KR100342949B1 - Erythritol derivatives having herbicidal activity and preparation process thereof - Google Patents

Abstract

PURPOSE: Provided are arylthiazol derivatives having herbicidal activity and a preparation process thereof. The prepared compounds have the novel structure and strong herbicidal activity. CONSTITUTION: Arylthiazol derivatives represented by the formula(1) are provided, wherein R is hydrogen, halogen, nitro, cyano, C1-C4 alkyl or C1-C4 alkoxy; n is an integer of 1 to 5; Q is hydroxy, C1-C4 alkoxy, C1-C4 alkylamino, 1 or 2 of C1-C4 dialkylamino, or C1-C4 alkyl, benzyl or phenyl substituted or unsubstituted morpholine, piperidine or piperazine; A is hydrogen, C1-C4 alkyl, carboxyl, C1-C4 alkoxycarbonyl or cyanomethylaminocarbonyl; and W is oxygen or sulfur. A process for preparing a compound of the formula(1a) comprises reacting a compound of the formula(2) with a compound of the formula(2) in solvent in the presence of base.

Description

Herbicidal arylthiazole derivatives and preparation method thereof

The present invention relates to a novel arylthiazole derivative represented by the following formula (1), a method for preparing the same, and a herbicide composition for combating plants that is harmful to a crop containing the compound.

Formula 1

In the above formula

R represents hydrogen, halogen, nitro, cyano, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy,

n represents an integer of 1 to 5,

Q is hydroxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylamino, C ₁ -C ₄ alkylamino or di represent, C ₁ -C ₄ alkyl, benzyl or substituted phenyl or unsubstituted by from 1 to 2 Ring morpholine, piperidine or piperazine,

A represents hydrogen, C ₁ -C ₄ alkyl, carboxyl, C ₁ -C ₄ alkoxycarbonyl or cyanomethylaminocarbonyl,

W represents oxygen or a sulfur atom.

In the definition of the above substituents, the term "alkyl" is used alone or in a compound word such as "alkylamino", or as a straight or branched chain such as methyl, ethyl, n-propyl, isopropyl, 1-butyl and various butyl isomers, and the like. Refers to a saturated hydrocarbon group, the term "alkoxy" when used alone or as a compound term such as "alkoxycarbonyl" or the like means methoxy, ethoxy, n-propoxy, isopropoxy or various butoxy isomers , The term "halogen" means fluorine, chlorine, bromine or iodine.

It is well known that 1,3,4-thiadiazole derivatives are useful as herbicides, and active research has been conducted on them (see, for example, British Patent No. 2294928, European Patent No. 460479, Japanese Patent Publication No. 04330067, 05286969 and German Patent Nos. 4133827, 4412328 and 4420337, etc., little is known about herbicidal thiazole derivatives.

Accordingly, the present inventors have conducted intensive studies to develop a thiazole derivative having a novel structure and having excellent herbicidal power, and as a result, the arylthiazole derivative represented by Chemical Formula 1 meets the above-described purpose. It was completed. Hereinafter, the configuration of the present invention will be described in detail.

An object of the present invention is to provide a novel arylthiazole derivative of the formula (1).

Formula 1

In the above formula,

R represents hydrogen, halogen, nitro, cyano, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy,

n represents an integer of 1 to 5,

Q is hydroxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylamino, C ₁ -C ₄ alkylamino or di represent, C ₁ -C ₄ alkyl, benzyl or substituted phenyl or unsubstituted by from 1 to 2 Ring morpholine, piperidine or piperazine,

A represents hydrogen, C ₁ -C ₄ alkyl, carboxyl, C ₁ -C ₄ alkoxycarbonyl or cyanomethylaminocarbonyl,

W represents oxygen or a sulfur atom.

Representative examples of the compound of Formula 1 according to the present invention are as shown in Table 1 below with the physical data.

TABLE 1a

number R A W Q ¹ H NMR (270MHz, CDCl ₃ ) δ 1-1 H CO ₂ H S OMe 7.58-7.42 (m, 5H), 4.20 (s, 2H), 3.72 (s, 3H) 1-2 H CO ₂ Me S OMe 7.57-7.40 (m, 5H), 4.38 (s, 3H), 4.20 (s, 2H), 3.70 (s, 3H) 1-3 H CO ₂ Me S OH 1-4 H CO ₂ Me S 4-methylpiperazine 7.58-7.40 (m, 5H), 4.36 (s, 3H), 4.30 (s, 2H), 3.65-3.50 (m, 4H), 2.45-2.40 (m, 4H), 2.30 (s, 3H) 1-5 H CO ₂ Me S Morpholine 7.58-7.41 (m, 5H), 4.56-4.52 (m, 2H), 4.35 (s, 3H), 4.30 (s, 3H) 3.87-3.77 (m, 6H) 1-6 H CO ₂ Me S 2-ethylpiperidine 1-7 H CO ₂ Me S 4-phenylpiperazine 1-8 H CONHCH ₂ CN S OMe 7.53-7.42 (m, 5H), 7.08 (NH), 4.19 (s, 2H), 4.07 (s, 2H), 3.76 (s, 3H) 1-9 2-Cl, 4-Cl CO ₂ Me S OMe 1-10 2-Cl, 4-Cl CO ₂ Me S OH 1-11 2-Cl, 4-Cl CONHCH ₂ CN S OH 8.70 (NH), 7.70 (s, 1H), 7.50 (m, 2H), 4.20 (s, 3H), 4.19 (s, 2H) 1-12 2-Cl, 4-Cl CONHCH ₂ CN S OMe 1-13 2-Cl, 4-Cl CONHCH ₂ CN S 4-methylpiperazine 7.55 (s, 1H), 7.40 (m, 2H), 6.50 (NH), 4.30 (s, 2H), 4.15 (s, 2H), 3.65 (m, 2H), 3.5 (m, 2H), 2.40 (m , 4H), 2.30 (s, 3H)

TABLE 1b

1-14 2-Cl, 4-Cl CO ₂ Me S 4-phenylpiperazine 1-15 2-Cl, 4-Cl CO ₂ Me O OMe 1-16 2-Cl, 4-Cl H O OMe 7.80 (d, 1H), 7.45 (s, 1H), 7.30 (s, 1H), 7.24 (d, 1H), 5.04 (s, 2H), 3.80 (s, 3H) 1-17 4-MeO H O OMe 1-18 4-NO ₂ H O OMe 1-19 2-Cl, 4-Cl H O 4-methylpiperazine 7.80 (d, 1H), 7.44 (s, 1H), 7.26 (d, 1H), 5.13 (s, 2H), 3.66 (m, 2H), 3.49 (m, 2H), 2.42 (m, 4H), 2.30 (s, 3H) 1-20 2-Cl, 4-Cl CO ₂ Me O 4-methylpiperazine 1-21 2-Cl, 4-Cl CONHCH ₂ CN O 4-methylpiperazine 1-22 2-F, 4-Cl CONHCH ₂ CN O 4-methylpiperazine 1-23 2,4,6-trimethyl CO ₂ Me O 4-methylpiperazine 1-24 2-Cl, 4-Cl H O OH 7.80 (d, 1H), 7.69 (s, 1H), 7.58 (s, 1H), 7.51 (d, 1H), 5.00 (s, 2H) 1-25 2-Cl, 4-Cl H O N, N-diethylamino

On the other hand, the compound of formula (1) according to the present invention can be prepared according to the method shown in Schemes 1 and 2, and therefore the present invention aims to provide a method for preparing the compound of formula (1).

First, the compound of Formula 1a, wherein W is an oxygen atom, may be prepared by refluxing the compound of Formula 2 with the compound of Formula 3 in the presence of a base in a solvent.

[Formula 2]

[Formula 3]

[Formula 1a]

Wherein R, n, A and Q are as defined above.

Among the compounds of Formula 1, the compound of Formula 1b, wherein W is a sulfur atom, may be prepared by refluxing the compound of Formula 4 with the compound of Formula 5 in the presence of a base in a solvent.

[Formula 4]

[Formula 5]

[Formula 1b]

In the above formula

R, n, A and Q are as defined above,

X represents chlorine or bromine.

The two preparation methods according to the present invention can be represented simply as in Schemes 1 and 2.

Scheme 1

Scheme 2

As solvents in the reaction schemes 1 and 2, ethers such as tetrahydrofuran, diethyl ether and dimethoxyethane, polar solvents such as dimethylformamide and dimethyl sulfoxide, halogenated hydrocarbons such as dichloromethane and carbon tetrachloride, benzene, One or more selected from aromatic hydrocarbons such as toluene and xylene can be used, and inorganic bases such as potassium carbonate, sodium carbonate, sodium hydride, potassium hydride, sodium hydroxide and potassium hydroxide, triethylamine, 1,8- Organic bases, such as a diaza [5.4.0] bicycloundecese-7-ene and a pyridine, can be used. Preferably, potassium carbonate-dimethylformamide or sodium hydride-dimethylformamide reaction system is used. In addition, the reaction may be carried out in the temperature range of 10 to 100 ℃ ℃ is preferably in the range of 40 to 70 ℃.

Compounds of Formulas 2 and 4 used as starting materials in Schemes 1 and 2 can be easily prepared and used according to known thiazole synthesis methods as shown in Schemes 3, 4 and 5, respectively.

Scheme 3

Scheme 4

Scheme 5

It is another object of the present invention to provide a herbicide composition for combating plants harmful to crops, comprising the compound of formula 1 as an active ingredient together with a carrier commonly used in preparation of pesticides.

In the present invention, pot cultivation and drug treatment were performed on the assay plants in a greenhouse to test whether the compound of Formula 1 exhibits herbicidal efficacy as desired. A month view was conducted.

TABLE 2

Table of efficacy and weakness evaluation criteria

Evaluation standard Herbicide Crop characteristics 0 0-10% 0-10% One 11-30% 11-30% 2 31-50% 31-50% 3 51-70% 51-70% 4 71-90% 71-90% 5 91-100% 91-100%

To test the efficacy of the compounds according to the invention, field weeds include Echinochloa crus-galli var.caudata, Eleusine indica, Agropyron tsukushiense, Digitaria sanguinalis, Abboton theophrasti ), Aeschynomene indica, Ipomoea spp and Xanthium strumarium were selected, and weeds (Echinochloa crus-galli var. Oryzicola), Scirpus juncoides and Monocoria were weed vagina- lis), cyperus serotinus, and sagittaria trifolia were selected.

When preparing the herbicide composition containing the compound of the present invention, the compound of the formula (1) is a solid material such as clay, talc, diatomaceous earth or water, alcohol, benzene, toluene, ether, ketones, esters, acids, amides It may be mixed with a liquid substance to be formulated into any formulation such as liquid, emulsion, powder, granule, etc., and at least one selected from emulsifiers, dispersants, penetrants, electrodeposition agents and stabilizers may be added as necessary.

Depending on the object to be controlled, year-round time, the plant and the growth stage thereof, the amount of the active compound according to the present invention may vary, but is usually used at a ratio of 0.001 to 5.0 kg / ha of the active compound.

Hereinafter, the present invention will be described in more detail through the following Preparation Examples and Examples. However, these preparation examples and examples are only for the understanding of the present invention, and the scope of the present invention in any sense is not limited to these examples.

Preparation Example 1 Synthesis of 2-mercapto-4-phenylthiazole-5-carboxylic Acid Methyl Ester

5 g of 3-oxo-3-phenylpropanoic acid methyl ester and 2.2 g of ammonium dithiocarbamate were dissolved in 50 ml of dichloromethane and stirred at room temperature. After the reaction was completed, the reaction mixture was extracted with water and dichloromethane. The organic layer was dried over anhydrous sodium sulfate, distilled under reduced pressure and separated by column chromatography (hexane / ethyl acetate = 2/1, v / v) to give 4.2 g (yield 80%) of the title compound.

Preparation Example 2 Synthesis of N-cyanomethyl-4- (2,4-dichlorophenyl) -2-mercapto-thiazole-5-carboxamide

After dissolving 2.2 g of 4- (2,4-dichlorophenyl) -2-mercapto-thiazole-5-carboxylic acid methyl ester in 50 ml of 2N-sodium hydroxide aqueous solution, it stirred at 50 degreeC. After completion of the reaction, concentrated hydrochloric acid was added dropwise to the reaction mixture to neutralize the solution and the resulting solid was filtered. The filtered carboxylic acid white solid was dried in air, and then 3.0 g of dried carboxylic acid was added to 5 ml of thionyl chloride and heated to 50 ° C. After 1 hour excess thionyl chloride was distilled off. The resulting acyl chloride was dissolved in 20 ml of dichloromethane, and then 1.0 g of aminoacetonitrile and 1.0 g of triethylamine were added dropwise thereto. After the reaction was completed, the reaction mixture was extracted with water and dichloromethane, the organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure. The residue was separated by column chromatography (hexane / ethyl acetate = 4/1, v / v) to give 2.2 g (65% yield) of the title compound.

Preparation Example 3 Synthesis of 2-methanesulfonyl-4-phenylthiazole-5-carboxylic acid methyl ester

2.1 g of the compound obtained in Preparation Example 1 and 1.1 g of potassium carbonate were dissolved in 10 ml of dimethylformamide, and an excess of 3 ml of methyl iodide was added dropwise thereto. The reaction mixture was heated at 70 ° C. to complete the reaction and extracted with water and diethyl ether. The organic layer was dried over anhydrous sodium sulfate, distilled under reduced pressure, and the residue was separated by column chromatography to obtain 1.6 g of 2-methylthio-4-phenylthiazole-5-carboxylic acid methyl ester. The obtained compound was dissolved in 20 ml of chloroform, and then 1.0 g of metachloroperbenzoic acid was slowly added dropwise at 0 占 폚. The reaction mixture was heated at 50 ° C. for 5 hours and then extracted with water and dichloromethane. The organic layer was washed with saturated aqueous sodium thiosulfate solution, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The residue was separated by column chromatography (hexane / ethyl acetate = 2/1, v / v) to give 1.4 g (yield 55%) of the title compound.

Example 1: Synthesis of 2-methoxycarbonylmethylthio-4-phenylthiazole-5-carboxylic acid methyl ester (1-2)

2.5 g of the compound obtained in Preparation Example 1 and 1.4 g of potassium carbonate were dissolved in 50 ml of dimethylformamide, and 1.5 g of methyl α-bromoacetate was added dropwise thereto. The reaction mixture was heated at 70 ° C. to complete the reaction and extracted with water and diethyl ether. The organic layer was dried over anhydrous sodium sulfate, distilled under reduced pressure and separated by column chromatography (hexane / ethyl acetate = 4/1, v / v) to give 2.7 g (yield 85%) of the title compound.

Example 2: Synthesis of [4- (2,4-dichlorophenyl) thiazol-2-yloxy] acetic acid methyl ester (1-16)

3.1 g of 4- (2,4-dichlorophenyl) -2-methanesulfonylthiazole, 0.9 g of methyl glycolate and 1.4 g of potassium carbonate were dissolved in 20 ml of dimethylformamide and the reaction mixture was heated at 70 deg. After the reaction was completed, the reaction mixture was extracted with water and diethyl ether. The organic layer was dried over anhydrous sodium sulfate, distilled under reduced pressure and separated by column chromatography (hexane / ethyl acetate = 4/1, v / v) to give 2.5 g (yield 78%) of the title compound.

Example 3: Synthesis of 2- [4- (2,4-dichlorophenyl) thiazol-2-yloxy] -1- (4-methylpiperazin-1-yl) ethanone (1-19)

2.5 g of the compound obtained in Example 2 was dissolved in 20 ml of an aqueous 2N-sodium hydroxide solution, and then stirred at 50 ° C. After the reaction was completed, neutralized by adding dropwise concentrated hydrochloric acid to the reaction mixture, and the resulting solid was filtered. After the filtered carboxylic acid white solid was dried in air, 2.3 g of the dried carboxylic acid was added to 5 ml of thionyl chloride and heated to 50 ° C. After 1 hour excess thionyl chloride was distilled off. The resulting acyl chloride was dissolved in 20 ml of dichloromethane, and then 0.8 g of 4-methylpiperazine and 0.8 g of triethylamine were added dropwise to the reaction mixture. After the reaction was completed, the reaction mixture was extracted with water and dichloromethane, the organic layer was dried over anhydrous sodium sulfate, distilled under reduced pressure and separated by column chromatography (hexane / ethyl acetate = 2/1, v / v) to obtain 1.5 g of the title compound. (Yield 58%) was obtained.

The following shows a part of the formulation and use examples of the herbicide containing the compound according to the invention as an active ingredient. However, these compounding examples and use examples are only one illustration, and do not limit the technical scope of the present invention.

Formulation Example 1: Emulsion

The compound of the present invention (10% by weight) was dissolved in an organic solvent (60% by weight, aromatic hydrocarbon such as acetone or xylene), and then a surfactant (30% by weight; tween 20 or tritone) was added to obtain an emulsion.

Formulation Example 2: Hydration

The compound of the present invention (10% by weight), the extender (80% by weight, zeolite, white carbon, bentonite) and the surfactant (10% by weight, polyoxyethylene alkylaryl sulfate) are uniformly mixed and then finely ground with an air mill A hydrating agent was obtained.

Formulation Example 3: Granulation

Spraying mixture in the form of pellets by uniformly mixing the compound of the present invention (3% by weight), the extender (92% by weight, talc and bentonite, white carbon) and the surfactant (5% by weight, polyvinylacetate or lignosulfate) Obtained.

Compounding Example 4: Liquid

The compound (20% by weight) of the present invention was dissolved in a solvent (70% by weight; isopropyl alcohol or water), and then a surfactant (10% by weight, polyoxyethyl alkylphenyl ether) was added to obtain a liquid.

Example 1: Field Conditions

After filling the sterilized soil (sand soil, pH 5.5-6.0) in a rectangular plastic container (20x15x10cm), the seeds of the test plants were sown separately by seeding at 0.5 cm after the surface area was 300 cm2. In order to test the herbicidal power before germination by soil treatment, a mixture of the active ingredients corresponding to the prescribed dose was sprayed uniformly on the soil surface after 1 day of watering. For the treatment after germination, the test plants were first grown to a growth size of 3 to 15 cm according to the growth type, and then the compounded solution of the active ingredient corresponding to the prescribed treatment dose was uniformly sprayed on the plant foliage. The plants were kept at a temperature of 10-25 ° C. or 20-30 ° C. depending on the species, and experiments were carried out over two to four weeks, during which time the plants were cared for and the plant's response to each treatment was evaluated.

Use Example 2: Rice Field Conditions

Four pots (30x15cm) were filled with sterilized paddy soil (plow soil, pH 5.5-6.0), and rice and paddy weeds were sown and mixed in soil with a surface area of 450 cm2. In order to test the herbicidal power before germination by soil treatment, a mixture of the active ingredients corresponding to the prescribed treatment amount was instilled after 1 day of irrigation. When the plants reached the 2-3 leaf stage, the compound solution of the active ingredient corresponding to the prescribed amount of treatment was uniformly sprayed on the plant foliage. After the cultivation and observation for 4 to 5 weeks after the treatment, the response of the plants with each treatment was evaluated.

Representatively, the herbicidal power of the compound of Formula 1 is shown in Table 3.

TABLE 3

Herbicidal power after germination by foliage treatment (field conditions, 2kg / ha)

compound Fidget Silkworm morning glory Macaw 1-2 5 5 5 5 1-4 5 5 4 5 1-5 4 4 3 5 1-8 5 5 4 5 1-13 5 5 5 5 1-16 4 4 4 5 1-19 4 4 3 5 1-24 5 5 4 5

Claims (10)

An arylthiazole derivative of the formula Formula 1

In the above formula, R represents hydrogen, halogen, nitro, cyano, C ₁ -C ₄ alkyl or C ₁ -C ₄ alkoxy, n represents an integer of 1 to 5, Q is hydroxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylamino, C ₁ -C ₄ alkylamino or di represent, C ₁ -C ₄ alkyl, benzyl or substituted phenyl or unsubstituted by from 1 to 2 Ring morpholine, piperidine or piperazine, A represents hydrogen, C ₁ -C ₄ alkyl, carboxyl, C ₁ -C ₄ alkoxycarbonyl or cyanomethylaminocarbonyl, W represents oxygen or a sulfur atom. A method of preparing a compound of Formula 1a, comprising reacting a compound of Formula 2 with a compound of Formula 3 in a solvent in the presence of a base: Formula 2

Formula 3

Formula 1a

Wherein R, n, A and Q are as defined in claim 1. The process according to claim 2, wherein the solvent is at least one selected from tetrahydrofuran, diethyl ether, dimethoxyethane, dimethylformamide, dimethyl sulfoxide, dichloromethane, carbon tetrachloride, benzene, toluene and xylene. 3. The base according to claim 2, wherein the base is potassium carbonate, sodium carbonate, sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, triethylamine, 1,8-diaza [5.4.0] bicycloundecese-7-ene and pyridine The method is one or more selected from. The process according to claim 2, wherein the reaction is carried out at a temperature in the range of 10 to 100 ° C. A method for preparing a compound of Formula 1b, comprising reacting a compound of Formula 4 with a compound of Formula 5 in a solvent in the presence of a base: Formula 4

Formula 5

Formula 1b

In the above formula R, n, A and Q are as defined in claim 1, X represents chlorine or bromine. The process according to claim 6, wherein the solvent is at least one selected from tetrahydrofuran, diethyl ether, dimethoxyethane, dimethylformamide, dimethylsulfoxide, dichloromethane, carbon tetrachloride, benzene, toluene and xylene. 7. The base according to claim 6, wherein the base is potassium carbonate, sodium carbonate, sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, triethylamine, 1,8-diaza [5.4.0] bicycloundecese-7-ene and pyridine The method is one or more selected from. The method of claim 6, wherein the reaction is carried out at a temperature in the range of 10 to 100 ° C. 7. A herbicidal composition for eradicating plants harmful to crops, comprising the compound of formula 1 according to claim 1 together with a carrier used in the preparation of pesticides.