JPH1121283A - Production of 2-(omega-alkoxycarbonylalkanoyl)-4-butanolide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound in high selectivity and yield in an industrially advantageous way using readily available and inexpensive raw materials by condensation reaction of a specific compound with γ-butyrolactone and an alkali metal alcoholate. SOLUTION: (A) A dicarboxylic ester of the formula ROOC(CH2 )n COOR ((n) is 7-13; R is an alkyl) (e.g. 1,12-dodecanediacid dimethyl ester) is agitated under heating followed by adding (B) γ-butyrolactone and (B) an alkali metal alcoholate (e.g. sodium methylate) to the component A to carry out a condensation reaction to obtain the objective compound. The reaction is pref. carried out under reduced pressures (pref. at 50-760 mmHg) while distilling the alcohol formed off the system; alternatively, for example, it is also preferable that, in the 1st step, a pressure is reduced under conditions enough to evaporate the alcohol formed, and in the 2nd step, the pressure is further reduced; namely, the pressure reduction is conducted in two or more steps.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide useful as various synthetic raw materials or intermediates.

[0002]

2. Description of the Related Art 2- (ω-alkoxycarbonylalkanoyl) -4-butanolides are useful as various synthetic raw materials or intermediates.
Ω is an important intermediate of macrocyclic lactone-based fragrances such as cyclopentadecanolide and cyclohexadecanolide.
-Effectively used as an intermediate in the production of hydroxy fatty acids.

Hitherto, as a method for synthesizing ω-hydroxy fatty acids, a method using ω-cyanoundecanoate and γ-butyrolactone as starting materials has been disclosed in Japanese Patent Laid-Open No. 5-86013.
And is known in the art. However, in this method, it is generally considered difficult to obtain a raw material, and furthermore, a relatively expensive raw material is used, and a nitrile group at the ω-position is finally converted to a carboxyl group. In this case, ammonia is generated, the treatment becomes complicated, and the aroma of the target product is adversely affected.

[0004] In addition, it is very easy and inexpensive to obtain the general formula ROOC (CH ₂ ) nCOOR (where n
= An integer of 7 to 13, R is an alkyl group), and a method using a dicarboxylic acid ester and γ-butyrolactone as starting materials is proposed in International Patent Application Publication No. WO97-06156. In this method, an excess amount of a dicarboxylic acid ester with respect to γ-butyrolactone is mixed at room temperature in the presence of a condensing agent comprising a base, and heated and stirred at normal pressure,
The reaction was carried out while removing the produced methanol to obtain 2- (ω-
(Alkoxycarbonylalkanoyl) -4-butanolide is obtained, and although this method is also an excellent method, the selectivity and the yield have not yet been sufficiently satisfied.

[0005]

SUMMARY OF THE INVENTION It is an object of the present invention to improve the above-mentioned prior art and to use a dicarboxylic acid ester, which is an easily available and inexpensive raw material, with a high yield and good selectivity, and It is an object of the present invention to provide a method for producing 2-([omega] -alkoxycarbonylalkanoyl) -4-butanolide which is most advantageous.

[0006]

DISCLOSURE OF THE INVENTION The present invention has been made to achieve the above-mentioned object, and a method for producing 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide according to the present invention is characterized by using γ-butyrolactone and Formula (1) ROOC (C
H ₂ ) nCOOR (where n is an integer of 7 to 13 and R is an alkyl group), a condensation reaction of a dicarboxylic acid ester represented by the general formula (2)

[0007]

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In the production of 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide represented by the formula (1), n is an integer of 7 to 13 and R is an alkyl group. A process for producing 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide, comprising heating and stirring a dicarboxylic acid ester, and adding γ-butyrolactone and an alkali metal alcoholate to cause a condensation reaction.

In the present invention, the condensation reaction is carried out under reduced pressure while distilling off the alcohol, and the degree of reduced pressure is changed in two or more stages, so that the 2- (ω-alkoxycarbonyl) is more efficiently obtained. Alkanoyl) -4-
A method for producing butanolide can be obtained.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The condensation reaction of a dicarboxylic acid ester and γ-butyrolactone in the presence of a basic condensing agent is complicated, and therefore differs depending on the method of charging the raw materials and the reaction method such as the method of removing generated methanol. It is presumed that the selectivity and the yield greatly influence. Thus, the present inventors have conducted intensive studies focusing on the reaction mechanism related to the above-mentioned alcohol production, and as a result, as shown below, 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide was excellent in both selectivity and yield as described below. It was found that it could be obtained.

That is, first, γ-butyrolactone and an alkali metal alcoholate are dropped into a dicarboxylic acid ester under heating and stirring under sufficient pressure to evaporate the alcohol produced in the first step, and the alcohol is removed from the system. The reaction is carried out while distilling off, and then the reaction is carried out while removing the remaining alcohol outside the system by further increasing the degree of vacuum and heating and stirring as a second step. By doing so, both the selectivity and the yield are favorably 2- (ω
-Alkoxycarbonylalkanoyl) -4-butanolide was obtained, and the present invention was completed.

As described above, one of the features of the present invention resides in that γ-butyrolactone and an alkali metal alcoholate are added to a dicarboxylic acid ester being heated and stirred to cause a condensation reaction. In this case, γ-butyrolactone and The alkali metal alcoholate may be mixed and added (dropped),
You may add individually.

This reaction is preferably carried out while distilling the alcohol out of the system under reduced pressure. In the present invention, if the selectivity and the yield are good, it is possible to continue the reaction while removing the remaining alcohol outside the system by further increasing the degree of vacuum and heating and stirring as a second step following the above. It is preferable for tightening.

R of the dicarboxylic acid ester represented by ROOC (CH ₂ ) nCOOR of the general formula (1) used in the present invention (where n is an integer of 7 to 13 and R is an alkyl group) is used. An alkyl group having 1 to 6 carbon atoms is particularly preferably used for convenience. As a specific example of this R,
Examples include a methyl, ethyl, propyl, butyl, isobutyl, pentyl, hexyl group and the like. Especially, a methyl group is preferable.

Preferred examples of the dicarboxylic acid ester represented by the general formula (1) include 1,12-dodecandioic acid dimethyl ester and 1,13-tridecandioic acid dimethyl ester (brasilic acid dimethyl ester). Can be

In the present invention, the condensation reaction is carried out in the presence of an alkali metal alcoholate. The alkali metal alcoholate is represented by the general formula R'OM (where R 'is an alkyl group having 1 to 4 carbon atoms, M Is an alkali metal).

Specific examples of the alkali metal alcoholate mentioned here include sodium methylate, sodium ethylate, sodium propylate, sodium butyrate, potassium methylate, potassium ethylate, potassium propylate, potassium butyrate and the like. .

In the present invention, the use amount of these alkali metal alcoholates is not particularly limited, but is preferably 0.1 to 5 equivalents, more preferably 0.5 to 3 equivalents to γ-butyrolactone. If the used amount of the alkali metal alcoholate is small, the yield is low, and if the used amount exceeds a certain level, the yield is saturated, and conversely, the selectivity may be reduced.

In the present invention, the amount of the dicarboxylic acid ester represented by the general formula (1) is preferably an excess molar amount relative to γ-butyrolactone, specifically, more preferably 2 times or more. This is because when the amount of the dicarboxylic acid ester is 2 moles or more, the selectivity is particularly improved.

In the practice of the present invention, if unreacted dicarboxylic acid ester remains, it is effective to recover the unreacted dicarboxylic acid ester from the reaction mixture and recycle it for the condensation reaction. Preferred. In the present invention, since the unreacted dicarboxylic acid ester can be easily recovered from the reaction mixture by simple distillation,
A more efficient reaction is realized by the combination of the excess use of the dicarboxylic acid ester and the recycling.

In the condensation reaction of the present invention, the condensation reaction is preferably performed under reduced pressure in order to efficiently remove the alcohol. The reduced pressure condition is preferably 50 to 760.
mmHg, particularly preferably in the range of 100 to 600 mmHg. The decompression can be performed in two or more stages.
For example, the reaction is performed by reducing the pressure to about 500 to 700 mmHg, which is sufficient for evaporating the alcohol generated as the first step,
As a second step, the degree of pressure reduction can be further increased to about 50 to 300 mmHg for reaction.

Here, the heating temperature conditions for the condensation reaction are not particularly limited, but suitable conditions are set in relation to the reduced pressure, preferably 30 to 200 ° C., particularly preferably 50 to 1 ° C.
A range of 50 ° C. is preferred.

In the present invention, it is not necessary to use a solvent, but the reaction can be carried out by adding a solvent used for general ester condensation as long as the solvent does not reduce the activity of the alkali metal alcoholate.

The reaction type of the present invention is a batch type, a continuous type,
Any of multi-stages can be performed.

The 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide obtained according to the present invention is
By the steps described below, the ω-hydroxy fatty acid represented by the general formula (4), which is an important intermediate of the macrocyclic lactone-based fragrance, is easily and in high yield.

[0026]

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That is, 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide of the general formula (2) is heated in an aqueous solution of an alkali metal hydroxide or a mixed solution of a water-soluble solvent and water to give a lactone. The site is hydrolyzed and decarboxylated to form an ω-hydroxy- (ω-3) -keto fatty acid represented by the general formula (3).

Next, the compound of the general formula (3) is derived into an ω-hydroxy fatty acid represented by the general formula (4) by reducing the ketone to methylene by a Wolff-Kishner reduction or the like.

As described above, the 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide of the present invention is particularly important in the perfumery industry in the use of macrocyclic lactone-based fragrances such as cyclopentadecanolide and cyclohexadecanolide. It is useful as an intermediate in the production of ω-hydroxy fatty acid, which is a simple intermediate.

[0030]

Next, the present invention will be described in detail with reference to examples. However, the following examples are given for illustrative purposes and should not be construed as limiting in any sense.

Example 1 1,12-Dodecanediacid dimethyl ester (105.00 g, 406.4 mmol)
Was charged into a reaction apparatus, and 10
The mixture was heated and stirred at 5 ° C. γ-butyrolactone (8.75
g, 101.6 mmol) and a 28% by weight sodium methoxide-methanol solution (19.60 g, 101.6).
mmol) at room temperature,
Methanol was distilled off while dropping into 12-dodecanediacid dimethyl ester over 30 minutes. After performing the reaction for 30 minutes as it is, the pressure was reduced to 200 mmHg for further 12 minutes.
The reaction was performed for 0 minutes.

Next, the pressure was returned to normal pressure, cooled, poured into dilute hydrochloric acid, and extracted with ethyl acetate. The organic layer is washed with water,
After drying over anhydrous magnesium sulfate, the solvent was distilled off.
The remaining oil was distilled under reduced pressure (oil bath temperature 170-180 /
(0.5-0.2 mmHg), and excess 1,12-dodecanediacid dimethyl ester was distilled off. 81.9 g of a fraction and 25.1 g of a distillation residue were obtained.

Analysis of the distillation residue by gas chromatography showed that 88.6% by weight of the compound represented by the general formula (2) (n = 10, R = Me) was contained. The yield was 80.2% and the selectivity was 83.2%.

Example 2 1,12-Dodecanedioic acid dimethyl ester (105.00 g, 406.4 mmol)
Was charged into a reaction apparatus, and 10
The mixture was heated and stirred at 5 ° C. γ-butyrolactone (8.75
g, 101.6 mmol) and a 28% by weight sodium methoxide-methanol solution (19.60 g, 101.6).
mmol) at room temperature,
Methanol was distilled off while dropping into 12-dodecanediacid dimethyl ester over 30 minutes. After the reaction as it is for 30 minutes, the pressure was reduced to 200 mmHg and the pressure was further reduced to 24 mmHg.
The reaction was performed for 0 minutes.

Next, the pressure was returned to normal pressure, cooled, poured into dilute hydrochloric acid, and extracted with ethyl acetate. The organic layer is washed with water,
After drying over anhydrous magnesium sulfate, the solvent was distilled off.
The remaining oil was distilled under reduced pressure (oil bath temperature 170-180 ° C /
(0.5-0.2 mmHg), and excess 1,12-dodecanediacid dimethyl ester was distilled off. 82.2 g of a fraction and 26.5 g of a distillation residue were obtained. As a result of examining the residue portion, 8
8.1% of the compound of general formula (2) (n = 10, R = M
e) was found to be included. The yield is 81.4%.
And the selectivity was 87.9%.

Example 3 1,12-Dodecanediacid dimethyl ester (105.00 g, 406.4 mmol)
Was charged into a reactor, and 10 mm under a reduced pressure of 500 mmHg.
The mixture was heated and stirred at 5 ° C. γ-butyrolactone (8.75
g, 101.6 mmol) and a 28% by weight sodium methoxide-methanol solution (19.60 g, 101.6).
mmol) at room temperature,
Methanol was distilled off while dropping into 12-dodecanediacid dimethyl ester over 30 minutes. After the reaction as it is for 30 minutes, the pressure was reduced to 100 mmHg and the pressure was further reduced to 12 mmHg.
The reaction was performed for 0 minutes.

After the pressure was returned to normal pressure, the mixture was cooled, poured into diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off. The remaining oil is distilled under reduced pressure (oil bath temperature 170-180 ° C / 0.5
０．２0.2 mmHg) to distill off excess 1,12-dodecandioic acid dimethyl ester. 81.4 g of a fraction and 27.2 g of a distillation residue were obtained. As a result of examining the residue portion, 88.3 was obtained.
% Of the compound of the general formula (2) (n = 10, R = Me). The yield is 81.6%,
The selectivity was 86.0%.

Comparative Example 1 1,12-Dodecanediacid dimethyl ester (105.00 g, 406.4 mmol)
And γ-butyrolactone (8.75 g, 101.6 mmol
l) and a 28% by weight sodium methoxide-methanol solution (19.60 g, 101.6 mmol) were mixed at 50 ° C, and the temperature was raised to 110 ° C over 45 minutes while distilling off methanol. After reacting for 30 minutes as it is, 630
The pressure was reduced to mmHg and the reaction was performed for 30 minutes.

After returning the pressure to normal pressure and reacting for further 30 minutes, the mixture was cooled, poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off. The remaining oil was distilled under reduced pressure (oil bath temperature 17
(0-180 ° C / 0.5-0.2 mmHg) to distill off excess 1,12-dodecanediacid dimethyl ester.
81.5 g of a fraction and 25.6 g of a distillation residue were obtained. As a result of examining the residue portion, 85.1% of the compound of the general formula 1 (n = 1
0, R = Me). The yield is 79.0
%, And the selectivity was 79.0%.

[0040]

According to the present invention, 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide can be obtained in high yield and good selectivity by using a dicarboxylic acid ester which is an easily available and inexpensive raw material. It can be obtained by an industrially advantageous production method.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Nobuhiko Ito 1573-4 Funagata, Noda-shi, Chiba Pref. (72) Inventor: Shinzo Imamura 9-1, Oecho, Minato-ku, Nagoya-shi, Aichi

Claims (4)

[Claims] 1. Gamma-butyrolactone and the general formula (1)
A dicarboxylic acid ester represented by OC (CH ₂ ) nCOOR (where n is an integer of 7 to 13 and R is an alkyl group) is subjected to a condensation reaction to obtain a compound represented by the general formula (2). (Where n is an integer of 7 to 13, R is an alkyl group) 2- (ω-alkoxycarbonylalkanoyl)-
When producing 4-butanolide, the above-mentioned general formula (1)
Wherein the dicarboxylic acid ester represented by the formula (1) is heated and stirred, and a condensation reaction is carried out by adding γ-butyrolactone and an alkali metal alcoholate thereto.
A method for producing (ω-alkoxycarbonylalkanoyl) -4-butanolide. 2. The compound represented by the general formula (1) wherein R is 1 to 6 carbon atoms.
2. The alkyl group according to claim 1, wherein
A method for producing-(ω-alkoxycarbonylalkanoyl) -4-butanolide. 3. The method according to claim 1, wherein the condensation reaction is carried out under reduced pressure while distilling off alcohol.
2- (ω-alkoxycarbonylalkanoyl)
-4- A method for producing butanolid. 4. The 2- (ω-alkoxycarbonylalkanoyl) -4-butanolide according to claim 1, wherein the condensation reaction is carried out by changing the degree of pressure reduction to two or more stages. Manufacturing method.