JPH072666B2 - Process for producing 3- (3-halogeno-4-alkoxyphenyl) -3-methylbutanals - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention is represented by the general formula (I). (In the formula, R represents a lower alkyl group, and X represents a fluorine atom, a chlorine atom, or a bromine atom.) 3- (3
-Halogeno-4-alkoxyphenyl) -3-methylbutanals.

INDUSTRIAL APPLICABILITY The compound of the present invention is useful in various industrial fields, and is particularly useful as an intermediate for agricultural medicines, especially insecticides.
That is, 3- (3-halogeno-4-alkoxyphenyl) -3-methylbutanals have high insecticidal and acaricidal activities, and have excellent characteristics in fast-acting, residual effect and low fish toxicity. (3-phenoxyphenyl) -4-
(3-Halogeno-4-alkoxyphenyl) -4-methylpentane derivative and 1- (3-phenoxyphenyl) -4- (4-alkoxyphenyl) -4-methylpentane derivative (JP-A-58-201737) Is an important intermediate.

[Conventional technology]

There is no known method for producing 3- (3-halogeno-4-alkoxyphenyl) -3-methylbutanal represented by the general formula (I).

[Problems to be Solved by the Present Invention]

An object of the present invention is to provide a method for producing 3- (3-halogeno-4-alkoxyphenyl) -3-methylbutanal which is a raw material of the insecticidal pentane derivative having the above-mentioned preferable characteristics.

[Means and Actions for Solving the Problems]

As a result of intensive studies by the present inventors to solve the above problems,
General formula (I) (In the formula, R and X have the above-mentioned meanings.) 3- (3-halogeno-4-alkoxyphenyl) -3
-Methylbutanals useful as insecticides 1- (3-
Phenoxyphenyl) -4- (3-halogeno-4-alkoxyphenyl) -4-methylpentane derivative and 1
It is useful as a starting material for producing a-(3-phenoxyphenyl) -4- (4-alkoxyphenyl) -4-methylpentane derivative, and has the general formula (II) (In the formula, R represents a lower alkyl group, X represents a fluorine atom, a chlorine atom or a bromine atom, and Y represents a chlorine atom or a bromine atom.) 2- (3-halogeno-4-)
The inventors have found that they can be industrially easily produced from alkoxyphenyl) -2-methylpropyl halides and completed the present invention.

The dialkyl acetals represented by the general formula (IV) have not been described in the literature, and are novel compounds first discovered by the present inventors.

In the general formula (I), the substituent R represents a lower alkyl group and represents a linear or branched alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, pentyl, etc., and the substituent X is fluorine. Indicates an atom, chlorine atom or bromine atom. Specific examples of 3- (3-halogeno-4-alkoxyphenyl) -3-methylbutanals represented by formula (I) include 3- (3-chloro-4-methoxyphenyl) -3-methyl. Butanal, 3- (3-chloro-4-ethoxyphenyl) -3-methylbutanal, 3
-(3-Chloro-4-propoxyphenyl) -3-methylbutanal, 3- (3-chloro-4-isopropoxyphenyl) -3-methylbutanal, 3- (3-chloro-4-butoxyphenyl) -3-methylbutanal, 3
-(3-Chloro-4-pentyloxyphenyl) -3-
Methylbutanal, 3- (3-chloro-4-hexyloxyphenyl) -3-methylbutanal, 3- (3-bromo-4-methoxyphenyl) -3-methylbutanal, 3- (3-bromo- 4-ethoxyphenyl) -3-
Methyl butanal, 3- (3-bromo-4-propoxyphenyl) -3-methylbutanal, 3- (3-bromo-4-isopropoxyphenyl) -3-methylbutanal, 3- (3-fluoro- 4-methoxyphenyl) -3
-Methylbutanal, 3- (3-fluoro-4-ethoxyphenyl) -3-methylbutanal, 3- (3-fluoro-4-propoxyphenyl) -3-methylbutanal and the like can be mentioned.

The compound represented by the general formula (I) can be produced by the following method.

(In the formula, R, X, Y, and R ¹ have the above-mentioned meanings.) 2- (3-halogeno-4-alkoxyphenyl) -represented by the general formula (II) which is a starting material for this production method Two
-Methylpropyl halides were synthesized from 2-halogenoalkoxybenzenes and methallyl halides by a known method (JP-A-60-149539) and used. Next, the manufacturing method of the present invention will be described. That is, 2- (3-halogeno-4-alkoxyphenyl) -2-methylpropyl halides represented by the general formula (II) are reacted with magnesium metal in a solvent of ethyl ether or tetrahydrofuran by a conventional method to obtain a Grignard reagent ( Grignard r
eagent) and then reacting with a trialkyl orthoformate represented by the general formula (III). As the trialkyl orthoformate represented by the general formula (III), specifically, trimethyl orthoformate or triethyl orthoformate is preferable.

In this reaction, a solvent such as ether or tetrahydrofuran used when preparing the Grignard reagent may be used, but it is preferable to remove ether or tetrahydrofuran. That is, the 2- (3-halogeno-
The reaction of 4-alkoxyphenyl) -2-methylpropyl halides with a Grignard reagent and a trialkyl orthoformate represented by the general formula (III) is carried out in the absence of a solvent, or an inert gas such as benzene, toluene, hexane or heptane. It is better to carry out in an aliphatic or aromatic hydrocarbon solvent.

The reaction temperature and reaction time can be varied over a wide range depending on the starting materials, but generally the reaction temperature is 20 ° C to
The temperature is 150 ° C., preferably 30 to 120 ° C., and the reaction time is 0.5 to 24 hours, preferably 0.5 to 15 hours.

Next, the acetals represented by the general formula (IV) obtained by this reaction are easily treated with an acidic condition to easily obtain the desired 3- (3-halogeno-formula represented by the general formula (I).
It can be 4-alkoxyphenyl) -3-methylbutanal. In this case, in a water solvent or a mixed solvent of water and a water-soluble organic solvent such as methanol, ethanol, acetone, tetrahydrofuran, dioxane, or an organic solvent such as toluene, benzene, hexane, heptane, ether, ethyl acetate, dichloromethane, chloroform. It can be carried out in a mixed solvent with water, but is preferably a water solvent or a mixed solvent of methanol, ethanol, acetone, tetrahydrofuran, dioxane and the like with water.

The acids used are mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid or acetic acid,
Organic acids such as propionic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid are preferred,
Organic acids such as acetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid are more preferable.

The reaction temperature and reaction time can be varied over a wide range depending on the starting materials, but generally the reaction temperature is from 0 ° C to
The temperature is 150 ° C, preferably 30 ° C to 100 ° C, and the reaction time is 0.1 to 24 hours, preferably 0.5 to 20 hours.

〔Example〕

Next, the present invention will be described in more detail with reference to synthetic examples and reference examples, but the present invention is not limited thereto.

Synthesis Example 1. (1) After adding 2.98 g of magnesium metal (shavings) to 80 ml of dry ether, 0.2 ml of dibromoethane was added dropwise with stirring under a nitrogen stream. Then, 2- (3-chloro-
30.0 g of 4-ethoxyphenyl) -2-methylpropyl chloride was added dropwise. After the dropping is completed, the mixture is heated under reflux for 2.0 hours,
20.0 g of trimethyl orthoformate was added. While removing ether under normal pressure, 60 ml of benzene was gradually added, and the internal temperature was 80-
When the temperature reached 82 ° C, stirring was continued for another 3 hours. After cooling to room temperature, water was added to remove the formed precipitate by filtration, and the obtained benzene solution was washed with water and dried. Benzene was distilled off under reduced pressure to obtain 31.3 g of an oily residue. The oily residue obtained was subjected to column chromatography (Wako Gel C-
Purification with 200,650 g, developing solvent: toluene) gave 22.8 g of the target dimethyl acetal.

Elemental analysis value: C ₁₅ H ₂₃ ClO ₃ C H Cl Calculated value (%) 62.82 8.08 12.36 Measured value (%) 62.91 8.13 12.35 (2) Mixing 22.0 g of dimethyl acetal obtained in (1) with 100 ml of acetone and 20 ml of water Dissolved in solution. Then, 1 ml of methanesulfonic acid was added and stirred at 50 ° C. for 2 hours. After distilling off acetone, the mixture was extracted with toluene, and the obtained toluene solution was washed with water and dried. Toluene was distilled off under reduced pressure and 18.5 g
An oily residue of was obtained. Column chromatography (Wako
It was purified with GelC-200, 350 g, developing solvent: toluene) to obtain 17.6 g of the target 3- (3-chloro-4-ethoxyphenyl) -3-methylbutanal.

Elemental analysis value: C ₁₃ H ₁₇ ClO ₂ C H Cl calculated value (%) 64.86 7.12 14.73 measured value (%) 64.95 7.08 14.70 Synthesis Example 2. (1) 23.8 g of magnesium metal (cutting) in 600 ml of dry ether After the addition, 2 ml of dibromoethane was added dropwise with stirring under a nitrogen stream. Then, 2- (3-chloro-
240.0 g of 4-ethoxyphenyl) -2-methylpropyl chloride was added dropwise. After completion of dropping, the mixture was heated under reflux for 2.0 hours, and 160.0 g of trimethyl orthoformate was added. While removing ether under normal pressure, 500 ml of benzene was gradually added and the internal temperature was adjusted to 8
When the temperature reached 0 to 82 ° C, stirring was continued for another 3 hours.
After cooling to room temperature, water was added to remove the formed precipitate by filtration, and the resulting benzene solution was washed with water and dried. Benzene was distilled off under reduced pressure to obtain 252.8 g of an oily residue. The obtained oily residue was purified by distillation under reduced pressure (126.0 to 126.5 ° C / 0.22 mHg) to obtain 185.3 g of the target dimethyl acetal. As a result of analysis by gas chromatography, the purity was 98.6%.

(2) 250.0 g of dimethyl acetal obtained in (1) was dissolved in a mixed solvent of 1000 ml of acetone and 300 ml of water. Then, 10 ml of methanesulfonic acid was added, and the mixture was stirred at room temperature for 4 hours. After distilling off acetone, the mixture was extracted with toluene, and the obtained toluene solution was washed with water and dried. Toluene was distilled off under reduced pressure 21
0.5 g of oily residue was obtained. As a result of analysis by gas chromatography, 98.1% of 3- (3-chloro-4-ethoxyphenyl) -3-methylbutanal was contained.

Synthesis Example 3 (1) The procedure was carried out according to Synthesis Example 1 (1) except that 60 ml of dry tetrahydrofuran was used instead of 80 ml of dry ether and 60 ml of toluene was used instead of 60 ml of benzene, and 21.2 g of the target dimethyl acetal was obtained. Obtained.

(2) 20.0 g of dimethyl acetal obtained in (1) was added to 50 m of acetic acid.
1, and mixed with 50 ml of water, and stirred at 40 ° C. for 6 hours. Pour into ice water and extract with toluene. The toluene extract was washed with water and dried, and then toluene was distilled off under reduced pressure to obtain 15.4 g of an oily residue. As a result of analysis by gas chromatography, 97.3% of 3- (3-chloro-4-ethoxyphenyl) -3-methylbutanal was contained.

Synthesis Example 4. (1) 2.55 g of magnesium metal (shaved) was added to 70 ml of dry ether, and then 0.2 ml of dibromoethane was added dropwise while stirring under a nitrogen stream. Then, 2- (3-chloro-
24.7 g of 4-ethoxyphenyl) -2-methylpropyl chloride was added dropwise. After the dropping is completed, the mixture is heated under reflux for 2.0 hours,
80 ml of trimethyl orthoformate was gradually added at atmospheric pressure while removing the ether, and the internal temperature was kept at 85 ° C for 5 hours.

After cooling to room temperature, water was added to remove the formed precipitate by filtration, and the liquid was extracted with toluene. The obtained toluene solution was washed with water and dried. Toluene and triethyl orthoformate were distilled off under reduced pressure to obtain 27.2 g of an oily residue. The oily residue obtained is subjected to column chromatography (Wako Ge
l, C-200, 650 g, developing solvent: toluene) to obtain 13.1 g of the desired dimethyl acetal.

(2) 12.0 g of dimethyl acetal obtained in (1) was hydrolyzed according to Synthesis Example 1 (2) to obtain 9.7 g of an oily residue.
As a result of analysis by gas chromatography, 98.5% of 3-
Included (3-chloro-4-ethoxyphenyl) -3-methylbutanal.

Reference Example 1.1- (3-phenoxy-4-fluorophenyl) -4- (3-chloro-4-ethoxyphenyl) -4
-Synthesis of methyl pentane (1) Add 55.7 g of 3-phenoxy-4-fluorobenzyltriphenylphosphonium bromide to 120 ml of dry tetrahydrofuran, and keep 4.0 g of sodium hydride (60% in oil) for 1 hour while maintaining at 50-60 ° C. It was charged separately. After charging, the mixture was heated under reflux for 5.0 hours. Then, while maintaining 25 ° C, 3- (3-chloro-4-ethoxyphenyl)-
31.5 g of 3-methylbutanal was added dropwise over 30 minutes. 3 at 40 ° C
After stirring for 0 minutes, 10 ml of ethanol and 10 ml of water were added while cooling to decompose excess sodium hydride. After the tetrahydrofuran was distilled off, water was added and the mixture was extracted with benzene. The benzene solution was washed with water and dried, and then benzene was distilled off under reduced pressure. When 500 ml of hexane was added to this residue, triphenylphosphine oxide was precipitated. Then, triphenylphosphine oxide was removed by filtration to obtain a hexane solution. Hexane was distilled off to obtain 53.4 g of an oily residue. Column chromatography (silica gel, 1200
g, developing solvent: Toluene-hexane (1: 2))
40.9 g of 1- (3-phenoxy-4-fluorophenyl) -4- (3-chloro-4-ethoxyphenyl) -4
-Methyl-1-pentene was obtained.

(2) 10.2 g of 1- (3-phenoxy-4-fluorophenyl) -4- (3-chloro-4-ethoxyphenyl) -4-methyl-1-pentene obtained in (1) was added to 50 m of ethyl acetate.
After dissolving in 1L, add 5% Pd-C 1.0g and add hydrogen pressure 20kg / c at room temperature.
The mixture was stirred at m ² G for 3 hours. Then, Pd-C was separated and ethyl acetate was distilled off to obtain 10.1 g of an oily residue. Purify by column chromatography (silica gel, 200 g, developing solvent; toluene-hexane (1: 2)) to obtain the desired 1- (3
-Phenoxy-4-fluorophenyl) -4- (3-chloro-4-ethoxyphenyl) -4-methylpentane 9.
Got 5g Reference Example 2. 1- (3-phenoxy-4-fluorophenyl) -4- (3-chloro-4-ethoxyphenyl) obtained in Reference Example 1.
Emulsion was obtained by uniformly stirring and mixing 20 parts of -4-methylpentane, 10 parts of Solpol 355 (surfactant manufactured by Toho Kagaku Co., Ltd.) and 70 parts of xylene. This emulsion was diluted with water so that the concentration of the active ingredient was 100 ppm, and sprayed on rice seedlings (3 leaf stage) planted in a Wagner pot of 1 / 10,000 are so that the liquid medicine would drip lightly on the turntable. did. After air drying,
The seedlings are covered with a metal cylinder, and 10 female adults of the resistant leafhopper (Nakagawabara system) are released and left at room temperature.
Mortality was investigated 24 hours later. All the tests were carried out in a double system. As a result, the mortality rate was 100%.

〔The invention's effect〕

As is clear from the above description, the novel 3 according to the present invention
The-(3-halogeno-4-alkoxyphenyl) -3-methylbutanals are compounds which are useful as intermediates in the agricultural and pharmaceutical fields, especially insecticides, and can be easily produced by the production method according to the present invention. . Therefore, the present invention is useful.

Claims (1)

[Claims] 1. General formula (II) (In the formula, R represents a lower alkyl group, X represents a fluorine atom, a chlorine atom or a bromine atom, and Y represents a chlorine atom or a bromine atom.) 2- (3-halogeno-4-)
After reacting an alkoxyphenyl) -2-methylpropyl halide with magnesium metal, it is represented by the general formula (III) CH (OR ¹ ) ₃ (III) (wherein R ¹ represents a lower alkyl group). Reacts with trialkyl orthoformates to give the general formula (IV) (In the formula, R, X and R ¹ have the above-mentioned meanings.) An acetal derivative represented by the following general formula (I) is characterized by being hydrolyzed under acidic conditions. (In the formula, R and X have the above-mentioned meanings.) 3- (3-halogeno-4-alkoxyphenyl) -3
-Method for producing methylbutanals.