JPS58131937A - Substituted cyclopropanecarboxylic acid and its preparation - Google Patents

Abstract

NEW MATERIAL:Optical and geometrical isomers of a substituted cyclopropanecarboxylic acid of formulaI(R1 is 1-8C alkyl; R2 is methyl, Cl), having l- conformation. EXAMPLE:(l)-trans-2,2-Dimethyl-3-methoxycyclopropanecarboxylic acid. USE:An acid component of insecticides: it shows high insecticidal effects, low toxicity to warm-blood animals and very high stability to light. PREPARATION:The reaction of an ether of formula II with a diazoacetic ester to form a substituted cyclopropanecarboxylic ester, which is hydrolyzed to give the compound of formulaI.

Description

Detailed Description of the Invention The present invention relates to substituted cyclopropanecarboxylic acids represented by the general formula (wherein R represents an alkyl group having 1 to B carbon atoms, and & represents a methyl group or a chlorine atom). The present invention relates to optical and geometrical isomers having conformation and methods for producing the same.

Various alcohol components of chrysanthemum acid esters have been studied and put into practical use, but they tend to be easily oxidized and decomposed by light, and there are no restrictions on their outdoor use.

Recently, research into acid components has become active, and a compound that is more stable to light than conventional pyrethroids has been discovered by directly replacing the methyl group of the isobutynyl 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 the above formula (
The ester whose acid component is a substituted cyclopropanecarboxylic acid having an alkoxy group represented by il is extremely effective as an insecticidal component against various sanitary pests and agricultural and horticultural pests, and has extremely low toxicity to warm-blooded animals. I learned that it is much more stable against light than conventional pyrethroids.

The optically active 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 found that
A semi-mixture was obtained which could be prepared by resolution using an optically active amine.

That is, the following eight methods were suitable for obtaining a racemic mixture.

(1) The ether represented by the general formula (in the formula, n, -r have the same meanings as above) is reacted with a diazoacetic acid ester to form a substituted cyclopropane carboxylic acid ester, which is then hydrolyzed and substituted. Method for Obtaining Cyclopropane Carboxylic Acid (2) General Formula %Formula % (In the formula, L has the same meaning as above, and X represents).Rogen atom. ) is reacted with sodium benzenesulfinate to give phenylalkoxyargyl sulfone, and then the general formula (where RI/Ii has the same meaning as above and RIili
Indicates a methyl group or an ethyl group. ) A method of reacting a substituted acrylic acid Nisder represented by () and further hydrolyzing it to obtain a substituted cyclopropanecarboxylic acid.

(8) General formula % Formula % (In the formula, R has the same meaning as above, RI is a methyl group,
Indicates an ethyl group or a tertiary butyl group.

) is reacted with chloroform in the presence of dimethyldiazomethane or caricum tertiary butyrad, and then hydrolyzed to obtain a substituted cyclopropanecarboxylic acid.

In addition, the lower alkyl ester is cis.

The trans mixture can be separated, for example, by column chromatography, and when heated in the presence of a basic catalyst, it can be converted into only the trans form by K.

The thus obtained racemic carboxylic acid i;jc&! - Easily resolved using optically active amines such as phenyl-β-(p-tolyl)ethylamine, α-(1-naphthyl)ethylamine, p-nitrophenyl-2-dimethylamino-1,8-propanediol I can do it.

For example, (1)-cyclopropanecarboxylic acid can be obtained using (1)-α-phenyl-β-(P-tolyl)ethylamine.

Next, as the raw material used in the production method of the present invention, for example, the ether in methods (1) and (2) is obtained by reacting an alcohol and an aldehyde in the presence of hydrogen halide to obtain an alkyl haloalkyl ether.

This product becomes a raw material for production method (2), and by reacting this product with a suitable base and dehydrohalogenating it, an alkyl alkenyl ether can be obtained as a raw material for method 1). Also, the alkali metal alcolade and β-
There is also a method of reacting methyl allyl halide and then isomerizing it to obtain an alkyl alkenyl ether. (8)
Kawahara's raw material ester can be easily obtained by reacting a β-halogen acid ester with an alkali metal alcoholade.

Various derivatives of the substituted cyclopropanecarboxylic acid #'i of the present invention are used in the production of Nisdel with alcohol, 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) (1)-trans-2,2-dimethyl-8-methoxysif0 lopropanecarboxylic acid nD 1.4491 (
2) (1)-trans-2,2-dimethy/l/-3
-n-propoxycyclopropanecarboxylic acid ngo
1.4508(8) (1)-cis, trans-2,
2-dichloro-8-inpropoxycyclopropanecarboxylic acid 0 n, 1.4581 ((trans)(1)-cis, trans-2,2-dimethyl-
g -n-amyloxycyclopropanecarboxylic acid 0 n, 1.4551 (5) (1)-cis-2,2-dichloro-8-ynamyloxy0 cyclopropanecarboxylic acid nD 1.4560 (
6) (1)-cis,trans-2,2-dichloro-g
-n-amyloxycyclopropanecarboxylic acid 1go1.4598 (η(1)-trans-2,2-dimethyl-g -n-
Hexyloxycyclopropanecarboxylic acid n” 1
．． 4580(8)(1)-cis-2,2-dimethyl-8
-(B-ethylhexyloxy)cyclopropanecarboxylic acid n" 1.461g +91 (1)-trans-2,2-dimethy/L/-3
-n-heptyloxycycloprobancarvone* n
20 ShilO8 Next, each reaction condition for the production method of the present invention will be explained.

(1) For the reaction J6 between alkyl alkenyl ether and ethyl diazoacetate, no solvent is used and alkyl alkenyl ether is used in excess of the solvent, and nitrogen gas is continuously generated under heating conditions of 10,060 or higher. Do it under conditions. The reaction can also be carried out in the presence of rounded copper sulfate or copper, which facilitates the reaction.

(The reaction between 21-furkylhaloalkylneedle and benzenesulfinic 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 phenylalkoxyalkylsulfone, which is then replaced with a substituted acrylic acid. The esterification is carried out in an inert solvent, for example benzene, toluene, tetrahydrofuran, preferably dimethylformamide, dimethyl sulfoxide, acetonitrile, in the presence of a basic agent, under anhydrous conditions.

The basic agent is preferably an alkali amide, an alkali metal hydride, or an alcoholade, and preferably sodium methylate or calicum royal butylade.

(8) In the reaction of 1111-substituted acrylic ester and dimethyldiazomethane, an excess of Km-substituted acrylic ester is used in the same manner as in (1) for alkyl alkenyl ether and ethyl diazoacetate, and the reaction is carried out by heating in the presence of copper or copper sulfate. conduct. The reaction between a substituted acrylic acid ester and chloroform in the presence of calicum tertiary butyrad is performed by reacting the substituted acrylic ester with chloroform in the presence of calicum tertiary butyrad in an inert solvent, for example, benzene. A substituted cyclopropanecarboxylic ester is obtained, which is then hydrolyzed to obtain a substituted cyclopropanecarboxylic acid.

Hydrolysis is the same for (1), (2), and (8), but
It can be easily converted into an acid by alkaline hydrolysis.

Next, the present invention will be explained in detail in Examples.

Example 1 28 g of n-amyl-1-isobutenyl needles and tg of copper sulfate are placed in an 800-mm three-neck flask, and 0.5 g of ethyl diazoacetate is added. The mixture is heated to 6120''C, and when the reaction starts with continuous nitrogen evolution, 11 g of ethyl diazoacetate is gradually added dropwise, keeping the temperature around tgo'c.After the reaction is completed, filter and remove the P solution. Distilled under reduced pressure to obtain 2
．． Ethyl ester of 2-dimethyl-3-n-amyloxycyclopropanecarboxylic acid (bp 188-187°
5 g of C/2(lIllHg)I L was obtained. 2N for this
After adding $1001 of sodium hydroxide in methanol and heating and refluxing for 80 minutes, the methanol was removed under reduced pressure, water was added, concentrated hydrochloric acid was added to make it acidic, and the mixture was extracted 8 times with 50% chloroform. Combine the chloroform layer with
After drying over anhydrous sodium sulfate, chloroform was distilled off under reduced pressure to obtain 145 gt of 2,2-dimethyl-3-n-γ-miloxycyclopropanecarboxylic acid.

Examples & Isopropyl-2,2-dichlorovinyl ether 8&
Put 8g and 1.5g of copper powder into an 800-mm three-loaf flask,
Add 5 g of methyl diazoacetate α.

The mixture is heated to about 180'C and nitrogen is continuously added dropwise to the mixture.

The temperature is maintained at around 140'C, and the addition is carried out so that nitrogen generation occurs continuously. After the dropwise addition, heating was continued for 80 minutes, then cooled, and 50 s of benzene was added to dissolve it, followed by filtration.

Benzene was distilled off from the F solution under reduced pressure, and then distilled to give 2.
Methyl ester of 2-dichloro-8-isopropoxycyclopropanecarboxylic acid (bp 121-1g6°C/
8 ■aug) jil & 78 obtained 9. Add this to 1 methanol
Potassium hydroxide gOg was dissolved in 50m of water, a solution was added thereto, and the mixture was heated under reflux for 1 hour. After cooling, methanol was distilled off under reduced pressure, water was added, concentrated hydrochloric acid was added to make the mixture acidic, and the mixture was extracted with chloroform 5011d. The chloroform layers were combined and dried over anhydrous sulfuric acid, and then chloroform was distilled off under reduced pressure to obtain 2&1st-2,2-dichloro-3-isopropoxycyclopropanecarboxylic acid.

Example & Add 8 g of sodium carbonate and 18 g of sodium phenylsulfinate in methanol, and add 1 nag of propoxymethyl bromide dropwise to the suspension at room temperature over about 80 minutes.

After stirring for about 2 hours at room temperature, the reaction mixture is poured into ice water and extracted 8 times with 100 ml of ether. The ether layers were combined and dried over anhydrous sodium sulfate, the ether was removed under reduced pressure, and phenyl-n-propoxymethylsulfone 2
α5g was obtained. Add 88 g of Calicum tertiary butyrad in dimethylformamide g O0sff and dissolve phenyl-n-propoxymethylsulfone 2a5 in the solution.
g and stirred for 80 minutes. Next, 6 g of ethyl ester of β-dimethylacrylic acid is added dropwise. Stir at room temperature for 2 hours, cool to 0°C, pour into a mixture of water and dilute hydrochloric acid solution, extract 8 times with 10G of ether, and combine the ether layers. This ether solution was washed with brine, sodium bicarbonate and again with brine, dried over anhydrous sodium sulfate, the ether was distilled off under reduced pressure, and 21g-dimethyl-3-
Ethyl ester of n-propoxycyclopropanecarboxylic acid (bplOg~106°C/15mmHg)17.
6g was obtained. Dissolve this in 50 wIt of methanol and
Add 0% sodium hydroxide solution gOsff, heat under reflux for 1 hour, cool and add methanol under reduced pressure.
After drying with i2 sodium, chloroform was distilled off under reduced pressure to obtain $15 g of 2,2-dimethyl-3-n-propoxycyclopropane carpon.

Example Table Ethyl ester of β-n-hexyloxyacrylic acid 8
0 g and 2 g of copper sulfate are placed in an 800-glass flask, and approximately 5 g of dimethyldiazomethane is added. Mixture about 10
After heating to 08C and ensuring that nitrogen is continuously generated to start the reaction, dimethyldiazomethane flag and β
-n-hexyloxyacrylic acid ethyl ester 10
Gradually add the mixture of g. The temperature is maintained at around 100'C, and nitrogen is continuously generated while being kept under am. After the reaction is complete, 100 d of benzene is added to dissolve the mixture and filtered. Benzene was distilled off from the P solution under reduced pressure, and the solution was distilled to obtain ethyl nisder of 2,8-dimethyl-3-n-hexyloxycyclopropanecarboxylic acid (bp1g6-14
0''''C/12mmHg) gl, 8g'5r was obtained. Dissolve this in 100 methanol, add 20ml of 40% sodium hydroxide solution, and heat under reflux for 1 hour. After cooling, under reduced pressure. Distill off methanol. Add 60% water to the residual liquid.
The mixture was acidified with hydrochloric acid and extracted 8 times with chloroform 501. The chloroform layers were combined, dried over anhydrous sodium sulfate, and then chloroform was distilled off under reduced pressure to obtain 111 g of 2,2-dimethyl-3-n-hexyloxycyclopropanecarboxylic acid.

Example & Calicum tertiary petitlar in anhydrous benzene 100sd)
60 g of tertiary glutyl ester of β-n-amyloxyacrylic acid is added to the suspended solution of 1a8 gt. To this solution, 18 g of chloroform was added dropwise at 100 C over about 1 hour. After the dropwise addition was completed, the mixture was stirred at room temperature for 8 hours, poured into water, and extracted 8 times with 100ml of ether. The ether layers are combined, washed with water, and dried over anhydrous sodium sulfate. The ether was distilled off under reduced pressure and distilled to give tertiary butyl ester of 2,2-dichloro-8-n-amyloxycyclopropanecarboxylic acid (bp1g7 to 85'C15a).
imHgC15ai was obtained. Add this to methanol 10G-
Add 80 d of 80% potassium hydroxide solution and heat under reflux for 1 hour. After cooling, methanol is distilled off under reduced pressure, 50% of K water is added, hydrochloric acid is added to make it acidic, and the mixture is extracted 8 times with 50W11 of chloroform. The chloroform layers were combined and dried over anhydrous sodium sulfate, and the chloroform was distilled off under reduced pressure to give 2,2-dichloro-g-n-
g & 1 gt of amyloxycyclopropanecarboxylic acid were obtained.

Example: 27g of dl-trans-dimethyl-8-isobutoxycyclopropanecarboxylic acid was added to 27g of methanol 0w
Dissolve 1K and use this! -α-phenyl-β-(P-tolyl)ethylamine & Og was added and left overnight at room temperature.

The obtained crystals were recrystallized 8 times from methanol,
7 g of l-α-phenyl-β-(P-tolyl)ethyl 1 miniz salt of l-trans acid was obtained. Add 25 d of benzene and 1 g of Bm-HC (5 ml) to the amine salt, shake well,
After thoroughly washing the benzene layer and removing the solvent,
g, 0.75 gt of 2-dimethyl-8-isobutoxycyclopropanecarboxylic acid was obtained*.

Patent applicant Katsu 1) Pure Department

Claims (1)

[Scope of Claims] (1) General formula (in the formula, &Fi represents an alkyl group of 1 to 8, Jj
Indicates a methyl group or a chlorine atom. ) Optical and geometric isomers having the l conformation of substituted cyclopropanecarboxylic acids. (2) General formula (wherein RIFi represents an alkyl group having 1 to 8 carbon atoms, F
b#'i Indicates a methyl group or a chlorine atom. A method for producing a substituted cyclopropane carboxylic acid, which comprises reacting the ether represented by the following formula with a diazoacetic acid ester to obtain a substituted cyclopropane carboxylic acid ester, and then hydrolyzing the ether. (8) The ether represented by the general formula % formula % (in the formula, R represents an alkyl group having 1 to 8 carbon atoms, and X represents a halogen atom) is reacted with sodium benzenesulfinate to produce phenylalkoxyalkylsulfonate. and then react with a substituted acrylic ester represented by the general formula (in the formula, R represents a methyl group or a chlorine group, and R represents a methyl group or an ethyl group), and further hydrolyzed. A method for producing a substituted cyclopropanecarboxylic acid. (4) General formula % Formula % (In the formula, R represents an alkyl group having carbons tkl to 8, and RI
represents a methyl group, an ethyl group or a tertiary butyl group. ) is reacted with chloroform in the presence of dimethyldiazomethane or caricum tertiary butyrad,
1. A method for producing substituted cyclopropanecarboxylic acid, which comprises subsequently hydrolyzing it.