JPH0587057B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for racemizing primary chrysanthemum acids, and more specifically, the present invention relates to a method for racemizing primary chrysanthemum acids, and more specifically,

[Chemical formula] (In the formula, R represents a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group, or an aralkyl group, and * represents an asymmetric carbon.) In the presence of oxides or azo compounds, carboxylic acid bromides,
The present invention relates to a method for racemizing optically active chrysanthemum acids, which comprises reacting with at least one compound selected from silicon bromination, thionyl bromide, and N-bromine compounds. Daiichichrysanthemum acid constitutes the acid component of esters that are well known as so-called pyrethroid insecticides such as pyrethrin, allethrin, and phthalthrin, which are useful as low-toxicity and fast-acting insecticides, and has the general formula () The primary chrysanthemum acids represented by are useful as raw materials for these pyrethroid insecticides. The primary chrysanthemum acids represented by the general formula () have cis and trans geometric isomers, and each of them has (+) and (-) optical isomers, so there are a total of four isomers. exists. Generally, among these isomers, pyrethroid esters derived from the trans isomer exhibit stronger insecticidal activity than the corresponding pyrethroid esters derived from the cis isomer; It is known to exhibit much higher activity than the corresponding (-) esters. Daiichichrysanthemum acid is usually produced as a racemic mixture of cis and trans forms, that is, the (±) form, and by optically resolving this using an optically active organic base, the (+) form is obtained. Used in the production of highly active insecticidal compounds. The remaining (-) isomer optically resolved here has almost no activity as a pyrethroid ester, and therefore this useless (-) isomer is efficiently racemized and used as the raw material for the above optical resolution. To be able to serve as
This is especially a big problem when producing (+) bodies on an industrial scale. However, as mentioned above, cyclopropanecarboxylic acid represented by the general formula () has a _C1 position and
Since it has two asymmetric carbon atoms at the _C3 position, its racemization is accompanied by various difficulties. Up until now, the racemization method for primary chrysanthemum acids has been to oxidize the isobutenyl group at the _C3 position of (-)trans- primary chrysanthemum acid to convert it into a ketoalcohol group, and then convert it into a keto alcohol group _.
A method of esterifying a carboxylic acid in position and heating the reaction with an alkali metal alcoholate in the presence of a solvent (Japanese Patent Publication No. 39-15977), or using (-)-trans-carboxylic acid as a photosensitizer. A method of irradiating ultraviolet rays in the presence of
However, the former requires many reaction steps, and the latter has an inferior reaction rate, high power consumption of the light source, and a relatively short lifespan of the light source, making it difficult to implement industrially. It has various problems. The present inventors previously proposed a racemization method (Japanese Patent Publication No. 53-1973) in which an optically active primary chrysanthemum acid is used as an acid halide and a Lewis acid is made to act on this as a catalyst.
37858, JP-A-52-144651), a racemization method by reacting iodine to an anhydride of optically active cyclopropanecarboxylic acid (JP-A-57-1988),
-163341), and a racemization method in which a special catalyst such as boron bromide or aluminum bromide is applied to the primary chrysanthemum derivative (Japanese Patent Application Laid-open No. 174744/1983).
61-5045). As a result of further various studies, the present inventors found that carboxylic acid bromides, brominated silicons,
It was discovered that thionyl bromide and N-brome compounds, when used in combination with peroxides or azo compounds, surprisingly facilitated the racemization of optically active dichroic acids, and further conducted various studies. The present invention was completed by adding the following. That is, the present invention is based on the general formula ()

[Chemical formula] (In the formula, R represents a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group, or an aralkyl group, and * represents an asymmetric carbon.) In the presence of oxides or azo compounds, carboxylic acid bromides,
The present invention provides a method for racemizing optically active chrysanthemum acids, which comprises reacting with at least one compound selected from silicon bromination, thionyl bromide, and N-brome compounds. The method of the present invention is extremely advantageous because it can racemize optically active chrysanthemum acid itself or its ester without converting it into other derivatives. chrysanthemum acids separated and removed, for example, invalid (-) separated by a physicochemical resolution method using an optical resolving agent - (-) separated and removed by a biochemical resolution method using primary chrysanthemum acids or enzymes, etc. - It becomes possible to directly, efficiently and effectively utilize primary chrysanthemum acid esters, etc. Furthermore, the racemate obtained by the method of the present invention is rich in more effective trans isomers, and the method of the present invention is advantageous in this respect as well. The method of the present invention will be explained in detail below. Examples of the optically active primary chrysanthemum acids represented by the general formula () which are raw materials of the present invention include primary chrysanthemic acid, methyl primary chrysantheate, ethyl primary chrysantheate, propyl primary chrysantheate, and primary chrysanthemic acid. Butyl, cyclohexyl monochrylate,
Examples include optically active substances such as cyclohexylmethyl monochrylate and benzyl monochrylate. Each of the primary chrysanthemum acids has four isomers, and one of them can be used alone, or a mixture of these in any proportion can be used, and any level of optical purity can be used. However, it goes without saying that, in view of the purpose of the present invention, its significance is exhibited when a (-)-isomer or a carboxylic acid rich in (-)-isomer is used. As the carboxylic acid bromides used in the present invention, carboxylic acid bromides having 1 to 18 carbon atoms are usually used, such as acetyl bromide, propionyl bromide, butyryl bromide, isobutyryl bromide, valeryl bromide, isovaleryl bromide, pivaloyl bromide, hexanoyl bromide, heptanoyl bromide, cyclohexanecarbonyl bromide, octanoyl bromide,
inanoyl bromide, decanoyl bromide, 3-
Aliphatic monocarbonyl bromides such as (2-methylpropenyl)-2,2-dimethylcyclopropane carbonyl bromide, undecanoyl bromide, palmitoyl bromide, stearoyl bromide,
Aliphatic dicarboxylic acid dibromides such as malonyl dibromide, succinyl dibromide, glutaryl dibromide, adipoyl dibromide, pimeloyl dibromide, suberoyl dibromide, azeroyl dibromide, sebacoyl dibromide, benzoyl bromide, Acid bromides of mono- and dicarboxylic acids having aromatic groups such as enylacetyl bromide, phenylpropionyl bromide, phenylbutyryl bromide, naphthalenecarbonyl bromide, phthaloyl dibromide, terephthaloyl dibromide, isophthaloyl dibromide, etc. . Examples of the brominated silicones include lower alkylsilyl bromides such as trimethylsilyl bromide, dimethylsilyl dibromide, methylsilyl tribromide, and triethylsilyl bromide, and silyl tetrabromide. Examples of N-bromo compounds include N-bromo succinimide, N-bromoacetamide, N-bromopropionamide, N-bromobutyramide, and N-bromopareramide. Of these,
Preferably, carboxylic acid bromides are used, more preferably acetyl bromide, propionyl bromide and the like. The amount of these used is usually in the range of 1/1000 to 1/4 mole per mole of the primary chrysanthemum acid to be treated. Examples of peroxides include hydrogen peroxide, t
-butyl hydroperoxide, 1,1,3,
Hydroperoxides produced by oxidation of ethers such as 3-tetramethylbutyl hydroperoxide, tetrahydrofuran and dioxane, hydroperoxides such as kyumene hydroperoxide and diisopropylbenzene hydroperoxide, benzoyl peroxide, and lauroyl. Diacyl peroxides such as peroxide, peroxy esters such as t-butyl perbenzoate, t-butyl peracetate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, ketone peroxide such as methyl ethyl ketone peroxide, cyclohexanone peroxide, etc. Examples include oxides, dialkyl peroxides such as di-t-butyl peroxide and dicumyl peroxide, and peracids such as peracetic acid.
Among these, hydroperoxides, diacyl peroxides, and peroxy esters are preferred. The amount of peroxide used is generally 1/20 to 5 mol, preferably 1/10 to 2 mol, per mol of the bromine compound. Examples of azo compounds include azobisisobutyronitrile, 2,2'-azobis(2,4-dimethylvaleronitrile), 1,1'-azobis(cyclohexane-1-carbonitrile), 4,4'-
azobis-4-cyanopentanoic acid,
Azonitriles such as 2-phenylazo-2,4-dimethyl-4-methoxyvaleronitrile and 2-cyano-2-propylazoformamide, azo esters such as methyl azobisisobutyrate and ethyl azobisisobutyrate, and alkylazos such as azo-t-butane. etc. Preferably, azonitriles and azo esters are used. The amount used is generally 1/20 to 5 mol, preferably 1/10 to 2 mol, per 1 mol of the bromine compound. When carrying out the reaction, it is preferable to use an inert solvent, and examples of such solvents include saturated hydrocarbons, aromatic hydrocarbons, their halides, and ethers. Although the reaction temperature depends on the peroxide or azo compound used, it is arbitrary within the range of -20°C to the boiling point of the primary chrysanthemum acid (if a solvent is used, the boiling point), and is usually -20°C to It is 100℃. The time required for the reaction may vary depending on the amount of bromine compound and peroxide or azo compound used and the reaction temperature, but usually several minutes to 10 hours is sufficient to achieve the purpose. When carrying out the method of the present invention, the primary chrysanthemum acids to be treated are usually mixed with a peroxide or an azo compound in the presence of a solvent, and then a bromine compound is added thereto, or This is carried out by dissolving an acid in a solvent and then adding a peroxide or an azo compound and a bromine compound thereto. The degree of progress of the reaction can be determined by sampling a portion of the reaction solution and measuring the optical rotation, or by analysis using gas chromatography or the like. The racemized primary chrysanthemum acids obtained as described above can be converted into insecticidal esters through an esterification reaction with various pyrethroid alcohols. Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 Levorotatory primary chrysanthemum acids ((+)-cis form 1.8%, (-)
-cis form 17.6%, (+) -trans form 10.1%, (-)
- 10.0g of toluene (consisting of 70.5% trans isomer)
Azobisisobutyronitrile 0.19 dissolved in 20ml
Add 0.18g of acetyl bromide and stir at 80℃.
was dripped. After the reaction, dilute hydrochloric acid was added, stirred, and separated, and the organic layer was extracted twice with 27 g of 10% caustic soda aqueous solution.
The resulting aqueous layer was acidified with hydrochloric acid and extracted twice with toluene. The toluene layer was washed with water, dried over sodium sulfate, the solvent was distilled off under reduced pressure, and the residual liquid was then distilled to obtain 9.34 g of a fraction with a boiling point of 110-119°C/2.5 mmHg.
I got it. This substance was confirmed to be chrysanthemum acid by infrared absorption spectrum. A part of the distillate was induced into (+)-2-octyl ester, and the optical isomer ratio was measured by gas chromatography. As a result, the (+)-cis form was 3.5%;
(-)-cis form 3.5%, (+)-trans form 44.3%,
The (-)-trans form was 48.7%. Example 2 Add 20 g of toluene to 10.0 g of Daiichi Chrysanthemum acid used in Example 1.
ml and 0.58 g of t-butyl perbenzoic acid and heated to 100°C.
A solution of 0.37 g of acetyl bromide in carbon tetrachloride was added dropwise while stirring at the same temperature, and the mixture was stirred for 20 minutes at the same temperature. The same treatment as in Example 1 was carried out to obtain 8.3 g of Daiichi chrysanthemum acid. When a part of the distillate was measured in the same manner as in Example 1 to measure the optical isomer ratio of Daisic Chrysanthemum acid, it was found that the (+)-cis form was 3.4%, the (-)-cis form was 3.6%, and the (+)-cis form was 3.4%. The -trans form was 44.5%, and the (-)-cis form was 48.5%. Example 3 4.00 g of Daishu chrysanthemum acid used in Example 1 was added to toluene.
Azobisisobutyronitrile 98% dissolved in 20.0ml
91 mg of trimethylsilyl bromide was added dropwise while stirring at 80°C. The same treatment as in Example 1 was carried out to obtain 3.68 g of Daiichi chrysanthemum acid. The optical isomer ratio is (+)-cis isomer 3.5%, (-)-
3.5% cis form, 45.4% (+)-trans form, (-)-
The trans form was 47.6%. Example 4 2.00 g of chlorinated chrysanthemum acid used in Example 1 was dissolved in 10.0 ml of chlorobenzene, and 0.23 g of t-butyl perbenzoic acid was dissolved.
g, and 87 mg of trimethylsilyl bromide was added dropwise while stirring at 100°C. The same treatment as in Example 1 was carried out to obtain 1.63 g of Daiichi chrysanthemum acid. The optical isomer ratio is (+)-cis 3.8
%, (-)-cis form 3.6%, (+)-trans form 45.1
%, (-)-trans form was 47.2%. Example 5 2.1 g of Daiichi Chrysanthemum acid used in Example 1 was added to 10 g of toluene.
0.11 g of t-butyl hydroperoxide dissolved in ml
added. Trimethylsilyl bromide 0.19 at 20℃
g was added thereto, and the mixture was stirred at the same temperature for 20 minutes. The same treatment as in Example 1 was carried out to obtain 1.9 g of Daiichi chrysanthemum acid. The optical isomer ratio is (+)-cis 2.1%,
(-)-cis form 2.1%, (+) trans form 46.3%,
The (-)-trans form was 49.5%. Example 6 0.50 g of (-)-cis primary chrysanthemum acid and 47 mg of azobisisobutyronitrile were dissolved in 10 ml of toluene. 80
Add 59 mg of thionyl bromide dropwise while stirring at ℃,
Stir for a minute. The same treatment as in Example 1 was carried out to obtain 0.4 g of Daiichi chrysanthemum acid. The optical isomer ratio is (+)-cis isomer 3.6%,
(-)-cis form 7.1%, (+)-trans form 44.8%,
The (-)-trans form was 44.5%. Example 7 1.0 g of chrysanthemum acid used in Example 1 and 98 mg of azobisisobutyronitrile were dissolved in 10 ml of dioxane.
N-bromsuccinimide with stirring at 80 °C.
0.15g was added and reacted for 20 minutes. After the reaction, 1 g of 40% aqueous sodium hydroxide solution was added, and the solvent was distilled off under reduced pressure. Water and toluene were added to the residue, and extraction was performed to separate the layers. The aqueous layer was neutralized with dilute sulfuric acid, extracted with toluene, and then washed with water.
Next, the organic layer was concentrated and distilled to obtain 0.79g of daisies chrysanthemum acid.
I got it. (Boiling point 110-119℃/2.5mmHg) Optical isomers are (+)-cis 2.1%, (-)-cis 2.1%,
(+)-trans form 40.6%, (-)-trans form 55.2%
It was %. Example 8 1.0 g of chrysanthemum acid used in Example 1 and 98 mg of azobisisobutyronitrile were dissolved in 10 ml of toluene. 80
While stirring at °C, 0.11 g of benzoyl bromide was added dropwise, and the mixture was allowed to react for 20 minutes. Analysis of the optical isomer ratio of this product revealed that the (+)-cis form was 3.3%, the (-)-cis form was 2.4%, and the (+)-cis form was 2.4%.
The trans-isomer accounted for 43.6% and the (-)-trans-isomer accounted for 50.7%. Example 9 2.0 g of chrysanthemum acid used in Example 1 and 0.15 g of azobisisobutyronitrile were dissolved in 20 ml of toluene.
0.25 g of adiboyl dibromide while stirring at 80℃
was added dropwise and allowed to react for 20 minutes. Analysis of the optical isomer ratio of this product revealed that the (+)-cis form was 3.8%, the (-)-cis form was 3.4%, and the (+)-cis form was 3.4%.
The trans-isomer accounted for 43.4% and the (-)-trans-isomer accounted for 49.4%. Example 10 (+)-cis form 1.8%, (-)-cis form 18.3%,
(+)-trans form 11.1%, (-)-trans form 68.8%
% ethyl ester of chrysanthemum acid and 0.27 g of azobisisobutyronitrile in 20 ml of toluene.
dissolved in While stirring at 80°C, 0.38 g of trimethylsilyl bromide was added and reacted for 20 minutes. The reaction solution was washed with a 2% aqueous sodium hydroxide solution, and the solvent was distilled off. Distilled under reduced pressure with the following, boiling point 85-88
2.6 g of distillate at ℃/10 mmHg was obtained. This product was confirmed to be ethyl ester of chrysanthemum acid based on infrared absorption spectrum. The carboxylic acid obtained by hydrolyzing a part of it by a conventional method was converted into an ester with (+)-2-octanol, and the optical isomer ratio was determined by gas chromatography. 3.5%,
(-)-cis form 3.5%, (+)-trans form 43.5%,
The (-)-trans form was 49.5%. Example 11 Ethyl chrysanthemum ester used in Example 10 0.32
g and benzoyl peroxide 50mg to chlorobenzene 10ml
dissolved in 29 mg of acetyl bromide was added at 80°C and reacted for 20 minutes. A part of this material was sampled, hydrolyzed using a conventional method, and the optical isomer ratio was determined: (+)-cis isomer 3.5%, (-)-cis isomer 3.5%, (+)-
The trans isomer was 42.0%, and the (-)-trans isomer was 51.0%.

Claims (1)

[Claims] 1 Represented by the general formula: (wherein, R represents a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group, or an aralkyl group, and * represents an asymmetric carbon.) In the presence of a peroxide or an azo compound, carboxylic acid bromides,
A method for racemizing optically active chrysanthemum acids, which comprises reacting with at least one compound selected from silicon bromination, thionyl bromide, and N-bromine compounds.