WO1997003977A1

WO1997003977A1 - Thiopyrans microbicides

Info

Publication number: WO1997003977A1
Application number: PCT/EP1996/002940
Authority: WO
Inventors: Martin Zeller
Original assignee: Novartis Ag
Priority date: 1995-07-14
Filing date: 1996-07-04
Publication date: 1997-02-06
Also published as: ZA965937B; AU6519196A; AR002809A1

Abstract

Novel 2H-3,4-dihydrothiopyrans of general formula (I) and the salts thereof, wherein R = hydrogen, C1-C8alkyl, C3-C8alkenyl or C3-C8alkynyl, n is 0, 1 or 2, are valuable microbicides. They can be used in plant protection in the form of suitable compositions, typically for controlling fungal diseases.

Description

THIOPYRANS MICROBICIDES

The present invention relates to novel 2H-3,4-dihydrothiopyrans of formula I below, to the preparation of these substances and to agrochemical compositions comprising at least one of these compounds as active ingredient. The invention also relates to the preparation of said compositions as well as to the use of the compounds or compositions for controlling or preventing the infestation of plants with phytopathogenic microorganisms, preferably fungi.

The compounds of this invention correspond to the general formula I

wherein R has the following meaning:

R = hydrogen, C_rC₈alkyl, C₃-C₈alkenyl or C₃-C₈alkynyl, and n = 0, 1 or 2; and, if R = hydrogen, also to salts of the compounds of formula I, i.e. acid addition salts as well as salts with bases.

The alkyl, alkenyl and alkynyl radicals can be straight-chain or branched.

Depending on the number of carbon atoms indicated, alkyl itself will be taken to mean, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl as well as their isomers, typically isopropyl, isobutyl, tert-butyl or sec-butyl, isopentyl, 2-methylhexyl, isooctyl.

As a consequence of the presence of asymmetric carbon atoms in the compounds of formula I, the compounds can be in optical isomeric forms. Geometrical isomerism can also occur owing to the possible presence of an aliphatic -C=C double bond and to the presence of at least two substituents at the six-membered ring. Formula I should embrace all these possible isomeric forms as well as mixtures thereof. As a consequence of the presence of an asymmetrical sulfur atom in the compounds of formula I, the compounds can likewise be in optical isomeric forms. Formula I should embrace all these possible isomeric forms as well as mixtures thereof.

An important group of plant fungicides is that of formula I, wherein

R = hydrogen, C_rC₈alkyl, C₃-C₈a]kenyl or C₃-C₈alkynyl, and n = 0 (subgroup A).

Particularly preferred compounds are those of subgroup A, wherein R = hydrogen (subgroup Aa).

Preferred compounds of formula I and their subgroups are also those, wherein the amino group and the COOR group are in cis position to one another (subgroup B).

Preference is given to the cis representatives of subgroup A (subgroup Ab).

A particularly preferred compound is cis-4-amino-2H-3,4-dihydrothiopyran-3-carboxylic acid.

Description of the process for the preparation of compounds of this invention

The compounds of formula I can be prepared in accordance with the following reaction scheme

Reaction step a)

Compounds of formula IV can be prepared by reacting a 2,3-dihydrothiopyran-4-one of formula II in an inert diluent such as a hydrocarbon, typically n-hexane, or in an ether, typically diethyl ether or tetrahydrofuran, or in a phosphoric triamide, typically hexamethylphosphoric triamide, or in mixtures of such inert diluents, first with a strong base such as alkali amide, typically lithium diisopropylamide or lithium tetramethyl- piperidide and then with a cyanoformate of formula III in the temperature range from -100° to +100°C, preferably from -80° to 0°C.

Reaction step b)

Compounds of formula VI can be prepared by reacting a compound of formula IV with an oxime of formula V, wherein R_j is hydrogen or C_rC₆alkyl, in an inert diluent such as an alcohol, typically methanol or ethanol, where appropriate in the presence of a base such as an organic base, typically triethylamine or pyridine, or an inorganic base, typically potassium carbonate or sodium carbonate, in the temperature range from -20°C to the reflux temperature of the reaction mixture, preferably from 0° to 50°C.

Reaction step c)

Compounds of formula I can be prepared by reducing compounds of formula VI with metallic zinc in an inert organic or inorganic diluent such as an alcohol, typically methanol or ethanol, or in water or in a mixture of such inert diluents in the presence of an inorganic or organic acid such as a mineral acid, typically hydrochloric acid, or in a carboxylic acid, typically formic acid, in the temperature range from -70° to +100°C, preferably from -20° to +30°C.

The compounds of formula I, wherein R is hydrogen, can be obtained by saponification of the esters on which they are based.

This is achieved by hydrolising esters of formula I, where appropriate in a diluent such as alcohol, typically methanol or ethanol, with optional addition of an inorganic or organic base such as an alkali metal hydroxide or alkaline earth metal hydroxide, typically sodium hydroxide, potassium hydroxide or barium hydroxide, with water in the temperature range from 0° to 150°C, preferably from 20° to 80°C.

The acid addition salts of the compounds of formula I can be prepared by reacting the compounds of formula I with the corresponding acid, where appropriate in an inert diluent.

The basic salts of the compounds of formula I, wherein R is hydrogen, can be prepared by reacting the compounds of formula I, wherein R is hydrogen, with the corresponding base, where appropriate in an inert diluent.

The basic salts of the compounds of formula I, wherein R is hydrogen, are obtained as products in reaction step c). They can be isolated by foregoing the separation of the alkali metal ion or alkaline earth metal ion.

The compounds of formula I are oils or solids which are stable at room temperature and which are distinguished by valuable microbicidal properties. They can be used in the agricultural sector or related fields preventively and curatively for controlling plant-injuring microorganisms. The novel compounds of formula I are not only distinguished by excellent microbicidal and, in particular, fungicidal, action at low rates of concentration, but also by being particularly well tolerated by plants.

Surprisingly, it has now been found that compounds of formula I have, for practical purposes, a very advantageous biocidal spectrum for controlling phytopathogenic microorganisms, in particular fungi. They have very useful curative and preventive properties and are used for protecting numerous cultivated plants. The compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phyto- pathogenic fungi.

The novel compounds of formula I are particularly effective against special species of the fungal classes Fungi imperfecti (e.g. Cercospora, Botrytis, Helminthosporium, Fusarium Septoria, Pyricularia and Alternaria), Basidiomycetes (e.g. Hemileia, Rhizoctonia, Puccinia) and also Ascomycetes (e.g. Podosphaera, Monilinia, Uncinula, Cercosporella, Erysiphe and Venturia), Deuteromycetes (e.g.. Rhynchosporium) and, in particular, against Oomycetes (e.g. Plasmopara, Peronospora, Pythium, Bremia and Phytophthora). They therefore constitute an important enrichment of the compositions for controlling phytopathogenic fungi. The compounds of formula I can also be used as dressing agents for the treatment of seeds (fruit, tubers, grains) and plant cuttings for the protection against fungus infections as well as against phytopathogenic fungi which occur in the soil.

The invention also relates to compositions which contain compounds of formula I as active components, in particular plant-protecting compositions, as well as to their use in the agricultural sector or related fields.

In addition, this invention also embraces the preparation of said compositions, which comprises intimately mixing the active substance with one or more than one substance or substance group described herein. The process for the treatment of plants is also included, which process is distinguished by the application of the novel compounds of formula I or the novel compositions.

Within the scope of this invention, target crops to be protected as disclosed above typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum, spelt, triticale and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, straw¬ berries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinache, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamonium, camphor) or plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.

The compounds of formula 1 are normally applied in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be both fertilisers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides, insecticides, fungicides, bactericides, nematicides, mollusicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.

Suitable carriers and adjuvants can be solid or liquid and correspond to the substances ordinarily employed in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilisers.

A preferred method of applying a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The number of applications and the rate of application depend on the risk of infestation by the corresponding pathogen. The compounds of formula I may also be applied to propagation material (grains, fruit, tubers, shoots, seedlings, roots etc.) (dressing) either by drenching, for example, cereal grains (seeds) or potato tubers or freshly cut shoots with a liquid formulation of the compound or by coating them with a solid formulation.

The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation and are usefully formulated in known manner to, for example, emulsifiable concentrates, coatables pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.

Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha and, most preferably, from 20 g to 600 g a.i./ha.

The formulations, i.e. the compositions containing the compound of formula I and, if desired, a solid or liquid adjuvant, are prepared in known manner, typically by intimately mixing and/or grinding the compound with extenders, e.g. solvents, solid carriers and, optionally, surfacte active compounds (surfactants).

Suitable solvents may typically be: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms such as xylene mixtures or substituted naphthalenes; phthalates such as dibutyl or dioctyl phthalate; aliphatic hydrocarbons such as cyclohexane or paraffins; alcohols and glycols and their ethers and esters such as ethanol, diethylene glycol, 2-methoxyethanol or 2-ethoxyethanol; ketones such as cyclohexanone; strongly polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethyl formamide; as well as vegetable oils or epoxidised vegetable oils such as epoxidised coconut oil or soybean oil; or water.

The solid carriers typically used for dusts and dispersible powders are usually natural mineral fillers such as calcite, talcum, kaolin, montmorillonite or attapulgite. To improve the physical properties it is also possible to add highly dispersed silicic acid or highly dispersed absorbent polymers. Suitable granulated adsorptive carriers are porous types, including pumice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are materials such as calcite or sand. In addition, innumerable pregranulated materials of inorganic or organic origin may be used, especially dolomite or pulverised plant residues.

Depending on the compound of formula I to be formulated, suitable surfactants are nonionic, cationic and/or anionic surfactants having good emulsifying, dispersing and wetting properties. Surfactants will also be understood to include surfactant mixtures.

Suitable anionic surfactants may be so-called water-soluble soaps as well as water-soluble synthetic surface-active compounds.

Illustrative examples of nonionic surfactants are nonylphenol polyethoxyethanols, castor oil polyglycol ether, polyadducts of polypropylene and polyethylene oxide, tributyl- phenoxy polyethoxyethanol, polyethylene glycol and octylphenoxy polyethoxyethanol.

Fatty acid esters of polyoxyethylene sorbitan are also suitable nonionic surfactants, typically polyoxyethylene sorbitan trioleate.

Cationic surfactants are preferably quaternary ammonium salts carrying, as N-substituent, at least one C₈-C ₂alkyl radical and, as further substituents, unsubstituted or halogenated alkyl, benzyl or hydroxy-lower alkyl radicals. Further surfactants customarily employed in the art of formulation are known to the expert or can be found in the relevant literature.

The agrochemical formulations will usually contain from 0.1 to 99 % by weight, preferably from 0.1 to 95 % by weight, of the compound of formula I, from 99.9 to 1 % by weight, preferably from 99.8 to 5 % by weight, of a solid or liquid adjuvant, and from 0 to 25 % by weight, preferably from 0.1 to 25 % by weight, of a surfactant.

Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.

The compositions may also contain further adjuvants such as stabilisers, antifoams, viscosity regulators, binders or tackifiers as well as fertilisers, micronutrient donors or other formulations which influence plant growth for obtaining special effects.

The following non-limitative Examples illustrate the above-described invention in more detail. Temperatures are given in degrees Celcius.

Preparation Examples for intermediates of formula I:

I-l. : 2H-3,4-dihvdro-4-oxothiopyran-3-carboxylic acid methyl ester

3.4 ml of diisopropylamine are added, with stirring, to 40 ml of tetrahydrofuran under nitrogen at -30°C. At this temperature, 15 ml of a 1.6 M solution of butyl lithium in n-hexane are added dropwise and stirred for 30 min at -30°C. The reaction mixture is cooled to -70°C and a solution of 2.3 g of 2H-3,4-dihydro-4-oxothiopyran in 30 ml of tetrahydrofuran is added dropwise. The reaction mixture is then stirred for 90 min at -70°C. Subsequently, 3.5 ml of hexamethylphosphoric triamide are added at -70°C and the reaction mixture is stirred for 15 min at -70°C. 1.9 ml of methyl cyanoformate are added at -70°C and the reaction mixture is stirred for 75 min and then poured into 200 ml of ice/water. The mixture is extracted twice with 400 ml each of ethyl acetate. The organic phases are washed once with 100 ml of a saturated solution of hydrochloric acid, combined, dried over sodium sulfate and concentrated under vacuum. The residue is purified by chromatography over silica gel with ethyl acetate/n-hexane, giving 2H-3,4-dihydro-4-oxothiopyran-3-carboxylic acid methyl ester in the form of a solid, m.p. 44-45°C.

The intermediates listed in Table 1 are prepared in analogous manner.

Table 1 (Intermediates)

O

Cmpd R Phys. No. data m.p.°C

1.1 methyl 0 44-45°C

1.2 ethyl 0

1.3 methyl 2

2. : 2H-3,4-dihydro-4-oxothiopyran-3-carboxylic acid methyl ester-O-methyloxime

A mixture of 1.9 g of 2H-3,4-dihydro-4-oxothiopyran-3-carboxylic acid methyl ester, 0.9 g of O-methylhydroxylamine hydrochloride, 1.8 ml of pyridine and 30 ml of methanol is stirred for 3 hours at room temperature. The reaction mixture is concentrated by evaporation to dryness. The resulting residue is diluted with 150 ml of water. The mixture is extracted twice with 400 ml each of ethyl acetate. The organic phases are washed once with 100 ml of a saturated solution of hydrochloric acid and are then combined, dried over sodium sulfate and concentrated under vacuum. The residue is purified by chromato¬ graphy over silica gel with ethyl acetate/n-hexane, giving 2H-3,4-dihydro-4-oxothio- pyran-3-carboxylic acid methyl ester-O-methyloxime in the form of a resin.

The compounds listed in Table 2 are prepared in analogous manner.

Table 2 (Intermediates)

.OR,

N ^"

R_j= H or lower alkyl, preferably methyl

Cmpd R n Ri Stereochemistry Phys.

No. of the C=N bond data m.ρ.°C

2.1 methyl 0 methyl E/Z mixture resin

2.2 methyl 0 H E/Z mixture

2.3 ethyl 0 methyl E/Z mixture

2.4 methyl 2 methyl E/Z mixture

Preparation Examples for end products

P- 1. : 2H-4-amino-3,4-dihydrothiopyran-3-carboxylic acid methyl ester (cis and trans)

5 g of 2H-3,4-dihydro-4-oxothiopyran-3-carboxylic acid methyl ester-O-methyloxime are dissolved in 130 ml of methanol and 75 ml of water and then 120 ml of formic acid are added. The reaction mixture is cooled, with stirring, to 0°C. A total of 6.5 g of zinc powder is then added in 4 increments over 30 min. The reaction mixture is stirred for 12 hours at -5°C and filtered. The filtrate is concentrated by evaporation. The residue is taken up in 100 ml of 2n hydrochloric acid and the mixture is extracted once with 500 ml of ethyl acetate. The aqueous phase is adjusted to pH > 9 with 2 n of sodium hydroxide solution and extracted twice with 500 ml each of ethyl acetate. The organic phases are washed once with 200 ml of a saturated solution of sodium chloride, dried over potassium carbonate and concentrated under vacuum, giving 2H-4-amino-3,4-dihydrothiopyran-3- carboxylic acid methyl ester (cis/trans-diastereoisomeric mixture) in the form of an oil (compound 3.1).

The product obtained (mixture of diastereoisomers) is chromatographed over silica gel with ethyl acetate/n-hexane. The first component to elute is cis-2H-4-amino-3,4- dihydrothiopyran-3-carboxylic acid methyl ester (compound 3.2) in the form of an oil; the second component to elute is trans-2H-4-amino-3,4-dihydrothiopyran-3-carboxylic acid methyl ester (compound 3.3) in the form of an oil.

The compounds listed in Table 3 are prepared in analogous manner. Table 3

Cmpd R n Stereochemistry between Phys.

No. NH₂ and COOR data m.ρ.°C

3.1 methyl 0 cis/trans mixture oil

3.2 methyl 0 cis oil

3.3 methyl 0 trans oil

3.4 ethyl 0 cis/trans mixture

3.5 ethyl 0 cis

3.6 ethyl 0 trans

3.7 methyl 2 cis/trans mixture

3.8 methyl 2 cis

3.9 methyl 2 trans

H.-2.: cis-2H-4-amino-3,4-dihvdrothiopyran-3-carboxylic acid

A mixture of 1.5 g of cis-2H-4-amino-3,4-dihydrothiopyran-3-carboxylic acid methyl ester and 100 ml of 0.088M barium hydroxide is stirred for 15 hours at 150°C. To this mixture are then added dropwise 8.8 ml of IM sulfuric acid. The resulting suspension is collected by suction filtration over cellite. The clear filtrate is concentrated to dryness by evaporation. The residue obtained is stirred in 50 ml of methanol, filtered and dried in an exsiccator over phosphorus pentoxide, giving cis-2H-4-amino-3,4-dihydrothiopyran- 3-carboxylic acid in the form of a solid (compound 4.2), m.p. 210-215°C.

The compounds listed in Table are prepared in analogous manner.

Table 4

Cmpd Stereochemistry between Phys.

No. NH₂ and COOH data m.p.°C

4.1 0 cis/trans mixture

4.2 0 cis 210-215

4.3 0 trans >220

4.4 2 cis/trans mixture

4.5 2 cis

4.6 2 trans 2. Formulation Examples for compounds of formula I (% = percent by weight)

F-2.1. Wettable powders a) b) c) compound of Table 3 or 4 25 % 50 % 75 % sodium ligninsulfonate 5 % 5 % - sodium laurylsulfate 3 % - 5 % sodium siisobutylnaphthalenesulfonate - 6 % 10 % octylphenol polyethylene glycol ether - 2 % - (7-8 mol ethylene oxide) highly disperse silica 5 % 10 % 10 % kaolin 62 % 27 % -

The compound is thoroughly mixed with the adjuvants and the mixture is well ground in a suitable mill to give wettable powders which can be diluted with water to suspensions of any desired concentration.

F-2.2. Emulsifiable concentrates compound of Table 3 or 4 10 % octylphenol polyethylene glycol ether 3 %

(4-5 mol ethylene oxide) calcium dodecylbenzenesulfonate 3 % castor oil polyglycol ether 4 %

(35 mol ethylene oxide) cyclohexanone 34 % xylene mixture 50 %

Emulsions of any desired concentration can be prepared by diluting such concentrates with water.

F-2.3. Dusts a) b) compound of Table 3 or 4 5 % 8 % talcum 95 % _ kaolin - 92 %

Ready for use dusts are obtained by mixing the compound with the carrier on a suitable mill. F-2.4. Extruder granulates compound of Table 3 or 4 10 % sodium ligninsulfonate 2 % carboxymethyl cellulose 1 % kaolin 87 %

The compound is mixed with the adjuvants, ground and moistened with water. The mixture is extruded and then dried in a stream of air.

F-2.5. Coated granulates compound of Table 3 or 4 3 % polyethylene glycol (MW 200) 3 % kaolin 94 %

(MW = molecular weight)

The finely ground compound mixture is uniformly applied in a mixer to the kaolin moistened with polyethylene glycol. Non-dusty coated granulates are obtained in this manner.

F-2.6. Suspension concentrates compound of Table 3 or 4 40 % ethylene glycol 10 % nonylphenol polyethylene glycol ether 6 %

(15 mol ethylene oxide) sodium ligninsulfonate 10 % carboxymethyl cellulose 1 %

37% aqueous solution of formaldehyde 0.2 % silicon oil in the form of a 75% aqueous emulsion 0.8 % water 32 %

The finely ground compound is intimately mixed with the adjuvants to give a suspension concentrate from which suspensions of any desired concentration can be prepared by dilution with water. Biological Examples

B-l: Action against Plasmopara viticola on vine a) Residual-protective action

Vine seedlings in the 4-5 leaf stage are sprayed with a spray mixture prepared from a wettable powder formulation of the compound (0.02 % active ingredient). After 24 hours, the treated plants are infected with a spore suspension of the fungus. Evaluation of the fungus attack is made after a 6-day incubation at 95-100 % relative humidity and at 20°C.

The compounds of Tables 3 and 4 inhibit the fungus infestation completely (residual infestation 0 to 10 %), whereas Plasmopara infestation of untreated but infected control plants is 100 %.

B-2: Action against Phytophthora on tomato plants a) Residual-protective action

After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture prepared from a wetttable powder formulation of the compound (0.02 % active ingredient). After 48 hours, the treated plants are infected with a spore suspension of the fungus. Evaluation of the fungus attack is made after a 4-day incubation of the infected plants at 90-100 % relative humidity and at 18°C.

b) Systemic action

After a cultivation period of 3 weeks, tomato plants are treated with a spray mixture prepared from a wettable powder formulation of the compound (0.002 % active ingredient, based on the volume of soil), taking care that the spray mixture does not come into contact with the parts of the plant above the ground. After 4 days, the treated plants are infected with a spore suspension of the fungus. Evaluation of the fungus attack is made after a 4-day incubation of the infected plants at 90-100 % relative humidity and at 18°C.

The compounds 3.1, 3.2, 4.1, 4.2 and others inhibit the infestation almost completely (0 to 5 % infestation), whereas Phytophthora infestation of untreated, infected control plants is 100 %. B-3: Residual-protective action against Cercospora arachidicola on groundnut plants Groundnut plants 10 to 15 cm high are sprayed to drip point with an aqueous spray mixture (0.02% active ingredient) and infected with a conidia suspension of the fungus 24 hours later. The plants are incubated for 96 hours at 24°C and high humidity and then stood in a greenhouse until the typical leaf specks occur. Evaluation of the action of the active ingredient is made 12 days after infection and is based on the number and size of the specks.

Compounds of formula I reduce the specks on the leaves to less than about 10% in comparison with untreated controls. In some cases the disease is completely inhibited (0-5% infestation).

B-4: Action against Puccinia recondita on wheat a) Residual-protective action

Wheat plants are sprayed 6 days after sowing with an aqueous spray mixture (0.02% active ingredient) to drip point and infected with a uredospore suspension of the fungus 48 hours later. After a 48-hour incubation (conditions: : 95-100% relative humidity at 20°C), the plants are stood in a greenhouse at 22°C. Evaluation of the rust pustule development is made 10 days after infection.

b) Systemic action

Wheat plants are watered 4 days after sowing with an aqueous spray mixture (0.002% active ingredient, based on the volume of the soil), taking care that the spray mixture does not come into contact with parts of the plant above the ground. 96 hours later, the plants are infected with a uredospore suspension of the fungus. After a 48-hour incubation (conditions: 95 to 100% relative humidity at 20°C), the plants are stood in a greenhouse at 22°C. Evaluation of rust pustule development is made 10 days after infection.

Compounds of formula I markedly reduce the fungus infestation, in some cases to 10-0% of the untreated control.

B-5: Action against Phytophthora on potato plants a) Residual-protective action

After a cultivation period of 3 weeks, potato plants (Bintje) are sprayed with a spray mixture prepared from a wettable powder formulation of the compound (0.02% active ingredient). After 24 hours, the treated plants are infected with a spore suspension of the fungus. Evaluation of the fungus attac is made after a 5-day incubation of the infected plants at 90-100% relative humidity and at 20°C. b) Systemic action

After a cultivation period of 3 weeks, potato plants (Bintje) are treated with a spray mixture prepared from a wettable powder formulation of the compound (0.002 % active ingredient, based on the volume of soil), taking care that the spray mixture does not come into contact with parts of the plants above the ground. After 48 hours, the treated plants are infected with a spore suspension of the fungus. Evaluation of the fungus attack is made after a 5-day incubation of the infected plants at 90-100% relative humidity and at 20°C.

Compounds of foramula I are generally able to reduce the infestation to less than 20%, in some cases even completely, in particular the compounds 3.2 and 4.2.

B-6: Action against Septoria nodorum on wheat

Wheat plants (7 days old) are sprayed with spray mixture prepared from a formulated test substance (0.02% a.i.) and are infected with a conidia suspension of the fungus 48 hours later. After a 48-hour incubation time (95-100 % relative humidity and at 20°C), the plants are stood in a greenhouse at 21°C. Evaluation of the infestation is made 11 days after infection.

The compounds of formula I reduce the infestion to less than 20 % compared with the untreated control.

Claims

What is claimed is

1. A compound of formula I

wherein

R = hydrogen, C_rC₈alkyl, C₃-C₈alkenyl or C₃-C₈alkynyl, and n = 0, 1 or 2; and, if R = hydrogen, acid addition salts as well as salts with bases.

2. A compound of formula I according to claim 1, wherein R = hydrogen or C_rC₈alkyl, and n is 0, 1 or 2.

3. A compound of formula I according to claim 2, wherein R is hydrogen.

4. A compound of formula I according to claim 2, wherein n is O.

5. A compound of formula I according to claim 1, wherein the amino group and the COOR group are in cis position to one another.

6. A compound of formula I according to claim 2, wherein the amino group and the COOR group are in cis position to one another.

7. A method of preparing a compound of formula I according to claim 1, which comprises reacting in reaction step a) a 2,3-dihydrothiopyran-4-one in an inert diluent first with a strong base and then with a methyl cyanoformate NC-COOR in the temperature range from -100° to +100°C, preferably from -70° to 0°C, reacting in reaction step b) this 2,3-dihydrothiopyran-4-one-3-carboxylic acid ester with an oxime H₂NOR_j, wherein

R_j is hydrogen or lower alkyl, in an inert diluent, if desired in the presence of a base, in the temperature range from -20°C and the reflux temperature of the reaction mixture, preferably from 0° to 50°C, and reducing in reaction step c) the 4-oximino compounds obtained with metallic zinc in an inert diluent or in water or in a mixture of such inert diluents in the presence of an inorganic or organic acid in the temperature range from -70° to +100°C, preferably from -20° to +20°C.

8. A composition for controlling and preventing the infestation of plants by microorganisms, which comprises a compound of formula I as claimed in claim 1 as active ingredient, together with a suitable carrier.

9. A composition according to claim 8, wherein the active component is a compound of formula I according to any one of claims 2 to 6.

10. A method of controlling and preventing the infestation of plants by microorganisms, which comprises applying as active ingredient a compound of formula I to the plant, to parts of the plant or to the culture medium of the plant.

11. A method according to claim 10, which comprises controlling phytopathogenic fungi.

12. A method according to claim 11, which comprises controlling Oomycetes.