NO142714B - ANILIDES WITH FUNGICIDE EFFECT. - Google Patents

Description

The present invention relates to anilides with fungicidal action of formula I

in which

means C 1 -C 4 -alkyl, C 1 -C 4 -alkyloxy or halogen, R 2 means hydrogen, C 1 -C 4 -alkyl or halogen,

<R>5 means hydrogen, C 6 -alkyl or halogen

Rg means hydrogen or methyl, whereby the total number of C atoms of the substituents R^, R£, R5 and R, in the phenyl ring does not exceed the number 8,

CH

X means -CH5- or 1 3 ,

-CH-

R 3 means -COOR', or

whereby

R<1>, R" and R"<1> independently of each other mean hydrogen, methyl or ethyl and

R 4 means an optionally halogen-substituted 2-furanyl or 2-tetrahydrofuranyl group

with the condition that the phenyl ring contains a further "substituent, when it is substituted in the 2,6- or 2,3,6-position with methyl and when at the same time R^ means the 2-furanyl residue and —X-R^ means the a-propionic acid methyl ester.

By alkyl and as the alkyl part of an alkoxy group, the following groups are to be understood, each according to the number of the indicated carbon atoms: methyl, ethyl, n-propyl, isopropyl or n-, iso-, sec- or tert.butyl. Examples of halogen include fluorine, chlorine, bromine or iodine.

Furan-3-carboxylic acid anilides are known as fungicides from DOS 2,006,471 and from Danish patent 123,063 (DE-AS 1,768,686), and also furan-2-carboxylic acid anilides are previously known from DAS 1,187,420, but are classified as herbicides . The effect limits for the above-mentioned compound types appear from the biological comparison tests carried out. Below, the structurally most comparable or the most effective known compounds were used as comparison.

It has now surprisingly been found that compounds with the clearly deviating formula I have a very favorable fungicidal spectrum for practical purposes for the protection of cultivated plants. Cultivated plants in the scope of the present invention are, for example, cereals, maize, rice, vegetables, sugar beets, soya, peanuts, fruit trees, ornamental plants, primarily vines, hops, cucumber plants (cucumbers, pumpkins, melons), Solanaceans such as potatoes, tobacco and tomatoes, as well as banana-cocoa and natural rubber plants.

With the active substances of formula I, the fungi appearing on plants or plant parts (fruits, flowers, foliage, stems, tubers, roots) of these and similar crops can be strongly inhibited or destroyed, whereby later growing plant parts are also spared from these fungi . These active substances are effective against phytopathogenic fungi belonging to the following classes: Ascomycetes (e.g. Erysiphaceae), Basidiomycetes such as primarily rust fungi, Fungi imperfecti, and also especially against Oomycetes belonging to the class Phycomycetes such as Phytophthota, Peronospora, Pseudoperonospora, Pythium or Plasmopara. In addition, the compounds of formula I act systemically. They can further be used as a mordant for the treatment of seeds (fruits, tubers, grains) and plant cuttings for protection against fungal infections as well as against phytopathogens

fungi that occur in the soil.

Within this latter group are compounds such as fungicides

of particular importance, in which -X-R^ produces the α-propionic acid methyl ester group and in which the total number of C atoms at the substituents R-^, R2, R^ and Rg does not exceed the number 4, for example

The 2,3,5,6-tetramethylaniline, 2,6-dimethyl-3-ethylaniline^ or 2,6-dimethylaniline derivatives as well as such 2,6-dimethylaniline derivatives which contain, in addition, a third substituent R,-or R^ in the phenyl nucleus.

The preparation of compounds of formula I takes place by acylation of a compound of formula II

with a carboxylic acid of formula III

or its acid halide, acid anhydride or ester, in individual cases with one of its acid amides (omamidation).

According to another method, the compounds of formula I can also be transferred from the acylanilides of formula IV with butyl lithium or Na hydride to the corresponding alkali salt, which then leads to the desired end product with a compound of formula V

or is prepared from the acylanilides of formula IV with the compound of formula V in the presence of an alkali carbonate (such as Na2C03 or K2C03^ as proton acceptor, preferably with the addition of catalytic amounts of alkali iodine (such as KJ).

In formulas II, III, IV and V, R, to R& and X have the meanings given for formula I, while "Hal" stands for a halogen atom, preferably chlorine or bromine, or another easily cleavable residue. The term "acid halide" preferably stands for the acid chloride or acid bromide.

The reaction can be carried out in the presence or absence of solvents or diluents inert to the reactants. Examples include: aliphatic or aromatic hydrocarbons, such as benzene, toluene, xylenes, petroleum ether, halogenated hydrocarbons such as chlorobenzene, methylene chloride, ethylene chloride, chloroform, ether and ether-like compounds such as dialkyl ether, dioxane, tetrahydrofuran, nitriles such as acetonitrile, N, N-dialkylated amides such as dimethylformamide, anhydrous acetic acids, dimethyl sulfoxide, ketones such as methyl ketones and mixtures of such solvents with each other.

The reaction temperatures are between 0° and 18°C, preferably between 2° and 12°. In many cases, the use of acid-binding agents or condensing agents beneficial. As such, tertiary amines such as trialkylamines (e.g. triethylamine), pyridine and pyridine bases, or inorganic bases, such as the oxides and hydroxides, hydrogen carbonates and carbonates of alkali and alkaline earth metals as well as sodium acetate are mentioned. An excess of the relevant aniline derivative of formula II can also serve as acid-binding agents in the first method.

The method of preparation starting from compounds of formula II

can also be carried out without acid-binding agents, whereby in some cases the passage of nitrogen is used to expel the formed hydrogen halide. in other cases, an addition of dimethylformamide as a reaction catalyst is very advantageous.

Details for the preparation of the intermediate products of formula II can be read from the methods as they are generally described for the preparation of anilino-alkanoic acid esters in the following publications:

J. Org. Chem. 3o, 41ol (1965),

Tetrahedron 1967, 487,

Tetrahedron 1967, 493.

CH-

I 3 The compounds of formula I with the meaning X = -<X>CH- possess an asymmetric carbon atom ( ) and can be cleaved in the usual way into optical antipodes. In this way, the enantiomeric D-form has the stronger fungicidal effect.

Within the scope of the invention, based on this, the compounds which have the D-configuration of formula I are preferred. The D-forms, when measured in ethanol or acetone, usually have a negative angle of rotation.

For the production of the pure optical D antipodes, e.g.

the racemic compound of formula VI

wherein R^, R^, R5 and R^ have those of formula I

stated meanings,

prepared and then in a manner known per se reacted with an N-containing optically active base to the corresponding salt. By fractional crystallization of the salt and subsequent release of the acid of formula VI which is enriched with the optical D antipode and possible repetition (also several times) of the salt formation, crystallization and release of the α-anilinopropionic acid of formula VI, the pure D is gradually obtained - the shape. From this, it is then possible, as far as desired, in the usual way, e.g. in the presence of HCl or H2S°4 me<^ methanol or ethanol prepare the optical D configuration of the ester underlying formula II, or prepare with the corresponding amine of the formula HN(R")(R'") the amide corresponding formula II. As optically active organic bases, e.g. a-phenylethylamine in speech.

Instead of the fractional crystallization, the enantiomeric D form of formula VI can also be obtained by replacing the hydroxyl group

in the naturally occurring L(+)lactic acid against halogen and further reaction of this product under configuration inversion with the desired aniline of formula VII

Regardless of the optical isomerism, an atropisomerism about the phenyl N< axis is usually observed in those cases where the phenyl ring is at least substituted in the 2,6-position and at the same time is substituted asymmetrically to this axis (possibly also through the presence of additional substituents. This phenomenon is subject to the steric hindrance of the residues -X-R^ further introduced on the N-atom of the aniline of formula VII, but especially of the heterocyclic residue -CO-R^. As long as no targeted synthesis is carried out to isolate pure isomers , normally precipitates a product as a mixture of two optical isomers or two atropisomers or as a mixture of these four possible isomers.The basic more favorable fungicidal effect of the enantiomeric D-form (in comparison to D,L-form or to L-form) however, remains retained and is not significantly affected through the atropisomerism.

The following examples serve to explain the invention in more detail. The temperature indications are in °C. If nothing else is mentioned, when mentioning an active substance of formula I, which can appear in optically active forms, the racemic mixture is always meant.

EXAMPLE 1

Manufacture of

N-(1'-methoxycarbonyl-ethyl)-N-(furan-(2")-carbonyl)-2, 3-dimethyl-6-ethylaniline. a) loo g 2,3-dimethyl-6-ethylaniline, 223 g of 2-bromopropionic acid methyl ester and 84 g of NaHCO3 were stirred for 17 hours at 14o°,

then cooled, diluted with 3oo ml of water and extracted with diethyl ether. The extract was washed with a little water, dried over sodium sulfate, filtered and the ether was evaporated. After the distillation of the excess of the 2-bromopropionic acid methyl ester, the crude product was distilled in high vacuum,

Kp. 88-9o°C/o,o4 Dry.

b) To 17 g of the ester obtained according to a), 2 ml of dimethylformamide and 15o ml of abs. toluene, 13 g of furan-2-carboxylic acid chloride was added dropwise with stirring and heated for one hour under reflux conditions. After evaporation of the solvent, the crude product was brought to crystallization by rubbing with petroleum ether,

m.p. llo.5-126°C (ethyl acetate/petroleum ether).

Compound No. 2 is the mixture of two pairs of diastereomers.

If one acylates the D-form of α-(2,3-dimethyl-6-ethylanilino)-propionic acid methyl ester with furan-(2)-carboxylic acid or one of its reactive derivatives, one obtains the D-form of both atropisomers (comp. 2a and 2b).

EXAMPLE 2

Manufacture of

N-(dimethylaminocarbonylmethyl)-N-(furan-(2")-carbonyl)-2,6-dimethylaniline. 28 g of the N-(methoxycarbonyl-methyl)-N-(furan(2") prepared analogously to example 1 -karaonyl)-2,6-dimethylaniline, m.p. 98-99° is stirred for one day with 150 ml of 40% aqueous dimethylamine solution and 0.5 g of triethylenediamine at room temperature. Unreacted starting material is removed by two ether extractions and then the aqueous phase is evaporated on the rotary evaporator. The remaining viscous oil is brought to crystallization by trituration with hexane.

After recrystallization from hexane/tetrahydrofuran, the final product has a melting point of 142-145°C.

In this way or by one of the methods stated above

the following tri- or tetra-substituted compounds of formula Ib in the phenyl nucleus are prepared: (R1= 2-position)

In the following, compounds are mentioned which are mono- or di-substituted in the phenyl nucleus:

Below can compounds of formula

Additional compounds of the general formula

The compounds of formula I can be used together with other suitable pesticides or active substances that promote plant growth, in order to make their spectrum of action wider.

The compounds of formula I can be used by themselves or together with suitable carriers and/or other additives. Suitable carriers and additives can be solid or liquid and correspond to substances common in formulation technology, such as e.g. natural or regenerated mineral substances, dissolving, dispersing, netting, binding; thickening, binding or fertilizing agents.

The content of active substance in products for sale is between o.l - 9o%.

Biological comparisons of action between the compound according to the present invention and structurally most comparable, previously known compounds.

Comparative compounds:

Effect test 1

Effect on Phytophora on tomatoes

Ia Curative effect.

Tomato plants of the species "Roter Gnom" became after three weeks of culture

sprayed with a zoospore suspension of the fungus and incubated in a cabin at 18 - 2o° and saturated humidity. Interruption of

the humidification after 24 hours. After drying the plants, they are sprayed with a soup, which contains active substances formulated as spray powder in a concentration of o.o5%. After drying the spray coating, the plants are again placed in the humidity cabin for 4 days. The number and size of the typical leaf spots that appear after this time are assessment standards

for the business of the substances provided. Infected, though

untreated control plants served as a comparison.

The compounds of formula I achieved the following effect:

Compounds No. 1, 4, 8 and 60 in the same experiments at application concentrations of only 0.02% reduced the fungal attack to

< 20%.

Impact test 2

Action against Plasmopara viticola (Bert. et CUrt.) (Berl. et DeToni) on grapevines.

Residual preventive effect

Grape cuttings of the species "chasselas" are grown in greenhouses. At the 10-leaf stage, 3 plants are sprayed with a slurry made from the active substance formulated as a spray powder (with 0.02% active substance). After drying the spray coating, the plants are uniformly infected on the underside of the leaves with a spore suspension of the fungus.

The plants are then kept for 8 days in a humidity chamber. After this time, you can see clear disease symptoms on the control plants. The number and size of the infection sites on the treated plants is the assessment yardstick for the effect of the investigated substances. Infected but untreated control plants serve as a reference.

With the active ingredients no. 1, 5, 5a, 5b, 6, 7, 12, 15, 41, 42,

51 and 53, the fungal attack is completely or almost completely inhibited (0-5% attack), and with the help of the other active ingredients, the fungal attack remains below 20%.

The comparison connections give the following picture:

Impact test 3

Effect against Pythium debaryanum on Beta vulgaris (sugar beet).

a) Effect after soil application.

The fungus is cultivated on sterile oat grains and a

soil-sand mixture. The thus infected soil is filled in flower pots and sown with sugar beet seeds. Immediately after sowing, the trial preparations are formulated as spray powder completely over the soil as an aqueous suspension (20 ppm active substance with reference to the soil volume.).

The pots are then placed in a greenhouse for 2 - 3 weeks at 2o-24°C. The soil is kept evenly moist by lightly sprinkling with water. When evaluating the trials, the growth of the sugar beet plants as well as the proportion of healthy and diseased plants is determined.

b) Effect after stain application

The fungus is cultivated on sterile oat grains and a

soil-sand mixture. The thus infected soil is filled in flowerpots and sown with sugar beet seed, which has been stained with the pre-soak preparations formulated as a staining powder

(looo ppm active substance with reference to seed weight). The sown pots are placed in a greenhouse for 2-3 weeks at 2o-24°C. The soil is thereby kept evenly moist by lightly sprinkling with water. During assessment, the growth of the sugar beet plants as well as the proportion of sick and healthy plants is determined.

After treatment with the active substances of formula I grew,

both under test conditions a) and b), more than 85% of the sugar beet plants up and had a healthy appearance. In the untreated controls, less than 2o% of the plant grew up with a partially diseased appearance.

Claims (1)

Anilides with fungicidal action characterized by formula I where R1 means C₁-C₁-alkyl, C₁-C₁-alkyl or halogen, R2 means hydrogen, C₁-C₁-alkyl or halogen,, R 5 means hydrogen, C 1 -C 1 -alkyl or halogen, R& means hydrogen or methyl, whereby the total number of C atoms of the substituents R^ R2, R_ and R, in the phenyl ring does not exceed the number 8, D PH X means -CHy or ■ 3 , -CH- R 3 means -COOR' or whereby R', R", R'" independently of each other means hydrogen, methyl or ethyl and R means an optionally substituted with halogen 2-furanyl or 2-tetrahydrofuranyl group with the condition that the phenyl ring contains an additional substituent, when it is substituted in the 2,6- or in the 2,3,6-position with methyl and when at the same time R^ means the 2-furanyl residue' and - X-R3 means the α-propionic acid methyl ester.