium ° with the compound of the formula (II) admits.  

The compound of formula (II) can be prepared thereby that is a compound of formula (III) with thioacetamide in a suitable solvent (such as dioxane).

The compound of formula (III) can be prepared thereby that a compound of formula (IV) with a suitable Bromination agent (such as bromine) in the presence of a suitable acid (such as acetic acid) is brominated.

The compound of formula (IV) can be prepared thereby that 2,6-dibromopyridine with an alkyllithium (as z. B. n-butyllithium) and then N, N-dimethylacetamide admits.

2,6-dibromopyridine is commercially available and can be obtained under Use of methods described in the literature prepared become.

Compounds of general formula (I) wherein R¹ is R² can also be prepared as shown in Scheme 2 is shown. Throughout Scheme 2, R¹ is R² and has R² is the meaning given above.

Thus, compounds of general formula (I) wherein R¹ R² is and R² has the abovementioned meaning, be prepared by making a compound of general formula (VII) with thioacetamide in the presence of a suitable solvent (such as dioxane).

A compound of the general formula (VII) can thereby be prepared that a compound of the general Formula (V) with a suitable brominating agent (such as e.g. Bromine) in the presence of a suitable acid (such as acetic acid) brominated.

A compound of the general formula (V) can be produced thereby  be that one is a compound of the general Formula (VI) couples with an acetyl group. The coupling reaction can be carried out by making a connection of the general formula (VI) with acetaldehyde in Presence of a suitable acid (such as sulfuric acid), a suitable metal salt (such as iron (II) sulfate heptahydrate) and a suitable oxidizing agent (such as z. B. tert-butyl hydroperoxide) in a suitable solvent (such as water).

A compound of the general formula (VI) can thereby be prepared by reacting 2-bromopyridine with a compound R²Hal, wherein R² has the meaning given above and Hal represents a suitable halogen atom (chlorine, bromine or Iodine), couples. The coupling reaction can thereby be carried out be that the 2-bromopyridine with n-butyllithium and then treated with zinc chloride followed by tetrakis (triphenylphosphine) palladium ° with a compound R²Hal (wherein R² and Hal have the meanings given above) admits.

Acid addition salts of the compounds of general formula (I) can be prepared by adding 1 equivalent a strong acid, such as. Hydrochloric acid, sulfuric acid or Nitric acid, to a solution of (I) in a suitable Solvent admits.

The present invention includes methods of preparation the compounds of the formula (I) as defined above and of intermediates of the formula (II), (V) and (VII) according to above definition.

The compounds are active fungicides and can be used to fight one or more of the following pathogens used are: Pyricularia oryzae on rice; Puccinia recondita, Puccina striiformis and other rust diseases on wheat, Puccinia horei, Puccinia striiformis and other rust diseases  on barley and rust diseases on others Host plants, such. Coffee, pears, apples, peanuts, Vegetables and ornamental plants; Erysiphe graminis (powdery mildew) on barley and wheat and other mildews at various Host plants, such. Sphaerotheca macularis on hops, Sphaerotheca fuliginea on pumpkins (eg cucumbers), Podosphaera leucothricha a apples and Uncinula necator vines; Helminthosporium spp., Rhynchosporium spp., Septoria spp., Pyrenophora spp., Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals; Cercospora arachidicola and Cercosporidium personata Peanuts and other Cercospora species on other host plants, such as Beet, bananas, soybeans and Rice; Botrytis cinerea (gray mold) on tomatoes, strawberries, Vegetables, vines and other host plants; Alternaria spp. on vegetables (eg cucumbers), oilseed rape, apples, tomatoes and other host plants; Venturia inaequalis (scab) on apples; Plasmopara viticola on vines; other downy mildew diseases, such as B. Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and others Host plants, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucumbers; Phytophthora infestans on potatoes and tomatoes and other Phytophthora species Vegetables, strawberries, avocado, peppers, ornamental plants, tobacco, Cocoa and other host plants; Thanatephorus cucumeris Rice and other Rhizoctonia species on different host plants) such as As wheat and barley, vegetables, cotton and lawn.

Some of the compounds show a wide range of activity against fungi in vitro. You can also have an activity against various diseases occurring after the harvest on fruits (such as Penicillium digitatum and italicum and Trichoderma viride on oranges, Gloeosporium musarum on bananas and Botrytis cinerea on grapes).

Furthermore, some of the compounds may be used as seed stains be effective against pathogens, for. Fusarium spp.,  Septoria spp., Tilletia spp. (Brand, a seed-borne Disease of wheat), Ustilago spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.

The compounds migrate acropetally / locally in the plant tissue. In addition, the compounds are sufficiently volatile, that they are active in the vapor phase against fungi on plants.

The invention therefore further relates to a method for Fighting mushrooms, in which on a plant, on a seed of a plant or the location of the seed or the plant has a fungicidally effective amount of one above defined compound or a composition containing same is applied.

The compounds can be directly for agricultural purposes but are suitably used in compositions formulated as a carrier or diluent contain. The invention therefore also relates fungicidal compositions which have one defined above Compound and a pharmaceutically acceptable carrier or Diluents are included. It is preferred that these compositions are 0.0001 to 95%, especially 0.001 to 60%, and most preferably 0.01 to 1%, of the compound contain.

The compounds can be applied in various ways become. For example, they may be formulated or unformulated directly on the foliage of a plant on seed or on other media in which plants grow or planted be applied, or they can be sprayed, dusted or as a cream or paste formulation be applied. Finally, they can also be called Steam or applied as granules with slow release of active ingredient become.  

The application can be applied to any part of the plant, such. B. Foliage, stems, branches or roots, or on the the Roots surrounding soil or seeds before sowing or on the ground in general or on irrigation water or on hydropone culture systems are applied. The invention Compounds can also be injected into plants or on vegetation using electrodynamic Spray techniques or other low volume working Methods are sprayed on.

The term "plant" as used herein includes seedlings, Bushes and trees. Furthermore, the invention relates to Fungal control a representative, protective, Prophylactic and eradicating treatment.

The compounds are preferably for agricultural and horticultural uses in the form of a composition. The type of composition that is in a given Case used depends on the intended Application method.

The compositions may take the form of dusting powders or granules containing the active ingredient (inventive Compound) and a solid diluent or Carrier contain such. B. fillers, for. Kaolin, Bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth, gypsum, diatomaceous earth and china clay. Such granules may be previously prepared Granules that are suitable for application to the Soil are suitable without further treatment. These granules can be prepared either by adding pellets from the Filler impregnated with the active ingredient, or that a mixture of the active ingredient and powdered Pelletized filler. Compositions for the Seed pickling may contain an agent (such as a mineral oil), which the adhesion of the composition to the seed promotes. Alternatively, the active ingredient may be for seed dressing purposes using an organic solvent  (such as N-methylpyrrolidone, propylene glycol or N, N-dimethylformamide) be formulated. The compositions can also take the form of wettable powders or in water have dispersible granules, which net or Dispersants contain to the dispersion in liquids to facilitate. The powders and granules can also contain fillers and suspending agents.

Emulsifiable concentrates or emulsions can thereby be prepared that the active ingredient in an organic solvent, optionally contains a wetting or emulsifying agent, and then the mixture in water, which is also a network or May contain emulsifier. Suitable organic solvents are z. As organic solvents, for. B. alkylbenzenes and alkylnaphthalenes, ketones, e.g. B. cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons, z. As chlorobenzene and trichloroethane, and alcohols, eg. B. Benzyl alcohol, furfuryl alcohol, butanol and glycol ether.

Suspension concentrates of largely insoluble solids can be prepared by putting them in one Grinds ball mill with a dispersant, where also adding a suspending agent to settle the solid to prevent.

Compositions used as sprays may be in the form of aerosols, the Formulation in a container under the pressure of a propellant, such as Fluorotrichloromethane or dichlorodifluoromethane, is held.

The compounds according to the invention can be in the dry state be mixed with a pyrotechnic mixture, to make a composition suitable for production a smoke containing the compounds in closed Rooms are suitable.  

Alternatively, the compounds may be used in microcapsule form become. They can also be biodegradable Polymeric formulations are processed to a slower rate and to achieve controlled release of the active substance.

By the inclusion of other additives, such. B. of additives to improve distribution, adhesion and resistance against rain on treated surfaces, The different compositions can be better for different Applications are adapted.

The compounds of the invention can be used as mixtures with Fertilizers (such as nitrogen, potassium or phosphorus-containing Fertilizers). compositions containing only fertilizer granules, which for example coated with the compound are preferred. Such Granules suitably contain up to 25% by weight of the connection. The invention also relates to fertilizer compositions, a fertilizer and a compound of the general formula (I) or a salt or a metal complex included.

Wettable powders, emulsifiable concentrates and suspension concentrates usually contain surfactants, such as As wetting agents, dispersants, emulsifiers or Suspending agent. These agents can be cationic, anionic or non-ionic nature.

Suitable cationic agents are quaternary ammonium compounds, such as B. cetyltrimethylammonium bromide. suitable Anionic agents are soaps, salts of aliphatic monoesters sulfuric acid (e.g., sodium lauryl sulfate) and Salts of sulfonated aromatic compounds (such as Sodium dodecylbenzenesulfonate, sodium, calcium or Ammonium lignosulfonate, butylnaphthalene sulfonate and mixtures sodium diisopropyl and triisopropylnaphthalenesulfonate).  

Suitable nonionic agents are the condensation products of ethylene oxide with fatty alcohols, such as. B. oleyl or cetyl alcohol, or with alkylphenols, such as. Eg octyl or nonylphenol and octylcresol. Other nonionic agents are the partial esters that are different from long-chain fatty acids and Hexitanhydriden derive the condensation products of this Partial ester with ethylene oxide and the lecithins. suitable Suspending agents are hydrophilic colloids (such as polyvinylpyrrolidone and sodium carboxymethylcellulose) and swelling clays, such as. B. bentonite or attapulgite.

Compositions for use as aqueous dispersions or emulsions are generally in the form of a Concentrate supplied, which has a high proportion of active Ingredient contains, taking the concentrate before use to dilute. These concentrates should preferably endure longer storage times and after such Storage can still be diluted with water to aqueous Preparing preparations for a sufficient amount of time remain homogeneous so that they pass through a conventional spray device can be applied. The concentrates contain suitably up to 95% by weight, preferably 10 to 85 wt .-%, z. B. 25 to 60 wt .-%, of the active Component. After dilution to produce aqueous Preparations such preparations may contain different amounts of active ingredient contained, what of the intended Application depends, but an aqueous preparation, the 0.0005 or 0.01 to 10% by weight of the active ingredient contains, can be used well.

The compositions of the invention may contain other compounds containing biological activity, such as. B. Compounds with a similar or complementary fungicidal Activity or with a plant growth regulating, herbicidal or insecticidal activity.

A fungicidal compound found in the inventive  Compositions may be present, such is one Ear diseases on cereals (such as wheat), eg. B. Septoria, Gibberella and Helminthosporium spp., From seed and ground borne diseases and fluffy and Powdery mildew diseases on vines and powdery mildew diseases and can fight scab on apples, etc. The inclusion of other fungicides may cause the compositions get a broader spectrum of activity than it does the compound of the general formula (I) alone. Furthermore, the additional fungicid may be synergistic Effect on the fungicidal activity of the compound of the general Exercise formula (I). Examples of fungicidal compounds, in the compositions of the invention can be incorporated are (±) -cis-1- (4-chlorophenyl) - 2- (1H-1,2,4-triazol-1-yl) cycloheptanol, (2RS, 3RS) -1- [3- (2- Chlorophenyl) -2- (4-fluorophenyl) oxiran-2-ylmethyl] -1H- 1,2,4-triazole, (RS) -1-aminopropylphosphonic acid, (RS) -4- (4-chlorophenyl) -2-phenyl-2- (1H-1,2,4-triazol-1-ylmethyl) - butyronitrile, (Z) -N-But-2-enyloxymethyl-2-chloro-2 ', 6'- diethylacetanilide, 1- (2-cyano-2-methoxyiminoacetyl) -3- ethyl urea, 3- (2,4-dichlorophenyl) -2- (1H-1,2,4-triazole) 1-yl) quinazolin-4 (3H) -one, 4- (2,2-difluoro-1,3-benzodioxole) 4-yl) pyrrole-3-carbonitrile, 4-bromo-2-cyano-N, N-dimethyl-6- trifluoromethylbenzimidazole-1-sulfonamide, 5-ethyl-5,8- dihydro-8-oxo (1,3) -dioxol (4,5- g) quinoline-7-carboxylic acid, α- [N- (3-chloro-2,6-xylyl) -2-methoxyacetamido] -γ-butyrolactone, Aldimorph, anilazine, benalaxyl, benomyl, biloxazole, Binapacryl, Bitertanol, Blasticidin S, Bromuconazole, Bupirimat, buthiobate, captafol, captan, carbendazim, carboxin, Chlorobenzothiazone, chloroneb, chlorothalonil, chlorozolinate, copper-containing compounds, eg. B. copper oxychloride, copper sulfate and Bordeaux mixture, cycloheximide, cymoxanil, Cyproconazole, cyprofuram, di-2-pyridyl disulfide, 1,1'-dioxide, Dichlofluanid, Dichlone, Diclobutrazole, Diclomethine, Dicloran, Difenoconazole, dimethamorph, dimethirimol, diniconazole, Dinocap, Ditalimfos, Dithianon, Dodemorph, Dodin, Edifenphos, Etaconazole, ethirimol, (Z) -N-benzyl-N - ([methyl (methyl  thioethylidenamino-oxycarbonyl) amino] thio) -beta-alaninatethylester, Etridiazole, Fenapanil, Fenarimol, Fenfuram, Fenpiclonil, fenpropidin, fenpropimorph, fentin-acetate, Fentin hydroxide, Flutolanil, Flutriafol, Flusilazole, Folpet, Fosetyl aluminum, Fuberidazole, Furalaxyl, Furconazole cis, Guazatine, hexaconazole, hydroxyisoxazole, imazalil, imibenconazole, Iprobenfos, iprodione, isoprothiolane, kasugamycin, Mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, methfuroxam, Metsulfovax, myclobutanil, neoasocin, nickel dimethyldithiocarbamate, Nitrothal isopropyl, nuarimol, Ofurac, organo-mercury compounds, oxadixyl, oxycarboxin, Pefurazoate, penconazole, pencycuron, phenazine oxide, phthalide, Polyoxin D, polyram, probenazole, prochloraz, procymidone, Propamocarb, propiconazole, propineb, prothiocarb, pyrazophos, Pyrifenox, Pyrochilon, Pyroxyfur, Pyrrolnitrin, Chinomethionat, Chintozen, streptomycin, sulfur, tebuconazole, Techlofthalam, Tecnazene, Tetraconazole, Thiabendazole, Thicyofen, thiophanate-methyl, thiram, tolclofos-methyl, Triacetate salt of 1,1'-iminodi (octamethylene) diguanidine, Triadimefon, triadimenol, triazobutyl, tricyclazole, Tridemorph, Triforin, Validamycin A, Vinclozoline, Zarilamide and Zineb. The compounds of general formula (I) can be mixed with soil, peat and other rotting media be used to protect the plants against seed, soil-borne and foliar fungal diseases.

Suitable insecticides present in the compositions according to the invention Buprofezin, Carbaryl, carbofuran, carbosulfan, chlorpyrifos, cycloprothrin, Demeton-s-methyl, diazinon, dimethoate, ethofenprox, Fenitrothion, fenobucarb, fenthion, formothione, isoprocarb, Isoxathione, monocrotophos, phenthoate, pirimicarb, propaphos and XMC.

Plant growth regulating compounds are compounds, which is the formation of grasses or seed heads influence or which selectively reduce the growth of less  suppress desired plants (eg grasses).

Examples of suitable plant growth regulating Compounds for use with the invention Compounds are 3,6-dichloropicolinic acid, 1- (4-chlorophenyl) - 4,6-di-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid), 3,6-dichloroanisate methyl ester, abscisic acid, Asulam, Benzolprop-ethyl, Carbetamide, Daminozide, Difenzoquat, Dikegulac, ethephon, fenpentezole, fluoride amide, glyphosate, Glyphosine, hydroxybenzonitriles (eg bromoxynil), inabenfid, Isopyrimol, long-chain fatty alcohols and acids, maleic hydrazide, Mefluidide, morphactins (eg chlorofluoroecole), Paclobutrazole, phenoxyacetic acid (eg 2,4-D or MCPA), substituted benzoic acids (eg, trÿodobenzoic acid), substituted quaternary ammonium and phosphonium compounds (eg chloro-quat, chlorophonium or mepiquat chloride), Tecnazen, the auxines (eg, indoleacetic acid, indolebutyric acid, Naphthylacetic acid or naphthoxyacetic acid), which Cytokinins (eg, benzimidazole, benzyladenine, benzylaminopurine, Diphenylurea or kinetin), the gibberellins (eg GA₃, GA₄ or GA₇) and tri-penthenol.

The following examples illustrate the invention. In the Examples consistently use the following abbreviations:

GC = Gas Chromatography
HPLC = high performance liquid chromatography
Mp = melting point
TLC = thin layer chromatography
mol = mole

Example 1

This example illustrates the preparation of 2-acetyl-6 bromopyridine.

2,6-Dibromopyridine (23.7 g, 0.1 mol) was dissolved in diethyl ether (250 ml - freshly distilled from sodium and benzophenone)  in a drying apparatus under a dry nitrogen atmosphere dissolved. The stirred solution was (in one Dry ice / acetone bath) cooled to -60 ° C, with 2,6-dibromopyridine failed. A solution of n-butyllithium in one Hexane mixture (2.5 molar, 44 ml, 0.11M) was then added in a Portion was added, and the reaction mixture was stirred, until all solid dissolved (15 min). N, N- Dimethylacetamide (9.6 g, 0.11 mol, distilled from barium oxide and dried over 4Å molecular sieves) was then grown in a portion added, with an exothermic rise in temperature to -40 ° C occurred. The resulting emulsion was Stirred with cooling for 5 min, whereupon it was at room temperature was allowed to warm. Water (200 ml) was then added and the two layers were separated. The watery Layer was extracted with diethyl ether (2 x 200 ml portions), and the combined ether solutions were anhydrified Dried magnesium sulfate, filtered and evaporated, whereby a brown liquid (26.4 g) was obtained.

GC showed unreacted starting material 24%, one second main peak 56% and five other peaks that the Make up the rest.

The liquid was purified by flash vacuum chromatography Silica gel, eluting with Arcton 113. The fractions that were rich at the second main peak were evaporated to give a pale yellow liquid which crystallized on standing. The solid became recrystallized from hexane to give the title compound (3.2 g, mp 51.8-52.3 ° C) (Beilstein 54-5 ° C) was obtained.

The mother liquor from the recrystallization was washed with the less pure fractions from the chromatography column combined and rechromatographed, with another 7.1 g of the title compound were obtained as a pale yellow solid. Total yield, 10.3 g (51.5%) of the title compound.  

example 2

This example illustrates the preparation of 2-acetyl-2 ', 6- dibromopyridine (also referred to as 2-bromo-6-bromoacetylpyridine).

2-Acetyl-6-bromopyridine (9.2g, 0.046M, prepared as in Example 1) was dissolved in glacial acetic acid (25 ml), and the Solution was stirred at 70 ° C, dropwise bromine (7.4 g, 2.4 mL, 0.046 mol) was added over 30 min. Upon completion of the addition, stirring and heating were still Continued for 1 h until the brown coloration disappeared. [GC analysis showed a mixture of 2-acetyl-6-bromopyridine (11%), 2-acetyl-2 ', 6-dibromopyridine (77%) and 2-acetyl 2 ', 2', 6-tribromopyridine (13%).] The resulting dark green Solution was then allowed to warm to room temperature, with Quenched with water (50 ml) and with sodium hydroxide solution (2 molar), followed by two servings Ethyl acetate (200 ml) was extracted. The United Ethyl acetate extracts were treated with saturated sodium bicarbonate Solution washed over anhydrous magnesium sulfate dried, filtered and evaporated, giving a brown Liquid was obtained. Colored impurities and 2-Acetyl-6-bromopyridine was purified by flash-vacuum chromatography on silica gel, using dichloromethane was eluted. The resulting two-component mixture was separated by preparative HPLC, using dichloromethane was eluted. These were 2-acetyl-2 ', 2', 6-tribromopyridine (1.5 g) as a pale yellow liquid and 2-acetyl-2 ', 6-dibromopyridine (8.5 g, 66% yield) as a pale yellow liquid receive. 1 H NMR (CDCl₃): δ 2.71 (3H, s); 7.69 (2H, m); 7.99 (1H, dd) ppm.

example 3

This example illustrates the preparation of 2-bromo-6 (2-methylthiazol-4-yl) pyridine.

2-Acetyl-2 ', 6'-dibromopyridine (10.4 g, 37.3 mol) was added in Dioxane (100 ml, dried over 4Å molecular sieves) dissolved,  and a solution of thioacetamide (2.9 g, 38.7 mol) in dry dioxane (100 ml) was stirred with stirring temperature added. The solution was stirred for 5 minutes, while a white solid precipitated. The suspension was then refluxed with stirring for 1 h, allowed to cool to room temperature and by pouring in a 10% solution of ethylenediaminetetraacetic acid Monosodium salt with pH 8 to 9 (150 ml) quenched. The pH of the mixture was adjusted by adding saturated sodium Hydrogen carbonate solution adjusted to 8, followed by Ethyl acetate (3 x 200 ml portions) was extracted. The combined ethylene acetate extracts were washed with water (250 ml) washed and evaporated, giving a pale green solid was obtained. The solid was flash-evaporated Chromatography on silica gel eluting with increasing Concentrations of dichloromethane in Arcton 113 were purified and then with carbon treatment from hexane crystallized. The title compound became white obtained, mp 95.0 to 95.7 ° C, yield 7.3 g (76.8%).

example 4

This example illustrates the preparation of 2-benzyl-6 (2-methylthiazol-4-yl) -pyridine (Compound No. 1 of Table III).

N, N, N ', N'-tetramethylethylenediamine (0.65 ml, 0.0073 M) in dry toluene (30 ml) under a nitrogen atmosphere dissolved. A solution of n-butyllithium in hexane (2.8 ml, 2.5 molar, 0.007 mol) was then added, and the mixture was stirred for 45 min at 80 ° C, with a cloudy orange color solution was obtained. This was at room tempera cooled, and a solution of anhydrous zinc chloride in tetrahydrofuran (20 mL, 1.0 molar, 0.02 mol) was added give. The yellow color disappeared and an exothermic heat rise to 34 ° C was observed while a white feast failed. When added more zinc chloride solution was, the solid dissolved again. A solution from  Tetrakis (triphenylphosphine) palladium ° (0.1 g, catalyst) and 2-bromo-6- (2-methylthiazol-4-yl) -pyridine (1.0 g, 0.0039 in dry tetrahydrofuran (25 ml) were then added and the solution was heated at 70 ° C for 2 hours. During this time a solid precipitated, the solution becoming dark has been. GC analysis showed complete disappearance of 2-Bromo-6- (2-methylthiazol-4-yl) -pyridine and occurrence a new major peak (91%) with triphenylphosphine (4%) and triphenylphosphine sulfide (5%). The reaction mixture was then cooled to room temperature and by the addition of 10% ethylenediaminetetraacetic acid monosodium salt quenched with pH 8 to 9 (100 ml) and with ethyl acetate (2 x 100 ml). Evaporate the ethyl acetate solutions gave a dark green oil by flash chromatography was purified on silica gel, using dichloromethane and then Diethyl ether was eluted. Evaporation of the united Diethyl ether fractions gave the product as a dark yellow Oil 1.01 g (97% yield), which is a single GC Pointed and showed a single spot on TLC.

example 5

This example illustrates the preparation of 2- (2-methyl thiazol-4-yl) -6- (2-methylphenoxy) pyridine (Compound No. 5 in Table II).

o-cresol (2.6 g, 0.024 mol), 6-bromo-2- (2-methylthiazole-4- yl) pyridine (1.02 g, 0.004 M), potassium carbonate (1.11 g, 0.008 mol) and copper (I) chloride (approximately 0.05 g, catalyst) were combined in dry dimethylformamide (5 ml) stir. The mixture was heated with stirring at 140 ° C for 4 h, Let cool to room temperature and stand overnight calmly. GC showed that all the starting bromopyridine was consumed. The mixture was poured into water (150 ml) poured and diethyl ether (100 ml) was added. This Mixture was filtered through a bed of HYFLO SUPERCEL and with 50 ml portions of water and diethyl ether durchge to wash. The filtrate was transferred to a separatory funnel,  and the organic layer was separated. The watery Layer was washed with another portion of diethyl ether (100 ml) extracted, and the organic extracts were ver with 5% aqueous sodium hydroxide solution (2 × 80 ml) and water (100 ml) and magnesium dried sulfate. The mixture was filtered and the Filtrate was evaporated (rotary evaporator, water bath at 35 ° C) to give a brown oil (0.7 g) which was on a silica column eluting with 3: 7 ethyl acetate: Hexane was chromatographed. It became the desired pro product as a clear orange oil, 0.65 (58%).

example 6

This example illustrates the preparation of 2- (2-chloro phenyl) pyridine.

2-Bromopyridine (15.8 g, 0.1 mol) was dissolved in tetrahydrofuran (500 ml, freshly distilled from sodium and benzophenone) dissolved. The solution was stirred under a stick atmosphere to -78 ° C in a dry ice / acetone bath cooled, and a solution of n-butyllithium in one Hexane mixture (2.5 molar, 44 ml, 0.11 mol) was added during Added at -70 ° C or less for 20 minutes. The obtained dark red solution was stirred for 30 min at -78 ° C, whereupon a solution of anhydrous zinc chloride in diethyl ether (1 molar, 300 ml, 0.3 mol) with vigorous stirring during 45 minutes at -70 ° C or below was added. The Reak tion mixture, which was now a pale green solution, which a dark green viscous oil was stirred allowed to warm until -30 ° C to obtain a total solution had been. A solution of tetrakis (triphenylphosphine) - palladium ° (1.0 g, catalyst) and 2-chlorobromobenzene (19.2 g, 0.1 mol) in dry tetrahydrofuran (60 ml) then added and the solution was heated to reflux calmly. Upon heating, a white solid precipitated from the solution fabric out. The heating was continued until ge as monitored by GC, that the product  peak had reached a constant level of 52% (6 h). The reaction mixture was cooled to room temperature and by the addition of a 10% solution of ethylenediamine Tetraacetic acid monosodium salt with pH 8 to 9 (1000 ml) deterred. The pH was adjusted by adding a 2 molar Sodium hydroxide solution adjusted to 8, followed by two Layers formed. The aqueous layer was washed with three Extracted portions of ethyl acetate (250 ml). The organic ones Solutions were combined, washed with water (250 ml) and then extracted with 2 molar hydrochloric acid (2 x 200 ml). The combined acidic solutions were washed with ethyl acetate (200 ml). washed, whereupon the pH by addition of 2 molar Sodium hydroxide solution was adjusted to 9. The watery Layer was then washed with ethyl acetate (3 x 250 ml portions) extracted, and the combined organic solutions were dried over anhydrous magnesium sulfate and evaporated, to give a pale orange liquid (11.7 g). The product was purified by preparative HPLC on silica gel eluted with 40% t-butyl methyl ether in hexane, the desired product being a yellow liquid, 8.8 g (46% yield), which according to GC a pure of 96%. 1 H NMR (CDCl₃): δ 7.30 (3H, m); 7.48 (1H, dd); 7.60 (1H, dd); 7.65 (1H, d); 7.76 (1H, dt); 8.72 (1H, dd) ppm.

example 7

This example illustrates the preparation of 2-acetyl-6 (2-chlorophenyl) pyridine.

2- (2-Chlorophenyl) pyridine (8.8 g, 0.046 mol) became 2 molar Sulfuric acid (50 ml) was dissolved and the solution became by using an ice / salt bath below 0 ° C abge cools. Acetaldehyde (6.3 g, 0.143 mol) was added, with a pale yellow solution was obtained. This solution was mechanically stirred. Solutions of ferrous sulfate hepta hydrate (40.1 g, 0.144 mol) in water (100 mL) and tert -butyl 70% hydroperoxide in water (18.5 ml, 0.144 mol)  added at the same time. The rate of addition of the two Solutions were adjusted so that the reaction temperature kept below 0 ° C. When the addition was complete, the Stirring continued for another 15 min, whereupon the buff Solid, which had now precipitated, filtered off was (3.4 g). The solid was purified by preparative HPLC on silica gel eluting with 40% t-butyl methyl ether in Hexane isolated.

• 1) 2-Acetyl-6- (2-chlorophenyl) pyridine (1.2 g, 11% from booty) as a pale yellow gum, ver and recrystallized from hexane, mp 70.8-71.3 ° C.
• 2) 2- (2-chlorophenyl) -4,6-diacetylpyridine (1.3 g, 10% Yield) as a white solid, that of hexane crystal liter, mp 114.3-114.7 ° C.

example 8

This example illustrates the preparation of 2- (2-bromo acetyl) -6- (2-chlorophenyl) pyridine.

2-acetyl-6- (2-chlorophenyl) pyridine (1g, 0.0043mol) dissolved in glacial acetic acid (20 ml) at 70 ° C, and bromine (0.25 ml, 0.0043 mol) was added in one portion. The solution was stirred at 80 ° C for 45 min. The solution was cooled and by adding a 2 molar sodium hydroxide solution neutralized, followed by three portions of ethyl acetate (100 ml) was extracted. The combined ethyl acetate Solutions were mixed with saturated sodium bicarbonate Solution and then washed with water, whereupon they are over water dried free magnesium sulfate. The solution was then filtered and evaporated using an orange oil This was achieved by preparative HPLC on silica gel Elution was purified with dichloromethane. Yield 0.88 g (6%) of a pale yellow solid, which according to GC a pure of 97%. 1 H NMR (CDCl₃): δ 4.92 (2H, s); 7:40  (2H, m); 7:52 (1H, m); 7.67 (1H, m); 7.95 (2H, m); 8.10 (1H, dd) ppm.

example 9

This example illustrates the preparation of 2- (2-chloro phenyl) -6- (2-methyl-4-thiazolyl) pyridine (Compound No. 11 in Table I).

2- (2-Bromoacetyl) -6- (2-chlorophenyl) pyridine (0.85 g, 0.0027 mol) was dissolved in dioxane (25 ml) and a solution of Thioacetamide (0.23g, 0.0031mol) in dioxane (25ml) added with vigorous stirring. The solution was at 100 ° C heated and after about 15 minutes, the precipitation of a Solid, which then dissolved again. After another 15 min fell again a solid. The reaction mixture was then left to stand overnight, whereupon it was in a 10% solution of ethylenediaminetetraacetic acid monosodium Salt with pH 8 to 9 (200 ml) was poured, followed by an extraction with two portions of ethyl acetate (150 ml) joined. The combined ethyl acetate solutions were washed with Washed with water and evaporated, giving an orange liquid (1.0 g) obtained by HPLC on silica gel eluting with a 50% mixture of hexane and t- Butyl methyl ether was purified. Yield 0.7 g (89%) a colorless rubber that solidified on standing and recrystallized from hexane. It was the title obtained with a mp of 64.5-65.1 ° C.

example 10

This example illustrates the preparation of 2- (4-methoxy phenyl) -6- (2-methylthiazol-4-yl) pyridine (Compound No. 4 in Table I).

4-Bromoanisole (1.2 g, 0.0064 mol) was dissolved in tetrahydrofuran (25 ml, freshly distilled from sodium and benzophenone) in a drying apparatus under a nitrogen atmosphere solved. The solution was abge with stirring to below -70 ° C abge  cool, using a dry ice / acetone bath, and a solution of n-butyllithium in a hexane mixture (3.0 ml, 2.5 molar, 0.0075 mol) was with such Geschwin added that the temperature remained below -70 ° C. The reaction mixture was then stirred for a further 15 minutes, whereupon a solution of anhydrous zinc chloride in diethyl ether (20 ml of a 1 molar solution, 0.02 mol) with a was added at such a rate that the temperature remained below -70 ° C. After stirring for a further 15 min became a solution of tetrakis (triphenylphosphine) palladium ° (0.1 g, catalyst) and 2-bromo-6- (2-methylthiazol-4-yl) - pyridine (1.0 g, 0.0039 mol) in dry tetrahydrofuran (25 ml) was added and the stirred solution was poured into room Allow the temperature to rise. It started the precipitation of a Solid, and the suspension was refluxed for 2 hours hold. The reaction mixture was cooled to room temperature Let it warm, then add 10% Solution of ethylenediaminetetraacetic acid monosodium salt with pH 8 to 9 (100 ml) was quenched. The pH was through Addition of saturated sodium bicarbonate solution set to 8, whereupon two layers separated. The aqueous layer was extracted with ethyl acetate (2 x 50 ml) extra and the combined organic solutions became one evaporated to give a light yellow gum (1.5 g). This was purified by preparative HPLC on silica gel Elution with 40% tert-butyl methyl ether in n-hexane, where a pale yellow solid, 1.03 g (93% yield), he was holding.

The solid was made from n-hexane under treatment with carbon recrystallized, the title compound, mp 104.9-105.9 ° C, was obtained.

The following examples show compositions that are suitable for agricultural and horticultural purposes and formulated from the compounds of the invention can be. Such compositions constitute another Appearance of the invention. Percentages are in  Weight expressed.

example 11

An emulsifiable concentrate is prepared by mixing and stirring the following ingredients until dissolved is:

Compound No. 1 of Table I | 10% benzyl alcohol 30% Calcium dodecylbenzenesulfonate 5% Nonylphenol ethoxylate (13 mol ethylene oxide) 10% alkylbenzenes 45%

example 12

The active ingredient is dissolved in methylene dichloride, and the resulting solution is precipitated on granules of attapulgite Clay sprayed on. The solvent is then evaporated off to give a granular composition.

Compound No. 2 of Table I | 5% Attapulgite granules 95%

example 13

A composition that is suitable as a seed dressing is prepared by milling and mixing the following three ingredients:

Compound No. 1 of Table I | 50% mineral oil 2% kaolin 48%

example 14

A dusting powder is prepared by grinding and mixing of the active ingredient with talc.

Compound No. 1 of Table I | 5% talc 95%

example 15

A suspension concentrate is prepared by grinding the Ingredients in a ball mill to an aqueous suspension  of the ground mixture with water.

Compound No. 1 of Table I | 40% Sodium lignosulphonate 10% Bentonite clay 1% water 49%

This formulation may be diluted with water as a Sprays used or applied directly to seeds become.

example 16

A wettable powder formulation is prepared by that the following ingredients are mixed and ground until everything is mixed carefully:

Compound No. 1 of Table I | 25% sodium lauryl sulfate 2% Sodium lignosulphonate 5% silica 25% kaolin 43%

example 17

The compounds were against the various leaf fungus diseases of plants tested. The technique used was as follows:

The plants were grown in John Innes potting compost (# 1 or no. 2) in mini pots with a diameter of 4 cm ge pulled. The test compounds were formulated by ground with aqueous DISPERSOL T in a ball mill and immediately before use to the desired Kon were diluted. For the leaf diseases were the formulations (100 ppm active ingredient) on the Foliage sprayed on the roots of the plants in the Soil infused. The sprays were up to one maximum retention and root drenching up to one Final concentration corresponding to approximately 40 ppm active loading used in dry soil. TWEEN 20 was with  a final concentration of 0.05% used when spraying were applied to cereals.

For most tests, the compounds were on the ground (Roots) and on the foliage (by spraying) one or two Days before inoculation of the plant with the disease brought. An exception made the test against Erysiphe graminis, in which the plants are inoculated 24 hours before treatment were liert. Leaf pathogens were obtained by spraying a Spore suspension applied to the leaves of the test plants. After inoculation, the plants were transformed into a suitable Environment so that the infection could develop, and then incubate until the disease for the determination was ready. The time between inoculation and the Determination varied from 4 to 14 days, depending on the Er illness and the environment.

The disease classification was as follows:

4 = no illness
3 = trace to 5% disease compared to untreated plants
2 = 6 to 20% disease compared to untreated plants
1 = 26 to 59% disease compared to untreated plants
0 = 60 to 100% disease compared to untreated plants

The results are given in Table V.  

Table V

Table V (continued)

Chemical formula in the description

Scheme 1

Scheme 2

Claims (10)

1. Compound of the general formula (I) wherein R¹ is R², R²O or R²R³R⁴C; R² is phenyl optionally substituted by halo, C _1-4 alkyl or C _1-4 alkoxy; and R³ and R⁴ are independently hydrogen or methyl; and the acid addition salts and metal complexes thereof. 2. A compound according to claim 1 of the general formula (I), wherein R¹ is R²O or R²R³R⁴C; R² is phenyl optionally substituted by halo, C _1-4 alkyl or C _1-4 alkoxy; and R³ and R⁴ are independently hydrogen or methyl; and the acid addition salts and metal complexes thereof. 3. A compound according to claim 1 or 2 of the general formula (I), wherein R¹ is R²R³R⁴C; R² is phenyl optionally substituted with halo, C _1-4 alkyl or C _1-4 alkoxy; and R³ and R⁴ are independently hydrogen or methyl. 4. A compound according to claim 1, 2 or 3, wherein R³ and R⁴ are both hydrogen. A process for producing a compound of the general formula (I) of claim 1, wherein either

• a) a compound of the formula (II) with a compound of the formula R²Hal, R²OH or R²R³R⁴CHal, in which R², R³ and R⁴ have the meanings given in claim 1 and Hal is halogen, or with a compound of the formula R²R³R⁴CH, in which R² is phenyl which is optionally substituted by fluorine, Chlorine, C _1-4 alkyl or C _1-4 alkoxy, and R³ and R⁴ are as defined in claim 1, is coupled; or
• b) a compound of the formula (VII) wherein R¹ has the meaning given above, is reacted with thioacetamide.

6. Fungicidal composition which is a fungicidally active same amount of a compound according to claim 1 and a fungi cid admissible diluent or carrier therefor ent holds. 7. A method for controlling fungi, in which Plants, on seeds of plants or on the estate Place the plants or seeds compound according to An Claim 1 or a composition according to claim 6 is brought. 8. A fungicidal composition which comprises a fungicidally effective amount of a compound of the general formula (I) wherein R¹ is R² and R² is phenyl optionally substituted with halo, C _1-4 alkyl or C _1-4 alkoxy, or an acid addition salt or metal complex thereof, and a fungicidally-acceptable carrier or diluent contains for this. 9. A method of controlling fungi, in which Plants, on seeds of plants or on the estate location of the plants or seeds according to a composition Claim 8 is applied. 10. Intermediate compounds of the formulas (II), (V) and (VII), wherein R¹ has the meaning given in claim 1.