JPH11130768A - Production of optically active 5-hydroxy-2-decenoic acid and optically active massoia lactone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an optically active massoia lactone simply and industrially. SOLUTION: This method for producing an optically active 5-hydroxy-2- decenoic acid is to react (±)-5-hydroxy-2-decenoic acid with an optically active 1-aminotetralin to form diastereomer salts of 5-hydroxy-2-decenoic acid, then separate the diastereomer salts to each diastereomer salt and decompose the obtained diastereomer salt. The method for producing an optically active massoia lactone is to perform an intramolecular esterification of the optically active 5-hydroxy-2-decenoic acid obtained by the above method in the presence of an acid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing optically active 5-hydroxy-2-decenoic acid and a method for producing optically active masoiyalactone.

[0002]

2. Description of the Related Art Masoyalactone is a useful chemical substance in the fields of cosmetics and food preparation fragrances because it is fat-like and sweet and has a characteristic butter and milk-like odor. Also,
Massoyalactone is known to be contained in nature such as tuberose (sugar perfume), sugarcane, and butter. By the way, Masoyalactone is represented by the following formula (1)
Is represented by

Embedded image As is clear from the formula (1), Masoyalactone has one chiral center in a six-membered ring, and has two kinds of optical isomers ((+)-masoyalactone and (−)-masoyaya). Lactone). For example, it has been reported that the soyalactone contained in natural tuberose is (R)-(−) masojalactone (Tetrahe).
drNetters, 20, 1659, (197
6)). However, a method of isolating optically active soyalactone from natural products is not a practical method because it requires a great deal of labor and cost.

[0003] On the other hand, generally, soyalactone produced industrially is a mixture of two optical isomers. However, if a specific optical isomer can be obtained at a high concentration,
Its industrial significance is great. Heretofore, there has been little research on optical resolution of masoiyalactone. As one of the few reports, for example, a synthesis method for obtaining an optical isomer of masoiyalactone via an optically active epoxide intermediate has been reported (Tetrahedron).
Letters, 33, 4761, (1990)). However, this method is not suitable as an industrial production method because of the use of peroxide and the large number of steps.

[0004] Therefore, it is conceivable to perform optical resolution by reacting an optically active amine as a resolving agent with masoial lactone to form a diastereomeric salt mixture. There was no optical resolving agent suitable for obtaining a good salt.

[0005]

The present inventors have conducted intensive studies to find an optical resolving agent suitable for optically resolving masoiya lactone. It has been found that when a specific optically active amine is allowed to act on decenoic acid as a resolving agent, 5-hydroxy-2-decenoic acid can be efficiently optically resolved.

[0006]

Thus, according to the present invention, (±) -5-hydroxy-2-decenoic acid is reacted with optically active 1-aminotetralin to form 5-hydroxy-
After preparing a mixture of diastereomeric salts of 2-decenoic acid and separating the diastereomeric salt mixture into the respective diastereomeric salts, the resulting diastereomeric salts are decomposed to give optically active 5-hydroxy- There is provided a process for producing optically active 5-hydroxy-2-decenoic acid, which comprises obtaining 2-decenoic acid. Furthermore, according to the present invention,
(±) -5-hydroxy-2-decenoic acid and optically active 1
-Aminotetralin is reacted to give 5-hydroxy-2-
After preparing a mixture of diastereomeric salts of decenoic acid, separating the diastereomeric salt mixture into the respective diastereomeric salts, and decomposing the resulting diastereomeric salt to synthesize an optically active 5-hydroxy- There is provided a method for producing an optically active soyalactone obtained by intramolecularly esterifying 2-decenoic acid in the presence of an acid.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION (±) -5-Hydroxy-2-decenoic acid used in the present invention is a known compound represented by the formula (2).

Embedded image (±) -5-Hydroxy-2-decenoic acid usually hydrolyzes (±) -masoyalactone represented by the formula (1) with an alkali such as sodium hydroxide and neutralizes with an acid such as hydrochloric acid. Can be easily obtained.

Embedded image The method for producing (±) -masoyalactone used in this reaction is not particularly limited, and may be a known method described in JP-A-7-165668 or the like. (±) -5-Hydroxy-2-decenoic acid used in the present invention comprises (+)-5-hydroxy-2-decenoic acid and (−)-
It is a mixture of 5-hydroxy-2-decenoic acid. (+)
Both -5-hydroxy-2-decenoic acid and (-)-5-hydroxy-2-decenoic acid are not limited to a one-to-one mixture, and one of them may be more than the other.

In the present invention, (±) -5-hydroxy-2
Decenoic acid and optically active 1-aminotetralin are dissolved and reacted in a solvent to form a diastereomeric salt mixture. The amount of the optically active 1-aminotetraline used is not particularly limited, but is usually 0.3 to 2.0 mol, preferably 0.1 to 2.0 mol per mol of (±) -5-hydroxy-2-decenoic acid. It is in the range of 8-1.3 mol.

In the present invention, it is necessary to cause optically active 1-aminotetralin to act on (±) -5-hydroxy-2-decenoic acid. That is, (±) -5
Only by reacting hydroxy-2-decenoic acid with optically active 1-aminotetralin, a sparingly soluble diastereomer salt can be precipitated. On the other hand, even if other known optically active amines are used as the resolving agent, it is difficult to efficiently separate them.

The solvent used is 5-hydroxy-2-
There is no particular limitation as long as it does not inhibit the formation of a mixture of diastereomeric salts of decenoic acid. Examples thereof include water; ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dibutyl ether, and dioxane; methanol, ethanol Alcohols such as, 2-propanol; esters such as methyl acetate and ethyl acetate; ketones such as acetone and methyl ethyl ketone; aromatic hydrocarbons such as benzene and toluene;
And aliphatic hydrocarbons such as hexane and cyclohexane; and among them, water, alcohols, esters and the like are preferable. These may be used alone or as a mixture of two or more. The amount of solvent used is
Usually, the amount is 200 to 3000 parts by weight, preferably 500 to 2,000 parts by weight, based on 100 parts by weight of (±) -5-hydroxy-2-decenoic acid.

The reaction temperature for producing a diastereomer salt mixture from (±) -5-hydroxy-2-decenoic acid and optically active 1-aminotetralin is usually a temperature between the freezing point and the boiling point of the solvent. The reaction is preferably carried out within a temperature range from room temperature to the boiling point. The reaction time of the reaction is usually 0.1 to 12 hours, preferably 0.5 to 6 hours. After the reaction, the reaction solution containing the diastereomer salt mixture may be subjected to solvent evaporation. The above operation produces a mixture of diastereomeric salts of 5-hydroxy-2-decenoic acid.

Next, in the present invention, 5-hydroxy-2
Separating the diastereomeric salt mixture of decenoic acid into the respective diastereomeric salts. Although any known method may be used for the separation, a method of separating each diastereomer salt using a difference in solubility of each diastereomer salt in a solvent is preferable. The method of using the solubility difference is
Usually, after distilling off the solvent of the reaction solution, it is separated by recrystallization, or the reaction solution is cooled, and one of the diastereomeric salts of 5-hydroxy-2-decenoic acid having a lower solubility is crystallized. Precipitate. This is separated by a solid-liquid separation method such as filtration or centrifugation.

The crystal of the separated diastereomeric salt can be recrystallized as required to increase its purity. The solvents used for recrystallization are the same as those that can be used to form a mixture of diastereomeric salts of 5-hydroxy-2-decenoic acid. These may be used alone or as a mixture of two or more. The number of times of recrystallization is usually 1 to 5 times, preferably 2 to 5 times.

The decomposition of the separated diastereomeric salt of 5-hydroxy-2-decenoic acid may be carried out by any known method. As a decomposition method, for example, an aqueous solution of a water-soluble base is added to the diastereomer salt of 5-hydroxy-2-decenoic acid obtained by the above recrystallization, and the mixture is stirred.
Optically active 1-aminotetralin is released. The released 1-aminotetralin is recovered by extraction with an organic solvent.

The water-soluble base is, for example, sodium hydroxide or potassium hydroxide. The concentration of the aqueous solution of the water-soluble base is not particularly limited, but is, for example, 1 to 6N. The amount of the aqueous solution of the water-soluble base used is not particularly limited, but may vary depending on the concentration of the water-soluble base.
The amount of the water-soluble base used may be about 1 to 5 mol per 1 mol of the diastereomer salt of decenoic acid. The organic solvent used for recovering the released 1-aminotetralin is not particularly limited, and is, for example, ether or benzene. The amount of the organic solvent used is not particularly limited, and is, for example, 100 to 1000 parts by weight based on 100 parts by weight of 1-aminotetralin.

Next, when an inorganic acid is added to the aqueous layer separated by extraction and stirred, optically active 5-hydroxy-2-decenoic acid is released. By extracting the liberated optically active 5-hydroxy-2-decenoic acid with an organic solvent, optically active 5-hydroxy-2-decenoic acid can be obtained. The inorganic acid is not particularly limited, and includes, for example, hydrochloric acid, sulfuric acid and the like. The concentration of the inorganic acid is, for example, 1 to 6
It is a rule. The amount of the inorganic acid used is, for example, such that the amount of the inorganic acid is about 1 to 10 mol per mol of the released optically active 5-hydroxy-2-decenoic acid, depending on the concentration of the inorganic acid. Should be used. The organic solvent used here is the same as the organic solvent that can be used when the above-mentioned optically active 1-aminotetralin is recovered. After drying the obtained organic solvent layer, the organic solvent is distilled off under reduced pressure to obtain an optically active 5-hydroxy-
This gives 2-decenoic acid.

According to the present invention, the optically active 5-hydroxy-2-decenoic acid obtained as described above is intramolecularly esterified in a solvent in the presence of an acid to give an optically active masoialactone. obtain.

The above-mentioned reaction for intramolecular esterification in the presence of an acid refers to intramolecular esterification of the hydroxyl group and carboxyl group in the molecule of optically active 5-hydroxy-2-decenoic acid in the presence of an acid. To produce optically active soyalactone.

Embedded image

Examples of the acid include organic sulfonic acids such as p-toluenesulfonic acid and methanesulfonic acid; inorganic acids such as hydrochloric acid and sulfuric acid; carboxylic acids such as trifluoroacetic acid and oxalic acid; Among them, organic sulfonic acids and inorganic acids are preferred. The amount of the acid to be used is generally 0.01-0.1 mol, preferably 0.02-0.1 mol, per 1 mol of 5-hydroxy-2-decenoic acid.
0.08 mol.

The solvent used in the intramolecular esterification reaction includes, for example, aromatic hydrocarbons such as benzene, toluene, ethylbenzene and xylene; saturated hydrocarbons such as hexane, cyclohexane and octane; Hydrogen is preferred. These solvents may be used alone or in combination of two or more.

[0021] The reaction temperature of the intramolecular esterification reaction is usually from 80 to 160 ° C, preferably from 100 to 150 ° C. The reaction time of the intramolecular esterification reaction is usually 2
~ 48 hours, preferably 4-24 hours. After the intramolecular esterification reaction, the reaction solution was washed with an aqueous alkali solution such as sodium bicarbonate, and then with a saturated saline solution.
After drying the organic layer over anhydrous magnesium sulfate or the like, the solvent is distilled off to obtain optically active mosaialactone. The masoyalactone may be purified by a method such as distillation under reduced pressure.

(+)-Masoyalactone is (±) -5
It is formed from a sparingly soluble diastereomer salt obtained by reacting (+)-1-aminotetralin with -hydroxy-2-decenoic acid. In addition, (-)-masoyalactone is formed from a salt of a poorly soluble diastereomer obtained by reacting (±) -5-hydroxy-2-decenoic acid with (−)-1-aminotetralin. I do.

The preferred embodiments are summarized below. 1. (±) -5-Hydroxy-2-decenoic acid per 1 mol, optically active 1-aminotetralin 0.8 to 1.3.
A method for producing optically active 5-hydroxy-2-decenoic acid, characterized by reacting a molar reaction. 2. Reacting (±) -5-hydroxy-2-decenoic acid with optically active 1-aminotetralin in a solvent such as water, alcohols, ethers or esters; A method for producing 2-decenoic acid. 3. A method for producing optically active masoiyalactone, comprising intramolecularly esterifying optically active 5-hydroxy-2-decenoic acid in the presence of an organic sulfonic acid. 4. The amount of the acid (3) is 0.01 to 0.1 mol per 1 mol of optically active 5-hydroxy-2-decenoic acid.

[0024]

The present invention will be described more specifically with reference to the following examples. Parts and% in Examples and Comparative Examples
Are by weight unless otherwise noted. Production Example 1 (Production of (±) -5-hydroxy-2-decenoic acid
Production Method) To 1.68 g (10.0 mmol) of (±) -masoyalactone, 15 ml of a 1N aqueous sodium hydroxide solution was added, and the mixture was stirred at 95 ° C. for 1 hour. The temperature of the reaction solution was cooled to room temperature, and 15 mL of 1 N hydrochloric acid was slowly added dropwise with stirring to make the acid of Congo Red acidic. Then, the released (±) -5-hydroxy-2-decenoic acid was dissolved in 10 mL of ethyl acetate. Extracted. Example 1 Method for producing diastereomer salt mixture To the extract obtained in Production Example 1, 1.44 g (9.8 mmol) of (+)-1-aminotetralin was added and dissolved by stirring at room temperature. Then, the solvent was removed under reduced pressure, and (±)
3.22 g (9.66 mmol) of a salt (crude) of -5-hydroxy-2-decenoic acid and (+)-1-aminotetralin was obtained. 1.67 g of a salt of (±) -5-hydroxy-2-decenoic acid and (+)-1-aminotetralin (5.0
(Mmol) was dissolved by heating in 17.5 ml of a mixed solvent of ethanol and tert-butyl methyl ether (both volume ratios were 1: 9). The mixture was gradually cooled to room temperature, allowed to stand overnight, and the precipitated crystals were separated by filtration to obtain 0.666 g (2.0 mmol) of diastereomer salt crystals. The yield was 80.0% based on half the amount of the racemic massoylactone. The mother liquor obtained by filtration was evaporated under reduced pressure to remove the solvent, and a diastereomer salt mixture (1.01 g, 3.04 mmol) was obtained.
I got Physical properties of the obtained diastereomer salt were as follows. Crystal side [α] ₄₃₅ ²³ -13.7 ° (c 1.09, methanol) [α] _D ²⁶ -7.55 ° (c 1.09, methanol) Melting point 117.0-121.0 ° C Mother liquor side [α] ₄₃₅ ²³ -16.6 ゜ (c1.04, methanol) [α] _D ²⁶ -4.23 ゜ (c1.04, methanol) Melting point 65.0-71.5 ° C Purification of diastereomeric salt on the crystal side Crystal The diastereomer salt 0.666 g (2.0 mmol) was recrystallized twice more with a mixed solvent of ethanol and tert-butyl methyl ether (the volume ratio of both was 1: 9) to give a diastereomer. 0.333 g (0.997 mmol) of crystals of the mer salt were obtained. The yield was 39.9% with respect to half of the racemic mass of masoyalactone. Physical properties of this diastereomer salt were as follows. [Α] ₄₃₅ ²⁰ -19.1 ° (c1.13, methanol) [α] _D ²² -9.66 ° (c1.13, methanol) diastereomer salt mp 126.5-127.0 ° C. crystal side To 0.307 g (0.919 mmol) of the crystals obtained above, 2.0 ml of a 1N aqueous sodium hydroxide solution was added, and the released (+)-1-aminotetralin was extracted and removed with diethyl ether. The aqueous layer was added with 2.0 ml of 3N hydrochloric acid and the released 5-hydroxy-2-decenoic acid was extracted with diethyl ether. The ether layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. 0.17 g of 5-hydroxy-2-decenoic acid (0.
914 mmol). Intramolecular esterification of 5-hydroxy-2-decenoic acid obtained above 0.15-0.1% of 5-hydroxy-2-decenoic acid obtained above
g (0.914 mmol) was dissolved in 1.5 ml of benzene, and 0.05 equivalent of p-toluenesulfonic acid of 5-hydroxy-2decenoic acid was added, followed by heating under reflux for 3 hours. After completion of the reaction, the organic layer was washed with a 5% by weight aqueous solution of sodium hydrogen carbonate and then with a saturated saline solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain crude optically active masoiyalactone 0. .15 g were obtained. When this optically active massoyalactone was identified by measuring the infrared absorption spectrum and the specific rotation, it was found that this was (+)-masoyalactone. This was distilled and purified to give (+)-masoyalactone 0.1.
41 g (0.828 mmol) were obtained, and the yield of (+)-masoyalactone was 90.6% based on the 5-hydroxy-2-decenoic acid obtained above. Physical properties of the obtained (+)-masoyalactone were as follows. [Α] ₄₃₅ ²³ + 304 ° (c1.03, chloroform) [α] _D ²⁴ + 117 ° (c1.03, chloroform) Melting point 115-120 ° C. (1.0 mmHg) Also obtained (+)-masoyalactone Was analyzed by high performance liquid chromatography to find that the optical purity was 98.3.
% E. e. Met. HPLC measurement conditions Column: CHIRALCEL OB-H φ4.6 mm
× 250 mm Mobile phase: 2-propanol was added to 4.0% (v / v) hexane. Flow rate: 0.5 ml / min Detection wavelength: 220 nm 5-hydroxy-2-decenoic acid on the mother liquor side and (-)-1-
Method for producing salt of aminotetralin 11.0 g (3.04 mmol) of diastereomer salt obtained by evaporating the solvent on the first mother liquor side obtained above was added with 1
After adding 4.5 ml of a specified aqueous sodium hydroxide solution and extracting and removing free (+)-1-aminotetralin with diethyl ether (10 ml), the aqueous layer was stirred at 95 ° C. for 30 minutes. The temperature of the reaction solution was cooled to room temperature, and while stirring, 4.5 ml of 1N hydrochloric acid was slowly added dropwise to acidify Congo Red, followed by liberation of the released 5-hydroxy-2-decenoic acid with diethyl ether (10 ml). Extracted. In the obtained extract,
After 0.458 g (3.1 mmol) of (-)-1-aminotetralin was added and dissolved by stirring at room temperature, the solvent was removed under reduced pressure, and 5-hydroxy-2-decenoic acid and (-)
1.01 g (3.04 mmol) of the salt of -1-aminotetralin were obtained. The physical properties of the obtained diastereomer salt are
It was as follows. [Α] ₄₃₅ ²⁴ +15.3 ゜ (c1.20, methanol) [α] _D ²⁶ +7.01 ゜ (c1.20, methanol) Melting point 110.0-116.5 ° C Purification of diastereomer salt on mother liquor side 1.01 g of the diastereomer salt on the mother liquor side obtained above
(3.04 mmol) was recrystallized twice with a mixed solvent of ethanol and tert-butyl methyl ether (the volume ratio of both was 1: 9) to give 0.281 g (0.01 g) of crystals of diastereomeric salts. 842 mmol). The yield of the diastereomer salt was 33.7% with respect to half of the racemate of masoiyalactone. Physical properties of this diastereomer salt were as follows. [Α] ₄₃₅ ²⁴ + 15.9 ° (c 1.05, methanol) [α] _D ²⁶ + 10.2 ° (c 1.05, methanol) Melting point 125.0-126.0 ° C Decomposition of diastereomer salt on mother liquor side To 0.269 g (0.806 mmol) of the crystals obtained above was added 2.0 mL of a 1N aqueous sodium hydroxide solution, and the liberated (-)-1-aminotetralin was extracted and removed with diethyl ether (5 mL). After that, 2.0 ml of 3N hydrochloric acid was added to the aqueous layer, and the released 5-hydroxy-2-decenoic acid was extracted with diethyl ether (5 ml). The ether layer was dried over anhydrous magnesium sulfate and then dried under reduced pressure. The solvent was distilled off to obtain 0.151 g (0.809 mmol) of 5-hydroxy-2-decenoic acid. Intramolecular esterification of 5-hydroxy-2-decenoic acid obtained above 0.15-0.1% of 5-hydroxy-2-decenoic acid obtained above
1 g (0.809 mmol) was intramolecularly esterified in the same manner as described above to obtain 0.124 g of a crude optically active mazoialactone. When this optically active masoialactone was identified by measurement of the infrared absorption spectrum and specific rotation, it was found to be (−)-masoyalactone. This was distilled to obtain 0.117 g (0.696 mmol) of purified (-)-masoyalactone, and the yield of (-)-masoyalactone was 5-hydroxy- It was 86.0% based on 2-decenoic acid. The physical properties of the obtained (-)-masoyalactone were as follows. [Α] ₄₃₅ ²⁴ -303 ゜ (c 0.640, chloroform) [α] _D ²⁷ -116 ゜ (c 0.640, chloroform) Boiling point 115-120 ° C (1.0 mmHg) Also obtained (-)-maso As a result of analyzing the earlactone by high performance liquid chromatography, the optical purity was 99.2.
% E. e. Met.

Comparative Example 1 An experiment was conducted in the same manner as in Example 1 except that the resolving agent was changed as shown in Table 1 in the process of Example 1. Table 1 shows the recrystallization solvents used. As a result, even if a resolving agent other than 1-aminotetralin was used, optically active massoyalactone could not be obtained.

[0026]

According to the present invention, the optically active 1-aminotetralin is reacted with the (±) -5-hydroxy-2-decenoic acid obtained by opening the ring of masoialactone by the diastereomer method. 5-hydroxy-2-decenoic acid. Further, by optically esterifying this optically active 5-hydroxy-2-decenoic acid in the presence of an acid, optically active masoiyalactone can be easily and industrially produced.

[Table 1]

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Claims (2)

[Claims] (1) reacting (±) -5-hydroxy-2-decenoic acid with an optically active 1-aminotetralin to prepare a mixture of diastereomeric salts of 5-hydroxy-2-decenoic acid; An optically active 5-hydroxy compound, comprising separating a diastereomer salt mixture, separating the diastereomer salt, and obtaining an optically active 5-hydroxy-2-decenoic acid. -2
-A process for producing decenoic acid. 2. A mixture of (±) -5-hydroxy-2-decenoic acid and optically active 1-aminotetralin to produce a mixture of diastereomeric salts of 5-hydroxy-2-decenoic acid. After separating the diastereomer salt from the diastereomer salt mixture, the resulting diastereomer salt is decomposed to synthesize optically active 5-hydroxy-2-.
A process for producing an optically active mosaialactone obtained by intramolecularly esterifying decenoic acid in the presence of an acid.