KR830002433B1 - Preparation of organophosphate ester - Google Patents

Abstract

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Description

Preparation of organophosphate ester

The present invention relates to the preparation of novel organophosphate esters having insecticidal properties. In more detail

General formula

The present invention relates to an organic phosphate ester represented by [wherein n represents 0, 1 or 2], an organic phosphate ester (I) and a pesticide composition containing a carrier. From the point of view of food production and health hygiene, many insecticides, mainly organic phosphates, have been imported or produced in large quantities in Korea, and have been used for a long time. Combined with the negative effect of failure, it became a social problem. On the other hand, in insects, similar insecticides are used and frequently used, resulting in resistance and resistance to insect mites, resulting in an unfavorable situation of significantly reducing the effectiveness of existing insecticides. Reached. In these respects, the emergence of new insecticides that are safer and have excellent effects on insects and mites that have obtained multiple drug resistance to existing insecticides has become hungry.

In order to meet these demands, the present inventors, with their intensive research, have developed a group of novel compounds represented by the general formula (I), which is a kind of asymmetric phosphate ester which is slightly different from conventional insecticidal organophosphate compounds. The organic phosphate esters were found to have suitable properties for solving these problems, and based on this knowledge, the present invention was completed.

의 결합위치에서 보아서, 2-위(0-위)또는 3-위(m-위)에만 1개 치환되어 있는 것을 특징으로 한다.Methoxyl groups of the CH ₃ O In the formula (I) is a benzene ring group

In view of the bonding position of, it is characterized in that one is substituted only in 2-position (0-position) or 3-position (m-position).

의 결합위치에서 보아서 4-위(P-위)만으로 한정되어 있는 것을 특징으로 한다.Therefore, the basic skeleton is characterized in that it is a derivative of curry or resorcinol. n represents 0.1 or 2. Accordingly, when n is 0, CH ₃ S (O) n- means methylthio group, when n is 1, methylsulfinyl group and when n is 2, methylsulfonyl group. Sulfur-substituted group containing this [CH ₃ S (O) n] is a group of benzene ring

It is characterized in that it is limited to 4-position (P-position) only from the combined position of.

As such a preferable thing in the object (I) of this application, for example,

(1), 0-ethyl S-n-propyl 0- (4-methylthio-2-methoxyphenyl) phosphorothiolate

(2), 0-ethyl S-n-propyl 0- (4-methylthio-3-methoxyphenyl) phosphorothiolate

(3), 0-ethyl S-n-propyl 0- (4-methylsulfonyl-2-n-methoxyphenyl) phosphorothiolate

(4), 0-ethyl S-n-propyl 0- (4-methylsulfonyl-2-n-methoxyphenyl) phosphorothiolate

(5), 0-ethyl S-n-propyl 0- (4-methylsulfinyl-3-methoxyphenyl) phosphorothiolate

(6), 0-ethyl S-n-propyl 0- (4-methylsulfonyl-3-methoxyphenyl) phosphorothiolate

Among them, the preceding two-(1) and (2) have excellent insecticidal effects, and can be used as a pesticidal composition for the harmful insects and mites described below with the carrier. .

The organophosphoric acid ester (I) which concerns on this invention can be used widely as a pesticidal composition.

The organic phosphate ester (I) according to the present invention is extremely effective in killing various harmful insects and mites widely, for example, insect pests and wild insects that chew pesticides and useful objects for horticulture (Spodopiera liiura). ), Moth (Pluttella xylosiella), White butterfly (Pieris rapaecrucivora), Chilo suppressalis, Tobacco moth (Helicoverpaassulta), Leucania separata, Memestra brassicae Moth (Adoxophyesorana) Cnaphalocrocis medinalis), larvae of the potato moth (Phthorimaea operculella), echidna vermin spotted ladybug (Epilachna vigintioctopunctata), yellow leaf beetle (Phyllotreta striolata), larva beetle (Oulema oryzae) migratoria, caterpillars, semi-larvae pests, Scotinophara lurida, Stephanitis nashi, Laodephax striatellus, Nep-hotettix cincticeps, Yanoneca Aphids (Un Aspis yannonensis, soybean aphids (Aphis glycines), cotton aphids (Aphis gossypii), larvae, leaf mite, leaf mite (Tetraychus urticae), mandarin leaf mite (Panonychus citri), Nematodes, parasitic nematodes (Meloidogyne hapla) parasitic in the roots of the plant, insects, grain weeds (Sitophilus zeamais), grain beetles (Tribolium castaneum), etc. , Home pests such as Tinea pellionella, Attagenus piceus and Ctenolepisma villosa Domestica, Lucilia caesar, Black cockroach (Periplanetafuliginosa), Brown cockroach (Blattela germanica), Ixodes japonensis, hygiene, livestock pest, Boophilis microplus Indicates. On top of that, it is low in toxicity to warm animals, has little effect on the environment such as toxicity, and does not show any weakness in plants. In addition, since it is similarly effective against insects and green beans that exhibit resistance to many existing insecticides, it can be safely used not only as an agricultural pesticide composition but also widely as a horticultural insect for horticulture, household, pest control, and livestock.

Specifically, one kind or two or more kinds of the compound of the general formula (I) may be directly used depending on the purpose of use, dissolved in a suitable carrier (for example, a solvent), or dispersed therein, or a suitable solid. Either it is mixed with or adsorbed on a carrier (e.g., a weight loss agent), and if necessary, emulsifiers, dispersants, suspending agents, electrodeposition agents, penetrants, lubricants, store agents, stabilizers, etc. (I) It is used as a formulation, such as an agent, an emulsion, a hydrating agent, a powder, a granule, a tablet, an aerosol.

Generally, the concentration of the active ingredient in the pesticidal composition is generally about 10 to 90% as an emulsion, a hydrating agent, etc., and about 0.1 to 10% is suitable as an oil, a powder, etc. You may also change these concentrations accordingly. In addition, an emulsion, a hydrating agent, etc. can also be sprayed by dilution increase by 500-2000 times with water etc. in use, for example.

As a solvent used for the composition of this invention, alcohols (for example, methyl alcohol, ethyl alcohol, ethylene glycol, etc.) ketones (for example, acetone, methyl ethyl ketone, etc.), ethers (for example, dioxane, tetrahydrofuran , Cellosolves, etc.), aliphatic hydrocarbons (e.g. gasoline, kerosene, machine oil, fuel oil, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, solvent naphtha, methylnaphthalin, etc.), organic bases (e.g., For example, suitable solvents such as pyridine, glycine, etc., acid amides (e.g., dimethylformamide, etc.), esters (e.g., ethyl acetate, etc.), nitriles (e.g., acetonitrile, etc.), 1 type, or 2 or more types of these is mixed and used. As a dilution and extender, a plant powder (e.g., soy flour, tobacco powder, hoe powder, wheat flour, wood powder, etc.), mineral powder (e.g. clay, talc powder, pyrophyllite, such as kaolin, bentonite, acidic clay, etc.) Talc, diatom, silica, such as mica powder, etc.) Alumina, silica gel, emulsified powder, activated carbon, calcium phosphate, etc. are also used, and these 1 or 2 or more types of mixtures are used. As needed, you may add phosphate ester etc. again. As surfactant used as an electrodeposition agent, an emulsifier, a penetrant, a dispersing agent, a solubilizing agent, etc., For example, soap, sulfuric acid ester of higher alcohol, olefin sulfate, sulfated oil, ethylolamine, higher fatty acid ester, alkynyl sulfone Cargoes, quaternary ammonium salts, alkylene oxide-based activators, anhydrosulfitol-based activators and the like are used. Depending on other needs, casein, gelatin, agar, starch bentonite, aluminum hydroxide or the like may be used or added.

Other types of insecticides (synthetic insecticides, natural insecticides), various acaricides, nematicides, fungicides, herbicides, plant growth regulators, cooperative agents, attractants, repellents, fragrances and the like may be added to these combinations. If desired, various plant-affecting agents, fertilizers and the like can be blended and mixed. The amount of the active ingredient or the combination of the mixture with other kinds of drugs and the mixing ratio thereof may be determined depending on the growth stage of the target plant, the growth situation, the type of disease, the condition of the disease, the time of use or the method of use of the drug, etc. Although different, in general, the effective ingredient (I) 10 ardan tablets, 10 ~ 300g degree may be adjusted. In addition, as the use concentration, the effective ingredient (I) may be in the range of 10 to 000 ppm, and as the use method, the spray may be applied to the crop, the powder, the irrigation, or the seed, and used safely and effectively for the crop. However, any amount, concentration or method of use does not impose any limitation on the present invention.

Such an object (I) of the present invention is formula

In the formula, n has the same meaning as above.

It can be produced by reacting a phosphate halide represented by [wherein X represents a halogen atom such as chlorine or bromine].

In the reaction between the above-mentioned phenols (II) and phosphide halides (III), generally, the reaction is preferably carried out in an organic solvent, and any organic solvent may be used as long as it does not interfere with this reaction. Protic solvents are preferred. For example, aliphatic halogenated hydrocarbons (chloroform, methylene chloride, ethylene chloride, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene, etc.), esters (ethyl acetate, butyl acetate, etc.), kerons (acetone, Methyl ethyl keron, methyl isobutyl ketone, etc.), ethers (diethyl ether, tetrahydrobutane, dioxane, dimethoxyethane, etc.), amides or nitriles (dimethylformamide, N-methylpyrrolidone, acet nitrile, etc.) ), Sulfur-containing compounds (dimethyl sulfoxide, tetramethylene methylene sulfone, hexamethyl phosphate triamide, etc.) and the like can be used alone or in various mixing ratios as two or more mixed solvents. However, if desired, water or alcohols (methanol, ethanol, i-propanol, n-butanol, methyl cellosolve, etc.) may be used, and in some cases, a small amount of water or alcohol may promote the reaction. There is work. The reaction is advantageously carried out in the presence of an acid binder, and as such an acid binder (or deoxidizer), an organic or inorganic base is usually used, but as representative organic bases, for example, triethylamine and tributylamine , Triethylenediamine, 1,4-diazabicyclo [2, 2, 2] octane, 1,8-diazabicyclo [5, 4, 0] -7-undecene, 1, 5-diazabicyclo [4 And tertiary amines such as 3,0] -5-nonene, dimethylaniline, diethylaniline, pyridine, 4-dimethylaminopyridine, and S-clidine are preferable, and the reaction solvent is used by using an excess of these organic bases. You can also combine. As the inorganic salt, for example, oxides, hydroxides, carbonates, bicarbonates or alcoholates of alkali metals or alkali metals can be used. In other cases, basic ion exchange resins may be used. These acid binders may be added in the reaction system, but they may be reacted with phenols (II) in advance, and once made into phenols, they may be reacted with phosphate halide (III) again.

Since this reaction proceeds smoothly slightly in general, it is not necessarily necessary to heat it with sufficient agitation. However, when it is desired to complete the reaction in a short time, heating may be required. The reaction temperature is preferably preferably from room temperature (-10 ° C) to around 100 ° C, but may require a higher temperature. In addition, when exothermicity is remarkable, in order to control the reaction, it may be desirable to cool the temperature to around 10 to -20. In addition, the reaction is usually performed under normal pressure. It may be. The reaction medium does not require additives, but may take several days if desired. The reaction does not require particularly catalytic additives, but if desired, copper powder (such as acetone), potassium iodide (such as acetone, crown ethers (such as acetonitrile), or phase transfer catalysts) A small amount of water, toluene, etc.) may be added to work.

The organophosphate esters of the general formula (I) can be produced most efficiently by the above-described method, but can also be produced by other methods. Some of these outlines are shown below in chemical reactions, for example.

[In the market, n is the same meaning as above, M represents hydrogen atom, alkali metal, ammonium group, etc.]

The above methods (A) to (C) can be carried out according to a known method, for example, JP 49-24656, JP 48-26221, JP 51-20506, JP 52-86, UK Patent No. 1295418. It can be performed according to the description or the like.

The organophosphate ester (I) thus prepared is usually a slightly viscous oily substance having a slight odor, colorless to slightly yellow at room temperature, and is used in the organic solvent of soy flour except water and petroleum aliphatic hydrocarbons. Melt well. Therefore, after completion of the reaction, it is dissolved in an organic solvent which is not mixed with water, washed with dilute alkali carbonate or alkaline hydroxide aqueous solution and water, and dehydrated and concentrated to obtain almost pure or high purity reactive body (I). If desired, it can be purified again by column chromatography or by high vacuum distillation.

In addition, 4-methylthio-2- or 3-methoxy phenols represented by general formula (II) in a raw material compound, for example, a sulfenylating agent suitable for 2- or 3-methoxy phenols (for example, Methyl sulfide, methyl disulfide, methyl sulfoxide, menylsulfenyl halide, methyl thiol sulfonate, etc. may be appropriate catalysts (e.g. halogens, inorganic acids, inorganic and organic acid halides, inorganic and organic acid anhydrides, Lewis acids, inorganic and organic It is obtained easily by making it react in presence of basic acids etc.). Moreover, the melcap group introduced into 4-position (P-position) by the diazotization method etc. can also be easily methylated by the appropriate methylation agent (for example, methyl halide, methyl sulfate ester, methyl sulfonic acid ester, etc.). You can get it.

Furthermore, the corresponding 4-thiocyanate waste phenols [Konishi: Tada, et al., 24,233 (1965)] can also be obtained by reacting alkali hydroxide or alkali cyanide in methanol. In addition, 4-methylsulfinylphenol (n = 1) and 4-methylsulfonylphenol (N = 2) each use a corresponding 4-methylthiophenol (n = 0) as an appropriate oxidizing agent (for example, hydrogen peroxide). , Halogens, inorganic and organic peracids, acetic acid, potassium permanganate, sodium metaperiodate, N-halogenated amides, imides, and the like).

Of the phenols represented by the general formula (II), 4-methylthio-3-methoxyphenol is a compound based on literature and synthesized using the above method. [B.S. Farah & EE, Gilbert: Journal of Organic Chemistry (J. Org. Chem), 28,2807 (1963): Ucay and Hirose: Chemical and Pharm.Britant, 16,202 (1968) ]. However, it is not described in the literature as far as the inventors know other than this. Therefore, a constant is described next about some of the novel phenols newly prepared by any of the above-mentioned methods, or the approximate method.

In addition, the phosphate halide represented by General formula (III) is a compound of literature document [Japanese drama special office 52-86], and the method of other literature documents (AE Lippman: J. Org. Chem, 30). , 3217 (1965).

Example 1

6.81 g (0.04 mol) of 4-methylthio-2-methoxyphenol is dissolved in 100 ml of toluene, followed by 5.06 g (0.05 mol) of triethylamine. In this solution, 8.11 g (0.04 mol) of 0-ethyl-sn-propyl thiophosphate chloride was dissolved in 20 ml of toluene while slowly stirring at room temperature. After a while, triethylamine hydrochloride begins to precipitate and the internal temperature rises slightly above room temperature. After completion of the dropwise addition, the plate is continued for several hours at room temperature. The reaction solution is filtered to remove crystals. The filtrate is washed sequentially with water, 10% aqueous sodium carbonate solution, water, 1N hydrochloric acid, and aqueous saturated sodium chloride solution, and dehydrated with anhydrous sodium sulfate. This toluene solution is filtered through a thin layer of decolorized carbon and the filtrate is concentrated under reduced pressure using a rotary vacuum evaporator. The remaining oily substance is sucked back into the vacuum pulp until it reaches a high amount as a pale yellow oily substance. 0-ethylsn-propyl 0- (4-methylthio-2-methoxyphenyl (phosphothioate (Compound NO. 1) is obtained quantitatively (13.92g). The organophosphate ester thus obtained is already thin layer chromato by chromatography (silica gel / ether) almost a single highly pure enough to indicate a winning spot on, and purified by column chromatography (toluene / chloro form) using a silica gel again. refraction n ₂₀ ^D 1.5519, boiling point: 176 ~ 179 ℃ / 0.2mm , Oral acute toxicity value of the mouse [ddy-SLC] crab 5 weeks old (26 ± 2g) 5 mice]: LD ₅₀ (mg / kg) => 300.

Example 2

5.9 g (0.035 mol) of 4-methylthio-3-methoxyphenol is added to 100 ml of toluene, and 4.55 g (0.45 mol) of triethylamines are added, and it becomes a uniform solution. 7.90 g (0.035) of 0-ethyl sn-propyl thiol phosphate chloride was dissolved in 20 ml of toluene and slowly added dropwise to this solution while stirring at room temperature. When treated in the same manner as in Example 1 below, 0-ethylsn-propyl 0- (4-methylthio-3-methoxyphenyl (phosphorothiolate (Compound Mole No. 2)) was obtained quantitatively as a pale yellow oily substance. (11.87 g) Refractive index n ₂₀ ^D 1.5521. Oral acute toxicity value of mouse [ddy-SLC (5 mice (26 ± 2 g) commonly used): n ₂₀ ^D (mg / kg) = 300.

Example 3

The structures, properties, and physical constants of the compounds Nos. (3) and (4) of the present invention prepared in the same manner as in Example 1 are as follows.

Compound no. CH ₃ S (O) n Phase Refractive Index N ₂₀ ^D

(3) CH ₃ SO pale yellow oil 1.5394

(4) CH ₃ SO ₂ Pale yellow oil 1.5290

Example 4

Powder made by mixing 2 parts of compound (1) and 98 parts of talc.

Example 5

25 parts of compounds (2), Tween 20 (manufactured by Kao Atlas) 20, liquid solution of 55 parts of acetone

Example 6

An oil agent obtained by mixing 50 parts of compound (2), 25 parts of polyoxyethylene diphenyl ether, and 25 parts of xylene.

Example 7

A hydrating agent obtained by mixing and grinding 20 parts of compound (2), 4 parts of sodium lignin sulfonate, 4 parts of pulleyoxyethylene alkylaryl ether, 3 parts of white carbon, and 69 parts of clay.

Example 8

Granules granulated by adding a small amount of water to a mixture of 5 parts of the compound (1) and 95 parts of bentonite.

Reference Example 1

Preparation of 4-methylthio-2-methoxyphenol

25 g (0.2 mole) of 2-methoxyphenol and 16 g (0.2 mole) of dimethyl sulfoxide are mixed, kept at 10 DEG C or lower under ice cooling, and dried with stirring to saturate hydrochloric acid gas. After that, stirring was continued at room temperature for another 1 hour, and then a small amount of methanol was added to the viscous reaction solution to precipitate the precipitated white crystals. Wash with ether and dry under reduced pressure over potassium hydroxide in a drying vessel.

Quantity 34g (76%), Melting point 135 ° C (decomposition)

32.5 g (0.15 mole) of this crystal is placed in a Klygen flask and heated to 120 to 130 ° C. to start decomposition, generating methyl chloride gas. When the oily substance remaining after gas generation stops is distilled and refine | purified under reduced pressure, the desired phenol is obtained as a slightly colored viscous oil.

Yield 22.5 g (88%), boiling point 124-126 degreeC / 4mmHg.

When a part of the crystallized solid is taken by standing and recrystallized from gray methanol, colorless needles having a melting point of 50 ° C are obtained.

In addition, this crystal is a compound obtained by selectively methylating 4-mercapto-2-methoxyphenol (bp 100 ° C / 4mmHg) obtained by the diazotization method selectively by a melcapto group by the dimethyl sulfate (boiling point 124-126). ° C / 4mmHg).

Reference Example 2

Preparation of 4-methylthio-3-methoxyphenol

14.25 g (0.08 mol) of 4-thiocyanate-3-methoxyphenol is dissolved in 300 ml of methanol, and 7.84 g (0.16 mol) of sodium cyanide is added little by little while stirring under ice cooling. After the addition is finished, stirring is continued as it is. After standing at room temperature overnight, reflux for several hours to boil. A small amount of bleached carbon is added to filter and the filtrate is concentrated under reduced pressure using a rotary vacuum evaporator. The remaining viscous oil is dissolved in a small amount of water, converted to hydrochloric acid, and extracted three times with benzene. The benzene solution is washed with water, dehydrated with anhydrous sodium sulfate, and concentrated to dryness under reduced pressure with a rotary vacuum evaporator. The remaining crude crystals are recrystallized from a mixed solvent of cyclohexane and benzene. Yield 9.60 g (70%). When this crystal is recrystallized using decolored carbon again in the same solvent, colorless needle crystal of 96-98 degreeC of melting | fusing point is obtained. In addition, this crystal | crystallization corresponded with the volume (melting point 97-99 degreeC) obtained when the same method is implemented using 3-methoxyphenol instead of 2-methoxyphenol in the reference example 1.

[Test Example]

Target compounds Nos. (1) to (10) and the following known compounds having a similar structure (a), (b), (c) and (d)

Iso 48-26221 Compound No. One)

Insecticidal effect on the locust layer, moth, cabbage chestnut moth, and spotty of ladybug were tested (repeated twice) by the following method, respectively.

Test method for the wild stratum

다께다야꾸힝고오교오 가부시기가이샤 제3000배 첨가)로 희석한 100ppm의 약액 20ml를 플라스틱 컵으로 수경한 대두의 실생묘(발아후 10일에 분무실내에서 분무기(분출압력 1kg/㎠))를 사용해서 살포하였다. 살포후의 대두실생묘는 온실내에 보관하였다. 살포 6일후에 대두의 본잎 2메를 잘라서, 각각 한장씩 플라스틱컵(직경 6cm, 깊이 4cm) 속에넣어, 야도층의 2령유충 10마리를 방사하여, 방충후 컵을 실내(25℃)에 두고, 48시간후의 사망층수를 조사하였다.Each prepared compound was emulsified in the formulation of Example 6, and water (electrode dye

Fresh seedlings of soybean seeded with 20 ml of 100 ppm chemical solution diluted with Yada Hingyo Kyokyo Co., Ltd. Sprayed. Soybean seedlings after spraying were stored in the greenhouse. After 6 days of spraying, 2 pieces of main leaves of soybeans are cut and placed into a plastic cup (6 cm in diameter and 4 cm in depth), each 10 larvae of the horticultural layer are radiated. The number of deaths after 48 hours was examined.

Test method for moths

20 ml of 200 ppm of the chemical solution adjusted to the same prescription as for the worm was sprayed on the radish (20 days after germination) by the same spraying method as for the urea layer.

After 1 day of spraying, 2 pieces of radish were cut and put into a plastic cup, one by one, 10 10 3 larvae of moths were spun off, and after the insect repellent, the cup was placed indoors (25 ° C) and examined for death after 48 hours. It was.

Test method for Chinese cabbage chestnut moth

Each test compound was sprayed on the soybean seedlings in the same concentration (100 ppm) as in the case of wild worms. After 1 day of spraying, two pieces of main leaves of soybeans are cut out, and each one is put in a plastic cup, and 10 three-larvae larvae of Chinese cabbage chestnut moth are discharged. It was.

Test method for spotty ladybug.

, 5000배 첨가)라 희석한 500ppm의 약액속에 감자의 토막을 10초간 침지하여, 풍건후 유리접시(직경9cm)에 넣고, 점백이 무당벌레의 3령유충 10마리를 방사하였다. 방충후 접시를 실내(25℃)에 두고 24시간후의 사망충수를 조사하였다.Each test compound was prepared as a liquid according to the formulation of Example 5.

The potato chips were immersed in a 500 ppm diluted chemical solution for 10 seconds, and then placed in a glass dish (9 cm in diameter) after air drying, and 10 larvae of ladybugs were spun off. After insect repellent, the plate was placed indoors (25 ° C.) and the number of deaths after 24 hours was examined.

Where test results are

The survival rate (%) was calculated | required by the following, and it was put together in the following table.

Claims (1)

Phenols and cations represented by [wherein n represents 0, 1 or 2]

Wherein X represents a halogen atom, wherein the phosphate halide is reacted

The manufacturing method of the organophosphate ester represented by [wherein n represents the same meaning as mentioned above].