JPH0759530B2 - Process for producing 2,3-disubstituted cyclopentanone mixture - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing a 2,3-disubstituted cyclopentanone mixture.

(Prior Art) 2,3-Disubstituted cyclopentanones represented by methyl jasmonate and methyl dihydrojasmonate are used as fragrances, drugs, and
It is a useful chemical substance in fields such as chemicals.

Such 2,3-disubstituted cyclopentanone has stereoisomers of cis and trans isomers as shown by the following general formulas (I) to (IV). It has been found to be excellent in terms of evaluation and physiological activity.

(In the formula, R ₁ represents a hydrocarbon residue, and R ₂ represents a hydrocarbon residue which may have a substituent.) For example, in the case of methyl jasmonate, the essence of the odor exists in the cis form (Agricultural and Biological Chem
istry. 49, p. 769, 1985), and it was also reported that the cis form is more active than the trans form or a mixture of the cis form and the trans form in the physiologically active action on plants (plant physiology). Proceedings of the conference, 347 pages, 1989, Pla
nt Physiology, 66 , 246, 1980).

From these findings, research on the synthesis of cis-2,3-disubstituted cyclopentanone has been actively conducted.For example, regarding the synthesis of methyl jasmonate and methyl dihydrojasmonate, the 29th fragrance / terpene and essential oil Proceedings of the Symposium on Chemistry, 222 pages, 1985, The 30th Symposium, 101 pages, 1986, The 32nd Symposium, 132 pages,
It was reported in 1988. However, this method has a problem in that it is not practical because a cis-form cannot be obtained efficiently and an expensive reagent having a long number of reaction steps is used.

On the other hand, it is generally known that the trans form is more advantageous in equilibrium between the cis form and the trans form. Therefore, a method for efficiently obtaining the cis form by converting the trans form into the cis form has been studied, and recently, a method of treating methyl jasmonate with paratoluenesulfonic acid in the presence of a solvent was reported (perfume. Sangyo Shimbun, No. 247, published April 15, 1988, p. 6). However, with this method, the yield of the cis isomer was as low as about 5%, and there was a concern that side reactions were likely to occur.

(Problems to be Solved by the Invention) As a result of intensive research to solve the above-mentioned drawbacks, the present inventors have found that
When the trans form of 3-disubstituted cyclopentanone is heated in the presence of a metal salt of carbonic acid, a cis form can be obtained in good yield without causing a side reaction. It was found that a cis isomer can be efficiently obtained by adjusting the amount to a small amount, and the present invention has been completed based on this finding.

(Means for Solving the Problems) Thus, according to the present invention, as a first invention, cis characterized by heating trans-2,3-disubstituted cyclopentanone in the presence of a metal salt of carbonic acid. As a second invention, a method for producing a 2,3-disubstituted cyclopentanone mixture containing -2,3-disubstituted cyclopentanone is trans-2,3-
A cis-2,3-disubstituted cyclopentan, characterized in that the disubstituted cyclopentanone is heated in the presence of 100 ppm or less (weight basis) of a metal salt of carbonic acid with respect to the cyclopentanone, and then distilled. A method of making a 2,3-disubstituted cyclopentanone mixture containing nonones is provided.

In the present invention, the raw material is trans-2,3-disubstituted cyclopentanone, which is represented by the above general formulas (III) and (IV).
In the formula, R ₁ is an alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group or a nonyl group, an alkenyl such as a vinyl group, a propenyl group, a butenyl group, a pentenyl group or a hexenyl group. Group, ethynyl group, propynyl group, butynyl group, pentynyl group,
And hydrocarbon residues such as alkynyl groups such as hexynyl groups.

On the other hand, R ₂ represents a hydrocarbon residue similar to R ₁ and may be a hydrocarbon residue having a substituent such as an alkoxycarbonyl group, an alkoxyalkyl group and an alkoxycarbonylalkyl group.

In the present invention, a metal salt of carbonic acid is used as a catalyst. Specific examples of the metal salt of carbonic acid include, for example, alkali metal salts such as sodium carbonate, potassium carbonate, lithium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate, alkaline earth metal salts such as calcium carbonate and magnesium carbonate, Examples thereof include transition metal salts such as copper carbonate and nickel carbonate, and among them, alkali metal salts are preferable.

The amount of such a metal salt of carbonic acid cannot be unconditionally limited depending on the type and reaction conditions, but usually, the raw material trans-2,
10 ppb (weight basis) for 3-disubstituted cyclopentanone
Or more, preferably 100 ppb or more. The upper limit of the amount used is not particularly limited, but since it does not dissolve at the reaction temperature, it becomes a slurry and only exists in the system and does not contribute to the reaction, so it is usually set within the range of solubility or lower.

In the present invention, when the post-treatment is carried out by distillation after the completion of the reaction, it is preferable to adjust the amount of the metal salt of carbonic acid to a small amount, and the upper limit is 10 ppb (weight by weight) with respect to trans-2,3-disubstituted cyclopentanone. Standard) or higher, preferably 100 ppb
Hereafter, it is more preferably set in the range of 1 ppm or less. Examples of the method for preparing a trace amount include a method of dissolving a metal salt of carbonic acid at a dissolution temperature for a desired dissolution concentration, a method of removing insoluble matter by filtration, and a method of using a diluent prepared in advance. To be Generally, the equilibrium of the trans form of the cis form moves favorably to the cis form at high temperatures, but the distillation operation must be performed at a temperature lower than the temperature at the time of equilibrium formation in order to prevent the generation of offensive odors and coloration, and to increase the distillation efficiency. . However, in this case, when the upper limit of the amount of the metal salt of carbonic acid used is outside the above range, that is, when it is used in a range exceeding 100 ppm, the equilibrium shifts from the cis form to the trans form during distillation, and the yield of the cis form decreases. There is a drawback that.

The reaction of the present invention proceeds by heating the raw material in the presence of a metal salt of carbonic acid. The reaction temperature is usually 60 to 300 ° C, preferably 100 to ≠ 250 ° C, more preferably 110 to 220 ° C. The reaction time is usually 5 minutes to 36 hours.

A diluent may be present during the reaction, and specific examples thereof include nitriles such as acetonitrile and benzonitrile, amides such as dimethylformamide and dimethylacetamide, ethers such as tetrahydrofuran and dioxane, and acetone. Ketones such as methyl ethyl ketone, methyl acetate,
Examples thereof include esters such as ethyl acetate, alcohols such as ethanol and propanol, sulfoxides such as dimethyl sulfoxide and diethyl sulfoxide, and hydrocarbons such as n-hexane, benzene and toluene.

After completion of the reaction, by performing a post-treatment according to a conventional method,
It is possible to obtain high quality objects. As a method of post-treatment, for example, a method by distillation, a method by solvent extraction,
Examples of the method include washing with water, and the method using distillation is preferable from the viewpoint of operability. When carrying out the distillation operation, it is necessary to adjust the amount of the metal salt of carbonic acid to be small for the reasons described above. The distillation conditions are appropriately selected depending on the type of reaction product, but it is preferable to carry out the reaction at a low temperature for the above-mentioned reason, and the boiling point is usually 170 ° C or lower, preferably 160 ° C or lower,
More preferably, it is selected in the range of 150 ° C. or lower and the liquid temperature is 250 ° C. or lower, preferably 220 ° C. or lower, more preferably 200 ° C. or lower.

The 2,3-disubstituted cyclopentanone thus obtained is a mixture containing the cis-2,3-disubstituted cyclopentanone represented by the general formulas (I) and (II). In the reaction of the present invention, the side chain at the 2-position of cyclopentanone is selectively inverted, so the structure of the cis isomer in the product differs depending on the structure of the raw material. That is, the cis form of the general formula (III) is obtained from the trans form of the general formula (III), and the cis form of the general formula (II) is obtained from the trans form of the general formula (IV).

(Effect of the Invention) Thus, according to the present invention, it is possible to obtain cis-2,3-disubstituted cyclopentanone in a higher yield than in the prior art.

Hereinafter, the present invention will be described more specifically with reference to examples. In addition,% in the examples and comparative examples is based on weight unless otherwise specified.

Example 1 100% pure methyl jasmonate (cis content 0.6%,
When 20 mg of metal salt of carbonic acid shown in Table 1 was mixed with 2.0 g of trans content 99.4%) and stirred at 180 ° C for a predetermined time in a nitrogen atmosphere, side reactions such as decomposition did not occur and the purity was 100%.
2.0 g of% methyl jasmonate was obtained. The cis-form content of this product was as shown in Table 1.

The cis-form content (%) is the ratio of cis-form to the total of cis-form and trans-form determined from the peak area value of gas chromatography.

Comparative Example 1 When the same operation as in Example 1 was carried out without using a metal salt of carbonic acid, the reaction product had a cis content of 2.4 after a reaction time of 19 hours.
(%)Met.

When the reaction was further continued for 5 hours, side reactions such as coloring and decomposition occurred.

Example 2 Using the metal salts of carbonic acid shown in Table 2, the reaction temperature was 120 ° C,
The same operation as in Example 1 was carried out except that the reaction period was 10 hours. The results are shown in Table 2.

Example 3 Experiment number 1-of Example 1 except that 2.0 g of methyl jasmonate having a trans isomer content of 100% (purity 100%) was used.
When operated in the same manner as in 1, 2.0 g of methyl jasmonate having a cis content of 10.2% (purity 100%) was obtained.

Example 4 2.0 g of methyl dihydrojasmonate having a cis content of 6.7%
The same operation as in Experiment No. 1-1 of Example 1 except that (purity 100%) was used, and 2.0 g of methyl dihydrojasmonate (purity 100%) having a cis content of 12.7% was obtained.

Example 4 The procedure of Example 5 was repeated except that the reaction temperature was 120 ° C., and 2.0 g of methyl dihydrojasmonate (100%) having a cis content of 12.2% was obtained.

Example 6 100% pure methyl jasmonate (cis content 0.6%,
1.0 g of sodium carbonate was added to 100 g of trans content 99.4%, and the mixture was stirred at the temperature shown in Table 3 for 3 hours. Next, when the insoluble sodium carbonate was removed by filtration, the concentration of sodium carbonate dissolved in the filtrate was as shown in Table 3. When this filtrate was stirred at 180 ° C for 13 hours, 100 g of methyl jasmonate with a cis content of 10.6% (purity
100%) was obtained. Subsequent distillation (1 mmHg, boiling point 122 ° C)
As a result of purification by the method described above, 94 g of methyl jasmonate (purity 100%) having a cis-form content shown in Table 3 was obtained (Experiment Nos. 3-1 to 3-3).

Further, when the same operation as described above was carried out except that the filtration operation was not carried out, 94 g of methyl jasmonate (purity 100%) was obtained. The cis-form content is shown in Table 3 (Experiment No. 3-
4).

From Table 3, the cis-form content of methyl jasmonate obtained by distillation is lower than that before the distillation, but by adjusting the amount of sodium carbonate used in a small amount, the cis-form content at the time of distillation is reduced. It turns out that it can be suppressed (Experiment No. 3-1 to 3-3).

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Claims (2)

[Claims] 1. A 2,3-containing cis-2,3-disubstituted cyclopentanone, characterized in that the trans-2,3-disubstituted cyclopentanone is heated in the presence of a metal salt of carbonic acid. Method for producing disubstituted cyclopentanone mixture. 2. A trans-2,3-disubstituted cyclopentanone is heated in the presence of a metal salt of carbonic acid of 100 ppm or less (weight basis) with respect to the cyclopentanone, and then distilled. A method for producing a 2,3-disubstituted cyclopentanone mixture containing cis-2,3-disubstituted cyclopentanone.