JPH0443894B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing a 2-arylethyl ether derivative or a thioether derivative. For more details, please refer to the general formula [] [In the formula, Ar is a phenyl group or a halogen atom,
Represents a phenyl group or naphthyl group substituted with a lower alkyl group, lower alkoxy group, lower haloalkyl group, lower alloalkoxy group, lower alkylthio group or methylenedioxy group, and X ₁ and X ₂ represent a hydrogen atom or a halogen atom. They may be the same or different. Y represents an oxygen atom or a sulfur atom,
Z represents a nitrogen atom or a -CH= group, and R ₁ and R ₂ represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group] and dihalocarbene, dimethylcarbene or tetrahaloethylene. By reacting, the general formula [] [In the formula, Ar, X ₁ , X ₂ , Y, Z, R ₁ and R ₂ all represent the above meanings, and X ₃ and X ₄ represent a hydrogen atom, a halogen atom and a methyl group, and may be the same or different. You can leave it there. n represents 1 or 2]. The 2-arylethyl ether derivative or thioether derivative represented by the general formula [] is effective as a low-toxicity insecticide or acaricide. The compound represented by the general formula [] is a starting material for this production method and is a new compound. The method for producing this compound will be described in detail as follows. (X ₈ represents a chlorine atom or a bromine atom) An example manufacturing route is shown in the formula above. That is, an α-methylstyrene derivative is subjected to an addition reaction with chlorine or bromine to form [] and []. This reaction is usually carried out in an inert solvent, such as dichloromethane, chloroform,
Carbon tetrachloride, dichloroethane, chlorobenzene,
A halogenated hydrocarbon solvent such as dichlorobenzene is preferred. The reaction temperature is -100°C to 100°C, preferably -50°C to 50°C. Then a mixture of [] and [] or [],
[] General formula for each alone [] [In the formula, Z, R ₁ and R ₂ each represent the above-mentioned meanings, and the group B represents a Y-M group (Y represents an oxygen atom or a sulfur atom, and M represents a hydrogen atom)] Compound [] can be obtained by reacting alcohol or thiol with alcohol or thiol in a suitable solvent in the presence of a base at room temperature or under heating. The base mentioned here includes alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal oxide, alkali metal carbonate, sodium amide, alkali metal hydride, triethylamine, and the like. Examples of solvents include water, aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as hexane, heptane, and petroleum benzyl, halogenated hydrocarbons such as chloroform and dichloromethane, dimethylformamide, and dimethylsulfoxide. , sulfolane, aprotic polar solvents such as 1,3-dimethyl-2-imidazolidinone, ethers such as diisopropyl ether, diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, and dioxane, and nitriles such as acetonitrile and propionitrile. You can use ``class'', etc. Further, if necessary, the target compound [V] can be obtained in a good yield by using a phase transfer catalyst such as tetra-n-butylammonium bromide or triethylbenzyl chloride as a catalyst. Above, we have described the production method when both X ₁ and _{X 2 are hydrogen} atoms in the general formula []. The method for producing the general formula [] when both ₁ and X ₂ are halogen atoms is shown in the reaction route below. (X ₁ and X ₂ represent halogen atoms) Next, the general formula [] [wherein, Ar, X ₁ , X ₂ , Y,
Z, R ₁ and R ₂ each have the above meanings]
By reacting the compound represented by dihalocarbene, dimethylcarbene or tetrahaloethylene, the compound represented by the general formula [] [wherein Ar, X ₁ , X ₂ , X ₃ , X ₄ ,
Examples of production routes for the _production of 2-arylethyl ether derivatives and thioether derivatives represented by the following formulas are shown _below . The group CX ₃ X ₄ can be produced by any of the following reactions. (1) When X ₃ = Cl and X ₄ = F, Cl, Br, use appropriate haloform HC(X ₃ ) ₂ X ₄ or HCX ₃
(X ₄ ) ₂ is reacted with an alkali in the presence of a phase transfer catalyst such as triethylbenzylammonium chloride. (Example) HCCl ₃ −→: CCl ₂ HCCl ₂ F−→: CClF HCBr ₂ Cl−→: CBrCl (2) When X ₃ = X ₄ = F or Cl, respectively
From CF ₂ ClCO ₂ Na or CCl ₃ CO ₂ Na (3) If X ₃ = X ₄ = CH ₃ References Chem.Ber., 111 , 2206 (1978) In addition to dimethylcarbene

The same purpose can be achieved with [Formula]. Reference Tetrahedron Letters, 3911 (1976) An example of a route for producing a compound represented by the general formula [] by reacting the general formula [] with tetrahaloethylene is shown below. The above reaction is preferably carried out in an inert solvent at a temperature of 100°C to 300°C, more preferably 150°C to 250°C. The reaction is preferably carried out under pressure in an autoclave. Inert solvents include benzene, toluene, xylene,
Hydrocarbon solvents such as heptane and octane are preferred. Further, as the tetrahaloethylene, tetrafluoroethylene is preferable. In the case of tetrafluoroethylene, it is also desirable to add limonene as a stabilizer if necessary. Next, specific examples of novel 2-arylethyl ether derivatives and thioether derivatives represented by the general formula [] are shown in Table 1, but it goes without saying that the compounds represented by the general formula [] are not limited to these. It is.

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[Table] Next, the method for producing 2-arylethyl ether derivatives and thioether derivatives of the present invention will be explained in detail with reference to synthetic examples below. Synthesis Example 1 (Synthesis of Compound 3) Synthesis of 3-phexybenzyl 1-(4-methoxyphenyl)-2,2-dichloro-1-cyclopropyl methyl ether Synthesis was performed according to the following sequence. (1) 3.4 g of 4-methoxy-α-methylstyrene was dissolved in 50 ml of carbon tetrachloride, and 1 ml of bromine was added dropwise at a temperature of 0 to 10°C. After the dropwise addition was completed, the solution was washed with a dilute aqueous alkali solution and then with water, and then dried. Distill the carbon under the tetrachloride under reduced pressure to obtain 6.2 g of crude dipromide.
I got it. (2) 5.8g obtained in (1) above, 4.4g of 50% NaOH,
Dissolve 5.0 g of 3-phenoxybenzyl alcohol in 100 ml of dimethyl sulfoxide and heat at 100℃.
Stirred for 3.0 hours. After cooling to room temperature, it was poured into water and extracted with hexane. The hexane layer was washed with water and dried. 9.0 g of the residue obtained by distilling off the solvent under reduced pressure was purified by column chromatography (180 g of silica gel, developing solvent: benzene-hexane (2:3)) to obtain 3-
4.2 g of phenoxybenzyl 2-(4-methoxyphenyl)-2-propenyl ether was obtained. mp33.5~35.0℃ ν ^KBr _nax 1615, 1590, 1520, 1495, 1450, 1260,
1220, 1190, 1080, 1040, 910, 840, 700cm
^-1 δCCI ₄ TMS (ppm) 3.64 (s, 3H), 4.27 (s,
2H), 4.41 (s, 2H) 5.27 (s, 1H), 5.36
(s, 1H), 6.62-7.40 (m, 13H) (3) 3-phenoxybenzyl 2 synthesized in (2) above
-(4-Methoxyphenyl)-2-propenyl ether 2.0g in chloroform 0.85g, 50%
The mixture was stirred at 40° C. for 2.0 hours with 20 g of NaOH and 0.3 g of triethylbenzylammonium chloride. Water was added to the reaction solution, and the mixture was extracted with benzene. After washing the benzene layer with water and drying, benzene was distilled off under reduced pressure to obtain 2.6 g of a residue. The desired 3-phenoxybenzyl 1-(4
-methoxyphenyl)-2,2-dichloro-1-
1.4 g of cyclopropyl methyl ether was obtained. n ²⁰ _D 1.5914 ν ^Neat _nax 1620, 1590, 1520, 1495, 1455, 1370,
1255, 1220, 1185, 1130, 1040, 840, 775,
700cm ^-1 δCCl ₄ TMS (ppm) 1.63 to 1.88 (m, 2H), 3.72
(s, 5H), 4.35 (s, 2H), 6.65-7.40 (m,
13H) C ₂₄ H ₂₂ Cl ₂ O ₃ Calculated value (%) C 67.14 H 5.16 Cl 16.52 Actual value (%) C 67.20 H 5.14 Cl 16.45 Synthesis Example 2 (Synthesis of Compound 12) 3-Phenoxybenzyl 1- (4-methoxyphenyl)-2,2,3,3,-tetrafluoro-1-
Synthesis of cyclobutyl methyl ether 3-Phenoxybenzyl 2-(4-ethoxyphenyl)-2 in a 200cc stainless steel autoclave
- 2.0 g of propenyl ether, 20 ml of toluene, and 0.05 g of limonene were charged, and then tetrafluoroethylene gas was charged at room temperature until it reached 4 to 5 kg/cm ² G. The mixture was kept at 180° C. for 8.0 hours with stirring, then cooled to room temperature, and the solvent was distilled off under reduced pressure to obtain 2.6 g of a residue. Column chromatography (silica gel 60
g, developing solvent: benzene-hexane (2:1))
The target 3-phenoxybenzyl 1-
(4-Methoxyphenyl)-2,2,3,3-tetrafluoro-1-cyclobutyl methyl ether
I got 1.8g. n ²⁰ _D 1.5490 ν ^Neat _nax 1580, 1485, 1345, 1255, 1210, 1165,
1140, 1100, 1085, 690 cm ^-1 δCCl ₄ TMS (ppm) 2.50-3.00 m, 2H), 3.70 (s,
5H), 4.28 (s, 2H), 6.60-7.40 (m, 13H) C ₂₅ H ₂₂ F ₄ O ₃ Calculated value (%) C 67.26 H 4.97 F 17.02 Actual value (%) C 67.31 H 4.92 F 17.14 Synthesis implementation Example 3 (Synthesis of Compound 16) Synthesis of 3-phenoxybenzyl 1-(4-methoxyphenyl)-2,2-dibromocyclopropyl methyl ether 3-Phenoxybenzyl 2-(4-methoxyphenyl) Enyl-2-propenyl ether 2.5g, bromoform 5.0g, triethylbenzylammonium bromide 0.2g, methylene chloride 2ml, 50
One drop of ethyl alcohol was added as a catalyst to a mixture of 20 g of NaOH and stirred at room temperature for 3.5 hours. After adding water, the mixture was extracted with methylene chloride. After washing with water and drying, the solvent is distilled off under reduced pressure to leave a residue.
4.7g was obtained. Column chromatography (wako)
Gel (100 g, developing solvent: benzene) to obtain 2.4 g of the desired 3-phenoxybenzyl 1-(4-methoxyphenyl)-2.2-dibromocyclopropyl ether. n ²⁰ _D 1.6100 ν ^Neat _nax 1610, 1580, 1515, 1485, 1440, 1250,
1215, 1180, 1115, 1035, 830, 690cm ^-1 δCCl ₄ TMS (ppm) 1.84 (d, J _AB = 8.0Hz, 1H) 1.98 (d, JAB = 8.0Hz, 1H) 〓 AB type 3.60 ~ 3.84 (m , 5H), 4.33 (s, 2H), 6.64-7.36 (m, 13H) C ₂₄ H ₂₂ Br ₂ O ₃ Calculated value (%) C 55.62 H 4.28 Br 30.84 Actual value (%) C 55.28 H 4.26 Br 31.05 Synthesis Example 4 (Synthesis of Compound 7) Synthesis of 3-phenoxybenzyl 1-(4-chlorophenyl)-2,2-dichloro-1-cyclopropyl methyl ether Synthesis was performed in the following order. (1) 10 g of 4-chloro-α-methylstyrene was dissolved in 50 ml of carbon tetrachloride, and 10.5 g of bromine was added dropwise at 3 to 7°C. After dropping, wash with a dilute alkali aqueous solution and then with water, dry, and evaporate the solvent under reduced pressure to obtain crude dipromide.
Obtained 22g. (2) 3-phenoxybenzyl alcohol 15g, 50
%NaOH 14g to 120ml dimethyl sulfoxide
Dipromide synthesized in (1) above
20g/30ml dimethyl sulfoxide solution 100℃30
The mixture was added dropwise within minutes, and stirring was continued for an additional hour at the same temperature. The reaction solution was poured into ice water and extracted with hexane. The hexane layer was washed with water, dried, and the solvent was distilled off under reduced pressure to obtain 27 g of a residue. It was purified by column chromatography (450 g of silica gel, developing solvent: benzene-hexane (2:3)) to obtain 7.6 g of the desired 3-phenoxybenzyl 2-(4-chlorophenyl)-2-propenyl ether. n ²⁰ _D 1.6048 ν ^Neat _nax 1595, 1500, 1460, 1265, 1225, 1105,
1020, 915, 840, 780, 700 cm ^-1 δCCl ⁴ TMS (ppm) 4.23 (s, 2H), 4.40 (s,
2H), 5.25 (s, 1H), 5.41 (s, 1H), 6.75~
74.0 (m, 13H), (3) 3-phenoxybenzyl 2 synthesized in (2) above
-(4-chloro-phenyl)-2-propenyl ether 2.1 g, chloroform 0.8 g, 50%
A mixture of 12 ml of NaOH and 0.3 g of triethylbenzylammonium chloride was stirred at 40°C for 2.0 hours. Water was added to the reaction solution, and the mixture was extracted with benzene. The benzene layer was washed with water, dried, and the solvent was distilled off under reduced pressure to obtain 2.8 g of a residue. Column chromatography (60 g of silica gel, developing solvent: benzene)
Purified with hexane (2:1)), 3-phenoxybenzyl 1-(4-chlorophenyl)-2,
2-dichloro-1-cyclopropyl methyl ether
0.9 g of tel was obtained. n ²⁰ _D 1.5952 ν ^Neat _nax 1590, 1495, 1445, 1365, 1260, 1220,
1095, 1020, 835, 760, 695 cm ^-1 δCCl4 TMS (ppm) 1.87-19.0 (m, 2H), 3.69 (s,
2H), 4.35 (s, 2H), 6.68-7.40 (m, 13H), C ₂₃ H ₁₉ Cl ₃ O ₂ Calculated value (%) C 63.69 H 4.42 Cl 25.52 Actual value (%) C 63.81 H 4.39 CI 25.48 Synthesis Example 5 (Synthesis of compound 18) 3-phenoxybenzyl 1-phenyl-2,2-
Synthesis of dichloro-1-cyclopropyl methyl ether Synthesis was performed according to the following sequence. (1) 24g of α-methylstyrene in dichloromethane
In addition to 150 ml, chlorine gas was blown in at 0 to 10°C. The end point of the reaction was defined as the point at which the reaction solution turned pale yellow. Next, it was washed with a dilute alkali aqueous solution and then with water, and then dried. The solvent was distilled off under reduced pressure to obtain 38.2 g of crude dichloride. (2) Add 15.0 g of 3-phenoxybenzyl alcohol and 15.6 g of 50% NaOH to 200 ml of sulfolane,
Dichloride synthesized in (1) above at a temperature of 120℃
Drop 18.4g/30ml of sulfolane over 1.0 hours,
Stirring was further continued at the same temperature for 1.5 hours. After cooling to room temperature, it was poured into water and extracted with hexane. The obtained hexane solution was washed with water, dried, and the solvent was distilled off under reduced pressure to obtain 23.1 g of a residue. It was purified by column chromatography (460 g of silica gel, developing solvent: benzene-hexane (2:1)) to obtain 13.5 g of 3-phenoxybenzyl 2-phenyl-2-propenyl ether. n ²⁰ _D 1.6002 ν ^Neat _nax 1580, 1485, 1460, 1250, 1210, 1070, 755,
685cm ^-1 δCCl4 TMS (ppm) 4.31 (s, 2H), 4.51 (s, 2H),
5.31 (s, 1H), 5.48 (s, 1H), 6.80~7.50
(m, 14H) (3) Add 3.0 g of 3-phenoxy-benzyl 2-phenyl-2-propenyl ether synthesized in (2) above to 20 g of 50% NaOH, and 0.5 g of triethylbenzylammonium chloride as a catalyst.
Add 4.8 g of chloroform dropwise over 30 minutes at ℃.
Stirring was continued for an additional 30 minutes at the same temperature. Water was added and extracted with benzene. The resulting benzene solution was washed with water, dried, and the solvent was distilled off under reduced pressure to obtain 3.6 g of a residue.
Column chromatography (silica gel 70g,
The product was purified using benzene-hexane (2:1) as a developing solvent to obtain 3.4 g of the desired 3-phenoxybenzyl-1-phenyl-2,2-dichloro-1-cyclopropylmethyl-tel. n ²⁰ _D 1.5918 ν ^Neat _Max 1590, 1495, 1455, 1260, 1220, 1130,
1110, 1090, 785, 765, 700cm ^-1 δCCl4 TMS (ppm) 1.73 (d, J _AB = 8.0Hz, 1H) 1.86 (d, J _AB = 8.0Hz, 1H) 〓 AB tipe 3.67 (d, J _AB = 11.0Hz, 1H). 3.81 (d, J _AB = 11.0Hz, 1H) = AB tipe 4.33 (s, 2H) 6.7-7.4 (m, 14H) Next, the compound that can be produced by the method of the present invention is
Although some examples of formulations for use as acaricides are shown below, the present invention is not limited thereto. All "parts" indicate parts by weight. Formulation Example 1 Compounds that can be produced by the method of the present invention Table 1, 20 parts of compound numbers 1 to 20 (the same applies hereinafter), and each of them, Solbol 355TLL (a mixture of an emulsifier, a nonionic surfactant, and a special anionic surfactant) Ten
1 part and 70 parts of xylene, and stir well to dissolve and form an emulsion. Formulation Example 2 1 part of the compound produced by the method of the present invention is dissolved in 10 parts of acetone, 99 parts of clay for powders are added, and the mixture is stirred and mixed to evaporate the acetone to form a powder. Formulation Example 3 5 parts of a surfactant are added to 20 parts of the compound produced by the method of the present invention, and after mixing, 75 parts of diatomaceous earth is added and mixed with stirring in a Raikai machine to prepare a wettable powder. Formulation Example 4 Add 2 parts of meta-tolyl-methyl carbamate to 0.5 parts of the compound that can be produced by the method of the present invention, further add 0.3 parts of PAP (isopropyl acid phosphate) to each, dissolve in 10 parts of acetone, and prepare powder clay. Add 97.2 parts and mix with stirring to evaporate the acetone and form a powder. Formulation Example 5 0.5 parts of the compound that can be produced by the method of the present invention was added with 2 parts of Offnatsu (registered trade name of Mitsui Toatsu Chemical),
Furthermore, add 0.3 parts of PAP (mentioned above), dissolve it in 10 parts of acetone, add 97.2 parts of powder clay, stir and mix, and evaporate the acetone to form a powder. Formulation Example 6 S-
Add 0.5 part of 421 (bis(2,3,3,3-tetrachloropropyl)ether) and dissolve in 99.4 parts of white kerosene to obtain an oil agent. Formulation Example 7 Mix and dissolve 0.4 parts of the compound that can be produced by the method of the present invention, 2.0 parts of piperonyl butoxide, 6 parts of xylol, and 7.6 parts of deodorized kerosene, fill it into an aerosol container, and attach the valve part. If 84 parts of propellant (oxidized petroleum gas) is pressurized and filled through the tank, it becomes an aerosol. Formulation Example 8 1 part of the compound that can be produced by the method of the present invention, 3 parts of Ofnatsu (mentioned above), 2 parts of Celogen 7A (Daiichi Kogyo Seiyaku brand name), 2 parts of Sunextract (Sanyo Kokusaku Valve product)
Add 92 parts of clay to the mixture, mix with stirring, add water, granulate, and then size to obtain granules. When applying the compound that can be produced by the method of the present invention, the application amount is generally per 10a of the active ingredient.
The amount is 500g to 1g, preferably 100g to 5g, and more preferably 50g to 10g. Next, in order to clarify that the compound that can be produced by the method of the present invention has excellent insecticidal and acaricidal efficacy, and has low toxicity to warm-blooded animals and fish, the following will be explained. A test example is shown. Test Example 1 Effect on Spodoptera spp. Emulsions of each test compound prepared according to Formulation Example 1 are diluted with water to give concentrations of 100 and 20 ppm. Sweet potato leaves were immersed in each chemical solution for 10 seconds, air-dried, placed in 10 cm plastic cups, 10 2nd instar larvae of Spodoptera japonica were released per cup, and the cups were covered with lids and allowed to stand in a constant temperature room at 25°C. After 72 hours of treatment, the number of live and dead insects was investigated, and the mortality rate was calculated. The test is 3
The test was repeated several times, and the results are shown in Table 1 as the average value.

[Table] Test Example 2 Effect on black leafhopper Rice seedlings (2 to 3 true leaves) were grown hydroponically in 5 cm pots, and each test chemical prepared in the same manner as Test Example 1 was diluted with water to 200 ppm and 20 ppm. 3 ml/pot was applied to each pot using a sprayer. After air-drying, the seedlings were covered with a wire mesh cylinder, 20 female adult leafhoppers were released per pot, and left in a thermostatic chamber at 25°C. After 48 hours of treatment, the number of live and dead insects was investigated, and the mortality rate was calculated. The results are shown in Table 2 as the average value of three runs.

[Table] Test Example 3 Effect on house fly larvae The emulsion of each test compound prepared in Formulation Example 1 was diluted with water to give a concentration of 50 ppm. 3 ml/shear of each chemical solution was applied to a glass shear with a diameter of 9 cm and a height of 6 cm, and final instar house fly larvae were released.
(20 cows/sheer) The upper part of the shear was covered with nylon gauze and placed in a thermostat at 25°C. After 24 hours, the number of live and dead insects was examined. The results are shown in Table 3.

[Table] Test Example 4 Effect on two-spotted spider mites Potted green beans (two true leaves) were inoculated with ten adult two-spotted spider mites. After 2 days, dilute the wettable powder prepared according to Formulation Example 3 with water to adjust the concentration of the test drug.
It was set to 500ppm. This was thoroughly sprayed with a 5 ml sprayer per pot, and after air-drying, the pots were left in a glass room.
The number of adult larvae was investigated 10 days after the drug treatment, and the degree of increase was investigated. The results are shown in Table 4 as the average density of the three series.

[Table] Test Example 5 Toxicity test on mice A predetermined amount of the drug substance (0.2 ml/10 g body weight) dissolved or suspended in corn oil was orally administered to male mice (body weight 19-23 g), and the number of deaths was investigated after 7 days. did. Results: All of the compounds produced by the method of the present invention had an LD-50 value of 300 mg/Kg or more. Test example 6 Fish toxicity Fill a water tank with width 60cm, length 30cm, and height 40cm.
Ten mature carp fish with a body length of approximately 5 cm were released, and after acclimatization, each test chemical was added to 1 ppm.
After some time, we checked the number of dead and alive fish to see the effect on the fish. Results: The TLm48 value (drug concentration at which half of the test subjects died within 48 hours) of all the compounds that could be produced by the method of the present invention was 1 ppm or more.

Claims (1)

[Claims] 1. General formula [] [In the formula, Ar is a phenyl group or a halogen atom,
Represents a phenyl group or naphthyl group substituted with a lower alkyl group, lower alkoxy group, lower haloalkyl group, lower alloalkoxy group, lower alkylthio group or methylenedioxy group, and X ₁ and X ₂ represent a hydrogen atom or a halogen atom. They may be the same or different. Y represents an oxygen atom or a sulfur atom, and Z
represents a nitrogen atom or a -CH= group, and R ₁ and R ₂ represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group] and dihalocarbene, dimethylcarbene or tetrahaloethylene are reacted. Let, general formula [] [In the formula, Ar, X ₁ , X ₂ , Y, Z, R ₁ and R ₂ all represent the above meanings, and X ₃ and X ₄ represent a hydrogen atom, a halogen atom and a methyl group, and may be the same or different. You can leave it there. n represents 1 or 2] A method for producing a 2-arylethyl ether derivative or a thioether derivative. 2 Claim 1 characterized in that in the general formula [], both X ₁ and X ₂ are hydrogen atoms.
Manufacturing method described in section.