JPS5817177B2 - Process for producing 2-alkyl-4-cyclopenten-1-one - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2-alkyl-4-cyclopenten-1-one with good selectivity.

2-Alkyl-4-cyclopenten-1-one can be used as a variety of physiologically active substances such as plant growth hormones, insect pheromones,
Although it is a useful compound as a synthetic intermediate for aroma substances, etc., it is unstable in both acidic and alkaline conditions, so
It is easy to isomerize to -alkyl-4-cyclopenten-1-one, and it has been difficult to produce only 2-alkyl-4-cyclopenten-1-one with good selectivity and high yield.

Up until now, the method for producing 2-alkyl-4-cyclopenten-1-one has been to react cyclobentenone with diphenyl disulfide in the presence of lithium diisopropylamine, oxidize it, and then halogenate the product in the presence of lithium diisopropylamine salt. A method in which alkyl is reacted and then thermally decomposed, 2-alkyl-5-hydroxy-4-
A reaction that dehydrates cyclobentenone is known, but
The former requires expensive reagents and strict conditions, and the light is unsuitable for industrial methods, while the latter has difficulty in obtaining the raw material α-ketol and has a low yield. Therefore, it is impractical.

The present inventor has conducted extensive research to develop a method for producing 2-alkyl-4-cyclopenten-1-one with easy operation and high selectivity using easily available raw materials. When alkyl-1-alkyl-2-oxo-1-cyclopencunecarboxylate, which is easily brominated, is heated with lithium chloride in a polar solvent, dehydrobromation and dealkoxycarbonyl occur simultaneously, resulting in the desired reaction. It has been found that 2-alkyl-1-ones are produced with good selectivity, and the present invention has been completed based on this finding.

That is, the present invention provides a compound obtained by brominating an alkyl 1-alkyl-2-oxo-1-cyclopencune carboxylate represented by the general formula (I) (in which R1 and R2 represent an alkyl group). 2-, which is characterized by heating a bromide with lithium chloride in an aprotic polar solvent, represented by the general formula (R1 in the old formula has the same meaning as in the general formula 〇) Alkyl-4-cyclopene 7-7-1
-On's manufacturing method.

R1 in general formulas (I) and (II) is methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
It is a linear or branched alkyl group having 1 to 10 carbon atoms such as t-butyl.

Further, R2 in general formula (I) is a lower alkyl group such as methyl, ethyl, propyl, etc.

The compound represented by the general formula (I) can be produced in high yield by a known method using, for example, an adipic acid ester as a raw material.

Examples of the compound represented by general formula (II) include 2
-Methyl-4-cyclopenten-1-one, 2-ethyl-4-cyclopenten-1-one, 2-n-propyl-
4-cyclopenten-1-one, 2-inbutyl-4-
Examples include cyclopenten-1-one.

In the present invention, alkyl 1-al of general formula (■).

The bromination reaction of kyl-2-oxo-cyclopencune carboxylate can be easily carried out with bromine in a solvent that is not monocentric with bromine, such as a chlorinated alkane such as carbon tetrachloride, chloroform, or dichloroethane.

At this time, the solvents may be used alone or in a mixture of several solvents in any proportion.

The reaction is preferably carried out in the absence of moisture.

The reaction temperature must be 20°C or lower to prevent side reactions, but since heat is generated, it is preferable to cool the reaction to -10'C to 5°C.

The reaction time varies depending on the type of solvent and reaction temperature, but is usually several hours to several tens of hours.

; After the reaction is complete, the bromide is separated by conventional methods.

For example, pour the reaction solution into ice water, neutralize with a weak alkali such as sodium bicarbonate, separate the organic layer, extract the aqueous layer with the same solvent used in the reaction, combine with the organic layer, and wash with water. After that, it is dried and the solvent is distilled off to obtain a crude confectionery product.

There is no need for further purification and the crude confectionery product can be used as it is for the next heat treatment.

In the present invention 1, this brominated compound is heated to dehydrobromide, a double bond is introduced, and an alkoxycarbonyl group is removed, resulting in the desired compound of general formula (n).

That is, the general formula (■ ) compounds are produced.

At this time, the solvent may be used alone or in combination.

It is preferable to use lithium chloride in an amount of 3 or more light per 1 equivalent of the compound of general formula (I) as a raw material.

Further, the amount of nitrogen introduced is preferably 9.2 d/sec or more.

The heating temperature varies depending on the type of solvent, but is usually 70℃~
A range of 160°C is preferred.

The reaction is carried out by stirring while cutting off moisture.

The time required to complete the reaction varies depending on the reaction temperature, the type of solvent, the amount of lithium chloride, etc., but is usually in the range of ten or more hours to several days.

After the reaction is completed, the target compound of general formula (II) can be isolated by a conventional method.

For example, the reaction solution is cooled to room temperature, poured into water, extracted with water-immiscible solvents such as ether, benzene, etc., the organic layer is washed with water and dried, then the solvent is distilled off, and the residue is distilled. By doing so, the general formula (formerly 2-alkyl-4-cyclopenten-1-one) can be obtained.

The production method of the present invention can produce 2-alkyl-4-cyclopenten-1-one with good selectivity through simple operations and is suitable for industrial implementation.

Next, the present invention will be explained in more detail with reference to Examples.

Example Methyl 1-methyl-2-oxo-1-cyclopencune carboxylate 2i was placed in a 1 ton three-necked flask, and 300 ml of carbon tetrachloride was added thereto to dissolve it.

Attach the dropping funnel, thermometer, and calcium chloride tube to the flask, and stir the solution with a magnetic cooler while cooling the flask with a mixture of ice, salt, and water.
After the liquid temperature drops below 0°C, add bromine 25. A mixture of i and 150 ml of carbon tetrachloride was added dropwise from the dropping funnel over a period of 1 hour to 1 hour and 30 minutes.

During this time, the liquid temperature was kept below 5°C.

After the dropwise addition was completed, the mixture was stirred at 5° C. or below for 1 hour, and further stirred at room temperature for 4 hours.

Pour the reaction mixture into II cold water, stir well, and then
Transferred to a separatory funnel and separated the organic layer.

The aqueous layer was extracted with 100 ml of carbon tetrachloride, combined with the previously separated organic layer, and the organic layer was washed twice with 150 ml of a saturated aqueous solution of sodium bicarbonate, then washed with brine, and then washed with anhydrous sulfuric acid. The solvent was then evaporated to give the bromide as a pale brown liquid.

This bromide was transferred to a 1 ton three-necked flask, 350 ml of .\xamethylphosphoramide was added thereto to dissolve it, and 4 Cl of anhydrous lithium chloride was added thereto.

A gas introduction tube and a reflux condenser were attached to the flask, and a calcium chloride tube was attached to the upper end of the reflux condenser.

While introducing dry nitrogen into the flask at a flow rate of 0.2 to Q, 5 crrL'' for 7 seconds, the solution was stirred using a magnetic cooler and reacted for 20 hours at a bath temperature of 110°C using an oil bath.

After the reaction was completed, the reaction solution was cooled to room temperature, poured into 1 ton of water, and stirred well.

It was transferred to a separatory funnel and extracted twice with 1 t of ether, the ether layer was washed with brine, dried over dry sodium sulfate, and then the ether was distilled off to give a light brown liquid.

This liquid is distilled to a boiling point of 44-45°C/11torr.
When the fraction was separated, 4.8 g of the desired 2-methyl-4-cyclopenten-1-one was obtained.

Yield coefficient 31 NMR spectrum (δ) for the raw material methyl 1-methyl-2-oxo-1-cyclopencune carboxylate:

Claims (1)

[Claims] 1. Obtained by brominating an alkyl 1-alkyl-2-oxo-1-cyclopencune carboxylate represented by general formula (1) (R1 and R2 in the formula represent an alkyl group) It is characterized by heating a bromide with lithium chloride in an aprotic polar solvent and is represented by the general formula (II) (wherein R1 has the same meaning as in the general formula (1)). 2-alkyl-4-cyclopentene-1-
On's manufacturing method.