JPH0359052B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to the general formula () (In the formula, R ₁ represents an allyl group or a propargyl group, R ₂ represents an alkyl group or an aryl group, and * represents an asymmetric carbon.)

More specifically, the present invention is based on the general formula () (In the formula, R ₁ represents the same meaning as above.) A carboxylic acid represented by the general formula () R ₂ COCHO () (In the formula, R ₂ represents the same meaning as above.) Substituted glyoxal represented by the general formula () The present invention relates to a method for producing an optically active alcohol represented by the above general formula (), which comprises reacting the following in the presence of an optically active base.

The alcohol represented by the general formula (), which is the object of the present invention, is a compound that is a raw material for the alcohol component of a pyrethroid ester compound known as an insecticide.

It is known that the insecticidal efficacy of pyrethroid insecticides differs significantly depending on their optical isomer form, and therefore there is a strong desire to develop optically active pyrethroid insecticides that exhibit higher activity.

Under these conditions, the present inventors conducted research on the production of an optically active form of the alcohol component of a pyrethroid ester compound, and found that the optically active alcohol represented by the above general formula () is an intermediate raw material. As a result of investigating a method for industrially advantageous production of
The inventors discovered that the desired optically active alcohol could be advantageously produced through the process, and after conducting various studies, the present invention was completed.

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

The carboxylic acid represented by the general formula () used in the method of the present invention has the general formula () (In the formula, B ₁ represents the same meaning as above, and R ₃ represents an alkyl group having 1 to 5 carbon atoms.) The ester compound represented by the formula is treated with an aqueous solution of alkali hydroxide to saponify it, or General formula () (In the formula, R ₁ and R ₃ have the same meanings as described above.) It can be obtained by treating the diester compound represented by the following with an aqueous solution of an alkali hydroxide, followed by saponification and decarboxylation.

In addition, the substituted glyoxal represented by the general formula () which is the other raw material in the method of the present invention includes alkylglyoxal or arylglyoxal, specifically methylglyoxal, t-butylglyoxal, phenylglyoxal,
Mesitylglyoxal, β-naphthylglyoxal, etc. can be mentioned, and methylglyoxal and phenylglyoxal are preferably used. These substituted glyoxals can be used in the form of an aqueous solution or a hydrate.

In the method of the present invention, examples of the optically active base used include optically active tertiary amines such as cinchonine, cinchonidine, quinine, quinidine, and N-methyl ephedrine, and preferably cinchonine, N-methyl ephedrine, and the like. Optically active amino alcohols such as efuedrin can be used, and cinchonine is more preferably used.

In addition, in the method of the present invention, an inert solvent can be used during the reaction, and such solvents include aromatic hydrocarbons such as toluene and benzene, halogenated carbonates such as dichloroethane, chloroform, and ethylene dichloride. Hydrogen, esters such as ethyl acetate, ethers such as diethyl ether, etc. can be used.

When the substituted glyoxal represented by the general formula () used in the reaction is an aqueous solution, the reaction can also be carried out in a two-layer system with the above-mentioned organic solvent.

The reaction temperature is usually -5℃ to 60℃, preferably 0℃
-40°C, more preferably 0°C - 20°C.

Incidentally, by adding a metal salt such as nickel during the reaction, it is possible to improve the optical purity of the target alcohol represented by (). Examples of such a metal salt include nickel acetate. Can be mentioned.

After carrying out the reaction as described above, the reaction solution is washed with dilute hydrochloric acid to remove the optically active base used, and the desired alcohol is obtained by conventional means such as distillation and silica gel column chromatography. can do.

Incidentally, by neutralizing and then extracting the above-mentioned gaseous hydrochloric acid washing solution, the optically active base can be easily recovered and reused.

EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto in any way.

Example 1 0.56 g of ethyl 3-oxo-6-heptenoate
2.0 ml of 2.5N aqueous sodium hydroxide solution was added and stirred at 40°C for 5 hours. Then, after cooling the reaction solution to 0°C
After neutralization by adding 5.0 ml of 1N hydrochloric acid, the mixture was extracted with ethylene dichloride. The extract was previously cooled to 0°C.
10% methylglyoxal aqueous solution 2.5ml, cinchonine 1.00g and nickel acetate tetrahydrate 1.00g
was added dropwise to the mixture and stirred at 0°C for 5 hours. The reaction solution was washed with 2% hydrochloric acid and saturated brine, dried, and then concentrated. The residue was purified by silica gel column chromatography to obtain 0.33 g of 3-hydroxy-8-nonene-2,5-dione. Obtained.

The compound was treated with the optical activity shift reagent Tris[3-
(heptafluoropropyl hydroxy methylene)-d
- camphorato], europium () derivative (Eu
As a result of measuring the proton peak on the methyl group by ¹ H-NMR using (hfc) ₃ ), (S):(R)=
It was 70:30.

Example 2 Ethyl 3-oxo-6-heptenoate (purity 73
%) 0.77g to 2.0ml of 2.5N sodium hydroxide aqueous solution
was added and stirred at 40°C for 5 hours. Then the reaction solution was reduced to 0.
After cooling to 0.degree. C., 5.0 ml of 1N hydrochloric acid was added to neutralize the mixture, followed by extraction with ethylene dichloride. The extract was previously cooled to 0°C, and a 10% aqueous methylglyoxal solution was added.
Drop into a mixture of 2.5 ml and 1.00 g of cinchonine,
The mixture was stirred at 0°C for 5 hours. The reaction solution was washed with 2% hydrochloric acid and saturated brine, dried, and concentrated. The residue was purified by silica gel column chromatography to obtain 0.31 g of 3-hydroxy-8-nonene-2,5-dione. Obtained.

The compound was measured by ¹ H-NMR using an optical activity shift reagent (Eu(hfc) ₃ ) in the same manner as in Example 1, and the result was that (S):(R)=60:40.

Example 3 The same procedure as in Example 2 was carried out except that 1.47 g of quinine was used instead of cinchonine.
0.34g of product was obtained. (S) of the product: (R)
The ratio was 55:45.

Example 4 The same procedure as Example 2 was carried out except that cinchonidine was used instead of cinchonine.
0.28g of product was obtained. (S) of the product: (R)
The ratio was 41:59.

Example 5 In Example 2, l- was used instead of cinchonine.
The same procedure as in Example 2 was carried out except that 0.73 g of N-methylephedrin was used to obtain 0.29 g of product. The (S):(R) ratio of the product was 44:56.

Example 6 Dimethyl α-propargylacetonecarboxylate
7.00 ml of 2.5N aqueous sodium hydroxide solution was added to 1.50 g, and the mixture was stirred at 40°C for 5 hours. Next, 2.0 g of cinchonine was added to this, and then 17.5 ml of 1N hydrochloric acid was added at 0°C, followed by extraction with ethylene dichloride. 0°C on the night of the extraction.
A 10% aqueous methylglyoxal solution was added thereto, and the mixture was stirred for 5 hours. The reaction solution was washed with 2% hydrochloric acid and saturated brine, dried, and concentrated. The residue was purified by silica gel column chromatography to obtain 0.49 g of 3-hydroxy-8-nonine-2,5-dione. Obtained.

The product was analyzed by ¹ H-NMR using an optical activity shift reagent (Eu(hfc) ₃ ) in the same manner as above (S):(R)
As a result of measuring the ratio of (S):(R)=55:45.

Example 7 The procedure of Example 2 was repeated using 0.55 g of phenylglyoxal hydrate instead of the 10% methylglyoxal aqueous solution, and 0.48 g of 2-hydroxy-1
-Phenyl-7-octene-1,4-dione was obtained.

[α] ₃₆₅ +8.3° (c0.52, CH ₂ Cl ₂ ).

Comparative Example 1 In Example 2, D-
N-(2-hydroxyphenyl)-phenylamine
Same as Example 2 except using 0.852g.
0.196g 3-hydroxy-8-nonene-2,5
-Dione was obtained.

The ratio of (S):(R) was 51:49.

Comparative Example 2 Example 6 except that 1.33 g of ethyl 3-oxo-heptenoate (purity 73%) was used instead of α-propargylacetone dicarboxylic acid and 0.74 g of (+)-phenethylamine was used instead of cinchonine. An oily substance was obtained in the same manner as above.

As a result of NMR analysis, no formation of 3-hydroxy-8-nonene-2,5-dione was observed.

Comparative Example 3 Comparative Example 2 was carried out in the same manner as Comparative Example 3 except that 0.78 g of L-proline was used instead of (+)-phenethylamine, and 0.26 g of 3-hydroxy-8
-Nonene-2,5-dione was obtained.

The ratio of (S):(R) was 50:50.

Claims (1)

[Claims] 1. General formula (In the formula, R ₁ represents an allyl group or a propargyl group.) A substituted glyoxal represented by the general formula R ₂ COCHO (In the formula, R ₂ represents an alkyl group or an aryl group.) is reacted in the presence of an optically active base selected from cinchonine, cinchonidine, quinine, quinidine, and N-methylephedrin. (In the formula, R ₁ and R ₂ represent the same meanings as above, and * represents an asymmetric carbon.) A method for producing an optically active alcohol.