JP2591084B2 - Method for producing racemic dihalovinylcyclopropanecarboxylic acid halide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to (I) (Wherein X and Y represent a halogen atom and * represents an asymmetric carbon). A racemization is carried out by reacting phosphorus iodide and silicon iodide with an optically active dihalovinylcyclopropanecarboxylic acid halide represented by the formula: The present invention relates to a method for producing a racemic dihalovinylcyclopropane carboxylic acid halide by sintering.

<Prior art and problems to be solved by the invention> In the formula (I), dihalovinylcyclopropanecarboxylic acid in which Y corresponds to a hydroxyl group, that is, 2,2-dimethyl-3
-(2,2-Dihalovinyl) -cyclopropanecarboxylic acid (hereinafter abbreviated as dihalic acid) is a low-toxic insecticide permethrin, which is effective not only for household and epidemic control but also for agricultural pests and forest pests. It constitutes an acid component such as cypermethrin. Dihalic halides are useful as intermediates for these pesticides.

The dihalo acid halide represented by the formula (I) has cis,
Since there are trans isomers and each of them has (+) and (-) optical isomers, there are a total of four isomers. In general, among these isomers, (+)
Pyrethroid esters derived from the body show stronger insecticidal activity than the corresponding pyrethroid esters derived from the (-) body, and the safety against warm-blooded animals shows that the trans-esters correspond to the corresponding cis-form esters. It is known to be much higher than esters (for example, Nature , 24
4 , 456 (1973)).

Dihalo acids are usually produced as a racemic mixture of cis- and trans-forms, that is, (±) -form. In the case of an acid, this is optically resolved using an optically active organic salt to obtain
In the case of an ester, the (+) form is obtained by asymmetric hydrolysis using an enzyme or the like, and is used for producing a more highly active insecticidal compound. The remaining (-) form which has been optically resolved has almost no activity as a pyrethroid ester, and therefore, the non-useful (-) form is efficiently racemized to provide a more effective (±) form. The conversion to is a significant problem, especially in the production of pyrethroid esters on an industrial scale.

However, as described above, since the cyclopropanecarboxylic acids represented by the formula (I) have two asymmetric carbons at the C ₁ and C ₃ positions, the racemization involves various difficulties. .

Heretofore, as a method for racemizing dihalo acids, there has been known a method of irradiating dihalic acid with light in the presence of a photosensitizer (JP-A-50-160242).

However, this method has various difficulties for industrial implementation, such as requiring a special device for photochemical reaction and consuming a large amount of power.

The present inventors have conducted intensive studies in order to find an industrially superior method of racemizing optically active dihalo acids, and as a result, have found that the optically active dihalo acid halide represented by the formula (I) can be used as an iodide of phosphorus, It has been found that the racemization reaction proceeds unexpectedly and conveniently by the action of silicon iodide and the like. When the iodide of phosphorus acts, the coexistence of the halide of iodine, when the iodide of silicon acts, the coexistence of iodine, the racemization reaction proceeds more smoothly if this is performed. The present inventors have found that the present invention has been completed, and the present invention has been completed.

<Means for Solving the Problems> That is, the present invention provides (1) Formula (I) (Wherein X and Y represent a halogen atom and * represents an asymmetric carbon). The reaction of an optically active dihalovinylcyclopropanecarboxylic acid halide represented by the formula with phosphorus iodide or silicon iodide. A method for producing a racemic-dihalovinylcyclopropanecarboxylic acid halide,
It is intended to provide (2) a method of reacting phosphorus iodide in the presence of iodine halide and (3) a method of reacting silicon iodide in the presence of iodine.

 Next, the method of the present invention will be described in detail.

Optically active dihalo halide (I) which is a raw material of the present invention
Examples thereof include optically active substances such as dichloric acid chloride, dichloric acid bromide, dibromoic acid chloride and dibromoic acid bromide. Industrially, dihalic acid chloride is usually used in terms of ease of handling, cost and the like.

As described above, there are four types of isomers in dihalic acid halides. One of them alone or a mixture of these at any ratio can be used,
Needless to say, when a dihalo acid halide rich in (−) form or (−) form is used in view of the object of the present invention, its significance is exhibited.

Typical examples of the phosphorus iodide and silicon iodide used in the present invention include phosphorus triiodide and silicon tetraiodide.

The amount used is generally 1/1 with respect to the dihalic acid halide to be treated.
The molar ratio is 200 to 1 times, preferably 1/100 to 1/10 times.

The present invention allows the racemization reaction to proceed more smoothly by allowing iodide halides to coexist when using iodide of phosphorus and by allowing iodine to coexist when using iodide of silicon. it can. The amount used is usually 1/200 with respect to the dihalic acid halide to be treated.
It is 1 to 1 mole times, preferably 1/100 to 1/10 mole times.

Examples of iodine halides include iodine,
Bromo iodide, chloro iodide and the like can be mentioned.

The reaction is usually performed in the presence of a solvent. Any solvent may be used as long as it does not hinder the reaction. Examples thereof include aromatic hydrocarbons such as benzene, toluene, xylene, cumene, trimethylbenzene, and nitrobenzene, chloroform, carbon tetrachloride, chlorobenzene, 0-dichlorobenzene, and bromobenzene. Halogenated hydrocarbons such as, hexane, heptane, cyclohexane, saturated hydrocarbons such as cycloheptane, tetrahydrofuran, 1,4-dioxane,
Examples thereof include ethers such as 1,3-dioxane, tetrahydropyran, 2-methyltetrahydrofuran, isopropyl ether, butyl ether and butyl methyl ether, and nitriles such as acetonitrile, ppionitrile, and butyronitrile, and are preferably halogenated hydrocarbons.

In practicing the present invention, dihalic acid halide is usually dissolved in a solvent, phosphorus iodide, silicon iodide and the like are added, and when iodine halide and the like are used, it is further added. Is done.

The reaction temperature varies depending on the amount and type of phosphorus iodide, silicon iodide, iodine halide and the like, but is usually 40 to 150 ° C, preferably 80 to 120 ° C.

The reaction time is also phosphorus iodide, silicon iodide,
Although it varies depending on the amount and type of iodine halide used, it is usually about 30 minutes to 20 hours.

The degree of progress of the reaction can be determined by sampling a part of the reaction solution and analyzing by gas chromatography, NMR or the like.

After the reaction, the target substance can be isolated by, for example, distillation after removing the catalyst from the reaction mass.

Further, according to the present invention, 3-phenoxybenzyl alcohol, 5-benzyl-3-furylmethyl alcohol and the like may be added directly to the reaction mass without isolation to induce a direct reaction to a low-toxic insecticide. it can.

Further, it can be directly esterified by adding ethanol or the like to the reaction mass and used as a raw material for biochemical optical resolution, or can be derived into a free acid by adding an aqueous alkaline solution and hydrolyzing according to a conventional method. it can.

<Effects of the Invention> According to the present invention, a racemic dihaloacid can be efficiently produced without requiring a special reactor.

In addition, the racemized product according to the present invention is enriched in the trans form, which is less toxic to warm-blooded animals, and the present invention is also advantageous in this regard.

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

Example 1 Left-handed dichlorochloride ((+)-cis form: 18.6)
%, (-)-Cis form: 78.0%, (+)-trans form: 1.6
% (-)-Trans form: 1.8%) was dissolved in 22 g of chlorobenzene, and then 300 mg of phosphorus triiodide and 50 mg of iodine were added under a nitrogen atmosphere, followed by stirring at 100 ° C for 10 hours.

After the reaction, the sample was sampled and led to an ester of (+)-2-octanol. As a result of analysis by gas chromatography, the optical isomer ratio was (+)-cis isomer: 10%.
(-)-Cis form: 14.6%, (+)-trans form: 39.4%,
(-)-Trans form: 36.0%.

The reaction solution was cooled to room temperature, 230 mg of ethanol and 390 mg of pyridine were added, and the mixture was stirred at room temperature for 1 hour, washed with water, distilled off the solvent, and then distilled to give a boiling point of 88 to 90 ° C / 1.
960 mg of a fraction of mmHg were obtained. The product was confirmed to be ethyl dichlorate from the infrared absorption spectrum.

Example 2 Left-handed dichloric acid chloride ((+)-trans form:
After dissolving 1.95 g of the compound (7.1%, (-)-trans form: 92.2%) in 24 g of chlorobenzene, 150 mg of phosphorus triiodide and 92 mg of iodine were added under a nitrogen atmosphere, followed by stirring at 100 ° C for 13 hours.

After the reaction, the mixture was treated in the same manner as in Example 1 to obtain 1.91 g of ethyl dichlorate. The optical isomer ratio was (+)-cis isomer: 9.9%, (-)-cis isomer: 8.5%, (+)-trans isomer: 34.4%, and (-)-trans isomer: 47.2%.

Example 3 3.24 g of the same dichloric acid chloride used in Example 1
Was dissolved in 47 g of chlorobenzene, 750 mg of phosphorus triiodide and 150 mg of chloroiodide were added under a nitrogen atmosphere, and the mixture was heated to 100 ° C.
For 6 hours.

After the reaction, the mixture was cooled to room temperature, hydrolyzed with a 15% aqueous sodium hydroxide solution, acidified with 70% sulfuric acid, and extracted with toluene. When the toluene was distilled off, 2.67 g of a white solid was obtained. This product was confirmed to be dichloroic acid from the infrared absorption spectrum.

A part was sampled and made into (+)-2-octyl ester by a conventional method, and analyzed by gas chromatography. As a result, the optical isomer ratio was (+)-cis isomer: 7.9%,
(-)-Cis form: 11.5%, (+)-trans form: 41.6%,
(-)-Trans form: 39.0%.

Example 4 1.05 g of the same dichloric acid chloride used in Example 1
Was dissolved in 16 g of chlorobenzene, and 260 mg of phosphorus triiodide and 140 mg of bromoiodide were added under a nitrogen atmosphere, and 100
Stirred at C for 4 hours.

After the reaction, the mixture was treated in the same manner as in Example 1 to obtain 1.03 g of ethyl diculololate. Optical isomer ratio is (+)
-Cis-form: 8.6%, (-)-cis-form: 11.6%, (+)-trans-form: 41.8%, (-)-trans-form: 38.0%.

Example 5 Same 930 mg of dichloric acid chloride as used in Example 1
Was dissolved in 20 g of 1,4-dioxane, 310 mg of phosphorus triiodide and 190 mg of iodine were added under a nitrogen atmosphere, and the mixture was stirred at 100 ° C. for 4 hours.

After the reaction, the mixture was treated in the same manner as in Example 1 to obtain 856 mg of ethyl diculololate. Optical isomer ratio is (+)
-Cis form: 7.3%, (-)-cis form: 10.8%, (+)-trans form: 45.7%, (-)-trans form: 36.2%.

Example 6 980 mg of the same dichloric acid chloride used in Example 2
Was dissolved in 23 g of 1,2-dichloroethane, and 550 mg of phosphorus triiodide and 170 mg of iodine were added under a nitrogen atmosphere.
Stirred for hours.

The optical isomer ratio was (+)-cis isomer: 7.9%, (-)-cis isomer: 8.0%, (+)-trans isomer: 38.7%, and (-)-trans isomer: 45.4%.

Example 7 Left-handed dichloric acid chloride ((+)-cis form: 4.1)
%, (-)-Cis form: 2.9%, (+)-trans form: 13.8
%, (-)-Trans form: 72.2%) was dissolved in 18 g of chlorobenzene, 590 mg of silicon tetraiodide and 140 mg of iodine were added under a nitrogen atmosphere, and the mixture was stirred at 100 ° C for 4 hours.

A part of the reaction solution was sampled and led to an ester of (+)-2-octanol, and then analyzed by gas chromatography. As a result, the optical isomer ratio was (+)-cis isomer:
9.4%, (-)-cis form: 7.8%, (+)-trans form: 3
4.7% and (-)-trans form: 48.1%.

The reaction solution was cooled to room temperature, 660 mg of ethanol and 1.13 g of pyridine were added, and the mixture was stirred at room temperature for 1 hour, washed with water,
Evaporate the solvent and then distill it to a boiling point of 88-90 ° C.
2.37 g of a / 1 mmHg fraction were obtained.

The product was confirmed to be ethyl dichlorate from the infrared absorption spectrum.

Example 8 After dissolving 2.5 g of dichloric acid chloride used in Example 7 in 11 g of chlorobenzene, 625 mg of silicon tetraiodide and 100 mg of iodine were added under a nitrogen atmosphere, followed by stirring at 110 ° C. for 6 hours.

After the reaction, the mixture was treated in the same manner as in Example 7 to obtain 2.18 g of ethyl dichlorate.

The optical isomer ratio was (+)-cis isomer: 9.3%, (−)-cis isomer: 8.2%, (+)-trans isomer: 36.3%, and (−)-trans isomer: 46.2%.

Example 9 After dissolving 2.5 g of dichloric acid chloride used in Example 7 in 14 g of toluene, 1.08 mg of silicon tetraiodide and 274 mg of iodine were added under a nitrogen atmosphere, followed by stirring at 110 ° C. for 8 hours.

The optical isomer ratio was (+)-cis isomer: 8%, (-)-cis isomer: 7.3%, (+)-trans isomer: 37.7%, and (-)-trans isomer: 46.9%.

Example 10 1.01 g of the same dichloric acid chloride used in Example 2
Was dissolved in 23 g of chlorobenzene, 630 mg of phosphorus triiodide was added under a nitrogen atmosphere, and the mixture was stirred at 100 ° C. for 9 hours. The same treatment as in Example 1 was carried out to obtain ethyl dichlorate. The optical isomer ratio is (+)-cis isomer: 8.9%, (−)
-Cis form: 8.6%, (+)-trans form: 37.5%, (-)
-Trans form: 45.0%.

Example 11 After dissolving 2.5 g of dichloric acid chloride used in Example 7 in 14 g of chlorobenzene, 567 mg of silicon tetraiodide was added under a nitrogen atmosphere, followed by stirring at 100 ° C. for 4 hours.

The same treatment as in Example 7 was carried out, and ethyl dichlorate was obtained.
2.17 g were obtained.

The optical isomer ratio was (+)-cis isomer: 11.3%, (-)-cis isomer: 5.7%, (+)-trans isomer: 25.3%, and (-)-trans isomer: 57.7%.

Example 12 After dissolving 2.5 g of dichloric acid chloride used in Example 7 in 31 g of acetonitrile, 1.17 g of silicon tetraiodide was added under a nitrogen atmosphere, followed by stirring at 80 ° C. for 8 hours.

This was treated in the same manner as in Example 7 to obtain ethyl dichlorate.

The optical isomer ratio was (+)-cis isomer: 8.6%, (−)-cis isomer: 4.8%, (+)-trans isomer: 27.9%, and (−)-trans isomer: 58.7%.

──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical indication location C07B 61/00 300 C07B 61/00 300 (72) Inventor Hiroko Sakane 2-10 Tsukahara, Takatsuki-shi, Osaka No. 1 Sumitomo Chemical Industries, Ltd. (56) References JP-A-2-62843 (JP, A)

Claims (3)

(57) [Claims] (1) Expression (Wherein X and Y represent a halogen atom and * represents an asymmetric carbon). The reaction of an optically active dihalovinylcyclopropanecarboxylic acid halide represented by the formula with phosphorus iodide or silicon iodide. A method for producing a racemic-dihalocyclopropanecarboxylic acid halide, which is characterized by the following. 2. The process according to claim 1, wherein the iodide of phosphorus is allowed to act in the presence of a halide of iodine. 3. The method according to claim 1, wherein iodide of silicon is allowed to act in the presence of iodine.