JPH0465065B2 - - Google Patents

Description

[Detailed description of the invention]

(a) Industrial Application Field The present invention relates to a novel method for producing (±)cis-γ-iron having an iris-like odor useful as a fragrance substance. More specifically, the present invention is based on the following formula (2) cis-γ-methylcyclocitral represented by the following formula in an organic solvent: The following formula (1) characterized by contacting with acetylidene triphenylphosphorane represented by The present invention relates to a method for producing (±)-cis-γ-iron represented by (b) Prior art Key aroma substances in natural iris oil include (+)-cis-α-ylon, (-)-trans-
α-Iron, (+)-β-Iron, (+)-cis-γ
-iron, (-)-cis-γ-iron, and the like are known. The presence of the above formula (1)(±)-cis-γ-yron of the present invention in natural iris oil is not known. The present applicant has previously developed the (±)-cis-
We established a method for selectively producing only γ-ilon, and also revealed that the compound of formula (1) has a characteristic of having an aroma comparable to that of natural iris oil, and we have already published Japanese Patent Application No. 59-65094. (Japanese Unexamined Patent Publication No. 60-209562) and Japanese Patent Application No. 59-217414 (Japanese Unexamined Patent Publication No. 61-97251). Also, as another suggestion,
Agric.Biol.Chem., 47(3)581-586 (1983).
(±)-trans-γ-iron and (±)-cis-γ
- It is known that irons can be formed as mixtures. Furthermore, the above formula (2) which is a raw material in the method of the present invention
The following formula (2)' is an isomer of cis-γ-methylcyclocitral From trans-γ-methylcyclocitral represented by the formula (1) in the method of the present invention, the target compound (±)- which is an isomer of cis-γ-ylon (±)-
A method of producing trans-γ-yron as shown by the following formula has been proposed (Japanese Patent Publication No. 19535/1983). (c) Problems to be solved by the invention In the above conventional proposal (Agric.Biol.Chem.), a mixture of trans- and cis-isomers is formed, and cis-
In addition to the problem of not being able to selectively form cis-isomers, the ratio of cis-isomers to trans-isomers: cis-isomers = trans-isomers: cis-isomers =
There is a disadvantage that the ratio is extremely low at 9:1. Furthermore,
There are disadvantages such as extremely complicated and multi-step operations, and further disadvantages such as the need for expensive raw materials and low yields, making it unsuitable for industrial implementation. Furthermore, according to the earlier proposal of the present inventor in the aforementioned Japanese Patent Application No. 59-65094 and Japanese Patent Application No. 59-217414, the cis-isomer of the above formula (1) can be selectively produced without producing the trans-isomer. Although it has the advantage of being able to obtain compounds,
Improvements in shortening the process are desired. Furthermore, the proposal of Japanese Patent Publication No. 59-19535 is a method for obtaining trans-form γ-ylon, but it requires an extremely low reaction temperature (-78°C) and has the drawbacks of low yield. (d) Means for Solving the Problems In order to solve the problems of the above-mentioned conventional proposals, the present inventors particularly attempted to convert cis-γ-methylcyclocitral of the above formula (2) into (1) of the above formula (1). We have been conducting research on methods for synthesizing ±)-cis-γ-iron. As a result, the above formula (2) cis-γ-methylcyclocitral was converted into acetylidene triphenylphosphorane in an organic solvent.

By contacting with [Formula], the formula (1) of the object compound of the present invention can be obtained at once.
It has been discovered that (±)-cis-γ-ylon can be synthesized easily and in good yield. This reaction can be expressed as follows in a reaction process diagram. In the above process diagram, the starting compound of formula (2) is
γ-Methylcyclocitral is a compound that was synthesized for the first time by the present inventors and has not been described in any literature.
It can be easily synthesized from (3,3,4-trimethyl-1-cyclohexen-1-yl)-methyl alcohol in three steps. The compound of formula (2) is itself a compound useful in a wide range of fields as an aroma and flavor imparting or modulating agent, and the compound of formula (2), its production method, and its use are disclosed by the same applicant dated the same date as the present application. Patent Application No. 1982-82629 (Japanese Unexamined Patent Publication No. 1983
-243035). Acetylidene triphenylphosphorane used in the reaction with cis-γ-methylcyclocitral (formula (2)) can be easily prepared by treating a phosphonium salt, which can be obtained from chloroacetone and triphenyphosphine, with an alkali. can be obtained. According to the method of the present invention, the formula (1) (±)-cis-γ-
Iron has the formula (2) cis-γ-methylcyclocitral and the acetylidene triphenylphosphorane,
It can be easily formed by contacting in an organic solvent. This reaction is carried out under appropriate temperature conditions, e.g., in a temperature range of about -30°C to about 200°C, preferably in a temperature range of about 0°C to about 150°C, and for example, about 1 to about 30°C.
Reaction times range from about 5 to about 20 hours, preferably from about 5 to about 20 hours.
The reaction can be carried out under any suitable reaction time conditions, ranging for hours. When carrying out the reaction, the amount of acetylidene triphenylphosphorane to be used can be selected and changed as appropriate, but it is, for example, about 1 to about 10 mol, more preferably about 1 to about 5 mol, based on the compound of formula (1) above. Examples include usage amounts in the range of . Examples of organic solvents include toluene, acetonitrile, tetrahydrofuran, dimethoxyethane, ether, and diglyme. The amount of these organic solvents to be used can be selected as appropriate, but for example, about 1 to about 100
An example of the range is about twice the weight, more preferably about 1 to about 20 times the weight. After the reaction is completed, the compound of formula (1) can be easily obtained in a good yield by post-treatment according to a conventional method. The formula (2) cis-γ-methylcyclocitral used in the method of the present invention is, for example, the following formula (3) However, in the formula, R' and R'' each represent a lower alkyl group, or R' and R'' together represent a lower alkylene group, and cis-2-(2-methylene-5, 6,
6-trimethylcyclohexan-1-yl)-N,
N-dialkyl or -alkylene acetonitrile can be prepared by contacting it with silver nitrate in an organic solvent. The compound of formula (3) is, for example, the compound of formula (4) below. 1-(3,3,
The following formula (4) can be formed by reacting 4-trimethyl-1-cyclohexen-1-yl) methyl alcohol with a halogenating agent, mesylating agent, or tosylating agent in an organic solvent in the presence of a base. However, in the formula, X is a halogen such as Br, Cl, I,
1-(3,3,4-trimethyl-1) representing mesyloxy group (OMs) or tosyloxy group (OTs)
-cyclohexen-1-yl) methylene halide or mesylate or tosylate can be easily obtained by reacting with N,N-dilower alkyl- or lower alkylene-aminoacetonitrile in an organic solvent in the presence of a base. An example of a synthesis example for producing cis-γ-methylcyclocitral of formula (2) according to the above embodiment can be expressed as follows in a process diagram. 1-(3,3,4-trimethyl-1 of the above formula (4)
-Cyclohexen-1-yl)-methylene halide is synthesized by adding 1-(3,3,4-trimethyl-1-cyclohexen-1-yl)-methyl alcohol of the above formula (5) to a base, preferably in an organic solvent. This can be easily carried out by reacting with a halogenating agent, mesylating agent, or tosylating agent in the presence of a halogenating agent, a mesylating agent, or a tosylating agent. The reaction can preferably be carried out, for example, at a temperature of about -78° to about +150°C, for a reaction time of about 1 to about 5 hours. Specific examples of the organic solvent used in the reaction include ethers such as ether and tetrahydrofuran. There are no particular restrictions on the amount of these organic solvents to be used, and they may be selected as appropriate;
A preferable example is a usage amount in a range of about 10 times the weight. Further, examples of the halogenating agent, mesylating agent, and tosylating agent used in the reaction include phosphorus tribromide, phosphorus trichloride, methanesulfonyl chloride, p
-Toluenesulfonyl chloride and the like can be mentioned. In the example of the process diagram above, phosphorus tribromide is used as the halogenating agent. The amount of these agents to be used can be selected and changed as appropriate, and for example, a preferable example of the amount to be used is about 1 to about 3 moles for the above formula (5). Furthermore,
Examples of the base include organic bases such as pyridine and triethylamine.
In the example of the process diagram above, pyridine is used. The amount of these bases to be used may be selected appropriately, for example, about 0.1 to about 2
Preferred amounts are in the molar range. After completion of the reaction, for example, the organic layer is subjected to post-treatment such as washing with water and neutralization, and after distilling off the solvent, it is purified using means such as distillation and column chromatography.
The compound of formula (4) can be easily obtained. For example, from the compound of formula (4) that can be obtained as described above, 2-(2
-methylene-5,6,6-trimethylcyclohexan-1-yl)-N,N-dialkyl or alkyleneaminoacetonitrile, for example, the compound of formula (4) is mixed with potassium carbonate, sodium carbonate, N,N- in the presence of a base such as lithium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, etc.
It can be easily synthesized by reacting with di-lower alkyl or lower alkylene-aminoacetonitrile. The reaction can preferably be carried out at a temperature of about -78 to about +200°C for a reaction time of about 0.5 to about 48 hours, for example. The amount of N,N-dilower alkyl or lower alkylene-aminoacetonitrile used in the above reaction is preferably in the range of, for example, about 1 to about 2 moles based on the compound of formula (4) above. I can list them. In addition, the amount of the base to be used is, for example, about
The amount used can preferably range from about 0.1 to about 10 moles. In addition, as an organic solvent, dimethylformamide, tetrahydrofuran, acetonitrile, dimethyl sulfoxide, toluene,
Examples include ether and dioxane. The amount of these organic solvents to be used is not particularly limited and may be selected as appropriate.
A preferred example of the amount used is about 100 times the weight. After the reaction is completed, the reaction product is extracted with an organic solvent such as hexane, ether, or toluene, washed with water, dried, and purified by means such as column chromatography or distillation to easily obtain the compound of formula (3). I can do it. Cis-γ-methylcyclocitral, the raw material compound of formula (2) used in the present invention, can be easily synthesized, for example, by contacting the compound of formula (3), which can be obtained as described above, with silver nitrate in an organic solvent. be able to. The reaction is preferably carried out in an organic solvent, and organic solvents such as tetrahydrofuran, ether, etc. are preferably used. The reaction temperature and reaction time can be appropriately selected depending on the solvent used, but for example, a reaction temperature of about -20 to about +50 and,
For example, a reaction time of about 2 to about 48 hours can be exemplified. The amount of the organic solvent to be used is preferably in the range of about 1 to about 100 times the weight of the compound of formula (3). The amount of silver nitrate used in the above reaction can be selected and changed as appropriate, but for the compound of formula (3), for example,
A range of about 0.1 to about 10 moles can be exemplified. After the reaction is completed, the raw material compound of formula (2) can be easily obtained by removing the generated crystals, separating the organic layer, drying, and purifying it by means such as distillation and column chromatography. The compound of formula (5) used in the production example of the compound of formula (2) mentioned above is a compound of
The compound described in JP-A No. 57-134428 can be produced by the method disclosed in JP-A-57-134428, but an improved method (Japanese Patent Application No. 1983-1989) related to an application filed by the same applicant dated the same date as the present application is −82628, JP-A-61−
243034), which is preferable. According to the improved method, formula (b) shown in the process diagram below
The compound of formula (5) can be easily produced by hydrogenating 3,3,4-trimethyl-1-cyclohexene-1-carbaldehyde. A process diagram including the manufacturing mode of the compound of formula (b) is shown below. The method for synthesizing the compound of formula (5) above will be explained in more detail below according to the process diagram above. In the above process diagram, the formula (d) 2,2,3-tolumethyl-6-hydroxymethylenecyclohexanone is a 2,3-
Dimethylhexanone can be easily synthesized, for example, by methylation with methyl bromide in the presence of sodium hydride, followed by reaction with ethyl formate in the presence of sodium methoxide. Formula (d) compound to formula (c) 2,2,3-tolumethyl-
6-(1-Ethoxyethoxymethylene)cyclohexanone can be easily synthesized by reacting the compound of formula (d) with ethyl vinyl ether in the presence of an acid. Examples of acids used in this reaction include phosphoric acid, sulfuric acid, hydrochloric acid, and p-toluenesulfonic acid. The amount of these acids to be used varies depending on the type of acid, but for example, for the compound of formula (d). Approximately 0.5~
A preferable example is a range of about 10%. Further, the amount of ethyl vinyl ether to be used can be selected as appropriate, and may range, for example, from about 1 to about 10 moles relative to the compound of formula (d). The reaction can be easily carried out, for example, at a temperature of about 0° to about 50°C for about 1 to about 5 hours. After the reaction is complete, for example,
Pouring into aqueous sodium bicarbonate solution, drying over magnesium sulfate, and concentration can provide the compound of formula (c). To synthesize the above formula (b) 3,3,4-trimethyl-1-cyclohexene-1-carbaldehyde,
For example, expressions that can be composed as described above
It can be easily synthesized by hydrogenating the compound (c) in a solvent in the presence of a reducing reagent. Although the reaction temperature and reaction time can be selected appropriately, for example, about 0 to about 50°C and about 1 to about 5 hours can be exemplified. Examples of solvents include ethanol, water, isopropyl alcohol, ether,
THF can be mentioned. The amount of these organic solvents to be used can be selected as appropriate, and for example, it can be in the range of about 0.5 to about 5% by weight based on the compound of formula (c). In addition, as reducing reagents, for example,
Examples include sodium borohydride and lithium aluminum hydride. The amount of these reducing reagents to be used is, for example, about 1/4 to about 2 moles based on the compound of formula (c). After the reaction is completed, post-treatment is carried out according to conventional methods to obtain the formula
(b) The compound can be easily synthesized. To synthesize 1-(3,3,4-trimethyl-1-cyclohexen-1-yl)-methyl alcohol of formula (5), a compound of formula (b) which can be obtained as described above, for example, is It can be easily synthesized by hydrogenation in an organic solvent in the presence of a reducing reagent. The reaction conditions and reaction method were carried out in accordance with the method described above for synthesizing the compound of formula (b) from the compound of formula (c), thereby producing the compound of formula (5).
Compounds can be easily synthesized. (e) Examples and Reference Examples Synthesis example of compound of raw material formula (2): - (1) Synthesis of N,N-dimethylacetonitrile. Dimethylamine 50% in 90g of aqueous solution under water cooling
Add 114 g of glycononitrile aqueous solution and stir at room temperature for 3 hours. Add ether, salt out with common salt, and then perform extraction. After extraction, the desired product is obtained by drying with magnesium sulfate and distillation. 67g Boiling point 130-135℃/760mmHg Yield 80% (2) Synthesis of 1-(3,4,4-trimethyl-1-cyclohexen-1-yl)methylene bromide formula (4). 1-(3,4,4-trimethyl-1-cyclohexen-1-yl)methyl alcohol formula (5) 15.4g
(0.1 mol) with 1 g of pyridine in dry ether
Pour into 100ml. Cooling internal temperature in ice water bath to 10±5℃
Keep it. At the same temperature, 10.8 g (0.04 mol) of phosphorus tribromide is added dropwise. After the addition was completed, stirring was continued for 1 hour and the mixture was left overnight. The reaction solution was poured into ice water, the ether layer was separated, washed with brine, hydrated with heavy sodium sulfate, dried with magnesium sulfate, and concentrated. Purify by silica gel column chromatography. Rf=0.731 (n-hexane/ethyl acetate=3/1)
16g yield 70% (Wakogel C-200 150g, n-
Hexane/ethyl acetate = 9/1) (3) cis-2-(2-methylene-5,6,6-trimethylcyclohexan-1-yl)N,N-
Synthesis of dimethylacetonitrile formula (3). 2.3 g (10 mmol) of formula (4), 0.84 g (10 mmol) of N,N-dimethylaminoacetonitrile, and 2.2 g (16 mmol) of potassium carbonate are charged into a 50 ml flask together with 12 ml of DMF, and reacted under argon for 24 hours with stirring at room temperature. After finishing, add 100ml of n-hexane and wash with water. Rf = 0.602 by drying magnesium sulfate, concentrating, and silica gel column chromatography.
Formula (3) having (n-hexane/ethyl acetate = 3/1)
Obtained 1.8g. Yield 82% (4) Synthesis of cis-γ-methylcyclotoral formula (2) 12 g of formula (3) was charged with 150 ml of 0.5N silver nitrate, 240 ml of tetrahydrofuran, and 120 ml of ether, and stirred at room temperature for 24 hours. The calcined crystals are filtered and the obtained layer is separated and dried over magnesium sulfate (anhydrous). After concentrating with an evaporator, the residual liquid is rectified under reduced pressure to achieve a boiling point of 54-56℃ (2mmHg).
cis-γ-methylcyclocitral with formula (2)
Obtained 5.3g. Yield 58.8% IR: 3060, 1720, 1640, 895 cm ^-1 Example Synthesis example of compound of formula (1): - 1 Synthesis of (±)-cis-γ-yron 32.5 g of chloroacetone and 100 g of triphenylphosphine Heat in chloroform for 45 minutes and pour into ether. The generated crystals were collected to obtain 112 g of acetonitrile triphenylphosphonium chloride.
Acetonyltriphenylphosphonium chloride
Stir 130 g with 10% aqueous sodium carbonate solution for 8 hours. 107 g of the obtained acetylidene triphenylphosphorane was reconsolidated from methanol-water,
Obtained 99g of pure product. 318 g of acetylidene triphenylphosphorane obtained as described above are dissolved in 3 toluene. 50 g of cis-γ-methylcyclotoral formula (2) was added to the mixture and heated under reflux for 24 hours. After completion of the reaction, toluene is distilled off using an evaporator, and n-hexane is added to the residue for extraction. After the extractions are combined and concentrated, the residual liquid is distilled under reduced pressure to a boiling point of 110° to 113°C/
(±)-cis-γ-iron 51 g (Y
= 82.5%). 2 Synthesis of (±)-cis-γ-ylon The procedure was repeated in the same manner as in Example 1 except that acetonitrile was used instead of toluene, and (±)
-cis-γ-ylon 57.5g (Y=93%) was obtained. (f) Effects According to the method of the present invention, in addition to being able to selectively synthesize (±)-cis-γ-iron without producing a trans-isomer, the method also enables the synthesis of (±)-cis-γ-irones selectively, compared to the number of steps proposed conventionally. It has the advantage that it can be synthesized with a greatly reduced number of steps, and can be synthesized at low cost and with a good yield.

Claims (1)

[Claims] 1. The following formula (2) cis-γ-methylcyclocitral represented by the following formula in an organic solvent: The following formula (1) is characterized by contacting with acetylidene triphenyl phorphoran represented by A method for producing (±)-cis-γ-iron represented by