JPS61212566A - 2-azolylpropionic acid ester derivative and fungicide - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R1 is phenyl which may be mono- or polysubstituted with halogen, CH3, OCH3 or NO2; R2 is alkylthio; R3 is alkylthio, cycloalkylthio or phenylthio; R4 is imidazol-1-yl or 1,2,4-triazol-1-yl). EXAMPLE:Ethyl 3-(2,4-dichlorophenyl)-3-ethylthio-2-(1-imidazolyl)-propionate. USE:An antimycotic agent for agricultural use. It has preventive, remedying or systemic fungicidal activity against various phytopathogens. PREPARATION:The compound of formula I can be produced by reacting the compound of formula II with the thiol of formula R3-H in an alcohol in the presence of a catalytic amount of piperidine, at a temperature near the boiling point of the solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a parent compound 2-azolylpropionate derivative represented by the following general formula, which has antifungal activity and is useful as an agricultural antifungal agent.

5R4 [In the formula, R1 may be mono- or polysubstituted with the same or different substituents selected from a phenyl group (], a rhodan atom, a methyl group, a methoxy group, and a nitro group. ), R2 is an alkyl group, R3 is an alkylthio group, cycloalkylthio group, or phenylthio group, R4
is imidazol-1-yl or 1,2.4-triazol-1-yl] The present invention also provides agriculturally acceptable compounds represented by the above general formula or agriculturally acceptable salts thereof.

The present invention provides an antifungal composition for plants or seeds containing a diluent or carrier.

The present invention also provides for the use of antifungal compositions of compounds of the general formula above, or, where appropriate, agriculturally acceptable salts thereof, to treat plants or seeds infected with fungi or to prevent said plants from growing. It provides a way to treat all the places where you are.

When R4 represents an optionally di-substituted phenyl group as described above, 1 to 3 substituents each independently selected from C1, F, OCH3 and CH3, preferably 1 to
Preferably, it is a phenyl group which is di-substituted by two. Preferred various groups 1d represented by R1:, 4-fluorophenyl, 4-10ruphenyl, 3.4-dichlorophenyl, 2.4-dichlorophenyl, 2-chloro-6
The most preferred group represented by -fluorophenyl@R1 is 2,4-dichlorophenyl. A preferable group represented by R2 is a straight chain or branched chain having 2 to 3 carbon atoms.

A preferred group represented by R3 is a straight or branched alkylthio group having 2 to 4 carbon atoms.

The compound represented by the above general formula is produced by conventional method 9 according to the following reaction mechanism.

R, -CH= C-C0□R2([) ■ 3R4 In a typical reaction, the boiling point of the solvent for 24 hours in alcohol in the presence of olephy7 (II) 'e thiol R3-H and a co-trapping catalytic amount of piperidine. Either by heating at a temperature in the vicinity, or by suspending Alcolade R2-0Na in diethyl ether and adding thiol R3-H thereto, stirring at room temperature for several hours, then adding olefin (II) e little by little for 24 hours at room temperature. Stir. The reaction is preferably carried out under a nitrogen stream. The product (1) f is then isolated and purified according to a conventional method.

The compound represented by formula (I[) is produced by a conventional method according to the following reaction mechanism.

R4-CHO + CH2-Co2-R2(III)
(IV) ■ In a typical reaction, aldehyde (III) and compound (IV) are reacted in acetic anhydride in the presence of anhydrous potassium carbonate.
Heat to 0°C to 90°C.

Alternatively, it can also be produced by the following reaction mechanism.

H4R4 (III) (IV)
(V) The compound represented by formula (V) is prepared by combining aldehyde (I[I) and compound (IV) with a suitable base (a catalytic amount of alcoholade or potassium t-butoxide). Furthermore, compound (V) is reacted with trifluoroacetic anhydride in anhydrous tetrahydrofuran at a temperature from room temperature to around the boiling point of the solvent. The product (I[)'r is then isolated and produced according to a conventional method.

The compound represented by formula (1) has at least two chiral centers, and the present invention exists in two pairs of diastereomers.

Agriculturally acceptable acid addition salts of the compounds of this invention are those formed from strong acids such as hydrochloric, hydrobromic, sulfuric, ciuric, and sulfonic acids that form non-toxic acid addition salts.

Salts can be obtained in conventional manner, for example, by mixing solutions containing equimolar amounts of the free base and the desired acid, and if the desired salt is insoluble or soluble, it can be collected by filtration or evaporation of the solvent. be done.

The compound of the present invention represented by the above general formula has preventive, therapeutic, or systemic fungicidal activity against many plant pathogens.

These plant pathogens include powdery mildew of wheat (Ery
siphe graminis f, Sp, hor
dei, L 8p.

tritici) *Eye spot (Pseudoc)
ercosporellaherpotrichoid
es) + apple monilia disease (5clerotin
ia malt), pear scab disease (Venturi
anashicola), pear black spot (Alte
rnariakikuchiana), powdery mildew of cucurbits (5phaerotheca fuligin)
ea ), green onion rust (Puccinia all
ii), -f- Powdery mildew (Erysip)
When the compound of the present invention is used as an agricultural or horticultural fungicide, it may be used as it is without adding any other ingredients, but it is usually used in combination with a solid carrier, liquid carrier, surfactant, etc. It may also be used by mixing it with a formulation auxiliary agent and preparing it into an emulsion, an aqueous solution, a suspension, a granule, a gravel solution, etc. These preparations contain the compound of the present invention represented by the general formula as an active ingredient in a weight ratio of 0.1 to 99.
9N, preferably 0.2 to 80X.

Solid carriers include fine powders or granules such as kaolin clay, Atta i4/L/gytoclay, bentonite, acid clay, norophyllite, talc, diatomaceous earth, calcite, and synthetic hydrous silicon oxide, and liquid carriers include xylene. , aromatic hydrocarbons such as methylnaphthalene, Ingrono 4
Examples include alcohols such as alcohol, ethylene glycol, and ceasorp, ketones such as acetone, cyclohexanone, and isophorone, vegetable oils such as soybean oil and cottonseed oil, dimethyl sulfoxide, and acetonitrile.

Surfactants used for emulsification, dispersion, wetting layers, etc. include alkyl sulfate ester salts, alkyl (aryl) sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkyl ether sulfates,
Examples include anionic surfactants such as naphthalene sulfonic acid formalin condensate, nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene block copolymer, and sorbitan fatty acid ester.

Formulation adjuvants include lignin sulfonate, alginate, polyvinyl alcohol, gum arabic, and Cal? Examples include oxymethylcellulose and acidic isopropyl phosphate.

Hereinafter, typical agricultural methods for compounds will be explained with specific examples.

Synthesis Example 1 Ethyl 3-(2,4-dichlorophenyl)-2-(
1-imidazolyl) cinnamate 2.4-dichlorobenzaldehyde 45g and ethyl 2
-imidazolylacetate-) 39.8g to 300g of toluene
m1VC plus potassium tert-butoxyl'2
．． Add F and reflux with stirring for 18 hours.

After that, the solvent is distilled off under reduced pressure and n-hexane is added to the residue. The oil will solidify, so the n-hexane is removed by decantation and acetone is added to the residue to obtain white crystals, which are filtered with suction. It can be separated and purified by doing this.

The yield of this white crystal is 44.7F. This product is suspended in anhydrous tetrahydrofuran, trifluoroacetic anhydride 35,9 is added dropwise, and the suspension is heated under reflux for 5 hours. Cool to room temperature, filter out insoluble matter, pour the filtrate into a large amount of water, and neutralize with saturated sodium carbonate water. Extract with dichloromethane, dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure. The residue is subjected to column chromatography on silica and eluted with dichloromethane:acetone 9:1. The desired product was obtained as a pale yellow oil that gradually solidified.

Yield 34.2.9 Birth value 7.95 pprn-heavy line Imidazole IH7,
35-6.80 ppm Multiplet Aromatic Proton 3H + Imidazole 2H6, 40ppm Doublet J = 10Hz Methyl/Proton IH N 1, 35 ppm Triplet J = 7 Hz Methyl Proton 3H Synthesis Example 2 Ethyl 3-(2,4 -dichlorophenyl)-3-ethylthio-2-(1-imidazolyl)propionate (
Compound 8) Rhizium ethylate 6.8. i- Ethanethiol 6,2 suspended in 100 WL of anhydrous diethyl ether at room temperature.
Drop g'e. Stir at room temperature for 2 hours after dropping.
D extraction fk 3- (2,4-dichlorophenyl)-
Add 2.961 ml of 2-(1-imidazolyl)cinnamate in portions. After further stirring at room temperature for 24 hours, 5Qml of water was added.
After adding f and stirring for 10 minutes, the reaction solution was extracted with ether. After washing with water, it is dried over anhydrous sodium sulfate and the ether is distilled off under reduced pressure. The residue is subjected to silica column chromatography and eluted with chloroform:methanol CJ6':5. The desired product is obtained as a pale yellow oily substance.

Yield 2.0g Yield 54% Tow value 7.45 ppm to 6.80 ppm Multiplet imidazole group proton 3H + aromatic proton 3H 5.05 to 4.95 ppm Multiplet methine proton 2H 4.40 to 3.95 ppm Quadruple methylene proton 2H (ester) 2.70~
2.05 ppm Multiplet Methylene proton 2H 1,45-1゜00 ppm Multiplet Terminal methyl proton 3H+ 3H synthesis example 3 Tertiary-butyl 3-(2,4-dichlorophenyl)-2-(1-imidazolyl) cinname 2.4-Dichlorobenzaldehyde I 7.6.9 To 14II' of anhydrous potassium carbonate, add 250 rllllFC of acetic anhydride and while stirring at room temperature, add tertiary-butyl 2-imidazolylacetate 18.2.1- little by little, then 60°C (inner temperature) Stir for 5 hours. After the reaction, the mixture was gradually added to 50°C hot water and stirred at that temperature for 30 minutes. Cool to room temperature and neutralize the reaction solution with anhydrous potassium carbonate. Thereafter, it is extracted with dichloromethane, washed with water, and dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure and the residue is purified by silica gel column chromatography. Dichloromethane:acetate/9:1
When eluted with , the desired product was obtained as a yellow oil, which gradually solidified on standing.

Yield 18.6 & Value 7.85 ppm - Heavy line imidazole proton I
H7, 45-6.80ppm Multiplet aromatic zolotone 3H + imidazole proton 2
H 6, 30 ppm Double line J = 9Hz Methine proton IH 1, 55 ppm -Double line Tert-butyl proton 9H Synthesis example 4 Tert-butyl 3-(2,4-dichlorophenyl)-3-isopropylthio-2-(1- imidazolyl)
Tert-butyl propionate 3-(2,4-dichlorophenyl)-2-(1-imidazolyl)cinnamate 3.39.
Dissolve 50 ml of 9't ethanol and dropwise add piperidine II, then add 0.76 g of isopropyl mercaptan.
Stir at ~70°C for 24 hours. After the reaction, the contents are poured into a large amount of water and extracted with methylene chloride. After washing with water, it is dried over anhydrous sodium sulfate and the solvent is distilled off under reduced pressure. The residue is purified by silica column chromatography. Elution with n-hexane:ethyl acetate 3:2 yields the target product as a yellow oil, yield 2.85g, yield 69% ■Value 7.40-6.90 ppm Multiplet Aromatic proton 3H + Imidazole proton 3H 5.00-
4.85 ppm Multiplet Methine proton 2H 2,70-2.15 ppm Multiplet Methine proton IH 1,55-1.05 ppm Multiplet Terminal methyl 3H+ 3H+ 3H+ 3H+3
Table 1 shows compounds of the present invention synthesized by a method substantially similar to the above method.

In addition, R1 to R4 in the table represent substituents of the above formula. However, R3 is represented by R' of the R'S- group, and R4 is represented as A: imidazol-1-yl or B: 1,2.4-triazol-]-yl.

The compounds of the present invention are effective in controlling a wide range of diseases of agricultural and horticultural crops, and the main ones include the following.

Paddy rice Blast, sesame leaf blight, sheath blight, bastard seedling disease, etc. Wheat Rust, powdery mildew 9 spots, naked smut, etc. Potato Phytophthora, summer blight, black bruising Legumes Soybean Purpura 1 spot , Rust disease Adzuki bean Rust, powdery mildew, etc. Tobacco Red star blight, Phytophthora, etc. Beet Brown spot, seedling blight, etc. Vegetables Tomato Gray mold 9 Leaf mold, Sclerotinia, Phytophthora 2 Ring spot disease, Seedling establishment Blight and other cucurbits Downy mildew, gray blight, gray mold, sclerotium, scab, seedling damping off, anthracnose.

Vine blight, etc., onions, gray rot, downy mildew, etc., lettuce, sclerotinia, etc., fruit trees, citrus, gray mold, black spot, scab, etc. apples, monilia disease, powdery mildew, scab disease, etc.

As mentioned above, the compound of the present invention can be used for agricultural purposes such as leaf spot disease, peach leaf spot, black spot, black spot, etc., grape rot, downy mildew, black pox, gray mold, late rot, etc. It is used as a horticultural fungicide, either as it is or mixed with carriers (diluents, etc.) in the form of powders, granules, water preparations, emulsions, oils, and other suitable dosage forms commonly used in low-agrochemical preparations.

In this case, spreading agents, emulsifiers, wetting agents, fixing agents, etc. are used as appropriate, and other types of fungicides, insecticides,
It can also be used or mixed with herbicides, fertilizers, etc.

Example 1. Powder Compounds found in the table 3 parts Clay 40 parts Merck 57 parts Example 2. Compounds in the list of irrigation agents: 25 parts polyoxyethylene alkyl allyl ether 9 parts White car? 16 parts talc
50 copies Example 3. Emulsion 1001nl weight table Compounds
259 Tsurupol 2680■ 10g Xylene Residual Tsurupol 2680 Toho Chemical Industry There is no restriction on the amount of spraying, but usually when spraying on fields where crops grow, the active ingredient compound (A
, 1. ) as 50-1000g/10a, and when applied in soil, 9A in 0.5-8, 1. /10
A value of about a is appropriate.

Of course, this is only a guideline, and may be adjusted as necessary, taking into account factors such as the type of crop, type of disease, degree of damage, season, weather, and dosage form of the drug.

Hereinafter, in order to specifically explain the effects of the compounds of the present invention,
A typical test example is shown.

However, these are merely examples, and it goes without saying that the application examples of the present invention are not limited to these.

Test Example-1 Pear Black Spot Efficacy Test Test Method> A chemical solution diluted to a predetermined concentration was sprayed at 20% per 5 leaves for the development of pears (variety 220th Century) and air-dried indoors.

Alternaria cultured in apricot medium after air drying
The conidia of Kikuchi ana were inoculated by spraying and immediately left to stand for 3 days at 25° C. and humidity of 10 liters, and after 3 days, the diseased area was examined.

However, the number of runs shall be 5.

<Test results> Compound concentration Average disease control value Chemical damage (a, i, pp
m) Area (%) (%) 4 500 13
．． 5 86.5 -24 // 20
．． 3 79.7 -28 7
16.4 83.6 -29
II 12.9 87.1 -41
1/ 8.7 91.3 -44
// 7.0 93.0 -45
/l 6.8 93.2 -46
1/7.8 92.2 -47
// 6.9 93.1 -49
p 16.6 8
3.4 -50 p 18.2
81.8 -51 II
20.4 79.6 -Rovral
/' 7.1 92
．． 9 - No treatment - 100 - Test Example 2 Rice sheath blight efficacy test Test method> After spraying a chemical solution at a predetermined concentration onto the primary leaves of Indan (variety: Masterpiece), they were air-dried indoors.

After air-drying, the rice sheath blight fungus (Rh1z
octonia 5olani IA) was punched out from a cork and inoculated.

After inoculation, the seeds were kept at a temperature of 28° C., a humidity of 100%, and a dark condition for 3 days, and the presence or absence of disease development was examined.

However, the number of runs shall be 5.

Test results> Compound concentration Average disease area Control value Plant damage (a-t-
ppm) (ch) (%)2 p
8 92 -3#1090- 6 〃11 89
-g/' 0 100
- Compound concentration Average disease area Control value Plant damage (a
-i, ppm) (ch) (%)10
tt 13 87
-11 p 21
79 -12 n
9 91 -1.8
/I 7 93
-20 tt 23
77 -23 tt
18 82 -25 〃22
78-31 p.
12 88 -32 u
O100-34 /I
9 91 -41 p
13 87 -44 tt
24 76 -49
tt 28 72 - Validacin tt 25
75 - No treatment /l 100 -
-Test Example-3 Test Method for Rice Blast Efficacy Test> An amount equivalent to 200-e/10a of a chemical solution with a predetermined concentration is sprayed at the 3-leaf stage of potted rice (variety Nijukoku).

Rice blast fungus (Pyriculari) cultured after air-drying
A suspension of 40 conidia of P. aoryzae per field of view under a microscope at 100 magnification was inoculated by spraying.

Immediately after inoculation, the plants were kept under dark conditions at a temperature of 23° C. and a humidity of 100° C. for 48 hours, and then left in a greenhouse. Ten days after inoculation, the degree of disease onset was determined using the following criteria.

However, the number of runs shall be three.

f: Index by severity of disease N: Number of investigated leaves Index by severity of disease Number of lesions per leaf 2 2 ~ 5 3 6 ~ 10 4 11 ~ ,, 0 Ro Ro 00 Ro Prisoner! Test Example 4 Wheat rust efficacy test test method> Wheat rust fungus (Puccinia reconditaf, s
A suspension of P. tritici) was prepared by spraying and inoculating 20 diaspores per field of view under a microscope at 100x magnification.

Immediately after inoculation, the seeds were kept in the dark at a temperature of 23° C. and a humidity of 100° C. for 28 hours, and then left in a greenhouse.

20013 of the drug solution diluted to the specified concentration on the third day after inoculation.
An amount equivalent to 710 a was sprayed. The investigation was conducted according to the criteria below 100 days after inoculation. However, the number of runs shall be 5.

Σnf Disease severity -X100 n: Number of diseased lateral leaves N f: Index by disease severity N: Number of inspected leaves Index by disease severity 0: Number of non-symptomatic leaves (affected area 0%) 1: Small 1 (〃
1-25) 3: Medium // (tt 26-50) 5: High /
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After air-drying, the treated cucumber fungi were left in a greenhouse to infect cucumber powdery mildew' (5phaerofheca ful).
iginea) was naturally infected.

After 14 days of standing, an investigation was conducted according to the following criteria.

However, the number of rows was 5, and 10 leaves were investigated.

Σnf Disease severity = X100 n: Number of lateral leaves affected by disease N f: Index by disease severity N: Number of investigated leaves Index by disease severity 0: Number of leaves without disease (affected area 0%) 1: Small t
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Claims (1)

[Claims] 1) General formula ▲ Numerical formula, chemical formula, table, etc. each may be monosubstituted or polysubstituted), R_2 is an alkyl group, R_3 is an alkylthio group, a cycloalkylthio group, or a phenylthio group,
R_4 is imidazol-1-yl or 1,2,4-triazol-1-yl] A 2-azolylpropionic acid ester derivative. 2) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ), R_2 is an alkyl group, R_3 is an alkylthio group, a cycloalkylthio group, or a phenylthio group,
R_4 is imidazol-1-yl or 1,2,4-triazol-1-yl] A fungicide containing a 2-azolylpropionate derivative as an active ingredient.