DE3719225A1 - (2-Cyano-2-methoximinoacetyl)amino acid derivatives - Google Patents

Abstract

(2-Cyano-2-methoximinoacetyl)amino acid derivatives of the general formula (I) <IMAGE> in which R<1> represents the groups -(CH2)n-CO-NHCH3 or <IMAGE> where n represents the numbers 2 to 5, their geometric and optical isomers and isomer mixtures, and their use for controlling pests. The novel (2-cyano-2-methoximinoacetyl)amino acid derivatives of the formula (I) can be prepared by analogous processes, for example by reacting suitable, carboxyl-activated derivatives of 2-cyano-2-methoximinoacetic acid or 2-cyano-2-methoximinoacetic esters with suitable primary amines.

Description

The present invention relates to new (2-cyan-2-meth oximino-acetyl) amino acid derivatives, several processes for their production and their use as pesticides, especially as fungicides.

It is already known that certain substituted 2- Cyan-2-methoximino-acetamide good fungicidal activity own (compare e.g. EP 02 01 999 and DE-OS 36 02 243). However, the action of these compounds is, in particular at low application rates and concentrations, not always fully satisfactory.

There were new (2-cyan-2-methoximinoacetyl) amino acid derivatives of the general formula (I)

in which
R¹ for the groupings - (CH₂) _n -CO-NHCH₃ or

stands where
n represents the numbers 2 to 5,
found.

The compounds of formula (I) can be of various types geometric isomers occur, depending on the arrangement of the Substituents on the C = N group (E or Z isomers).

Some of the connections are asymmetrical Carbon atom, they can also be used as optical Isomers are present (D and L configuration), which are in different Ratios of quantities may arise.

It was also found that the new (2-cyan-2- methoximinoacetyl) amino acid derivatives of the general Formula (I)

in which
R¹ for the groupings - (CH₂) _n -CO-NHCH₃ or

stands where
n stands for the numbers 2 to 5, for example if

• a) carboxy-activated derivatives of 2-cyano-2-methoxyimino-acetic acid of the general formula (II) with amines of the formula (III) H₂N-R¹ (III) in which
  R¹ has the meaning given above,
  if appropriate in the presence of a catalyst and if appropriate in the presence of an acid binder and if appropriate in the presence of a diluent or
• b) 2-cyano-2-methoximino-acetic acid ester of the general formula (IV) in which
  R represents alkyl, preferably methyl or ethyl,
  with amines of the formula (III) H₂N-R¹ (III) in which
  R¹ has the meaning given above,
  if appropriate in the presence of a diluent and if appropriate in the presence of a base.

Finally, it was found that the new (2-cyan-2- methoximinoacetyl) amino acid derivatives of the formula (I) u. a. have strong fungicidal properties. Here surprisingly show the compounds of the invention a higher impact than that of the prior art Technically known substituted 2-cyano-2-methoximinoacetamides, which are constitutional or effective are obvious connections.

If, for example, (E) -2-cyano-2-methoximinoacetyl chloride and ε- aminocaproic acid methylamide are used as starting materials, the sequence of process (a) according to the invention can be represented by the following formula:

If, for example, (E) -2-cyano-2-methoximinoacetic acid ethyl ester and ε- aminocaproic acid methyl amide are used as starting materials, the sequence of process (b) according to the invention can be represented by the following formula:

As carboxy-activated derivatives of 2-cyano-2-methoximino-acetic acid of formula (II) for the process (a) used as starting materials, all come carboxy-activated derivatives, such as acid halides, such as B. acid chlorides, acid azides, also symmetrical and mixed anhydrides such as the mixed O-alkyl carbonic anhydrides, further activated esters, e.g. B. p-nitrophenyl ester or N-hydroxysuccinimide ester as well as with condensing agents, such as B. dicyclohexylcarbodiimide or carbonyldiimidazole, activated forms of carboxylic acids generated in situ.

Preferably those of 2-cyano-2-methoximino-acetic acid acid chlorides corresponding to formula (II) are used. They can be made by using the Acetic acid of formula (II) or its salts with a Halogenating agents, such as phosphorus pentachloride, Thionyl chloride or oxalyl chloride, in general known manner implements. Use is preferred of oxalyl chloride together with the sodium or Potassium salt of acetic acid of formula (II).  

The 2-cyano-2-methoximino-acetic acid of formula (II) and their carboxy-activated derivatives are known (cf. e.g. B. Pesticide Science 12, 27 (1981) and DE-OS 35 21 131).

For the implementation of process (b) as starting materials 2-Cyan-2-methoximino-acetic acid ester to be used of formula (IV) are known (cf. e.g. Pesticide Science 12, 27 (1981) and EP-OS 02 01 999).

The also for the implementation of the invention Process (a) and also of process (b) as Amines of the formula (III) to be used as starting materials are also known (see, e.g., J. Chem. Soc. (C) 1969, 1358 and Beilstein, handbook of organic chemistry 22, EIV, 6409).

Suitable diluents for the invention Process (a) inert organic solvents in question. These include ketones, such as acetone or ethyl methyl ketone; Esters such as ethyl or methyl acetate; Amides such as dimethylformamide; Nitriles such as acetonitrile; Chlorinated hydrocarbons, such as methylene chloride or carbon tetrachloride; Hydrocarbons such as toluene; or ether, like Tetrahydrofuran; or their mixtures.

Suitable acid binders for the invention Process (a) usual inorganic and organic Acid binder in question. These preferably include tertiary Amines such as triethylamine, pyridine or N-methylmorpholine and inorganic bases such as sodium carbonate or calcium carbonate.  

Process (a) according to the invention is, if appropriate carried out in the presence of a catalyst. For example 4-dimethylaminopyrine and 1-hydroxybenzotriazole may be mentioned or dimethylformamide.

Temperatures can vary when performing the procedure (a) can be varied over a wide range. In general, you work between -60 ° C to + 120 ° C, preferably at -20 ° C to + 40 ° C.

When carrying out the method according to the invention (a) one works preferably in equimolar amounts. The Carrying out the reaction, working up and isolating the Reaction products of the formula (I) are generally usual way.

Suitable diluents for the invention Process (b) water and organic solvents in question. These preferably include alcohols such as Methanol, ethanol or isopropanol; Ethers such as tetrahydrofuran or 1,2-dimethoxyethane; Amides such as dimethylformamide; Nitriles, such as acetonitrile and tertiary Amines such as pyridine.

Process (b) according to the invention is, if appropriate carried out in the presence of a base, depending on whether the respective amines used in the form of acid addition salts will. Here come the usual organic and inorganic bases in question. May be mentioned tert. Amines such as triethylamine; Alcoholates such as sodium methylate and alkali carbonates, such as potassium carbonate.  

The temperatures can be when carrying out the invention Method (b) in a larger area can be varied. Generally one works between -20 ° C and the reflux temperature, preferably at Room temperature.

When carrying out the method according to the invention (b) all reactants can be used in excess will; preferably one works with equimolar ones Amounts. The implementation of the reaction, workup and Isolation of the reaction products of formula (I) takes place in the usual way.

The active compounds according to the invention have a strong microbicidal action Effect on and can be used to combat unwanted microorganisms practically used will. The active ingredients are for use as Pesticide suitable.

For example, fungicidal agents are used in crop protection used to fight Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, Deuteromycetes.

Some pathogens are exemplary but not limiting of fungal diseases listed below Generic terms fall, called.

Pythium species, such as, for example, Pythium ultimum;
Phytophthora species, such as, for example, Phytophthora infestans;
Pseudoperonospora species, such as
Pseudoperonospora humili or Pseudoperonospora cubensis;
Plasmopara species, such as, for example, Plasmopara viticola;
Peronospora species, such as, for example, Peronospora pisi or P. brassicae;
Erysiphe species, such as, for example, Erysiphe graminis;
Sphaerotheca species, such as, for example, Sphaerotheca fuliginea;
Podosphaera species, such as, for example, Podosphaera leucotricha;
Venturia species, such as, for example, Venturia inaequalis;
Pyrenophora species, such as, for example, Pyrenophora teres or P. graminea
(Conidial form: Drechslera, Syn: Helminthosporium);
Cochliobolus species, such as, for example, Cochliobolus sativus (conidial form: Drechslera, Syn: Helminthosporium);
Uromyces species, such as, for example, Uromyces appendiculatus;
Puccinia species, such as, for example, Puccinia recondita;
Tilletia species, such as, for example, Tilletia caries;
Ustilago species, such as, for example, Ustilago nuda or Ustilago acenae;
Pellicularia species, such as, for example, Pellicularia sasakii;
Pyricularia species, such as, for example, Pyricularia oryzae;
Fusarium species, such as, for example, Fusarium culmorum;
Botrytis species, such as, for example, Botrytis cinerea;
Septoria species, such as, for example, Septoria nodorum;
Leptosphaeria species, such as, for example, Leptosphaeria nodorum;
Cercospora species, such as, for example, Cercospora canescens;
Pseudocercosporella species, such as, for example, Pseudocercosporella herpotrichoides.

The good plant tolerance of the active ingredients in the Control of plant diseases necessary concentrations allows treatment from above ground Parts of plants, of seedlings, and of the soil.

The pesticides according to the invention can Active substances with particularly good success for combating of Phytophthora species, such as Phytophthora infestans, used on tomatoes will; as well as for the control of Plasmopara species, such as Plasmopara viticola, on vines.

It should be particularly emphasized that the invention Active substances not only have a protective effect, but also have a curative effect, i.e. when used after contamination with the spores of the fungus.

The active compounds according to the invention are also very suitable good for combating Pyricularia species, such as Pyricularia oryzae, on rice.

The active ingredients can be in the usual formulations are transferred, such as solutions, emulsions, suspensions, Powders, foams, pastes, granules, aerosols,  Fine encapsulation in polymeric materials and in encapsulation materials for seeds, as well as ULV cold and warm mist formulations.

These formulations are prepared in a known manner e.g. B. by mixing the active ingredients with extenders, i.e. liquid solvents, under pressure liquefied gases and / or solid carriers, optionally using surfactants Agents, ie emulsifiers and / or dispersants and / or foam-generating agents. In case of use of water as an extender can e.g. B. also organic Solvents are used as auxiliary solvents. As Liquid solvents are essentially: Aromatics, such as xylene, toluene, or alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic Hydrocarbons such as chlorobenzenes, chlorethylenes or Methylene chloride, aliphatic hydrocarbons, such as Cyclohexane or paraffins, e.g. B. petroleum fractions, alcohols, such as butanol or glycol and their ethers and esters, Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as Dimethylformamide and dimethyl sulfoxide, as well as water; With liquefied gaseous extenders or carriers are meant such liquids, which in normal Temperature and under normal pressure are gaseous, for. B. Aerosol propellants, such as halogenated hydrocarbons as well Butane, propane, nitrogen and carbon dioxide; as fixed Carriers come into question: z. B. natural stone powder, such as kaolins, clays, talc, chalk, quartz, Attapulgite, montmorillonite or diatomaceous earth and synthetic Rock powder, such as highly disperse silica,  Alumina and silicates; as solid carriers for Granules are possible: B. broken and fractionated natural rocks such as calcite, marble, pumice, Sepiolite, dolomite and synthetic granules inorganic and organic flours and granules organic material such as sawdust, coconut shells, Corn cobs and tobacco stalks; as an emulsifier and / or Foaming agents are possible: z. B. non-ionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, Polyoxyethylene fatty alcohol ether, e.g. B. Alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, Aryl sulfonates and protein hydrolyzates; as a dispersant come into question: z. B. lignin sulfite and Methyl cellulose.

In the formulations, adhesives such as carboxymethyl cellulose, natural and synthetic powdery, granular or latex-shaped polymers can be used, such as Gum arabic, polyvinyl alcohol, polyvinyl acetate, as well natural phospholipids, such as kaphalins and lecithins, and synthetic phospholipids. Other additives can mineral and vegetable oils.

Dyes such as inorganic pigments, e.g. B. Iron oxide, titanium oxide, ferrocyan blue and organic dyes, such as alizarin, azo and metal phthalocyanine dyes and trace nutrients such as salts of iron, manganese, Boron, copper, cobalt, molybdenum and zinc can be used.

The formulations generally contain between 0.1 and 95 wt .-% active ingredient, preferably between 0.5 and 90%.  

The active compounds according to the invention can be used in the formulations or in a mixture of the various application forms with other known active ingredients, such as Fungicides, bactericides, insecticides, acaricides, nematicides, Herbicides, bird repellants, growth agents, Plant nutrients and soil structure improvers.

The active ingredients as such, in the form of their formulations or those prepared from it by further dilution Application forms, such as ready-to-use solutions, Emulsions, suspensions, powders, pastes and granules be applied. The application is done in the usual way Way, e.g. B. by pouring, spraying, spraying, scattering, Dusting, foaming, brushing, etc. It it is also possible to use the active ingredients according to the ultra-low-volume method apply or the drug preparation or inject the active ingredient into the soil yourself. It can also treat the seeds of the plants will.

When treating parts of plants, the drug concentrations can in the application forms in one larger range can be varied. They are in the generally between 1 and 0.0001% by weight, preferably between 0.5 and 0.001%.

When treating seeds, amounts of active ingredient are generally used from 0.001 to 50 g per kilogram of seed, preferably 0.01 to 10 g.

When treating the soil are active ingredient concentrations from 0.00001 to 0.1% by weight, preferably from 0.0001 to 0.02% by weight required at the site of action.

Manufacturing examples Example 1

7.4 g (0.05 mol) are added dropwise at 0 ° C. to a solution of 7.2 g (0.05 mol) of ε- aminocaproic acid methylamide and 5.1 g (0.05 mol) of triethylamine in 100 ml of dry dimethylformamide. (E) -2-Cyan-2-methoximino-acetyl chloride and stirred for 1 hour at 0 ° C and 19 hours at room temperature. After the solvent has been distilled off in vacuo, the residue is dissolved in methylene chloride, the solution is washed with 1 M hydrochloric acid, 10% sodium hydrogen carbonate solution and water, dried and evaporated. 5.3 g (42% of theory) of N ^ε - [(E) -2-cyano-2-methoximino-acetyl)] - ε -aminocaproic acid methylamide with a melting point of 124-16 ° C. are obtained.

Manufacture of the starting product

20 g (0.12 mol) of the potassium salt of (E) -2-cyano-2-methoximinoacetic acid are in 250 ml of dry ether suspended and after adding a few drops of dimethylformamide at 0 ° C dropwise with 76.2 g (0.6 mol) Oxalyl chloride added. The reaction mixture is  Stirred at 0 ° C for 2 hours, filtered, the filtrate in Vacuum evaporated at room temperature and the residue by evaporating twice with methylene chloride from remaining oxalyl chloride freed. 13.5 g (77% of theory) of (E) -2-cyano-2-methoximinoacetyl chloride are obtained as a yellow oil that is immediately implemented further.

In a solution of 124.8 g (0.672 mol) of 84 percent (E) -2-Cyan-2-methoximino-acetic acid ethyl ester in 500 ml Ethanol becomes a solution of 45.1 g (0.806 mol) at 20 ° C. Potassium hydroxide dropped in 500 ml of water and that Reaction mixture stirred at 40 ° for one hour. The Solution is evaporated in vacuo at 40 ° C, the residue stirred with methanol for 30 minutes, suction filtered, with Washed ethanol, acetonitrile and dichloromethane and at Room temperature dried.

58.6 g (53% of theory) of the potassium salt are obtained the (E) -2-cyano-2-methoximino-acetic acid.

In a suspension of 164 g (1 mol) of (E) -2-cyano-2-hydrox iminoacetic acid ethyl ester sodium salt (G. Kinast, Liebigs Ann. Chem., 1981, 1561) and 138 g powdered Potassium carbonate in 1.5 l acetone, 161 g (1.25 mol) Dimethyl sulfate (98%) dropped in 30 minutes and that The reaction mixture was heated under reflux for 3 hours. To Cooling is filtered through diatomaceous earth and evaporated.  

124.8 g (68% of theory) of (E) -2-cyano-2-methoximino-acetic acid ethyl ester are obtained as red-brown oil of 85% Purity (GC). After chromatography at five times Amount of silica gel 60 with chloroform gives a 93 percent light yellow oil.

In an analogous manner and according to the information on the procedures (a) and (b) are the following (2-cyan-2-methox iminoacetyl) amino acid derivatives of the general formula (I) received:

Examples of use

In the following application examples, the following are Compounds listed as reference substances used:

Example A

Phytophthora test (tomato) / curative

Solvent: 4.7 parts by weight of acetone Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

For the preparation of a suitable active ingredient preparation is mixed 1 part by weight of active ingredient with the specified Amounts of solvent and emulsifier and dilute that Concentrate with water to the desired concentration.

Young plants are used to test for curative effectiveness with an aqueous spore suspension of Phytophthora infestans inoculated. The plants remain for 7 hours at 20 ° C and 100% relative humidity in one Incubation cabin. After a short drying time the plants are dripping wet with an active ingredient preparation sprayed.

The plants are grown in an incubation cabin at 100% relative air humidity and approx. 20 ° C.

Evaluation is carried out 3 days after the inoculation.

A clear superiority in effectiveness over the compounds A, B and C from the prior art Technology show in this test z. B. the connections according to the production examples: 1, 3 and 4.  

Example B

Plasmopara test (vines) / protective

Solvent: 4.7 parts by weight of acetone Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

For the preparation of a suitable active ingredient preparation is mixed 1 part by weight of active ingredient with the specified Amounts of solvent and emulsifier and dilute that Concentrate with water to the desired concentration.

To test for protective efficacy one splashes young plants with the active ingredient preparation up to Dripping wet. After the spray coating has dried on, the Plants with an aqueous spore suspension of Plasmopara viticola inoculated and then remain in for 1 day a moist chamber at 20 to 22 ° C and 100% relative Humidity. Then the plants 5 Days in a greenhouse at 22 ° C and approx. 80% humidity set up. The plants are then moistened and placed in a wet room for 1 day

Evaluation is carried out 7 days after the inoculation.

A clear superiority in effectiveness over show the compound D from the prior art in this test e.g. B. the compounds according to the preparation examples: 1 and 4.

Claims (6)

1. (2-cyano-2-methoximinoacetyl) amino acid derivatives of the general formula (I) in which
R¹ for the groupings - (CH₂) _n -CO-NHCH₃ or stands where
n stands for the numbers 2 to 5, their geometric and optical isomers and isomer mixtures. 2. Process for the preparation of (2-cyano-2-methoximinoacetyl) amino acid derivatives of the general formula (I) in which
R¹ for the groupings - (CH₂) _n -CO-NHCH₃ or stands where
n stands for the numbers 2 to 5, their geometric optical isomers and isomer mixtures, characterized in that

• a) carboxy-activated derivatives of 2-cyano-2-methoxyimino-acetic acid of the general formula (II) with amines of the formula (III) H₂N-R¹ (III) in which
  R¹ has the meaning given above, optionally in the presence of a catalyst and optionally in the presence of an acid binder and optionally in the presence of a diluent or
• b) 2-cyano-2-methoximino-acetic acid ester of the general formula (IV) in which
  R represents alkyl, with amines of the formula (III) H₂N-R¹ (III) in which
  R¹ has the meaning given above, optionally in the presence of a diluent and optionally in the presence of a base.

3. Pest control, characterized by contains at least one (2-cyan-2-methox iminoacetyl) amino acid derivatives of the formula (I) according to claims 1 and 2. 4. Use of (2-cyano-2-methoximinoacetyl) amino acid derivatives of formula (I) according to claims 1 and 2 for pest control. 5. Method of combating pests, thereby characterized in that (2-cyan-2-methoximino acetyl) amino acid derivatives of the formula (I) according to the Claims 1 and 2 on pests and / or their Living space. 6. Process for the production of pesticides, characterized in that (2- Cyan-2-methoximinoacetyl) amino acid derivatives of Formula (I) according to claims 1 and 2 with extenders and / or surfactants mixed.