CS219946B2 - Fungicide means and method of making the active substances - Google Patents

Description

The present invention provides novel fungicidal compositions. in particular, compositions containing as active substances novel fungicides from the 3-aminooxazolidin-2-one group, which exhibit a high fungicidal activity associated with good tolerability for higher plants, which makes it possible to protect these plants from fungal attack. The invention further relates to a process for the production of the aforementioned active substances.

The fungicidally active compounds belonging to the N-phenyl-1,3-oxazolidine-2,4-dione group have already been described, for example, in Dutch Patent Application Publication No. 68/17249 (Sumitomo), in French Patent No. 2,172,295 (BASF). ) and Belgian Patent Specification No 874 406 in the name of the same applicant.

Recently, the bactericidal and fungicidal activity of some aniline and glycine derivatives carrying differently substituted phenyl and acyl groups of different character on the nitrogen atom has also been described.

These acyl groups may in particular be - or .beta.-haloalkanoyl groups (cf. DOS No. 2,513,789 - CIBA-GEIGY) or an acetyl group substituted in the .beta.-position by an oxygen or sulfur atom attached to groups of different nature (see British patent, U.S. Pat. No. 1,500,581 to CIBA-GEIGY], or a 2-furoyl, 2-thienyl or pyridine-2-carbonyl group (see DOS Nos. 2,513,732 and 2,513,788 - CIBA-GIGY). The activity of methylalaninates bearing a 2,6-dialkylphenyl group on the nitrogen atom and any of the following groups: cyclopropanoyl, acryloyl, crotonoyl (see British Patent No. 1,500,576).

Other derivatives derived from fungicidally active acylanilides have recently been described in Belgian Patent Specification No. 863,615 (CIBA-GEIGY) and DOS No. 2,745,533 (Chevron).

The interest in developing and researching new acylaniline derivatives having fungicidal activity is dictated by the urgent need to find new acylaniline derivatives that exhibit high fungicidal activity without being phytotoxic.

The fact is that some of the products already known, while showing excellent fungicidal activity, are at the same time toxic to the plants to be protected against fungal infections.

The damage caused by the phytotoxicity of the active substances to the protected plants is difficult to avoid by using a dose of the fungicidally active compound which represents the best compromise between the fungicidal activity and the phytotoxicity of the compound.

In practical agricultural applications, the amount of active substance actually remaining on the plant varies considerably, depending on various factors, such as weather conditions (in particular the frequency of rainfall), the correct execution and the frequency of the application by the grower.

It is therefore necessary to have fungicidal substances with good fungicidal activity and at the same time safe enough that even large amounts of these substances do not cause damage to the treated plants.

It has now been found that the compounds of formula I

in which

R, R ¹ and R ² , which may be the same or different, each represent a hydrogen atom or a methyl group, n is 0 or 1, and

R * represents ^a hydrogen atom, a chlorine atom, a hydroxyl group, an alkyl group having 1 to 4 carbon atoms, methoxy, methoxycarbonyl, acetoxy, phenoxy or phenyl group, possess fungicidal activity, and have very low phytotoxicity.

Accordingly, the present invention provides a fungicidal composition comprising as active ingredient one or more compounds of formula (I) above.

Only one of the compounds of formula I is known. The compound is N-phenyl-N-acetyl-3-aminooxazolidin-2-one of formula II

--C-CHii- ³ O (ID

described in Journal of Organic Chemistry, 31, p. 968 (1966).

However, the compound of formula (II) was not known to exhibit fungicidal activity.

Accordingly, the present invention provides novel compounds of the above formula (I) wherein at least one of R, R ¹ and R ² is other than hydrogen when the - (CH ₂ ) _n - R ⁴ group is methyl.

The compounds of formula (I) are prepared by methods known per se from organic chemistry.

Examples of reactions that can be used to produce compounds of Formula I are shown in the following reaction scheme:

reaction 1) nh ₉

Scheme 1 n = n

Θ

Cl

RR

R ^z

R ‘(1) (2) reducing

->

agent

NH - NH _Z

(3) reaction 2) reaction 3] (6) + X-C-CH 2 CH 3) 1-Cl-C-O-CH 2 CH. O (4)

(AND)

For example, arylhydrazine (3) can be prepared by reacting the corresponding aniline (1) with sodium nitrite in hydrochloric acid and reducing the resulting diazonium salt (2) (see Scheme 1, Reaction 1j, as described, for example, in the Journal of American Chemical Society, 81). 4673 (1959),

The arylhydrazine is then reacted with 2-Ialogenethyl chloroformate (4) (prepared by treatment with phosgene to halohydrin) in the presence of a base and the thus obtained intermediate (5) is cyclized in the presence of bases to give intermediate (6) (see Scheme). 1, reaction 2). This procedure is described in Journal of the American Chemical Society, 48, 1951 (1926).

Intermediate (6) is then condensed in a known manner with the corresponding acyl halide (7) (see Scheme 1, Reaction 3). Instead of the condensation reaction between intermediate (6) and the acyl halide (7), other analogous reactions known in the literature for introducing the corresponding acyl groups can be used. For example, compounds of formula I wherein R ^{4 is} methoxy, acetoxy, phenoxy, or hydroxyl in the acyl moiety may be prepared by reacting intermediate (6) with phosgene or a haloacetyl halide (such as Cl-C-CH ₂₎ (C1) and then a halogen atom substitution in a known manner.

In the above reaction scheme 1, X is a halogen atom and R, R ¹ , R ² , R ⁴ and n are as defined above. Reaction 3) is carried out in an inert solvent, in the presence of a hydrogen halide-binding base, at reflux.

The compounds of formula (I) exhibit excellent fungicidal activity against phytopathogenic fungi and have both a preventive (i.e., anti-vision) and curative (i.e., anti-fungal) action.

The most important phytopathogenic fungi that can be combated with the compounds and compositions of the invention are Phycomycetes, including Plasmopara, Phytophthora, Peronospora, Pseudoperonospora and Pythium.

The fungicidally active compounds of the invention can be used to combat fungal infections on useful plants such as vines, tomatoes, tobacco, potatoes and the like.

The disclosed compounds have good systemic activity (i.e., they are transferred to different parts of the plants), and thus they can be applied to both foliar and soil.

In addition, the compounds of the formula I are well tolerated by plants which protect them against fungal attack.

Most of the compounds of formula I do not exhibit in the amounts applied

21S94G showed no signs of phytotoxicity, the remaining substances then show only low phytotoxicity, which in each case and at each dose administered is always lower than that of known fungicides.

In practical agricultural applications, the fungicidally active compounds of the formula I can be used as such or not. in the form of suitable compositions containing as active ingredient at least one compound of the formula I, furthermore solid or liquid inert carriers and, if appropriate, surface-active agents and other additives. If desired, other active substances, such as other fungicides, insecticides, plant growth regulators and the like, may be present in these compositions.

The active compounds according to the invention can be formulated, in accordance with conventional agricultural practice, with dusts, powders, wettable powders, emulsifiable liquid preparations, granular preparations and the like.

The amount of the compounds of the formula I to be applied to combat fungal infections depends on a number of different factors, such as the active substance used, the type of composition, the type and extent of infection, the type of agricultural crop to be protected against fungal infections. protect it, in climatic and weather conditions, etc.

In general, application of a fungicidally active compound of the formula I at a dose of between 10 and 500 g / ha, preferably from 100 to 250 g / ha, is sufficient.

The invention is illustrated by the following non-limiting examples.

Example 1

Preparation of N- (methoxyacetyl) -N- (2,6-dimethylphenyl) -3-aminooxazolidin-2-one A) Preparation of 2,6-dimethylphenylhydrazine

To a solution of 220 ml of concentrated hydrochloric acid in 150 ml of water is added dropwise 107 g of 2,6-xylidine, the mixture is cooled to -5 DEG C. and a solution of 66 g of sodium nitrite in 150 ml is added thereto under vigorous stirring. water. 450 g of tin (II) chloride dihydrate in 600 ml of a 5N aqueous solution of hydrogen chloride are added to the resulting yellow-orange suspension at 0 ° C over about 4 hours.

The reaction mixture was stirred for 24 hours while the temperature was allowed to rise to + 20 ^Q C, the solid was filtered off, dissolved in 700 ml of water to the solution at a temperature between 10 and 15 ^Q C was added a solution of 230 g of sodium hydroxide 300 ml of water and the product was extracted three times with 250 ml of diethyl ether each time.

The ether extracts were washed with water and dried over sodium sulfate, diluted with diethyl ether to 1500 ml and then anhydrous hydrogen chloride gas was added until precipitation of 2,6-dimethylphenylhydrazine hydrochloride was complete.

The precipitated salt was filtered off and dried, yielding 40 g of a white solid melting at 205-207 ° C with decomposition. Treatment with sodium hydroxide gives 2,6-dimethylphenylhydrazine from the hydrochloride.

Bj Preparation of 3- (2,6-dimethylanilinjoxazolidin-2-one)

To 41.4 g of 2-bromoethyl chloroformate, prepared from phosgene and ethylene bromohydrin, in 200 ml of benzene at 10 ° C was added 36.5 g of 2,6-dimethylphenylhydrazine (see AJ and 18 g of pyridine in 100 ml of benzene). After complete addition, the temperature of the mixture was allowed to rise to 20 ° C with vigorous stirring.

The pyridine hydrochloride was removed by washing with water, the benzene solution was further washed with hydrochloric acid and water to neutral pH, dried over sodium sulfate and evaporated. 61 g of an oily product are obtained which, after crystallization from ligroin, gives 43 g of a slightly colored solid, m.p. 58-63 ° C, which is 1- (2,6-dimethylphenyl) -2- (N-bromoethyl) oxycarbonylhydrazine. ,

IR: v (0 = 0) = 1710 cm ^-1 , v (NH-CO) = 3180 cm ^-1 , v (NH-Ar) = 3340 cm ^-1 .

g of this intermediate is dissolved in

Toluene (500 ml) was added and tetramethylguanidine (16 g) was added. The mixture was heated to reflux for 3 hours with stirring, then cooled, washed with 200 ml of water, then with 100 ml of dilute hydrochloric acid and finally with 200 ml of water. The combined aqueous phases were extracted twice with 200 ml of dichloromethane each time, the combined organic phases were dried over sodium sulfate and the solvent was evaporated.

The solid residue yielded 22.5 g after crystallization from ligroin / ethyl acetate (2: 1)

3- (2,6-dimethylanilino) oxazolidin-2-one, m.p. 107-110 ° C.

IR: v (C = O) = 1770 cm ^"1, (NH) = 3340 cm ^'1.

The cyclization reaction is repeated by dissolving the intermediate having a melting point of 58-62 ° C in ethanol containing sodium ethoxide and heating the solution to reflux. After the reaction mixture is worked up analogously to the above, the same intermediate as above melting at 107 DEG-110 DEG C. is isolated.

C) To 2 g of intermediate prepared in paragraph Bj in 70 ml of toluene and 0.2 ml of dime219946

10 ml of thylformamide, 1.1 g of methoxyacetyl chloride are added and the reaction mixture is heated under reflux for 8 hours. After cooling, the reaction mixture was evaporated to dryness. The residue, 2.9 g of a thick oily product, was purified by silica gel column chromatography using a mixture of equal parts of benzene and ethyl acetate as eluent.

After evaporation of the solvents gave 1.1 g of syrupy product which spontaneously crystallized and after recrystallization from a mixture of ligroin and ethyl acetate poTabulka L ¹ 'skytne 1 g of the desired compound, together with physical data in the following Table I (compound no. 6j.

IR spectrum:

v _(N-CO-CH2 J = 1680 cm ^-1, v (N-CO-O) = 1780 cm- ^first

Example 2

The compounds of the following Table I were prepared in an analogous manner to Example 1:

compound no. R R ¹ R ² 1 H H II 2 H II II 3 II H H 4 2-CH ·, 6-CH ·, H 5 2-CH.j 6-CH, H 6 2-CH ·, 6-CH3 H H 7 H H 8 2-CH ·, 6-CH ;; H 9 2-CH, 6-CH ·, H 10 2-CH _{: i} 6-CH3 H 11 2-CH, 6-CH, H 12 _2-CH! 6-CH3 H Comment to Table I: ¹¹ elementary analysis all compounds

talk said structures ²¹ Melting points are uncorrected ³⁾ include only bands corresponding to C = ^41, OH = 3300 cm ^1st

Example 1 a d 3

Curative efficacy on grape peronospore [Plasmopara viticola (B. et Cj Berl et de Toni)]

The undersides of the vine leaves (cultivar Dolcettoj, potted in an air-conditioned chamber, maintaining a temperature of 25 ° C and 60% relative humidity) are sprayed with an aqueous suspension of Plasmopara viticola conidia (200,000 conidia / ml). keep in an air - conditioned chamber saturated with water vapor at a temperature

11 R ⁴ melting point (° C) ^2> IR spectrum (cm ^-1 ) ³¹ 1 Cl 71— 74 1690—1760 1 C ₆ H ₅ 112—114 1680—1760 1 I-C3H7 oil 1680—1770 1 Cl 88— 92 1835—1770 1 C ₆ H ₅ oil 1670—1770 1 OCH3 103—106 1680—1780 1 OCH3 86— 91 1690—1760 1 O — CO — CH ₃ oil 1890—1770 1 OH 135—138 ^! 1690-1770 ⁴¹ 0 CO — OCII3 116—119 1680—1730— —1790 1 H 132—135 1670—1770 1 OC ₆ H ₅ 109—112 1690—1780 21 ° C, whereupon treats so that with both sides

their leaves are sprayed with a solution of the test compound in 20% (v / v) aqueous acetone.

After the incubation period (7 days), the degree of infestation is visually determined using a 0 to 4 scale, where each value has the following meaning:

= no effect; the extent of infection is the same as that of untreated infected plants

- suppressing why. infection ranging 1 to 20 May = suppressing why. infection ranging 20 May to 60 = suppressing why. infection ranging 60 to 90

= greater than 90% suppression of infection.

The results are shown in the following table ΙΪ:

1 9 9 4 S

Table II

Curative efficacy of grapevine peronospora when applied to the leaf at a concentration of 0.5% ₀ compound number activity

9

4 4 4 4 4 4 4 4

Example 4

Curative efficacy against peronospora (Peronospora tabacina Adam)

The underside of leaves of tobacco plants (cultivar Burley) grown in pots in an air-conditioned chamber is sprayed with a conidia suspension of Peronospora tabacina (200,000 conidia / ml).

The infected plants are kept in a water-saturated chamber for 6 hours and then transferred to a conditioned chamber to maintain the temperature of 20 ° C and 70% relative humidity for incubation of the fungus. 24 hours after infection, the plants are treated by spraying both sides of their leaves with a solution of the test compound in 20% (v / v) aqueous acetone.

After the incubation period (6 days), the extent of infection was visually evaluated using the same scale as in Example 3.

The results obtained are shown in Table III below:

Table III

Curative activity against peronospora tobacco when applied to the leaf at a concentration of 0.5% ₀ compound number activity

4

4

Example 5

Determination of the degree of phytotoxicity

Both sides of the leaves of the vine plants (cultivar Dolcetto) grown in pots in an air-conditioned chamber at 25 ° C and 60% relative humidity are sprayed with a solution of the test compound in 20% (v / v) aqueous acetone.

After. Visually evaluated for 7 days. the range of phytotxicity symptoms using a scale of 100 (completely, destroyed plants) to 0 (healthy plants).

The data are shown in Table IV below, which also compares the degree of phytotoxicity of the two compounds present on the market for a short time, namely the preparations "Furalaxyl" (see British Patent Specification No. 1448 810 - Giba-Geigy) and "Ridomil". '(See French Patent Specification 2 267042 - Ciba-Geigy).

Table IV

Phytotoxicity index at application of the active substance at a concentration of 0.6% ₀ Compound No. Phytotoxicity index

0

10

0

0 'Furalaxyl' ¹ '100' Ridomil ' ² ' 60

Legend:

¹¹ "Furalaxyl" = N- (2-6-dimethylphenyl) -N- (Γ-methoxycarbonylethyl) -2-furoylamide of formula

² '' Ridomil '= N- (2'-methylethylphenyl) -N- (1'-methoxycarbonylethyl) mothoxyacetamide of the formula

EXAMPLE 6 Systemic Fungicidal Activity Against Vine Peronospora (Plasmopara viticola)

Both sides of the leaves of vine plants 20 cm high (cultivar Dolcetto), cultivated

1 3 3 4 ° in pots at 25 ° C and 60% relative humidity, are sprayed with an aqueous-acetone solution (20% acetone by volume) of the test compounds.

The treated plants are then transferred out of the greenhouse and allowed to grow further.

21 days after treatment, when the plants reach an average height of 80 cm, all their leaves are inoculated on the underside of a suspension of Plasmopara viticola spores (200,000 spores / ml). Both previously treated and newly developed leaves are inoculated.

The plants are then placed in a humid chamber (70% relative humidity) at 21 ° C for 24 hours to develop the disease.

After 7 days, the efficacy of the test compounds is evaluated using a scale of 0 to 4, where 0 represents complete disease infestation of the leaves and 4 represents no infestation. The results are shown in the following overview:

test substance dose of active substance (g / 100 liters) systemic efficacy (average) old leaves new leaves compound 6 (Table I) 50

Ridomil 50

Claims (2)

OBJECT OF THE INVENTION A fungicidal composition, characterized in that it contains at least one compound of the general formula as active substance (a) in which: R, R ¹ and R ^{* 2 R} , which may be the same or different, each represent a hydrogen atom or a methyl group, n is 0 or 1, and R ⁴ represents a hydrogen atom, a chlorine atom, a hydroxyl group, a C 1 -C 4 alkyl group, a methoxy group, a methoxycarbonyl group, an acetoxy group, a phenoxy group or a phenyl group. 2. A process for the preparation of the active compounds of the formula I according to claim 1, characterized in that the compound of the formula I is used R, R ¹ and R ² are as defined above and reacted with an acyl halide of formula (I) in an inert solvent in the presence of a base acting as a hydrogen halide acceptor. X - C - (CH ₂ ) _n - R ⁴ O in which X represents a halogen atom and R ⁴ and n are as defined above.