JPS5939401B2 - Microbial control agent and its manufacturing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a microbial control agent containing a novel N-N-[wo-substituted aniline derivative as an active ingredient, and a method for producing the same.

The active ingredient used in the present invention has the following general formula (1):
In the formula, R1 represents an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, R2 is a hydrogen atom,
represents an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, R5 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a halogen atom, and R6 represents a hydrogen atom or represents a methyl group, and substituents R,, R2, R5 and R6 on the phenyl ring
The total number of carbon atoms in does not exceed 8, and R3 is -C
OOW (in the group, R represents a methyl group or an ethyl group), and R4 is an alkyl group having 1 to 6 carbon atoms. Kyl group: Alkyl group having 1 to 6 carbon atoms substituted with a rotazo (-SCN) group: Represents an alkenyl group having 2 to 5 carbon atoms or a cycloalkyl group having 3 to 7 carbon atoms.

] This is a compound represented by

The alkyl group in the alkyl group and the alkyl group in the alkoxy group may be one of the following groups depending on the number of carbon atoms mentioned above: methyl group, ethyl group, n-
Propyl, isopropyl, n-butyl, isobutyl, sec- or tert-butyl, pentyl and hexyl isomers.

Examples of the alkenyl group include vinyl group, allyl group, methallyl group, butenyl group, methylbutenyl group, and isomers thereof.

Further, the cycloalkyl group includes a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group.

Halogen atoms are fluorine, chlorine or iodine. DE 2212268 A1 generally discloses that N-haloacylated anilinoalkane carboxylic acid esters have selective herbicidal action.

However, a number of N-haloacylated 2,6-dialkylanilinoacetic acids and their esters are only listed and only indicated as herbicides. There is no mention of microbicidal activity, especially the bactericidal effect on fungi that cause plant diseases. The present invention is based on the surprising observation that compounds of formula (1) with significantly different structural formulas have an advantageous microbicidal spectrum for the protection of cultivated plants for practical purposes.

Cultivated plants within the scope of the present invention include, for example, cereals, corn, rice, vegetables, sugar bean, soybeans, peanuts, fruit trees, ornamental plants, but especially vines, hops, cucumbers and their related plants (cultivars, pumpkins, etc.). , melons), and nightshade plants such as potatoes, tobacco, and tomatoes, as well as bananas, cocoa, and rubber trees. The active substance represented by formula (1) is capable of killing fungi on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots), and on plant parts that grow later. It can also protect against such fungi. The active substance acts against phytopathogenic fungi belonging to the following classes: Ascomycete
s〕Erysiphaceae〉o Basidiomycetes〉Especially Aspergillus Aspergillus (
Rustfungi).

Fungi perfecti (Moniliales), but especially Oomycetes (00
mycetes), such as Phytophythra (PhytO
phthOra), PerOnOspOr
a), Pseudoperonospora
OspOra), Pythium or PlasmOpara.

Furthermore, the compound of formula () has osmotic action. seed(
It is also used as a seed treatment to protect fruits, tubers, grains) and cuttings from fungal infections and phytopathogenic fungi found in the soil. A desirable microbial control agent has a formula (1) in which R1 is a methyl group, R2 is present at the ortho position to the amino group and represents a methyl group, an ethyl group, or a chlorine group, and -X-R3
represents a CH-COOR' group, and R4, R5, R6 and R are compounds in which they have the meanings described in formula (1).

These compound groups are referred to as group (1a). Compounds of group (a) which are preferred for special mention in their action are those in which R is a methyl group and R4 has 2 carbon atoms.
-4 represents an alkyl, alkenyl or cycloalkyl group, R5 and R6 represent the meanings described in formula (1), and substituents R1, R2, R5 and R6 on the phenyl ring
A compound having a structure in which the number of carbon atoms does not exceed 4. Another important subgroup of compounds is the formula (1
), R2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a halogen atom, substituents R5 and R6 represent a hydrogen atom, while substituents R1, R3, R4, X and R
consists of a compound in which it has the meaning given in formula (1).

In special fields such as seed treatment agents or applications against soil fungi, compounds of formula (1) and subgroup (1a), where R4 is a cyanomethyl group or a rotasomethyl group, are effective.

According to the present invention, the compound represented by formula (1) is the compound represented by the following formula (
6): [In the formula, R1, R2, R3, R5, R6, and X represent the meanings described in the formula ().

] A compound represented by the following formula (self): [In the formula, R4 represents the meaning described in formula (1)] obtained by
As a special example, acylation with one of its acid amides (
transamidation).

According to another method according to the invention, the compound of formula (1) is prepared by preparing an acyl compound of the following formula (substitution): The anilide is converted to the corresponding alkali salt with butyllithium or sodium hydride, and the alkali salt is expressed by the following formula (V
): [In the formula, X and R3 represent the meanings described in formula (1)] to produce the desired final product 5
Alternatively, an acylanilide of formula (2) can be prepared by converting the acyl anilide of formula (2) into an alkali iodide, preferably an alkali iodide (e.g. potassium iodide), in the presence of an alkali carbonate C (e.g. Na2cO3 or K2CO3) as a proton acceptor. It is produced by adding a catalytic amount of and reacting with the compound of formula (7).

"Hal" represents a halogen atom, preferably chlorine or bromine, or a group that is easily eliminated.

The phrase "acid halide" preferably refers to acid chloride or acid bromide. The reaction is carried out without a solvent or in a solvent or diluent that is inert to the reactants. Examples of suitable solvents or diluents include aliphatic or aromatic hydrocarbons such as benzene, toluene, xylene, petroleum ether; halogenated hydrocarbons such as chlorobenzene, methylene chloride, ethylene chloride, chloroform; ethers or dialkyl ethers. , dioxane, tetrahydrofuran; nitriles such as acetonitrile; N-N-dialkylamides such as dimethylformamide; other ketones such as acetic anhydride, dimethyl sulfoxide, methyl ethyl ketone, and these solvents. It is a mixture. The reaction temperature is between 0°C and 180°C, preferably between 20°C and 120°C.

Often the use of acid acceptors or condensing agents is effective. Suitable examples include tertiary amines such as trialkylamines (e.g. triethylamine), pyridine and pyridine base, real alkali metal and alkaline earth metal oxides, hydroxides, hydrogen carbonates, and carbonates, and sodium acetate. Inorganic bases such as Furthermore, in the first manufacturing method,
An excess of each aniline derivative of formula () can also be used as an acid acceptor. The production process from the compound of formula (6) can also be carried out without an acid acceptor.

For example, it is suitable to pass nitrogen gas through to remove the hydrogen halide formed. As another example, it is very effective to use dimethylformamide as a reaction catalyst. For details of the method for producing the intermediate represented by formula (), reference may be made to the method commonly described as a method for producing aniline-alkanoic acid esters in the publications listed below. In the compound of the wooden formula (), when X is -, it contains an asymmetric carbon atom (*), which can be optically resolved by a conventional method.

In this relationship, the optical antipodal D form has a more pronounced microbicidal effect. Compounds belonging to the D-configuration, their compositions and their uses are therefore preferred within the scope of the invention. These D forms have negative optical rotation in ethanol or acetone. The pure optical antipode D is produced by preparing a racemic compound of the following formula (in which R1, R2, R5 and R6 represent the meanings described in formula (1)); It can be obtained by reacting with a nitrogen atom-containing optically active base by a known method to form the corresponding salt.

The pure D-form is obtained stepwise by fractional crystallization of its salt, followed by liberation to an acid of formula (b) enriched in the optical antipodal D-form, and if appropriate, salt formation and fractionation. It can be obtained by repeating (several times) crystallization and liberation into α-anilino-propionic acid represented by formula (b). If desired, from this pure D form, e.g.
Optical D-configurations of esters of formula (11) can be prepared in methanol or ethanol in the presence of Cl or H2SO4. A suitable optically active organic base is, for example, d-phenylethylamine. Instead of fractional crystallization, the following formula (to): [wherein R1, R2, R5, R6 and k represent the meanings described in formula ()].

The optical antipode D form of ] is obtained by diazotizing the amino group of naturally occurring L-alanine in the presence of HCl or HBr, thereby replacing it with a halogen atom with elimination of N2,
If appropriate, the ester is esterified with methanol or ethanol, retaining the L-coordination, and the ester is then converted into a compound of the following formula: It can be produced by reacting with the aniline represented by the formula, and almost all the inversion of the formula M to the D configuration occurs [Journal of American
Chemical Society (J.Ar) 1.Chem.S0
c. ) Volume 76, page 6065].

Regardless of the above-mentioned optical isomerization, with respect to the axis of rotation of the phenyl-nitrogen atom, for example, at least the two on the phenyl ring
- Internal rotational optical isomerization is observed, such as when the 6-position is substituted and at the same time asymmetrical with respect to this axis of rotation (i.e. optionally by additional substituents). This phenomenon is caused by steric hindrance by -X-R3 and -CO-R4 additionally introduced into the nitrogen atom. Regardless of optical isomerism, when R4 is an alkenyl group, cis/trans isomerization also occurs with respect to the double bond. Unless synthesized with the goal of isolating pure isomers, the product will have two optical isomers, two internal rotational optical isomers,
It is obtained as a mixture of two cis/trans isomers or as a mixture of these possible isomers.

However, the essentially better bactericidal action of the enantiomer D-form (compared to the D.L-form, L-form) is preserved and is not significantly affected by internal rotational optical isomerism or cis/trans isomerism.
The examples that follow describe the invention in more detail, but are not intended to limit the invention within the scope described therein.

Unless otherwise specified, active substances of the formula () are understood as racemic mixtures. Example 1 (a) 2,3-dimethyl-6-ethylaniline 100
A mixture of y, 2-bromopropionic acid methyl ester 2237 and NaHCO3847 was stirred at 140°C for 17 hours, then cooled, diluted with 300 ml of water and extracted with diethyl ether.

The extract was washed with a small amount of water, dried over sodium sulfate, filtered, and the ether was distilled off. After distilling off the excess 2-bromopropionic acid methyl ester, the crude product was distilled under high vacuum: boiling point 88-90°C/0.04m
Ester 177 obtained by mHg0(b)(a)
A mixture of 10.47 ml of crotonic acid chloride, 2 ml of dimethylformamide and 150 ml of anhydrous toluene was heated under reflux for 1 hour.

By distilling off the solvent and distilling the crude product under vacuum, a compound represented by the following formula: N-(1'-methoxycarbonyl-ethyl)-N-crotonyl-2●3-dimethyl-
6-ethylaniline was obtained (boiling point 128-129°C/
0.03mmHg).

This compound is designated as compound 141. The D form of both cis/trans monoisomers (compounds 141a and 141b) is d
It was obtained by acylating the pure D form of -(2,3-dimethyl-6-ethylanilino)-propionic acid methyl ester with crotonic acid or a reactive derivative thereof. Other intermediates such as the following compound represented by the following general formula (a) (R1 is 2-position) were obtained in the same manner as in Example 1(a).

Example 2 51.8 V of d(2,6-dimethylanilino)-propionic acid methyl ester in 200 ml of anhydrous toluene were treated with 31.37 V of cycloprobanecarboxylic acid chloride in 50 ml of anhydrous toluene at room temperature while stirring.

After addition of 2 ml of dimethylformamide, the reaction mixture was diluted with 2 ml of dimethylformamide.
The mixture was heated to reflux for an hour and then the solvent and excess cycloprobanecarboxylic acid chloride were distilled off under vacuum. The residual oily substance is crystallized by treatment with a small amount of petroleum ether to form the compound N-(V-methoxycarbonyl-ethyl)-N-cyclopropylcarbonyl 2,6-
Dimethylaniline was obtained.

This is designated as compound (1). When recrystallized from toluene/petroleum ether, compound (1) exhibited a melting point of 84-87°C. Example 3 80.67 acrylic acid chloride in 150 ml of anhydrous toluene is mixed with d-(2,6-dimethylanilino)-propionic acid methyl ester 1607 in 600 ml of anhydrous toluene at 20° C. under good stirring. Add dropwise to pyridine 70.47.

The reaction mixture is stirred for 20 hours and then the precipitated pyridine hydrochloride is washed off. The solvent is distilled off in vacuo and the remaining oily substance is fractionated in vacuo to obtain a compound N-(V-methoxycarbonyl-ethyl)-N represented by the following formula:
-vinylcarbonyl-2.6 dimethylaniline was obtained.
This is designated as compound (2) (boiling point 130-135℃/0
．． 01mmHg). The following general formula (Ib): (R1 is 2
The following compounds represented by (1) were prepared by this method or the method shown herein.

The following compounds of the following general formula (Ic) were also prepared in Examples 1-3 or one of the methods described above: (R1 is in the 2nd position).

The following compounds represented by the following general formula (Id): (R1 is in the 2nd position) were also synthesized by Examples 1-3 or one of the methods described above.

The compounds of general formula (1) can be used in combination with other suitable pesticides or plant growth promoting active substances in order to widen their activity spectrum.

The compound of general formula (1) can be used alone or in combination with a suitable supporting material and/or additive. Suitable support materials and additives may be solid or liquid;
Substances commonly used in formulations, such as natural or regenerated minerals;
Solvents, dispersants, wetting agents, adhesives, thickeners, binders or fertilizers. Commercially available composition concentrations of active ingredients range from 0.1 to 9.
It is between 0%. The compounds of general formula (1) can be used in the following formulation forms (the weight percentages in the container indicate the advantageous amounts of active ingredient): Solid formulations: dusts and spreaders (up to 10%), granules, coated granules,
Impregnated granules and homogeneous granules (1-80%) Solutions: (a) Water-dispersible active ingredient concentrates: Wettable powders and pastes (commercially available
5-90%, 0.01-15% for ready-to-use solutions
), concentrated emulsions and concentrated solutions (10-50%, 0.01-15% for ready-to-use solutions) (b) solutions (
0.1-20%) Next, the formulation format of the compound of formula (1) will be illustrated.

"Part" refers to "part by weight". Dusting agent: The following materials are used to prepare (a) 5% dusting agent and (b) 2% dusting agent.

The active ingredient is mixed with the carrier material and ground.

This formulation process produces a dust agent for application. Granules: The following materials are used to prepare the 5% granules.

The active ingredient is mixed with epichlorohydrin and dissolved in 6 parts of acetone.

Then polyethylene glycol and cetyl polyglycol ether are added. The solution thus obtained is sprayed onto the kaolin and the acetone is then evaporated in vacuo. This granule is effective against soil fungi.
Wettable powder: (a) 70%, (b) 40%, (c) and (d
) 25%, (e) 10% The following ingredients are used to formulate the hydrating powder.

The active ingredient is thoroughly mixed with the excipients using a suitable mixer and ground using a mill and rolls appropriate to the dosage form.

In this way, a wettable powder is obtained, which can be diluted with water to obtain a suspension of any desired concentration,
This is especially applied to the leaves. Emulsion 7 concentrate: A 25% emulsion concentrate is prepared using the following raw materials, respectively.

By diluting this, an emulsion with the desired concentration can be prepared.
This is particularly suitable for foliar application.

Example 4 Tomato (SOlanunllycOpersicum)
(1a) Residual preventive action against plant pathogenic bacteria (1a)
On) Red fruit seed cultivated for 3 weeks (ROterGnOw
) in a diluted suspension containing 0.05% of the active substance (
(prepared from a wettable powder of the active ingredient) was sprayed, dried and then infected with a suspension of sexual spores of the phytopathogenic fungus.

They are made to have high humidity with artificial fog and the temperature is from 18℃ to 2℃.
It was left in a constant temperature room kept at 0°C for 6 days. After this, typical leaf spots appeared. Their number and size were taken as criteria for evaluating the test material. (Ib) Curative action A suspension of fungal spores was sprayed onto small red-fruited tomatoes grown for 3 weeks and cultured at 18°C to 20°C in a thermostatic chamber with saturated humidity.

Moisture was discontinued after 24 hours.

After the plants had dried, they were sprayed with a diluted suspension containing the active ingredient at a concentration of 0.05% prepared from a wettable powder. Once the spray coating had dried, the tomatoes were again placed in the humidity chamber for 4 days. Typical leaf spots that appeared during this period were taken as a criterion for evaluating the effectiveness of the test substance. (6) Preventivesystemicact
iOn) After cultivating small red tomatoes in pots for 3 weeks, the active ingredient was added to the soil surface of the pot at a concentration of 0.05% (
(with respect to soil volume) and was applied as a hydrating powder.

After 3 days, the lower parts of the leaves of the plants were sprayed with a suspension of sexual spores of phytopathogenic fungi.

The plants were kept in a constant humidity room at a temperature of 18°C to 20°C under saturated humidity for 5 days, after which typical leaf spots were formed.
The number and size of these spots were used as criteria for evaluating the effectiveness of the test substance. These three tests revealed that the compound represented by formula (1) has a remarkable bactericidal effect on fungi that grow on plant leaves. In other words, the degree of bacterial infection is 20% when applying a subgroup 1a compound when k is a methyl group.
(average value) or less. Compounds 1, 2, 7, 12, 2
2, 37, 39, 49, 66, 81, 117, 121,
1001103, 104, 105, 111, 112, 1
13, 114, 115, etc., bacterial infection was almost completely inhibited. (0-5%) Origin Example 5 Grapevine Plasmobola biticola [PlasmOpOraviticOla (Bert.
etCurt. ) (Berl.etDeTOni)] 1) Residual preventive action
as) Grape cuttings of the species were grown in a greenhouse.

Three trees were sprayed at the 10 leaf stage with a diluted suspension prepared from a wettable powder containing the active substance.

After the coating layer had dried, the lower part of the leaves of the plants were infected with a suspension of fungal spores. They were then kept in a humid room for 8 days and signs of disease were observed on the control plants. The number and size of infected areas of the test plants were taken as criteria for evaluating the effectiveness of the tested active substances. )) Curative action Grape cuttings of the Casellas variety were grown in a greenhouse and at the 10-leaf stage, the lower parts of the leaves were infected with a spore suspension of Plasmovora biticola.

After being kept in a humid chamber for 24 hours, the plants were sprayed with a diluted suspension prepared from a wettable powder of the active substance.

Signs of disease appeared in the control plants when they were then placed in a humid chamber for an additional 7 days. The number and size of infected areas on the treated plants were taken as criteria for evaluating the effectiveness of the test substance. In both these tests, the compound of formula (1) showed significant bactericidal 0J activity.

Compounds of subgroup 1a without exception (R1 is a methyl group)
The bacterial infection rate was reduced to less than 20%. Many compounds such as compounds 1, 2, 7, 10, 12, 13, 22
, 37, 39, 40148, 49, 66, 81, 82,
123, 1001101, 103, 104, 105, 1
09, 115, 116], almost no infection occurred. (0-5%) Example 6 Erysiphegr-Amin in barley (HOrdeumVl] 1gare)
Barley with a residual preventive effect of 8C against is) was sprayed with a dilute suspension for spraying (0.05% active ingredient) prepared from a wettable powder of the active ingredient.

After 48 hours, the treated plants were dusted with fungal conidia powder.

The infected barley was placed in a greenhouse at 22°C, and the degree of fungal infection was evaluated after 10 days. Many of the compounds represented by formula (1) are
For example, compounds 33, 34, 50, 56, 57, 58, 6
9, 73, and others have a bacterial infection rate of 20% in this test.
reduced to less than Example 7 Pythium debaryanum of Betabulgaris m
(a) Effect when applied to soil The bacteria were cultured on sterile oat grains and added to the oat and sand mixture.

I filled flowerpots with infected soil and sowed sugarcane seeds. Immediately after sowing, the test drug prepared as a wettable powder was poured onto the soil in the form of an aqueous suspension (concentration of active substance of 0.002% with respect to the volume of the soil). The pot is 20 in a greenhouse.
It was left for 2-3 weeks at ~24°C. The soil was kept constantly moist by gently spraying water. The number of germinated sugar plants and the number of healthy and diseased plants were confirmed through test evaluation. (5) In the case of application by seed treatment, the active bacteria were cultivated on sterile oat grains and added to the soil and sand mixture.

Flowerpots were filled with infected soil and planted with sugarcane seeds treated with the test drug prepared as a seed treatment powder (0.1% active substance relative to the weight of the seeds). 20 pots
It was left in a greenhouse between 24°C and 24°C for 2-3 weeks. The soil was maintained at a constant level of moisture by being gently sprayed with water. The number of germinated sugar plants and the number of healthy and diseased plants were confirmed. After treatment with one of the active ingredients represented by formula (1) under the conditions of Test 1 (a) and (b), 85% of the sugarcane sprouted and no lesions were observed in the germinated plants. Nakatsuta.

Claims (1)

[Scope of Claims] 1 Together with a suitable carrier and optionally accelerating additives, the following formula (I): ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [wherein R_1 is the number of carbon atoms 1 ~4 alkyl group or an alkoxy group having 1 to 4 carbon atoms, R_2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, and R_5 represents represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a halogen atom, R_6 represents a hydrogen atom or a methyl group, and substituents R_1, R_2, R_5 and R_ on the phenyl ring
The total number of carbon atoms in 6 does not exceed 8, and X represents ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and R_3 is -C
OOR' (in the group, R' represents a methyl group or an ethyl group), R_4 is an alkyl group having 1 to 6 carbon atoms;
An alkyl group having 1 to 6 carbon atoms substituted with a rhodano (-SCN) group; an alkenyl group having 2 to 5 carbon atoms or a cycloalkyl group having 3 to 7 carbon atoms. ] A microbial control agent characterized by containing a compound represented by the following as an active ingredient. Secondary formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (II) [In the formula, R_1 represents an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, and R_2 represents hydrogen. atom, an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, R_5 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a halogen atom, and R_6 represents hydrogen. represents an atom or a methyl group and substituents R_1, R_2, R_5 and R_ on the phenyl ring
The total number of carbon atoms in 6 does not exceed 8, and X represents ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and R_3 is -C
OOR' (in which R' represents a methyl group or an ethyl group). ] A compound represented by the following formula (III): HO-CO-R_4(III) [wherein R_4 is an alkyl group having 1 to 6 carbon atoms; 1 carbon atom substituted with a rhodano (-SCN) group ~6 alkyl group; represents an alkenyl group having 2 to 5 carbon atoms or a cycloalkyl group having 3 to 7 carbon atoms. ] By acylating with carboxylic acid represented by, its acid halide, acid anhydride, acid amide or ester, the following formula (I): ▲Mathematical formula, chemical formula, table, etc.▼(
I) [In the formula, R_1, R_2, R_5, R_6, X and R_3 represent the same meaning as in the above formula (II),
_4 represents the same meaning as in formula (III) above. ] A method for producing a microbial control agent, characterized by obtaining a compound represented by the following.