NL8004962A - NEW N-ARYL-N-ACYL-3-AMINO-OXAZOLIDINE-2-ONES AND ITS USE AS A FUNGICIDE. - Google Patents

Description

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Novel N-aryl-N-acyl-3-amino-oxazolidine-2-ones, and their use as a fungicide.

The invention relates to new fungicides and more particularly to new fungicides of the class of 3-amino-oxazolidin-2-ones which are endowed with a strong fungicidal action combined with good compatibility with the superior plants to be protected against fungal attack and their application.

Fungicidal compounds belonging to the class of N-phenyl-1,3-oxazolidin-2,4-diones are described, for example, in Dutch patent application 68.17249, French patent 2.172.295 and Italian patent application 20579 A / 78.

Recently, the bactericidal and fungicidal activity of some derivatives of aniline and glycine which carry a variously substituted phenyl group and an acyl group of varying nature on the nitrogen atom has also been described.

More specifically, this acyl group may consist of an α or β-haloalkanoyl group (German Offenlegungs script. 2,513,789) or of an acetyl group substituted at the α position with a sulfur or oxygen atom which in turn is associated with groups of varying nature (French patent application 20 75.10722) or also from a 2-furoyl, 2-thienoyl or pyridyl-2-carbonyl group (German Offenlegungsschrift 2,513,732 and 2,513,788).

The microbicidal activity of methylalaninates bearing a 2,6-dialkylphenyl group and one of the following groups: cyclopropanoyl, acryloyl, crotonoyl (Swiss patent applications 4988/74 and 2906/75) has also been described.

Other derivatives of fungicidal acylanilines have recently been described in Belgian patent 863,615 and 800 40fi. \ 2

German Offenlegungsschrift 2,745,533.

The importance of looking for new derivatives of acylanilines with a fungicidal activity lies in the need to find acylaniline derivatives with a high fungicidal activity, combined with a lack of phytotoxicity.

In fact, some of the previously known products, while developing excellent fungicidal activity, have also been found to be toxic to the plants that are protected against fungal infections.

The damage caused by the phytotoxicity to the plants to be protected can hardly be avoided by using a dosage of fungicidal compound which can be the best compromise between the fungicidal activity of the compound and its phytotoxicity.

In fact, in practical application in agricultural cultures, the amount of product that actually remains on the plant varies considerably depending on various factors, such as, for example, weather conditions (in particular the frequency of control drop), the correctness and the frequency of application. gene performed by the farmer.

It is therefore necessary to have fungicidal compounds having a good fungicidal action and at the same time having a high safety margin, so that even large amounts of the product do not cause damage to the treated plants.

It has now been found that the compounds of formula 1, wherein R, R 1 and R 2, equal to or different from each other, are hydrogen, halogen, alkyl of 1 to 4 carbon atoms or alkoxyl of 1 to 4 carbon atoms; R1 is hydrogen or methyl; A is a group of formula 2 or 3; n is 0 or 1; R 1 hydrogen, an alkyl group of 1 to 5 carbon atoms, optionally substituted with halogen atoms; a cycloalkyl group of 3 to 6 carbon atoms; an alkenyl group with 2 to 5 carbon atoms; ethynyl; halogen (when n = 1); CN; SCN; phenyl, optionally substituted with 35 alkyl groups of 1 to 5 carbon atoms or with halogen atoms; 5- or 6-membered heterocycles containing 1 to 3 hetero-8004962 # <3 atoms (especially furyl, tetrahydrofuryl, thienyl, pyrimidyl, pyridyl, imidazolyl, pyrazolyl, triazolyl); acetyl; COOalkyl; -OR,.; -SR, .; a group of formula 4 (wherein R 1 and R 8, which are the same or different, are hydrogen, alkyl of 1 to 5 carbon atoms, alkenyl of 2 to 5 carbon atoms, alkynyl of 2 to 5 carbon atoms, phenyl; a heterocyclic group of 5 or 6 members, containing 1 to 3 heteroatoms, which is SO 2 -alkyl or acetyl), are endowed with a fungicidal action and at the same time have very low phytotoxicity.

The present invention therefore relates to the use of the compounds of formula 1 in combating fungal infections in beneficial plants.

Only one of the compounds covered by the general formula 1 has been described in the literature, namely 15 N-phenyl-N-acetyl-3-amino-oxazolidin-2-one of formula 5. This compound is described in "Journal of Organic Chemistry *, 31_, p.

968 (1966).

However, the fungicidal activity of this compound of formula 5 was unknown.

- A further object of the invention is therefore to provide compounds of formula 1 in which at least one of the groups R, R 1, R 2 and R 1 is different from hydrogen when - (A) -R, - CH 2.

n 4 3

The preparation of the compounds of formula I is carried out by methods known in the normal practice of organic chemistry.

For example, one can prepare an arylhydrazine of formula 13 by reacting the corresponding aniline of formula 11 with sodium nitrite (NaITC2) in hydrochloric acid and then reducing according to the diazonium salt of formula 12 thus obtained (reaction scheme A, reaction equation 1 ), as described, for example, in "Journal of American Chemical Society", 81, p. 4673 (1959).

The arylhydrazine is then reacted with 2-haloethyl- or 1-methyl-2-haloethyl-chloroformate of formula 14 (which in turn was obtained by the action of 8004962-4 phosgene on a halogen hydrin) in the presence of a base, and the intermediate compound of formula 15 thus obtained is then cycled in the presence of bases, to give the intermediate compound of formula 16 (reaction scheme A, reaction equation 2). This method is described in Jour. or Am. Chem. Soc. 48, 1951 (1926).

The intermediate of formula 16 is then condensed by means of the appropriate acyl halide of formula 17, according to known techniques (reaction scheme A, equation 3). The condensation reaction between the intermediate of formula 16 and the acyl halide of formula 17 can be replaced by analogous reactions described in the literature which allow the introduction of certain acyl groups. For example, the compounds of the general formula II wherein the acyl moiety is R 1 -OR,. -SR ,, or a group of formula 4 can be prepared by reacting the intermediate of formula 16 with phosgene or with haloacetyl or halopropiony .1 halides (such as, for example, the compounds of formulas 6 and 7, respectively) and by subsequently substituting the halogen atom according to known techniques.

The compounds of formula 1 wherein the acyl moiety is a group of formula 8 wherein R 1 NHR 3. can be prepared by reacting the intermediate of formula 16 with an isocyanate of formula 9.

The compounds of formula 1 wherein the acyl portion is represented by formula 10 (A = C 1; R 3 = R acetyl) can be prepared by reacting the intermediate of formula 16 with diketene.

In reaction scheme A, X is halogen and R, R i, R 30, R y R, R, A and n have the meanings given above for formula 1.

Reaction 3 is performed in an inert solvent, in the presence of hydrogen halide acid accepting base at reflux temperature.

The compounds of the formula I have an excellent fungicidal action against phytopathogenic fungi and their action has both a preventive character (ie they counteract the occurrence of the disease) and a curative character (ie when the infection has already started).

The most important class of phytopathogenic fungi that can be controlled using the compounds of the invention is that of Phycomicetes, which includes Plasmopara spp., Phytophtora spp., Peronospora spp.,

Pseudoperonospora spp. and Phythium spp.

The fungicidal compounds of the invention are useful for controlling fungal infections on beneficial plants, such as wine, tomato, tobacco, potato and other cultures.

They have good systemic characteristics (ie they are introduced into the various parts of the plant) which makes it possible to apply these products both on the leaves and on the soil.

In addition, the compounds of formula 1 were found to be compatible with the plants to be protected against the fungal attack.

Most of the compounds of formula 1 do not show any sign of phytotoxicity in the amounts tested, while the remainder showed only slight phytotoxicity, however lower than that of known fungicides.

In practical agricultural application, the fungicidal compounds of formula 1 may be used as such or in the form of suitable compositions consisting of the compounds of formula 1 as active ingredient, solid or liquid inert ingredients and optionally surfactants and other additives. If desired, the compositions may contain other active compounds, such as other fungicides, insecticides, plant growth regulators, etc.

The compounds can be formulated according to normal agricultural practice as dusty materials, powders, wettable powders, emulsifiable liquids, granular formulations etc.

The amounts of the compounds of formula 1 8004962 6 that must be spread to combat fungal infections depend on various factors such as the active compound used, the type of composition or formulation, the nature of the infection and its severity, the type of agricultural culture swam infestation 5 must be protected, climatic and weather conditions, etc.

Generally, amounts of the fungicidal compound of formula 1 of 10 to 500 g per hectare are sufficient, the preferred amount being from 100 to 250 g / ha.

A number of examples are given below to illustrate the invention.

Example I

Preparation of N- (Methoxyacetyl) -N- (2,6-dimethylphenyl) -3-amino-oxazolidine-2-0n.

A) Preparation of 2,6-dimethylphenylhydrazine: 107 g of 2,6-xylidine were dropped into a solution of 220 ml of concentrated HClin 150 ml of water. After cooling to -5 ° C, a solution of 66 ml NaNO 2 in 150 ml 10 O was added to this mixture over a period of about 1 hour and stirring vigorously. To the yellow-orange colored suspension thus obtained, 450 g of SnCl 2 O in 600 ml of 5N aqueous HCl was added over a period of about 4 hours at 0 ° C.

The mixture was then stirred for 24 hours, raising the temperature to + 20 ° C. The solid thus formed was filtered off, dissolved in 700 ml water and then treated with a solution of 230 g NaOH in 300 ml water at a temperature between 10 and 15 ° C, after which the product was extracted with diethyl ether (3 x 250 ml ).

The ethereal extract, after washing with water and drying over Na2SO4, was made up to a volume of 1500 ml with diethyl ether and then treated with anhydrous gaseous HCl until complete precipitation of the hydrochloride of the 2,6-dimethylhydrazine was prepared.

The salt was then filtered and dried to give 40 g of a white solid, mp 205 to 207 ° C with decomposition. 8004 962 7 was obtained from the hydrochloride 2,6-dimethyl-phenylhydrazine by treatment with NaOH.

B) Preparation of 3- (2,6-dimethylaniline) oxazolidin-2-one

To 41.4 g of 2-bromoethyl chloroformate, prepared from phosgene and ethylenic bromohydrin in 200 ml of benzene, the following reagents were added at 10 ° C: 36.5 g of 2,6-dimethyl-phenylhydrazine (see under A), and 18 g of pyridine in 100 ml of benzene. Once this addition was complete, the temperature was allowed to rise to 20 ° C with continuous vigorous stirring.

The pyridine hydrochloride was removed by washing with water.

The benzene solution was then further washed with HCl and with water to a neutral pH and then dried over Na 2 SO 4 and evaporated to give 61 g of an oily product which, after crystallization from ligroin, gave 43 g of a light colored solid. mp 58-63 ° C, consisting of 1- (2,6-dimethylphenyl) -2- (3-bromoethyl) -oxycarbonylhydrazine. / IR spectroscopy gave: v (C = 0) = 1710 cm -1; v (NH-CO) = 3180 cm -1; v (NH-Ar) = 3340 cm_1_7.

40 g of this intermediate was dissolved in 500500 ml of toluene and then treated with 16 g of tetramethylguanidine. This mixture was then heated under reflux for 3 hours with stirring. After cooling, the mixture was washed with 200 ml of water and then with 100 ml of dilute HCl and finally again with 200 ml of water.

The reunited aqueous phases were extracted with (2 x 200 ml).

The combined organic phases were dehydrated over <280> and then the solvent was evaporated to give a solid residue which was crystallized from ligroin ethyl acetate (2: 1).

This gave 22.5 g of 3- (2,6-dimethylaniline) -oxazolidin-2-one, m.p. 107 ° C. / IR spectrum: v (C = 0) = 1770 cm v (NH) = 3340 cm * _ ?.

The cyclization reaction was repeated, dissolving the intermediate compound, mp 58-62 ° C, in ethanol containing sodium ethylate, and then heating 8004962 δ with reflux of the solution.

After an analogous treatment of the reaction mixture, the same intermediate compound was isolated, m.p. 107 to 110 ° C.

C) To 2 g of the intermediate compound prepared as described under B), in 70 ml of toluene and 0.2 ml of dimethylformamide, 1.1 g of methoxyacetyl chloride was added. The reaction mixture was then heated at reflux for 8 hours. After cooling, the reaction mixture was subjected to complete evaporation of the solvents. The residue, consisting of 2.9 g of a thick oily product, was purified on a silica gel column using as an eluant a mixture of benzene and ethyl acetate in the ratio 1: 1.

Thus, after removal of the solvents, 1.1 g of a syrupy product which spontaneously crystallized crystal and which after recrystallization from a mixture of ligroin and ethyl acetate in the ratio 1: 1 yield 1 g of the desired compound, the characteristics of which are registered in Table A (Compound No. 6).

20 / IR spectrum: v (N-CO-CH 3) = 1680 cm 2; v (N-CQ-O) * 1780 cm

Example II

Proceeding in an analogous manner as described in Example I, the compounds shown in Table A were prepared.

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Example III

Curative effect on vine Peronospora. (Plasmopara viticola (B. et C) Berl et de Toni).

Grape vine leaves from Cv. Dolcetto grown in 5 pots in a conditioned environment, stabilized at 25 ° C and 60% relative humidity, were sprinkled on the bottom leaf surface with an aqueous suspension of Plasmopara viticola conidia (200,000 conidia / ml). After 24 hours in a moisture-saturated environment, stabilized at 21 ° C, the 10 plants were treated by sprinkling both leaf surfaces with the products to be tested in a hydroacetonic solution with 20% by volume acetone. At the end of the 7-day incubation period, the degree of infection was determined by eye on the basis of a rating scale, on which the figures have the following meanings: 15 0: no effect, infection equal to that of control plant (infected but not treated plants), 1: 1-20% reduction in infection; 2: 20-60% reduction of the infection; 3: 60-90% reduction of the infection; 20 4: reduction of the infection by more than 90%.

Table B below shows the results obtained;

Table B

Curative action against vine Peronospora by application to the leaves at a dose of 0.5 ° / o.

Connection no. Operation Connection no. Operation 13 7 4 2 3 8 4 3 4 9 4 30 4 4 10 4 5 4 11 4 6 4 12 4

Example IV

35 Curative effect against Peronospora in tobacco (Peronospora tabacina Adam).

8004962 11

The leaves of tobacco plants Cv. Burley, grown in pots in a conditioned environment, were sprinkled on the lower leaf surfaces with a Peronospora tabacina conidia suspension (200,000 conidia / ml).

After 6 hours in a moisture-saturated environment, the plants were transferred to a conditioned environment, stabilized at 20 ° C and 70% relative humidity, for incubation of the fungus. 24 hours after infection, the treatment was carried out by sprinkling both leaf surfaces with the product to be tested in a hydroacetonic solution with 20% by volume acetone.

At the end of the 6-day incubation period, the degree of infection by eye was determined on a value scale with an index range similar to that of Example III.

The results of the test are set out in Table C.

Table C

Curative effect upon application to the foliage of plants infected with tobacco peronospora in doses of 0.5 ° / o.

Connection No._ Operation_ 4 4 6_4_

Example V

Determination of the degree of phytotoxicity.

Browse Cv. Dolcetto wine plants, grown in pots in a conditioned environment, stabilized at 25 ° C and 60% relative humidity, were treated by sprinkling both leaf surfaces with a hydroacetonic solution containing 20% by volume of acetone of the products to be tested.

After 7 days, the severity of the phytotoxic symptoms was visually evaluated according to a rating scale with indices ranging from 100 (completely damaged plant) to 0 (for a healthy plant).

The corresponding data are recorded in Table D in comparison to the phytotoxicity indices of two compounds 8004962 12 compounds known to have recently been on the market, namely "Furalaxyl" (British Patent 1,448,810 and "Ridomil" (French Patent Application 2,267). .042).

Table D

5 Phytotoxicity index for doses of 0.6 ° / o

Compound no. Phytotoxicity index 1 0 3 10 4 0 10 6 0 "Furalaxyl" 100 "Ridomil” (2) __ 60_ (1) "Furalaxyl" = N- (2,6-dimethylphenyl) -N- (1-carbomethoxy-ethyl -2- uroyl amide (formula 18).

(2) "Ridomil" * N- (2,6-dimethylphenyl) -N- (1'-carbomethoxy-ethyl) -methoxyacetamide (Formula 19).

8004962

Claims (20)

Method for combating fungal infections on useful plants, characterized in that compounds of the general formula 1, wherein R, R 1 and R 2, are spread on the plants, as such or in the form of suitable preparations. which are the same or different, are hydrogen, halogen, alkyl of 1 to 4 carbon atoms or alkoxyl of 1 to 4 carbon atoms; Rg is hydrogen or methyl; A is a group of formula 2 or 3; n is 0 or 1; hydrogen; an alkyl group of 1 to 5 carbon-10 atoms, optionally substituted with halogen atoms; a cycloalkyl group of 3 to 6 carbon atoms; an alkenyl group with 2 to 5 carbon atoms; ethynyl; halogen (when η is 1); CN; SCN; phenyl, optionally substituted with alkyl groups of 1 to 5 carbon atoms or with halogen atoms; a 5- or 6-membered heterocyclic group containing 1 to 3 heteroatoms; an acetyl group; COOalkyl; -0R,.; -SR, .; or is a group of formula 4; wherein R 1 and R 2 equal to or different from each other are hydrogen; O alkyl of 1 to 5 carbon atoms; alkenyl of 2 to 5 carbon atoms; alkynyl of 2 to 5 carbon atoms; phenyl; a 5- or 6-membered heterocyclic group containing 1 to 3 heteroatoms; SO 2 -alkyl or acetyl. Method according to claim 1, characterized in that the infection is caused by vine Peronospora (Plasmopara viticola). Method according to claim 1, characterized in that the infection is caused by Peronospora of the tobacco plant (Peronospora tabacina). A fungicidal composition, characterized in that it contains as active ingredient one or more of the compounds of formula 30.. Compounds of formula 1, wherein R, R 1 and R 2, which are the same or different, represent hydrogen, halogen, alkyl or alkoxyl of 1 to 4 carbon atoms; R1 is hydrogen or methyl; A is a group of formula 2 or 3; n is 0 or J; 35 and R 2 hydrogen; alkyl of 1 to 5 carbon atoms, optionally substituted with halogen atoms; cycloalkyl of 3 to 6 carbon 8004962 atoms; alkenyl of 2 to 5 carbon atoms; ethynyl; halogen (when η is 1); CN; SCN; phenyl, optionally substituted with alkyl groups of 1 to 5 carbon atoms or with halogen atoms; a 5- or 6-membered heterocyclic group containing 1 to 3 hetero-5 atoms; acetyl; COOalkyl; -OR,.; -SR ,, or a group of formula 4; where R ,. and Rg, which are the same or different from each other, hydrogen; alkyl of 1 to 5 carbon atoms; alkenyl of 2 to 5 carbon atoms; alkenyl of 2 to 5 carbon atoms; phenyl; a 5- or 6-membered heterocyclic group containing 1 to 3 heteroatoms; SO 2 -alkyl or acetyl; provided that when - (A) -R 1 = CH 2, at least one of the n 4 3 groups R, R 1, R 1 and R 1 is different from hydrogen. Compounds according to claim 5, characterized in that R, Rj, and all are hydrogen and η is 1. 7. The compound N-phenyl-N-chloroacetyl-3-amino-oxazolid in-2-one. 8. The compound N-phenyl-N-phenylacetyl-3-aminooxazolidin-2-one. 9. The compound N-phenyl-N- (g-methyl-propionyl) -20 3-amino-oxazolidin-2-one. 10. The compound N-phenyl-N-methoxyacetyl-3-amino-oxazolidin-2-one. Compounds according to claim 5, characterized in that R 1 and R 1 are methyl and R 2 and R 1 are hydrogen, 12. The compound N- (2,6-dimethylphenyl) -N-chloroacety1-3-amino-oxazolidin-2-one. 13. The compound N- (2,6-dimethylphenyl) -N-phenyl-acetyl-3-amino-oxazolidin-2-one. 14. The compound N- (2,6-dimethylphenyl) -N-methoxyacety 1-3-amino-oxazo 1 idin-2-one. 15. The compound N- (2,6-dimethylphenyl) -N-acetoxy-acetyl-3-amino-oxazolidin-2-one. 16. The connection. N- (2,6-dimethylphenyl) -N-hydroxyacetyl-3-amino-oxazolidin-2-one. 17. The compound N- (2,6-dimethylphenyl) -N-carbomethoxycarbonyl / "" or N-methoxyoxalyl / -3-amino-oxazolidin-2-one. 8004962 18. The compound N- (2,6-dimethylphenyl) -N-acetyl-3-amino-oxazolidin-2-one. 19. The compound N- (2,6-dimethylphenyl) -N-phenoxy-acetyl-3-amino-oxazolidin-2-one. 20. Methods and articles essentially as described in the description and / or the examples. Qi! 800 4 962