JPH0688935B2 - Method for racemization of optically active primary chrysanthemic acids - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial field of application> The present invention relates to a method for racemizing primary chrysanthemic acids, and more specifically to the general formula (I) (In the formula, X represents a hydroxyl group, a halogen atom, an alkoxy group having 1 to 20 carbon atoms, 2,2-dimethyl-3-isobutenylcyclopropanecarboxyl group, and * represents an asymmetric carbon.). The present invention relates to a racemization method of an optically active primary chrysanthemic acid, which comprises reacting an optically active primary chrysanthemic acid with an SH compound in the presence of a peroxide or an azo compound.

<Prior arts and problems to be solved by the invention> Primary chrysanthemic acid is an acid of an ester well known as a so-called pyrethroid insecticide such as pyrethrin, allethrin and phthalthrin, which is useful as a low-toxic and fast-acting insecticide. The primary chrysanthemic acid, which constitutes the component and is represented by the general formula (I), is useful as a raw material for these pyrethroid insecticides.

The primary chrysanthemic acids represented by the general formula (I) have cis and trans geometric isomers, and each of them has (+) and (−) optical isomers. There is a body. In general, among these isomers, the pyrethroid-type ester derived from the trans-form has stronger insecticidal activity than the corresponding pyrethroid-type ester derived from the cis-form, and the (+)-form ester is It is known to show much higher activity than the corresponding (-)-form esters.

The primary chrysanthemic acid is usually produced as a racemic mixture of cis and trans isomers, that is, a (±) isomer, and by optically resolving this with an optically active organic base, a (+) isomer can be obtained. Used in the production of highly active insecticidal compounds. The remaining (-) form optically resolved here has almost no activity as a pyrethroid-type ester, and therefore, this (-) form which is not useful is efficiently racemized to obtain a more effective (±) form. The conversion of the above into a major problem becomes a serious problem especially when the pyrethroid ester is produced on an industrial scale.

However, as described above, the cyclopropanecarboxylic acids represented by the general formula (I) have two asymmetric carbons at the C ₁ position and the C ₃ position, and therefore various racemates are involved in their racemization. U

As a racemization method for primary chrysanthemic acids, the present inventors have previously described a racemization method by reacting optically active primary chrysanthemic acid as an acid halide with a Lewis acid as a catalyst.
58-87858, JP-A-52-144651), a racemization method by reacting iodine with an optically active anhydride of cyclopropanecarboxylic acid (JP-A-57-163341), and A racemization method by reacting chrysanthemic acid with a special catalyst called aluminum bromide (Japanese Patent Laid-Open No. 60-174744)
Japanese Patent Laid-Open No. 61-5045).

As a result of further various investigations by the present inventors, the compound having an SH group showed little racemization effect on the optically active primary chrysanthemic acid represented by the general formula (I) by itself. However, surprisingly, it was found that racemization proceeds extremely conveniently by sharing it with a peroxide or an azo compound, and various studies were added to this to complete the present invention.

<Means for Solving the Problems> That is, the general formula (I) of the present invention (In the formula, X represents a hydroxyl group, a halogen atom, an alkoxy group having 1 to 20 carbon atoms, a 2,2-dimethyl-3-isobutenylcyclopropanecarboxyl group, and * represents an asymmetric carbon.) It is intended to provide an industrially excellent method for racemizing an optically active primary chrysanthemic acid, which comprises reacting an active primary chrysanthemic acid with an SH compound in the presence of a peroxide or an azo compound.

The method of the present invention will be described in detail below.

Examples of the optically active primary chrysanthemic acid represented by the general formula (I) which is a raw material of the present invention include primary chrysanthemic acid, primary chrysanthemic acid chloride, primary chrysanthemic acid bromide, methyl primary chrysanthemic acid, and primary dichrysanthemic acid Examples thereof include optically active substances such as ethyl acid salt, propyl primary chrysanthemate, butyl primary chrysanthemate, cyclohexyl primary chrysanthemate, cyclohexyl methyl primary chrysanthemate, benzyl primary chrysanthemate, and anhydrous monochrysanthemate.

Each of the primary chrysanthemic acids has four kinds of isomers, but one kind of them can be used alone or a mixture of them at any ratio can be used, and the optical purity is not limited to any degree. However, it goes without saying that when the (−) form or the carboxylic acid rich in the (−) form is used for the purpose of the present invention, its significance is exhibited.

The SH compound used in the present invention may be any compound having a —SH group, and thiols, thiocarboxylic acids, dithioacids and the like are usually used. Specific compounds include, for example, thiophenol, o-, m- and p-thiocresol, o-, m- and p-methoxybenzenethiol,
1- and 2-naphthalenethiol, thiocatechol,
Aromatic thiols such as thioresorcin, thiohydroquinone, dithiocatechol, dithioresorcin, dithiohydroquinone, aralkyl thiols such as benzyl mercaptan, methanethiol, ethanethiol, 1-propanethiol, 2-propanethiol, butanethiol,
Pentanethiol, hexanethiol, heptanethiol, octathiol, nonanethiol, decanethiol, dodecanethiol, dithiothritol, dithioerythritol, alkylthiols such as butanedithiol, thioglycolic acid, thiosalicylic acid, thiolactic acid, thiomalic acid, etc. And thiocarboxylic acids such as thiocarboxylic acid, thioacetic acid, thiopropionic acid, thiobutyric acid, and thiobenzoic acid, and dithioacids such as dithioacetic acid, dithiopropionic acid, dithiobutyric acid, and dithiobenzoic acid.

Preferably aromatic thiols, thiol carboxylic acids,
Thiocarboxylic acids and dithioacids are preferable, and thiophenol, thiocresol, thiosalicylic acid, and thiobenzoic acid are more preferable.

The amount of the SH compound used is usually 1/500 to 1/2 mol for the primary chrysanthemic anhydride and usually 1/1000 to 1 for the other primary chrysanthemic acid, relative to 1 mol of the treated primary chrysanthemic acid. / 4 mol range.

Examples of the azo compound include azobisisobutyronitrile, 2,2′-azobis (2,4-dimethylvaleronitrile), 1,1′-azobis (cyclohexane-1-carbonitrile) and 4,4′-azobis. -4-Cyanopentanoic acid, 2-phenylazo-2,4-dimethyl-4
-Azonitriles such as methoxyvaleronitrile, 2-cyano-2-propylazoformamide, azobisisobutanol diacetate, azoesters such as methyl azobisisobutyrate and ethyl azobisisobutyrate, azo-t
And alkylazos such as butane. Azonitriles and azoesters are preferably used.

The amount used is usually 1/20 to 5 per mol of SH compound.
It is in the range of 1/10 to 2 mol, preferably 1/10 to 2 mol.

Examples of the peroxide include hydrogen peroxide, t-butyl hydroperoxide, 1,1,3,3-tetramethylbutyl hydroperoxide, tetrahydrofuran, hydroperoxide produced by oxidation of ethers such as dioxane, Hydroperoxides such as cumene hydroperoxide, diisopropylbenzene hydroperoxide, benzoyl peroxide,
Diacyl peroxides such as lauroyl peroxide, t-butyl perbenzoate, t-butyl peracetate, diisopropyl peroxydicarbonate,
Peroxyesters such as dicyclohexylperoxydicarbonate, methyl ethyl ketone peroxide, ketone peroxides such as cyclohexanone peroxide, di-t-butyl peroxide, dialkyl peroxides such as dicumyl peroxide,
Examples include peracids such as peracetic acid. Among these, diacyl peroxides and peroxyesters are preferably used.

The amount of peroxide used is usually 1/20 to 1 mol of SH compound.
The amount is 5 mol, preferably 1/10 to 2 mol.

In carrying out the reaction, it is preferable to use an inert solvent, and examples of such a solvent include saturated hydrocarbons, aromatic hydrocarbons and their halides, ethers and the like.

The reaction temperature is in the range of −20 ° C. to the boiling point of the primary chrysanthemic acid (the boiling point of the solvent used when a solvent is used), but usually 40
It is in the range of ℃ to 100 ℃.

The time required for the reaction may vary depending on the amounts of the SH compound, peroxide and azo compound used and the reaction temperature, but usually several minutes to 7 hours can sufficiently achieve the purpose.

The degree of progress of the reaction can be determined by sampling a part of the reaction solution and measuring the optical rotation, or by analysis by gas chromatography or the like.

<Effects of the Invention> Although racemic chrysanthemic acids are thus produced, according to the present invention, any optically active carboxylic acid, acid halide, ester or anhydride can be directly used without leading to other derivatives. Can be converted to the corresponding racemic compound and the general SH compound can be used as an industrial raw material, which is particularly advantageous in industrial implementation.

Further, the racemate obtained by the method of the present invention is rich in the more effective trans isomer, and the method of the present invention is also advantageous in this respect.

<Examples> Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 1.0 g of (-)-cis primary chrysanthemic acid and 48 mg of azobisisobutyronitrile were dissolved in 5 ml of toluene, and a solution of 55 mg of thiophenol in toluene was added dropwise with stirring at 80 ° C.
The stirring was continued for a minute.

After the reaction, dilute hydrochloric acid was added and the mixture was stirred and separated.
% Aqueous sodium hydroxide 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 then the residual liquid was distilled to obtain 0.92 g of a fraction having a boiling point of 110 to 119 ° C./2.5 mmHg. This product was confirmed to be chrysanthemic acid from the infrared absorption spectrum.

A part of the distillate was derivatized to (+)-2-octyl ester, and the optical isomer ratio was measured by gas chromatography to obtain (+)-cis isomer 3.8%, (-)-cis 6.7%,
(+)-Trans form 44.7%, (-)-trans form 44.8%
Met.

Example 2 1.0 g of levorotatory primary chrysanthemic acid (consisting of (+)-cis isomer 1.8%, (-)-cis isomer 17.6%, (+)-trans isomer 10.1%, (-)-trans isomer 70.5%) And t-butyl perbenzoate 0.11
g was dissolved in 5 ml of toluene, and a toluene solution of 110 mg of thiophenol was added dropwise with stirring at 100 ° C., and stirring was continued at the same temperature for 80 minutes.

After the reaction, the same treatment as in Example 1 was carried out to obtain 0.89 g of primary chrysanthemic acid.

The optical isomer ratios were (+)-cis isomer 6.9%, (−)-cis isomer 7.0%, (+)-trans isomer 41.5%, and (−)-trans isomer 44.6%.

Example 3 (+)-cis form 1.8 in a 100 ml flask in a nitrogen stream.
%, (−)-Cis form 18.3%, (+)-trans form 11.1
%, (1-)-trans form 68.8% of ethyl ester of primary chrysanthemic acid 1.31 g and azobisisobutyronitrile 82 mg are dissolved in toluene 5 ml, and a toluene solution of thiophenol 110 mg is added dropwise while stirring at 80 ° C. Then, stirring was continued for 30 minutes at the same temperature.

After the reaction, 2% aqueous sodium hydroxide solution was added for extraction, and the organic layer was washed with water. The obtained organic layer was concentrated under reduced pressure and then distilled to obtain 1.17 g of a distillate having a boiling point of 85 to 88 ° C./10 mmHg.

It was confirmed from the infrared absorption spectrum that this was ethyl ester of primary chrysanthemic acid, and a part of it was hydrolyzed by a conventional method to obtain the obtained carboxylic acid into an ester with (+)-2-octanol. Then, the optical isomer ratios were determined by gas chromatography. (+)-Cis isomer 4.3%, (-)-cis isomer 4.4%, (+)-trans isomer 4
It was 4.9% and (-)-trans isomer 46.4%.

Example 4 The same ethyl chrysanthemate 1.31 g and t-butyl perbenzoate 0.12 g used in Example 3 were dissolved in toluene 5 ml, and a toluene solution of thiophenol 110 mg was added dropwise with stirring at 90 ° C. Stirred at temperature for 30 minutes.

After the reaction, the same operation as in Example 3 was performed to obtain 1.16 g of ethyl primary chrysanthemic acid ester.

Optical isomer ratio is (+) cis isomer 6.1%, (-)-cis isomer 6.2
%, (+)-Trans form 43.4%, (-)-trans form 4
It was 4.3%.

Example 5 (-)-cis Chrysanthemic acid 500 mg and azobisisobutyronitrile 4
8 mg was dissolved in 5 ml toluene. While stirring at 80 ℃ p-
Toluene solution of thiocresol 55 mg was added dropwise over 10 minutes,
Stirring was continued for 30 minutes at the same temperature.

As a result of performing optical isomer analysis by gas chromatography, (+)-cis isomer 4.3%, (-)-cis 6.9%,
(+)-Trans form 44.3%, (-)-trans form 44.5%
Met.

Example 6 (-)-cis Chrysanthemic acid 500 mg and azobisisobutyronitrile 4
8 mg was dissolved in 5 ml toluene. While stirring at 80 ° C 1-
Toluene solution of 40 mg butanethiol was added dropwise over 10 minutes,
Stirring was continued for 30 minutes at the same temperature.

Results of optical isomer analysis by gas chromatography (+)-cis isomer 3.4, (-)-cis isomer 45.0%,
(+)-Trans form 25.7%, (-)-trans form 25.9%
Met.

Example 7 (+)-cis isomer 1.8%, (-)-cis isomer 18.3%, (+)
-1.21 g of primary chrysanthemic acid chloride consisting of 11.1% of trans isomer and 68.8% of (-)-trans isomer and 82 mg of azobisisobutyronitrile were dissolved in 5.0 ml of toluene, and a solution of thiophenol 100 mg in toluene was stirred at 80 ° C. And add 3 at the same temperature.
Stirring was continued for 0 minutes. Results of optical isomer analysis by gas chromatography (+)-cis 5.6%,
(-)-Cis 5.8%, (+)-trans 42.5%,
(-)-Trans form was 46.1%.

EXAMPLE 8 2.0 g of the same levorotatory primary chrysanthemic acid and azobisisobutyronitrile used in Example 2 in a 50 ml flask in a stream of nitrogen were used.
2 g of benzene was dissolved in 10 ml of benzene, and a solution of 0.25 g of thiobenzoic acid in benzene was added dropwise while stirring at 75-80 ° C.
Stirring was continued for hours.

After the reaction, the same treatment as in Example 2 was performed to obtain 1.74 g of primary chrysanthemic acid.
Got

The optical isomer ratio of this product is (+)-cis 3.4%,
(-)-Cis 3.7%, (+)-trans 44.6%,
(−)-Trans isomer was 48.3%.

Example 9 In a 50 ml flask, in a nitrogen stream, 2.0 g of the same levorotatory primary chrysanthemic acid and 0.46 g of perbenzoic acid tert-butyl ester used in Example 2 were dissolved in 10 ml of benzene and stirred at 75-80 ° C. While adding 0.14 g of thioacetic acid in benzene dropwise, stirring was continued for 2 hours at the same temperature.

After the reaction, optical isomer analysis was carried out by gas chromatography. As a result, (+)-cis isomer 3.2%, (-)-cis isomer
The proportions were 4.1%, (+)-trans isomer 42.5%, and (-)-trans isomer 50.2%.

Example 10 (+)-cis body 0.6 in a nitrogen stream in a 50 ml flask.
%, (−)-Cis isomer 18.3%, (+)-trans isomer 2.7
%, (−)-Trans isomer 78.4% of the primary methyl chrysanthemic acid 2.0 g and azobisisobutyronitrile 0.18 g were dissolved in benzene 10 ml, and thiobenzoic acid 0.23 g was added with stirring at 75 to 80 ° C. The benzene solution was added dropwise and stirring was continued at the same temperature for 1 hour.

After the reaction, the same operation as in Example 3 was performed to obtain 1.62 g of methyl primary chrysanthemate.

The optical isomer ratio of this product is (+)-cis 4.3%,
(-)-Cis form 4.3%, (+)-trans form 42.7%,
(-)-Trans form was 48.7%.

Example 11 In a 50 ml flask, 2.0 g of levorotatory primary chrysanthemic acid and 0.28 g of thiosalicylic acid dissolved in Example 2 were dissolved in benzene in a nitrogen stream, and lauroyl peroxide was added while stirring at 60 ° C.
47 g of benzene solution was added dropwise, and stirring was continued at the same temperature for 2 hours.

After the reaction, optical isomer analysis was carried out by gas chromatography. As a result, (+)-cis isomer 3.5%, (-)-cis isomer
The percentages were 3.4%, (+)-trans form 44.6%, and (-)-trans form 48.5%.

Example 12 (+)-cis form 1.8 in a 50 ml flask under a nitrogen stream.
%, (−)-Cis form 17.6%, (+)-trans form 10.1
%, (-)-Trans isomer 70.5%, and the first chrysanthemic anhydride
2 g, toluene 20 g and azobisisobutyronitrile 0.2
1 g was added and 0.95 ml of a toluene solution containing 0.21 g of thiophenol was added dropwise while stirring at 80 ° C.

After stirring at the same temperature for 2 hours, a part of the reaction solution was sampled, and after hydrolysis, it was induced into an ester with (+)-2-octanol to obtain the optical isomer ratio of primary chrysanthemic acid.
(+)-Cis form 4.5%, (-)-cis form 4.1%, (+)-
The trans form was 44.7% and the (-)-trans form was 46.7%.

Further, the content of primary chrysanthemic anhydride in the reaction solution was determined by gas chromatography to be 1.78 g.

Example 13 The procedure of Example 12 was repeated except that 0.26 g of thiobenzoic acid was used instead of thiophenol.

The optical isomer ratios were (+)-cis isomer 3.7%, (−)-cis isomer 4.1%, (+)-trans isomer 42.6%, and (−)-trans isomer 49.6%.

Example 14 In Example 12, dioxane 20 g instead of toluene,
Example 12 except that 0.32 g of benzoyl peroxide was used instead of azobisisobutyronitrile, and 0.95 ml of a toluene solution containing 0.26 g of thiobenzoic acid was used instead of a toluene solution of thiophenol, and the reaction was carried out at 90 ° C. for 1 hour. I went the same way.

The optical isomer ratio was (+)-cis isomer 3.5%, (−)-cis isomer 4.0%, (+)-trans isomer 44.1%, and (−)-trans isomer 48.4%.

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Claims (1)

[Claims] 1. A general formula (In the formula, X represents a hydroxyl group, a halogen atom, an alkoxy group having 1 to 20 carbon atoms, 2,2-dimethyl-3-isobutenylcyclopropanecarboxyl group, and * represents an asymmetric carbon.). A method for racemizing an optically active primary chrysanthemic acid, which comprises reacting an optically active primary chrysanthemic acid with an SH compound in the presence of a peroxide or an azo compound.