JPH0528214B2 - - Google Patents

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing benzylpropyl ethers, and more specifically, the present invention relates to a method for producing benzylpropyl ethers, and more specifically, a compound of the general formula (I) which has extremely high insecticidal activity and is useful as an insecticide with low fish toxicity. [In the formula, R ₁ and R ₂ are hydrogen atoms, chlorine atoms, or bromine atoms, and at least one is a chlorine atom,
Or a bromine atom. Further, R is a lower alkyl group, and R ₃ and R ₄ are hydrogen atoms or fluorine atoms. ] When producing the benzylpropyl ether derivative represented by the general formula () [In the formula (), R, R ₁ and R ₂ have the same meanings as in the above general formula (I), and X represents a halogen atom. ] and the general formula () [In formula (), R ₃ and R ₄ are the above general formula (I)
and R ₅ represents a hydrogen atom or a lower alkyl group. ] 3-phenoxybenzyl esters shown in an aprotic polar solvent in the presence of a base,
The present invention relates to a method for producing a benzylpropyl ether derivative, which is characterized by a reaction.

[Conventional technology]

Pesticides have played an extremely important role in improving agricultural production, and the appearance of synthetic organic pesticides has completely changed the food situation for humankind, and has also brought great benefits in terms of epidemic prevention, such as preventing infectious diseases transmitted by insects. .

However, organochlorine insecticides DDT and BHC
The amount of pesticides used is limited because they remain in the environment for a long time after use, and organophosphorus insecticides and carbamate pesticides that have replaced them are widely used. Various pests have developed resistance to these insecticides.

In recent years, against this background, synthetic pyrethroid insecticides have been attracting attention because of their excellent insecticidal power, their outstanding effectiveness against pests resistant to organic phosphorus or carbamate agents, and their relatively low toxicity to humans and livestock. I came flying. However, the disadvantage of this synthetic pyrethroid insecticide is that it is highly toxic to fish, which limits its range of use. Furthermore, they are more expensive than conventionally developed insecticides.

Recently, benzylpropyl ether derivatives represented by the general formula (I) have extremely high insecticidal and acaricidal activity, and are excellent in immediate effect and residual effect.
It has been found to have low toxicity not only to humans and livestock, but also to fish, and has been provided as a pest control agent (Japanese Patent Application Laid-Open No. 154427, 1983, 57-64632, 57-
72928, 58-32840).

The above publication also describes a method for producing the compound of formula (I), including a method for producing the desired product by reacting neophyl alcohols and 3-phenoxybenzyl halides represented by the following reaction formula (I), and A method is disclosed in which a desired product is obtained by reacting a neophyl halide represented by 2 with 3-phenoxybenzyl alcohol. However, in the method shown in Reaction Formula 1, the production of neophyl alcohols is complicated and cannot be carried out in a factory, and in the method shown in Reaction Formula 2, 3-phenoxybenzyl alcohol is expensive. be.

[In the formula, R ₆ and R ₇ are the same or different hydrogen atoms, halogen atoms, cyano groups, nitro groups, or optionally substituted lower alkyl groups, alkenyl groups, lower alkoxy groups, acyloxy groups, lower alkylthio groups, Represents a lower acyl group or alkoxycarbonyl group, R ₃ and R ₄ represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, m and n each represent an integer of 0 to 4, and m + n represents 0 to 4. , X, and Y represent halogen. ] Furthermore, among the compounds of formula () disclosed in the above publication, the present inventors discovered a compound in which either R ₆ or R ₇ in formula () is a lower alkoxy group at the 4-position, i.e., a lower alkoxy group at the 4-position. It was discovered that a 3-phenoxybenzyl ether compound having a neophyl group substituted with a lower alkoxy group has a particularly large insecticidal effect among these compounds, and as a method for producing it, the formula () [In formula (), Y ₁ and Y ₂ are a hydrogen atom, a chlorine atom, or a bromine atom, and at least one of Y ₁ and Y ₂ is a chlorine atom or a bromine atom. R is a lower alkyl group, and X is a halogen atom. ] 4-alkoxyneophyl halides represented by the formula () [In formula (), X ₁ and X ₂ are hydrogen atoms or fluorine atoms. ] 3-phenoxybenzyl alcohols represented by the formula () are subjected to a condensation reaction. [In formula (), Y ₁ and Y ₂ are hydrogen atoms, chlorine atoms,
or a bromine atom, and at least one of Y ₁ and Y ₂ is a chlorine atom or a bromine atom. Further, R is a lower alkyl group, and X ₁ and X ₂ are hydrogen atoms or fluorine atoms. ] We have previously applied for a method for producing 3-phenoxybenzyl 2-(4-alkoxyhalogenophenyl)-2-methylpropyl ethers (Japanese Patent Application Laid-Open No.
59−88440).

However, when the condensation reaction is carried out by the method shown in Reaction Formula 2 above, 3-phenoxybenzyl alcohols are relatively easily oxidized by heating during the condensation reaction, so neophyl halides and 3-phenol The condensation yield with enoxybenzyl alcohols was also unsatisfactory, and it could not necessarily be said to be an advantageous industrial production method, especially as a method for producing the benzylpropyl ether derivative represented by the formula ().

[Means to solve the problem]

As a result of various studies on the synthesis method of the benzylpropyl ether derivative represented by the general formula (I), the present inventors discovered that the neophilic halides represented by the general formula () and the 3-fluoryl halides represented by the general formula () It was discovered that a benzylpropyl ether derivative represented by general formula (I) can be obtained in good yield by reacting enoxybenzyl esters in an aprotic polar solvent in the presence of a base, and the present invention was completed. did.

That is, the present invention provides general formula (I) [In the formula, R ₁ and R ₂ are hydrogen atoms, chlorine atoms, or bromine atoms, and at least one is a chlorine atom,
Or a bromine atom. Further, R is a lower alkyl group, and R ₃ and R ₄ are hydrogen atoms or fluorine atoms. ] When producing the benzylpropyl ether derivative represented by the general formula () [In formula (), R, R ₁ and R ₂ are the above general formula (I)
, and X represents a halogen atom. ]
Neophyl halides shown by and the general formula () [In formula (), R ₃ and R ₄ are the above general formula (I)
and R ₅ represents a hydrogen atom or a lower alkyl group. ] This is a method for producing a benzylpropyl ether derivative, which is characterized by reacting 3-phenoxybenzyl esters represented by the following in an aprotic polar solvent in the presence of a base.

The benzylpropyl ether derivative that can be produced by the method of the present invention has the general formula (I) Specifically, R is a lower alkyl group such as methyl, ethyl, propyl, etc., R ₁ and R ₂ are a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, R ₃ and R ₄ examples include hydrogen atoms and fluorine atoms.

In addition, 3-phenoxybenzyl esters used as raw materials in the method of the present invention, general formula () [In formula (), R ₃ , R ₄ and R ₅ are the same as above]
can be produced by a known method from 3-phenoxybenzyl halides obtained by halogenating 3-phenoxytoluenes and alkali metal salts of the corresponding carboxylic acids. It can also be obtained by esterifying 3-phenoxybenzyl alcohols, which are known as alcohol components of synthetic pyrethroids, by a known method.

In the method of the present invention, neophyl halides,
The ratio of 3-phenoxybenzyl esters used is 0.1 to 5 molar ratio of neophyl halides to 1 mol of 3-phenoxybenzyl esters,
Preferably, it is appropriate to use a molar ratio of 0.4 to 2,
If the ratio used is outside this range, the reaction will be slow and more by-products will be produced, resulting in a lower yield.

Aprotic polar solvents used in the method of the present invention include dimethyl sulfoxide, sulfolane, N-methyl-2-pyrrolidone, N,N-dimethylformamide, 1,3-dimethyl-4-imidazolidinone, and tetramethylurea. , N,N-dimethylacetamide, hexamethylphosphoryltriamide, etc., and the amount used is -
0.5 per part of phenoxybenzyl esters
~50 parts, preferably 2 to 20 parts is suitable. If the amount used is less than this, the reaction will be very slow, and if it is more than this, the reaction will be slow and productivity will be low.

In addition, the bases used in the method of the present invention include, specifically, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and lithium hydroxide, and alkaline earth metal hydroxides such as calcium hydroxide and magnesium hydroxide. , alkali metal hydrides such as sodium hydride, alkali metal alcoholates such as sodium methylate, potassium ethylate, potassium t-butoxide, alkali metal oxides such as sodium oxide, alkali metal carbonates such as potassium carbonate and sodium carbonate. ,
Examples include sodium amide, triethylamine, and pyridine, and the amount used is 1.0 to 10 mol, preferably 2 to 10 mol, based on the 3-phenoxybenzyl ester.
6 moles is suitable. If the amount used is less than this, the reaction rate will be low, and if it is more than this, more by-products will be produced and the yield will be lowered.

When sodium hydroxide or potassium hydroxide is used as the base, the usual granular or flake products can be used, but in some cases, finely divided products can be used to speed up the reaction and improve yields.

In this reaction, the water content in the system is suitably 10% or less, preferably 3% or less based on the solvent at the start of the reaction.

A general embodiment of the invention is as follows.

Neophyll halides, 3-phenoxybenzyl esters, a base, and an aprotic polar solvent are placed in a reactor and heated to a temperature ranging from 50°C to the boiling point, preferably 80°C.
or boiling point (80 to 200°C if the boiling point exceeds 200°C), and stir at the same temperature for 0.5 to 50 hours, preferably 3 to 30 hours. After cooling to room temperature, insoluble inorganic salts are filtered off, the solvent is removed from the filtrate by distillation under reduced pressure, and the residue is washed with water and dehydrated to obtain the desired benzylpropyl ether derivative.
This product can be used as an insecticide or acaricide as it is, but in some cases it may be further processed by vacuum distillation or
It is also possible to purify by recrystallization or column chromatography.

This reaction is usually carried out in an air atmosphere, but in some cases, if the reaction is carried out after replacing the system with an inert gas such as nitrogen, the production of by-products can be suppressed and the yield can be improved.

Further, the order of adding the neophyl halides, 3-phenoxybenzyl esters, and the base may be arbitrary, and in some cases, it is also possible to charge them in portions instead of charging them all at once.

〔Example〕

Hereinafter, the details of the present invention will be explained with reference to Examples.

Example 1 In a reactor equipped with a stirring bar, a thermometer and a condenser, 6.2 g of 2-methyl-2-(3-chloro-4-ethoxyphenyl)propyl chloride, 7.3 g of 3-phenoxybenzyl acetate, 6.0 g of flaky sodium hydroxide and 30 ml of 1,3-dimethyl-2-imidazolidinone were charged, heated to 140°C while stirring under a nitrogen stream, and stirred at the same temperature for 15 hours.

After cooling the reaction mixture to room temperature, it was poured into 200 ml of water and made weakly acidic using agricultural hydrochloric acid. The precipitated oil layer was extracted three times using 50 ml of benzene, and the combined benzene layer was thoroughly washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 12.5 g of a crude product.
I got it. As a result of analysis using the internal standard method of gas chromatography, this product was found to be 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl).
It contained 53.4% -2-methylpropyl ether.

Yield of target product: 65.0% [vs. 2-methyl-2-(3
-chloro-4-ethoxyphenyl)propyl chloride].

This product was separated and purified by silica gel column chromatography to obtain pure 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl) 2-methylpropyl ether with a melting point of 42.5°C.

・Elemental analysis results C ₂ H ₂₇ ClO ₃ C H Cl Calculated value 73.07 6.62 8.63 Actual value 72.89 6.75 8.72 ・NMR spectrum δCDCl ₃ : 1.28 (S.6H), 1.4 (t, 3H), 3.35 (S.3H), 4.0
(q.2H), 4.39 (S.2H), 6.68-7.32 (m.12H) ppm Comparative Example 1 2-Methyl-2-(3- 6.2 g of chloro-4-ethoxyphenyl)propyl chloride, 6.0 g of 3-phenoxybenzyl alcohol, 6.0 g of flaked sodium hydroxide and 1,3-dimethyl-2-
30 ml of imidazolidinone was charged, heated to 140°C while stirring under a nitrogen stream, and stirred at the same temperature for 15 hours.

After cooling the reaction mixture to room temperature, it was poured into 200 ml of water and made into a weak acid using concentrated hydrochloric acid. The precipitated oil layer was extracted three times using 50 ml of benzene, and the combined benzene layer was thoroughly washed with water, dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure to obtain 12.2 g of a crude product.
I got it. As a result of analysis using the internal standard method of gas chromatography, it was found that 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-
It contained 42.3% 2-methylpropyl ether.

Yield of target product: 50.2% [vs. 2-methyl-2-(3
-chloro-4-ethoxyphenyl)propyl chloride].

This product was separated and purified by silica gel column chromatography, and 3-phenoxybenzyl 2-(3-chloro-4-
A pure product of ethoxyphenyl)-2-methylpropyl ether was obtained.

Example 2 6.2 g of 2-methyl-2-(3-chloro-4-ethoxyphenyl)propyl chloride, 3-phenoxybenzylformate in a reactor equipped with a stir bar, thermometer, and condenser. 6.9g, flaked sodium hydroxide 6.0g and 1,3-dimethyl-2
- 30 ml of imidazolidinone was charged, heated to 140°C while stirring under a nitrogen stream, and stirred at the same temperature for 15 hours.

After cooling the reaction mixture to room temperature, it was poured into 200 ml of water and made weakly acidic using concentrated hydrochloric acid. The precipitated oil bath was extracted three times using 50 ml of benzene, and the combined benzene layer was thoroughly washed with water, dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure to obtain 12.0 g of a crude product.
I got it. As a result of analysis using the internal standard method of gas chromatography, it was found that 3-phenoxybenzyl 2-(30chloro-4-ethoxyphenyl)-2
- Contained 50.2% methyl propyl ether.

Yield of target product: 58.6% [vs. 2-methyl-2-(3
-chloro-4-ethoxyphenyl)propyl chloride]. This product was separated and purified using silica gel column chromatography, and the melting point was 42.8°C.
A pure product of -phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropylele was obtained.

Claims (1)

[Claims] 1 General formula (I) [In the formula, R ₁ and R ₂ are hydrogen atoms, chlorine atoms, or bromine atoms, and at least one is a chlorine atom,
Or a bromine atom. Further, R is a lower alkyl group, and R ₃ and R ₄ are hydrogen atoms or fluorine atoms. ] When producing the benzylpropyl ether derivative represented by the general formula () [In the formula (), R, R ₁ and R ₂ have the same meanings as in the above general formula (I), and X represents a halogen atom. ] and the general formula () [In formula (), R ₃ and R ₄ are the above general formula (I)
and R ₅ represents a hydrogen atom or a lower alkyl group. ] A method for producing a benzylpropyl ether derivative, which comprises reacting 3-phenoxybenzyl esters represented by the following in an aprotic polar solvent in the presence of a base.