JPS6159616B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to γ-diketones and methods for producing the same.

More specifically, the present invention provides a γ-diketone represented by the following formula (), which is a useful intermediate for agricultural chemicals, and a novel method for producing the same.

Allethrin (formula () below), which is known as a useful pesticide, was invented by MS Schechter in 1949 and is widely used all over the world due to its excellent insecticidal activity and low toxicity. Many synthesis methods are also known for the synthesis of the following formula ()).

On the other hand, esters of cyclopentenolone, which has a structure similar to allethrone and is represented by the following formula (), and various acids also have strong insecticidal activity similar to allethrin. It is known that the compound represented by the following formula (), which is an ester with cyclopropanecarboxylic acid, has extremely strong knockdown and lethal effects (Japanese Patent Publication No. 15843/1983).

However, a method for industrially synthesizing the cyclopentenolone represented by the above formula () with a high yield has not yet been established, and despite its excellent performance as an insecticide, the ester of the cyclopentenolone has not yet been established. has not been put to practical use.

As a method for synthesizing cyclopentenolone represented by the formula () at present, a method (scheme below) that is similar to the method for synthesizing allethrone (see scheme A below) that is currently being carried out industrially can be considered.

That is, the method uses propargyl chloride instead of allyl chloride in Scheme A, but in this method, the total yield of cyclopentenolone () from the starting material ethyl acetoacetate () is extremely low at 5%, making it impractical for practical use. Not the method. In particular, the yields in the process of obtaining compounds () and (XI), which are intermediates thereof, are 40% and 30%, respectively, and Scheme A
The yield is significantly lower than that of the corresponding allyl-substituted compounds () and (). Therefore, the total yield of γ-diketone ( ) from ethyl acetoacetate ( ) is only 9.6%, which is a major problem with this method.

Another possible method for synthesizing γ-diketone () is to use the dianion of ethyl acetoacetate () (scheme).

That is, a dianion is formed by reacting ethyl acetoacetate () with sodium hydride and n-butyllithium, which is then reacted with propargyl halide to obtain compound (XI), and then methylglyoxal is obtained in the same manner as in the scheme. This is a method to obtain γ-diketone () by reacting

This method had a higher total yield from ethyl acetoacetate (48%) than the method in Scheme.
However, (1) the alkynylation reaction process requires an ultra-low temperature of -50°C.

(2) Industrially, it is necessary to use n-butyllithium, which is not easy to handle.

This method has the following major drawbacks, and is not necessarily an industrially satisfactory method.

Against this background, the present inventors have conducted intensive studies on the production method of γ-diketone (), which is an important intermediate for the synthesis of cyclopentenolone (), which is used as an intermediate for insecticidal compounds, and have found that it is extremely advantageous. We discovered a method for producing this product, and based on this, we conducted various studies and completed the present invention.

That is, the present invention provides general formula (XII) [In the formula, R represents an alkyl group having 6 or less carbon atoms. ] After hydrolyzing the acetone dicarboxylic acid ester derivative shown in alkaline conditions, methylglyoxal The present invention provides a novel method for producing a γ-diketone represented by the above formula (), which is characterized by reacting the γ-diketone with the above formula ().

As a method similar to the present invention, the following method for synthesizing γ-diketone (), which is an intermediate of arethrolone, is known (USP No. 2, 768, 967).

However, the yield of this method is only 26% as described in the literature.
%, which was extremely low at 30% even in a follow-up test by the present inventors, and therefore, it could not be adopted at all in the industrial production method of Arethrolone.

However, when the present inventors used a propargyl-substituted compound (compound (XII)) corresponding to the above compound (), the γ-diketone () was unexpectedly obtained in a high yield of 80% or more. After discovering this, and further conducting various studies, the present invention was completed.

γ-diketone () obtained by the method of the present invention
can be easily led to cyclopentenolone represented by the above formula (), which is used as an important intermediate for agricultural chemicals, by reacting with a base.

Furthermore, the acetone dicarboxylic acid ester derivative represented by the general formula (XII), which is the starting material of the present invention, has the general formula () [In the formula, R has the same meaning as above. Acetone dicarboxylic acid ester represented by the general formula () HC≡C-CH ₂ -X () [wherein, X represents a halogen atom. ] can be easily synthesized by reacting the halogen compound shown in the following in the presence of a base.

In the acetone dicarboxylic acid ester derivative represented by general formula (XII), specific examples of R include:
Methyl, ethyl, n-propyl, isopropyl,
Examples include groups such as n-butyl, n-pentyl, and n-hexyl.

As the reagent used for the hydrolysis of the present invention, alkali hydroxides such as sodium hydroxide, barium hydroxide, lithium hydroxide, potassium hydroxide, etc. are convenient. As the solvent used in the reaction of the present invention,
Examples include water, lower alcohols, and hydrocarbons such as hexane, benzene, toluene, and xylene, and two or more of these can also be used as a mixture.

The reaction temperature of the present invention is arbitrary within the range of -20°C to the boiling point of the solvent, but it is generally preferably carried out in the range of 0°C to 50°C, and most preferably in the range of 30°C to 40°C. It's advantageous.

The reaction time conveniently ranges from 5 hours to 50 hours.

Although the method of the present invention consists of a two-step reaction,
It is advantageous industrially and in terms of yield to hydrolyze the hydrolyzate without isolating it and then to react with methylglyoxal.

Further, in this reaction with methylglyoxal, the yield varies depending on the pH of the reaction solution, but the most preferable pH is in the range of 7 to 8.

Although the molar ratio of each reagent used in the present invention does not need to be particularly limited, it is convenient for the alkali to be 2.0 to 4.0 times the molar ratio of the acetone dicarboxylic acid ester derivative represented by the general formula ().
The preferred amount of methylglyoxal is 1.0 to 2.0 times the molar amount.

As described above, the present invention provides a method for easily and efficiently producing γ-diketone (), which is an important intermediate in the synthesis of cyclopentenolone (), which is an important intermediate for agricultural chemicals. and
Currently, there is no advantageous method for producing cyclopentenolone (2), so it plays an extremely important role.

Next, the present invention will be explained in more detail with reference to examples, but it goes without saying that the present invention is not limited to these examples.

Example 1 After adding 10% aqueous sodium hydroxide solution (8.0 g of sodium hydroxide, 72 ml of water) to 21.2 g of dimethyl 2-(2'-propynyl)-3-oxoglutarate under ice cooling, the internal temperature was 30°C. After stirring for 5 hours and adjusting the pH of the reaction solution to 7.5 with 10% sulfuric acid under ice cooling,
60ml of toluene was added. Under a nitrogen stream, 20 g of methylglyoxal aqueous solution (40.7%) was added dropwise over 2 hours at an internal temperature of 35°C. After that, the mixture was stirred at an internal temperature of 35°C for 15 hours. After separating the reaction solution and saturating the aqueous layer with sodium chloride,
Extracted four times with ethyl acetate. The toluene layer and ethyl acetate layer were combined and the solvent was distilled off to obtain 13.8 g of 2,5-dioxo-3-hydroxy-8-nonine as a pale yellow oil.

(Yield 82.0%) n ¹⁷ _D 1.4581 NMR data (CDC ₃ , internal standard TMS, δ
Value) 1.94 (1H, t), 2.20 (3H, s), 2.1~3.0
(6H, m), 4.3 (1H, t) Example 2 Add 10% aqueous sodium hydroxide solution (8.0 g of sodium hydroxide, 72 ml of water) to 24.0 g of diethyl 2-(2'-propynyl)-3-oxoglutarate. After adding under ice cooling, the mixture was stirred at an internal temperature of 30°C for 5 hours. On ice, 10
After adjusting the pH of the reaction solution to 7.5 with % sulfuric acid, add toluene.
Added 60ml. Under a nitrogen stream, 20g of methylglyoxal aqueous solution (40.7%) was heated to an internal temperature of 35°C over 2 hours.
It was dripped. After that, the mixture was stirred at an internal temperature of 35°C for 15 hours. The reaction solution was separated into layers, the aqueous layer was saturated with sodium chloride, and extracted three times with ethyl acetate. The toluene layer and ethyl acetate layer were combined and the solvent was distilled off to give a pale yellow oil.
-Dioxo-3-hydroxy-8-nonine 14.1g
I got it.

Yield 83.8% n ²³ _D 1.4593 Reference example 1 Magnesium methoxide (metallic magnesium
25.0 g of dimethyl 3-oxoglutarate was added to 150 ml of methanol solution (prepared from 5.2 g) and stirred under reflux for 1 hour, then 18.0 g of propargyl bromide was added and stirred at 55-60°C for 6 hours. After methanol was distilled off, ethyl acetate and dilute hydrochloric acid were added to separate the layers.
The ethyl acetate layer was washed with brine and then dried over magnesium sulfate. After ethyl acetate was distilled off, the residue was distilled under reduced pressure to obtain dimethyl 2-(2'-propynyl)-3-oxoglutarate.

Boiling point 107-108℃ (0.4mmHg) Refractive index 1.4660 (24℃) Yield 49% NMR data ( _CCl4 , internal standard TMS, δ value) 1.92 (t, 1H), 2.66 (dd, 2H), 3.61 ( s,
2H), 3.81 (t, 1H), 3.66 (s, 3H), 3.70
(s, 3H) Reference example 2 NaOH aqueous solution (NaOH 1.6g, water 30ml) at -5℃
Cool to 2,5-dioxo-3-hydroxy-
A solution of 3.0 g of 8-nonine in 50 ml of toluene was added dropwise over 2 hours while stirring.

After further stirring the reaction solution at -5°C for 2 hours,
The pH was adjusted to 7 with 10% HCl water, and the aqueous solution was saturated with sodium chloride and then separated. After the aqueous layer was further extracted twice with ethyl acetate, the ethyl acetate layer was combined with the previous toluene layer, and the solvent was distilled off. The remaining oil was distilled under reduced pressure to obtain the target product, 2-methyl-3-2'-propynyl-cyclopent 2-en-4-one-1-ol (compound of formula ()), as a pale yellow oil at 1.47
I got g. (Yield 55%) Boiling point 100-110℃ (0.1mmHg) Refractive index 1.5275 (23.5℃) NMR data (solvent CDCl ₃ , internal standard TMS) δ value ppm δ1.94 (t, 1H), 2.18 (s , 3H), 2.1~3.0
(m, 2H), 3.05 (d, 2H), 4.67 (dm, 1H)

Claims (1)

[Claims] 1 formula γ-diketone represented by 2 General formula [In the formula, R represents an alkyl group having 6 or less carbon atoms. ] After hydrolyzing the acetone dicarboxylic acid ester derivative shown in alkaline conditions, methylglyoxal It is characterized by reacting with A method for producing a γ-diketone represented by