WO1982002713A1

WO1982002713A1 - Fungicides

Info

Publication number: WO1982002713A1
Application number: PCT/EP1982/000017
Authority: WO
Inventors: Ag Sandoz; Patent Gmbh Sandoz
Original assignee: Sandmeier Rudolf; Schelling Hans Peter
Priority date: 1981-02-05
Filing date: 1982-01-30
Publication date: 1982-08-19
Also published as: DE3231605A1; FR2499079A1; IT8219495A0; IT1151506B

Abstract

Novel 1-(N-R1?-N-R2?-amino)-4-R5?-4-R6?-5-R3?-5-R4?-oxazolidin-2-ones wherein R1? and R2? are as specified in the description and R3?, R4?, R5? and R6? are hydrogen or C1-4?alkyl having fungicidal activity. Other aspects of the invention are fungicidal compositions comprising such novel compounds, methods of combatting phytopathogenic fungi with the aid of said novel compounds, and the preparation of such novel compounds and fungicidal compositions.

Description

FUNGICIDES

The present invention provides compounds useful in the combating of phytopathogenic fungi. More specifically the present invention provides compounds of formula I,

wherein R₁ is

wherein R₇ und R₈ , independently , are C_{1 -4}alkyl, halogen or C_1-4alkoxy , and R₉ is hydrogen , C_{1- 4}alkyl or halogen ,

R₂ is COR₁₀ wherein R₁₀ is H; C_1-6alkyl; C_2-6alkenyl unsubstituted or substituted by halogen; C_2-6alkinyl; C_3-7cycloalkyl; C_3-7- cycloalkyl-C_1-3alkyl; C_2-6epoxyalkyl; phenyl, phenyl-C_1-3alkyl or phenylC_1-3alkenyl wherein the aromatic moiety is unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of C_1-4alkyl, C_1-4- alkoxy, halogen, NO₂, phenyl or phenoxy, R₃ , R₄, R₅ and R₆ are independently hydrogen or

C_1-4alkyl.

When any of R₃, R₄, R₅, R₆, R₇, R₈ or R₉ is or includes an alkyl group (e.g. alkoxy), this is preferably C_1-3alkyl, i.e. methyl, ethyl, n-propyl or i-propyl.

When either of R₇ or R₈ is halogen, this is F, Cl, Br or I, preferably F, Cl or Br, more preferably Cl or Br, particularly Cl.

When any of R₉ or R₁₀ is or includes halogen this is F, Cl, Br or I, preferably F, Cl or Br, particularly Cl or Br.

Preferred C_1-6alkyl significances of R₁₀ are C_2-4alkyl, particularly C₃alkyl.

Preferred C_2-6alkenyl significances of R₁₀ are C_2-4alkenyl, particularly C-alkenyl.

Preferred C_3-7cycloalkyl significances of R₁₀ are C_3-6Cycloalkyl, particularly C_3-4cycloalkyl.

When one of R₃ and R₄ is C_1-4alkyl, the other is preferably hydrogen.

When one of R₅ and R₆ is C_1-4alkyl, the other is preferably hydrogen.

Thus, a preferred group of compounds are the compounds of formula Ia,

wherein

R₇' and R₈' independently are CH₃, Cl or Br R₉' is H, Cl, Br or methyl and R₁₀' is C₃-alkyl, C₃-alkenyl or C_3-4cycloalkyl, R₇' and R₈' are preferably identical.

Particularly preferred meanings of R₁₀' are unbranched C₃-alkyl or unbranched C₃-alkenyl, e.g. n-propyl or 2-propenyl.

According to a further aspect of the present invention, the compounds of formula I are produced by intramolecular condensation of a compound of formula II

wherein R₁, R₃, R₄, R₅, R₆ and R₁₀ are as defined above and Y is halogen. Y is preferably chlorine or bromine, particularly chlorine.

The above intramolecular condensation can be carried out in a conventional manner. The reaction is exothermic. It can e.g. be carried out in a water-free medium using as solvent an ether such as dimethoxyethane, an hydrocarbon such as toluene or another solvent which is inert under the reaction conditions. The reaction temperature is not critical and can lie between about 0° and 100°C. Since the reaction is exothermic one starts the reaction conveniently at room temperature and allows the reaction temperature to rise gradually. The reaction is conveniently carried out in the presence of an acid binding agent such as sodium hydride, sodium amide or a sodium alcoholate e.g. sodium ethylate.

The intramolecular condensation can also be carried out in an aqueous/organic two-phase system in the presence of an anorganic base e.g. sodium hydroxide and optionally a catalytic amount of a phase transfer catalyst. The organic phase may comprise any appropriate inert water immiscible solvent such as hydrocarbons or halogenated carbons, e.g. xylene, toluene,o-dichloro benzene or dichloromethane. Appropriate phase transfer catalysts are quaternary ammonium compounds such as benzyltrimethyl ammonium bromide, quaternary phosphonium compounds such as benzyltriphenyl phosphonium chloride and crown ethers such as 18-crown-6. The compounds of formula I in which the significance of R₁₀ is epoxyaikyl may also be prepared from the corresponding compound of formula I, wherein R₁₀ is alkenyl, by epoxydation. The epoxydation is suitably carried out with an organic peroxiacid such as m-chloroperbenzoic acid or a mixture of hydrogen peroxide and an inorganic base, as e.g. sodium hydroxide.

The compounds of formula II are novel. They may be obtained by acylation of compounds of formula III

wherein R₁, R₃, R₄, R₅, R₆ and Y are as defined above, with a compound of formula IV,

wherein R₁₀ is as defined above, and

Z is halogen, particularly Cl, or O-COR₁₀, wherein R₁₀ is as defined above. Suitable solvents for this acylation reaction are hydrocarbons such as toluene or halogenated hydrocarbons such as chlorobenzene. The reaction is conveniently effected at a temperature of from about 50° to about 120°C, e.g. 80°C, optionally in the presence of a base as e.g. triethylamine or pyridine. The compounds of formula III may be obtained by conversion of compounds of formula V,

R₁ - NH - NH₂ V wherein R₁ is as defined above, with a compound of formula VI

wherein R₃, R₄, R₅, R₆ and Y are as defined above, and

X is halogen, particularly Cl. This conversion may be effected at a temperature of from about 0° to about 10°C in water or in an organic solvent which is inert under the reaction conditions, conveniently in the presence of a base e.g. an organic amine or sodium hydrogen carbonate.

The starting materials and reagents employed in the processes described above are either known or, insofar as they are not known, they may be produced in analogous manner to the processes described herein or to known processes.

The compounds of formula I have useful fungicidal activity, particularly against phytopathogenic fungi, especially against fungi of the class Oomycetes as indicated by a significant effect in the following tests. Test A : Fungicidal effect against Phytophthora infestans

Young potted potato plants (3-5 leaf stage) are sprayed with an aqueous spray suspension containing 0.003% (weight/volume) of a compound of formula I, e.g. N-(2,6-dimethylphenyl)-N-(2-oxo-3-oxazolidinyl)-2- butenamide (formulated in accordance with Formulation Example I). Two hours later, the treated plants are inoculated with a spore suspension of Phytophthora infestans and the plants are then transferred to a tent providing 100% relative atmospheric humidity at an ambient temperature of 16°C and a day length of 16 hours. Disease control is evaluated 4-5 days later by comparing the treated plants with untreated, similarly inoculated plants. With the above test compound, substantial control of the fungal infestation is observed without any sign of phytotoxicity on the host plants.

Test B : Fungicidal effect against Plasmopara viticola Young potted plants of grape vine (3-6 leaf stage) are sprayed with an aqueous spray suspension containing 0.0008% (weight/volume) of a compound of formula I, e.g. N-(2,6-dimethylphenyl)-N-(2-oxo-oxazolidinyl)-2-butenamide (formulated in accordance with Formulation Example I). Two hours later, the treated plants are inoculated with a spore suspension of Plasmopara viticola and the plants are then transferred to a tent providing 100% relative atmospheric humidity at an ambient temperature of 15~22°C (fluctuating over a 24hr-period) and a day length of 16 hours. Disease control is evaluated 6 days after inoculation by comparing the treated plants with untreated, similarly inoculated plants. With the test compound, substantial control of the fungal infection is observed without significant sign of phytotoxicity on the host plants. Test C : Curative fungicidal effect against Plasmopara viticola

Young potted plants of grape vine (3-6 leaf stage) are inoculated in the same way as determined in Test B, but the application of the compound, e.g. N-(2,6-dimethylphenyl)-N-(2-oxo-3-roxazolidinyl)-2-butenamide (formulated in accordance with Formulation Example I), follows only after 3 days after inoculation; the incubation conditions are the same as described in Test B. Disease control is evaluated as stated in Test B. With the test compound, substantial control of the fungal infection is observed. Test D : Eradicative fungicidal effect against Plasmopara viticola

The procedure to evaluate this kind of activity is evaluated as described in Test C, with the exception that the treatment is carried but only 6 days after inoculation, when sporulation on the lower leaf surface is already evident. Disease control evaluated 7 days after application of, e.g., 0.012% of the compound N-(2,6-dimethylphenyl)-N-(2-oxo-3-oxazolidinyl)-2-butenamide (formulation in accordance with Formulation Example I), reveals a stopping effect on already sporulating zones.

Test E : Translocation in treated leaves of grape vines

Excised leaves of grape vine are treated with an aqueous spray suspension containing 0.012% of a compound of formula I, e.g. N-(2,6-dimethylphenyl)-N-(2-oxo-3-oxazolidinyl)-2-butenamide (formulated in accordance with Formulation Example I), in that only the lower half of such leaves is treated. Two hours after treatment, the whole leaf is inoculated with a spore suspension of Plasmopara viticola after which the leaves are incubated in a tent providing 100% atmospheric humidity at conditions as described in Test B. Although only the lower half of the leaves was treated as stated above, with the test compound substantial disease control on the entire leaf inoculated was observed. The same effect was also observed, when only the upper half of the leaves was treated. This Test thus shows, that the N-(2,6-dimethylphenyl)-N-(2-oxo-3-oxazolidinyl)-2-butenamide (formulated in accordance with Formulation Example I), is distributed within a leaf both acropetally and basipetally. Test F : Soil Treatment In vivo, employing Pythium aphanidermatum. The fungus is cultivated in a sterile mixture of sand and corn meal (97:3 v/v); cultivation lasts for 4 days at 25°C. The fungus is then mixed into a semi-sterile mixture of peat and sand which then is treated with a suspension containing the formulated active ingredient to give concentration of 10 to 160 ppm (e.g. 10, 40 and 160 ppm) calculated per volume substrate). The substrate is transferred to pots of 5 cm diameter which are seeded with cucumber seeds. The planted pots are incubated at 24°C and 60 - 70% relative humidity in an incubation chamber for 7 days, after which disease attack is determined by comparing the number of healthy emerged plants with that in untreated, similarly inoculated check pots. The compound of Example 1, hereinafter, used in the wettable powder formulation given above provides significant disease control.

Tests analogous to Test F give similar results with peas and sugar beets.

Each of the compounds listed below in the following Examples is found to possess fungicidal properties indicating their usefulness as fungicides.

Particularly effective fungicidal activity is found in the above tests with the compounds of formula la, wherein R₇' and R₈' are CH₃; R₉' is H and R₁₀' is n-C₃H₇, CH₃-CH=CH-, cyclopropyl or cyclobutyl.

The invention therefore also provides a method of combating phytopathogenic fungi, especially of the class Oomycetes, in plants, seeds or soil, which process comprises treating the plants, seeds or soil with a fungicidally effective amount of a compound of formula I. Fungi of the class Oomycetes, against which the .method of the invention is particularly effective, are those of the genus Phytophthora in plants such as potatoes, tomatoes, tobacco, citrus, cacao, rubber, apples, strawberries, vegetables and ornamentals, e.g. Phytoohthora infestans in potatoes and tomatoes; of the genus Plasmopara viticola in grape vines; of the genus Peronospora in plants such as tobacco, e.g. Percnospora tabacina in tobacco; of the genus Pseudcoeronospora in plants such as hops and cucumber, e.g. Pseudopercr-ospcra humuli in hops; of the genus Bremia in plants such as lettuce, e.g. Bremia lactucae in lettuce; of the genus Pythium causing damping-off and root rots in a great number of plants, such as. vegetables, sugar beets, ornamentals and conifers, e.g. Pythium aphanidermatum in

sugar beets; of the genus Sclerospora in plants such as sorghum and corn, e.g. Sclerospora sorghis in sorghum.

For use in the method of the invention, the amount of the preparation to be employed will vary depending on such factors as the species of fungi to be combated, the time and nature of application and the amount and nature of the compound of formula I employed in the preparation.

However, in general, satisfactory results are obtained when applied to a locus, e.g. on crops or to soil with a dosage rate in the range of from 0.05 to 5 kg, preferably from 0.1 to 3 kg of a compound of formula I/ha treated locus, the application being

repeated as required. When employed as a seed dressing, satisfactory results are obtained when applied at a rate of from about 0.05 to 0.5, preferably about 0.1 to 0.3 g compound of formula I/kg seed. Depending on the circumstances, the compounds of formula I may be used in association with other pesticides e.g. fungicides, bactericides, insecticides, acaricides, herbicides or-plant growth regulating agents in order to enhance their activity or to widen their spectrum of activity.

A particularly preferred method of the invention comprises applying to the locus to be treated fungicidally effective aggregate amounts of a component a) comprising a compound of formula I and of one or more compounds selected from a copper fungicide, captan, folpet, mancozeb or maneb.

Examples of copper fungicides suitable for use in association with a compound of formula I are e.g. copper (II) carbonate, copper (II) calcium sulphate, copper (II) calcium oxychloride, tetracupric oxychloride, Bordeaux mixture, Burgundy mixture, cuprous oxide, cupric hydroxide, copper (II) oxychloride or also copper complexes such as copper tri-ethanolamine hydroxide of the formula [Cu N(CH-CH-OH)₃](OH)₂, commercially available under the Trademark K-Lox, or bis (ethylenediamine)-copper (II) sulphate of the formula [Cu(H₂NCH₂CH₂NH₂)₂]SO₄, commercially available under the Trademark Komeen, and mixtures thereof, particularly cuprous oxide, copper (II) oxychloride, cupric hydroxide and a mixture of copper (II) calcium sulphate and copper (II) oxychloride.

Captan, Folpet, Manoczeb and Maneb are the common names for pretective fungicides effective against foliage diseases (Pesticide Manual, 5th Ed., by H. Martin and C.R. Worthing, page 76, 281, 328 and 329 resp.).

The compounds of formula I are conveniently employed as fungicidal compositions in association with agriculturally acceptable carriers or diluents. Such compositions also form part of the present invention. They may contain, aside from a compound of formula I as active agent, other active agents, such as fungicides. They may be employed in either solid or liquid application forms e.g. in the form of a wettable powder, an emulsion concentrate, a water dispersible suspension concentrate ("flowable"), a dusting powder, a granulate, a delayed release form, incorporating conventional carriers, diluents and/or adjuvants. Such compositions may be produced in conventional manner, e.g. by mixing the active ingredient with a carrier and other formulating ingredients.

Particularly formulations to be applied in spraying forms such, as water dispersible concentrates or wettable powders may contain surfactants such as wetting and dispersing agents, e.g. the condensation product, of formaldehyde with naphthalene sulphonate, an alkylaryisulphonate, a lignin sulphonate, a fatty alkyl sulphate, an ethoxylated alkylphenol and an ethoxylated fatty alcohol. In general, the formulations include from 0.01 to 90% by weight of active agent, said active agent consisting either of at least one compound of formula I or mixtures thereof with other active agents, such as fungicides. Concentrate forms of compositions generally contain between about 2 and 80%, preferably between about 5 and 70% by weight of active agent.

Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. The invention is illustrated by the following Examples wherein parts and percentages are by weight and temperatures are in °C.

Formulation Example I : Wettable powder

50 Parts of N-(2,6-dimethylρhenyl)-N-(2-oxo-3-oxazolidinyl)-2-butenamide are ground with 2 parts of lauryl sulphate, 3 parts sodium lignin sulphonate and 45 parts of finely divided kaolinite until the mean particle size is below 5 microns. The resulting wettable powder so obtained is diluted with water before use to a concentration of between 0.01% to 5% active agent. The resulting spray liquor may be applied by foliar spray as well as by root drench application. Formulation Example 2 : Granulate Onto 94.5 parts by weight of quartz sand in a tumbler mixer is sprayed 0.5 parts by weight of a binder (non-ionic tenside) and the whole thoroughly mixed. 5 Parts by weight of powdered N-(2,6-dimethylphenyl)-N-(2-oxo-3-oxazolidinyl)-2-butenamide are then added and thoroughly mixing continued to obtain a granulate formulation with a particle size in the range of from 0.3 to 0.7 mm. The granulate may be applied by incorporation into the soil adjacent the plants to be treated. Formulation Example 3 : Emulsion Concentrate 25 Parts of a compound of formula I, e.g. the compound of Example 1, hereinafter given, 65 parts of xylene, 10 parts of the mixed reaction product of an alkylphenol with xyleneoxide and calcium-dodecylbenzene sulphonate are thoroughly mixed until a homogeneous solution is obtained. The resulting emulsion concentrate is diluted with water before use. EXAMPLE 1 : N-(2,6-dimethylphenyl)-N-(2-oxo-3-oxa- zolidinyl)-2-butenamide

15.0 g (0.048 mol) 2-chloroethyl 2-(2-butenoyl)-2- (2,6-dimethylphenyl)-hydrazine carboxylate in 100 ml dry methanol is slowly added to a cooled solution of 2.7 g (0.05 mol) sodium methoxide in 50 ml dry methanol. After stirring at room temperature for one hour, the solution is concentrated in vacuo, the residue taken up in dichloromethane and washed thoroughly with water. The organic phase is dried over MgSO₄, freed of the solvent, and the residue crystallized from diethyl ether to yield the title compound as colourless crystals, m.p. 123-4°C. EXAMPLE 2

Following the procedure of Example 1, but employing the appropriate compounds of formula II wherein R₃, R₄, R₅ and R₆ are H and Y is Cl, the following compounds of formula I, wherein R₃, R₄, R₅ and R₆ are H, are obtained.

EXAMPLE 3 : 2,3-Epoxy-N-(2,6-dimethylphenyl)-N-(2-oxo- 3-oxazolidinyl)-butanamide 3.8 g (13.9 mmol) N-(2,6-dimethylphenyl)-N-(2-oxo-oxazolidinyl)-2-butenamide in 40 ml methanol and 3.5 g hydrogen, peroxide (40 % solution in water) are cooled to 15°C with stirring, while a solution of 0.2-8 g (7 mmol) sodium hydroxide in 12 ml water is slowly added. The mixture is stirred for one hour at 20°, then poured into 500 ml water, extracted with dichloromethane, the organic phase washed with water, dried over MgSO₄, and the solvent evaporated to yield the title compound as colourless oil. EXAMPLE 4 :

Following the procedure of Example 3, but employing the appropriate compounds of formula I wherein R₃, R₄, R₅ and R₆ are H and R₁₀ is alkenyl, the following compounds of formula I wherein R₃, R₄, R₅ and R₆ are H and R₁₀ is epoxyalkyl are obtained.

INTERMEDIATES

EXAMPLE A : 2-Chlgroethyl 2- ( 2-butengyl ) - ( 2 , 6-dimethylph eny l ) -hydraz inecarboxyla te

A mixture of 20.0 g (0.032 mol) 2-chloroethyl 2- (2,6-dimethylphenyl)-hydrazinecarboxylate and 8.6 g (0.082 mol) 2-butenoyl chloride in 100 ml dry toluene is warmed to 50°C during 3 hours with stirring. After cooling to room temperature, the organic phase is consecutively washed with water, an aqueous solution of K₂CO₃ and water, dried over MgSO₄ and evaporated in vacuo, to yield the title compound as a yellow oil. A portion is crystallized from ethanol to yield colourless crystals, m.p. 138-40°C.

EXAMPLE B : 2-Chlgrgethyl 2-(2,6-dimethvlphenyl)- hydrazinecarboxylate

A mixtureof 17.7 g (0.1 mol) 2,6-dimethylphenylhydrazine hydrochloride and 21.2 g (0.2 mol) sodium carbonate in 50 ml water/50 ml xylene are stirred for 30 minutes at room temperature, then cooled to 5°C. 14.3 g (0.1 mol) chloroformic acid 2-chloroethylester is then added over a period of 1 hour, the temperature being maintained at 5°C with external cooling. The mixture is stirred at 5°C for another hour, at the end of which 100 ml water are added, the precipitate thus formed filtered off, washed with water and dried, to yield the title compound as slightly coloured solid, m.p. 69-70°C. Recrystallization from diethylether/ light petroleum raises the m.p. to 74-5°C.

Claims

What we claim is :

1. A compound of formula I

wherein R₁ is

wherein R₇ und R₈, independently, are C_1-4alkyl, halogen or C_1-4alkoxy, and R₉ is hydrogen, C_1-4alkyl or halogen, R₂ is COR₁₀ wherein R₁₀ is H; C_1-6alkyl; C_2-6alkenyl unsubstituted or substituted by halogen; C_2-6alkinyl; C_3-7cycloalkyl; C_3-7- cycloalkyl-C_1-3alkyl; C_2-6epoxyalkyl; phenyl, phenyl-C_1-3alkyl or phenylC_1-3alkenyl wherein the aromatic moiety is unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of C_1-4alkyl, C_1-4- alkoxy, halogen, NO₂, phenyl or phenoxy, R₃, R₄, R₅ and R₆ are independently hydrogen or

C_{1- 4}alkyl.

2. A method of combatting phytopathogenic fungi in plants, seeds or soil which comprises applying to the plants, seeds or soil a fungicidally effective amount of a compound of Claim 1.

3. A composition comprising a compound of Claim 1 in association with an agriculturally acceptable carrier or diluent.

4. A process for the production of a compound of Claim 1, characterized by intramolecular condensation of a compound of formula II

wherein R₁, R₃, R₄, R₅, R₆ and R₁₀ are as defined in Claim 1, and Y is halogen.

5. A compound of formula II as defined in Claim 4.