JPS6343379B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula (In the formula, R ₁ represents an alkyl group having 1 to 6 carbon atoms,
R ₂ represents a methyl group or a chlorine atom. ), its optical and geometric isomers, and its production method. Various alcohol components of primary chrysanthemum esters have been studied and put into practical use.
It is susceptible to oxidative decomposition due to light, which has limited its use outdoors. Recently, research into acid components has become active, and a compound that is more stable to light than conventional pyrethroids was discovered by replacing the methyl group of the isobutenyl group with a halogen atom. The present inventors further investigated various substituents of cyclopropanecarboxylic acid that are resistant to oxidative decomposition by light, and found that an ester having a substituted cyclopropanecarboxylic acid having an alkoxy group represented by the above formula () as an acid component is an insecticidal ingredient. It has been found that it has extremely excellent insecticidal effects against various sanitary pests and agricultural and horticultural pests, has extremely low toxicity to warm-blooded animals, and is much more stable against light than conventional pyrethroids. The substituted cyclopropanecarboxylic acid of the present invention is a new compound, and as a result of various studies on its production method, it has been confirmed that the conventional method for producing cyclopropanecarboxylic acid can be used as is. That is, the following three methods were suitable for the purpose of the present invention. (1) General formula (In the formula, R ₁ and R ₂ have the same meanings as above.) The ether represented by the formula (R 1 and R 2 have the same meanings as above) is reacted with a diazoacetate to form a substituted cyclopropane carboxylic acid ester, which is then hydrolyzed to produce a substituted cyclopropane carboxylic acid ester. How to get. (2) General formula (In the formula, R ₁ has the same meaning as above, and X represents a halogen atom.) The ether represented by (In the formula, R ₂ has the same meaning as above, and R ₄ represents a methyl group or an ethyl group.) A method of reacting a substituted acrylic acid ester represented by the formula and further hydrolyzing it to obtain a substituted cyclopropane carboxylic acid. . (3) General formula (In the formula, R ₁ has the same meaning as above, and R ₅ represents a methyl group, ethyl group, or tertiary butyl group.)
A method in which the ester represented by is reacted with chloroform in the presence of dimethyldiazomethane or potassium tertiary butyrate, and then hydrolyzed to obtain a substituted cyclopropanecarboxylic acid. Next, the raw materials used in the production method of the present invention are, for example,
Ethers in methods (1) and (2) are obtained by reacting alcohol and aldehyde in the presence of hydrogen halide to obtain alkyl haloalkyl ether. This product becomes a raw material for production method (2), and by reacting this product with an appropriate base and dehydrohalogenating it, an alkyl alkenyl ether can be obtained as a raw material for method (1). Also, alkali metal alcoholates and β
- There is also a method of reacting methyl allyl halide and then isomerizing it to obtain an alkyl alkenyl ether. The ester serving as the starting material for (3) can be easily obtained by reacting a β-halogen acid ester with an alkali metal alcoholate. The substituted cyclopropane carboxylic acids of the present invention are used as various derivatives to produce esters with alcohols, and in this case, the substituted cyclopropane carboxylic acids obtained by methods (1), (2), and (3) Acid esters can be used as they are, and acid halides, acid anhydrides, and alkali metal salts can also be used. The acids of the present invention can be easily converted into these acids. Representative examples of the substituted cyclopropanecarboxylic acids of the present invention include the following. (1) 2,2,3-trimethyl-3-methoxycyclopropanecarboxylic acid n ²⁰ _D 1.4497 (2) 2,2,3-trimethyl-3-n-propoxycyclopropanecarboxylic acid n ²⁰ _D 1.4523 (3) 2 ,2-dichloro-3-methyl-3-n-butoxycyclopropanecarboxylic acid n ²⁰ _D 1.4540 (4) 2,2,3-trimethyl-3-isobutoxycyclopropanecarboxylic acid n ²⁰ _D 1.4543 (5) 2, 2-dichloro-3-methyl-3-n-amyloxycyclopropanecarboxylic acid
n ²⁰ _D 1.4598 Next, each reaction condition for the production method of the present invention will be explained. (1) In the reaction between alkyl alkenyl ether and ethyl diazoacetate, an excess amount of alkyl alkenyl ether is used instead of the solvent without using a solvent.
The test is carried out under heating conditions of 100°C or higher, under which nitrogen gas is continuously generated. Note that the reaction can also be carried out in the presence of copper sulfate or copper in order to advance the reaction smoothly. (2) The reaction between an alkyl haloalkyl ether and benzene sulfuric acid is carried out in methanol or ethanol in the presence of a basic agent such as an alkali metal carbonate or acetate to obtain a phenyl alkoxyalkyl sulfone, which is then converted into a substituted acrylic acid. acid ester in an inert solvent,
For example, the reaction is carried out in benzene, toluene, tetrahydrofuran, preferably dimethylformamide, dimethylsulfoxide or acetonitrile in the presence of a basic agent in an anhydrous state. The basic agent is preferably an alkali amide, an alkali metal hydride, or an alcoholate, preferably sodium methylate or potassium tertiary butylate. (3) The reaction between substituted acrylic ester and dimethyldiazomethane is carried out by using an excess of substituted acrylic ester and heating in the presence of copper or copper sulfate, as in the case of alkyl alkenyl ether and ethyl diazoacetate in (1). conduct. In addition, the reaction between a substituted acrylic ester and chloroform in the presence of potassium tertiary butyrate is performed by reacting the substituted acrylic ester with chloroform in the presence of potassium tertiary butyrate in an inert solvent, for example, benzene, to form a substituted cyclopropanecarboxylic acid. The ester is obtained and then hydrolyzed to obtain the substituted cyclopropane carboxylic acid. Hydrolysis is the same for (1), (2), and (3), but it can be easily converted to an acid by alkaline hydrolysis. Next, the present invention will be explained in detail in Examples. Example 1 20 g of methyl-1-methyl-1-isobutenyl ether and 1 g of copper sulfate are placed in a 300 ml three-necked flask, and 0.5 g of ethyl diazoacetate is added. The mixture is heated to about 120°C, and when the reaction begins with continuous evolution of nitrogen, 11 g of ethyl diazoacetate is slowly added dropwise, keeping the temperature around 120°C. After the reaction was completed, the solution was filtered and distilled under reduced pressure to obtain 11.4 g of ethyl ester of 2,2,3-trimethyl-3-methoxycyclopropanecarboxylic acid (bp85-88℃/20mmHg).
I got it. Add 100ml of 2N sodium hydroxide methanol solution to this, heat, reflux for 30 minutes, remove methanol under reduced pressure, add water, make acidic by adding concentrated hydrochloric acid, and 50ml of chloroform.
The chloroform layers were combined, dried over anhydrous sodium sulfate, and then chloroform was distilled off under reduced pressure to obtain 10.2 g of 2,2,3-trimethyl-3-methoxycyclopropanecarboxylic acid. Example 2 37.2 g of n-butyl-1-methyl-2,2-dichlorovinyl ether and 1.5 g of copper powder are placed in a 300 ml three-necked flask, and 0.5 g of methyl diasoacetate is added. The mixture is heated to about 130 DEG C., and when nitrogen begins to evolve continuously, a mixture of 16 g of methyl diazoacetate and 18.7 g of n-butyl-1-methyl-2,2-dichlorovinyl ether is slowly added dropwise. The temperature is
The temperature is maintained at around 140℃, and the dropping is performed so that nitrogen generation occurs continuously. After dropping, continue heating for 30 minutes, cool, add 50 ml of benzene to dissolve, and filter. After removing benzene from the liquid under reduced pressure, it was distilled to give 2,2-dichloro-3-methyl-3-n-
28.1 g of methyl ester of butoxycyclopropanecarboxylic acid (bp 121-126°C/8 mmHg) was obtained.
Dissolve this in 100 ml of methanol, add 20 g of potassium hydroxide dissolved in 50 ml of water, and heat under reflux for 1 hour. After cooling, methanol is distilled off under reduced pressure, 50 ml of water is added, concentrated hydrochloric acid is added to make the mixture acidic, and the mixture is extracted three times with 50 ml of chloroform. The chloroform layers were combined and dried over anhydrous sulfuric acid, and the chloroform was distilled off under reduced pressure to give 2,2-dichloro-3-methyl-3-
26.3 g of n-butoxycyclopropanecarboxylic acid was obtained. Example 3 To a suspension of 2 g of sodium carbonate and 18 g of sodium phenylsulfinate in 100 ml of methanol, 16.3 g of 1-n-propoxyethyl bromide is added dropwise over about 30 minutes at room temperature. After stirring at room temperature for about 2 hours, the reaction mixture is poured into ice water and extracted three times with 100 ml of ether. The ether layers were combined and dried over anhydrous sodium sulfate, and the ether was distilled off under reduced pressure to obtain 21.5 g of phenyl-1-n-propoxyethyl sulfone. dimethylformamide
Add 21.5 g of phenyl-1-n-propoxyethyl sulfone to a solution prepared by adding 23 g of potassium tert-butyrate to 200 ml and stir for 30 minutes. Then ethyl ester of β-dimethylacrylic acid
Drop 25.6g. Stir at room temperature for 2 hours, cool to 0°C, and pour into a mixture of ice and dilute hydrochloric acid solution.
Extract three times with 100 ml of ether and combine the ether layers. This ether solution was washed with brine, then with sodium bicarbonate, and again with brine, dried over anhydrous sodium sulfate, the ether was distilled off under reduced pressure, and 2,2,3-trimethyl-3-n-propoxycyclopropane was distilled. Ethyl ester of carboxylic acid (bp106-109℃/15
mmHg) 18.4g was obtained. Dissolve this in 50 ml of methanol, add 20 ml of 40% sodium hydroxide solution, heat under reflux for 1 hour, and after cooling, methanol is distilled off under reduced pressure. Add 50 ml of water, then acidify with hydrochloric acid and extract three times with 50 ml of chloroform. The chloroform layers were combined, dried over anhydrous sodium sulfate, and chloroform was distilled off under reduced pressure.
16.0 g of 2,3-trimethyl-3-n-propoxycyclopropanecarboxylic acid was obtained. Example 4 30 g of ethyl ester of β-isobutoxy-β-methylacrylic acid and 2 g of copper sulfate are placed in a 300 ml three-necked flask, and about 0.5 g of dimethyldiazomethane is added. Heat the mixture to about 100°C, confirm that the reaction begins with continuous evolution of nitrogen, and then add 6.5 g of dimethyldiazomethane and β-isobutoxy-
A mixture of 9 g of ethyl ester of β-methylacrylic acid is slowly added dropwise. Keep the temperature around 100℃,
Perform this while making sure that nitrogen continues to be generated. After the reaction is complete, add 100 ml of benzene to dissolve the mixture and filter. Benzene was distilled off from the liquid under reduced pressure, and 20.9 g of ethyl ester of 2,2,3-trimethyl-3-isobutoxycyclopropanecarboxylic acid (bp 133-137°C/12 mmHg) was obtained.
Dissolve this in 100 ml of methanol, add 20 ml of 40% sodium hydroxide solution and heat under reflux for 1 hour. After cooling, methanol is distilled off under reduced pressure. Add 60 ml of water to the residual solution, acidify with hydrochloric acid, and extract three times with 50 ml of chloroform. The chloroform layers were combined, dried over anhydrous sodium sulfate, and chloroform was distilled off under reduced pressure to give 2,2,3-trimethyl-3-
18.4 g of isobutoxycyclopropanecarboxylic acid was obtained. Example 5 60 g of tertiary butyl ester of β-n-amyloxy-β-methylacrylic acid are added to a suspension of 16.8 g of potassium tert-butyrate in 100 ml of anhydrous benzene. Add 18g of chloroform to this solution.
Add dropwise over approximately 1 hour at 10°C. After dripping 3
After stirring at room temperature for an hour, it is poured into water and extracted three times with 100 ml of ether. The ether layers are combined, washed with water, and dried over anhydrous sodium sulfate. Ether was removed under reduced pressure and distilled to obtain 30.1 g of tertiary butyl ester of 2,2-dichloro-3-methyl-3-n-amyloxycyclopropanecarboxylic acid (bp 129-132°C/5 mmHg). Ta. Dissolve this in 100 ml of methanol, add 30 ml of 30% potassium hydroxide solution, and heat under reflux for 1 hour. After cooling, methanol is distilled off under reduced pressure and 50ml of water is added to the residual liquid.
, add hydrochloric acid to make acidic, and add chloroform 50
Extract 3 times with ml. The chloroform layers were combined, dried over anhydrous sodium sulfate, chloroform was distilled off under reduced pressure, and 2,2-dichloro-3-methyl-3
-n-amyloxycyclopropanecarboxylic acid
23.6g was obtained. Substituted cyclopropanecarboxylic acid thus prepared (In the formula, R ₁ represents an alkyl group having 1 to 6 carbon atoms,
R ₂ represents a methyl group or a chlorine atom. ) or its reactive derivative can be prepared using the general formula HO−R ₆ ...() (wherein R ₄ is a group represented by the formula (), (), (), ()) according to the general method for ester production. shows. Here, X represents an oxygen atom or a (-CH=CH-) group, and _R9 represents an allyl group, a propargyl group,
It represents a benzyl group, a phenoxy group or a 2,2-dichlorovinyloxy group, and R ₈ represents a hydrogen atom, a methyl group or a halogen atom. R ₉ is a hydrogen atom,
They are a cyano group, an ethynyl group, or a trifluoromethyl group, and m represents an integer of 1 to 2. R ₁₀ represents an allyl group or a pentadienyl group. Y is an oxygen atom or a methylene group, and R ₁₁ represents a hydrogen atom, a methyl group, an allyl group, or a halogen atom. ) can be easily converted into a pyrethroid compound by reacting with an alcohol represented by the following formula or a reactive derivative thereof. Examples of reactive derivatives of carboxylic acids include acid halides, acid anhydrides, lower alkyl esters, and alkali metal salts. Examples of reactive derivatives of alcohol include chloride. The reaction is carried out in a suitable solvent, optionally in the presence of an organic or inorganic base as a deoxidizing agent or catalyst, or an acid, and optionally with heating. Representative examples of useful pyrethroid compounds include, but are not limited to, the following.

【table】

【table】

[Table] A specific example of the synthesis of the pyrethroid compound is as follows. Synthesis Example 1 3.9 g of 2,2,3-trimethyl-3-isobutoxycyclopropanecarboxylic acid was dissolved in 50 ml of dimethylformamide, and 3-phenoxy-α
-Trifluoromethylbenzyl chloride 5.4g
Add. Add 4ml of triethylamine while stirring.
After reacting at 60 to 80°C for 3 hours, it was dissolved in ether, the ether solution was thoroughly washed with dilute hydrochloric acid, aqueous sodium bicarbonate, and brine, dried over nitric acid, and the ether was distilled off under reduced pressure to give 3'-phenoxy-α. 7.0 g of '-trifluoromethylbenzyl 2,2,3-trimethyl-3-isobutoxycyclopropanecarboxylate was obtained. Synthesis Example 2 3.4 g of 2,2,3-trimethyl-3-ethoxy-cyclopropanecarboxylic acid and 3,4,5,6-
and 3.7g of tetrahydrophthalimidomethylol.
Dissolved in 50 ml of dry benzene, 6.2 g of dicyclohexylcarbodiimide was added and left overnight. The next day, the reaction was completed by heating under reflux for 4 hours, and after cooling, the precipitated dicyclohexyl urea was filtered off.
The oily substance obtained by concentrating the filtrate was poured down a 100 g silica gel column to obtain 3',4',5',6'-tetrahydrophthalimidomethyl 2,2,3-trimethyl-3-ethoxy-cyclopropane. 5.4 g of carboxylate was obtained. Synthesis Example 3 2,2-dichloro-3-methyl-3-n-hexyloxycyclopropanecarboxylic acid chloride
Dissolve 4.7g in 15ml of dry benzene and add 5-
Add 4.2 g of benzyl-α-ethynyl-2-furyl methyl alcohol dissolved in 20 ml of dry benzene, and add 3 ml of dry pyridine as a condensation aid.
When added, crystals of pyridine hydrochloride precipitate. After sealing the cap and leaving it overnight at room temperature, the crystals of pyridine hydrochloride were separated, and the benzene solution was dried with sulfuric acid and the benzene was distilled off under reduced pressure to give 5'-benzyl-α'-ethynyl-2'-furylmethyl. 2,2-dichloro-3-
6.4 g of methyl-3-n-hexyloxy-cyclopropanecarboxylate were obtained. Next, in order to make it clearer that the final pyrethroid compound obtained using the intermediate of the present invention is extremely useful, insecticidal test results and stability test results will be shown. Test Example 1 Insecticidal test by spraying A 0.2% white light solution of the 10 pyrethroid compounds (A), a white light solution of 0.2% and 0.8% piperonyl butoxide (B), a white light solution of 0.1% and phthalthrine 0.1% Solution (C), and each of allethrin and phthalthrin
Using house flies with a 0.2% white light solution, the falling and turning rate of house flies was determined using the spray drop method, the relative effectiveness of the test drug was calculated, and the mortality rate after 24 hours was determined as follows. .

【table】

[Table] As a result of the test, the pyrethroid compound obtained from the intermediate of the present invention showed a higher knockdown effect and lethal effect than the conventional pyrethroid allethrin and phthalthrin. Test example 2 Stability test For testing, 10 mg of sample was placed in a glass shear dish (36 cm ² )
This was done by spreading the mixture thinly, exposing it to sunlight outdoors on a sunny day in April, and quantifying the amount of the compound remaining after a certain period of time using gas chromatography. The test drug numbers were the same as those in the pyrethroid compound examples, and several conventional pyrethroids were used as control drugs.

[Table] As a result of the test, it was found that the pyrethroid compound obtained from the intermediate of the present invention has extremely superior light resistance compared to conventional pyrethroids.

Claims (1)

[Claims] 1. General formula (In the formula, R ₁ represents an alkyl group having 1 to 6 carbon atoms,
R ₂ represents a methyl group or a chlorine atom. ) and its optical and geometric isomers. 2 General formula (In the formula, R ₁ represents an alkyl group having 1 to 6 carbon atoms,
R ₂ represents a methyl group or a chlorine atom. ) A method for producing a substituted cyclopropanecarboxylic acid, which comprises reacting an ether represented by the following formula with a diazoacetate to obtain a substituted cyclopropanecarboxylic acid ester, and then hydrolyzing the ether. 3 General formula (In the formula, R ₁ represents an alkyl group having 1 to 6 carbon atoms,
X represents a halogen atom. ) is reacted with sodium benzenesulfinate to form phenylalkoxyalkylsulfone, and then the general formula (In the formula, R ₂ represents a methyl group or a chlorine atom, and R ₄
represents a methyl group or an ethyl group. ) A method for producing substituted cyclopropanecarboxylic acid, which comprises reacting a substituted acrylic ester represented by the following formula and further hydrolyzing it. 4 General formula (In the formula, R ₁ represents an alkyl group having 1 to 6 carbon atoms,
R ₅ represents a methyl group, an ethyl group or a tertiary butyl group. 1. A process for producing substituted cyclopropanecarboxylic acids, which comprises reacting an ester represented by () with chloroform in the presence of dimethyldiazomethane or potassium tertiary butyrate, followed by hydrolysis.