JPS6247171B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides the following formula (1), which is an important intermediate for the synthesis of diasmonoids, However, in the formula, R represents a lower alkyl group such as a methyl group or an ethyl group. However, in the formula, R may be the same or different,
2-allyl-2,5-dialkoxycarbonyl-3-alkoxycarbonylmethyl-, each representing a lower alkyl group, such as a methyl group or an ethyl group;
The present invention relates to 1-cyclopentanone and methods for producing them.

Hitherto, no industrially satisfactory method for producing the compound of formula (1) has been proposed. For example, JP-A-53-103450 describes a method for producing 2-allyl-3-methoxycarbonylmethylcyclopentanone in the process of producing methyl cis-diasmonate. According to this production method, dicyclopentadiene is subjected to a hydroxylation step and an allylation step and then thermally decomposed to produce a mixture of 2-allylcyclopenten-2 (or -3 or -4)-one-1; This is isomerized and converted to 2-allylcyclopenten-2-one-1, and then reacted with dimethyl malonate to form 2-allyl-3-dicarbomethoxymethylcyclopentanone, which is then thermally decomposed. 2-allyl-3-methoxycarbonylmethylcyclopentanone is produced. This method has disadvantages in that it requires complicated operations and multiple steps that are not suitable for industrial implementation, and it also has disadvantages such as a large amount of by-products and a poor yield.

The present inventors conducted research in order to develop a new synthesis method that can overcome the disadvantages or defects of the above-mentioned conventional proposals.

As a result, a compound represented by the above formula (2) which has not been described in the literature can be synthesized, and by subjecting the compound of formula (2) to a decarboxylation reaction in the presence of an acid, an industrially advantageously shortened process can be performed. We have discovered that the compound of formula (1) can be produced with high yield and high purity.

According to the research of the present inventors, the following formula (3) can be easily produced from an inexpensive and easily synthesized acetone dicarboxylic acid ester derivative. However, in the formula, R may be the same or different,
Alkyl 2-allyl-3-oxoglutarate represented by and the following formula (4), each representing a lower alkyl group However, in the formula, R represents a lower alkyl group, and X represents a halogen atom. From the alkyl 4-halocrotonate represented by the formula (2), the compound of the formula (2), which has not been described in any literature, can be easily obtained in high yield. It was found that the compound of formula (1) can be produced with high purity, and that the compound of formula (1) can be produced all at once by subjecting the compound of formula (2) to a decarboxylation reaction.

Therefore, an object of the present invention is to provide a compound of formula (2) useful for producing the compound of formula (1) and a method for producing the same.

The above objects and many more objects and advantages of the present invention will become more apparent from the following description.

According to the method of the present invention, 2-allyl- of the formula (3)
The compound of the formula (1) is obtained from the alkyl 3-oxoglutarate via the novel 2-allyl-2,5-dialkoxycarbonyl-3-alkoxycarbonylmethyl-1-cyclopentanone of the formula (2). It can be produced by easy means and with high yield and high purity.

Regarding one specific example of the production method of the present invention, a reaction process diagram including a production example of the compound of formula (1) is shown below.

2-allyl-3 of the above formula (3) which is a raw material of the present invention
-Alkyl oxoglutarate can be easily synthesized with good yield and high purity by reacting an alkyl acetonedicarboxylate, which is easily available and easily synthesized, with allyl bromide, for example. Below, embodiments of the method for synthesizing the compound of formula (1) will be described according to the above process diagram.

In the present invention, the formation of 2-allyl-2,5-dialkoxycarbonyl-3-alkoxycarbonylmethyl-1-cyclopentanones of the formula (2) having a persistent floral aroma that can be used as a novel fragrance itself. The reaction can be carried out, for example, by reacting the alkyl 2-allyl-3-oxoglutarate of formula (3) with the following formula (4) in an inert organic solvent in the presence of a base. In the formula, R represents a lower alkyl group such as a methyl group or an ethyl group, and X represents a halogen atom. It can be easily done at a high rate.

The reaction temperature of the reaction can be selected as appropriate, for example,
A temperature range of about -20° to about +200°C, more preferably a temperature range of about 20 to about 100°C can be exemplified. The reaction time can be changed as appropriate depending on the reaction temperature, etc., and for example, from about 1 to about
A reaction time of about 100 hours can be exemplified.

Specific examples of the base used in the condensation ring closure reaction include NaOC ₂ H ₅ , t-BuOK, t
−AmOK, NaH, Mg( _OCH3 ) ₂ , Mg
(CO ₂ H ₅ ) ₂ , NaNH ₂ , KNH ₂ , [(CH ₃ ) ₂ CH] ₂ NLi,
CH ₃ SOCH ₂ Na, K ₂ CO ₃ , Na ₂ CO ₃ , NaOH and
KOH (t-Bu stands for tertiary butyl, t-Am
(indicates tertiary amyl), etc. The amount of these bases to be used can be selected as appropriate, for example, about 0.5 to 1 mole of the compound of formula (3).
A range of about 5 moles to about 5 moles is sufficient, and more preferably a range of about 1.5 to about 3 moles is often employed.

The amount of the alkyl 4-halocrotonate of the formula (4) used in the above reaction can be appropriately selected, and for example, per mole of the compound of the formula (3),
Amounts on the order of about 0.5 to about 30 moles are often employed.

Further, specific examples of the inert organic solvent used in the condensation ring-closing reaction include methanol,
Examples include ethanol, t-butanol, t-amyl alcohol, diethyl ether, diisopropyl ether, dibutyl ether, dimethoxyethane, digum, tetrahydrofuran, dioxane, benzene, toluene, xylene, DMF and DMSO. These solvents can be used alone or in combination of two or more. There is no particular restriction on the amount of these solvents used, but the amount used is about 1 to about 200 times, more preferably about 5 to about 50 times the weight of the compound of formula (3). I can give an example. After the completion of the above reaction,
For example, by injecting the reaction product into water, neutralizing it, extracting it with an appropriate solvent, washing the solvent layer with water, drying, and concentrating it, 2-allyl-2.5 represented by formula (2) can be obtained. -Dialkoxycarbonyl 3-alkoxycarbonylmethyl-1-cyclopentanones can be obtained with high yield and high purity. If desired, by means such as vacuum distillation or column chromatography,
Further purification is also possible.

In addition, in the reaction to obtain the compound of formula (2) by reacting the compound of formula (3) with the compound of formula (4), the reaction conditions, such as the amount of base used, reaction temperature, reaction time, etc., may be selected as appropriate. can do. When the amount of base used is relatively small and relatively mild reaction conditions are selected, the following formula (3)-1 However, in the formula, R is the same or different and each represents a lower alkyl group, such as a methyl group or an ethyl group.
Alkyl 6oxo-2.9-decanedienoates can be formed and isolated. Then, by further acting on the chain ketotriesters to cause ring closure, 2-allyl-2,5-dialkoxycarbonyl-3-alkoxycarbonylmethyl-1-cyclo Can be derived from pentanones.

In the present invention, for example, the compound of formula (2) obtained as described above is an oily compound that has not been described in any literature. Specific examples of new compounds included in the compound of formula (2) include (a) 2-allyl-2,5-dimethoxycarbonyl-3-methoxycarbonylmethyl-1;
-Cyclopentanone (b) 2-allyl-2,5-dimethoxycarbonyl-3-ethoxycarbonylmethyl-1-cyclopentanone (c) 2-allyl-2,5
-diethoxycarbonyl-3-methoxycarbonylmethyl-1-cyclopentanone (d)2-allyl-
Preferable examples include 2,5-diethoxycarbonyl-3-ethoxycarbonylmethyl-1-cyclopentanone. The boiling points of these new compounds are listed below.

Compound boiling point (a) 142-145℃/2mmHg (b) 145-148℃/2mmHg (c) 150-155℃/2mmHg (d) 153-158℃/2mmHg 2-allyl-3 of formula (1) above -Alkoxycarbonylmethyl-1-cyclopentanone can be produced from the compound of formula (2) by decarboxylation (or decarboxylation) in the presence of an acid in a hydroalcoholic solvent such as aqueous methanol or aqueous ethanol. reaction), it can be easily produced with good yield and selectivity.

This decarboxylation reaction can be carried out at a temperature range of about 10 to about 100°C, for example, about 50° to about 90°C.
A more preferable example is a temperature range of about The reaction time can be changed as appropriate depending on the reaction temperature and the like, and for example, a reaction time of about 1 to about 50 hours can be exemplified.

Specific examples of acids used in the above decarboxylation reaction include inorganic and organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, perchloric acid, p-toluenesulfonic acid, and benzenesulfonic acid. Can be done. There is no particular restriction on the amount of these acids to be used, but examples include about 1 to about 50 times the weight of the compound of formula (2), more preferably about 5 to about 30 times the weight of the compound. can do. After the completion of the above decarboxylation reaction, for example, the reaction product is poured into water, neutralized, extracted with an appropriate solvent, and the solvent layer is washed with water, dried, and concentrated, so that the 2- Allyl-3-alkoxycarbonylmethyl-1-cyclopentanones can be obtained with high yield and high purity. If desired, further purification can be carried out, for example, by means such as vacuum distillation or column chromatography.

Hereinafter, several aspects of the present invention will be explained in more detail with reference to Examples.

Reference example 1 500 ml of dry ethanol and magnesium 18 in a container for synthesis of ethyl 2-allyl-3-oxoglutarate.
(0.75 mol) and 0.2 g of iodine for 48 hours.
Perform reflux to prepare magnesium ethoxide ethanol solution. After cooling to 50° C., 150 g (0.75 mol) of diethyl acetonedicarboxylate was then added dropwise. After dropping, the mixture was refluxed for an additional hour, cooled again (30°C), and 60 g (0.75 mol) of allyl bromide was injected dropwise. Warm and react under reflux for 5 hours. After completion of cooling, ethanol is distilled off. Add 1,000 ml of 5% hydrochloric acid water and 500 ml of ether to the residual solution to decompose. Then add 500ml of ether to the aqueous layer.
extract and combine the ether layers. After washing the ether layer with water, washing with heavy sodium chloride, and washing with water, dehydration treatment with anhydrous magnesium sulfate is performed to distill off the ether.
The residual liquid is distilled under reduced pressure to obtain 164 g (90% yield) of a fraction having a boiling point of 113° C./2 mmHg.

Example 1 2-allyl-2,5-diethoxycarbonyl-
Synthesis of 3-methoxycarbonylmethyl-1-cyclopentanone.

40 g (0.99 mol) of NaH is suspended in 500 ml of toluene, and 108 g (0.45 mol) of ethyl 2-allyl-3-oxoglutarate is added dropwise thereto. After the evolution of hydrogen has ceased, 89 g (0.49 mol) of methyl γ-bromocrotonate is again added dropwise at room temperature.
After continuing the reaction at the same temperature for 15 hours, heat to 80°~
The reaction is carried out for 8 hours at a temperature of 85°C. The reaction solution was poured into 500 ml of 5% hydrochloric acid water and decomposed. After washing the toluene layer with water, washing with baking soda, and washing with water, the toluene was distilled off and the resulting residual liquid was distilled under reduced pressure to determine the boiling point.
130g of fraction from 150° to 155°C/2mmHg (yield: 84
%). The structure was confirmed by IR, NMR, MS, and GLC.

Example 2 Adopting the same reaction conditions as Example 1, the above formula (2)
We synthesized various compounds corresponding to . The results are shown below.

No. (Product) (a) 2-allyl-2,5-dimethoxycarbonyl-3-methoxycarbonylmethyl-1-cyclopentanone (b) 2-allyl-2,5-dimethoxycarbonyl-3-ethoxycarbonylmethyl -1-Cyclopentanone, (c) 2-allyl-2,5-diethoxycarbonyl-3-ethoxycarbonylmethyl-1-cyclopentanone No. (Boiling point) (Yield) (a) 142-145℃ /2mmHg 75% (b) 145-148°C/2mmHg 81% (d) 153-158°C/2mmHg 87% The structure was confirmed by IR, NMR, MS, and GLC.

Reference example 2 2-allyl-3-methoxycarbonylmethyl-
Synthesis of 1-cyclopentanone 2-allyl-2,5-diethoxycarbonyl-
45 g (0.132 mol) of 3-methoxycarbonylmethyl-1-cyclopentanone was charged into a reaction flask along with 250 ml of 6N hydrochloric acid and 250 ml of methanol.
Heat and reflux for an hour. After completion of the extraction, ether extraction is performed, the ether layers are combined, washed with water, washed with sodium chloride water, washed with water, and subjected to anhydrous magnesium sulfate dehydration treatment. The ether was distilled off, and the residual liquid was distilled under reduced pressure to obtain a fraction with a boiling point of 110° to 115°C/3 mmHg.
Obtain 22.5 g (87% yield). The structure is IR, NMR,
Confirmed by MS and GLC.

Claims (1)

[Claims] 1. The following formula (2) However, in the formula, R may be the same or different,
Each represents a lower alkyl group, represented by 2-allyl-2,5-dialkoxycarbonyl-3-alkoxycarbonylmethyl-1
- Cyclopentanone.