JPH0647567B2 - Racemization Method for Optically Active Primary Chrysanthemic Acids - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Field of Application> The present invention relates to a racemization method for primary chrysanthemic acids, and more specifically to the general formula (I) (In the formula, R is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms,
It represents a cycloalkyl group or an aralkyl group, and * represents an asymmetric carbon. ) The optically active primary chrysanthemic acid represented by the formula (1) is allowed to act with a brominated phosphorus compound in the presence or absence of an azo compound, and to a racemization method of the optically active primary chrysanthemic acid.

<Prior art, problems to be solved by the invention> Primary chrysanthemic acid is an ester of well-known pyrethroid insecticides such as pyrethrin, allethrin, and phthalthrin, which are useful as low-toxic and 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 geometrical isomers, and each of them has (+) and (-) optical isomers. There is a body. In general, among these isomers, the pyrethroid ester derived from the trans isomer has a stronger insecticidal activity than the pyrethroid ester derived from the corresponding cis isomer, and further the (+) ester is It is known to show much higher activity than the corresponding (-) ester.

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 using 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 useful (-) form is efficiently racemized and used as a raw material for the above optical resolution. Making it available is a major challenge, especially when producing the (+) form 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, (-) trans - after that led to the keto alcohol group by oxidizing the C ₃ position of isobutenyl groups of the first chrysanthemic acid, a carboxylic acid of the C ₁ position ester And reacting it with an alkali metal alcoholate in the presence of a solvent by heating (Japanese Examined Patent Publication No. 39-15977), or (-)-trans-primary chrysanthemic acid in the presence of a photosensitizer with ultraviolet light. An irradiation method (Japanese Patent Publication No. 47-30697) is known, but the former requires many reaction steps, and the latter has a poor reaction rate and a large power consumption of the light source, and also has a long life of the light source. There are various problems in industrial implementation such as being relatively short.

The present inventors have previously described a racemization method in which optically active primary chrysanthemic acid is used as an acid halide and a Lewis acid is allowed to act as a catalyst (JP-B-53-37858, JP-A-52).
-144651), a racemization method by reacting an optically active anhydride of cyclopropanecarboxylic acid with iodine (JP-A-57-163341), and a special chrysanthemum acid derivative called boron bromide. A racemization method (Japanese Patent Application Laid-Open No. 174744/1985) by using a catalyst has been proposed.

As a result of further various investigations by the present inventors, the inventors have found that a more general brominated phosphorus compound as an industrial raw material can unexpectedly and efficiently proceed the racemization reaction of an optically active primary chrysanthemic acid. It was found that the racemization reaction can proceed more efficiently and smoothly with a small amount of a catalyst by using the compound of (1) with an azo compound, and the present invention was completed by further various studies.

<Means for solving problems> (In the formula, R is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms,
It represents a cycloalkyl group or an aralkyl group, and * represents an asymmetric carbon. ) The optically active primary chrysanthemic acid represented by the formula (1) is allowed to react with a brominated phosphorus compound in the presence or absence of an azo compound, which is an industrially excellent racemization method. It is provided.

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 the raw material of the present invention, include, for example, primary chrysanthemic acid, methyl primary chrysanthemate, ethyl primary chrysanthemate, propyl primary chrysanthemate, and primary dichrysanthemate. Examples of the optically active substance include butyl acid salt, 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 is needless to say that when the (−) form or the (−) form-rich carboxylic acid is used for the purpose of the present invention, its significance is exhibited.

Examples of the phosphorus bromide compound used in the method of the present invention include phosphorus and bromide compounds such as phosphorus tribromide, phosphorus pentabromide and phosphorus oxytribromide, and mixtures thereof. The amount used is usually 1/1000 to 1 mol of the primary chrysanthemic acid to be treated.
It is in the range of 1/4 mol, preferably 1/20 to 1/4 mol when the brominated phosphorus compound is used alone, and 1/200 to 1/10 mol when used in the presence of the azo compound. Is.

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

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

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 -20 ° C to the boiling point of the primary chrysanthemic acid ester (the boiling point of the solvent used when a solvent is used), but is usually in the range of 0 ° C to 100 ° C.

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

In carrying out the method of the present invention, usually, the treated primary chrysanthemic acid and the azo compound are mixed in the presence of a solvent, and then the brominated phosphorus compound is added thereto, or the treated primary chrysanthemic acid is treated. Is dissolved in a solvent, and then an azo compound and the above-mentioned brominated phosphorus compound are co-injected thereto.

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> The method of the present invention is extremely advantageous because it is possible to racemize the optically active primary chrysanthemic acid itself or its ester as it is without leading to other derivatives. Chrysanthemic acids that are separated and removed by the optical resolution method, for example, ineffective (-)-primary chrysanthemic acid that is separated by the physicochemical resolution method using an optical resolution agent, or separated and removed by the biochemical resolution method using an enzyme or the like. It is possible to directly and efficiently use ru (-)-primary chrysanthemate.

Further, according to the present invention, a more general phosphorus bromide compound can be used as an industrial raw material, and the shared azo compound is also easy to use because it does not induce decomposability. Be advantageous in time.

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.

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

Example 1 Levorotatory primary chrysanthemic acid (1.8% of (+)-cis form, 17.6 of (-)-cis form)
%, (+)-Trans isomer 10.1%, (-)-trans isomer 70.5%) 1.78 g was dissolved in benzene 10 ml, azobisisobutyronitrile 43 mg was added, and tribromination was performed at 80 ° C. with stirring. A benzene solution containing 144 mg of phosphorus was added dropwise over 15 minutes.

After the reaction, diluted hydrochloric acid was added and stirred to deactivate and remove the catalyst. After separation, the organic layer was washed with 4.8 g of 10% caustic soda solution.
Extract twice, acidify the resulting aqueous layer with hydrochloric acid and add 2 with toluene.
Extracted twice. 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 1.51 g of a fraction having a boiling point of 110 to 119 ° C./2.5 mmHg. This product was confirmed to be chrysanthemic acid by infrared absorption spectrum, and a part of this was sampled and then converted to an ester with (+)-2-octanol, and its optical isomer ratio was determined by gas chromatography. , (+) Cis
The percentages were 2.5%, (-) cis form 2.5%, (+) trans form 47.8%, and (-) trans form 47.2%.

Example 2 1.26 g of the same levorotatory primary chrysanthemic acid used in Example 1 was dissolved in 10 ml of benzene, and azobisisobutylnitrile 50 was added.
mg was added, and a benzene solution of 220 mg of phosphorus pentabromide was added dropwise over 15 minutes while stirring at 70 ° C.

Thereafter, the same operation as in Example 1 was carried out to obtain 1.01 g of primary chrysanthemic acid.

Optical isomer ratio is (+)-cis 4.1%, (-)-cis 4.1%,
The (+)-trans form was 48.9% and the (-)-trans form was 47.9%.

Example 8 2.12 g of the same levorotatory primary chrysanthemic acid used in Example 1 was dissolved in 10 ml of benzene, 92 mg of methyl azobisisobutyrate was added, and the mixture was heated to 70 ° C. Then, a benzene solution of 171 mg of phosphorus tribromide was added dropwise over 15 minutes.

Thereafter, the same operation as in Example 1 was carried out to obtain 1.73 g of primary chrysanthemic acid.

Optical isomer ratio is (+)-cis isomer 3.6%, (-)-cis isomer 3.5%,
The (+)-trans form was 45.2% and the (-)-trans form was 47.7%.

Example 4 Levorotatory ethyl chrysanthemate ((+)-cis 2.5% (-)-cis 14.8
% (+)-Trans form 11.9% (-)-trans form 70.8%) 3.48
g was dissolved in 20 ml of benzene, 100 mg of azobisisobutyronitrile was added, and phosphorus pentabromide was added with stirring at 80 ° C.
0 mg of benzene solution was added dropwise in 30 minutes.

After the reaction, ice water was added to the reaction solution and stirred to deactivate the catalyst. Next, the aqueous layer was separated, and the organic layer was evaporated under reduced pressure. The residual liquid was heated under reflux with 20 g of a 10% aqueous sodium hydroxide solution for 3 hours, and then toluene was added for liquid separation to remove a neutral substance as a toluene layer. The aqueous layer was acidified with hydrochloric acid, extracted with toluene, the organic layer was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residual liquid was distilled next to a boiling point of 110 to 119 ° C. 2.49 g of a fraction of /2.5 mmHg was obtained. From the infrared absorption spectrum, this product was confirmed to be chrysanthemic acid.

The optical isomer ratio of this product is (+) cis 3.9%, (-) cis 3.2%, (+) trans 43.3%, (-) trans 49.6%
Met.

Example 5 In a 20 ml flask, 1.0 g of (+)-cis primary chrysanthemic acid and 9 g of toluene were added under a nitrogen atmosphere, and 0.24 g of phosphorus tribromide was added dropwise with stirring at 20 ° C. After stirring at the same temperature for 1 hour, the optical isomer ratio of the reaction solution was measured to be (+)-cis 6.9%, (-)-cis 4.8%, (+)-trans 44.6.
%, (−)-Trans isomer was 43.7%.

Claims (2)

[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.) A method for racemizing an optically active primary chrysanthemic acid, which comprises reacting a compound. 2. 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.) A method for racemizing an optically active primary chrysanthemic acid, which comprises reacting a brominated phosphorus compound in the presence of.