JPH0717565B2 - 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, 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). Alternatively, the present invention relates to a racemization method of an optically active primary chrysanthemic acid, which comprises reacting hydrogen bromide in the presence or absence of an azo compound.

<Problems to be Solved by Conventional Techniques and Inventions> Kikuichikiku acid is an ester of well-known pyrethroid insecticides such as pyrethrin, allethrin, and phthalthrin, which are useful as low-toxic fast-acting insecticides. The primary chrysanthemic acid, which constitutes the acid 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 ester, and thus the ineffective (-) form can be efficiently racemized and used as a raw material for the above optical resolution. Doing so becomes a big problem especially when the (+) form is produced on an industrial scale.

However, as described above, the cyclopropanecarboxylic acid represented by the general formula (I) has two asymmetric carbons at the C _1- position and the C ₃ -position, so that its racemization involves various difficulties. U

This up, the racemization method of the first chrysanthemum acids, the after that led to the keto alcohol group by oxidizing the position of isobutenyl groups C ₃ of the first chrysanthemic acid, carboxylic acid C ₁ position - (-) Truss A method of esterification and heating reaction with an alkali metal alcoholate in the presence of a solvent (JP-B-89-15977),
Alternatively, a method of irradiating (-)-trans-primary chrysanthemic acid with ultraviolet light in the presence of a photosensitizer (Japanese Patent Publication No. 47-80697).
However, the former requires many reaction steps, and the latter has a poor reaction rate and consumes a large amount of power for the light source, and the life of the light source is relatively short. It has various problems.

The present inventors have previously described a racemization method by using optically active primary chrysanthemic acid as an acid halide, and by causing a Lewis acid to act on this as a catalyst (Japanese Patent Publication No. 53-37858, JP-A No. 52-144).
651), a racemization method by reacting iodine with an optically active anhydride of cyclopropanecarboxylic acid (JP-A-57-163341), and primary chrysanthemic acid as boron bromide or aluminum bromide. A racemization method in which a special catalyst is allowed to act on its own or in the presence of a peroxide (JP-A-60-174744, 61-5045, 61-5046, 61-5).
No. 047) is proposed.

As a result of further studies, the inventors of the present invention have found that for the optically active primary chrysanthemic acid represented by the general formula (I),
Surprisingly, it was found that by applying hydrogen bromide, racemization proceeds, and by allowing hydrogen bromide to act in the presence of a peroxide or an azo compound, racemization proceeds more efficiently. The present invention has been completed by finding the heading and adding various studies thereto.

<Means for Solving Problems> That is, the present invention provides a compound represented by the general formula (I): (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). Another object of the present invention is to provide an industrially extremely excellent racemization method of an optically active primary chrysanthemic acid characterized by reacting hydrogen bromide in the presence or absence of 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, methyl primary chrysanthemate,
Ethyl primary chrysanthemate, propyl primary chrysanthemate, butyl primary chrysanthemate,
Examples of the optically active substance include cyclohexyl primary chrysanthemate, cyclohexyl methyl primary chrysanthemate, and benzyl primary chrysanthemate.

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 hydrogen bromide used in the present invention may be gaseous or may be dissolved in a solvent, and in some cases lithium bromide, sodium bromide, potassium bromide and other bromides and sulfuric acid and other acids. It may be generated in the reaction system by using.

The amount used is usually 1/1000 for 1 mol of the primary chrysanthemic acid to be treated.
It is in the range of 1/4 mol. As the solvent for hydrogen bromide, any solvent which does not inhibit the racemization reaction may be used, and examples thereof include organic solvents such as carboxylic acids, saturated hydrocarbons, aromatic hydrocarbons, halogenated saturated hydrocarbons, halogenated aromatic hydrocarbons and the like. Water etc. can be mentioned.

As the peroxide, for example, t-butyl hydroperoxide, 1,1,3,3-tetramethylbutyl hydroperoxide, tetrahydrofuran, cumene hydroperoxide produced by oxidation of ethers such as dioxane, etc. , Hydroperoxides such as diisopropylbenzene hydroperoxide, diacyl peroxides such as benzoyl peroxide and lauroyl peroxide, t-butyl perbenzoate, t-butyl peracetate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate Peroxyesters such as, methyl ethyl ketone peroxide, ketone peroxides such as cyclohexanone peroxide,
Examples thereof include dialkyl peroxides such as di-t-butyl peroxide and dicumyl peroxide, peracids such as peracetic acid, and hydrogen peroxide. Of these, hydroperoxides, diacyl peroxides and peroxyesters are preferable, and hydroperoxides are more preferable.

The amount of acetic acid used is usually 1/20 to 1 mol of hydrogen bromide.
The amount is 5 mol, preferably 1/10 to 2 mol.

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

The amount used is usually 1/10 with respect to 1 mol of the hydrogen bromide.
-5 mol, preferably 1 / 4-2 mol.

Further, when carrying out the reaction, it is preferable to use an inert solvent, and as such a solvent, a saturated hydrocarbon,
Aromatic hydrocarbons, their halides, ethers, etc. can be mentioned.

The reaction temperature is arbitrary in the range of -30 ° C to the boiling point of the primary chrysanthemic acid (the boiling point of the solvent used when the solvent is used),
It is usually in the range of -20 ° C to 100 ° C.

The time required for the reaction may vary depending on the amount of the hydrogen bromide and the peroxide or the 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, hydrogen bromide is usually added to the primary chrysanthemic acid to be treated in the presence of a solvent. When using a peroxide or an azo compound, usually, the primary chrysanthemic acid to be treated is mixed with the peroxide or the azo compound in the presence of a solvent, and then the hydrogen bromide is added thereto, or This is carried out by dissolving the primary chrysanthemic acid to be treated in a solvent, and then pouring a peroxide or an azo compound together with hydrogen bromide.

Further, when an aqueous hydrobromic acid solution is used as the bromine hydrogen and an organic solvent that is incompatible with water as the reaction solvent, such as an aromatic hydrocarbon, is used, the solubility in water is large and the reaction is inhibited. By allowing an inorganic salt or the like not to exist in the reaction system, the target reaction can proceed more smoothly. Examples of such inorganic salts include lithium bromide, lithium chloride, calcium bromide, calcium chloride, magnesium bromide, magnesium chloride, magnesium sulfate, phosphorus pentoxide, and the like. Further, by mixing an aqueous solution of hydrobromic acid with water and an organic solvent inert to hydrogen bromide, such as acetic acid or dioxane, the desired reaction can be proceeded more smoothly.

The 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.

The racemized primary chrysanthemic acid obtained as described above can also be converted into an insecticidal ester by an esterification reaction with various pyrethroid alcohols.

<Effects of the Invention> Thus, a cerami body of primary chrysanthemic acid is produced, but according to the method of the present invention, racemic form of optically active primary chrysanthemic acid itself or its ester as it is without leading to other derivatives. Is extremely advantageous because it can be converted to chrysanthemic acid which is separated and removed by various optical resolution methods,
For example, ineffective (-)-primary chrysanthemic acid separated by a physicochemical resolution method using an optical resolving agent, or separated and removed by a biochemical resolution method by an enzyme or the like (-)-primary chrysanthemic acid ester Can be directly and efficiently used.

Furthermore, according to the present invention, hydrogen bromide, which is more general as an industrial raw material, is stable with respect to moisture, etc., and is easy to handle, is advantageous especially in industrial practice.

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 From levorotatory primary chrysanthemic acid ((+)-cis form; 3.0%, (-)-cis form; 18.8%, (+)-trans form; 10.2%, (-)-trans form; 68.0% 25.0 g is dissolved in 38 ml of toluene and 25% hydrobromic acetic acid solution is added thereto while stirring at room temperature.
A toluene solution of 04 g and 0.23 g of t-butyl hydroperoxide was co-injected over 30 minutes.

After the reaction, dilute hydrochloric acid was added, and the mixture was stirred and separated.
A 0% caustic soda aqueous solution was added for extraction. Dilute sulfuric acid was added to the obtained aqueous layer to make it acidic, and then extracted twice with toluene.
After washing the toluene layer with water, the solvent was distilled off under reduced pressure, and the residual liquid was then distilled to give a boiling point of 110-119 ° C / 2.5 mmHg fraction 24.0 g.
Got It was confirmed from the infrared absorption spectrum that this product was chrysanthemic acid. A part of this is sampled (+)-
When the optical isomer ratio was determined by gas chromatography after leading to an ester with 2-octanol, (+)-cis isomer; 1.8%, (-)-cis isomer; 2.4%,
(+)-Trans isomer; 46%-(-)-trans isomer; 49.8%
Met.

Example 2 25.0 g of primary chrysanthemic acid used in Example 1 was dissolved in 38 ml of toluene, and 3.0 g of lithium bromide was suspended. While stirring at 20 ° C., a toluene solution of 0.44 g of t-butyl hydroperoxide and 2.23 g of a 48% hydrobromic acid aqueous solution were added dropwise over 30 minutes.

After the reaction, the same treatment as in Example 1 was carried out to obtain 24.0 g of primary chrysanthemic acid. Optical isomer ratio is (+)-cis 2.0%,
(−)-Cis form 2.0%, (+)-trans form 47.1%,
(+)-Trans form was 48.9%.

Example 3 25.0 g of primary chrysanthemic acid used in Example 1 was dissolved in 38 ml of toluene, and 3.0 g of calcium chloride was suspended. While stirring at 20 ° C, a toluene solution of 0.38 g of t-butyl hydroperoxide and an aqueous solution of hydrobromic acid-acetic acid (composition: HBr 38.4% acetic acid 2
2.51 g of 0%, 41.6% water) solution was added dropwise over 30 minutes.

After the reaction, the same treatment as in Example 1 was carried out to obtain 24.0 g of primary chrysanthemic acid. The optical isomer ratio is (+)-cis 2.4%,
(-)-Cis isomer 2.4%, (+)-trans isomer 45.2%,
The content of (−)-trans isomer was 50.0%.

Example 4 25 g of the same levorotatory primary chrysanthemic acid used in Example 1 was dissolved in 38 ml of toluene and t-butyl hydroperoxide was added.
69 g was added, and 1.5 g of hydrogen bromide gas was blown into this solution for 30 minutes while stirring at room temperature.

Thereafter, the same operation as in Example 1 was carried out to obtain 23.6 g of primary chrysanthemic acid. Optically active substance ratio is (+)-cis; 3.5%, (-)-
The cis form was 3.3%, the (+)-trans form was 44.0%, and the (-)-trans form was 49.2%.

Example 5 1.04 g of the same levorotatory primary chrysanthemic acid used in Example 1 was dissolved in 5 ml of toluene, 131 mg of benzoyl peroxide was added, and the mixture was heated at 80 ° C.
While stirring at, 430 mg of a 25% acetic acid solution of hydrogen bromide was added dropwise over 3 minutes.

Thereafter, the same operation as in Example 1 was carried out to obtain 940 mg of primary chrysanthemic acid.

The optical isomer ratios were (+)-cis isomer: 4.7%, (−)-cis isomer: 4.2%, (+)-trans isomer: 40.9%, (−)-trans isomer: 50.3%.

Example 6 2.00 g of the same levorotatory primary chrysanthemic acid used in Example 1 was dissolved in 20 ml of dioxane, 110 mg of t-butyl hydroperoxide was added, and 48% bromide was added thereto while stirring at room temperature. 300 mg of a hydrogen acid aqueous solution was added dropwise.

Thereafter, the same operation as in Example 1 was performed to obtain 1.70 g of primary chrysanthemic acid.

The optical isomer ratio is (+)-cis isomer: 2.3%, (−) cis isomer:
The proportions were 2.4%, (+)-trans form: 44.7%, and (-)-trans form 50.7%.

Example 7 Levorotatory ethyl chrysanthemate ((+)-cis form: 2.5%, (-)-cis form; 14.8%, (+)-trans form; 11.9%, (-)-trans form; 70.9%) 2.23 g was dissolved in 20 ml of dioxane, 95 mg of azobisisobutyronitrile was added, and a benzene solution of 370 mg of 25% hydrobromic acetic acid solution was added dropwise over 30 minutes while stirring at 80 ° C.

After the reaction, 2% aqueous sodium hydroxide solution was added to neutralize, the solvent was distilled off under reduced pressure, and then hexane and 2 were added to the residue.
% 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 2.06 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 ratio was determined by gas chromatography (+) cis isomer: 3.0
%, (−) Cis form: 3.1%, (+) trans form: 46.3%,
(−) Trans form: 47.6%.

Example 8 The same levorotatory ethyl chrysanthemate 2.50 g used in Example 7 was dissolved in dioxane 10 ml, t-butyl hydroperoxide 115 mg was added, and 25% hydrobromic acetic acid solution 410 mg was added with stirring at room temperature. added. Thereafter, the same operation as in Example 7 was carried out to obtain 2.25 g of ethyl chrysanthemate.

Optical isomer ratio is (+) cis isomer: 2.5%, (−) cis isomer 2.5
%, (+) Trans form: 47.1%, (−) trans form: 47.9
%Met.

Example 9 2.84 g of the same levorotatory primary chrysanthemic acid and 0.14 g of azobisisobutyronitrile used in Example 1 are dissolved in 25 ml of benzene, and 0.55 g of 25% hydrobromic acetic acid solution is added dropwise at 70 ° C. And allowed to react for 30 minutes.

The optical isomer ratio determined by gas chromatography was (+)-cis isomer 3.8% (-)-cis isomer 3.8% (+)-trans isomer 45.3% (-) trans isomer: 47.1%.

Example 10 10 g of the same levorotatory primary chrysanthemic acid used in Example 1 was added to toluene 1
It dissolved in 00 g. Add 25% hydrobromide acetic acid solution at 20 ℃ to 4.8
2 g was added and stirred for 1 hour.

Optical isomer ratio is (+)-cis isomer 2.7%, (-)-cis isomer
3.6% (+)-transformer 46.9%, (-)-transformer 4
It was 6.8%.

Example 11 320 mg of the same levorotatory chrysanthemate used in Example 7 was dissolved in 4 ml of toluene. To this was added 52 mg of 25% hydrobromic acid acetic acid solution at 20 ° C., and the mixture was stirred for 30 minutes.

Optical isomer ratio is (+)-cis form 3.6%, (-)-cis form
It was 3.6%, (+)-trans isomer 33.0%, and (-)-trans isomer 59.8%.

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Claims (1)

[Claims] 1. A general 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). Alternatively, a method for racemizing an optically active primary chrysanthemic acid, which comprises reacting hydrogen bromide in the presence or absence of an azo compound.