KR840000117B1 - Process for preparation of phenoxy-fattyacid derivatives containing heterocyclic ether - Google Patents

Abstract

The title compds. I (a=CH, N; X=halo; n=0,1,2; R1=H, lower alkyl; R2=OH, -0.alkyl, -n-R3R4;, R3,R4=H, lower alkyl), useful as herbicides, were prepd. Thus, 12g hydroxyquinone monobenzyl ether, 8.2g 2-chloroquinoline, and 8.3g K2CO3 were reacted with 50mL dimethylsulfoxide at 150˜160≰Cfor 4 hrs. to give 12g 2-(4-benzyloxphenoxy)quinoline, which was dissolved in 200mL mixt. contg. THF and ethanol to give 6.3g α-(4-hydroxyphenoxy)quinoline (II). 2.37g II, 2.1g-bromopropionateMe, and 2.0g K2CO3 were refluxed in 50mL methylethyl ketone for 4 hrs. to give 2.2g 2[4-(2-quinolyloxy)phenoxy ! propionateMe.

Description

Method for preparing heterocyclic ether phenoxy fatty acid derivative

The present invention relates to a heterocyclic ether phenoxy fatty acid derivative represented by the following general formula (I) (hereinafter referred to as a compound of the present invention) and a method for producing the salt thereof.

기(R³,R⁴는 수소원자 또는 저급알킬기를 나타냄)를 나타낸다][Wherein A represents a CH group or an N atom, X represents a halogen atom, n represents 0,1 or 2, R ¹ represents a hydrogen atom or a lower alkyl group, R ² represents an -OH group, -O- An alkyl group, an -OM group (M represents a salt forming atom, an inorganic or organic salt forming residue) or

Group (R ³ , R ⁴ represent a hydrogen atom or a lower alkyl group);

A variety of medicinal agents have been put to practical use from the research and development of herbicides for a long time, and these herbicides have contributed to the reduction of labor for weed control operations and the productivity of agrohorticultural crops.

In recent years, there has been a demand for the development of a new drug having more excellent herbicidal properties. In particular, as a horticultural herbicide, it is possible to selectively control only the target weeds with a small amount of medicine without damaging the crops. Preferred, none of the existing agents necessarily have suitable herbicidal properties.

The present inventors have conducted research on the herbicidal properties of various heterocyclic compounds in order to develop novel and useful herbicides, and as a result, the compounds of the present invention represented by the general formula (I) have been used for various weeds, especially rice- and weeds. It has been found to have an excellent bactericidal effect against, and to be substantially harmless to a broad-leaved crop, and to complete the present invention.

Conventionally, as a heterocyclic ether phenoxy fatty acid derivative, for example, substituted pyridyl oxyphenoxy fatty acid herbicides are known from Japanese Patent Application Laid-Open No. 51-106106735. In addition, Japanese Patent Application Laid-Open No. 53-40767 describes benzimidazole, benzthiazole, benzoxazole derivatives and their herbicidal action. However, the compound of the present invention, that is, a heterocyclic ether-based phenoxy fatty acid derivative having a quinoline or quinoxaline skeleton represented by the general formula (I), is a novel compound not described in the literature.

Next, a representative example of the compound of the present invention will be described in the first table, but the compound of the present invention includes the compound group represented by the above general formula (I), and the scope of the present invention is limited only to the compound described in the first table. It doesn't happen.

[Table 1]

Generally, the compound of this invention can be synthesize | combined using the following method. That is, the compound represented by the following general formula (IV) is produced by condensation reaction of the compound represented by the following general formula (III) with the monobenzyl ether of hydroquinone represented by the following general formula (III) in the presence of an inorganic or organic base. This product was subjected to catalytic hydrogenation, for example, debenzylation using a palladium-carbon catalyst to obtain a compound represented by the following general formula (V), followed by α represented by this compound and the following general formula (VI). The compound of the present invention is obtained by condensation of a halogenated fatty acid with an inorganic or organic base such as potassium carbonate in a polar solvent such as methyl ethyl ketone, acetonitrile or dimethyl formamide.

(Wherein A, X, n, R ¹ and R ² are as defined above and Hal represents a halogen atom.)

The compound obtained by the above-mentioned method is induced to another compound of the present invention by hydrolysis, esterification, ether exchange, salt formation, amidation reaction, and the like.

Next, some synthesis methods of the compound of this invention are illustrated.

Synthesis Example 1

2- [4- (2-quinolyloxy) phenoxy] methyl propionate (Compound No. 2 of the present invention)

In 50 ml of dimethyl sulfoxide, 12 g of hydroxyquinone monobenzyl ether, 8.2 g of 2-chloroquinoline, and 8.3 g of potassium carbonate were added, and the mixture was heated at 150 to 160 ° C for 4 hours. After cooling, the reaction solution was poured into water and extracted several times with ether, and the ether layer was washed with an aqueous solution of caustic soda, followed by water. The ether layer was dried over sodium sulfate and the crude crystals obtained by distilling off the solvent were washed with diisopropyl ether to obtain 12 g (yield 75%) of 2- (4-benzyloxyphenoxy) quinoline.

The total amount of the intermediate product was dissolved in 200 ml of a mixed solvent of tetrahydrofuran: ethanol = 5: 1, 1.5 g of a palladium-carbon based catalyst was added thereto, passed through 880 ml of hydrogen gas, and hydrogenation was performed under atmospheric pressure. After completion of the reaction, the catalyst was removed by suction filtration, and the residue obtained by distilling off the solvent was washed with a chloroform-n-hexane solvent to yield 6.3 g of a white crystal of α- (4-hydroxyphenoxy) quinoline (yield 7.4%). Got. (Melting point 177 ° C)

Further, 2.37 g of the product, 2.1 g of α-bromine propionate and 2.0 g of potassium carbonate were added to 50 ml of methyl ethyl ketone, and the mixture was reacted for 5 hours under reflux. After cooling to room temperature, the precipitated salt was filtered and the solvent was distilled off to obtain 2.2 g (yield 68%) of the title compound.

Synthesis Example 2

2- [4- (2-quinolyloxy) phenoxy] propionic acid-N, Ndimethylamide (Compound No. 6 of the present invention)

A mixture of 2.3 g of 2- (4-hydroxy phenoxy) quinoline, 1.8 g of N, N-dimethyl-α-bromine propionate amide and 1.4 g of potassium carbonate, which is an intermediate product of Synthesis Example 1, was added in a solvent of 100 ml of methyl ethyl ketone. It was heated to reflux for 5 hours. After completion of the reaction, the precipitated crystals were filtered off, and the filtrate was dried under reduced pressure after distilling off the solvent. The obtained crude crystal was recrystallized using a methanol-aqueous solvent to obtain 3.6 g (yield 88%) of white crystals of the title compound.

Synthesis Example 3

Synthesis of 2- [4- (6-chloro-2-quinoxalyloxy) phenoxy] ethyl propionate

18.0 g (0.164 mol) of hydroquinone was dissolved in 300 ml of acetonitrile, and 18 g (0.130 mol) of anhydrous potassium carbonate was added thereto, followed by heating to reflux for 1 hour. After cooling, a suspension of 400 g of acetonitrile of 9.0 g (0.0452 mol) of 2.6-dichloroquinoxaline was added, and the mixture was heated to reflux for 8 hours.

After completion of the reaction, the solvent acetonitrile was distilled off under reduced pressure, 200 ml of water was added to dissolve the remaining precipitate solid well, and then the liquid phase was weakly acidified with dilute hydrochloric acid, followed by filtration of the precipitate crystals. Precipitated crystals were washed well using hot water to remove excess hydroquinone. After the hydrothermal washing, the crystals were dissolved in 5% caustic soda solution, the insolubles were filtered off, and the filtrate was slightly acidic with dilute hydrochloric acid. The crystals were collected by filtration, dried after washing with water and recrystallized with a large amount of alcohol to obtain 9.0 g of white crystals having a melting point of 186 to 189 ° C as a target compound (yield 73%).

Elemental analysis values are as follows.

C (%) H (%) N (%)

Found 61.88% 3.25% 10.15%

Calculation 61.83% 3.30% 10.28%

Next, 2.7 g (0.01 mol) of 6-chloro-2- (4'-hydroxy) phenoxy quinoxaline obtained in this manner, 1.8 g (0.01 mol) of α-bromine propionate, 1.4 g of anhydrous potassium carbonate ( 0.01 mole) of methyl ethyl ketone was added to reflux for 10 hours.

After the reaction was completed, cooling was carried out to remove the solvent from the filtrate. The residue was then dissolved in chloroform and the chloroform layer was dried and evaporated to dryness. Subsequently, this residue was purified by column chromatography using silica gel (chloroform) to obtain 3.2 g of white crystals having a melting point of 84.0 g to 85.0 ° C. as a target compound (yield 85%).

Synthesis Example 4

Synthesis of 2-4- (6-fluoro-2-quinoxalyloxy) phenoxypropionate

2.6 g (0.01 mol) of 6-fluoro-2- (4'-hydroxy) phenoxyquinoxaline, 2.2 g (0.013 mol) of α-brompropionate potassium 2.1 g (0.015 mol) of anhydrous potassium carbonate, 100 ml of methyl ethyl ketone And refluxed for 5 hours.

After completion of the reaction, the precipitated salt was filtered off and the filtrate was evaporated to dryness. The residue was then dissolved in chloroform, the chloroform layer was washed with a small amount of 5% aqueous sodium hydroxide solution and then washed with water, and then the organic layer was dried and evaporated to dryness. The remaining solid was recrystallized using methanol to obtain 3.0 g of white crystals having a melting point of 124.0 to 125 ° C as a target compound (yield 87%).

In using the compound of the present invention as a herbicide, generally, a suitable carrier such as a solid carrier such as clay, talc, bentonite, diatomaceous earth or alcohols (methanol, ethanol, etc.) aromatic hydrocarbons (benzene, toluene, xylene, etc.), It can be used in combination with liquid carriers such as chlorinated hydrocarbons, ethers, ketones, esters (such as ethyl acetate), and acid amides (dimethylformamide, etc.), and if desired, emulsifiers, dispersants, suspending agents, penetrants, electrodeposition agents, By adding a stabilizer or the like, it can be practically provided as an arbitrary formulation such as a liquid, an emulsion, a hydrate, a powder, a granule, and the like. If necessary, the preparation or spraying may be mixed with other types of herbicides, various insecticides, fungicides, food preparations, aerodynamic agents and the like.

Next, a combination example of the herbicide containing the compound of the present invention as an active ingredient will be described. In addition, "part" in the following compounding example means a weight part.

Formulation Example 1 Hydration

50 parts of the compound of the present invention

D-Cright A (brand name) 46

Sorpol 5039 (surfactant, isochemical) 2 parts

Carplex (Antifreezing Agent, Shionogi Pharmaceutical Co., Ltd.) Part 2

The above is mixed and pulverized uniformly to be a hydrate. At the time of use, the hydrating agent is diluted 50 to 1,000 times with water, and sprayed so that the effective amount is 30 to 1000 g per 10 ares.

Formulation Example 2 Emulsion

20 parts of the compound of the present invention

Xylene Part 75

Sorpol 2680 (surfactant, isochemical) 5 parts

The above is mixed uniformly and it is set as an oil agent. In use, the emulsion is diluted 50 to 1,000 times with water and sprayed so that the effective amount is 30 to 1,000 g per 10 ares.

Formulation Example 3 Aqueous Solution

30 parts of the compound of the present invention

Sorpol W-150 (surfactant, isochemical) 10 parts

60 parts water

The above is mixed and dissolved to obtain an aqueous solution. In use, dilute the solution to 50-1000 times with water and spray it so that the effective amount is 30-1000 g per 10 ares.

The compound of the present invention exhibits extremely good herbicidal effect against various weeds, especially rice-plow weeds, in either soil spraying or foliage application, while broad-leaved crops such as soybean, radish, cabbage No harm to, eggplants, tomatoes, etc.

In addition, the compounds of the present invention can be applied to the control of various weeds in non-crop fields such as sports fields, public fields, tracks, etc. in addition to farming and horticulture fields such as fields, paddy fields, orchards, and the amount of the applied dose is the place of application, time of use, and method of use. Depending on the target weeds and crops, there is a difference, but in general, it is possible to spray 30 ~ 1000g per 10 areas as an effective presales.

Next, the usefulness of the compound of this invention as a herbicide is demonstrated concretely with reference to the following test example.

[Test Example 1]

Herbicide Effect Test by Soil Treatment

Put the sterilized red soil soil in a plastic box of 15cm width, 22cm height and 6cm height, and then plant rice, grass, scallop, moth, moth, iron dandruff, Hakidamegiku, and Inugarashi. After covering, the surface of the soil was evenly sprayed so that the amount of the active ingredient was in a predetermined ratio.

The chemical liquid at the time of spraying was diluted with water, an emulsion or a liquid agent of the above-mentioned compounding example and sprayed all over with a small atomizer. After three weeks of chemical spraying, herbicidal effects on rice and various weeds were investigated according to the following criteria.

The results are shown in Table 2.

Criteria

5... … More than 90% kill rate (almost completely dead)

4… … Flesh Rate 70 ~ 90%

3... … Flesh Rate 40 ~ 70%

2… … 20-40% Flesh Rate

One… … Flesh Rate 5 ~ 20%

0… … 5% or less kill rate (almost no effect)

[Table 2]

[Test Example 2]

Herbicide effect test by foliage treatment

Put the sterilized redness soil in a plastic box 15cm wide, 22cm long and 6cm high. I spotted purslane, purslane, Hagetamegi, Inugarashi, and tomato seeds, respectively, and covered with about 1.5 cm of soil. When the various weeds reached the 2-3 leaf stage, it spread | dispersed uniformly to the foliage part so that the amount of active ingredient might become a predetermined ratio.

The chemical liquid at the time of spraying was diluted with the water-repellent agent, emulsion, or liquid agent of the said compounding example with water, and was sprayed over the whole leaf part of various weeds by the small atomizer.

After two weeks of chemical spraying, the herbicidal effects on various weeds and tomatoes were examined according to the criteria of Test Example 1.

The results are shown in Table 3.

[Table 3]

[Test Example 3]

Weakness test on cultivated crops (foliar treatment)

In a plastic box 15 cm wide, 22 cm long and 6 cm high, sterilized red soil was placed, and then cotton, soybean, radish, cabbage and eggplant seeds were detected and covered with about 1.5 cm soil. When various crops reached the stage of vegetation development, they were evenly sprayed on the foliage so that the effective amount would be in a predetermined ratio. The chemical liquid at the time of spraying was diluted with water, an emulsion or a chemical agent of the said compounding example, and it spread | spreaded all over the foliage part of various crops as a small sprayer. After two weeks of chemical spraying, the damage to various crops was examined according to the following criteria.

The results are shown in Table 4.

Criteria

5... … Crop almost completely dead

4… … Weak against crops

3... … Weakness of crops appears

2… … Slight damage to crops

One… … Very little damage to crops

0… … No harm to crops

[Table 4]

Claims (1)

The compound represented by the following general formula (V) and the (alpha) -halogen fatty acid represented by the following general formula (VI) are condensed, and the heterocyclic ether-type phenoxy fatty acid derivative represented by the following general formula (I), and its manufacturing method are shown.

[Wherein A represents a CH group or an N atom, X represents a halogen atom, n represents 0,1 or 2, R ¹ represents a hydrogen atom or a lower alkyl group, R ² represents an -OH group, -O- Alkyl group, -OM group (M represents salt forming atom, inorganic or organic salt forming residue) or

Group (R ³ , R ⁴ represent a hydrogen atom or a lower alkyl group) and Hal represents a halogen atom.]