JP3550933B2 - Process for producing diastereomeric hydroxycarboxylic acid amides and process for producing optically active δ-lactones - Google Patents

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The invention of this application relates to a method for producing diastereomeric hydroxycarboxylic acid amides and a method for producing δ-lactones.
[0002]
[Prior art]
Conventionally, the following formula (I) such as δ-decalactone
[0003]
Embedded image
[0004]
(R represents a straight-chain saturated hydrocarbon group having 3 to 7 carbon atoms)
The δ-lactones represented by are known to be contained in many natural products such as peach fruit, raspberry, plum, butter, cheese, mango and the like, and have a creamy, green sweet character. Since it has a certain fruity aroma, it is a useful substance in the fields of food preparation flavors, cosmetics, synthetic flower essential oils, medicines, chemicals, and the like. These δ-lactones have one chiral center in the six-membered ring, and have two optical isomers, ie, (+)-δ-lactones and (−)-δ-lactones. Exists, but it has also been reported that the optical isomer contained varies depending on the type of natural product.
[0005]
For example, cheese contains δ-decalactone, which is one of δ-lactones, and its optical composition is (+)-δ-decalactone: (−)-δ-decalactone = 72: 28 (44% ee). It has also been reported that the same ratio of the (+)-form: (-)-form is reversed to 2:98 (96% ee) when raspberry is contained in the same δ-decalactone (Z Lebensm Unters). Forsch (1993) 196: 315p).
[0006]
Furthermore, it has also been reported that the odor quality of each corresponding optical isomer is slightly different (Z Lebensm Enters Forsch (1988) 187: 40-44p).
From such findings, it is taught that it would be very useful if the composition ratio of the optical isomer of δ-lactone can be arbitrarily adjusted. From this, it is extremely significant to separate and obtain the desired optical isomer of δ-lactone. For example, it is difficult to obtain an optical lactone having a composition exceeding 50% ee from the above-mentioned literature examples. It is a useful technique for reproducing naturally-derived fragrances in the fields of food compounding fragrances, cosmetics, and synthetic flower essential oils.
[0007]
However, at present, it is difficult to selectively obtain the desired optical isomer of δ-lactone. For example, a method of isolating from a natural product is not a practical method because it requires a great deal of labor and cost. . On the other hand, as a method for obtaining an optical isomer by synthesis, a method using an enzyme such as lipase or yeast or yeast has been reported.However, this method is not industrially preferable because yeast is used. There are also problems such as a large number of steps.
[0008]
Also, some methods for producing optical isomers by a synthesis method using a metal complex catalyst have been proposed, but the reaction operation is difficult, the number of steps is large, and it is difficult to improve the yield and optical purity. There was a problem.
[0009]
[Problems to be solved by the invention]
Thus, the invention of this application solves the above-mentioned drawbacks of the prior art, and provides a new technical measure that can obtain optical isomers of δ-lactones more selectively and by a simple method. It is an object of the invention to do so.
[0010]
[Means for Solving the Problems]
In order to solve the above-mentioned problems, the invention of this application firstly provides the following formula (I)
[0011]
Embedded image
[0012]
(R represents a straight-chain hydrocarbon group having 3 to 7 carbon atoms)
A mixture of optical isomers of δ-lactones represented by the following formula (II)
[0013]
Embedded image
[0014]
Reacting with an optically active 1-phenylethylamine represented by the following formula (III):
[0015]
Embedded image
[0016]
(R is the same as defined above).The invention of this application also relates to a second method for producing diastereomeric hydroxycarboxylic acid amides having a reaction temperature of 20 to 180 ° C., and thirdly, a diastereomeric method using an aromatic hydrocarbon as a solvent. Disclosed is a method for producing a merhydroxycarboxylic acid amide. Fourth, the invention of this application provides diastereomeric hydroxycarboxylic acid amides themselves obtained by these methods. And the invention of this application is the fifthDiastereomeric hydroxycarboxylic acid amidesA method for producing an optically active diastereomeric hydroxycarboxylic acid amide to be recrystallized and purified, and sixthly, an optically active diastereomeric hydroxycarboxylic acid amide obtained by such a method are provided.
[0017]
Further, the invention of this applicationSeventh,Hydrolyzing the diastereomeric hydroxycarboxylic acid amides represented by the above formula (III), and then subjecting them to a cyclization reaction in the presence of sulfonic acid.Or eighth,Cyclization directly in the presence of acidhandA method for producing an optically active δ-lactone is provided, which comprises obtaining an optically active form of the δ-lactone represented by the above formula (I).
[0018]
BEST MODE FOR CARRYING OUT THE INVENTION
The diastereomeric hydroxycarboxylic acid amides provided by the invention of the present application are indispensable for producing optically active δ-lactones, and they include optically active 1-phenylethylamine. The invention of this application as an optical resolving agent is a feature of the optical resolving process.
[0019]
Hereinafter, embodiments of the present invention will be described in detail.
First, in the present invention, an optical isomer mixture of δ-lactone represented by the above formula (I) is reacted with 1-phenylethylamine of the above formula (II) as an optical resolving agent. In the δ-lactones represented by the formula (I), R in the formula is a straight-chain hydrocarbon group having 3 to 7 carbon atoms, and is generally a straight-chain saturated hydrocarbon group. The carbon number is 4-5. The optical isomer mixture may be a mixture of the optical isomers in various ratios, and a racemic mixture (racemate) is one of them.
[0020]
Specifically, for example, as racemates, (±) -δ-octalactone, (±) -δ-nonalactone, (±) -δ-decalactone, (±) -δ-dodecalactone, (±) -δ- Undecalactone is exemplified. Among them, (±) -δ-nonalactone and (±) -δ-decalactone are preferred. As the resolving agent compound, specifically,
(+)-1-phenylethylamine
(-)-1-phenylethylamine
As shown. Any of these compounds will be selected according to the purpose of the optical resolution.
[0021]
In the reaction, the optically active 1-phenylethylamine as a resolving agent is used in an amount of 1.00 to 2.00 equivalents (based on lactone), preferably 1.00 to 1.20 equivalents, based on the δ-lactone.
For the reaction, a solvent is preferably used. In this case, as the type of the solvent, hydrocarbons, for example, benzene, toluene, xylene, ethylbenzene, cumene, aromatic hydrocarbons such as methylnaphthalene and hexane, aliphatic hydrocarbons of octane, ethers, for example Dimethyl ether, diethyl ether, methyl-tert-butyl ether dioxane, tetrahydrofuran and the like, and further, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-hexanol, ethylene glycol, diethylene glycol and glycerin.
[0022]
These may be used alone or in combination of two or more.
Among them, aromatic hydrocarbons such as benzene, toluene, and xylene are preferably used. The amount of these solvents used is 0.5 to 10 times by weight (based on lactone), preferably 2 to 5 times by weight. The reaction temperature is usually set to about 20 to 180 ° C, more preferably, to about 80 to 110 ° C. The reaction time varies depending on various conditions, but may be about 1 to 24 hours, more preferably about 3 to 8 hours.
[0023]
Diastereomeric hydroxycarboxylic acid amides represented by the above formula (III), which are produced by reacting a mixture of optical isomers of δ-lactones with optically active 1-phenylethylamine, are novel compounds which have not been known so far. It is. R in the formula (III) is the same as R in the formula (I). Specific diastereomer-hydroxycarboxylic amides include, for example, N- (1-phenylethyl) -5-hydroxyoctanoic acid amide, N- (1-phenylethyl) -5-hydroxynonanoic acid amide, N- (1 -Phenylethyl) -5-hydroxydecanoic acid amide, N- (1-phenylethyl) -5-hydroxyundecanoic acid amide, and N- (1-phenylethyl) -5-hydroxydodecanoic acid amide; -(1-phenylethyl) -5-hydroxynonanoic acid amide and N- (1-phenylethyl) -5-hydroxydecanoic acid amide.
[0024]
This is refined to a higher purity state by recrystallization.
As the solvent for recrystallization, for example, various solvents shown in Table 1 can be used, and aliphatic hydrocarbons, aromatic hydrocarbons, and esters are preferable. In addition, one of the solvents in Table 1 can be used, or a combination of two or more solvents can be used.
[0025]
[Table 1]
[0026]
The amount of the solvent to be used is generally 0.5 to 200 times by weight, more preferably 1 to 100 times by weight, relative to the amides. The crystallization temperature in the recrystallization operation is about -20 to 100 ° C, more preferably about 10 to 40 ° C. The crystallization time can be about 1 to 48 hours, more preferably about 4 to 12 hours. In addition, at the time of recrystallization refining, if a seed of the crystal is added, the recrystallization will be performed more effectively.
[0027]
The recrystallization may be repeated a plurality of times as necessary.
By the above recrystallization, the optically active diastereomer hydroxycarboxylic acid amide of the formula (III) is obtained as a substantially pure high-purity product.
This diastereomer is then converted by a cyclization reaction to optically active δ-lactones. This conversion proceeds almost quantitatively. Therefore, it can be seen that the production of the diastereomer itself is very important and indispensable for the production of optically active δ-lactones.
[0028]
The cyclization reaction can be carried out using a two-layer solvent of water or a mixture of water and an organic solvent. Examples of the organic solvent include aliphatic hydrocarbons such as pentane, cyclopentane, hexane, cyclohexane, octane, and decalin; and aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, cumene, and methylnaphthalene. Alcohols, for example, methanol, ethanol, n-propanol, ethylene glycol and the like are used, and among them, aromatic hydrocarbons and alcohols are preferable. The amount of the solvent used is such that water is 0.1 to 50 times by weight, more preferably 1 to 20 times by weight with respect to the amides, and the organic solvent is 0 to 50 times by weight with respect to the amides, more preferably. Is 0 to 10 times by weight.
[0029]
In the cyclization reaction, a hydrolysis treatment may be performed first, and then the cyclization reaction may be performed using a sulfonic acid, or the cyclization reaction may be directly performed using an acid.
As the acid used for the hydrolysis and the acid used for the direct cyclization reaction, an inorganic acid is preferable, and examples thereof include hydrochloric acid, sulfuric acid, and nitric acid. The use amount of these acids is 1.2 to 20 equivalents, more preferably 2 to 10 equivalents, based on the amides.
[0030]
The reaction temperature may be 40 to 120 ° C, preferably 80 to 110 ° C, and the reaction time may be 0.5 to 24 hours, and may be 4 to 10 hours under preferable conditions.
In the method using sulfonic acid after hydrolysis, aromatic sulfonic acids such as benzenesulfonic acid and toluenesulfonic acid are preferably used.
After completion of the cyclization reaction, the organic phase and the aqueous phase are separated, and then (1) the organic phase is directly distilled and purified to obtain the desired product. Or (2) washing the organic phase with a weak alkaline aqueous solution, neutralizing and washing with water, and then purifying and distilling the lactone from the organic layer.
[0031]
By the method as described above, the intended δ-lactone having desired optical activity can be obtained with very high optical purity and yield.
Then, an example is shown next and the present invention is explained in more detail.
[0032]
【Example】
Example 1
<1> Synthesis of amide
1.39 g (11.5 mmol) of (-)-1-phenylethylamine and 6 ml of dry benzene were added to 1.70 g (10.0 mmol) of (±) -δ-decalactone, and the mixture was stirred at 95 ° C for 3 hours. Next, 15 ml of 1M hydrochloric acid was added, and the mixture was extracted with benzene. After drying the organic layer, the solvent was distilled off under reduced pressure to obtain 2.76 g (9.47 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. The yield was 94.7%, the melting point was 69 to 75 ° C, and the specific rotation was as follows.
[0033]
[Α]₄₃₅-139.8 ° (c1.1, MeOH)
[Α]_D    -61.7 ° (c1.1, MeOH)
<2> Purification of amide
1.11 g (3.82 mmol) of the crude crystals were recrystallized from 8.7 ml of n-hexane and ethyl acetate (5: 1) to give 710 mg of N- (1-phenylethyl) -5-hydroxydecanoic acid amide (2 mg). .45 mmol). When 210 mg (0.71 mmol) of this was recrystallized with 8.5 ml of n-hexane and ethyl acetate (2: 1), 110 mg (0.38 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide was obtained. ) Got. The crystals were further recrystallized from 6.7 ml of n-hexane and ethyl acetate (4: 3) to obtain 80 mg (0.27 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. The conversion yield was 46.2% when one enantiomer contained in the used raw material was 100%. Further, the melting point was 105 to 107 ° C. and the specific rotation was as follows.
[0034]
[Α]₄₃₅-176.2 ° (c1.0, MeOH)
[Α]_D    -77.1 ° (c1.0, MeOH)
<3> Diastereomer excess assay
When this N- (1-phenylethyl) -5-hydroxydecanoic acid amide was analyzed by high performance liquid chromatography (HPLC), its diastereomer excess was 98.9% d. e. Met.
[0035]
HPLC conditions were as follows.
Column: wakosil 5 SIL (4.6 mm x 250 mm)
Mobile phase: 75% ethyl acetate / n-hexane
Flow rate: 1 ml / min
Detection wavelength: 254 nm
This N- (1-phenylethyl) -5-hydroxydecanoic acid amide¹The measurement results of H-NMR and IR were as follows.
[0036]
[Table 2]
[0037]
Example 2
To 1.70 g (10.0 mmol) of (±) -δ-decalactone, 1.21 g (10.0 mmol) of (-)-1-phenylethylamine and 5.5 ml of dry toluene were added, and the mixture was stirred at 95 ° C for 3 hours. Next, the mixture was gradually cooled to 50 ° C., and seed crystals were added. The precipitate was allowed to stand overnight at room temperature, and the precipitated crude crystals were collected by filtration to obtain 2.21 g (7.58 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. Yield 75.8%, m.p. p. 85-93 ° C, the specific rotation was as follows.
[0038]
[Α]₄₃₅-140.4 ° (c1.0, MeOH)
[Α]_D    -61.9 ° (c1.0, MeOH)
When 0.79 g (2.71 mmol) of this amide was recrystallized from 9.4 ml of toluene, 0.36 g (1.25 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide was obtained. Further, 0.21 g (0.72 mmol) of this amide was recrystallized from 4.0 ml of toluene to obtain 0.16 g (0.54 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. The conversion yield was 52.4% when one enantiomer contained in the used raw material was 100%. Further, the melting point was 102 to 105 ° C and the specific rotation was as follows.
[0039]
[Α]₄₃₅-174.6 ° (c1.0, MeOH)
[Α]_D    -78.9 ° (c1.0, MeOH)
This N- (phenylethyl) -5-hydroxydecanoic acid amide was analyzed by HPLC in the same manner as in Example 1, and the diastereomer excess was 94.9% d. e. Met.
Example 3
3.64 g (30 mmol) of (+)-1-phenylethylamine and 18 ml of dry toluene were added to 4.68 g (30 mmol) of (±) -δ-nonalactone, and the mixture was stirred at 95 ° C for 5 hours. Then, the solvent was distilled off under reduced pressure to obtain 8.01 g of crude crystals. When 7.44 g of the crude crystals were recrystallized from ethyl acetate and 80 ml of n-hexane (1: 1), 2.86 g (10.3 mmol) of N- (1-phenylethyl) -5-hydroxynonanoic acid amide was obtained. Was.
[0040]
When 2.47 g (8.9 mmol) of this was recrystallized from ethyl acetate and 30 ml of n-hexane (2: 1), 1.12 g of N- (1-phenylethyl) -5-hydroxynonanoic acid amide was obtained. .0 mmol). Further, 1.0 g (3.6 mmol) of the crystals were recrystallized from ethyl acetate and 18 ml of n-hexane (7: 2) to give 0.71 g (2%) of N- (1-phenylethyl) -5-hydroxynonanoic acid amide. 0.6 mmol). The conversion yield was 23.8% when one enantiomer contained in the used raw material was 100%. The melting point was 102 to 103 ° C, and the specific rotation was as follows.
[0041]
[Α]_D ²⁰= + 88.34 ° (c 0.07, CHCl₃)
This N- (1-phenylethyl) -5-hydroxynonanoic acid amide¹H-NMR and IR measurement results were as follows.
[0042]
[Table 3]
[0043]
Example 4
In the same manner as in Example 3, amides were synthesized from δ-undecalactone, δ-dodecalactone, and δ-octalactone, and the improvement in purity by the number of recrystallizations was evaluated by changing the recrystallization solvent. Table 4 shows the results. For comparison, the results for the case of γ-lactone are also shown.
[0044]
It has been confirmed that the effectiveness of the method of the present invention and the repetition of recrystallization are effective for further improving the purity.
[0045]
[Table 4]
[0046]
Example 5
Regarding the production of amides from decalactone and dodecalactone of the present invention, the relationship between the optical resolving agent, the solvent for fractionation (re) crystallization and the number thereof was evaluated. Table 5 shows the results.
For comparison, a case where a resolving agent other than the optically active 1-phenylethylamine of the present invention was used is also shown. It can be seen that the resolving agent according to the present invention exhibits extremely excellent effects in the yield and diastereomeric excess.
[0047]
[Table 5]
[0048]
Example 6
Diastereomeric excess 63.9% d. e. After adding 2.5 ml of 95% ethanol and 0.5 ml of 6M hydrochloric acid to 0.25 g (0.84 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid, and stirring at 90 ° C. for 5 hours, the pressure was reduced. The solvent was distilled off underneath. Then, 3 ml of distilled water was added and extracted with ether. After the organic layer was distilled off under reduced pressure, 1 ml of 2M sodium hydroxide was added, and the mixture was stirred at 95 ° C. for 2 hours. Thereto, 2M hydrochloric acid was added until the solvent became Congo Red, and the mixture was extracted with ether. After drying this ether solution, the solvent was distilled off under reduced pressure, a small amount of p-toluenesulfonic acid and 1 ml of benzene were added, and the mixture was heated under reflux for 1 hour. After washing with a 5% aqueous sodium hydrogencarbonate solution and saturated saline and drying the organic layer, the solvent was distilled off under reduced pressure. 0.13 g of (+)-δ-decalactone (0.78 mmol, yield 92.9%) ) Got. This was distilled in a Kugelrohr to obtain 0.11 g (0.63 mmol, yield: 75.0%) of (+)-δ-decalactone. The specific rotation was as follows.
[0049]
[Α]₄₃₅+ 76.3 ° (c1.0, THF)
[Α]_D  + 37.4 ° (c1.0, THF)
When this δ-decalactone was analyzed by high performance liquid chromatography (HPLC), the enantiomeric excess (ee) was 64.0% ee. e. Met.
HPLC conditions are as follows.
[0050]
Column: CHIRALCEL OB-H (manufactured by Daicel) 4.6 mmΦ × 250 mm
Developing solvent: 4% 2-propanol / n-hexane
Flow rate: 0.5 ml / min
Detection wavelength: 220 nm
Example 7
Diastereomer excess 98.2% d. e. To 1.47 g (5.04 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic amide was added 15 ml of 95% ethanol and 3.0 ml of 6M hydrochloric acid, and the mixture was stirred at 90 ° C. for 5 hours and then under reduced pressure. The solvent was distilled off. Then, 8 ml of distilled water was added and extracted with ether. After the organic layer was distilled off under reduced pressure, 4 ml of 2M sodium hydroxide was added, and the mixture was stirred at 95 ° C. for 2 hours. Thereto, 2M hydrochloric acid was added until the solvent became Congo Red, and the mixture was extracted with ether. After drying the ether solution, the solvent was distilled off under reduced pressure, a small amount of p-toluenesulfonic acid and 5 ml of benzene were added, and the mixture was heated under reflux for 1 hour. After washing with a 5% aqueous sodium hydrogencarbonate solution and saturated saline, drying the organic layer and distilling off the solvent under reduced pressure, 0.80 g of (+)-δ-decalactone (4.68 mmol, 92.9% yield). ) Got. This was distilled in a Kugelrohr to obtain 0.71 g (4.19 mmol, yield: 83.1%) of (+)-δ-decalactone. The specific rotation was as follows.
[0051]
[Α]₄₃₅+ 113.9 ° (c 1.79, THF)
[Α]_D    + 56.7 ° (c 1.79, THF)
When this δ-decalactone was analyzed by high performance liquid chromatography (HPLC), the enantiomeric excess (ee) was 98.1% ee. e. Met.
HPLC conditions are as follows.
[0052]
Column: CHIRALCEL OB-H (manufactured by Daicel) 4.6 mmΦ × 250 mm
Developing solvent: 4% 2-propanol / n-hexane
Flow rate: 0.5 ml / min
Detection wavelength: 220 nm
Example 8
20 ml of 1N hydrochloric acid was added to 1.02 g (3.50 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide having a diastereomeric excess (98.2% de), and the mixture was heated at 101 ° C. After stirring for 6 hours, ether extraction was performed. The organic layer was washed with a 5% aqueous solution of sodium hydrogen carbonate and saturated saline, and the organic layer was dried over magnesium sulfate and the solvent was distilled off under reduced pressure. As a result, 0.53 g of (+)-δ-decalactone was obtained (3.12 mmol). , Yield 89.1%). This was distilled in a Kugelrohr to obtain 0.49 g (2.88 mmol, yield: 82.3%) of (+)-δ-decalactone.
[0053]
The specific rotation was as follows.
[Α]_D= + 57.1 ° (c 0.53, CHCl₃)
When this δ-decalactone was analyzed by high performance liquid chromatography (HPLC), the enantiomeric excess (ee) was 98.3% ee. e. Met.
HPLC conditions are as follows.
[0054]
Column: CHIRALCEL OB-H (manufactured by Daicel) 4.6 mmΦ × 250 mm
Developing solvent: 4% 2-propanol / n-hexane
Flow rate: 1.0 ml / min
Detection wavelength: 220 nm
Example 9
Diastereomer excess obtained in Example 3 99.0% d. e. To 0.50 g (1.80 mmol) of N- (1-phenylethyl) -5-hydroxynonanoic acid amide was added 8.5 ml of 2N hydrochloric acid and 2 ml of toluene, and the mixture was stirred at 102 ° C. for 5 hours, and then the organic layer was separated. did. The organic layer was washed with a 5% aqueous sodium hydrogen carbonate solution and saturated saline, and the organic layer was dried over magnesium sulfate and the solvent was distilled off under reduced pressure. As a result, 0.26 g (1.67 mmol) of (-)-δ-nonalactone was obtained. , Yield 92.6%). This was distilled in a Kugelrohr to obtain 0.24 g (1.54 mmol, yield: 85.6%) of (-)-δ-nonalactone. The specific rotation was as follows.
[0055]
[Α]_D ²⁰= -50.8 ° (c0.50, CHCl₃)
When this δ-nonalactone was analyzed by high performance liquid chromatography (HPLC), the enantiomeric excess (ee) was 99.1%. HPLC conditions were the same as in Example 8.
Example 10
In Example 2, the solvent was removed from the first recrystallization solution of the crude crystals obtained by the reaction under reduced pressure to give 0.40 g (1.44 mmol) of N- (phenylethyl) -5-hydroxydecanoic acid amide. Obtained. The diastereomeric excess of this amide is 49.3% d. e. Met.
[0056]
After adding 8 ml of 2N hydrochloric acid and 2 ml of toluene to the amide and stirring at 102 ° C. for 6 hours, the organic layer was separated, and the organic layer was washed with a 5% aqueous sodium hydrogen carbonate solution and saturated saline, and the organic layer was sulfuric acid. After drying with magnesium, the solvent was distilled off under reduced pressure to obtain 0.23 g (1.35 mmol, yield: 93.8%) of δ-decalactone. The enantiomeric excess (ee) of this δ-decalactone is 50.1% ee. e. Met.
[0057]
0.17 g (1.40 mmol) of (+)-1-phenylethylamine and 3 ml of dry toluene were added to the δ-decalactone, and the mixture was stirred at 95 ° C. for 3 hours. Next, the mixture was gradually cooled to 50 ° C., and seed crystals were added. The resulting crystals were allowed to stand at room temperature overnight, and the precipitated crystals were separated by filtration to obtain 0.37 g (1.27 mmol, yield: 94.1%) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. The diastereomeric excess of this amide is 57.3% d. e. Met.
[0058]
The amide was recrystallized twice with toluene to give 0.12 g (0.41 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. The diastereomeric excess of this amide was 57. 3% de.
After adding 2 ml of 2N hydrochloric acid and 1 ml of toluene to the amide and stirring at 102 ° C. for 6 hours, the organic layer was separated, and the organic layer was washed with a 5% aqueous sodium hydrogen carbonate solution and saturated saline, and the organic layer was sulfuric acid. After drying with magnesium, the solvent was distilled off under reduced pressure to obtain 0.06 g (0.35 mmol, yield: 85.4%) of (-)-δ-decalactone. This was purified by thin-layer chromatography to obtain 0.05 g (0.29 mmol) of (-)-δ-decalactone. The specific rotation was as follows.
[0059]
[Α]_D= -56.8 ° (c0.30, THF)
When this δ-decalactone was analyzed by high performance liquid chromatography (HPLC), the enantiomeric excess (ee) was 98.9% ee. e. Met. HPLC conditions were the same as in Example 6.
Example 11
0.541 g (4.5 mmol) of (+)-1-phenylethylamine and 1.5 ml of dry benzene were added to 0.506 g (3.0 mmol) of (+)-δ-decalactone, and the mixture was stirred at 95 ° C. for 3 hours. Next, 3.5 ml of 1M hydrochloric acid was added, and the mixture was extracted with ethyl acetate. After drying the organic layer, the solvent was distilled off under reduced pressure to obtain 0.822 g (2.8 mmol) of N- (1-phenylethyl) -5-hydroxydecanoic acid amide. The yield was 93.3%, the melting point was 79 to 81 ° C, and the specific rotation was as follows.
[0060]
[Α]₄₃₅ ²²= + 154.2 ° (c1.0, MeOH)
[Α]_D ²⁵  = + 69.0 ° (c1.0, MeOH)
This N- (1-phenylethyl) -5-hydroxydecanoic acid amide¹The measurement results of H-NMR and IR were as follows.
[0061]
[Table 6]
[0062]
【The invention's effect】
As described in detail above, the description of this application makes it possible to selectively produce optically active saturated δ-lactones useful in various fields such as cosmetics, food preparation flavors, synthetic flower essential oils, medicines, and chemicals with high efficiency. Become. The diastereomeric hydroxycarboxylic acid amide of the present invention is an indispensable intermediate for that purpose, and is also useful as a raw material and an intermediate for other various fields.

Claims (8)

The following formula (I)
(R represents a straight-chain hydrocarbon group having 3 to 7 carbon atoms) represented by the following formula (II):
Reacting with an optically active 1-phenylethylamine represented by the following formula (III):
(R is the same as defined above). The method for producing diastereomeric hydroxycarboxylic acid amides according to claim 1, wherein the reaction temperature is 20 to 180 ° C. The method for producing diastereomeric hydroxycarboxylic acid amides according to claim 1 or 2, wherein an aromatic hydrocarbon is used as a solvent. The following equation (1) obtained by the method according to claim 1 III )
(R represents a straight-chain hydrocarbon group having 3 to 7 carbon atoms). The following formula (III)
(R is a straight-chain hydrocarbon a group of 3 to 7 carbon atoms) optically active diastereomer hydroxycarboxylic acid amides, characterized by recrystallizing purifying diastereomers hydroxycarboxylic acid amides represented by Manufacturing method.   Optically active diastereomeric hydroxycarboxylic acid amides obtained by the method of claim 5.   The following expression ( III )
(R represents a straight-chain hydrocarbon group having 3 to 7 carbon atoms) is hydrolyzed, and then subjected to a cyclization reaction in the presence of sulfonic acid to obtain the following formula: (I)
(R is the same as described above).   The following expression ( III )
(R represents a straight-chain hydrocarbon group having 3 to 7 carbon atoms).
(R is the same as described above).