JPH04297449A - N-hydroxybenzylguanidine derivative and germicide for agriculture and horticulture - Google Patents

Abstract

PURPOSE:To obtain a new 1-benzyl-1-cycloalkyl-3-hydroxyguanidine derivative having excellent germicidal activity and safety. CONSTITUTION:A N-hydroxybenzylguanidine derivative [e.g. 1-(4-chlorobenzyl-3- hydroxy-2-phenylguanidine] expressed by formula I (R<1> is 5-7C cycloalkyl; R<2> is H, halogen, 1-6C alkyl or phenyl which may be substituted by 1-6C alkoxy; R<3> is H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, hydroxycarbonylmethyl or 1-6C alkoxycarbonylmethyl; X is H, halogen, 1-6C alkyl, halo-1-3C alkyl, OH or methanesulfonyloxy; n is 1 or 2). The compound expressed by formula I is e.g. obtained by reacting a thiourea expressed by formula II with methyl iodide and then reacting the reaction product with a hydroxyamine derivative expressed by formula III.

Description

[Detailed description of the invention]

0001

[Purpose of the invention]

FIELD OF THE INVENTION This invention relates to novel N-hydroxybenzylguanidine derivatives. For more details 1-
The present invention relates to a benzyl-1-cycloalkyl-3-hydroxyguanidine derivative and an agricultural and horticultural fungicide containing the derivative as an active ingredient.

Therefore, the present invention is useful in the chemical industry and agricultural and horticultural fields, particularly in the agricultural chemical manufacturing field.

0003

BACKGROUND OF THE INVENTION There have been some literature descriptions of N-hydroxybenzylguanidine derivatives. For example, French Patent No. 2,098,352 describes that N-hydroxybenzylguanidine represented by the following general formula has herbicidal activity.

0004

[Formula 3] (In the formula, R and R1 represent a hydrogen atom, an alkyl group, an aralkyl group, etc., R2 and R3 represent an alkyl group, a halogen atom, etc., and n and m represent 0 or an integer of 1 to 5. ) However, the N-hydroxybenzylguanidine derivative represented by the general formula (I) of the present invention is not known.

[0005]

[Problems to be Solved by the Invention] Known N-hydroxybenzylguanidine does not exhibit any bactericidal activity for agricultural and horticultural purposes, as shown in the test examples below. On the other hand, various drugs have been used to treat downy mildew, late blight, and rust, which are important diseases of fruit trees, vegetables, and grains, and sheath blight, which is an important disease of rice. Some items are no longer usable due to problems, or their use has been restricted. Therefore, in these fields, there is a demand for a fungicide having a new chemical structure different from that of conventional drugs.

The object of the present invention is to provide a new fungicide that meets these needs.

[0007]

[Structure of the invention]

[Means for Solving the Problems] In order to achieve the above object, the present inventors synthesized many compounds and examined their bactericidal activity. As a result, it was found that the 1-benzyl-1-cycloalkyl-3-hydroxyguanidine derivative of the present invention has excellent bactericidal activity and safety.

Therefore, the gist of the first invention is that the general formula (I)

embedded image (wherein R1 represents a C5-C7 cycloalkyl group,
R2 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a phenyl group which may be substituted with a C1-C6 alkoxy group, and R3 represents a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 represents an alkynyl group, a hydroxycarbonylmethyl group or a C1-C6 alkoxycarbonylmethyl group, X represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo C1-C3 alkyl group, a hydroxy group or a methanesulfonyloxy group, and n represents an integer of 1 or 2).

In the compound of general formula (I), C5 to C7
Examples of the cycloalkyl group include cyclopentyl group, cyclohexyl group, cycloheptyl group, etc., and examples of C1-C6 alkyl group include methyl group, ethyl group, propyl group, isopropyl group, butyl group,
Examples include isobutyl group, sec-butyl group, tert-butyl group, pentyl group, and hexyl group.

Furthermore, examples of the C2-C6 alkenyl group include vinyl group, allyl group, 1-propenyl group, butenyl group, pentenyl group, hexenyl group, and examples of the C2-C6 alkynyl group include can include ethynyl group, propargyl group, 1-propynyl group, butynyl group, etc.

Furthermore, examples of the C1-C6 alkoxy group include methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, pentyloxy group, and representative examples of the halo C1-C3 alkyl group. has a trifluoromethyl group.

The second aspect of the present invention resides in an agricultural and horticultural fungicide characterized by containing the N-hydroxybenzylguanidine derivative of general formula (I) as an active ingredient.

Representative examples of the compounds of the present invention are shown in Tables 1 and 2 below along with their physical properties, but the present invention is not limited thereto.

[0014]

[Table 1]

[0015]

[Table 2]

Example (Part 1) Method for producing the compound of the present invention The compound of general formula (I) according to the present invention is produced by the following 3
It can be manufactured by any one of three methods, ie, method [A], [B], or [C].

[Method A] The compound of general formula (I) is prepared by reacting thiourea represented by general formula (II) with methyl iodide and then reacting with a hydroxyamine derivative represented by general formula (III). Can be manufactured.

[0018]

embedded image (In each of the above formulas, R1, R2, R3, X and n have the same meanings as above)

This production method is usually carried out under the following reaction conditions.

The amount of reagent used in the reaction is 1 to 2 equivalents of methyl iodide per mol of the compound of formula (II),
Preferably it is 1 equivalent, and the compound of formula (III) is 1 to
5 equivalents, preferably 1 equivalent.

The compounds of formula (III) can also be used in the form of mineral acid salts.

Examples of solvents include hydrocarbons such as toluene and hexane, halogenated hydrocarbons such as chloroform and chlorobenzene, ethers such as ethyl ether, dioxane and tetrahydrofuran, alcohols such as methanol, ethanol and amyl alcohol, and acetonitrile. , propionitrile, dimethylformamide, dimethyl sulfoxide, etc. can be used.

Although the reaction proceeds at room temperature, the reaction time can be shortened by heating it up to the boiling point of the solvent. After the reaction is completed, the target product can be obtained by distilling off the solvent. The compound of the present invention can also be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran, or chloroform, separating the desired product, and distilling off the solvent.

The starting materials, compounds of general formulas (II) and (III), are both known compounds. An example of the production of the compound of the present invention by method [A] is shown in Example 1 below.
It was shown to.

[Method B] The compound of general formula (I) is prepared by combining a chloroamidine derivative of general formula (IV) and a compound of general formula (I).
It can be produced by reacting the hydroxyamine derivative shown in II).

[0026]

[Formula 6] (In each of the above formulas, R1, R3, )

[0027] This condensation reaction is usually carried out in an organic solvent. Usable solvents include hydrocarbons such as toluene and hexane, halogenated hydrocarbons such as chloroform and chlorobenzene, ethers such as ethyl ether, dioxane and tetrahydrofuran, alcohols such as methanol and ethanol, and acetonitrile and dimethylformamide. , dimethyl sulfoxide, etc.

Other than using the compound of the general formula (III) in the form of a mineral acid salt, the acid binder can be substituted by using an excess amount since it itself is a basic substance, but sodium hydride, Inorganic bases such as sodium amide, sodium hydroxide, potassium carbonate, etc. or organic bases such as triethylamine, pyridine, etc. can also be used.

Although the reaction proceeds at room temperature, the reaction time can be shortened by heating up to the boiling point of the solvent. After the reaction is completed, if salts of the acid binder are present, they are filtered off and the solvent is distilled off to obtain the desired product. The compound of the present invention can also be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran, or chloroform, separating the desired product, and distilling off the solvent. An example of the production of the compound of the present invention by method [B] is shown in Example 2 below.

The starting material, the compound of general formula (IV), can be obtained by reacting a urea derivative with phosphorus pentachloride in hydrocarbons or halogenated hydrocarbons by a known method or a method similar thereto. It will be done. General formula (I
The compound V) is a new compound, and its production example is shown in Reference Production Example 1 below. Moreover, all the compounds of general formula (III) are known compounds.

[Method C] The compound of general formula (I) is prepared by combining N-hydroxyguanidine represented by general formula (V) and general formula (
It can be produced by reacting with a halide represented by VI).

[0032]

[Formula 7] (In each of the above formulas, R1, R2, or represents a C1-C6 alkoxycarbonylmethyl group, and Y represents a halogen atom.)

This reaction can be carried out by mixing the compound of formula (V) and the compound of formula (VI), usually in a solvent and in the presence of an acid binder.

Examples of solvents include hydrocarbons such as benzene, toluene and xylene, ethers such as tetrahydrofuran and dioxane, nitriles such as acetonitrile and propionitrile, alcohols such as ethanol and ethylene glycol, dimethylformamide and dimethylacetamide. Amides such as and dimethyl sulfoxide can be used.

As the acid binder, inorganic bases such as sodium hydroxide, sodium hydride and potassium carbonate, and organic bases such as sodium methoxide, sodium ethoxide, triethylamine and pyridine can be used.

Although the reaction proceeds at room temperature, the reaction time can be shortened by heating up to the boiling point of the solvent. After completion of the reaction, if salts of the acid binder are present, they are filtered off and the solvent is distilled off to obtain the target compound. The target compound can also be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran, or chloroform to extract the target compound, and then distilling off the solvent.

An example of the production of the compound of the present invention by method [C] is shown in Example 3 below. Note that the compound of formula (V), which is a starting material, is a compound of the present invention obtained by method [A]. Moreover, all of the compounds of formula (VI) are known compounds.

Example 1 1-(4-chlorobenzyl)-1-cyclopentyl-3
-Hydroxy-2-phenylguanidine (Compound No.
Production method of 2) [Method A] 34.4 g of 1-(4-chlorobenzyl)-1-cyclopentyl-3-phenylthiourea and 200 ml of amyl alcohol were placed in a 500 ml four-necked flask, and after cooling with water, methyl iodide was added. 14.2 g was added dropwise. After the dropwise addition, the mixture was stirred at room temperature for 1 hour, then 6.9 g of hydroxyamine hydrochloride was added, and the mixture was stirred at 80°C for 10 hours. After distilling off the amyl alcohol, water and toluene were added to the residue, and the toluene layer was separated and concentrated under reduced pressure to obtain 32.1 g of the title compound as a pale yellow oil. When this was purified by silica gel chromatography using a toluene-acetone mixed solution, pale yellow crystals (yield 22.9 g) were obtained.
It showed a melting point of 88-90°C.

Example 2 1-(4-chlorobenzyl)-1-cyclohexyl-3
-Hydroxy-2-phenylguanidine (Compound No.
12) Production method [Method B] N2-phenyl-N is placed in a 500 ml four-necked flask.
1-(4-Chlorobenzyl)-N1-cyclohexylchloroamidine (36.2 g) and toluene (200 ml) were added and cooled with ice water, followed by 6.9 g of hydroxyamine hydrochloride and 10.
2g of triethylamine was added. The mixture was stirred at room temperature for 1 hour. After adding water, the toluene layer was separated and concentrated under reduced pressure to obtain 34.9 g of the title compound as pale brown crystals. n-
When recrystallized with hexane-toluene mixed solvent, white crystals (
The yield was 28.2 g), and the melting point was 140-142°C.

Example 3 1-(4-chlorobenzyl)-1-cyclohexyl-3
-allyloxy-2-phenylguanidine (compound No.
．． 14) Production method [Method C] 1-(4-chlorobenzyl)-1-cyclohexyl-3-hydroxy-2-
After cooling with ice, 35.7 g of phenylguanidine (compound No. 12) and 200 ml of tetrahydrofuran were added, and 2.4 g of sodium hydride was added thereto, followed by stirring for 1 hour under ice cooling. Furthermore, 12.0 g of allyl bromide was added and stirred at room temperature for 1 hour. After adding water, the tetrahydrofuran layer was separated and concentrated under reduced pressure to obtain 37.3 g of the title compound as a brown oil. When this was purified by silica gel chromatography using a mixed solution of toluene and ethyl acetate,
White crystals (yield 23.8g), melting point 44-46℃
showed that.

Reference production example 1 N2-phenyl-N1-(4-chlorobenzyl)-N1
-Preparation of cyclohexylchloroamidine (raw material of Example 2) 1-(4-chlorobenzyl)-1-cyclohexyl-3-phenylurea 3
After cooling with water, 20.5 g of phosphorus pentachloride was added. The mixture was stirred at room temperature for 1 hour. When chloroform was distilled off under reduced pressure, 35.8 g of the title compound was obtained as a pale yellow oil, n23D = 1.5646.
showed that.

Example (Part 2) Method for formulating a fungicide for agriculture and horticulture The fungicide for agriculture and horticulture of the present invention can be used by formulating the compound of general formula (I) according to a conventional formulation. can. That is, the compound of general formula (I) is blended with appropriate carriers and auxiliary agents, such as surfactants, binders, stabilizers, etc., to form wettable powders, emulsions, liquids, sols (flowables), and oils. , powder, DL (driftless) powder, fine granules, coarse powder, granules, etc. The content of the compound of the present invention in these preparations is hydrated, emulsified,
In the case of liquid, sol, and oil agents, the range is 1 to 90% (weight%: the same applies hereinafter); in the case of powders, DL powders, fine granules, and coarse powders, the range is 0.5 to 5%; in the case of granules; can be contained in a range of 1 to 10%.

The method of using the agricultural and horticultural fungicide of the present invention is generally as follows. In other words, in the case of wettable powders, liquids, emulsions, sols (flowables), and oils, they are diluted 500 to 2000 times with water, and the active ingredients are generally 1 to 1.
The solution is prepared at a concentration of 10,000 ppm. and 10
50 to 300 liters of this diluted solution per are, usually 10
A quantity of 0 to 200 liters is sprayed on the leaves and foliage of the plant where the disease occurs. In addition, liquids, emulsions, and sol (flowables) can be used as concentrated liquids without diluting them with water, or by diluting them up to 10 times with water. 50-30 per 10 ares as ULV spraying agent)
00ml is sprayed using a helicopter or the like. In addition, for powders, DL powders, fine granules, and coarse powders, 2 to 5 kg (approximately 50 to 500 g of active ingredient) per 10 ares are used on the foliage, soil surface, soil, or water surface of the disease-infested areas of plants. Ru.

The present invention will be explained in more detail by the following examples, but is not limited thereto.

Example 4 (Powder) Compound No. 2 parts of compound 2, PAP (physical property improver)
1 part and 97 parts of clay were uniformly mixed and ground to obtain a powder containing 2% of the active ingredient.

Example 5 (hydrating powder) Compound No. 20 parts of the compound No. 12, 3 parts of potassium alkylbenzenesulfonate, 5 parts of polyoxyethylene nonylphenyl ether and 72 parts of clay were uniformly mixed and pulverized to obtain a wettable powder containing 20% of the active ingredient.

Example 6 (emulsion) Compound No. 30 parts of compound No. 14, 40 parts of methyl ethyl ketone and 30 parts of polyoxyethylene nonylphenyl ether were mixed and dissolved to obtain an emulsion containing 30% of the active ingredient.

Example 7 (Sol) Compound No. 40 parts of compound No. 10, 2 parts of lauryl sulfate, 2 parts of sodium alkylnaphthalene sulfonate, 1 part of acetoxypropyl cellulose, and 55 parts of water were uniformly mixed to obtain a sol containing 40% of the active ingredient.

[0049]

Effects of the Invention The compound of formula (I) of the present invention has a high control effect against downy mildew, late blight, and rust, which are important diseases of fruit trees, vegetables, and cereals, and sheath blight, which is an important disease of rice. Therefore, it is useful as a fungicide for agriculture and horticulture.

Next, specific examples of the usefulness of the compounds of the present invention represented by formula (I) are shown in Test Examples 1 to 4.

Test Example 1 Cucumber Downy Mildew Control Effect Test According to Example 5, cucumber seedlings (variety: Sagami Hanshiro) at the second leaf stage were cultivated in clay pots with a diameter of 9 cm in a greenhouse. 20 ml of the diluted solution of the prepared wettable powder at a predetermined concentration was sprayed. Then, with a damp brush, remove cucumber downy mildew (Pseudoperonospora) from leaves affected by cucumber downy mildew.
Spores of Pseudoperonospora cubensis were scraped off and suspended in a 50 ppm aqueous solution of a spreading agent (polyoxyethylene alkyl ether). Then, the spore concentration was adjusted to 5 x 106 spores/ml, and a spore suspension of cucumber downy mildew was inoculated by spraying one day after the chemical spraying. Then, it was left standing in a greenhouse at 20° C. and 100% humidity for 2 days to cause cucumber downy mildew to develop. Six days after inoculation, the lesion area ratio (%) per leaf was investigated, and the control value (%) was calculated using the following formula.

[0052] This test was conducted twice per chemical solution concentration area, and the average control value (%) was determined, and the evaluation value was determined according to the following criteria. In addition, chemical damage to cucumbers was investigated according to the following criteria. The results are shown in Tables 3 and 4.

[0053] The evaluation value of the control effect and the investigation index of chemical damage were similarly used in Test Examples 2 to 4 below.

[0054]

[Math 1]

Survey index of drug damage 5: Severe 4: Severe 3: Severe 2
: Slightly 1: Slightly 0: None

[0056]

[Table 3]

[0057]

[Table 4]

Test Example 2 Tomato late blight control effect test Example 5 was applied to 5th leaf stage seedlings of tomatoes (variety: Toko K) grown in soil in a greenhouse in a vinyl pot with a diameter of 9 cm.
Using an automatic spraying device, 30 ml of a predetermined concentration diluted solution of a hydrating powder prepared according to the above was sprayed per 3 pots. 2 on pre-sliced potato pieces the day after drug treatment.
Tomato Phytophthora blight bacteria (Phytopht) cultured at 0°C for 3 days
zoospores of Phytophthora infestans (Phytophthora infestans) were scraped (adjusted so that the concentration of zoospores was 10 5 /ml) and sprayed onto tomatoes using a spray gun. After storing the seeds in a greenhouse at 20°C and 100% humidity for 5 days, the percentage of diseased area of tomato late blight (%) for the 1st to 4th true leaves.
), the average diseased area ratio was determined in the same manner as Test Example 1, and the control value (%) was calculated from comparison with the non-sprayed area.

[0059] This test was conducted twice per chemical solution concentration area, and the average control value (%) was determined and converted into an evaluation value. In addition, phytotoxicity to tomatoes was investigated using the same criteria as in Test Example 1. The results are shown in Tables 5 and 6.

[0060]

[Math 2]

[0061]

[Table 5]

[0062]

[Table 6]

Test Example 3 Wheat rot disease control effect test Wheat seedlings at the first true leaf stage (variety: Norin No. 61) grown in clay pots with a diameter of 9 cm in a greenhouse were treated according to Example 5. A diluted solution of a hydrating powder with a predetermined concentration prepared in the above manner was sprayed in an amount of 20 ml per three pots. One day later, the wheat rot fungus (Puccinia
recondita: Puccinia recondita) using a microscope with a magnification of 150 times, the spore concentration per field of view was approximately 5.
Tween 20 (trade name of polyoxyethylene sorbitan monolaurate manufactured by Kao Corporation) 50p so that the number is 0.
The spore suspension was suspended in sterile water supplemented with pm, and the spore suspension was spray inoculated onto wheat leaves. After keeping it in a greenhouse at 20℃ and 100% humidity overnight, it was heated to 20℃.
The disease was then transferred to a greenhouse to encourage the onset of the disease. Ten days after inoculation, the leaves were taken out, the number of infected pedicelium per leaf was investigated, and the control value (%) was calculated using the following formula.

[0064] This test was conducted in three pots per drug concentration.
The average control value was determined and converted into an evaluation value. In addition, the degree of drug damage to wheat was investigated using the same criteria as in Test Example 1 and displayed. The results are shown in Table 7.

[0065]

[Math 3]

[0066]

[Table 7]

Test Example 4 Rice sheath blight control effect test Example 5 was applied to rice seedlings (variety: Asahi) at the 6-7 leaf stage grown in soil in a plastic pot with a diameter of 9 cm in a greenhouse.
30 ml of a predetermined concentration diluted solution of a hydrating powder prepared according to the method was sprayed per three pots. One day after the spraying, rice sheath blight bacteria previously cultured on a rice straw medium was placed at the base of the plants as an inoculum. 2
The rice was left standing in a greenhouse at 4°C and 100% humidity for 5 days to cause rice sheath blight to develop. Five days after inoculation, the length of the affected effective stems was measured, and the control value (%) was calculated using the following formula. The results are shown in Table 8.

[0068]

[Math 4]

[0069]

[Table 8]

Claims (2)

[Claims] Claim 1: General formula (I) [Formula 1] (wherein R1 represents a C5-C7 cycloalkyl group,
R2 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a phenyl group which may be substituted with a C1-C6 alkoxy group, and R3 represents a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 represents an alkynyl group, a hydroxycarbonylmethyl group or a C1-C6 alkoxycarbonylmethyl group, X represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo C1-C3 alkyl group, a hydroxy group or a methanesulfonyloxy group, and n represents an integer of 1 or 2). Claim 2: General formula (I) [Formula 2] (wherein, R1 represents a C5-C7 cycloalkyl group,
R2 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a phenyl group which may be substituted with a C1-C6 alkoxy group, and R3 represents a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 represents an alkynyl group, a hydroxycarbonylmethyl group or a C1-C6 alkoxycarbonylmethyl group, X represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo C1-C3 alkyl group, a hydroxy group or a methanesulfonyloxy group, is an integer of 1 or 2) as an active ingredient.