JPS6117524A - Production of benzyl propyl ether - Google Patents

Abstract

PURPOSE:The reaction between a neophyl halide and a 3-phenoxybenzyl ester in an aproteic solvent in the presence of a base give the title compound with very high insecticidal activity and low toxicity. CONSTITUTION:The reaction between a neophyl halide of formula I (R1, R2 are H, halogen, cyano, nitro, alkyl, alkenyl, alkoxy, acyl; m, n are 0-4; m+n is 0-4; X is halogen) such as 2-methyl-2-(3-chloro-4-ethoxy-phenyl)propyl chloride and a 3-phenoxybenzyl ester of formula II (R3, R4 are H, halogen, alkyl; R5 is H, alkyl) such as 3-phenoxybenzyl acetate is carried out an an aprotic solvent such as 1, 3-dimethyl-2-imidazolidinone in the presence of a base to give a benzyl propyl ester of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application 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 formula (I), R1
and R2 are the same or different hydrogen atoms, halo, gen atoms, cyano groups, nitro groups, or optionally substituted lower alkyl groups, alkenyl groups, lower alkoxy groups, acyloxy groups, lower alkylthio groups, lower acyl groups, alkoxy It represents a carbonyl group, R3 and R4 represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, m and n are each an integer of 0 to 4, and m + n is 0 to 4. ] When producing a benzyl propyl ether derivative represented by the general formula (TI) [In the formula (n), R1, 艮, m and n represent the same meanings as above, and X represents a halogen atom. ] Neophyll halides represented by the general formula (m) [In the formula (m), R3 and R4 represent the same meaning as in the above general formula (1), and R5 represents a hydrogen atom or a lower alkyl group. ] The benzyl propyl ether represented by the general formula (I) is prepared by reacting the 3-phenoxybenzyl ester represented by the formula (I) in an aprotic polar solvent in the presence of a base. Relates to methods for producing derivatives.

Conventional technological pesticides have played an extremely important role in improving agricultural productivity, and the appearance of organic synthetic pesticides has completely changed the food situation for humankind, and has also made a huge impact in terms of epidemic prevention, such as preventing infectious diseases transmitted by insects. brought benefits.

However, the amount of organochlorine insecticides DDT and BHC that can be used is limited because they remain in the environment for a long time after use. Although insecticides are widely used, various insect pests have developed resistance to these insecticides.

In recent years, against this background, synthetic pyrethroid insecticides have shown excellent insecticidal power and are highly effective against pests resistant to organic phosphorus or carbamate agents, and are relatively low toxic to humans and livestock. It has been in the spotlight. However, the disadvantage of this synthetic pyrethroid insecticide is that it is highly toxic to fish, which limits its range of use. and again,
It is more expensive than conventionally developed insecticides.

Recently, benzylpropyl ether derivatives represented by the above general formula (I) have extremely high insecticidal and acaricidal activity, are superior in immediate efficacy ratio and residual efficacy, and are toxic not only to humans and livestock but also to fish. It has been found to have low levels of oxidation and is offered as a pest control agent. (Unexamined Japanese Patent Publication No. 56-154
427, 57-64632, 57-7292gi, 58-
3284 The above-mentioned publication also describes a method for producing the compound of formula (I), including a method of reacting neophyll alcohols and 3-phenoxybenzyl halides shown by the following reaction formula 1) to obtain the desired product, and a method of producing the desired product by reaction formula 2). A method is disclosed in which a desired product is obtained by reacting neophyll halides represented by the formula with 3-phenoxybenzyl alcohol. however,
In the method shown by reaction formula 1), 3-phenoxybenzyl alcohols are expensive.

[In the formula, R1, R2, R3, R4, m and It has been discovered that a 3-phenoxybenzyl ether compound having a neophyll group substituted with an alkoxy group has a particularly large insecticidal effect among these compounds, and a method for producing the compound is the formula (IV)Y.

Step 2 [In formula (IV), Yl and Y2 are hydrogen atoms, chlorine atoms, or bromine atoms, and at least one of Yl and Y2 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 [In formula (v), n and d are hydrogen atoms or fluorine atoms,
be. ] 3-phenoxybenzyl alcohols represented by
A condensation reaction is carried out to form a compound of formula (Vl) [In formula (Vl), Yl and Y2 are a hydrogen atom, a chlorine atom, or a bromine atom, and at least one of Yl and Y2 is a chlorine atom or a bromine atom. Further, R is a lower alkyl group, and Xl and k are hydrogen atoms or fluorine atoms.

] We have previously applied for a method for producing 3-phenoxybenzyl 2-(4-alkoxyhalogenophenyl)-2-methylpro and ethers (Japanese Patent Application Laid-open No. 1988/140).
).

However, when the condensation reaction is carried out by the method shown in reaction formula 2), 3-phenoxybenzyl alcohol is relatively easily oxidized by heating during the condensation reaction, so neophyll halides and 3-phenoxybenzyl alcohol The condensation yield with 2
In particular, the method for producing the benzylpropyl ether derivative represented by formula (VI) has not necessarily been an advantageous industrial production method.

Means for Solving 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 found that
When neophyll halides represented by general formula (n) and 3-phenoxybenzyl esters represented by general formula (m) are reacted in an aprotic polar solvent in the presence of a base, general formula (I) is obtained. It was discovered that the benzylpropyl ether derivative represented by can be obtained in good yield, and as a result of intensive studies, the present invention was completed.

The benzylpropyl ether derivative that can be produced by the method of the present invention is a compound represented by the general formula (I), and specifically, R1 and R2 are a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxyethyl group, ethoxymethyl group, 1-methoxyethyl group,
1-engineering diethyl group, i-propenyl group, methoxy group, ethoxy group, i-propoxy group, n-butyloxy group, i-butyloxy group, 5ec-butyloxy group,
n-pentyloxy group, methylenedioxy group, difluoromethoxy group, ace! -oxy group, methylthio group, ethylthio group, l-propylthio group, acetyl group, ethoxycarbonyl group, cyano group, nitro group, etc., and R3
and R4 is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a 5ec-butyl group,
Examples include t-butyl group, methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butyloxy group, i-butyloxy group, and 5ec-butyloxy group.

In addition, 3-phenoxybenzyl esters used as raw materials in the method of the present invention, general formula (m) c formula (III
), where Ft3, K and R5 are the same as above] is 3-
It can be produced by a known method from 3-phenoxybenzyl halides obtained by halogenating phenoxytoluenes and an alkali metal salt of the corresponding carboxylic acid. 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, the ratio of neophyll halides and 3-phenoxybenzyl esters used is 0.1 to 5 molar ratio, preferably 0.1 to 5 molar ratio of neophyll halides to 1 mole of 3-phenoxybenzyl esters. It is appropriate to use a molar ratio of .4 to 2. If the ratio is out of this range, the reaction will be slow and more by-products will be produced, resulting in a lower yield.

The aprotic polar solvent used in the method of the present invention includes dimethyl sulfoxide, sulfolane, N-methyl-2-pyrrolidine, N,N-dimethylformamide,
Examples include 1,3-dimethyl-4-imidazolidinone, tetramethylurea, N,N-dimethylacetamide, hexamethylphosphoryltriamide, and the amount used is 1 part of 3-phenoxybenzyl ester. Te 0
5 to 50 parts, preferably 2 to 29 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, specific examples of the base used in the method of the present invention include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and lithium hydroxide, calcium hydroxide,
Alkaline earth metal hydroxides such as magnesium hydroxide, alkali metal hydrides such as sodium hydroxide, alkali metal alcoholates such as sodium methylate, potassium monobutoxide, potassium monobutoxide, and alkali metals such as sodium oxide. Examples include oxides, alkali metal carbonates such as potassium carbonate and sodium carbonate, sodium amide, triethylamine, and pyridine, and the amount used is 3
1.0 to ゛-phenoxybenzyl esters
10 mol, preferably 2 to 6 mol is suitable. If the amount used is less than this, the reaction rate will be low, and if it is more than this, byproducts will be produced in large quantities and the yield will be reduced.

When sodium hydroxide or potassium hydroxide is used as a base, a normal granular or flake product can be used, but in some cases, using a finely divided product will speed up the reaction and improve the yield.

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

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 reaction vessel, and the temperature is heated from 50°C to the boiling point, preferably from 80°C to the boiling point (
However, if the boiling point exceeds 200℃, 80-200℃
), heated at the same temperature for 05 to 50 hours, preferably 3 to 3
Stir for 0 hours. After cooling to room temperature, insoluble inorganic salts are separated, the solvent is removed from the p liquid by vacuum distillation, 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 can be further purified by vacuum distillation, recrystallization, or column chromatography.

This reaction is usually carried out in an air atmosphere, but 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 addition of neophyl halides, 3-phenoxybenzyl esters, and base may be arbitrary, and depending on the case, it is also possible to charge them in parts instead of charging them all at once.

Next, the details of the present invention will be explained with reference to examples.

[Implementation Instructions-1] In a reaction vessel equipped with a stirring bar, a thermometer, and a condenser, 2-
Methyl-2-(3-chloro-4-ethoxyphenyl)propyl chloride 6.2,9,3-phenoxybenzyl acetate 73 g, flaked sodium hydroxide 6,0
g and 1,3-dimethyl-2-imidazolidinone 30
- 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 discharged into 200ml of water.
It was made weakly acidic using concentrated hydrochloric acid. The precipitated oil layer was extracted three times using 50 ml of benzene, and the benzene layer was thoroughly washed with water, dried over anhydrous Kasashiro, and then the solvent was distilled off under reduced pressure to obtain a composition of 12.5p. As a result of analysis by the internal drift method of gas chromatography, this product was found to be 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl).
The yield of the target product was 65.0% [vs. 2-methyl-2-(3-chloro-4-ethoxyphenyl)propyl chloride], which contained 53.4% of -2-methylpro and ether.

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

・Elemental analysis results CQ5) (27clo3CH (J Calculated value 73.07 6.62 8.63 Actual value 72.89 6,75 8.72 ・NMR spectrum (lcDcA'3: [Comparative example-J]) Stirring bar, temperature 2 in a reaction vessel equipped with a meter and a condenser.
-Mejiru 2-(3-chloro-4-ethoxyphenyl)
Propyl chloride 6.2J, 3-phenoxybenzyl alcohol 6.0J? , 1-lium hydroxide in flake form6. Og and 30 mJ of 1,3-dimethyl-2-imidazolidinone were charged and heated for 14 hours while stirring under a nitrogen stream.
The mixture was heated to 0°C and stirred at the same temperature for 1.11 hours.

After cooling the reaction mixture to room temperature, it was discharged into 200 d of water,
It was made weakly acidic 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 an anhydrous core/sheath, and then the solvent was distilled off under reduced pressure to obtain crude product 12.2I. As a result of analysis using the internal standard method of gas chromatography, this product contained 42.3% of 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpro-ether.

The yield of the target product was 50.2% (vs. 2-methyl-2-(3T chloro-4-ethoxyphenyl)probylfluoratode).

This product was separated and purified by silica gel column chromatography to obtain a pure product of 3-phenoxybenzyl 2-(4-chloro-4-ethoxyphenyl)-2-methylpro-ether with a melting point of 425°C similar to that in Example-1. Ta.

[Example-2] In a reaction vessel equipped with a stirring bar, a thermometer, and a condenser, two
-Methyl-2-(3-chloro-4-ethoxyphenyl)
Propyl chloride 6.2.9,3-phenoxybenzylformate 6.9.9', flaky hydroxide 1~
Rium6. 30 g of Og and 1,3-dimethyl-2-imidazolidinone were charged, heated to 140° C. with 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 layer was extracted three times using 50 d of benzene, and the combined benzene layers were thoroughly washed with water, dried over anhydrous Kasashiro, and then the solvent was distilled off under reduced pressure to obtain 12.0 g of a crude product. 4 As a result of analysis using the internal standard method of gas chromatography, 3
-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether 50.2%
It contained.

Yield of target product: 58.6% [vs. 2-methyl-2-(3-
Chlor-4-ethoxyphenyl)propyl chloride]
Met.

This product was separated and purified by silica gel column chromatography to produce 3-phenoxybenzyl 2 with a melting point of 42.8°C.
-(4-chloro-4-ethoxyphenyl>-2-'yt
A pure product of thylpropyl ether was obtained.

Claims (2)

[Claims] (1) General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) [In formula (I), R_1 and R_2 are the same or different hydrogen atoms, halogen atoms, cyano groups, nitro groups, or substituted represents a lower alkyl group, alkenyl group, lower alkoxy group, acyloxy group, lower alkylthio group, lower acyl group, or alkoxycarbonyl group, which may be a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group. Representation, m and n
are each an integer from 0 to 4, and m+n is from 0 to 4. ]
When producing the benzylpropyl ether derivative represented by the general formula (II), there are mathematical formulas, chemical formulas, tables, etc.▼ (II) [In the formula (II), R_1, R_2, m and n are the general formula (I ), and X represents a halogen atom. ] There are neophyll halides shown by the general formula (III) ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (II
I) [In formula (III), R_3 and R_4 are represented by the 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. (2) The benzylpropyl ether derivative has the following formula ▲ Numerical formula, chemical formula, table, etc. It is a bromine atom. Further, R is a lower alkyl group, R_3,
R_4 is a hydrogen atom or a fluorine atom. ] 3-phenoxybenzyl 2-(4-alkoxyhalogenophenyl)-2-methylpropyl ethers shown in Claim 1).