JPH0753682B2 - Process for producing 2-cyclopentenone derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Field of Application> The present invention provides a compound represented by the general formula (I): (In the formula, n represents an integer of 4 to 8) A method for producing a 4-hydroxy-2-cyclopentenone derivative.

<Prior Art> The 4-hydroxy-2-cyclopentenone derivative represented by the general formula (I) is important as an intermediate for medicines and agricultural chemicals,
Especially, it is very useful as an intermediate of prostaglandin.

Heretofore, a method for producing such a 4-hydroxy-2-cyclopentenone derivative has not been known. A method of treating with a strong acid such as an acid in a mixture of water and an inert non-hydroxyl organic solvent miscible with water (JP-A-53-127462), (II) a method of treating with basic alumina 〔Tetrah
edron Lett., 13 , 1131-1134 (1977)] is known.

<Problems to be Solved by the Invention> However, even if these methods are applied to the method for producing the 4-hydroxy-2-cyclopentenone derivative represented by the general formula (I), which is the object compound of the present application, these Each of the methods requires a large amount of a reaction reagent with respect to the reaction substrate, and is not necessarily an industrially advantageous method from the viewpoint of reaction treatment.

Therefore, as a result of research on the industrially advantageous production method of the 4-hydroxy-2-cyclopentenone derivative represented by the general formula (I), the present inventors have solved the drawbacks of the above method. The present invention has been accomplished by finding a method of obtaining a target product with high purity and high yield and industrially advantageous.

<Means for Solving the Problem> The present invention has the following general formula (II). (Wherein n has the same meaning as described above), the hydroxycyclopentenone derivative is subjected to isomerization in the range of pH 6 to 9 in a solvent containing water as a main solvent. The present invention provides a method for producing a 4-hydroxy-2-cyclopentenone derivative represented by I).

The solvent used in the isomerization treatment of the present invention has water as a main solvent and is water alone or a mixed solvent having water as a main component in which a small amount of an organic solvent is mixed. Examples of the other organic solvent include ethylene glycol, 1,3-propanediol, methanol, ethanol, dioxane, tetrahydrofuran, DMF, DMSO, ethyl acetate, acetic acid, dichloromethane, toluene, dimethyl ether, and other aliphatic or aromatic carbonized solvents. Solvents inert to the reaction such as hydrogen, alcohol, fatty acid, ether, ester, halogenated hydrocarbon and the like can be mentioned. However,
Generally, the advantage of coexisting these organic solvents in water is not particularly observed.

This reaction does not necessarily require a catalyst, but its use is effective because the addition of the catalyst improves the reaction rate and increases the reaction rate.

When a catalyst is used in this reaction, examples of the catalyst include various metal salts, organic quaternary ammonium salts, surfactants,
Examples include alcohol.

Examples of various metal salts include phosphates such as sodium, potassium, magnesium, zinc, iron, calcium, manganese, cobalt, and aluminum, sulfates, chlorides, bromides, oxides, organic fatty acid salts, organic sulfonates, etc. Examples of the organic quaternary ammonium salt include tetrabutylammonium bromide, benzyltrimethylammonium chloride, tricaprylmethylammonium chloride, dodecyltrimethylammonium chloride, caprylbenzyldimethylammonium chloride, and the like. Are higher fatty acid salts, polyoxyethylene alkylphenol ethers, higher aliphatic alcohols, and the like, and as the alcohol, methanol, ethanol, ethylene glycol, etc., which are exemplified as the above-mentioned solvents, are used as catalysts. Also used, it is used alone or as a mixture.

When a catalyst is used, the amount used is usually in the range of 1/200 to 5 times the weight of the starting hydroxycyclopentenone derivative, but it is also applicable outside this range.

The catalyst used here can be recovered and reused after completion of the reaction.

The reaction pH is preferably in the range of 6-9, more preferably 7-9.

Examples of the acid used to maintain the pH include hydrochloric acid, sulfuric acid, phosphoric acid, boric acid, acetic acid, propionic acid, toluenesulfonic acid, normal inorganic acids such as methanesulfonic acid, and organic acids. Examples of the alkali include caustic soda, potassium carbonate, sodium hydrogen carbonate, phosphoric acid /
Ordinary inorganic bases and organic bases such as potassium hydrogen and organic amines can be used.

Alternatively, a buffer solution of the above acid-base combination may be used, and examples thereof include phosphoric acid / potassium hydrogen-phosphoric acid, sodium acetate-acetic acid, sodium acetate-phosphoric acid, phthalic acid-potassium carbonate, phosphoric acid / potassium hydrogen-hydrochloric acid. , Potassium dihydrogen phosphate-potassium hydrogen carbonate, succinic acid-sodium hydrogen carbonate, and the like.

Generally, it is more preferable to avoid strong acids such as hydrochloric acid and hydrobromic acid and strong alkalis such as caustic soda and potassium hydroxide as the acid or alkali used for pH adjustment.

The reaction temperature is 0 to 200 ° C., but it is preferably 20 to 1
60 ° C.

From the reaction mixture thus obtained, extraction, liquid separation,
By operations such as concentration, distillation and chromatography, the 4-hydroxy-2-cyclopentenone derivative represented by the general formula (I) can be obtained in good yield.

In the present invention, the hydroxycyclopentenone derivative that is a raw material does not necessarily have to be a single substance, and may contain other compounds that do not adversely affect the reaction. The compound may be contained in the raw material.

The hydroxycyclopentenone derivative represented by the general formula (II) is represented by, for example, the general formula (III) (In the formula, n has the same meaning as described above.) By transposing the furancarbinol derivative represented by the formula (3) in a solvent having water as a main solvent at a pH of 3.5 to 6, the compound is usually represented by the general formula (I). The resulting 4-hydroxy-2-cyclopentenone derivative is partially accompanied, and can be used as it is as a raw material for the isomerization treatment.

This rearrangement reaction is carried out in the range of pH 3.5 to 6, preferably 3.5 to 5, and other reaction conditions are carried out according to the isomerization reaction described above.

The raw material furan carbinol compound in this reaction is, for example, a method of performing Friedel-Crafts reaction, reduction reaction, etc. using furan as a raw material (JP-A-53-127462), and reacting furan with an aldehyde in the presence of a salt catalyst. It can be produced by the method [Tetrahedron Lett., No. 13, 1131 to 1134 (1977)].

<Effects of the Invention> Thus, according to the method of the present invention, the desired 4-hydroxy-2-cyclopentenone derivative can be easily and efficiently obtained from the hydroxycyclopentenone derivative represented by the general formula (II). The 4-hydroxy-2-cyclopentenone derivative is industrially advantageously produced by combining the rearrangement reaction and the isomerization reaction from the furancarbinol derivative represented by the general formula (III). be able to.

<Examples> Hereinafter, the present invention will be described with reference to Examples.

Example 1 In a four-necked flask equipped with a stirrer and a thermometer, 3-
A mixture of hydroxy-2- (ω-hydroxyheptyl) -4-cyclopentenone and 4-hydroxy-2- (ω-hydroxyheptyl) -2-cyclopentenone (composition ratio
3: 1) 64.8 g, 1980 g of water and 2.2 g of acetic acid and a buffer aqueous solution adjusted to pH 8 with 1N sodium hydroxide aqueous solution were charged, and 3-hydroxy-2-
Continue stirring until (ω-hydroxyheptyl) -4-cyclopentenone disappears. After completion of the reaction, the reaction mixture was cooled, extracted twice with 600 g of methyl isobutyl ketone and subjected to liquid separation treatment, and methyl isobutyl ketone was distilled off from the obtained organic layer to give 4-hydroxy-2- (ω-hydroxyheptyl). ) -2-Cyclopentenone (54.1 g, yield 83.5%) was obtained.

mp.55-57 ° C Example 2 α-in a four-necked flask equipped with a stirrer and a thermometer.
(Ω-hydroxyheptyl) furfuryl alcohol 91.0
g, 3600 g of water and 3 g of potassium monohydrogen phosphate and a buffered aqueous solution adjusted to pH 4.2 with phosphoric acid are charged, and the mixture is heated and stirred under a nitrogen atmosphere at 100 ° C. until the raw materials run out.

The reaction mixture was cooled and pH was adjusted to 7 with 1N aqueous potassium hydroxide solution.
After adjusting to 6, the mixture is heated and stirred again at 100 ° C. under a nitrogen atmosphere until the 3-hydroxy-2- (hydroxyheptyl) -4-cyclopentenone produced in the previous reaction is gone.

After completion of the reaction, the reaction mixture was cooled, extracted twice with 600 g of methyl isobutyl ketone and subjected to liquid separation treatment, and methyl isobutyl ketone was distilled off from the obtained organic layer to give 4-hydroxy-
62.1 g (yield 68.2%) of 2- (ω-hydroxyheptyl) -2-cyclopentenone was obtained.

Example 3 As a raw material compound, a mixture of 3-hydroxy-2- (ω-hydroxypentyl) -4-cyclopentenone and 4-hydroxy-2- (ω-hydroxypentyl) -2-cyclopentenone (composition ratio 4: 1) Reaction and post-treatment were conducted in the same manner as in Example 1 except that 10.5 g was used, and 4-hydroxy-2-
(Ω-Hydroxypentyl) -2-cyclopentenone 8.
1 g (yield 77.1%) was obtained.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Shizukazu Kai 3-1,98 Kasugade, Konohana-ku, Osaka City, Osaka Prefecture Sumitomo Chemical Co., Ltd. (72) Inventor Masayoshi Minai Kasuga, Konohana-ku, Osaka City, Osaka Prefecture Ichinaka 3-chome No. 98 Sumitomo Chemical Co., Ltd.

Claims (2)

[Claims] 1. A general formula (In the formula, n represents an integer of 4 to 8) A general formula characterized by subjecting the hydroxycyclopentenone derivative to isomerization in a solvent containing water as a main solvent in the range of pH 6 to 9. (In the formula, n has the same meaning as described above.) A method for producing a 4-hydroxy-2-cyclopentenone derivative. 2. General formula (In the formula, n represents an integer of 4 to 8), the flancarbinol derivative is rearranged in a solvent having water as a main solvent in the range of pH 3.5 to 6 to give a compound of the general formula (Wherein n has the same meaning as described above), and is subjected to isomerization within a range of pH 6 to 9 in a solvent containing water as a main solvent. General formula (In the formula, n has the same meaning as described above.) A method for producing a 4-hydroxy-2-cyclopentenone derivative.