JP2553335B2 - Optically active cyclopropanecarboxamides, enantiomeric pairs of the active and enantiomers thereof, and agricultural fungicides - Google Patents

Description

The present invention relates to an optically active cyclopropanecarboxamide, an enantiomer pair of the active substance and its enantiomer, a method for producing and obtaining them, and use as a rice blast disease controlling agent.

The specification of Japanese Patent Application Laid-Open No. 61-15867 known before the filing date of the present application describes that an N-benzyl-cyclopropanecarboxamide derivative is useful as a fungicide for agriculture and horticulture.

The present inventors have now found an optically active cyclopropanecarboxamide of the following formula (I) and an enantiomer pair of the active substance and its enantiomer.

formula: In the formula, X represents chlorine or bromine, R ¹ represents an alkyl group having 1 to 4 carbon atoms, R ² represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and in the formula, the amine moiety is The R (+)-form is shown.

The optically active cyclopropanecarboxamides of the formula (I) of the present invention and the enantiomer pair of the active substance and its enantiomer can be synthesized, for example, by the following method.

Production method a): [When formula (I) is an optically active substance] Formula: In the formula, X is the same as the above, and R (+)-benzylamines represented by the formula: In the formula, R ¹ and R ² are the same as above, and M is a hydroxyl group or a halogen atom. A process for producing optically active cyclopropanecarboxamides of the above formula (I) is characterized by reacting .

Production method b):-a racemate having the same formula as the above formula (I), or
A method for obtaining a pair of enantiomers or an enantiomer, which comprises subjecting an optically active cyclopropanecarboxamide compound in which either an acid site or an amine site is optically active to physical treatment.

The compound of the present invention represented by the formula (I) has a strong bactericidal action as a rice blast controlling agent.

According to the invention, the compound of formula (I) is, surprisingly and surprisingly, an acid having the same formula as the formula (I) of the invention described in the above-mentioned JP-A-61-15867. Compared with that having both racemic and amine moieties, it exhibits a bactericidal action which is substantially more excellent than the effect exhibited by the racemic one, and in particular, shows an excellent controlling effect against rice blast disease.

Therefore, an object of the present invention is to provide an optically active cyclopropanecarboxamide of the formula (I), an enantiomer pair of the active substance and an enantiomer thereof, a method for producing and obtaining them, and a rice blast control agent. Is available to provide.

These and many other objects and advantages of the present invention will become more apparent from the description below.

In the formula (I) of the present invention, particularly preferably, X represents chlorine or bromine, R ¹ represents methyl, ethyl or isopropyl, and R ² represents a hydrogen atom or methyl.

Then, specific examples of the compound of the formula (I) of the present invention include:
In particular, the following can be exemplified.

In the production method a), as a raw material, for example, R (+)
Using 4-bromo-α-phenethylamine and 1,3,3-trimethyl-2,2-dichlorocyclopropanecarboxylic acid chloride is represented by the following reaction formula.

In the production method a), the starting compound of the formula (II) is
It means based on the definition of X.

Some of the compounds of formula (II) are already known in the field of organic chemistry, and specific examples thereof include R (+) 4-bromo-α-phenethylamine and R (+) 4-chloro-α. Examples thereof include phenethylamine.

Similarly, the compound of formula (III) is based on the definition of R ¹ , R ² and M above.

In formula (III), R ¹ and R ² preferably have the same meanings as defined above, and M preferably represents a hydroxyl group or chlorine.

Some of the compounds of formula (III) are already known (as described in JP-A-61-15867). Specific examples thereof include 1,3,3-trimethyl-2,2-dichlorocyclopropanecarboxylic acid and its acid chloride.

In carrying out the process a) mentioned above, use may be made, as suitable diluent, of any inert organic solvent.

Examples of such diluents are water; aliphatic, cycloaliphatic and aromatic hydrocarbons (optionally chlorinated), for example hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene. , Xylene,
Methylene chloride, chloroform, carbon tetrachloride, ethylene chloride and trichloroethylene, chlorobenzene; Other ethers such as diethyl ether,
Methyl ethyl ether, di-iso-propyl ether,
Dibutyl ether, propion oxide, dioxane, tetrahydrofuran; ketones such as acetone, methyl ethyl ketone, methyl-iso-propyl ketone, methyl-iso-butyl ketone; nitriles such as acetonitrile, propionitrile, acrylonitrile; alcohols such as methanol, ethanol, iso-propanol, butanol, ethylene glycol; esters such as ethyl acetate, amyl acetate; acid amides such as dimethylformamide, dimethylacetamide; sulfones, sulfoxides such as dimethyl sulfoxide, sulfolane; and bases such as pyridine. You can

In the above method a), as the raw material of the formula (III),
When a carboxylic acid is used, it can be carried out in the presence of a dehydration condensing agent, and examples thereof include N, N'-dicyclohexylcarbodiimide.

In the method a), when an acid halide is used as the raw material of the formula (III), the reaction of the present invention can be carried out in the presence of an acid condensing agent.

Examples of the acid binding agent include hydroxides, carbonates, bicarbonates and alcoholates of commonly used alkali metals, and tertiary amines such as triethylamine, diethylaniline and pyridine. it can.

The process a) according to the invention can be carried out within a wide temperature range. For example, it can be carried out between about -20 ° C and the boiling point of the mixture, preferably between about 0 and about 100 ° C. Also, it is desirable to carry out the reaction under normal pressure,
It is also possible to operate under pressure or reduced pressure.

In carrying out the production method a), for example, by reacting the compound of the formula (II) with about 1 mol to a slight excess of the compound of the formula (II) in an inert solvent, the target compound of the formula The optically active substance (I) is obtained.

In carrying out the production method b), the target enantiomer pair or enantiomer can be obtained by performing, for example, a column chromatographic separation operation, as will be specifically shown in Examples described later.

A preferred pair of enantiomers having formula (I) is 4
A racemate consisting of three stereoisomers can be easily obtained by column chromatographic separation.

The preferred enantiomer having the formula (I) can be easily obtained by column chromatographic separation of an epimer having an R (+)-form at the amine site.

The active compounds according to the invention show a strong bactericidal action and can in fact be used for controlling unwanted phytopathogenic fungi.

The active compounds according to the invention are generally used as fungicides in Plasmodiophoromyces.
cetes), Oomycetes, chytridiomycetes, Zygomyce
tes), Ascomycetes, Basiomycetes and Deuterom
ycetes) can be used for various plant diseases and as a fungicide (bacterial) agent, Pseudomonas family (Pseu
domonadaceae), Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae, and Streptomycetaceae.

In particular, the compounds of the present invention are useful for rice blast (Pyricularia
oryzae), it shows an extremely excellent control effect.

The active compound of the present invention, at a concentration of the active compound necessary for controlling phytopathogenic fungi, shows good compatibility with plants, and therefore, in use, a drug treatment to the above-ground part of the plant, It enables chemical treatment of rootstocks and seeds, and soil treatment.

Further, the compound of the present invention has low toxicity to warm-blooded animals and can be safely used.

The active compound of the present invention can be formulated into a usual formulation. And as such a form, a liquid agent, emulsion,
Suspensions, powders, foams, pastes, granules, aerosols,
Active compound infiltration-natural and synthetic, microcapsules,
Seed coatings, formulations with combustion equipment (eg combustion equipment fumigation and fumigation cartridges, cans and coils), and ULV (cold mist, warm mist) .

These drugs can be manufactured by a known method.
Such a method may, for example, be carried out by adding the active compound to a developing agent, ie, a liquid diluent; a liquefied gas diluent; a solid diluent, or a carrier; And / or by mixing with a foam-forming agent.

If water is used as the spreading agent, organic solvents, for example, can also be used as auxiliary solvents.

Liquid diluents or carriers generally include aromatic hydrocarbons (eg, xylene, toluene, alkylnaphthalene, etc.), chlorinated aromatic or chlorinated aliphatic hydrocarbons (eg, chlorobenzenes, ethylene chloride, chlorides). Methylene etc.), aliphatic hydrocarbons [eg cyclohexane etc., paraffins (eg mineral oil fraction etc.)], alcohols (eg butanol, glycol and their ethers, esters etc.), ketones (eg acetone,
Mention may also be made of methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone), strongly polar solvents (eg dimethylformamide, dimethylsulfoxide etc.) and water.

The liquefied gas diluent or carrier is a gas at normal temperature and pressure,
Examples include butane, propane, nitrogen gas,
Mention may be made of carbon dioxide, and aerosol propellants such as halogenated hydrocarbons.

Examples of the solid diluent include soil natural minerals (for example, kaolin, clay, talc, chiyoke, quartz, attapulgite, montmorillonite, diatomaceous earth, etc.) and soil synthetic minerals (for example, highly dispersed silicic acid, alumina, silicates, etc.). be able to.

Solid carriers for granules include ground and fractionated rocks (eg, calcite, marble, pumice, sepiolite, dolomite, etc.), synthetic particles of inorganic and organic powders, and organic materials (eg sawdust, Coconut seeds, corn cobs, tobacco stems, etc.) can be mentioned as fine granules.

Examples of the emulsifier and / or foaming agent include nonionic and anionic emulsifiers [eg, polyoxyethylene fatty acid ester, polyoxyethylene fatty acid alcohol ether (eg, alkylaryl polyglycol ether, alkyl sulfonate, alkyl sulfate, aryl sulfone). Acid salt, etc.)], and albumin hydrolysis products.

As the dispersant, for example, lignin sulfite waste liquid,
And it includes methyl cellulose.

Adhesives may also be used in the formulation (powder, granules, emulsions) such adhesives including carboxymethyl cellulose and natural and synthetic polymers (eg gum arabic, polyvinyl alcohol and polyvinyl astate etc.). be able to.

A colorant can also be used, and as such a colorant,
Inorganic pigments (eg iron oxide, titanium oxide and Prussian blue), and organic dyes such as alizarin dyes, azo dyes or metal phthalocyanine dyes, and also iron,
Mention may be made of trace elements such as salts of manganese, boron, copper, cobalt, molybdenum, zinc.

The formulation may contain, for example, about 0.1 to about 95% by weight, preferably about 0.5 to about 90% by weight of the active ingredient.

The active compound of the present invention is used in the above-mentioned preparations or various use forms, for example, other known compounds, for example, fungicides (fangicides, bactericides), insecticides, acaricides, sentinelicides, herbicides, bird repellents, growth regulators. An agent, a fertilizer and / or a soil conditioner can be present together.

When the active compound of the present invention is used, it may be used directly as it is, or may be used in the form of preparation such as preparation liquid for dispersion, emulsion, suspension, powder, paste and granule, or further diluted. It can be used in the specified usage form. The active compound is then applied in the usual manner, for example by watering, dipping or spraying.
ng), fumigation, irrigation, suspension formation, application, dusting, dusting, dressing, wet-coating, pasty-coating or haori-coating.

In the treatment of each part of a plant, the concentration of active compound in the actual use form can be varied within a substantial range. And, generally, a concentration such as about 0.0001 to about 1% by weight, preferably about 0.001 to about 0.5% by weight can be exemplified.

For seed treatment, the active compound may be used in an amount such as, for example, about 0.001 to about 50 g, preferably about 0.01 to about 10 g per 1 kg of seeds.

For soil, for example, about 0.00001
Can be used at active compound concentrations of from about 0.1% by weight, in particular from about 0.0001 to about 0.002% by weight.

Next, the content of the present invention will be specifically described by way of examples, but the present invention should not be limited thereto.

Production Example: Example 1 R (+) 4-bromo-α-methylbenzylamine (4.
Dissolve 0 g) and triethylamine (2.2 g) in tetrahydrofuran (30 ml) and cool with ice. A solution of 1,3,3-trimethyl-2,2-dichlorocyclopropanecarboxylic acid chloride (4.28 g) in tetrahydrofuran (20 ml) was added dropwise to this solution while stirring. After the dropwise addition, the reaction temperature is returned to room temperature and stirred for 5 hours, and then at 60 ° C. for 2 hours. Tetrahydrofuran is distilled off, chloroform (50 ml) is added to the residue, the reaction mixture is washed with water, diluted hydrochloric acid, diluted aqueous sodium hydrogen carbonate solution and water in this order, and the chloroform layer is dried over anhydrous sodium sulfate. Chloroform was distilled off under reduced pressure, and the residue was recrystallized with a mixed solvent of 7 parts of n-hexane and 3 parts of ether to obtain the desired epimer ± 1,
3,3-Trimethyl-2,2-dichlorocyclopropanecarboxylic acid R (+) 4-bromo α-methylbenzylamide (8.
38 g) is obtained.

mp.148-159 ° C. [α] ²¹ _D ▼ + 61.2 ° (c = 1.02 g / 100 ml ethanol) In the same manner as in Example 1 above, R (+) 4-chloro-α was used.
-Methylbenzylamine and 1,3,3-trimethyl-2,2-dichlorocyclopropanecarboxylic acid chloride, the epimer ± 1,3,3-trimethyl-2,2-dichlorocyclopropanecarboxylic acid R (+ ) 4-Chloro-α-methylbenzylamide is obtained.

Example 2 The compound (7.0 g) obtained in Example 1 above was subjected to column chromatographic separation, and the desired melting point of colorless crystals from the first fraction was 147 to 148 ° C., ▲ [α] ²¹ _D ▼ + 64.2 ° (c = 1.13g / 100ml ethanol) enantiomer (3.48g)
Is obtained. (The compound is referred to as compound No. 2.) Rf = 0.22 (iatroscan; silica gel, chloroform: ethyl acetate: n-hexane = 4: 1: 5) -Chromatographic conditions-inner diameter 30 mm, length 500 mm, nitrogen flow Pressure 1.0 kg / cm ² Wako gel (C-300) 150 g Developing solvent n-hexane: ethyl acetate: chloroform = 8: 1: 1 In the same manner as in Example 2 above, epimers ± 1,3,3
The corresponding enantiomer is obtained from -trimethyl-2,2-dichlorocyclopropanecarboxylic acid R (+)-4-chloro-α-methylbenzylamide.

Example 3 1,3,3-Trimethyl-2,2-dichlorocyclopropanecarboxylic acid 4 which is a racemate consisting of four stereoisomers
Column chromatography separation of -bromo-α-methylbenzylamide under the same conditions as in Example 2 gives the desired enantiomer pair (0.97 g) with melting point 159.5-160.5 ° C from the first fraction. (The compound is referred to as Compound No. 3.) 1,3,3-Trimethyl-2,2-dichlorocyclopropanecarboxylic acid which is a racemate of four stereoisomers in the same manner as in Example 3 above. 4-Chloro-α-methylbenzylamide gives a pair of enantiomers with a melting point of 153-155 ° C. (The compound is referred to as Compound No. 4.) The compounds of the present invention are collectively shown in Table 1 below.

Biological test: Comparative compound A-1 (Compound described in JP-A-61-15867) Example 4 Foliar spraying efficacy test against rice blast Preparation of test compound Active compound: 50 parts by weight Carrier: Mixture of diatomaceous earth and kaolin (1: 5) 45 parts by weight Emulsifier; Polyoxyethylene alkylphenyl ether: 5 parts by weight Parts The above-mentioned amounts of active compound, carrier and emulsifier are ground and mixed to obtain a wettable powder, and a predetermined amount thereof is diluted with water.

Test method Paddy rice (variety: Asahi) was cultivated in a clay pot with a diameter of 12 cm, and 50 ml of 3 dilutions of the test compound having a predetermined concentration prepared as described above were sprayed in the third to fourth stages. Next day, spray-inoculate (twice) a suspension of rice blast fungus spores that had been artificially cultured on the next day at 25 ° C.
The animals were infected by keeping them in a humid room at 100% relative humidity. Seven days after the inoculation, the degree of morbidity per pot was classified and evaluated according to the following criteria,
Furthermore, the control value (%) was determined.

Degree of morbidity Area lesion rate 0 0 0.5 2 or less 1 3-5 2 6-10 3 11-20 4 21-40 5 41 or more This test is a result of 3 pots in 1 ward.

 The results are shown in Table 2 with a representative example.

Front page continuation (72) Inventor Katsuaki Wada 39-15 Namikicho, Hachioji City (72) Inventor Toshihito Kondo 39-15 Namikicho, Hachioji City (56) Reference JP-A 61-15867 (JP, A) Sho 61-18751 (JP, A) JP 62-201855 (JP, A)

Claims (9)

(57) [Claims] 1. A formula: (In the formula, X represents chlorine or bromine, and R ¹ has 1 to ¹ carbon atoms.
4 is an alkyl group, and R ² is a hydrogen atom or has 1 to 4 carbon atoms.
And an amine moiety is R
The (+)-form is shown. An optically active cyclopropanecarboxamide compound represented by: 2. The compound according to claim 1, wherein the amine moiety shows an R (+)-form and the acid moiety shows a racemate. 3. The compound according to claim 1, wherein the amine moiety is an enantiomer showing the R (+)-form. 4. The formula: ± 1,3,3-trimethyl-2,2-dichlorocyclopropanecarboxylic acid represented by the formula R (+) 4-bromo-α-methylbenzylamide.
The compound according to the item. 5. The formula: And the specific rotation ▲ [α] ²¹ _D ▼ + 64.2 ° (c
= 1.13 g / 100 ml ethanol), which is an enantiomer of an optically active cyclopropanecarboxamide. 6. The formula: (In the formula, X represents chlorine or bromine, and R ¹ has 1 to ¹ carbon atoms.
4 is an alkyl group, and R ² is a hydrogen atom or has 1 to 4 carbon atoms.
Is an alkyl group. ) A pair of enantiomers of cyclopropanecarboxamide represented by 7. The formula: And the specific rotation ▲ [α] ²¹ _D ▼ + 64.2 ° (c
= 1.13 g / 100 ml ethanol) which is a pair of enantiomers of the optically active substance and its enantiomer.
A pair of enantiomers according to item. 8. The formula: (In the formula, X represents chlorine or bromine, and R ¹ has 1 to ¹ carbon atoms.
4 is an alkyl group, and R ² is a hydrogen atom or has 1 to 4 carbon atoms.
And an amine moiety is R
The (+)-form is shown. ) A rice blast control agent containing as an active ingredient an optically active cyclopropanecarboxamide represented by: 9. The formula: (In the formula, X represents chlorine or bromine, and R ¹ has 1 to ¹ carbon atoms.
4 is an alkyl group, and R ² is a hydrogen atom or has 1 to 4 carbon atoms.
Is an alkyl group. ) A rice blast control agent containing, as an active ingredient, a pair of enantiomers of cyclopropanecarboxamide represented by