JPS61106537A - Production of cyclopentylacetic acid ester - Google Patents

Abstract

PURPOSE:The reaction between a 2-substituted-4-cyclopentenone and a malonic ester is followed by the reaction of the product with water under heating to enable industrially inexpensive and high-yield production of the titled compound of high purity which is used as a perfume. CONSTITUTION:2-Substituted-4-cyclopentenone of formula I (R is alkyl, alkenyl, alkinyl) is allowed to react with a malonic acid ester of formula II (R' is alkyl) in the presence of a basic catalyst such as sodium methylate in the absence or presence of a solvent such as methanol at -50-80 deg.C. Then, the resultant cyclopentanone derivative of formula III is heated together with water, prefer ably in the presence of a solvent at 90-300 deg.C under normal pressure to give the objective compound of formula IV which acts as an inhibitor of plant growth. The compound of formula I is obtained by rearrangement of a com pound of formula V, reduction of the product of formula VI and dehydration of the product of formula VII.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing cyclopentyl acetates represented by the general formula (1) (wherein R is an alkyl group, alkenyl is an alkynyl group, and B' is an alkyl group).

Among the compounds of the general formula [I], for example, compounds in which R is an n-pentyl group and R is a methyl group are well known to have effects such as fragrance or growth inhibition on plants.

Conventionally, as a method for producing cyclopentyl acetate represented by the general formula (1), the following method is known for, for example, a compound in which R is a low pentyl group and R' is a methyl group.

a) Agric, Biol, Chem, 44
(12)+2857~b) 5ynthetic
Communications, 4(6), 835-8.
89 (1974) However, this method requires different starting materials, reagents, reaction means, etc., making the production method extremely complicated, and it is by no means satisfactory for industrial production. For these reasons, the present inventors have investigated an industrially inexpensive method for producing such cyclopentyl acetates, and have discovered an industrially advantageous method for obtaining the desired product with high purity and high yield, leading to the present invention. Ta.

That is, the present invention provides a method for converting a substituted 4-cyclobentenone represented by the general formula (II) (wherein R represents an alkyl group, an alkenyl group, or an alkynyl group) into a compound of the general formula [ 11r] (% formula %) (in the formula, R' represents an alkyl group) by adding a malonic acid ester represented by the general formula (IV
Cyclopentyl represented by the above general formula [I], which is obtained by obtaining a cyclopentanone derivative represented by I (wherein and R' have the same meanings as above) and then heat-treating with water. The present invention provides a method for producing acetic acid esters.

The cyclobentenone compound represented by the general formula (ff) used as a raw material in the present invention can be produced, for example, by the method shown below.

011 O [[] Such 2-substituted-4-cyclobentenone is
For example, the following compounds are exemplified.

2-ethyl-4-cyclobentenone, 2-n-propyl-4-cyclobentenone, 2-isopropyl-4
-cyclobentenone, 2-lobentenone, 2-isobutyl-4-cyclobentenone, 2-
n-pentyl-4-cyclobentenone, 2-isopentyl-4-cyclobentenone, 2-n-hexyl-4-cyclobentenone, 2-n-hebutyl-4-cyclobentenone, 2-allyl- 4-cyclobentenone, 2-(ω-
butenyl)-4-cyclobentenone, 2 (2-butynyl)-4-cyclobentenone, 2-(2-cis-pentenyl)-4-cyclobentenone, 2-(2-trans-pentenyl)-4- Cyclobentenone, 2-(2-cis-hexenyl)-4-cyclopentynone EL I
2 (8-'i Z-”% Yaya= /L/ ) −
4-,'7゜bentenone, 2-(a-methylallyl)-
4-cyclobentenone, 2-propargyl-4-cyclobentenone, 2-(2-pentynyl)-4-cyclopentenone.

Such 2-substituted-4 cyclobentenone and the general formula [1+1
The addition reaction of malonic acid ester shown in 3 is carried out in the presence of a basic catalyst.

Malon esters used in this reaction include, for example, dimethyl malonate, diethyl malonate, di-n-propyl malonate, diisopropyl malonate, di-n-butyl malonate, di-n-pentyl malonate, etc. Di-lower alkyl esters of acids are mentioned, and the amount used is 1 mole or more, preferably 1 mole or more, based on the mixture.
．． It is 2 to 3 times the mole.

Examples of basic catalysts include sodium methylate,
Metal alcoholades such as sodium ethylate and potassium-1-butylade; metal hydrides such as sodium hydride, lithium hydride, and potassium hydride; sodium;
Examples include metals such as potassium and lithium, and strong basic amines such as DBU, and metal alcoholades are particularly preferably used. Incidentally, when a metal is used as a catalyst, alcohols are used as a solvent.

The amount of the catalyst used is usually 0.01 to 3 times the mole, preferably 0.03 to 1.5 times the mole of 2-f#-converted-4-cyclobentenone as a raw material.

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

Examples of reaction methods include adding a basic catalyst to 2-substituted-4-cyclobentenone and then adding malonic acid ester, or adding a basic catalyst to a mixture of 2-substituted-4-cyclobentenone and malonic acid ester. It can be carried out by any method such as a method of adding 2-substituted 4-cyclobentenone to a mixture of a malonic acid ester and a basic catalyst, and is not particularly limited.

However, in order to obtain the compound of the general formula [IV] in a good yield without using a solvent or minimizing the amount of the solvent used, and furthermore to suppress the amount of a basic catalyst used, it is necessary to obtain a compound of the general formula [IV] with a good yield.
A method in which a basic catalyst is added to a mixture of 4-cyclobentenone and malonic acid ester is preferred. When this method is used, there is no precipitation of crystals during cooling, and handling is extremely easy.

This reaction does not necessarily require a solvent, and can be carried out even with the addition of a solvent.

When using a solvent, it can be used without any particular restriction as long as it is insoluble in the reaction, such as alcohols such as methanol, ethanol, isopropyl alcohol, tetrahydrofuran, dioxane, and toluene, ether molecules, aromatic hydrocarbons, etc. They may be used alone or in mixtures.

When a solvent is used, the amount used is not particularly limited, but is generally 0.00% relative to 2-substituted-4 cyclobentenone.
It is 2 to 20 times the weight.

There is no particular restriction on the reaction time.

In this way, the cyclopentanone derivatives represented by the general formula (IV) can be obtained easily and in good yields, and these can be separated by conventional separation means such as extraction and separation.

Although it can be easily separated from the reaction solution by concentration, distillation, etc., the reaction mixture can be used as it is without any particular separation for the next process.

In order to obtain the desired cyclopentyl acetate represented by the general formula (1) from the cyclopentanone derivative thus obtained, the cyclopentanone derivative is heated together with water.

The amount of water used in this reaction is required to be at least equimolar to the cyclopentanone derivative, preferably 1 to 1.
The range is 20 moles.

There is no need to use a solvent in this reaction, but
Preferably, a solvent is used, such solvent being:
For example, methanol, ethanol, isopropyl alcohol, butanol, etc.
Ethers such as tetra8do°7u'/'oxane, dimethyl sulfoxide.

Sulfoxides such as sulfolane, sulfonic acids, dimethylformamide, dimethylacetamide.

Examples include amides such as N-methylpyrrolidone, N,N'-dimethylimidazolitone, and hexamethyltriamide phosphate, and generally water-soluble solvents are preferred.

In addition, when alcohol is used as a solvent in this reaction, the type of alcohol is based on the general formula (f
It is preferable to use an alcohol having the same alkyl group as that forming the ester of the cyclopentanone derivative shown in f), and if an alcohol having a different alkyl group is used, a transesterification reaction will not occur. , an ester different from the cyclopentanone derivative used as the raw material may be produced.

The amount of such a solvent used is usually 1 to 50 times the weight of the cyclopentanone derivative.

The reaction temperature is 90-300°C, preferably 100-24°C.
It is 0°C.

There is no particular restriction on the reaction time.

In this reaction, a catalyst can be used to improve the reaction rate and yield. Examples of such a gauze medium include sodium chloride, sodium bromide, potassium chloride, potassium bromide, lithium chloride, lithium iodide, Sodium iodide.

Examples include metal halides such as potassium iodide, and metal cyanides such as sodium cyanide and potassium cyanide.

When a catalyst is used, the amount used is usually 0.1 to 3 times the mole of the cyclopentanone derivative.

This reaction is usually carried out at normal pressure, but it can also be carried out under increased pressure.

Examples of the reaction method include heating a mixture of a cyclopentanone derivative, water and a solvent mixed in advance, or heating water or a mixture of water and a solvent in a mixed solution of a cyclopentanone derivative or a solvent. Any method may be employed, such as a method of supplying a mixture of a cyclopentanone derivative, water, and a solvent, and a method of heating a mixture of a cyclopentanone derivative, water, and a solvent for a short period of time through a pipe reactor or the like.

Through such a reaction, the desired cyclopentyl acetate represented by the general formula m can be easily obtained in a good yield, and these can be separated by conventional separation means such as extraction 1 separation, #
It can be easily removed from the reaction mixture by condensation, distillation, etc.

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

Example 1 2-n-
Pentyl-4-cyclobentenone (n-1) 15.2F
, malonic acid dimethyl ester (18.5F) and methanol (2-) were charged, and while cooling to -10 to -20°C, 2.69% of a 14% methanol solution of sodium methylate was added dropwise over 1 hour. After finishing dropping, keep warm at the same temperature for 8 hours.

After the reaction is complete, add 0.455' of acetic acid, then add 55' of hexane.
Add 0- and 20- of water.

After separation, the organic layer was washed with 20 m/ml of water, and hexane and dimethyl malonate were distilled off under reduced pressure.
n-pentyl-4-oxocyclopentylmalo*-) (
Concentrated residue containing If-1327, 84 y 29.20
I got P.

The entire amount of this residue was charged into a reaction device equipped with a distillation device, and 200~
While heating and stirring at 210° C., 15 m/m of a water-methanol mixture (water/methanol = 1/2 volume ratio) was supplied under the surface of the reaction liquid over a period of 3 hours. Unreacted water and by-product methanol are continuously distilled off.

After the reaction was completed, the reaction solution was distilled under reduced pressure to obtain 3-n-hentyl-4-oxo-cyclopentyl acetic acid methyl ester (1
-1121,275' was obtained.

b, p, 117-119℃/0.1 trrmH
9 Example 2 In a flask similar to that used in Example 1, 2-allyl-4-
Cyclobentenone (n-2) 12.229. Malonic acid dimethyl ester 19.1 brass '5', tp'-ib
1.87% of a 28% methanol solution of sodium methylate is added dropwise over a period of 1 hour while cooling to 0 to -15°C. After completion of the dropwise addition, the mixture is kept at the same temperature for 8 hours.

After the reaction is complete, add 90.45 y of vinegar, then add 40 y of hexane.
- and 20 g of water.

Hereinafter, dimethyl-3-allyl-4-oxo-cyclopentyl malonate (rv-2) was prepared in the same manner as in Example 1.
A concentrated residue of 25.987 containing 24.889 was obtained.

The entire amount of this concentrated residue was charged into a reaction device equipped with a distillation device, and
A water-methanol mixture (water/methanol = 1/2 volume ratio) 12- is heated and stirred at 0 to 215°C and is supplied under the surface of the reaction liquid over a period of 4 hours. Unreacted water and by-product methanol are continuously distilled off.

After completion of the reaction, the reaction solution was distilled under reduced pressure to obtain 3-allyl-4-oxo-cyclopentyl acetic acid methyl ester (1-2) 1
Obtained 8.22y.

b, p, ioo ~102°C/0.8~0.5
1ranH5' Example 8 In a flask similar to that used in Example 1, 2-2-cis-pentenyl-4-cyclobentenone [11-a) aop,
Charge malonic acid dimethyl ester 87.2 F and methanol 4-, and while cooling to -10 to -20°C, add 14% methanol solution of sodium methylate 5.22 to 1
It takes time to drip. After finishing dropping, keep warm at the same temperature for 4 hours.

After the reaction is complete, add 0.97 acetic acid, then add 60i of hexadiene.
and add 80 d of water.

Thereafter, the same treatment as in Example 1 was carried out to obtain an oily product 56.042 containing dimethyl-3-2-cis-pentenyl-4-oxo-cyclopentylmalonate [rv-3] 53.68F. Ta.

This oily substance (51.465') was charged into a reaction apparatus equipped with a distillation apparatus, and heated to 205 to 215°C while stirring, a water-methanol, -ol mixed solution (water/methanol = 173 volume ratio) 15
m4 was fed below the surface of the reaction liquid over a period of 3 hours. Unreacted water and methanol are continuously distilled off.

After the reaction was completed, the reaction solution was distilled under reduced pressure to obtain 2'-cis-pentenyl-4-oxo-cyclopentyl acetic acid methyl ester Cl-3) 85.66P.

b, p, 119~b Example 4 2-〇-pentyl-4-cyclobentenone [n-1) 30.4F and malonic acid dimethyl ester 87y were charged into a flask similar to that used in Example 1, and -5~ -10
While cooling to 0.degree. C., 5.2 y of a 14% solution of Natri"ram methylate in methanol is added dropwise over a period of 1 hour.

After completing the dropwise addition, keep it at the same temperature for 4 hours.After the reaction is complete,
Add 0.97 g of acetic acid, then add 60 g of hexane and 30 g of water.

Thereafter, the same treatment as in Example 1 was carried out, and dimethyl 3 n-hentyl-4-oxocyclopentylmalonete (I
V-1) A concentrated residue 58.065' containing 55.127 was obtained.

Dimethylformamide 15 was added to this concentrated residue 5a and aty.
09 and water 7.59 were added and stirred at 180-140°C for 15 hours. After the reaction is complete, cool the reaction solution and add 3 liters of water.
After adding 0rnl, extract with hexane. The extracted organic layer was washed with water, dried over magnesium sulfate, concentrated, and further distilled under reduced pressure to obtain 3-n-pentyl-4-oxo-cyclopentyl acetic acid methyl ester [T-1) 35.
I got 267.

Example 5 In a flask similar to that used in Example 1, 2-necked pentyl-4-cyclobentenone [11-1]80.4S'malonic acid dimethyl ester 36.87 and methanol 8 r
nl of sodium methylate was added over 1 hour while cooling to -10°C.

After finishing, keep warm at the same temperature for 3 hours.

After the reaction was completed, 0.97 ml of acetic acid was added, followed by 4.1 ml of hex.
Add Sun 80-/and Water 40-1.

After separating the organic layers, the organic layer was washed with 40% of water, and the hexane and dimethyl malonate were distilled off under reduced pressure.
Pentyl-4-oxocyclopentylmalo* -) (
A residue 57.92 F containing ff -1155,562 was obtained. This residue was mixed with 25 m of methanol and 8 rnl of water.
The solution was passed through a stainless steel tube with a diameter of 1 mm.
Leads into an oil bath at 210°C.

The residence time of the reaction solution in the oil bath is 10 minutes. The distilled reaction mixture is collected and distilled under reduced pressure. 41.6y of 3-n-pentyl-4-okylcyclopentyl acetic acid methyl ester (T-1) was obtained.

Claims (1)

[Claims] 2-substituted-4-cyclopentenone represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents an alkyl group, an alkenyl group, or an alkynyl group.) In the presence of a basic catalyst, a malonic acid ester represented by the general formula CH_2(COOR')_2 (in the formula, R' represents an alkyl group) is added to form the general formula ▲Mathematical formula, chemical formula, table, etc.▼ (1) (In the formula, R and R' have the same meanings as above) General formula ▲ Numerical formula, chemical formula, table etc. ▼ (In the formula, R and R' have the same meanings as above.) A method for producing cyclopentyl acetate esters represented by