NO144961B - FUNGICIDE N-ACYL ANILINED DIETIC ACID ESTERS. - Google Patents

Description

The present invention relates to N-acyl-aniline acetic acid esters for use as fungicides with the general formula I

in which

R 1 means C 1 -C 4 -alkyl,

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

R 5 means hydrogen, C 1 -C 3 -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 the number does not exceed 6,

R 3 means -COOCH 3 and

R 4 means C 1 -C 8 -alkyl which is optionally substituted with a rhodano group, C 2 -C 8 -alkenyl or C 3 -C 7 -cycloalkyl.

In DOS No. 2,212,268, it is stated in general terms that N-halo-acylated anilinoalkanecarboxylic acid esters possess selective herbicidal action. However, only some N-haloacetylated 2,6-di-alkylanilinoacetic acids and their esters are mentioned by name and proven herbicide. References to microbicide, especially plant-fungicidal effects are not given.

It has now surprisingly been found that compounds with the distinctly deviant structure of formula I exhibit a microbicide spectrum very favorable for practical needs for the protection of cultivated plants. Cultivated plants within the scope of the present invention are, for example, grain, maize, rice, vegetables, sugar beet, soya, peanuts, fruit trees, ornamental plants, but primarily vines, hops, cucumber plants (cucumbers, pumpkins, melons), sunflowers such as potatoes, tobacco and tomatoes , as well as banana, cocoa and natural rubber plants.

With the active compounds of formula I, the appearance of

fungi on plants or plant parts (the fruits, flowers, foliage, stems, tubers, roots) on these or related beneficial cultures are reduced or destroyed, whereby later growing plant parts are also spared from such fungi. The active compounds are effective against phytopathogenic fungi of the following classes: Ascomycetes (e.g. erysiphaceae), Basidiomycetes such as primarily rust fungi, Fungi imperfecti (e.g. Moniliales), but especially against Oomycetes belonging to the class Phycomycetes such as Phytophthora, Peronospora, Pseudo-peronospora, Pythium or Plasmopara. In addition, the compounds of formula I act systemically. They can also be used as a mordant for the treatment of seeds (fruits, tubers, grains) and plant cuttings for protection against fungal infections and against phytopathogenic fungi that occur in the soil.

Preferred for their effect are the compounds of formula I, whereby R1 means methyl, R2 stands in the ortho position to the amino group and means methyl, ethyl or chlorine, while R4, R5 and R1 have the indicated meaning. These shall be called connection group Ia.

From these compounds of group Ia, they should be emphasized on

due to their action in which R stands for an alkyl, alkenyl or cycloalkyl residue with 2-4 C atoms and Rc and R, have the above meaning, whereby the total number of C atoms of the substituents R^, R. ,, R<- and Rg in the phenyl ring do not exceed the number 4.

Another important subgroup of fungicidal compounds are those of formula I, in which R 2 means C 1 -C 1 -alkyl or halogen and the substituent R 1 and means hydrogen, while the substituents R 1 , R 1 and R 2 have that of formula I stated meaning.

In special areas of application, such as e.g. as a mordant or against soil fungi, further such fungicidal compounds of formula I or subgroup Ia are very advantageous in which R 1 means a rhodanomethyl group.

The preparation of the compounds of formula I can be carried out 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 also with the acid amide (omamidation).

According to another method, the connections can

of formula is also transferred from the acylanilides of formula

with butyl lithium or Na hydride to the corresponding alkali salt, as with a compound of formula V

leads to the desired end product, or can be prepared from the acylanilides of formula IV with the compound of formula V in the presence of an alkali carbonate (such as Na 2 CO 3 or K^ CO^ ) as proton acceptor, preferably with the addition of catalytic amounts of alkali iodine (such as KJ).

In formulas II, III, IV and V, R1 n - R„ b have the meaning 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 the following: 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 ethyl ketone 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), pyridines and pyridine bases, or inorganic bases, such as the oxides and hydroxides, hydrogen carbonates and carbonates such as alkali and alkaline earth metals as well as sodium acetate are mentioned. As an acid-binding agent can moreover, in the first process, an excess of the relevant aniline derivative of formula II is used.

The method of manufacture starting from compounds

of formula II can also be carried out without acid-binding agents, whereby in certain cases the passage of nitrogen is used to drive out the formed hydrogen halide. In other cases, an addition of dimethylfomamide as a reaction catalyst is very advantageous.

Mari can find out details for the preparation of the intermediate products of formula II from the methods that are generally indicated for the preparation of anilino-alkanoic acid esters in the following publications:

J. Org. Chem., 30, 41ol (1965),

Tetrahedron, 196 7, 487,

Tetrahedron, 1967, 493.

The compounds of formula I have an asymmetric carbon atom and can be resolved into optical antipodes in the usual way. The enantiomeric D form has the strongest microbiocidal effect.

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

For the production of the pure optical D antipode, e.g. the racemic compound of formula VI

wherein Ry R2' R5 °9 R6 has that for formula I indicated

importance,

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 enriched with the optical D antipode and eventual repetition (also several repetitions) of the salt formation, crystallization and release of the α-anilinopropionic acid of formula VI, the pure D form is obtained step by step . From this, it can be produced, as far as desired, in the usual way, e.g. in the presence of HC1 or H2SO4 with methanol the optical D configuration of the ester underlying formula II, preferably over the acid halide. As an optically active organic base, e.g. o-phenylethylamine in speech.

Instead of the fractional crystallization can also the enantiomeric D form of formula VII

is produced, if one diazotizes the amino group in naturally occurring L-alanine in the presence of e.g. HC1 or HBr and thus exchanges the L-configuration for halogen during ^-elimination and during retention and then esterifies with methanol and then reacts with the aniline of formula VIII whereby predominantly inversion occurs to the D-configuration of formula VII (J.Am. Chem . Soc. 76, 6056). Regardless of the aforementioned 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 is at the same time unsymmetrical to this axis (possibly also in the presence of additional substituents). This phenomenon is conditioned by the steric hindrance

Regardless of the aforementioned optical isomerism, in the case of R4 = alkenyl, a cis/trans isomerism can occur on the double bond.

As long as no directed synthesis is carried out to isolate pure isomers, a product is normally obtained which is a mixture of two optical isomers, two atropisomers, two cis, trans isomers or as a mixture of these possible isomers. The basic beneficial fungicidal effect of the enantiomeric D-form (in comparison with the D,L-form or with the L-form) is however retained and not significantly affected by the atropisomerism or the cis/trans isomerism.

The following examples serve to further explain the invention. The temperatures are in C. If nothing else is mentioned, an active substance of formula I, which can appear in optically active forms, always means the racemic mixture.

EXAMPLE 1

Manufacture of

N-(1<1->methoxycarbonyl-ethyl)-N-crotonoyl-2,3-dimethyl-6-ethylaniline. a) loo g of 2,3-dimethyl-6-ethylaniline, 223 g of 2-bromopropionic acid methyl ester and 84 g of NaHCO 3 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 some water, dried over sodium sulfate, filtered and the ether evaporated. After the distillation of the excess of 2-bromopropionic acid methyl ester, the crude product was distilled in high vacuum, bp. 88-9o°C/o,o4 Dry.

b) 17 g of the ester obtained in a), 1,4 g of crotonic acid chloride,

2 ml of dimethylformamide and 15o ml of abs. toluene is heated in

one hour in reverse. After evaporation of the solvent, the crude product was distilled in vacuo. Kp. 128-129°/ o,o3 Torr.

When the pure D form of α-(2,3-dimethyl-6-ethyl-anilino)-propionic acid methyl ester is acylated with crotonic acid or with one of its reactive derivatives, the D forms of both cis/trans isomers are obtained (forb 141a and 141b).

In an analogous way to example la), the other intermediate products are also produced, including e.g. the following of formula Ila:

EXAMPLE 2 Preparation of

(Connection No. 1)

N-(1<1->methoxycarbonyl-ethyl)-N-cyclopropylcarbonyl-2,6-dimethylaniline.

51.8 g α-(2,6-dimethylanilino)-propionic acid methyl ester in 2oo ml abs. toluene was: added with stirring at room temperature 31.3 g of cyclopropanecarboxylic acid chloride in 50 ml. abs. toluene. After adding 2 ml of dimethylformamide, it was heated for 2 hours under reflux and then the solvent and the cyclopropanecarboxylic acid excess were distilled off in vacuum.

By rubbing with some petroleum ether, the remaining oil was brought to crystallisation. After recrystallization in toluene-petroleum ether, compound No. 1 melted at 84-87°.

EXAMPLE 3

Manufacture of

(connection no. 2)

N-(1<1->methoxycarbonyl-ethyl)-N-vinylcarbonyl-2,6-dimethylaniline.

To 166 g of α-(2,6-dimethylanilino)-propionic acid methyl ester and 7o.4 g of pyridine in 6oo ml of abs. toluene with good stirring at 2o° 8o.6 g acrylic acid chloride in 15o ml abs. toluene added dropwise. After stirring for 20 hours at room temperature, the precipitated pyridine hydrochloride was filtered off, the solvent distilled off and the remaining oil rectified in vacuum. Kp. 13o-135°/o,ol Dry (compound no. 2).

In this way or according to one of the methods mentioned above, the following compounds of formula Ib are prepared:

Also the following compounds of formula Id are prepared according to the method according to examples 1-3 or one of the above-mentioned methods: The compounds of formula I can be used to make their . virus spectrum further with other suitable pesticides or active substances that stimulate plant growth.

The compounds of formula I can be used alone or together

with suitable carriers and/or other additives. Suitable

Carriers or additives may be solid or liquid

and correspond to the usual substances g^pm in the formulation technique, e.g. natural or regenerated mineral substances, dissolving, dispersing, netting, binding, thickening, binding or e.g. fertilisers.

l

i The content of active substance in commercial products is between o.1 - 9o%. £

f

y

For application, the compounds of formula I may be present i^

the following processed forms (whereby the weight-% indication

in parentheses shows beneficial amounts of active substance) :>.•

Solid processed forms: Thickening agents and flow agents (cf. to lo%), granules, encasing gravilates, impregnation granules and homo^ene granules (1 - 80%), |'

Liquid processed forms:

a) water-dispersible concentrates of active substance:

•in"

Spray powder (wettable powder) #>g pastes (25-9% in commercial packaging, oil - 15% in ready-to-use solution), emulsion and solution concentrates (oil - 5%, oil - 15% in ready-to-use solution) , ^

b) Solutions (o.1 - 2o%) , ^

f

The active substances of formula I according to the present invention can, for example, be formulated as follows:

in 1 •

Stove agents: For the production of a) 5% and b) 2%

fuel, the following substances are used:

a) 5 parts active substance

95 parts talc,

b) 2 parts active substance

1 part hydrodisperse silicic acid,

97 parts talc.

The active substances are mixed with the carrier substances and

ground and can be steamed for use in this form.

Granulate: For the production of a 5% granulate, the following substances are used:

5 parts active substance

o.25 parts epichlorohydrin

o.25 parts cetyl polyglycol ether,

3.5o parts polyethylene glycol

91 parts kaolin (particle size o.3 - o.8 mm).

The active substance is mixed with epichlorohydrin and dissolved with

6 parts acetone, then polyethylene glycol and cetyl polyglycol ether are added. The solution thus obtained is sprayed onto kaolin and then the acetone is evaporated in a vacuum. Such a microgranulate is advantageously used for combating soil fungi.

Spryte powder: For the production of a) 7o%'ig b9 4o%'ig

c) and d) 25% e) 10% spray powder, the following ingredients are used:

a) 7o divides the active substance

5 parts sodium dibutyl naphthyl sulfonate

3 parts naphthalene sulphonic acid-phenol sulphonic acid-formaldehyde condensate 3:2:1

lint parts kaolin

12 parts champagne chalk,

b) 4o parts active substance

5 parts equation sulfonic acid sodium salt

1 part dibutyl naphthalene sulfonic acid sodium salt

54 parts silicic acid

c) 25 parts active substance 4, 5 parts calcium lignin sulphonate

1.9 parts champagne chalk/hydroxyethyl cellulose mixture (1:1)

1.5 parts sodium dibutyl naphthalene sulfonate

19.5 parts silicic acid

19.5 parts champagne chalk

28.1 parts kaolin

d) 25 parts active substance 2.5 parts isooctylphenoxy-polyoxyethylene-ethanol

1.7 parts champagne chalk/hydroxyethyl cellulose mixture (1:1)

8.3 parts sodium aluminum silicate

16.5 parts diatomaceous earth

46 parts kaolin

e) lo parts active substance

3 parts mixture of sodium salts of saturated fatty alcohol sulfates

5 parts naphthalene sulfonic acid/formaldehyde condensate

82 parts kaolin.

The active substances are thoroughly mixed with the additives in suitable mixers and ground on the corresponding molds and rollers. Spray powders of excellent netability and suspension properties are obtained, which can be diluted with water to form suspensions of any desired concentration and can be especially used for foliar application.

Emulsifiable concentrates:

For the production of a 25% emulsifiable concentrate, the following substances are used:

25 parts active substance

2.5 parts epoxidized vegetable oil

lo parts of an alkylaryl sulfonate/fatty alcohol poly-

glycol ether mixture

5 parts dimethylformamide

57.5 " xylol.

From such concentrates, emulsions of any desired concentration can be prepared by dilution with water, which are particularly suitable for foliar application.

EXAMPLE 4

Effect against Phytophthora infestans on Solanum lycopersicum

(= tomatoes).

Ia) Residual-preventive effect. Solanum lycopersicum plants of the species "Roter Gnome" are infected after 3 weeks of culture after spraying with an o.o5% active-substance-containing soup (made from the substance of the active substance worked up into a spray powder) and its . , drying with a zoospore suspension of Phytophthora infestans. - They then stay in a climate chamber at 18 - 2o° and high humidity, which is created using an artificial spray mist, for 6 days. After this time, typical leaf spots appear. Their number and size are assessment criteria for the tested substances.

Ib) Curative effect.

After three weeks of culture, tomato plants of the species "Roter Gnom" are sprayed with a zoospore suspension of fungi incubated in a cabin at 18 - 2o° and saturated humidity. Discontinuation of the humidification after 24 hours. After drying the plants, they are sprayed with a soup, which contains active substances as spray powder in a concentration of 6.05%. 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 is the assessment norm for the activities of the substances provided.

II) Preventive-systemic effect.

Active substances formulated as a spray substance are given in

a concentration of o.o5% (with reference to the bottom volume) on the soil surface of 3-week-old potted tomato plants of the species

"Rotate Gnome". After a three-day waiting period, the underside of the leaves of the plants is sprayed with zoospore suspension of Phytophthora infestans. They are then kept in a spray booth at 18 - 2o° and saturated humidity for 5 days. After this time, typical leaf spots are formed, which number..

and size serve to assess the activities of the substances provided.

In these three experiments, the compounds of formula I show strong foliar fungicidal activity. When applying the compounds of subgroup Ia, a fungal attack of less than 20% (average values) is observed. With the compounds 1,2,7,12,22,37,39,49,66, 81,144,148,127,130,131,132,138,139,140,141,142 and others, the fungal attack is almost completely inhibited.

EXAMPLE 5

Effect against Plasmopara viticola Bert. et Curt) (Berl. et DeToni) on vines.

a) Residual-preventive effect.

In greenhouses, vine cuttings of the species "Chasselas" were cultivated.

In the down-leaf stage, 3 plants were sprayed with an active substance formulated from spray-powdered stock as a soup (o.o5% active substance). After drying the sprdyte coating, the plants are infected evenly on the underside of the leaves with the spore suspension of the fungus. The plants were then kept for 8 days in a humidity chamber. After this time, disease symptoms clearly appeared on the control plants. Amount and size of the infection sites on

the treated plants served as a standard of assessment for the activity of the substances provided.

b) Curative effect.

Vine cuttings of the species "Chasselas" were cultivated in greenhouses

and in the fluff-leaf stage infected with a spore suspension of Plasmopara viticola on the leaf underside. After 24 hours of stay

in the humidity cabin, the plants were sprayed with a 0.05% active substance soup, which was prepared from a spray powder of the active substance. The plants were then kept for a further 7 days in the humidity cabinet. After this time, disease symptoms appeared on the control plants. Number and size of the infection sites

on the treated plants served as a standard of assessment for the activity of the tested substances.

The compounds of formula I showed strong foliar fungicidal effects

in both of these trials. With the compounds of the subgroup Ia (R' = methyl), the fungal attack was generally reduced to below 20%, partly, as e.g. at the compounds 1,2,7,Io,12,13,22,37,39, 4o, 48, 49, 66, 81, 82, 15o, 127, 128, 13o, 131, 132, 136, 142,143 and others, almost no coating occurred (o-5%).'

EXAMPLE 6

Effect against Erysiphe graminis on Hordeum vulgare (barley) Residual protective effect.

About 8 cm high barley plants were sprayed with a spray soup prepared from spray powder of the active substance. After 48 hours, the treated plants were pollinated with conidia of the fungus. The infected barley plants were placed in a greenhouse at approx. 22°C and the fungal attack assessed after 10 days.

Some of the compounds of formula I, e.g. the compounds no. 33,58,69 and others showed in this experiment a reduction of the fungal attack of <^20%.

EXAMPLE 7

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

a) effect after soil application.

The fungus was cultured on sterile oat grains and added to a

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

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

b) Effect after stain application.

The fungus was cultivated on sterile oat grains and added to a soil-sand mixture. The thus infected soil is filled in flowerpots and sown with sugar beet seed, which has been stained with pre-soak preparations formulated as staining powder (looo ppm active substance with reference to the seed weight). The pots with seeds are set up in a greenhouse at 2o-24°C for 2 - 3 weeks. The soil is kept evenly moist by lightly spraying with water. During the assessment, the growth of the sugar beet plants as well as the proportion of healthy and diseased plants is determined.

After the treatment with the active substances according to formula I, both under the experimental conditions a) and b), more than 85% of the sugar beet plants grew up and had a healthy appearance. In the untreated controls, less than 2o% of the plants grow up with a partly diseased appearance.

Claims (1)

N-acyl-aniline acetic acid esters for use as fungicides, characterized by formula I in which R1 means C₁-C₁-alkyl, R₁ means C₁-C₁-alkyl or halogen, R 5 means hydrogen, C^-C^-alkyl or halogen Rc b hydrogen or methyl, whereby the total number of C atoms of the substituents R^, R^, R^ and Rg in the phenyl ring does not exceed the number 6 and R 4 means C 1 -C 8 -alkyl which is optionally substituted with a rhodano group, C 2 -C 6 -alkenyl or C 1 -C 4 -cycloalkyl.