JP2545289B2 - Method for producing γ-ionones - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing γ-ionones, more specifically, the following formula (B): However, in the formula, R ¹ , R ² and R ³ represent hydrogen or a lower alkyl group, and X represents a halogen atom, and halogen-containing cyclohexane represented by the following formula is used in the presence of an alkali metal salt of a lower fatty acid in an organic solvent. The following formula (A) characterized by reducing However, in the formula, R ¹ , R ² and R ³ have the same meanings as described above, and relate to a method for producing a γ-ionone.

[Prior Art] The synthesis of γ-ionones represented by γ-ionone, γ-methylionone and γ-iron has been carried out through a very multi-step process, and an industrially practical production method has not yet been established. Not not.

Conventionally, some proposals have been made regarding the production of γ-ionone, but γ-ionone could not be selectively obtained in high purity and high yield. For example, Helv.Chim.Act
a., Vol. 41, p. 1395 (1958), describes a method of synthesizing from γ-cyclocitral as shown in the following process chart.

According to this proposal, the starting material 2-carbalkoxy-3,3
[Gamma] -cyclocitral was synthesized from -dimethylsiclehexan-1-one through multiple steps to obtain [gamma] -ionone. The γ-ionone obtained by this proposal has a drawback that isomers of α-ionone are formed together, the production rate of γ-ionone is only 10 to 15%, and the rest is α-form, It is not possible to selectively obtain γ-ionone. Further, there are disadvantages and drawbacks such that it is extremely difficult to separate and obtain only the γ-form from the above mixture.

Further, the present applicant has previously described that 1- (3,3-dimethyl-1-cyclohexen-1-yl) methyl alcohol represented by the following formula (5), which is easy to synthesize by itself, is added to an organic solvent in the presence of a base. Below, 1- (3,3-dimethyl-1-cyclohexen-1-yl) methylene halide represented by the formula (4), which can be formed by reacting with a halogenating agent, in an organic solvent,
2 represented by formula (3) obtained by reacting with N, N-dilower alkylene-aminoacetonitrile in the presence of a base
-(2-methylene-6,6-dimethylcyclohexane-1
-Yl) -N, N-dialkylacetonitrile is subjected to catalytic reaction with an organic acid to obtain a γ represented by the formula (2).
-Easily converted to cyclocitral, and then catalytically reacting γ-cyclocitral of formula (2) with acetylidenetriphenylphosphorane to give γ-iono in good purity and without isomer formation. A method for synthesizing in good yield has been proposed (JP-A-62-51664). The reaction process diagram is as follows.

On the other hand, the following general formula Where the dotted line is defined by either a carbon-carbon-heavy bond or a carbon-carbon double bond; R ¹ , R ² and R ³ are the same or different from each other and each represent hydrogen or a methyl group. A substituted cyclohexene derivative having the formula HO
-X, where X is halogen, having the following general formula comprising reacting with a hypohalous acid having Where the dotted line is either a carbon-carbon-heavy bond or a carbon-carbon double bond; R ¹ , R ² and R ³ are the same or different from each other and each represent hydrogen or a methyl group, X
Represents a halogen, and a method for producing a halogen-substituted cyclohexane compound defined by and a composition containing the compound have been proposed (JP-A-57-500433).

Further, the halogen-substituted cyclohexane compound is reacted with a reagent capable of causing intramolecular cyclization of the halogen-containing cyclohexane compound in the presence of a non-proton donating solvent, and the following structure Here, R is a portion derived from the reagent.

Forming a bicyclic intermediate having the following structure, and hydrolyzing the intermediate to include ambrinol useful as an Ambergris-like flavoring material Here, a method for producing a bicyclic alcohol having R 1, R 2 and R 3 each is hydrogen or methyl is disclosed (Japanese Patent Publication No. 57-501082).

[Problems to be Solved by the Invention] Ionones and irons are violet-like or natural iris oil-like odors and are extremely important and expensive substances as fragrances.

However, as described above, these γ-ionones,
In particular, cis-γ-ionone is complicated in the production method and has not been produced on an industrial scale.

[Means for Solving the Problems] The present inventors have earnestly studied a method for industrially synthesizing γ-ionones in a short process.

As a result, the following formula (B), which is easily synthesized from α-ionones using hypohalous acid: However, in the formula, R ¹ , R ² and R ³ represent hydrogen or a lower alkyl group, and X represents a halogen atom, and a halogen-containing cyclohexane represented by the following formula is used in the presence of a lower fatty acid alkali metal salt in an organic solvent. , Fe, Co and Sn with reducing ability
By reducing with a metal such as the following formula (A) with ease and good yield in one step However, it was discovered that in the formula, R ¹ , R ² and R ³ have the same meaning as described above, and a γ-ionone represented by the following formula can be selectively synthesized. Especially from cis-α-irons to trans-
It was discovered that only cis-γ-irons can be industrially advantageously produced selectively through a completely new synthetic route that does not involve the production of γ-irons.

Further, the γ-ionones belonging to the formula (A) are conventionally known, for example, α-ionone, β-ionone, α-ionone.
Compared to the aroma and flavor exhibited by methylionone, β-methylionone, α-iron and β-iron, etc., it has a particularly excellent aroma and flavor, and also has an excellent sustainability, especially cis-
γ-iron had very good aroma and flavor characteristics.

Furthermore, the compound of the formula (A) is well harmonized with various natural flavors and synthetic flavors, and is mixed in flavor compositions such as wood-based, flower-based, green-based, fruit-based, musk-based and citrus-based flavors. As a result, it was found that it is a particularly useful compound that can be used as an excellent and persistent aroma and flavor imparting or modulating agent.

Therefore, an object of the present invention is to provide a novel method for producing the γ-ionone of the above formula (A).

The formula (A) γ-ionone of the present invention can be industrially advantageously produced, for example, as shown in the following reaction step.

Specific examples of the compound of the formula (A) include, for example,
Examples include (A-1) γ-ionone, (A-2) γ-methylionone, and (A-3) cis-γ-iron.

The production method of the compound of formula (A) will be described in more detail by taking the above embodiment as an example.

The halogen-containing cyclohexane of the above formula (B) can be easily synthesized by reacting the substituted cyclohexene compound with hypohalous acid by the known method as described above.

Further, the synthesis of the γ-ionone of the formula (A) is carried out by using the halogen-containing cyclohexane of the above formula (B), preferably in an organic solvent in the presence of a lower fatty acid alkali metal salt, Zn, Fe
It can be easily performed by reducing with a metal such as.

The reaction is, for example, under a temperature condition of about 0 to 100 ° C,
For example, it can be preferably carried out with a reaction time of about 0.5 to 10 hours. Specific examples of the organic solvent used in the reaction include, for example, alcohols such as methanol, ethanol and propanol, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as ethyl ether and THF and any of these. Mention may be made of mixtures. The amount of these organic solvents used is not particularly limited and may be appropriately selected.
A preferable range is about 50 times the weight.

Further, the catalyst used for the reduction reaction, for example, Zn, C
Preferable examples include o, Fe, Ni, Sn and the like. The amount of these catalysts used may be, for example, about 0.5 to 50 mol based on the compound of the formula (B).

Furthermore, examples of the lower fatty acid alkali metal salt used in the reaction include C _{1 to} C ₅ such as formic acid, acetic acid, propionic acid, etc.
Alkali metal salts such as sodium and potassium of lower fatty acids to a certain extent can be mentioned.

The amount of such an alkali metal salt of a lower fatty acid used may be, for example, about 0.5 to 5 mol based on the compound of the formula (B).

The reaction can be preferably carried out, for example, under a temperature condition of about 0 to 100 ° C. and for a reaction time of about 0.5 to 10 hours. After completion of the reaction, the compound of formula (A) can be easily synthesized by extraction, washing, drying and solvent recovery by a conventional method, and using a means such as column chromatography, distillation and the like.

The above-mentioned formula (A-1) γ-ionone that can be synthesized as described above is α or β whose aroma characteristics have been known so far.
-Having a more characteristic wood-like, grass-like violet-like aroma and flavor compared to ionone, and having the formula (A-2)
γ-Methylionone showed a more powerful and gorgeous flower-like aroma. Further, the formula (A-3) (±) -cis-γ-iron is extremely useful as a persistent aroma and flavor imparting or modulating agent, has a natural iris-like aroma or flavor, and has excellent sustainability. However, there is a mild and rich naturalness,
These γ-forms are particularly useful for various foods, cosmetics, insurance,
It has excellent persistence and unique aroma and flavor as an aroma or flavor component for hygiene and pharmaceuticals.

Hereinafter, embodiments of the present invention will be described in more detail with reference to Reference Examples and Examples.

[Example] Reference example 1: Chlorination of α-ionone with hypochlorous acid.

To a mixture of 2 l of methylene chloride, 115.2 g (0.6 mol) of α-ionone and 501 g (0.7 mol) of 10% NaOCl, 163 g of KH ₂ PO ₄ was added.
A solution of (1.2 mol) in 1000 g of water was added at 7 to 11 ° C over 1 hour, and the mixture was stirred at 10 ° C for 4 hours. 3 at room temperature
The reaction was allowed to stir for an hour to obtain 136 g of a crude product. Purification by silica gel column chromatography (hexane: ethyl acetate = 9: 1) gave 78 g (Y57%) of ionone chloride and 28 g of unreacted α-ionone (recovery rate of 24%).

Example 1: Reduction of ionone chloride with zinc.

61 g (0.2 g of purified ionone chlorinated product obtained in Reference Example 1)
7 mol) and 244 g of tetrahydrofuran, 95%
30 g under reflux conditions in a mixture of 610 g of ethanol, 35 g (0.54 mol) of zinc dust and 37 g (0.54 mol) of sodium formate.
The mixture was added in minutes and the reaction was allowed to stir for an additional 2.5 hours. After completion of the reaction, the mixture was cooled, filtered through diatomaceous earth, extracted with ether, washed with aqueous sodium hydrogen carbonate solution and water, dried over magnesium sulfate, and then the solvent was recovered to obtain 57 g of a crude product. As a result of analyzing this crude product by gas chromatography, γ
-Ionone 56%, α-ionone 17%, and other 25%. This crude product is subjected to precision distillation under reduced pressure to a boiling point of 127.
35 g (Y68%) of .gamma.-methylionone at .about.128 DEG C./2 mmHg was obtained.

Example 2: Reduction of α-methylionone chloride with zinc.

Chlorinated product of α-methylionone (α-iso-methylionone 65%: α-n-methylionone 20%) 44 g (0.1
8 mol) and THF 172 g, a mixed solution of sodium acetate 31 g,
The mixture was added dropwise to a mixture of 25 g of zinc dust and 95% ethanol under the reflux condition of ethanol for 30 minutes, and then stirred at the same temperature for 3 hours. After cooling, it was filtered and washed in the same manner as in Example 1, purified by column chromatography and then rectified to obtain 27 g of γ-methylionone having a boiling point of 128 to 130 ° C./2 mmHg. Gas chromatographic analysis of this mixture showed that γ-iso-methylionone 5
It was 0% and γ-n-methylionone was 15%.

Example 3: Reduction of cis-α-iron chloride with zinc.

A solution of 6 g of chlorinated cis-α-iron (cis content 95%) in 24 g of toluene was added to 3.4 g of sodium formate,
The mixture was added to a mixture of 3.3 g of zinc powder and 60 g of 95% ethanol for 30 minutes under the reflux condition of ethanol. The mixture was further stirred at the same temperature for 2 hours to cause a reaction, cooled, filtered through diatomaceous earth, and extracted with ether. The extract was washed with an aqueous sodium hydrogen carbonate solution, dried over magnesium sulfate, and then the solvent was removed to obtain 5.4 g of a crude product. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 9: 1) to obtain 2.82 g of cis-γ-iron (cis-γ-form content 77%).

[Effects of the Invention] According to the method of the present invention, one step is carried out by a very simple means of reducing a halide obtained by halogenating α-ionones by a known method with zinc in the presence of an alkali salt of a lower fatty acid. The corresponding γ-ionones can be synthesized by

In particular, it is epoch-making that cis-γ-iron, which has been conventionally difficult to synthesize and produced through a number of steps, can be similarly synthesized in a single step with high purity and high yield. The utility value is extremely high.

Claims (1)

(57) [Claims] 1. The following formula (B) However, in the formula, R ¹ , R ² and R ³ represent hydrogen or a lower alkyl group, and X represents a halogen atom, and a halogen-containing cyclohexane represented by the following formula is used in the presence of a lower fatty acid alkali metal salt in an organic solvent. The following formula (A) characterized by being reduced to However, in the formula, R ¹ , R ² and R ³ have the same meanings as described above, and a method for producing a γ-ionone.