JPS60224656A - Production of cyclopentanone derivative - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as an intermediate of perfumery and pharmaceuticals, economically, by carrying out the rearrangement of a 4- cyclopentenone compound, and reacting the resultant reaction mixture containing 2-cyclopentenone with a malonic acid ester without removing the catalyst from the system. CONSTITUTION:The 4-cyclopentenone compound of formula I (R is alkyl, alkenyl, cycloalkyl, substituted or unsubstituted aryl or aralkyl) is heated in the presence of 1,8-diaza-bicyclo(5,4.0)-undecene or its organic acid salt to effect the rearrangement to the 2-cyclopentenone compound of formula II. The obtained reaction mixture containing the 2-cyclopentenone compound is made to react with the malonic acid ester of formula III (R' is lower alkyl) in the presence of a basic catalyst such as sodium methylate, etc. to obtain the objective cyclopentanone derivative of formula IV (e.g. dimethyl-2-n-pentyl-3-oxo-cyclopentyl malonate).

Description

Detailed Description of the Invention The present invention is based on the general formula (I) (wherein R is an alkyl group, an alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, an aralkyl group, and generally a lower alkyl group). The present invention relates to a method for producing a cyclopentanone derivative.

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

Conventionally, the cyclopentanone derivative represented by the general formula (I) has been converted into a cyclopentanone derivative represented by the general formula (1) (wherein has the same meaning as above).
- Cyclobentenones and general formula (5) % formula % () 1 In the formula, "b" has the same meaning as above. ) is well known to be synthesized by reacting with malonic acid ester shown in the following in the presence of a basic catalyst.

By the way, conventionally, 2-cyclobentenones, which are the raw materials, have been rearranged to 4-cyclobentenones using an alkali such as NOH or a Lewis acid such as BFa as a catalyst (
Tetrahedron, 99-4 Q (1979)
, Japanese Unexamined Patent Publication No. 51-56481] or 2 without a catalyst.
It is produced by methods such as heating to 50 to 800°C and rearrangement, but all of these methods have the drawbacks of insufficient yields and a large number of by-products. In order to react these 2-cyclobentenones with malonic acid ester, the catalyst must be removed from the reaction mixture obtained by the above reaction, and the cyclopentanone derivative represented by general formula (I) must be removed. The method for producing -N from 4-cyclobentenones is very unsatisfactory.

By the way, the present inventors have previously calculated the following general formula (to) (in which R
has the same meaning as above. ) 4-cyclobentenones represented by 1,8-diaza-bicyclo(5,4,0)
It was discovered that 2-cyclobentenones represented by the general formula (10) can be obtained in high yield by heating and rearrangement in the presence of undecene or its organic acid salt (Patent Application No. 1983). 69566), and as a result of further investigation, it was found that the reaction mixture obtained from the above reaction 1ζ could be directly subjected to the reaction with the malonic ester without removing the catalyst, and therefore, 2- By combining the reaction of cyclobentenones and malonic acid ester with the above method, the cyclopentanone derivatives represented by the general formula (I) can be produced extremely advantageously, in contrast to the integrated production method from 4-cyclobentenones. This discovery led to the present invention.

That is, the present invention converts 4-cyclobentenones represented by the general formula (n) into 1,8-diaza-bicyclo(5,4
, 0) by heating in the presence of undescens (hereinafter referred to as DBU) or its organic acid salt, to form the compound of the general formula (Ill).
A reaction mixture containing 2-cyclobentenones represented by is obtained, and then a malonic acid ester represented by the general formula (■) is applied to the reaction mixture in the presence of a basic catalyst to form a reaction mixture of the general formula ( The present invention provides a method for producing a cyclopentanone derivative represented by I).

The 4-cyclobentenones used as raw materials in the present invention are easily produced from, for example, furancarbinols (Patent Publication No. 57-95985).

In the case of such a manufacturing method, 4-cyclobentenones may be obtained as a mixture with 2-cyclobentenones, but in the present invention, the raw material 4-cyclobentenones do not necessarily need to be used alone. Instead, it may be a mixture of cyclobentenones mixed with 2-cyclobentenones as described above in any proportion.

Examples of such 4-cyclobentenones include the following compounds, in which the double bond is rearranged from the 4-position to the 2-position to form 2-cyclobentenones due to the rearrangement reaction specified in the present invention. Become.

2-methyl-4-cyclobentenone, 2-ethyl-4-
Cyclobentenone, 2-n-propyl-4-cyclobentenone, 2-isopropyl-4-cyclobentenone, 2
-n-butyl-4-cyclobentenone, 2-isobutyl-4-cyclobentenone, 2-n-pentyl-4-cyclobentenone, 2-n-isopentyl-4-cyclobentenone, 2-n- xyl-4-cyclobentenone, 2
-n-hebutyl-4-cyclobentenone, 2-allyl-
4-cyclobentenone, 2-(2-cis-butenyl)-
4-cyclobentenone, 2-(2-cis-pentenyl)
-4-cyclobentenone, 2-(2-trans-pentenyl)-4-cyclobentenone, 2-(8-cis-hexenyl)-4-cyclobentenone, 2-cyclopentyl-4-cyclobentenone, 2 -Cyclohexyl-4-cyclobentenone, 2-cyclo18butyl-4-cyclobentenone, 2-phenyl-4-cyclobentenone, 2-
Toluyl-4-cyclobentenone, 2-benzyl-4-
Cyclobentenone.

The rearrangement reaction in the present invention uses DBU or D as a catalyst.
BU organic acid salt is used, but the amount used is 4-
Usually 0.0005 to 10 times the weight of cyclobentenones or cyclobentenone mixture, preferably o,
oot~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-cyclobentenones or cyclobentenone mixture.

The reaction temperature is 20-220°C, preferably 50-220°C.
The temperature is 200°C.

In this way, 2-cyclobentenones are produced in high yield,
A reaction mixture containing the compound 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, p-pyl malonate, di-n-butyl malonate, di-n-pentyl malonate, etc. The di-lower alkyl ester of malonic acid is mentioned, and the amount used is at least 1 mole, preferably 1.2 to 8 moles, relative to the 2-cyclobentenone in the reaction mixture.

Examples of basic catalysts include metal alcoholades such as sodium methylate, sodium ethylate, and potassium t-butylate; metal hydrides such as sodium hydride, lithium hydride, and potassium hydride;
Examples include metals such as potassium and lithium, and strong basic amines such as DBU, and metal alcoholades are particularly preferably used. However, when metals are used as catalysts, alcohols are used as solvents.

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

The amount of the catalyst used is usually 0.01 to 8 times the mole of the 2-cyclobentenone, preferably 0.08 to 1.5 times.
It is in the double molar range.

The reaction temperature is -50 to 80°C, preferably -40 to 60°C.
is within the range of

The reaction method is, for example, adding a basic catalyst to the reaction mixture obtained in the previous step and then adding malonic ester, adding malonic ester to the reaction mixture and then adding a basic catalyst, or adding malonic acid ester to the reaction mixture. This can be carried out by any method, such as adding a reaction mixture to a mixture of an acid ester and a basic catalyst, and is not particularly limited. Oka: In these methods, there are cases where it is not necessary to newly add a basic catalyst as described above.

This reaction does not necessarily require a solvent and 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 mentioned above are exemplified, but when the solvent is used in the previous step and is also used in this step, It is preferable to use the same type of solvent as used in the previous step in terms of recovery, purification, etc. of the solvent.

There is no particular restriction on the reaction time.

Thus, according to the method of the present invention, the desired general formula (
The cyclopentanone derivatives represented by D or 4-cyclobentenones can be easily obtained in good yields by an integrated process, and these can be obtained by conventional separation methods such as extraction, separation, concentration, vaporization angle, etc. It can be easily isolated from the reaction mixture by

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

Example 1 2-n-pentyl-4-cyclobentenone 10y-
, toluene 2f! Oyohi DB U O, add 2P, N
The mixture was stirred for 8 hours under reflux in a stream of air. Then cool, add 10.6 P of dimethyl malonate and 4 P of methanol.
- is added, t, and cooled to -15 to -1O<0>C. Add 28% of sodium methylate to this mixture in methanol. is added dropwise over a period of 2 hours. After keeping at the same temperature for 8 hours, acetic acid IP was added.

Next, the reaction mixture was poured into ice water and extracted with 10 ml of toluene. After washing the toluene layer with water, toluene was distilled off under reduced pressure, and the concentrated residue was further filtered to give dimethyl-2-n-
Pentyl-8-oxo-cyclopentylmalonate 17
．． I got 66i8.

b-988~91℃/o,o 1s+sHy"X0
1-4588 Actual Example 2 2-n-pentyl-4-cyclobentenone 10F and DBUO, 1y were added to the same apparatus as used in Example 1, and the mixture was stirred at 120°C for 7 hours in a N2 stream. After cooling, dimethyl malonate 10.6? and methanol are added, and the mixture is cooled to -15 to -10°C. A 28% methanol solution of sodium methylate 2F is added dropwise to this mixture over a period of 2 hours. After keeping it at the same temperature for 8 hours, acetic acid 1
Add 2. Thereafter, the product was post-treated and purified according to Example 1 to obtain dimethyl-2-,1-hentyl-8-oxo-cyclopentyl malonate is, oap.

b, p, 87-90℃/Q, QlsHynBot,
4596 Example 8 In an apparatus similar to that used in Example 1, 2-n-pentyl-
4-cyclobentenone (8-2-n-pentyl-2-
A mixture of cyclobentenone (B) ((A)/(B3=weight ratio 20/80) 4P Oyohi DBU0.08P was added, and the mixture was stirred at 120° C. for 4 hours in a N2 stream.

After the reaction is complete, the reaction mixture is cooled and dimethyl malonate 6
．． Add 854e and cool to -15 to -10°C 3. To this mixture, add 28 timethanol solution of sodium methylate 1? was added dropwise over a period of 1 hour at -15 to -10°C. After incubating at the same temperature for 4 hours, 0.4P of acetic acid was added. ,
After that, post-treatment was carried out according to Example 1, and dimethyl-2-
7.081 of n-pentyl-3-xocyclopentylmalonate was obtained.

Example 4 2-〇-pentyl-4 was added to the same apparatus as used in Example 1.
-Cyclobentenone 101 and DBU□, Iy were added, and the mixture was stirred at 150°C for 2 hours in a N2 stream. After the reaction is complete, the reaction mixture is cooled.

To another 4 flask add 10.1' of dimethyl malonate and 4 #I/methanol and to this mixture 1.5 % of the methanol solution of 28-sodium methylate. Add.

The reaction mixture obtained above was then added for 2 hours at -5-5°C. Insulate at -10 to 0°C for 8 hours. After the reaction is completed, 1y-acetic acid is added.

Then, according to Example 1, it was post-treated and purified to give dimethyl-2-
n-pentyl-8-oxo-cyclopentylmalonate 17.96F was obtained.

Example 5 In Example 2, 2-n-pentyl-4-cyclobentenone was replaced with a mixture of 2-allyl-4-cyclobentenone and 2-allyl-2-cyclobentenone ((
A)/(Bl = 20/80 (weight ratio)) 105' was reacted in the same manner as in Example 2, and post-treated and purified in the same manner to obtain dimethyl-2-allyl-8-oxo-cyclopentyl malo. nate 18.01y- was obtained.

b, p 90-94°C 10.08-0.051B Immediate Example 6 In a device similar to 1 used in Example 1, 2-n-pentyl-4-cyclobentenone ■ and 2-n-pentyl-2 were added.
- mixture of cyclobentenone [(^/(average = 107
90 (weight ratio)] Add LOP and DBU 2P, 1
The mixture was stirred at 10° C. for 2 hours in a nitrogen stream.

After the reaction is completed, the reaction mixture is cooled, 11.2 F+ of malonic acid is added, and the mixture is cooled to -10 to -20°C.

Then 28-methanol solution of sodium methylate 2
1 was added over 2 hours, stirred at the same temperature for 8 hours, and then acetic acid 21 was added.

Hereinafter, dimethyl-2 was post-treated and purified according to Example 1.
-n-pentyl-8-oxo-cyclopentyl malonate 17.545' was obtained Example 7 In Example 2, 2-cyclohexyl-4- Mixture of cyclobentenone tetra and 2-cyclohexyl-2-cyclobentenone [(A)/(equal=10/90 (weight ratio)
) The reaction was carried out in the same manner as in Example 2 except that IOP was used and DBU-phenol salt 0.11 was used in place of DBU, and dimethyl-2-cyclohexyl-8-oxo -Cyclopentylmalonate 17.42
I got y-.

b, p 94-98°C 10.0111IIli5' Example 8 2-n-pentyl-4-cyclopentyone IOP and DBU3Plt were charged in a 4-tubular flask equipped with a stirrer, a thermometer, and a cooling tube, in a N2 stream, at 100~ 110℃
Stir for 2 hours. After the reaction is complete, cool and dinotilma [
Conate 12.51 in methanol 5-solution from -15 to -
Add in 2 hours at 5°C. After keeping warm for 8 hours at the same humidity, pour into 2-hydrochloric acid ice water 4054, and add 2-hydrochloric acid to 50-50% of toluene.
Extract times. The organic layer is washed with water and then dried. Concentrate under reduced pressure and further distill to obtain dimethyl-2-n-pentyl-8
-Oxo-cyclopentylmalonate 16.61y- was obtained.

Claims (1)

[Claims] 4-cyclobentenones represented by the general formula (wherein R represents an alkyl group, an alkenyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or an aralkyl group), 1.8-diazahicyclo(5,4,0)undecene or an organic acid salt thereof is heated in the presence of 2-
A reaction mixture containing cyclobentenones was obtained, and then a malonic acid ester represented by the general formula % (% formula %) (wherein R represents a lower furkyl group) was added to the reaction mixture in the presence of a basic catalyst. A method for producing a cyclopentanone derivative represented by the general formula (wherein R and R have the same meanings as above) where 99 is