JPH1084989A - Production of optically active alpha-ionone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To profitably obtain the subject compound useful as a raw material for compounded perfumes by bringing optically active 3-(2,6,6-trimethyl-2- cyclohexen-1-yl)-acrylonitrile into contact with methyl lithium. SOLUTION: This method for producing optically active α-ionone of formula V comprises treating racemic 2,4,4-trimethyl-2-cyclohexene-1-ol compound of formula I [R is H, a group of the formula: COR' (R' is a 1-10C alkyl which may be substituted with a halogen, an alkenyl)] with a lipase originated from Penicillium chrysogenum, reacting the obtained optically active compound of formula II [the wavy line expresses (R)-isomer or (S)-isomer] with an alkylvinylether in the presence of pivalic acid, reacting the optically active aldehyde of formula III with KCN in the presence of acetic acid, dehydrating the reaction product, and subsequently bringing the obtained optically active 3-(2,6,6-trimethyl-2-cyclohexen-1-yl)acrylonitrile of formula IV into contact with methyl lithium.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a novel process for producing an optically active α-ionone represented by the above formula (1), which is useful as a raw material for a compounded fragrance, and more specifically, is included in the above formula (1). [(1) -1] and [(1) -2]

[0002]

Embedded image

The present invention relates to a novel process for producing (R)-(+)-α-ionone and (S)-(−)-α-ionone.

[0004]

2. Description of the Related Art Racemic α-ionone has a violet-like odor and has been used for a long time as a material of a compounded fragrance. On the other hand, optically active (R)-(+)-α-ionone and (S)-(−)-α-ionone are, for example, Blac
k tea (Solvent extract), Boronia megastigma Nees (ab
solute), Raspberry fruit juice concentrate, Tobacc
o Found from extract and the like, (R)-(+)-α-ionone has a violet-like, fruit-like, raspberry-like, flower-like strong aroma and (S)-(−)-α -Ionone is known to have woody, cedarwood-like, raspberry-like, β-ionone-like flavors [Lebe
nsmittel-Untersuchung und-Forshung (1991) 192: 111 ■ 1
15]. For the synthesis method, for example, α-cyclogelanoic acid is optically resolved to obtain (R)-(+)-α-cyclogelanoic acid and (S)-(−)-α-cyclogelanoic acid (Agric. Biol. Chem., 1987, 51,1271 ■ 1275), and using this as a raw material, (R)-(+)-α-ionone and (S)-
A method for synthesizing (−)-α-ionone shown in the following process diagram is known (Helv. Chim. Acta., 1969, 52, 1729-17).
31).

[0005]

Embedded image

In the formula, a wavy line indicates an (R)-(+)-form or an (S)-(-)-form. On the other hand, structurally similar to α-ionone, for example, the following formula (A)

[0007]

Embedded image

As a method for producing racemic γ-iron represented by the following formula, a method by the same applicant as the present application is known (Japanese Patent Application Laid-Open No. 60-209562, Japanese Patent Publication No. 2-90).
No. 13). The method according to this proposal is shown in the process chart as follows.

[0009]

Embedded image

[0010]

As described above, in the process for producing optically active α-ionone, the starting material (R)-
(+)-Α-cyclogelanoic acid and (S)-(−)-α-
In order to obtain cyclogelanic acid, optical resolution of α-cyclogelanoic acid is necessary, and the optical resolution by this method is not industrial, and it is strongly desired to develop an industrial method for further improved optically active α-ionone. That is the current situation.

[0011]

Means for Solving the Problems Accordingly, the present inventors have:
In view of the above circumstances, intensive studies have been made on a method for synthesizing optically active α-ionone. As a result, the following equation (2) not described in the conventional literature

[0012]

Embedded image

[Wherein the wavy line is the (R) -form or (S)-
By contacting optically active 3- (2,6,6-trimethyl-2-cyclohexen-1-yl) -acrylonitrile with methyllithium to give the following formula (1) of the present invention.

[0014]

Embedded image

The inventors have found that the optically active α-ionone represented by the formula (where the wavy line is as defined above) can be easily and industrially synthesized with good purity and good yield, and completed the present invention. further,
The present invention was filed by the present applicant on the same filing date (name of the invention, method for producing optically active 2,4,4-trimethyl-2-cyclohexen-1-ol and esters thereof).
Equation (6)

[0016]

Embedded image

[Wherein, R represents a hydrogen atom or a -COR 'group, and R' represents a linear or branched alkyl group or alkenyl group having 1 to 10 carbon atoms which may be substituted with a halogen atom. Asymmetric hydrolysis or asymmetric esterification of a racemic 2,4,4-trimethyl-2-cyclohexen-1-ol represented by the formula (1) using a lipase produced by Penicillium chrysogenum: The following equation (5)

[0018]

Embedded image

Wherein the wavy lines have the same meanings as defined above, and optically active 2,4,4-trimethyl-2-cyclohexene-
The present inventors have found that the optically active α-ionone represented by the above formula (1) of the present invention can be industrially and advantageously synthesized through 4-steps using 1-ol as a raw material, thereby completing the present invention. In the present invention, the optically active α-ionone of the above formula (1) may be synthesized using the compound of the above formula (5) as a starting material. Accordingly, an object of the present invention is to provide a flavor that is superior to the conventionally known racemic α-ionone, and is also excellent in persistence, and is useful as a material for compounded fragrances in a wide range of applications such as various foods and beverages and cosmetics. An object of the present invention is to provide a method for producing the optically active α-ionone of the above formula (1), which has never been used as a compounded perfume material. Hereinafter, the present invention will be described in more detail.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION An embodiment of the present invention can be represented as follows when shown in a process chart.

[0021]

Embedded image

[In the formula, wavy lines and R have the same meanings as described above] The present invention will be described below sequentially according to the above process chart. The optically active 2,4,4-trimethyl-2-cyclohexen-1-ol represented by the above formula (5) of the present invention has already been filed as a novel compound which has not been described in the literature by the same applicant of the present invention (patent application). JP-A-4-278097).

In order to synthesize the compound of the formula (5), a method described in the patent specification or a patent application (name of the invention, optical activity 2,
Method for producing 4,4-trimethyl-2-cyclohexen-1-ol and esters thereof).

According to the latter method, racemic 2,4,4-trimethyl-2-cyclohexen-1-ols represented by the above formula (6) cannot be prepared using lipase produced by Penicillium chrysogenum. It can be easily produced by asymmetric hydrolysis or asymmetric esterification. Specifically, the following formula (5) -1 included in the compound of the above formula (5)

[0025]

Embedded image

(R)-(+)-2,4,4-
To synthesize trimethyl-2-cyclohexen-1-ol, the following formula (6) included in the compound of the above formula (6) is used.
-1

[0027]

Embedded image

Wherein R represents a —COR ′ group, and R ′ has 1 to 10 carbon atoms which may be substituted with a halogen atom.
Represents a linear or branched alkyl group or alkenyl group]
Can be easily produced by asymmetric hydrolysis of the racemic 2,4,4-trimethyl-2-cyclohexen-1-yl ester represented by the formula (1) using a lipase produced by Penicillium chrysogenum. This can be represented as follows when shown in a process chart.

[0029]

Embedded image

[In the formula, R 'has the same meaning as described above.] Examples of the esters of the compound of the above formula [(6) -1] include, for example, acetate, propionate, isopropionate, butyrate, Preferred examples include butyrate, valerate, isovalerate, caproate, caprylate, caprate, monochloroacetate, trichloroacetate, and methacrylate.

The reaction is carried out, for example, by adding 1 part by weight of the compound of the above formula [(6) -1] to a 0.1M phosphate buffer aqueous solution (p
H about 7) Disperse in about 5 to about 50 parts by weight, add about 500 to about 10,000 units of lipase, and vigorously stir at room temperature for about 5 to about 250 hours.

After the reaction, the reaction solution is filtered through Celite, and the solid substance is extracted several times with ether or the like. The extract is washed by a conventional method, and dried by adding a dehydrating agent such as sodium sulfate, magnesium sulfate, and calcium chloride.
For example, the compound of the formula (5) -1 can be easily obtained by purification by means such as silica gel chromatography.

The lipase used in this reaction has already been filed by the same applicant of the present invention as a patent application (Japanese Patent Application Laid-Open No. 6-141858).
Lipase, and an enzyme produced by Penicillium chrysogenum . Next, the following formula (5) -2 included in the compound of the above formula (5)

[0034]

Embedded image

(S)-(-)-2,4,4-
To synthesize trimethyl-2-cyclohexen-1-ol, the following formula (6) included in the compound of the above formula (6) is used.
-2

[0036]

Embedded image

Racemic 2,4,4-trimethyl-2-cyclohexen-1-ol represented by the following formula is asymmetrically esterified using a lipase produced by Penicillium chrysogenum, and an unreacted product represented by the following formula (5) -2 can be easily produced by isolating the compound. This reaction can be represented as follows when shown in a process chart.

[0038]

Embedded image

[Wherein, R has the same meaning as described above;
Represents an alkenyl group.] Specific examples of RCOOR 'used in this reaction include:
For example, preferred examples include vinyl acetate, vinyl propionate, vinyl butyrate, vinyl chloroacetate, vinyl methacrylate, and vinyl benzoate.

The reaction is carried out, for example, by reacting the compound 1 of the formula (6) -2.
Parts by weight was dissolved in about 10 to 20 parts by weight of the RCOOR ', and the lipase was added thereto in an amount of 500 to 10,000 un.
It is carried out by vigorously stirring at room temperature for about 10 to about 200 hours.

After the reaction, the compound is treated and purified by the same means as the compound of the above formula (5) -1 to give the compound of the formula (5)
-2 can be easily produced.

In the asymmetric hydrolysis reaction, unreacted (S)-(-)-represented by the above formula (6) -3 is used.
Esters of 2,4,4-trimethyl-2-cyclohexen-1-ol and (R)-(+)-2, represented by the above formula (6) -4 obtained by the above asymmetric esterification reaction.
Esters of 4,4-trimethyl-2-cyclohexen-1-ol are also converted to the compound of the above formula (5) -2 and the compound of the above formula (5) -1 by performing a usual chemical hydrolysis reaction. The raw material of the optically active α-ionone of the present invention can also be used.

The above equation (5) obtained as described above
One compound and the compound of the formula (5) -2 can be converted into a 3,5-dinitrobenzoate form, and the optical purity can be further increased by recrystallization using an organic solvent such as isopropyl ether.

The (R) -form or (S) -form 2, which is included in the formula (5) of the present invention obtained as described above,
To synthesize an optically active 2,6,6-trimethyl-2-cyclohexen-1-ylacetaldehyde represented by the formula (4) from 4,4, -trimethyl-2-cyclohexen-1-ol, for example, The reaction is carried out by reacting the compound of formula (5) with an alkyl vinyl ether in the presence of pivalic acid in an organic solvent or in the absence of a solvent, preferably by heating. The reaction is carried out, for example, in a closed vessel, for example, at a temperature of about 50 ° C to about 300 ° C,
More preferably, it can be performed in a temperature range of about 150 ° C to about 250 ° C. The reaction time can also be appropriately selected. For example, the reaction can be easily carried out in the range of about 0.5 hour to about 10 hours, more preferably about 1 hour to about 5 hours to easily synthesize the formula (5). it can. The above reaction is, for example,
It is preferable to carry out in an inert gas such as nitrogen gas.

In the above reaction, the amount of the alkyl vinyl ether to be used can be appropriately selected and is, for example, about 1 to about 10 mol times, more preferably about 1.2 to about 2 mol times, relative to the compound of the formula (5). Use amounts in the range of about can be exemplified. Specific examples of the alkyl vinyl ether include:
For example, methyl vinyl ether, ethyl vinyl ether, propyl vinyl ether, isopropyl vinyl ether, isobutyl vinyl ether and the like can be exemplified.

Pivalic acid is a compound that can be easily obtained on the market, and the amount of the compound used is, for example, about 0.1 to about 50% by weight based on the compound of the formula (5). Preferably, the used amount is about 10 to about 30% by weight.

When the above reaction is carried out in the presence of an organic solvent, for example, about 10
The amount can be exemplified in the range of about to about 500% by weight, more preferably about 50 to about 200% by weight. Specific examples of such an organic solvent include, for example, toluene, xylene, benzene, petroleum ether, pentane, hexane,
Organic solvents such as ether, tetrahydrofuran, dioxane and diglyme can be exemplified.

After the completion of the reaction, the reaction product is washed with, for example, an aqueous solution of sodium hydrogen carbonate, the solvent is distilled off, and the mixture is distilled under reduced pressure to obtain the optically active 2,6 represented by the formula (4). 6
-Trimethyl-2-cyclohexen-1-ylacetaldehyde can be easily obtained with high purity.

From the compound of formula (4) obtained as described above, the optically active 3- (2,6,
6-trimethyl-2-cyclohexen-1-yl) -2
The synthesis of -hydroxypropionitrile is carried out according to the above formula (4)
It can be easily carried out by contacting the compound with potassium cyanide, preferably in an organic solvent in the presence of acetic acid.

The reaction is carried out, for example, at about -30 ° C to about 100 ° C.
C, more preferably about -10C to about 50C, for example, for a reaction time of about 1 to about 5 hours. Specific examples of the organic solvent used in the reaction include, for example, methanol, ethanol,
Alcohols such as propanol can be exemplified. The amount of these organic solvents to be used is not particularly limited and may be appropriately selected. For the compound of formula (4),
For example, a usage amount of about 1 to about 30 mole times can be exemplified. Further, the amount of acetic acid to be used is, for example, about 1 to about 10 times the amount of potassium cyanide.

After completion of the reaction, the reaction mixture is extracted with, for example, an organic solvent such as ether, neutralized with an appropriate alkali, washed with water to distill off the solvent, and purified by means of, for example, distillation or column chromatography. And the compound of formula (3) can be easily produced.

Further, for example, the optically active 3- (2,6,6-trimethyl-2-cyclohexene 1-) represented by the above formula (2) can be obtained from the compound of the above formula (3) which can be obtained as described above. To synthesize yl) -acrylonitrile, for example, the compound of formula (3) is contacted with mesyl chloride (MeCl) in the presence of a base to form a mesylate of the compound of formula (3). It can be easily synthesized by bringing it into contact with lithium bromide in the presence of calcium carbonate.

Preferred examples of the base catalyst used in the above reaction include organic bases such as pyridine, piperidine, triethylamine and pyrrolidine. Preferred examples of the use amount of these base catalysts are, for example, about 1 to about 5 times the use amount of mesyl chloride.

The reaction can be carried out more preferably, for example, under a temperature condition of about -5 ° C. to about 50 ° C., for a reaction time of about 1 to about 5 hours. The mesylate of the compound of formula (3) thus formed is reacted with lithium bromide (LiBr) in dimethylformamide in the presence of calcium carbonate to form the compound of formula (2). be able to.

The amount of dimethylformamide used in this reaction is not particularly limited, but is, for example, about 10 to 100 parts by weight based on the mesylate compound. Calcium carbonate is a mesylate compound 1
It is usually used in the range of, for example, about 10 to about 50 mol per mol. The amount of lithium bromide to be used is preferably, for example, about 5 to about 20 mol per 1 mol of the mesylate compound. The reaction is about 50
The reaction is performed at a temperature of about 150 ° C. for about 2 to 20 hours.

After completion of the reaction, the desired product is extracted with a suitable organic solvent according to a conventional method, and the extract is washed and dried, and then purified by a means such as silica gel chromatography to obtain the compound of the above formula (2). Can be easily obtained.

The optically active 3- (2,6,6-trimethyl-2-cyclohexen-1-yl) -acrylonitrile of the compound of formula (2) obtained as described above is a novel compound which has not been described in the literature. Yes, it is an important synthetic intermediate of the optically active α-ionone formula (1) of the present invention.

The synthesis of the optically active α-ionone of the above formula (1) of the present invention from the compound of the above formula (2) can be easily carried out, for example, by bringing the compound of the formula (2) into contact with methyllithium. be able to.

The reaction is preferably carried out in an organic solvent, for example, an organic solvent such as ether, tetrahydrofuran or the like can be preferably used. The reaction temperature and the reaction time can be appropriately selected depending on the solvent used.
A reaction temperature of about 60 ° C to about 50 ° C and, for example, about 1 to 1
About 5 hours can be exemplified.

The amount of methyllithium used in the above reaction is preferably, for example, in the range of about 1 to about 10 mol times based on the compound of formula (2).

After completion of the reaction, for example, the product is treated with ammonium chloride, extracted with an organic solvent such as ether, washed with water, and the solvent is distilled off. The product is purified by a purification means such as distillation or column chromatography. The compound of the formula (1) of the present invention can be easily synthesized.

The optically active α-ionone of the formula (1), which can be synthesized as described above, has a natural violet-like odor which is superior to the conventionally known racemic α-ionone, and is excellent. It has a long-lasting, mild and rich naturalness, especially for various foods and beverages, cosmetics, health and
As a scent or flavor component for hygiene and pharmaceuticals, excellent durability and unique scent can be imparted.

Examples will be given below to explain the formula (1) of the present invention.
Several aspects of the production examples of the compounds will be described in more detail.

Example 1 (R)-(+)-2,4,4-trimethyl-2-cyclo
Synthesis of hexen-1-ol [Formula (5) -1] 0.1 mol of 14.6 g (80.2 mol) of 2,4,4-trimethyl-2-cyclohexenyl acetate formula [(6) -1] The mixture was dispersed in 300 ml of a phosphate buffer (pH 7.0), 14.6 g (8,000 units) of lipase produced by Penicillium chrysogenum was added, and the mixture was stirred at room temperature for 114 hours to perform enzymatic degradation. After completion of the reaction, ethyl acetate and celite were added to the reaction solution, and the mixture was stirred for a while, filtered, and the solid substance was washed with ethyl acetate, combined with the previous filtrate, concentrated, and concentrated to give the formula [(5) -1 ] And a crude product 14.0 of the formula [(6) -2] compound.
g was obtained. The crude was then purified by silica gel chromatography. As a result, the equation [(5) -1]
Compound (R)-(+)-2,4,4-trimethyl-2-
3.44 g of cyclohexen-1-ol (bp 63
６４64 ° C./3 Torr; 86.9% e. e. ) And the compound (S)-(−)-2,4,4- of the compound [(6) -2]
7.88 g of trimethyl-2-cyclohexen-1-yl acetate (bp 57 to 57.5 ° C./2 Torr; 7
3.3% e. e. ) Got. The optical purity was measured by GLC using a cyclodextrin derivative as a chiral phase.

The equation [(5) −
5] g (0.36 mol, 89.4%
e. e. ), 86 g (1.1 mol) of pyridine, 400 ml of methylene chloride and 1.0 g of DMAP are added, and while stirring, 100 g of 3,5-dinitrobenzoyl chloride is added.
(0.44 mol) was added little by little. After stirring for 3 hours at room temperature, the reaction solution was poured into ice water and extracted several times with ether. The extract was washed with a diluted hydrochloric acid aqueous solution, a sodium hydrogen carbonate aqueous solution, and a saline solution, and dried over magnesium sulfate. The ether was recovered to obtain 98 g of crude crystals. This was recrystallized from isopropyl ether to obtain 90 g of the obtained crystals.
Is hydrolyzed according to a conventional method, and purified by distillation to obtain 31 g of a pure compound of the formula [(5) -1] [b. p. 98 ~
99 ° C./28 Torr, [α] _D = + 95.0 ° (20
C), (C = 1.04; MeOH); 97% e. e. ]
I got

Example 2 (S)-(-)-2,4,4-trimethyl-2-cyclo
Synthesis of hexen-1-ol [formula (5) -2] 10 g of 2,4,4-trimethyl-2-cyclohexen-1-ol formula [(6) -2] was dissolved in 100 ml of vinyl acetate at room temperature. 10 g (6,400 units) of the same lipase used in Example 1 was added to
The mixture was stirred for 37 hours to perform an esterification reaction. After completion of the reaction, the reaction solution was extracted with chloroform, chloroform was distilled off, and the compound of the formula [(5) -2] and the formula [(6)-
4] 11 g of a crude product consisting of a mixture of compounds was obtained. Then, the crude product was purified by silica gel chromatography to obtain a compound of the formula [(5) -2] compound (S)-(-)-2,
6.5 g of 4,4-trimethyl-2-cyclohexen-1-ol [b. p. 62-64 ° C / 3 Torr; 39% e.
e. ] And the compound of formula ((6) -4] (R)-(+)-
3.5 g of 2,4,4-trimethyl-2-cyclohexenyl acetate [b. p. 61-63 ° C / 3 Torr;
2% e. e. ]was gotten.

The compound of the formula [(5) -2] obtained here was recrystallized in the same manner as in Example 1 to give 3 g of the pure compound of the formula [(5) -2] [b. p. 93-94 ° C /
22 Torr, [α] _D = −95.2 ° (20 ° C.), (C =
1.10; MeOH); 98% e. e. ] Was obtained.

Example 3 (R)-(+)-2,4,4-trimethyl-2-cyclo
Hexen-1-ylacetaldehyde Synthesis of Formula (4) (R)-(+)-2,4,4-
20 g of trimethyl-2-cyclohexen-1-ol
(0.14 mol), 21 g of ethyl vinyl ether (0.
29 mol), 3 g (29 mmol) of pivalic acid and 21 ml of toluene are stirred and stirred at 200 ° C. for 8 hours (during this time, the pressure rises to 6 kg / cm ² ).

After completion of the reaction, 500 ml of toluene was added to the reaction solution.
After washing with aqueous sodium bicarbonate, washing with brine, and drying over anhydrous magnesium sulfate. Thereafter, toluene was distilled off, and the obtained crude product was subjected to silica gel chromatography (SiO ₂ 5
00g, n-hexane: ethyl acetate = 20: 1) to obtain 15 g of the compound (R) -formula (4). Yield 60%.

Example 4 (S)-(−)-2,6,6-trimethyl-2-cyclo
Hexen-1-ylacetaldehyde (S)-(-)-2,4,4-trimethyl-2-
The procedure was performed in the same manner as in Example 1 except that cyclohexen-1-ol was used, to obtain 13 g of the (S) -formula compound of the formula (4). Yield 52%.

Example 5 (R)-(+)-3- (2,6,6-trimethyl-2-
Cyclohexen-1-yl) -2-hydroxypropio
Nitrile Synthesis of Formula (3) 12 g (72 mmol) of the (R) -formula (4) compound obtained in Example 3 in a 1 liter flask, 24 g of KCN
(0.36 mol) and 220 ml of ethanol,
Cool to 0 ° C. in an ice bath. 35 g (0.58 mol) of acetic acid is added dropwise over 10 minutes, and the mixture is stirred at 0 ° C. for 1 hour, heated to room temperature, and further stirred for 2 hours.

After completion of the reaction, the reaction solution is poured into water and extracted with ether. The organic layer was washed sequentially with an aqueous solution of sodium bicarbonate and brine,
Dry over anhydrous magnesium sulfate. The crude product obtained after concentration was subjected to silica gel chromatography (SiO ₂ 200
g, n-hexane: ethyl acetate = 20: 1) to obtain 12 g of the compound (R) -formula (3). Yield 8
5.6%.

Example 6 (S)-(-)-3- (2,6,6-trimethyl-2-
Cyclohexen-1-yl) -2-hydroxypropio
The nitrile was prepared in the same manner as in Example 5, except that the (S) -formula (4) compound obtained in Example 4 was used as the synthesis raw material of the formula (3), and the (S) -formula (3) compound Was obtained in 11.2 g. Yield 80%.

Example 7 (R)-(+)-3- (2,6,6-trimethyl-2-
Cyclohexen-1-yl) -acrylonitrile formula
Synthesis of (2) 10 g (52 mmol) of the compound (R) -formula (3) obtained in Example 5 in a 500 ml flask and pyridine 23
After charging 0 ml and cooling to 0 ° C. in an ice bath, 17.8 g (0.16 mol) of methanesulfonyl chloride is added. 0 ° C
After stirring for 3 hours, the reaction mixture was poured into water and extracted with ether.
The ether layer is washed three times with an aqueous solution of copper sulfate, and then washed sequentially with water, an aqueous solution of sodium bicarbonate and brine. , Dried over anhydrous magnesium sulfate and concentrated to obtain 12 g of a crude product. 800 ml of dimethylformamide, 100 g of CaCO ₃ , L
Add 45 g of iBr and stir at 100 ° C. for 9 hours. After cooling, the reaction solution is filtered, and the filtrate is diluted with water and extracted with ether. The ether layer was washed successively with a 2N aqueous hydrochloric acid solution, an aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated, and the crude product obtained was subjected to silica gel chromatography (S
iO ₂ 200 g, n-hexane: ethyl acetate = 20:
Purified by 1) to give the (R) -form of the compound of formula (2) 3.4
g was obtained. Yield 37.4%.

Example 8 (S)-(-)-3- (2,6,6-trimethyl-2-
Cyclohexen-1-yl) -acrylonitrile formula
Example 7 was repeated except that the (S) -formula (3) compound obtained in Example 6 was used as the synthesis raw material of (2). 0.4 g was obtained. Yield 70%.

Example 9 Synthesis of (R)-(+)-α-ionone Formula (1) 3 g (17 mmol) of the compound (R) -formula (2) obtained in Example 7 was placed in a 500 ml flask. Ether 100
ml and cool to -60 ° C. In this solution:
31 ml (43 mmol) of a 4M MeLi / ether solution is added, and the mixture is stirred at the same temperature for 2 hours and then at 0 ° C. for 1 hour.

The reaction solution is poured into a cooled aqueous solution of ammonium chloride, and the solution which is kept stirring for 12 hours is separated. The organic layer is washed successively with an aqueous solution of sodium bicarbonate and brine, and dried over anhydrous magnesium acetate sulfate. The crude product obtained by concentration was purified by silica gel chromatography (SiO ₂ 60 g, n-hexane: ethyl acetate = 20: 1) to give (R)-
1.1 g of (+)-α-ionone was obtained. Yield 33.7
%. The optical purity was measured by GLC using cyclodextrin as a chiral phase and found to be 98.5% e.g. e. Met. [Α] _D = + 423.9 ° (20 ° C.), (C = 0.9
7; CHCl ₃ )

Example 10 (S)-(-)-α-ionone Example 9 was repeated except that the (S) -formula (2) compound obtained in Example 8 was used as a raw material for the synthesis of the formula (1). (S)-(-)-
1.2 g of α-ionone was obtained. Yield 36.8%. Optical purity is GLC using cyclodextrin as chiral phase
98.2% e. e. Met. [Α] _D = −412.6 ° (20 ° C.), (C = 0.9
4: CHCl ₃ )

[0079]

According to the present invention, an optically active α-ionone which is superior in aroma and sustainability to the known racemic α-ionone and which has never been used as a compounded fragrance, is industrially produced. A novel production method which can be advantageously synthesized is provided.

Claims (3)

[Claims] [Claim 1] The following formula (2) [Wherein the wavy line represents the (R) -form or the (S) -form], the optically active 3- (2,6,6-trimethyl-2-)
(Cyclohexen-1-yl) -acrylonitrile is brought into contact with methyllithium, wherein the compound is represented by the following formula (1): [Wherein the wavy line has the same meaning as in the formula (2)]
-The preparation of ionone. 2. The following formula (6): [Wherein, R represents a hydrogen atom or a —COR ′ group;
R 'has 1 carbon atom which may be substituted by a halogen atom;
Represents 10 to 10 linear or branched alkyl groups or alkenyl groups].
The following formula (5) obtained by asymmetric hydrolysis or asymmetric esterification of 2-cyclohexen-1-ols using a lipase produced by Penicillium chrysogenum. [Wherein the wavy line represents the (R) -form or the (S) -form], the optically active 2,4,4-trimethyl-2-cyclohexen-1-ol is alkylated in the presence of pivalic acid. By reacting with vinyl ether, the following formula (4) [Wherein the wavy line has the same meaning as in formula (5)] to form an optically active 2,6,6-trimethyl-2-cyclohexen-1-ylacetaldehyde represented by the formula (5). By contacting the reaction with potassium cyanide below, the following formula (3) is obtained. [Wherein the wavy line has the same meaning as in formula (5)]
-(2,6,6-trimethyl-2-cyclohexene-1
-Yl) -2-hydroxypropionitrile, the compound of formula (3) is contacted with mesyl chloride (MsCl) in the presence of a base, and then the product is converted to lithium bromide (LiBr) in the presence of calcium carbonate. ) To give the following formula (2): [Wherein the wavy line has the same meaning as in formula (5)]
-(2,6,6-trimethyl-2-cyclohexene-1
-Yl) -acrylonitrile, the compound of formula (2)
A compound represented by the following formula (1), wherein the compound is brought into contact with methyllithium: [Wherein the wavy line is synonymous with the formula (5)]
-The preparation of ionone. 3. The following formula (5): [Wherein the wavy line represents the (R) -form or the (S) -form], the optically active 2,4,4-trimethyl-2-cyclohexen-1-ol is alkylated in the presence of pivalic acid. By reacting with vinyl ether, the following formula (4) [Wherein the wavy line has the same meaning as in formula (5)] to form an optically active 2,6,6-trimethyl-2-cyclohexen-1-ylacetaldehyde represented by the formula (5). By contact reaction with potassium cyanide below, the following formula (3) [Wherein the wavy line has the same meaning as in formula (5)]
-(2,6,6-trimethyl-2-cyclohexene-1
-Yl) -2-hydroxypropionitrile, the compound of formula (3) is contacted with mesyl chloride (MsCl) in the presence of a base, and then the product is converted to lithium bromide (LiBr) in the presence of calcium carbonate. ) To give the following formula (2): [Wherein the wavy line has the same meaning as in formula (5)]
-(2,6,6-trimethyl-2-cyclohexene-1
-Yl) -acrylonitrile, the compound of formula (2)
Contacting the compound with methyllithium; [Wherein the wavy line is synonymous with the formula (5)]
-The preparation of ionone.