JPH0481977B2 - - Google Patents

Description

Detailed Description of the Invention [Industrial Field of Application] The present invention relates to an optical resolution method for (±)-trans-chrysanthemum carboxylic acid, and a method for optical resolution of (±)-trans-chrysanthemum carboxylic acid, and
-Relating to methylbutylamine or an optically active substance thereof. More specifically, the formula 2-(4-methylphenyl)-3-methylbutylamine or an optically active form thereof, and
(±)-trans-Chrysanthemum carboxylic acid, general formula [] (In the formula, R represents a hydrogen atom or a methyl group.) This is a method of optically decomposing (±)-trans-chrysanthemum carboxylic acid by using an optically active amine represented by the following formula.

(±)-Trans-Chrysanthemum carboxylic acid is a carboxylic acid component of an ester called pyrethroid, which is an insecticide component in pyrethrum, but trans-Chrysanthemum carboxylic acid produced by chemical synthesis method is Optically inactive ceramic body, i.e. (±)
-trans- chrysanthemum carboxylic acid. However,
Contained in (±)-trans-chrysanthemum carboxylic acid. Since (-)-trans-chrysanthemum carboxylic acid has significantly inferior insecticidal power compared to (+)-trans-chrysanthemum carboxylic acid, in order to produce a synthetic pyrethroid that is more effective as an insecticide, ( It has been desired to develop a technique for efficiently optically resolving ±)-trans-chrysanthemum carboxylic acid to obtain highly pure (+)-trans-chrysanthemum carboxylic acid.

[Conventional technology]

Conventionally, as a method for obtaining an optically active form of trans-chrysanthemum carboxylic acid, quinine and an optically active 1-
Method using phenylethylamine (IGM
Camp-bell and SHHarper, J.Sci.Food
Agric., 3 , 189 (1952)], method using L-lysine [M.Matsui and F.Horiuchi, Agr.Biol.
Chem., 35 , 1984 (1971)], method using L-2-benzylaminopropanol [F.Horiuchi
and M.Matsui, Agr.Biol.Chem., 37 1713
(1973)] and a method using optically active 1-(1-naphthyl)ethylamine [German Patent No. 2300325 (1975)].

[Problem that the invention seeks to solve]

Conventional techniques have drawbacks such as expensive resolving agents and low yields of optically active trans-chrysanthemum carboxylic acid obtained by resolution, and are not necessarily satisfactory optical resolution methods. There has been a strong desire to obtain highly purified (+)-trans-chrysanthemum carboxylic acid in high yield and economically.

[Means for solving the problems and aspects of the invention]

As a result of intensive research to overcome the difficulties of the prior art, the present inventors have discovered that (+)-trass-kikucarboxylic We have discovered a method for obtaining acids with high purity and high yield.

That is, the present invention is a method of treating (±)-trans-chrysanthemum carboxylic acid with the optically active amine to form a diastereomeric salt, and optically decomposing the salt by utilizing the difference in solubility thereof.

In the present invention, the molar ratio of the optically active amine as a resolving agent and (±)-trans-chrysanthemum carboxylic acid is not particularly limited, but (±)-
When substantially 0.5 to 1 equivalent of the amine is used relative to trans-carboxylic acid, (±)-trans-
This method is preferable because chrysanthemum carboxylic acid can be efficiently resolved and highly pure optically active trans-chrysanthemum carboxylic acid can be obtained. In addition, (±)-trans-chrysanthemum carboxylic acid and the amine are reacted in a solvent, and the solvents used include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol,
Organic solvents such as 2-butanol, acetone, and methyl ethyl ketone alone or in mixtures or water-containing solvents are preferred.

2-(4-methylphenyl)-3- according to the invention
Methylbutylamine is produced by reacting 4-methylbenzyl cyanide and isopropyl bromide with triethylbenzylammonium chloride in a 50% sodium hydroxide solution to obtain 2-(4-methylphenyl)-isobutyl cyanide, and adding hydrogen to this compound. Obtained by reacting lithium aluminum oxide. The reaction formula is shown below.

In addition, optically active 2-(4-methylphenyl)-
3-Methylbutylamine is obtained by making use of the fact that a crystalline diastereomeric salt is formed with optically active anderic acid, by fractionally crystallizing this salt in a suitable solvent, and then recrystallizing it, and then liberating it.

The optical resolution of (±)-trans-chrysanthemum carboxylic acid of the present invention is carried out, for example, by the following method. Add (±)-trans-chrysanthemum carboxylic acid and 0.5 to 1 equivalent of the optically active amine to (±)-trans-chrysanthemum carboxylic acid to a solvent such as methanol, dissolve by heating, and then cool to supersaturate. Preferably, a small amount of seed crystals of an optically active trans-chrysanthemum carboxylic acid/amine salt is inoculated to precipitate a sparingly soluble salt of the same type. After separating this salt, it is recrystallized if necessary. The crystals thus obtained are treated with a base such as sodium hydroxide, potassium hydroxide, or ammonia, and extracted with an organic solvent such as ether or benzene to obtain the optically active amine. Further, the mother liquor is acidified with a mineral acid, extracted with an organic solvent such as ether or methylene chloride, dried and concentrated to obtain optically pure (-) or (+)-trans-chrysanthemum carboxylic acid.

〔Effect of the invention〕

General formula for (±)-trans-chrysanthemum carboxylic acid [] (In the formula, R represents a hydrogen atom or a methyl group) The (±)-trans-chrysanthemum carboxylic acid is optically resolved by acting on an optically active amine represented by the formula (R represents a hydrogen atom or a methyl group) to obtain optically active trans-chrysanthemum carboxylic acid with high purity. By developing a method that can be obtained in high yield, it has become possible to advantageously industrially produce optically active trans chrysanthemum carboxylic acid, which is an effective ingredient of excellent insecticides.

[Examples and reference examples]

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

Example 1 Synthesis of 2-(4-methylphenyl)-3-methylbutylamine 2-(4-methylphenyl)ethanonitrile
An aqueous solution of 66.7 g of sodium hydroxide dissolved in 125 ml of water was added to a mixture of 41.5 g of isopropyl bromide, 58.4 g of isopropyl bromide, and 1.90 g of benzyltriethylammonium chloride, and the mixture was refluxed for 5 hours. After cooling, 60 ml of water was added to the brown reaction solution, and the mixture was extracted twice with benzene. This benzene solution was washed with 30 ml of saturated brine and dried over anhydrous sodium sulfate. After removing benzene, it is distilled under reduced pressure to produce 2-(4-methylphenyl).
43.5 g of -3-methylbutanonitrile was obtained.

Yield: 79.3% Boiling point: 118-123℃ (12mmHg) Next, the previously obtained 2-
A solution of 34.5 g of (4-methylphenyl)-3-methylbutanonitrile dissolved in 35 ml of ether was added dropwise. Thereafter, the mixture was refluxed for 8 hours to obtain a cream-colored solution. Continue to stir this solution while cooling it with ice, and add water.
13.7 ml was added dropwise, and further 14.6 ml of 10% sodium hydroxide solution was added dropwise. To this was added 70 ml of ether, and the mixture was stirred at room temperature overnight. The resulting precipitate was filtered, and the mother liquor was acidified with 130 ml of 2N hydrochloric acid, and extracted and separated with ether. Further, 2 ml of 2N hydrochloric acid was added to this ether and treated in the same manner. The resulting aqueous layers were combined and made alkaline by adding a solution of 18.0 g of sodium hydroxide in 20 ml of water, and the resulting oil was extracted with ether, dried over anhydrous sodium sulfate, and the ether was distilled off. After that, it is distilled under reduced pressure to obtain the target product 2-(4-
methylphenyl)-3-methylbutylamine 23.3
I got g.

Boiling point 123-134℃ (20mmHg) Yield 66.0% [Yield from 2-(4-methylphenyl)-3-methylbutanonitrile] ¹ H-NMR (CCl ₄ ), δ = 0.683 (d, 3H), 0.950
(d, 3H), 1.10 (S, 2H), 1.60~2.50 (m,
broad, 2H), 2.30 (S, 3H), 2.77-2.93 (m,
2H), 6.96 (S, 4H) Example 2 Optical decomposition of 2-(4-methylphenyl)-3-methylbutylamine (±)-2-(4-methylphenyl)-3-methylbutylamine 5.31 g and (+)- mandelic acid
After heating and dissolving 4.56g in 69ml of 5% methanol,
It was left at room temperature. Filter the precipitated crystals (-)
3.70 g of -2-(4-methylphenyl)-3-methylbutylamine (+)-mandelate was obtained.

Melting point: 164-165℃ [α] ³² ₄₃₅ +79.6° (c1.0, methanol) Recrystallize this salt with 44.4ml of 5% methanol,
1.95 g of purified (-)-2-(4-methylphenyl)-3-methylbutylamine/(+)-mandelate was obtained.

Melting point 171-172℃ [α] ³¹ ₄₃₅ +69.5° (c1.0, methanol) Yield 39.5% [Used (±)-2-(4-methylphenyl)-3
-Yield based on (-)-2-(4-methylphenyl)-3-methylbutylamine in methylbutylamine) To 1.85g of this salt was added an aqueous sodium hydroxide solution, extracted with ether, and dried over anhydrous sodium sulfate to extract the ether. After distillation, distill under reduced pressure (-)
0.91 g of -2-(4-methylphenyl)-3-methylbutylamine was obtained.

Boiling point 126℃ (20mmHg) [α] ²⁷ ₄₃₅ −35.4° (C1.0, methanol) This was converted into an amide with optically active benzylmethylphenylsilylacetic acid, and analyzed by ¹ H-NMR. The optical purity was 92%.

Furthermore, 3.30 g of (+) excess 2-(4-methylphenyl)-3-methylbutylamine was added from the mother liquor side.
was recovered. This was treated with 2.80 g of (-)-mandelic acid, heated and dissolved in 62.5 ml of 5% methanol to precipitate crystals, collected by filtration, and (+)-2-(4-methylphenyl)-3-methylbutylamine. (−)−
3.30 g of mandelate was obtained.

[α] ³² ₄₃₅ −73.0° (C1.0, methanol) This salt was recrystallized and purified with 39.6 ml of 5% methanol to form (+)-2-(4-methylphenyl)-3-methylbutylamine.(-) - 1.95 g of mandelic acid salt was obtained.

Melting point 171-172℃ [α] ³⁰ ₄₃₅ −68.8° (C1.0, methanol) Yield 39.5% [Used (±)-2-(4-methylphenyl)-3
- Yield based on (+)-2-(4-methylphenyl)-3-methylbutylamine in methylbutylamine) 1.90 g of this salt was added to (-)-2-(4-methylphenyl)-3-methylbutylamine. - 0.93 g of (+)-2-(4-methylphenyl)-3-methylbutylamine treated in the same manner as mandelate
I got it.

Boiling point 126℃ (20mmHg) [α] ³⁰ ₄₃₅ +37.5° (C1.0, methanol) Optical purity 97.4% Example 3 8.40 g of (±)-trans-Chrysanthemum carboxylic acid and (+)- in 261 ml of 65% methanol Add 6.20 g of 2-(4-methylphenyl)-3-methylbutylamine,
After heating and dissolving at 77°C, the mixture was allowed to cool to 28°C. The mixture was stirred at that temperature for 45 minutes to precipitate crystals, yielding 5.36 g of (+)-trans-chrysanthemum carboxylic acid (+)-2-(4-methylphenyl)-3-methylbutylamine salt.

[α] ²⁵ ₄₃₅ +31.8° (c1.14, MeOH), melting point: 174.5-177.5°C Yield: 62.0% ((+)-trans-kikucarboxylic acid in the (±)-trans-kikucarboxylic acid used) Yield based on acid) 11.6 ml of 2N aqueous sodium hydroxide solution was added to 5.30 g of this salt and extracted with benzene. Subsequently, 5.8 ml of 6N hydrochloric acid was added to the aqueous layer and extracted with methylene chloride, and the solvent was distilled off under reduced pressure to obtain 2.56 g of (+)-trans-chrysanthemum carboxylic acid.

[α] ²⁵ ₅₈₉ +27.0° (c1.00, chloroform) Optical purity
98.5%.

Yield: 60.8% Furthermore, 2.62 g of (+)-2-(4-methylphenyl)-3-methylbutylamine was recovered from the benzene layer.

[α] ²⁷ ₄₃₅ (c1.03, methanol) Optical purity: 96.9% Recovery rate: 96.3% Example 4 In 126 ml of 2-propanol, 8.40 g of (±)-trans-Chrysanthemum carboxylic acid and (-)-2-(4 7.08 g of -methylphenyl-3-methylbutylamine was added and dissolved by heating at 78°C, and then allowed to cool to 34°C.
Stir at that temperature for 10 minutes to precipitate crystals, (-)-
Trans-Chrysanthemum carboxylic acid (-)-2-(4-methylphenyl)-3-methylbutylamine salt 7.47g
I got it.

[α] ²⁷ ₄₃₅ −29.7° (c1.02, MeOH), melting point: 167.5-172.5°C By recrystallizing 6.42 g of this salt from 45.0 ml of methanol, (-)-trans-chrysanthemum carboxylic acid.
3.95 g of (-)-2-(4-methylphenyl)-3-methylbutylamine salt was obtained.

[α] ²⁵ ₄₃₅ −31.6° (c1.02, MeOH), melting point: 175.5-177.5°C Yield: 52.8% ((−)-trans-Chrysanthemum carboxylic acid in the (±)-Trans-Chrysanthemum carboxylic acid used) 3.90 g of this salt was treated in the same manner as in Example 3, yielding (-)
1.79 g of -trans-chrysanthemum carboxylic acid was obtained.

[α] ²⁴ ₅₈₉ −27.0° (c0.998, chloroform) Optical purity: 98.5% Yield: 42.4% In addition, 1.79 g of (-)-2-(4-methylphenyl)-3-methylbutylamine was obtained from the benzene layer. Recovered.

[α] ²⁴ ₄₃₅ −37.6° (c0.946, methanol) Optical purity: 97.7% Recovery rate: 89.4% Example 5 1.76 g of (±)-trans-Chrysanthemum carboxylic acid and (-)-3 in 24 ml of 2-propanol -methyl-2
1.71 g of -phenyl-butylamine was added and dissolved by heating. This was allowed to stand at room temperature for 12 hours, and the precipitated crystals were collected by filtration, and (-)-trans-chrysanthemum carboxylic acid.
1.56 g of (-)-3-methyl-2-phenyl-butylamine salt was obtained. Add this salt to 2-propanol17.7
ml to give purified (-)-trans-chrysanthemum carboxylic acid (-)-3-methyl-2-phenyl-
0.99 g of butylamine salt was obtained.

[α] ³² ₅₈₉ −13.20° (c1.01, MeOH), melting point: 161-163°C Yield: 57.1% ((−)-trans-Chrysanthemum carboxylic acid in the (±)-Trans-Chrysanthemum carboxylic acid used) ) To this salt was added 3 ml of 2N aqueous sodium hydroxide solution.
was added and extracted with ether. Subsequently, 3 ml of 3N hydrochloric acid was added to the aqueous layer and extracted with methylene chloride, and the solvent was distilled off under reduced pressure to obtain 0.47 g of (-)-trans-chrysanthemum carboxylic acid.

[α] ³² ₅₈₉ −230° (c1.01, chloroform) Optical purity 83.9% Yield: 53.5% Example 6 845 mg of (±)-trans-chrysanthemum carboxylic acid and (+)-3-methyl in 14 ml of 2-propanol -2-
816 mg of phenyl-butylamine was added and dissolved by heating. This was left at room temperature and (+)-trans-chrysanthemum carboxylic acid (+)-3-methyl-2-phenyl-
A small amount of seed crystals of butylamine salt was inoculated, and the mixture was further left at room temperature for 12 hours. Filter the precipitated crystals,
Purified (+) by recrystallizing twice with 2-propanol
-trans-Chrysanthemum carboxylic acid (+)-3-methyl-
471 mg of 2-phenyl-butylamine salt was obtained.

[α] ^27.2 ₅₈₉ +14.34℃ (c0.998, MeOH), melting point: 163-166℃ Yield: 56.7% ((+)-trans-Chrysanthemum carboxylic acid in the (±)-Trans-Chrysanthemum carboxylic acid used) Yield based on acid) This salt was treated in the same manner as in Example 3 to obtain 221 mg of (+)-trans-chrysanthemum carboxylic acid.

[α] ^31.8 ₅₈₉ +24.39° (c2.03, chloroform) Optical purity 89.0%.

Yield: 52.0%

Claims (1)

[Claims] 1 formula 2-(4-methylphenyl)-3-methylbutylamine or an optically active substance thereof. 2 When performing optical resolution of (±)-trans-Chrysanthemum carboxylic acid, the general formula [] (In the formula, R represents a hydrogen atom or a methyl group.) A method for optical resolution of (±)-trans-chrysanthemum carboxylic acid, characterized in that an optically active amine represented by the following formula is used.