WO2002004436A1

WO2002004436A1 - Processes for the preparation of pyrone compounds

Info

Publication number: WO2002004436A1
Application number: PCT/JP2001/005681
Authority: WO
Inventors: Tatsuya Mori; Noritada Matsuo
Original assignee: Sumitomo Chemical Company, Limited
Priority date: 2000-07-12
Filing date: 2001-06-29
Publication date: 2002-01-17
Also published as: AU2001266362A1

Abstract

A process for the preparation of 4-hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone by reacting 3-acetyl-4-hydroxy-6-methyl-2pyrone with isobutyraldehyde in the presence of both a secondary amine represented by the general formula: R1R2NH (wherein R1 and R2 are linear C1-4 alkyl) and a molecular sieve at -5 to 25°C; and a process for the preparation of 4-hydroxy-6-methyl-3-(4-methylpentanoyl)-2- pyrone by reducing 4-hydroxy-6-methyl-3-(4methyl-2-pentenoyl)-2-pyrone. According to these processes, active ingredients of insecticides or intermediates for the preparation of the ingredients can be prepared advantageously.

Description

Description Manufacturing method of pyrone compounds Technical field

The present invention relates to a process for producing 4-hydroxy-6-methyl-1- (4-methyl-12-pentenyl) -1-pyrone and 4-hydroxy-6-methyl-13- (4-methylpentanoyl) -12-pyrone. About. Background art

Equation (1)

4-Hydroxy-6-methyl-1- (4-methylpentanoyl) -12-pyrone represented by is a compound that can be used as an active ingredient of an insecticide as shown in Reference Examples below. .

On the other hand, equation (2)

As a method for producing 4-hydroxy-1-6-methyl-3- (4-methyl-2-pentenyl) -1-pyrone represented by the following formula, dehydroacetic acid (3-acetyl-4-hydroxy) is disclosed in JP-B-41-20720. A method is described in which (6-methyl-2-pyrone) and isobutyraldehyde are heated for several hours in the presence of a few drops of piperidine in chloroform.

However, after that, in Chemistry and Industry 1969 _P 1306-1307, a compound having a melting point of 178.5 to 181.3 ° C reported in the above-mentioned JP-B-41-20720 was used. The product is not actually 4-hydroxy-16-methyl-3- (4-methyl-12-pentenyl) -1-pyrone. From the data of nuclear magnetic resonance spectrum and infrared spectrum,

It was confirmed that the compound was 3,4-dihydro-12-isopropyl-17-methyl-1H, 5H-pyrano [4,3-1b] -pyran-1,4,5-dione. That is, according to the method described in JP-B-41-20720, 4-hydroxy-16-methyl-13- (4-methyl-12-pentenyl) is prepared from 3-acetyl-4-hydroxy-6-methyl-2-pyrone and isobutyraldehyde. Substantially no 2-pyrone could be obtained. Disclosure of the invention

The present invention relates to 4-hydroxy-16-methyl-13- (4-methyl-12-pentenyl) -12-pyrone represented by the above formula (2) from 3-acetyl-14-hydroxy-6-methyl-1-pyrone. Is produced in high yield, and is further converted to 4-hydroxy-6-methyl-13- (4-methylpentanoyl) -12-pyrone represented by the formula (1), whereby the active ingredient of the insecticide is obtained. An object of the present invention is to provide a method for industrially and advantageously producing the compound 4-hydroxy-16-methyl-3- (4-methylpentanoyl) -1-pyrone.

That is, the present invention relates to formula (3)

The 3-acetyl-4-hydroxy-6-methyl-1-pyrone and isobutyl aldehyde represented by the formula are represented by the formula R ¹ R ² NH (wherein R ¹ and R ² each represent a linear C1-C4 alkyl group). By reacting at 15-25 ° C. in the presence of the indicated secondary amine and molecular sieves, 4-hydroxy-16-methyl-13- (4-methyl-12-pentenyl) 1-2 —Pyrone can be produced in high yield, and 3-acetyl-1-hydroxy-1-6 1-methyl-2-pyrone and isobutyraldehyde are combined with a secondary amine having the formula R ¹ R ² NH (wherein R ¹ and R ² have the same meanings as described above) and molecular sieves. Reaction at ° 25 ° C., and then reducing the resulting 4-hydroxy-6-methyl-3- (4-methyl-12-pentenyl) -1-pyrone by reducing 4-hydroxy-6-methyl-3- (4-methylpentane). This means that 2-yl-pyrone can be produced in high yield.

First, the first process of reacting 3-acetyl-14-hydroxy-16-methyl-2-pyrone with isobutyl aldehyde will be described. The process is illustrated by the following scheme.

(3)

(2) In the reaction, commercially available molecular sieves can be used as they are. Molecular sieves 3A powder is preferably used as the molecular sieve. The amount of molecular sieves used in the reaction is usually 0.5 to 4 parts by weight, preferably 0.5 to 3 parts by weight, based on 1 part by weight of 3-acetyl-14-hydroxy-6-methyl-2-pyrone. Is the ratio of

Examples of the secondary amine which can be used in the reaction include getylamine, methylethylamine, dipropylamine and dibutylamine.

The reaction temperature of the reaction is set at a low temperature, which requires a longer time to complete the first process. On the other hand, when the temperature is set at a high temperature, the yield of the desired product tends to decrease. It is in the range of 5-25 ° C, preferably in the range of 15-20 ° C, more preferably in the range of 0-10 ° C.

The reaction between 3-acetyl-4-hydroxy-16-methyl-1-pyrone and isobutyraldehyde can be carried out without a solvent, but is usually carried out in a solvent. The solvent used in the reaction is not particularly limited as long as it is a solvent inert to the reaction, but the use of tetrahydrofuran, methyl isobutyl ketone or acetone is preferred from the viewpoint of yield. The reaction time required for the first process is usually 0.5 to 24 hours.

After completion of the reaction, the molecular sieves are removed by filtration, and the filtrate is subjected to a normal post-treatment operation such as extraction of an organic solvent and concentration to obtain 4-hydroxy-16-methyl-3-.

(4-Methyl-2-pentyl) -1-pyrone can be isolated. Further, if necessary, it can be purified by recrystallization, chromatography or the like.

Then, 4-hydroxy-16-methyl-3- (4-methyl-1-pentenyl) -1-pyrone is reduced to give 4-hydroxy-16-methyl-3- (4-methylpentanoyl) -1

A second process for producing 2-pyrone is described.

The reduction reaction of the second process is usually carried out in a solvent in the presence of a transition metal catalyst, in a solvent, with 4-hydroxy-16-methyl-1- (4-methyl-12-pentenyl) -12-pyrone and hydrogen. The reaction is carried out. The solvent used in the reaction is a solvent inert to the reduction reaction, and examples thereof include esters such as ethyl acetate and butyl acetate, ketones such as methyl isobutyl ketone, and aromatic hydrocarbons such as toluene. .

Examples of the transition metal catalyst include a palladium catalyst and a platinum catalyst, and more specific examples include palladium-carbon and platinum oxide. The amount of the transition metal catalyst to be used is usually a ratio of 100 parts by weight to 100 parts by weight of 4-hydroxy-16-methyl-13- (4-methyl-2-pentenyl) -12-pyrone.

The reaction time required for the second process is usually 0.5 to 24 hours.

After completion of the reaction, the reaction mixture is filtered to remove the catalyst, and the filtrate is subjected to ordinary post-treatment operations such as extraction with an organic solvent and concentration to give 4-hydroxy-6-methyl-3- (4-methylpentanoyl). L) It is possible to isolate 1-2-pyrone. Further, if necessary, it can be purified by distillation, chromatography, crystallization, amine salt crystallization, or the like.

After the first process, it is not necessary to isolate 4-hydroxy-16-methyl-3- (4-methyl-2-pentenoyl) -12-pyrone. For example, if necessary, remove the molecular sieves by filtering the reaction mixture. After that, a reduction reaction, which is a second process, can be performed by adding a transition metal catalyst. In such a case, the amount of the transition metal catalyst to be used is usually 1 to 10 parts by weight based on 100 parts by weight of 3-acetyl-4-hydroxy-6-methyl-1-pyrone. The starting material 3-acetyl-4-hydroxy-16-methyl-12-pyrone used in the method of the present invention is also known as dehydroacetic acid and is a known compound which is commercially available as a preservative. Example

Hereinafter, the present invention will be described in more detail with reference to Production Examples, but the present invention is not limited to only these Examples.

Production Example 1

Under a nitrogen atmosphere, 3-acetyl-4-hydroxy-6-methyl-1-pyrone 3.Og, isobutyraldehyde 1.9g and molecular sieves 3A powder 3.Og were added to 15ml of dry tetrahydrofuran 15ml, and getylamine at 0-5 ° C under stirring. 0.53 g of a 1 Oml solution of dry tetrahydrofuran was added dropwise over about 1 hour. After the dropwise addition, the mixture was further stirred at 0 to 5 ° C for 2 hours. Thereafter, the reaction mixture was filtered through celite, and the celite was washed with 50 ml of ethyl acetate. The combined filtrate and washings were washed once with 0.1% hydrochloric acid, twice with water and once with saturated saline, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and concentrated under reduced pressure. 3.9 g of —methyl-1- (4-methyl-12-pentenyl) -12-pyrone was obtained.

1H-NMR (CDCI ₃ , TMS internal standard) (5 (ppm): 1.13 (d, 6H), 2.27 (s, 3H), 2.60 (m, 1H), 5.93 (s, 1H) , 7.23 (dd, 1H), 7.58 (d, 1H)

Production Example 2

Under a nitrogen atmosphere, 4-hydroxy-16-methyl-3- (4-methyl-2-pentenyl) -12-pyrone 1.Og was dissolved in 10 ml of ethyl acetate, and 0.05 g of 5% palladium / carbon was added thereto. The nitrogen in the reaction vessel was replaced with hydrogen, and the mixture was stirred at room temperature for 3 hours. Thereafter, the reaction mixture was filtered through celite and concentrated under reduced pressure. The residue obtained was subjected to silica gel column chromatography to give 0.85 g of 4-hydroxy-6-methyl-3- (4-methylpentanoinole) -12-pyrone. I got

'H-NMRCCDCI 3, TMS internal standard) 5 (ppm): 0.94 (6H, d), 1.54 (2H, q), 1.63 (1H, m), 2.27 (3H, s) , 3.08 (2H, t), 5.93 (1H, s), 17.88 (1H, s)

Production Example 3

Under a nitrogen atmosphere, 3-acetyl-4-hydroxy-6-methyl-1-pyrone 10g, isobutyraldehyde 6.4g and molecular sieves 3A in 60g of methyl isobutyl ketone 20 g of the powder was added, and a solution of 1.7 g of getylamine in 5 g of methyl isobutyl ketone was added dropwise at about 0 ° C. over about 15 minutes. After the addition, the mixture was further stirred at about 0 ° C for 20.5 hours. Thereafter, the reaction mixture was filtered through celite, and the celite was washed with 1 Og of methyl isobutyl ketone. Under a nitrogen atmosphere, 0.5 g of 5% palladium-carbon was added while keeping the combined solution of the filtrate and the washing solution at about 0 ° C. The nitrogen in the reaction vessel was replaced with hydrogen, and the mixture was stirred at about 0 ° C for 1.3 hours while adding hydrogen. Thereafter, the reaction mixture was filtered through celite, 2.5 g of agricultural hydrochloric acid and 50 g of water were sequentially added to the filtrate under stirring, and the mixture was further stirred for 30 minutes, followed by separation. 10.4 g of 4-hydroxy-6-methyl-3- (4-methylpentanoyl) -12-pyrone was obtained. Reference examples show that 4-hydroxy-6-methyl-1- (4-methylpentanoyl) -12-pyrone obtained as described above is useful as an active ingredient of an insecticide. Reference example

0.5 parts by weight of 4-hydroxy-6-methyl-1- (4-methylpentanoyl) -12-pyrone was dissolved in 10 parts by weight of dichloromethane, and this was dissolved in Isopa-M (isoparaffin manufactured by Exxon Chemical) 89.5 0.5 parts by weight of an oil agent was prepared by mixing with 0.5 parts by weight.

House flies (M / sca io / 7? Esi / a) 10 adults (5 males and 5 females) were released into a cubic glass chamber (0.34 m ^{3 in} volume) with a side of 70 cm. 0.7 ml of the oil was sprayed into the chamber at a pressure of 0.9 kgZcm ^{2 with} a spray gun from a small window on one side of the chamber. Fifteen minutes later, the state of the housefly knockdown was observed. As a result of two replicate tests, the knockdown rate was 95%. Industrial applicability

The present invention advantageously produces 4-hydroxy-6-methyl-1- (4-methyl-2-pentanoyl) -12-pyrone and 4-hydroxy-16-methyl-3- (4-methylpentenyl) -12-pyrone. These compounds are useful as an active ingredient of an insecticide or an intermediate in the production thereof.

Claims

The scope of the claims

1.3-Acetyl-4-hydroxy-6-methyl-1-pyrone and isobutyl aldehyde are represented by the formula R ¹ R ² NH (wherein R ¹ and R ² each represent a straight-chain C1-C4 alkyl group). Of 4-hydroxy-16-methyl-3- (4-methyl-12-pentenyl) -12-pyrone, characterized by reacting at 15-25 ° C in the presence of secondary amine and molecular sieves Manufacturing method.

2. The method according to claim 1, wherein the secondary amine is getylamine, methylethylamine, dipropylamine or dibutylamine.

3. The method according to claim 1, wherein the secondary amine is getylamine.

4. The process according to claim 1, wherein the reaction is carried out in a solvent of tetrahydrofuran, methyl isobutyl ketone or acetone.

5. 3-Acetyl-4-hydroxy-6-methyl-1-pyrone and isobutyl aldehyde are represented by the formula R ¹ R ² NH (wherein R ¹ and R ² each represent a straight-chain C1-C4 alkyl group). Characterized by reacting at 15 to 25 ° C. in the presence of a secondary amine and molecular sieves represented by the following formula, and then reducing the product: 4-hydroxy-6-methyl-3- (4- Methylpentanoyl) A process for producing 2-pyrone.

6. The method according to claim 5, wherein the secondary amine is getylamine, methylethylamine, dipropylamine or dibutylamine.

7. The method according to claim 5, wherein the secondary amine is getylamine.

8. The production method according to claim 5, wherein the reduction is performed using a transition metal catalyst.

9. The method according to claim 8, wherein the transition metal catalyst is a palladium catalyst or a platinum catalyst.

10. The process according to claim 5, wherein the reduction is carried out in an ester or aromatic hydrocarbon solvent.