JPH02169541A - Production of racemic chrysanthemum-monocaboxylic acids - Google Patents

Abstract

PURPOSE:To efficiently obtain the objective compounds in the same manner as that in the case of a coexisting assistant, such as peroxide or azo compound, by the coexistence of a specific amount of oxygen in a reaction system for reacting optically active chrysanthemum-monocarboxylic acids with hydrogen bromide and producing the corresponding racemic modification. CONSTITUTION:Optically active chrysanthemum-monocarboxylic acids expressed by the formula (R is H, 1-20C alkyl, cycloalkyl or aralkyl; * indicates asymmetric carbon) are reacted with hydrogen bromide to provide the corresponding racemic modification. In the process, the above-mentioned reaction is carried out in the presence of oxygen and the total molar amount of the oxygen is simultaneously >=1/70, preferably (1/150)-(1/2) based on the chrysanthemum- monocarboxylic acids. Thereby, the objective compounds useful as a raw material for pyrethroid-based insecticides are industrially and advantageously obtained. Not only the hydrogen bromide which is normally used as an industrial raw material and readily handleable for moisture, etc., can be utilized but also inexpensive and easily handleable oxygen or air can be used in place of the afore-mentioned assistant by the above-mentioned method.

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention relates to a method for racemizing chrysanthemum acids,
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 a method for producing a racemate, it is carried out in the presence of oxygen, and the total amount of oxygen used is 1/17 compared to chrysanthemum acids.
The present invention relates to a method for producing racemic chrysanthemum acids, characterized in that the amount is 0 times or more by mole.

<Prior art/problems to be solved by the invention> Chrysanthemum acid is a compound of esters that are well known as pyrethroid insecticides such as pyrethrin, allethrin, and phthalthrin, which are used as low-toxicity and fast-acting insecticides. The chrysanthemum acids that constitute the acid component and are represented by the above-mentioned formula (1) are:
It is useful as a raw material for these pyrethroid insecticides.

The chrysanthemum acids represented by the general formula (1) have cis and trans geometric isomers, and each of them has (+) and (-
), there are a total of 4 types of isomers. Generally, among these isomers, the pyrethroid esters derived from the trans isomer exhibit stronger insecticidal activity than the corresponding pyrethroid esters derived from the cis isomer, and the (+) esters also exhibit stronger insecticidal activity than the corresponding pyrethroid esters derived from the cis isomer. It is known that it exhibits much higher activity than the (=) form of esters.

Chrysanthemum 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 can be obtained, resulting in higher activity. used in the production of insecticidal compounds. The remaining (-) isomer optically resolved here has almost no activity as a pyrethroid ester, so this ineffective (-) isomer can be efficiently racemized and used as a raw material for the above optical resolution. This poses a major challenge, especially when producing (+) bodies on an industrial scale.

However, as mentioned above, since the cyclopropanecarboxylic acid represented by the general formula (N) has two asymmetric carbon atoms at the C1 and C1 positions, its racemization is accompanied by various difficulties.

Until now, the racemization method for chrysanthemum acids has been to oxidize the isobutenyl group at the C3 position of (-)-trans chrysanthemum acid to form a keto alcohol group, then esterify the carboxylic acid at the 01 position, and convert this into an alkali metal alcohol group. A heating reaction method in the presence of a rate and a solvent (Japanese Patent Publication No. 39-15977),
Alternatively, a method of irradiating (-)-trans chrysanthemum acid with ultraviolet rays in the presence of a photosensitizer (Japanese Patent Publication No. 30697/1983)
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 have proposed a method for producing a racemate, in which optically active chrysanthemum acid is first used as an acid halide, and a Lewis acid is made to act on this as a catalyst (Japanese Patent Publication No. 53-37858, Japanese Patent Publication No. 61-8048). (publication), a method in which iodine acts on an anhydride of optically active cyclopropanecarboxylic acid (
JP-A-57-163341), a method in which a special catalyst such as boron bromide or aluminum bromide is applied to chrysanthemum acid (JP-A-60-174744, JP-A-61-5045), and a method in which hydrogen bromide is applied to chrysanthemum acid. , a method in which it acts alone or in the coexistence of a peroxide or an azo compound (Patent application 1986-
164802), etc.

The present inventors subsequently conducted further detailed studies on the method for producing racemic chrysanthemum acids by the action of hydrogen bromide, and found that if a specific amount of oxygen is allowed to coexist, peroxides, azozoic acids, etc. They discovered that the racemization reaction proceeded as efficiently as in the case of the coexistence of compounds, etc., and completed the present invention after further various studies.

<Means for solving IJIB> That is, the present invention is based on the general formula (1) % formula % (wherein R is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms,
Represents a cycloalkyl group or an aralkyl group, and * represents an asymmetric carbon.) A method for producing the corresponding racemate by reacting hydrogen bromide with an optically active chrysanthemum acid represented by However, the total amount of oxygen used is 1/17 compared to chrysanthemum acids.
The purpose of the present invention is to provide an industrially excellent method for producing racemic chrysanthemum acids, which is characterized in that the amount is 0 times or more by mole.

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

Examples of the optically active chrysanthemum acids represented by the general formula (1), which are the raw materials of the present invention, include st-chrysanthemum acid, methyl chrysanthemum acid, st-chrysanthemum acid,
Ethyl chrysanthemum, brobyl chrysantherate, butyl chrysantherate, di-
Cyclohexyl chrysanthemum acid, cyclohexylmethyl chrysanthemum acid,
Examples include optically active substances such as benzyl chrysanthemum acid.

Chrysanthemum acids each have four types of isomers, and ill alone or a mixture of these in any proportion can be used, and any degree of optical purity may be used. It goes without saying that, considering the purpose of the invention, its significance is exhibited when using carboxylic acids in the (-) form or in the (-) form.

The hydrogen bromide used in the present invention may be in a gaseous state or dissolved in a solvent, and in some cases, bromides such as lithium bromide, sodium bromide, potassium bromide, etc. and acids such as sulfuric acid may be used. It may be generated within the reaction system using.

The amount used is usually 1/100 per mole of chrysanthemum acids to be treated.
0~! The range is 15 moles. The solvent for hydrogen bromide may be any solvent that does not inhibit the racemization reaction, such as organic solvents such as carboxylic acids, saturated hydrocarbons, aromatic hydrocarbons, halogenated saturated hydrocarbons, and halogenated aromatic hydrocarbons; Examples include water.

The present invention is characterized in that hydrogen bromide is applied in the presence of oxygen, but air can also be used in addition to oxygen itself. It can also be used after being diluted with an inert gas such as nitrogen. Oxygen is 1/1 to the chrysanthemum acid to be treated.
By using 70 moles or more, racemization can proceed efficiently. Although good results can be obtained in a system open to the atmosphere, it is preferable to use 1/150 to 1/2 mole of oxygen.

In addition, it is preferable to use an inert solvent when carrying out the reaction, and such solvents include saturated hydrocarbons,
Examples include aromatic hydrocarbons and halides thereof.

The reaction temperature is arbitrary within the range of 0°C to the boiling point of the chrysanthemum acids (if a solvent is used, the boiling point of the solvent used), but is usually in the range of -20°C to 100°C.

The time required for the reaction may vary depending on the amounts of hydrogen bromide and oxygen 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 mixture of the solvent and the chrysanthemum acids to be treated is usually brominated in an atmosphere containing a predetermined amount of oxygen, or under the flow of a gas prepared in advance to contain a predetermined amount of oxygen. Add hydrogen.

Here, the oxygen partial pressure in the reaction system is usually determined in consideration of safety and volumetric efficiency so that it is outside the explosive limit of the reaction solvent. -Numerically, 3 to 10% is preferable.

In addition, when using an aqueous solution of hydrobromic acid as hydrogen bromide and using an organic solvent that is incompatible with water, such as an aromatic hydrocarbon, as the reaction solvent, the solubility in water is high and the reaction is inhibited. By allowing the presence of an inorganic salt or the like in the reaction system, the desired 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. Furthermore, by mixing an aqueous solution of hydrobromic acid with an inert organic solvent such as acetic acid or dioxane, which is compatible with water and hydrogen bromide, the desired reaction can proceed smoothly.

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 racemic acid derivatives obtained as described above can also be converted into insecticidal esters by esterification reaction with various pyrethroid alcohols.

<Effects of the Invention> In this way, the racemic form of chrysanthemum acids is produced, but according to the method of the present invention, hydrogen bromide, which is more common as an industrial raw material, is stable against moisture, etc., and is easy to handle. Not only can oxygen and air be used instead of auxiliary agents such as peroxides and azo compounds, but oxygen and air, which are inexpensive and easy to handle, can be used, which is particularly advantageous in industrial implementation.

Furthermore, according to the invention, without leading to pond derivatives,
It is extremely advantageous because optically active Chrysanthemum acid itself or its ester can be racemized as it is, and furthermore, it can be separated and removed by various optical resolution methods, such as physical chemistry using optical resolution agents. Invalid (-) phase formation separated by physical resolution method, or (-)- separated and removed by biochemical resolution method using enzymes, etc.
It becomes possible to directly and efficiently utilize primary chrysanthemum acid esters and the like.

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.

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

Example 1 At 20°C, in a flask with a dropping tube of about 10 ld, levorotatory phase-formation ((+)-cis isomer = 2.3%, (-)-cis isomer: 16.8%, (+)-trans form: 11.3
%, (-)-) lance form: Consisting of 69.6%) Lo
g and 15 g of toluene were added. The space of the flask is Lo
ojlJ! Met.

Next, the space is filled with a mixed gas prepared from air and nitrogen (
After sufficiently replacing the flask with a molar ratio of oxygen and nitrogen (-1 = 9), while maintaining the pressure with nitrogen so that the inside of the flask is always at atmospheric pressure,
1.35 g of 25% hydrogen bromide-acetic acid solution under stirring at the same temperature.
A solution consisting of 0 and 7.5 g of toluene was added dropwise over 30 minutes.
The molar ratio of oxygen to nitrogen after dropping was 0.8 + 99.2.

After dropping, add dilute hydrochloric acid, stir, and separate the layers.
g of 10% aqueous caustic soda solution was added thereto for extraction. After making the resulting aqueous layer acidic by adding dilute sulfuric acid, it was extracted twice with toluene, the toluene layer was washed with water, the solvent was distilled off, and the residual liquid was distilled to give a boiling point of 110 to 119°C/2.5 m
986 g of Hg fraction was obtained.

It was confirmed from the infrared absorption spectrum that this product was a synthetic product. After sampling a portion of this and converting it into an ester with -2-octatool, the optical isomer ratio was determined by gas chromatography (+)
-cis form: 2.2%, (=) -cis form: 2.4%, (+
) -) Lance body: 46.3%, (-)-) Lance body:
It was 49.1%.

Example 2 Example 1 was carried out in the same manner as in Example 1 except that nitrogen was used instead of the mixed gas, and the molar ratio of oxygen and nitrogen was 3: It was 97.

The optical isomer ratio is (+)-cis: 2.2%, (-)-
Cis form: 2.1%, (+)-trans form: 46.7%,
(-)-) lance form: 49.0%.

Example 3 The same procedure as in Example 2 was carried out except that pressure compensation was performed with oxygen instead of nitrogen. The optical isomer ratio is (+
)-cis form = 2.5%, (-)-cis form = 2.7%, (
+)-)trans isomer: 42.3%, (-)-trans isomer: 52.5%.

Example 4 After displacing a flask of about 300 d with a mixed gas (molar ratio of oxygen and nitrogen -7.5:92.5), 82 g of the same levorotatory phase as used in Example 1), 123 g of toluene 1 chloride 3.88g of calcium was added. under stirring at 20'C.
While blowing the same mixed gas as above at 6 cc/min,
5.75 g of a 5% aqueous hydrogen bromide solution was added dropwise over 40 minutes.

After the dropping was completed, the mixed gas was continued to be blown for another 5 hours and 20 minutes, during which time the gas coming out from the outlet was continuously monitored with an oxygen analyzer. After the gas injection was completed, the amount of oxygen in the reactor was measured, and the amount of oxygen consumed was found to be 150 cc. After the blowing was completed, the same treatment as in Example 1 was carried out.
．． 9 g of the first stage product was obtained.

The optical isomer ratio is (+)-cis form = 2.4%, (-)-cis form: 2.4%, (+)-) lance form: 45.2%,
(-)-) lance form: 50.0%.

Example 5 Example 4 was carried out in the same manner as in Example 4, except that the reaction temperature was 10° C. and the gas blowing after dropping the hydrogen bromide aqueous solution was 3 hours. Oxygen consumption was 120 cc, and 78.7 g of the first stage product was obtained.

The optical isomer ratios are (+)-cis form: 2.9%, (-) cis form: 2.9%, (+)-) lance form = 45° 8%, (-
)-) Lance form: 48.4%.

Example 6 In Example 1, about 35111 flasks were used, and levorotatory primary ethyl ((+)-cis form=2.
5%, (-)-cis form: 14.7%, (+)-trans form: 11.9%, (-)-) lance form: 70.9
%) 640 m and 5.4 g of toluene,
95mg of 25% hydrogen bromide-acetic acid solution and 390ml of toluene
Example 1 was carried out in the same manner as in Example 1, except that a solution consisting of g was added dropwise. Note that the space volume was 3011, and the molar ratio of oxygen to nitrogen after the reaction was 1:99.

After the reaction, 2% aqueous sodium hydroxide solution was added to neutralize, and the solvent was distilled off under reduced pressure.
% aqueous sodium hydroxide solution was added to perform extraction, and the organic layer was washed with water. The obtained organic layer was concentrated under reduced pressure and then distilled to obtain 600 ml of a distillate having a boiling point of 85 to 88°C/10 mmHH.

This product was determined to be ethyl ester of chrysanthemum acid based on its infrared absorption spectrum. This - part was hydrolyzed by a conventional method, and the obtained carboxylic acid was converted into an ester with (+)-2-octatool, and the optical isomer ratio was determined by gas chromatography. (+) cis form: 3 .6
%, (-) cis form: 3.5%, (+) trans form: 3
7.7%, (-)trans form: 55.2%.

Example 7 In Example 6, the molar ratio of oxygen and nitrogen in the mixed gas was set to 3.
．． 3: The same procedure as in Example 6 was carried out except that 106 cm of 25% hydrogen bromide acetic acid solution was used instead of 96.1, and 600
The molar ratio of oxygen and nitrogen after the 0 reaction to obtain the stage ethyl in (2) is 0.8? It was 99.2.

The optical isomer ratio is (+)-cis: 3.4%, (-)-cis: 3.3%, (+)-)lance: 39.9%,
(-)-Trans form: 53.4%.

Comparative Example 1 In Example 1, the molar ratio of oxygen and nitrogen in the mixed gas was set to 7.
The molar ratio of oxygen and nitrogen after 9 reactions was carried out in the same manner as in Example 1 except that the ratio was changed to 93:93.

The optical isomer ratio is (+)-cis 2.8%, (-)-cis 2.5%, (+)-trans 40.2%, (-)-
) The lance form was 54.5%.

Comparative Example 2 In Example 1, the molar ratio of oxygen and nitrogen in the mixed gas was changed to 5.
The molar ratio of oxygen and nitrogen after the zero reaction was carried out in the same manner as in Example 1 except that the ratio was changed to 0.7:99.3.

The optical isomer ratio is (+)-cis 2.3%, (-)-cis 2.3%, (+)-trans 35.7%, (-)
-1-lance form was 59.7%.

Comparative Example 3 In Comparative Example 2, the 25% hydrogen bromide acetic acid solution was
The same procedure as Comparative Example 2 was carried out except that g was used.

The molar ratio of oxygen to nitrogen after the reaction was 0.4:99.6.

The optical isomer ratio is (+)-cis 2.6%, (-)-cis 2.7%, (+)-)lance 45.8%, (-)-
The trans-isomer content was 48.9%.

Comparative Example 4 In Example 6, the molar ratio of oxygen and nitrogen in the mixed gas was changed to 1.
The same procedure as in Example 6 was carried out except that the value was changed to 99. The molar ratio of oxygen to nitrogen after the reaction was 0.2=99.8.

The optical isomer ratio is (+)-cis form: 3.0%, (-)-cis form: 3.1%, (+)-trans form: 29.8%,
(-)-) lance form: 64.1%.

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (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. ) In the method of producing the corresponding racemate by reacting the optically active chrysanthemum acids with hydrogen bromide, the method is carried out in the presence of oxygen, and the total amount of oxygen used is at least 1/170 times the mole of the chrysanthemum acids. A method for producing racemic chrysanthemum acids, characterized by: