JPH0517216B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula () (wherein R is an alkyl group, an alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group,
R' represents an aralkyl group, and R' represents a lower alkyl group. ) The present invention relates to a method for producing a cyclopentanone derivative shown in the following.

The cyclopentanone derivative represented by the above general formula () is a compound useful as an intermediate for a diasmonic acid derivative, which is a fragrance, or as a pharmaceutical or agricultural intermediate.

Conventionally, cyclopentanone derivatives represented by the general formula () have been converted into cyclopentanone derivatives represented by the general formula (). (In the formula, R has the same meaning as above.) 2-cyclopentenones represented by the general formula () CH ₂ (COOR') ₂ () (In the formula, R' has the same meaning as above) It is well known that it can be synthesized by reacting malonic acid ester shown in (.) in the presence of a basic catalyst.

By the way, 2-cyclopentenones, which are the raw materials, have conventionally been rearranged to 4-cyclopentenones using an alkali such as KOH or a Lewis acid such as _BF3 as a catalyst [Tetrahedron, 89-40]
(1979), Japanese Unexamined Patent Publication No. 51-56431] or by a method of rearrangement by heating at 250 to 800°C without a catalyst, but all of these methods have insufficient yields. Moreover, it not only has the disadvantage of producing many by-products, but also requires removing the catalyst from the reaction mixture obtained by the above reaction in order to react the produced 2-cyclopentenones with malonic acid ester. , 4- to obtain a cyclopentanone derivative represented by the general formula ()
As an integrated production method from cyclopentenones, it is extremely unsatisfactory.

By the way, the present inventors previously calculated the general formula () (wherein, R has the same meaning as above) is heated in the presence of 1,8-diazabicyclo(5,4,0)undecene or an organic acid salt thereof. By rearranging the 2-
It was discovered that cyclopentenones could be obtained (Japanese Patent Application No. 58-69566), but as a result of further investigation,
The reaction mixture obtained by the above reaction can be directly subjected to the reaction with malonic acid ester without removing the catalyst. It has been found that by combining these compounds, a cyclopentanone derivative represented by the general formula () can be produced extremely advantageously by an integrated production method from 4-cyclopentenones, leading to the present invention.

That is, the present invention provides 4-cyclopentenones represented by the general formula () in the presence of 1,8-diaza-bicyclo(5,4,0)undecene (hereinafter referred to as DBU) or an organic acid salt thereof. to obtain a reaction mixture containing 2-cyclopentenones represented by the general formula (), and then a malonic acid ester represented by the general formula () is treated with the reaction mixture in the presence of a basic catalyst. The present invention provides a method for producing a cyclopentanone derivative represented by the general formula ().

The 4-cyclopentenones used as raw materials in the present invention can be easily produced using, for example, furancarbinols as raw materials (Japanese Unexamined Patent Publication No. 57-118).
Publication No. 95935).

In addition, when using such a production method, 4-cyclopentenones may be obtained as a mixture with 2-cyclopentenones, but in the present invention, the raw material 4-cyclopentenones do not necessarily need to be used alone. Instead, it may be a mixture of cyclopentenones in which 2-cyclopentenones such as those mentioned above are mixed in at an arbitrary ratio.

Examples of such 4-cyclopentenones include the following compounds, in which the double bond is rearranged from the 4-position to the 2-position by the rearrangement reaction specified in the present invention, resulting in 2-cyclopentenones. 2-Methyl-4-cyclopentenone, 2-ethyl-4-cyclopentenone, 2-n-propyl-4-cyclopentenone, 2-isopropyl-4-cyclopentenone, 2-n-butyl-4- cyclopentenone,
2-isobutyl-4-cyclopentenone, 2-n
-Pentyl-4-cyclopentenone, 2-n-isopentyl-4-cyclopentenone, 2-n-hexyl-4-cyclopentenone, 2-n-heptyl-4-cyclopentenone, 2-allyl-4 -cyclopentenone, 2-(2-cis-butenyl)-4
-cyclopentenone, 2-(2-cis-pentenyl)-4-cyclopentenone, 2-(2-trans-pentenyl)-4-cyclopentenone, 2-(3
-cis-hexenyl)-4-cyclopentenone,
2-cyclopentyl-4-cyclopentenone, 2
-cyclohexyl-4-cyclopentenone, 2-
Cycloheptyl-4-cyclopentenone, 2-phenyl-4-cyclopentenone, 2-toluyl-
4-cyclopentenone, 2-benzyl-4-cyclopentenone.

The rearrangement reaction in the present invention uses DBU or a DBU organic acid salt as a catalyst, and the amount used is usually 0.0005 to 10 times the weight of the 4-cyclopentenone or cyclopentenone mixture, preferably 0.001. ~5 times the weight.

Here, when DBU is used as its organic acid salt, examples of the organic acid include aromatic compounds having an OH group such as phenol and cresol, or aliphatic acids such as oleic acid and octylic acid.

This reaction is carried out without solvent, but a solvent can also be used.

When using a solvent, it can be used without particular limitation as long as it does not interfere with the reaction, such as methanol, ethanol, isopropyl alcohol, tetrahydrofuran, dioxane, benzene, toluene, methyl isobutyl ketone, alcohol, ether, ketone, aliphatic or aromatic. Examples include group hydrocarbons alone or in mixtures.

When a solvent is used, the amount used is not particularly limited, but is generally 1 to 20 times the weight of the 4-cyclopentenone or cyclopentenone mixture.

The reaction temperature is 20-220℃, preferably 50℃
~200℃.

In this way, 2-cyclopentenones are produced in high yield, and a reaction mixture containing the compounds is easily obtained.

The reaction mixture obtained here is used as it is for reaction with malonic acid ester, and this reaction is carried out in the presence of a basic catalyst.

Examples of malonic acid esters used in this reaction include dimethyl malonate, diethyl malonate, di-n-propyl malonate, diisopropyl malonate, di-n-butyl malonate, and di-n-pentyl malonate. Examples include di-lower alkyl esters of acids, and the amount used is 1% to 2-cyclopentenones in the reaction mixture.
The amount is at least twice the molar amount, preferably 1.2 to 3 times the molar amount.

Examples of basic catalysts include metal alcoholates such as sodium methylate, sodium ethylate, and potassium t-butylate; metal hydrides such as sodium hydride, lithium hydride, and potassium hydride; metals such as sodium, potassium, and lithium; Examples include strong basic amines such as DBU, and metal alcoholates are particularly preferably used. Incidentally, when a metal is used as a catalyst, alcohols are used as a solvent.

Here, the fact that DBU can be used as a basic catalyst means that the reaction mixture containing DBU obtained in the previous reaction can be used as it is to react with malonic acid ester without using a new catalyst. This is a major feature of the present invention.

The amount of the catalyst used is usually 0.01 to 3 times the mole of the 2-cyclopentenone, preferably 0.03 to 3 times the mole.
The range is 1.5 times the mole.

Reaction temperature is -50~80℃, preferably -40~60℃
is within the range of

Reaction methods include, for example, adding a basic catalyst to the reaction mixture obtained in the previous step and then adding malonic acid ester, adding malonic acid ester to the reaction mixture and then adding a basic catalyst, or combining malonic acid ester and a base. It can be carried out by any method such as adding the reaction mixture to a mixture of reactive catalysts,
It is not particularly limited. In addition, in these methods, there are cases where it is not necessary to newly add a basic catalyst as described above.

A catalyst is not necessarily required for this reaction;
It can be carried out without a solvent.

When using a solvent, the solvent is not particularly limited as long as it is inert to the reaction, and the same solvents as above are exemplified, but when the solvent is used in the previous step and is also used in this step, In terms of solvent recovery, purification, etc., it is preferable to use the same type of solvent as used in the previous step.

There is no particular restriction on the reaction time.

Thus, according to the method of the present invention, the target cyclopentanone derivatives represented by the general formula () can be easily obtained in good yields by an integrated process from 4-cyclopentenones, and these It can be easily isolated from the reaction mixture by conventional separation means such as extraction, separation, concentration, distillation, etc.

The present invention will be explained below with reference to Examples.

Example 1 10 g of 2-n-pentyl-4-cyclopentenone, 2 g of toluene and 0.2 g of DBU were added to a 4-neck flask equipped with a stirrer, a thermometer, and a water condenser, and the mixture was heated under reflux in a N ₂ atmosphere. The mixture was stirred and kept warm for 3 hours.
Thereafter, it is cooled, 10.6 g of dimethyl malonate and 4 ml of methanol are added, and the mixture is cooled to -15 to -10°C.
2 g of a 28% methanol solution of sodium methylate is added dropwise to this mixture over a period of 2 hours. After maintaining the same temperature for 3 hours, 1 g of acetic acid was added. next,
Pour the reaction mixture into ice water and add 10 ml of toluene for extraction. After washing the toluene layer with water, toluene was distilled off under reduced pressure, and the concentrated residue was further distilled to obtain 17.66 g of dimethyl-2-n-pentyl-3-oxo-cyclopentylmalonate.

bp 88-91℃/0.01mmHg n ²⁰ _D 1.4588 Example 2 Into the same apparatus as used in Example 1 was added 10 g of 2-n-pentyl-4-cyclopentenone and 0.1 DBU.
g was added thereto, and the mixture was stirred at 120° C. for 7 hours in a N ₂ stream.
After cooling, 10.6 g of dimethyl malonate and 2 ml of methanol are added, and the mixture is cooled to -15 to -10°C. 2 g of a 28% methanol solution of sodium methylate is added dropwise to this mixture over a period of 2 hours. At the same temperature 3
After incubating for an hour, add 1 g of acetic acid. Below, Example 1
Dimethyl-2-n-pentyl-3-oxocyclopentylmalonate was processed and purified according to
18.03g was obtained.

bp 87-90℃/0.01mmHg n ²⁰ _D 1.4596 Example 3 2-n-pentyl-4-cyclopentenone (A) and 2-n-pentyl-2-cyclopene were placed in the same apparatus as used in Example 1. Tenon (B) mixture ((A)/(B)=
Add 4g (weight ratio 20/80) and 0.08g DBU,
Stirred at 120° C. for 4 hours in a N ₂ stream. After the reaction is complete, the reaction mixture is cooled and dimethyl malonate 6.8
g and cooled to -15 to -10°C. To this mixture, 1 g of a 28% methanol solution of sodium methylate is added dropwise over a period of 1 hour at -15 to -10°C. After incubating at the same temperature for 4 hours, add 0.4 g of acetic acid. Thereafter, the product was post-treated and purified according to Example 1 to obtain 7.08 g of dimethyl-2-n-pentyl-3-oxo-cyclopentylmalonate.

Example 4 Into the same apparatus as used in Example 1, 10 g of 2-n-pentyl-4-cyclopentenone and
0.1 g of DBU was added, and the mixture was stirred at 150° C. for 2 hours in a N ₂ stream. After the reaction is complete, the reaction mixture is cooled.

In another 4-necked flask, 10.4 g of dimethyl malonate.
and 4 ml of methanol were added to this mixture to give a 28%
Add 1.5 g of a methanol solution of sodium methylate.

The reaction mixture obtained above is then added for 2 hours at -5 to 5°C. Insulate at -10 to 0°C for 3 hours. After the reaction is complete, 1 g of acetic acid is added. After, Example 1
Dimethyl-2-n-pentyl-3-oxo-cyclopentylmalonate was processed and purified according to
17.96g was obtained.

Example 5 In Example 2, 2-n-pentyl-4-cyclopentenone was replaced with a mixture of 2-allyl-4-cyclopentenone (A) and 2-allyl-2-cyclopentenone (B) [ (A)/(B)=20/80 (weight ratio)] The reaction was carried out in the same manner as in Example 2 except that 10 g was used, and the dimethyl-2-allyl-3-
18.01 g of oxo-cyclopentyl malonate was obtained.

bp 90-94℃/0.03-0.05mmHg Example 6 In the same apparatus as used in Example 1, 2-n-pentyl-4-cyclopentenone (A) and 2-n-pentyl-2-cyclopentenone ( B) mixture [(A)/(B)=
10/90 (weight ratio)] Add 10g and DBU2g,
The mixture was stirred at 110° C. for 2 hours in a nitrogen stream.

After the reaction is completed, the reaction mixture is cooled, 11.2 g of dimethyl malonate is added, and the mixture is cooled to -10 to -20°C.
Next, 2 g of a 28% methanol solution of sodium methylate was added over 2 hours, and after stirring at the same temperature for 3 hours, 2 g of acetic acid was added.

Thereafter, the product was post-treated and purified according to Example 1 to obtain 17.54 g of dimethyl-2-n-pentyl-3-oxo-cyclopentyl malonate.

Example 7 In Example 2, 2-cyclohexyl- was used instead of 2-n-pentyl-4-cyclopentenone.
4-cyclopentenone (A) and 2-cyclohexyl-
Mixture of 2-cyclopentenone (B) [(A)/(B)=10/
90 (weight ratio)] Use 10g, DBU instead of DBU
- Example 2 except that 0.1 g of phenol salt was used.
The reaction was carried out in the same manner as above, and 17.42 g of dimethyl-2-cyclohexyl-3-oxo-cyclopentyl malonate was obtained by post-treatment and purification in the same manner.

bp 94-98℃/0.01mmHg Example 8 10g of 2-n-pentyl-4-cyclopentenone and 3g of DBU were charged into a 4-necked flask equipped with a stirrer, a thermometer, and a cooling tube, and the mixture was heated to 100% in a N ₂ stream.
Stir at ~110°C for 2 hours. After the reaction is completed, cool
A solution of 12.58 g of dimethyl malonate in 5 ml of methanol is added over a period of 2 hours at -15 to -5°C. After keeping it warm for 3 hours at the same temperature, pour it into 40g of 2% hydrochloric acid ice water.
Extract twice with 50 ml of toluene. The organic layer is washed with water and then dried. The mixture was concentrated under reduced pressure and further distilled to obtain 16.61 g of dimethyl-2-n-pentyl-3-oxo-cyclopentylmalonate.

b.p. 124-127℃/0.1mmHg

Claims (1)

[Claims] 1. General formula (wherein R is an alkyl group, an alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group,
Indicates an aralkyl group. ) 4-cyclopentenones represented by 1,8-
By heating in the presence of diaza-bicyclo(5,4,0)undecene or its organic acid salt, the general formula A reaction mixture containing 2-cyclopentenones represented by (wherein R has the same meaning as above) was obtained, and then a reaction mixture containing the general formula CH ₂ (COOR') ₂ (wherein R' is A general formula characterized by reacting a malonic acid ester represented by (representing a lower alkyl group) in the presence of a basic catalyst. (In the formula, R and R' have the same meanings as above.) A method for producing a cyclopentanone derivative represented by the following.