JP2929218B2 - Method for producing 3-oxo-α-ionone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention has been highly evaluated as a fragrance for foods and drinks, cosmetics, tobacco and the like, and is also useful as an intermediate for carotenoids, fragrances, pharmaceuticals and the like. The present invention relates to a method for producing 3-oxo-α-ionone.

[Conventional technology]

Conventionally, the following method has been proposed as a method for producing a homolog of yonone. For example, "Helv.Chim Acta" 35 Vol. 986
Page (1952) has the following formula Discloses a method for synthesizing 3-oxo-α-ionone. However, this method has the disadvantage that the reaction time is long, the conversion and the yield are low, and the chromium wastewater requires a great deal of labor.

JP-A-56-145269 discloses a method for synthesizing 3-oxo-α-yonone according to the following formula.

However, this method has a low conversion and produces a large amount of by-products, resulting in a low yield. Also, the operation for separating the target substance becomes complicated, which is unsuitable for industrial practice. Furthermore, "Helv.Chim
Acta, 65: 944 (1982) discloses a method for synthesizing 3-oxo-α-yonone according to the following formula.

However, this method has drawbacks such as a large number of reaction steps and a need for use of a reaction reagent which is disadvantageous in operation.

[Problems to be solved by the invention]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing an yonone homolog that is industrially advantageous by overcoming the disadvantages or deficiencies of the above-mentioned conventional methods. In particular, an object of the present invention is to provide a method for industrially producing an yonone homologue from inexpensive raw materials in a high yield by a simple reaction operation and a shortened synthesis route as compared with the conventional method.

[Means for solving the problem]

The present invention relates to the general formula (1) Wherein X represents an alkoxy group or an acyloxy group, and an olefinic compound represented by the general formula: (Wherein, R ^{1 to} R ³ represent an aliphatic hydrocarbon group having 1 to 5 carbon atoms) in the presence of a Lewis acid, followed by treatment with an acid if desired. And a method for producing 3-oxo-α-ionone.

By utilizing the method of the present invention, 3-oxo-α-ionone can be industrially advantageously obtained by a simpler reaction operation and a shorter reaction man-hour than the conventional method. As the olefinic compound used in the method of the present invention, essentially any compound can be used as long as the general formula (1) is satisfied.
X in the general formula, that is, an alkoxy group (—OR ⁴ ) or an acyloxy group As R ⁴ and R ⁵ , an aliphatic hydrocarbon group represented by an alkyl group and an aryl group such as a phenyl group and a tolyl group are preferably used. In particular, an alkyl group having 1 to 5 carbon atoms such as methyl, ethyl, propyl, butyl and pentyl is preferably used. Specific examples of the olefinic compound include 4-acetoxy-3-buten-2-one, 4-pentyloxy-3-buten-2-one, 4-propionyloxy-3-buten-2-one, and Butyryloxy-3-buten-2-one, 4-benzooxy-3-buten-2-one, 4-methoxy-3-buten-2-one,
4-ethoxy-3-butene, 4-butoxy-3-buten-2-one, 4-propoxy-3-buten-2-one,
Α, β- such as 4-phenoxy-3-buten-2-one
Examples thereof include unsaturated ketones.

The diene compound used in the method of the present invention has the general formula (2)
As long as the above formula is satisfied, essentially any compound can be used. In the general formula, R ^{1 to} R ³ are preferably alkyl such as methyl, ethyl, propyl and butyl, and particularly preferably methyl and ethyl. These diene compounds are prepared by reacting isophorone with a Grignard reagent in the presence of a catalytic amount of iron (III) chloride and then treating with a chlorotrialkylsilane [J. Am.
m. Soc., 106 7619-7621 (1984)]. The process of the present invention is carried out by reacting the olefinic compound (1) with the diene compound (2) in the presence of a non-hydrogen ion type Lewis acid.

Essentially any Lewis acid can be used as long as it can accept electrons without releasing hydrogen ions. Examples of such Lewis acids include zinc chloride, zinc bromide, zinc iodide, stannic chloride, titanium tetrachloride, aluminum chloride, aluminum bromide, boron trifluoride dientyl ether complex, boron trifluoride acetate complex, Examples include gallium chloride, antimony pentachloride, dimethylaluminum chloride, diethylaluminum chloride, and ethylaluminum dichloride. The reaction can be carried out under normal pressure or under pressure. The reaction temperature is preferably −70 to 100 ° C., particularly preferably −20 to 50 ° C. The reaction can be carried out in the presence or absence of a solvent. Examples of the reaction solvent include hydrocarbon solvents such as hexane, benzene, toluene, and xylene, ether solvents such as diethyl ether, dibutyl ether, tetrahydrofuran, diisobutyl ether, dioxane, mono- or diethylene glycol diethyl ether, and tetrahydrofuran, monochloroethane, dichloromethane, and chloroform. , Carbon tetrachloride, 1,2
And a mixed solvent comprising a halogen-based solvent such as -zochloro-enter and any combination thereof. The amount of the olefinic compound represented by the general formula (1) is determined by the formula (2)
0.1 to 10 times, especially 0.8 to 2 times, the mole of the diene compound of formula (I). The amount of the Lewis acid to be used is preferably from 0.01 to 5 times, particularly preferably from 0.1 to 2 times, the moles of the diene compound of the general formula (2). The reaction can be carried out at other molar ratios as long as the selectivity of the reaction is not hindered.
The reaction time is preferably 0.05 to 48 hours, particularly preferably 1 to 10 hours.

After completion of the reaction, for example, the reaction solution is poured into a large excess of a basic solution such as an aqueous solution of sodium hydrogen carbonate, and extracted using an appropriate extraction solvent, for example, benzene, toluene, carbon tetrachloride, chloroform, ethyl acetate, and the like. After collecting the solvent layer, it is washed with water, dried with, for example, sodium sulfate, and the solvent is distilled and recovered, whereby 3-oxo-α-ionone can be obtained.

In the method of the present invention, first, a Diels-Alder type reaction occurs between the olefinic compound (1) and the diene compound (2) by the action of a Lewis acid, followed by elimination accompanied by a reverse aldol condensation reaction. It is believed that a type of reaction proceeds to produce 3-oxo-α-ionone. As described above, in the reaction of the present invention, the desired product can be obtained directly without obtaining an intermediate product. However, depending on the amount and type of Lewis acid used, the reaction time and the reaction temperature, the desired product can be obtained. In addition to 3-oxo-α-ionone, which is May be obtained in some cases. In this case, the bicyclooctene compound (4) once produced is subjected to a so-called reverse aldol condensation and subsequent elimination type reaction in a state of a mixture with 3-oxo-α-ionone, so that 3-oxo-α is easily obtained. −
It can be converted to ionone. The bicyclooctene compound (4) may be subjected to a similar reaction after being separated from the mixture with 3-oxo-α-yonone by distillation or column chromatography. In this reaction, a mixture of bicyclooctene compound (4) and 3-oxo-α-yonone, or bicyclooctene compound (4) is converted to a mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acid, perchloric acid, acetic acid, formic acid,
Organic acids such as oxalic acid, malonic acid, p-toluenesulfonate, aluminum chloride, aluminum bromide, boron trifluoride diethyl ether complex, gallium chloride, antimony pentachloride, dimethyl aluminum chloride, diethyl aluminum chloride, ethyl dichloride This is done by treatment with a Lewis acid such as aluminum. Reaction temperature is -30
C. to 150.degree. C., particularly preferably 0 to 100.degree. The reaction solvent is not essential, but alcoholic solvents such as methanol, ethanol, butanol, and propanol, hexane, benzene,
Examples include hydrocarbon solvents such as toluene and xylene, ether solvents such as diethyl ether, dibutyl ether, tetrahydrofuran, diisobutyl ether, dioxane, mono- or diethylene glycol dimethyl ether, mono- or diethylene glycol diethyl ether, and tetrahydropyran, and mixed solvents thereof.
After completion of the reaction, for example, a large excess aqueous sodium carbonate solution,
An aqueous potassium carbonate solution, poured into a basic solution such as an aqueous solution of sodium hydrogencarbonate, a suitable extraction solvent, for example, benzene,
After extracting with toluene, carbon tetrachloride, chloroform, ethyl acetate and the like, collecting the solvent layer, washing with water and drying with, for example, sodium sulfate, and distilling off the solvent, 3-oxo-α-.
Ionone can be obtained.

3-oxo-α-ionone is optionally distilled under reduced pressure,
It can be purified by means such as column chromatography. Thus, a simple process with a short process and high yield
Oxo-α-ionone can be obtained. Next, the present invention will be described based on examples.

Example 1. A mixture of 0.96 g (7.22 mmol) of anhydrous aluminum chloride and 30 ml of dichloromethane was cooled to -3 ° C, and 2.06 g (16.09 mmol) of 4-acetoxy-3-buten-2-one was mixed with 2 ml of dichloromethane. Was added dropwise over 2 minutes. Then 1
-Trimethylsiloxy-3,5,5-trimethyl-1,3-cyclohexadiene 3.04 g (14.48 mmol), dichloromethane 2 m
l of the mixture was added dropwise over 13 minutes. After stirring at the same temperature for 2 hours, the reactants were slowly added to an ice-cooled saturated aqueous sodium hydrogencarbonate solution. The mixture was extracted with 400 ml of ethyl acetate, washed four times with 50 ml of saturated saline, and dried over anhydrous magnesium sulfate. After filtration, the solvent is recovered and distilled under reduced pressure to a boiling point of 113 to 145.
3.56 g of a fraction having a temperature of 3 ° C./3 mmHg was obtained.

This fraction was subjected to gas chromatography (PEG-20M1wt% 7
As a result of analysis at 0 to 200 ° C./m), 3-oxo-α-ionone, 8-acetoxy-7-acetyl-3,5,5-trimethyl-1-trimethylsiloxybicyclo [2.2.2] oct-2- 7-endo-8-exo form of ene (a) 39.3%, 23.6% of 7-exo-8-endo form (b)
It contained 29.2%. The 3-oxo-α-ionone, 7-endo-8-exo form (a), and 7-exo-8-endo form (b) were isolated by silica gel chromatography.

Oxo -α- ionone ^{IR: (Neat) 1667,1600,1260,993cm -1 1} H-NMR: (δTMS ppm in CDCl 3) 1.05 (s, 3H) 1.12 (s, 3H) 1.95 (d, J = 2Hz, 3H) 2.
25 (d, 2H) 2.33 (s, 3H) 2.78 (d, J = 10 Hz, 1H) 5.99
(S, 1H) 6.15 (d, J = 18 Hz, 1H) 6.70 (dd, J = 10, 18 Hz, 1
H) 7- endo-8 exo (a) IR: (Neat) 1738,1720,1260,880,840cm -1 1 H-NMR: (δTMS ppm in CDCl 3) 0.12 (s, 9H) 0.87 (s , 3H) 1.22 (s, 3H) 1.52 (AB,
2H) 1.83 (d, J = 2 Hz, 3H) 1.97 (s, 3H) 2.15 (s, 3H)
2.76 (d, J = 6 Hz, 1H) 4.57 (dd, J = 3 Hz, J = 6 Hz, 1H)
5.60 (m, 1H) 7- exo-8- endo isomer (b) IR: (Neat) 1740,1720,1259,882,845cm -1 1 H-NMR: (δTMS ppm in CDCl 3) 0.12 (s, 9H ) 0.86 (s, 3H) 1.06 (m, 1H) 1.26 (s, 3H)
H) 1.52 (s, 1H) 1.80 (d, J = 2 Hz, 3H) 1.92 (s, 3H)
1.99 (m, 1H) 2.20 (s, 3H) 2.59 (m, 1H) 5.07 (m, 1
H) 5.82 (m, 1H) Example 2. 7-acetyl-8-acetoxy-3,5,5-trimethyl-1-trimethylsiloxybicyclo [2.2.2] oct-
50.1 mg of 2-ene (0.148 mmol, 7-endo-8-exo form (a): 7-exo-8-endo form (b) = 64: 36) was mixed with ₂ ml of methanol and 1 ml of 1NH ₂ SO ₄ and mixed. Stirred at C for 15 h. Remove methanol, extract with 100 ml of ethyl acetate,
Washing was carried out in the order of a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution. Next, after drying over anhydrous magnesium sulfate to remove the solvent, silica gel chromatography was performed to obtain 29.4 mg of a fraction. This was 3-oxo-α-ionone, which formed a single peak by gas chromatography. (Reaction yield = 96.3%) Example 3. After mixing anhydrous aluminum chloride (1.02 g, 7.67 mmol) and dichloromethane (30 ml), the mixture was cooled to -3 ° C and 1-trimethylcyclooxy-3,5,5-trimethyl-1 was added. 3.17 g (15.10 mmol) of 3,3-cyclohexadiene, 2.17 g (1695-mmol) of 4-acetoxy-3-buten-2-one, 3 ml of dichloromethane
Was added dropwise at 0 ° C. over 6 minutes.

After the dropwise addition, the mixture was stirred at −3 to 0 ° C. for 1 hour, then the reaction product was slowly added to an ice-cooled saturated aqueous sodium hydrogen carbonate solution, and the mixture was further stirred for 5 minutes.

Next, the mixture was extracted with 400 ml of ethyl acetate, washed with 70 g of 5% hydrochloric acid and 100 g of saturated saline in that order, and the solution was collected to obtain 4.35 g.
Oil was obtained. The oil was analyzed by gas chromatography. As a result, 3-oxo-α-ionone and 8-acetoxy-7-acetyl-3,5,5-trimethyl-1-trimethylsiloxybicyclo [2.2.2] oct-2-ene were obtained. 7
-End-8-exo form (a) and 7-exo-8-endo form (b) were contained at 36.9%, 28.0% and 17.0%, respectively. Next, 30 ml of methanol and 15 ml of 1N sulfuric acid were added to this oil, and the mixture was stirred at 20 ° C. for 17 hours, and then neutralized with a saturated aqueous solution of sodium hydrogen carbonate to recover methanol. Ethyl acetate
The mixture was extracted with 500 ml, washed twice with 50 ml of saturated saline, and dried over anhydrous magnesium sulfate. After filtration, ethyl acetate was recovered and distilled under reduced pressure to obtain 2.33 g of a fraction having a boiling point of 128 to 139 ° C./3 mmHg. This was analyzed by gas chromatography to find that it contained 95.4% of 3-oxo-α-ionone. (Reaction yield = 71.5%) Example 4. Boron trifluoride diethyl ether complex 97.2mg (0.685m
mol), cooled to 0 ° C., 1-trimethylsiloxy-3,
5,5-trimethyl-1,3-cyclohexadiene 407.0 mg
(1.94 mmol), 4-methoxy-3-buten-2-one 28
4.0 mg (2.56 mmol) and 5 ml of dichloromethane
After dropwise addition at 2 ° C., the mixture was stirred at the same temperature for 5 hours. The contents were added to saturated sodium bicarbonate and stirred for 2 minutes. Next, the mixture was extracted with ethyl acetate, washed with saturated saline and dried over anhydrous magnesium sulfate. Solvent is recovered and distilled under reduced pressure to the boiling point.
374.mg of a 70-150 ° C / 3mmHg fraction was obtained. This fraction was analyzed by gas chromatography and found to be 3-oxo-α-ionone, 7-acetyl-8-methoxy-3,5,5-trimethyl-1-trimethylsiloxybicyclo [2.2.2] oct-2-ene. 7-endo-8-exo form (c), 7-
The exo-8-endo form (d) was 5.8% and 47.2%, respectively.
%, 33.9%. According to silica gel chromatography, 3-oxo-α-ionone, 7-endo-8-
The exo form (c) and the 7-exo-8-endo form (d) were isolated.

7-endo-8 exo (c) IR: (Neat) 1715,1100,840cm -1 1 H-NMR: (δTMS ppm in CDCl 3) 0.12 (s, 9H) 0.85 (s, 3H) 1.25 (s , 3H) 1.52 (Ab,
2H) 1.82 (d, J = 2Hz, 1H) 2.13 (m, 1H) 2.22 (s, 3H)
2.80 (d, J = 6Hz, 1H) 3.20 (s, 3H) 3.49 (dd, J = 3Hz,
6Hz, 1H) 5.60 (m, 1H) 7- endo-8 exo (d) IR: (Neat) 1715,1100,890,851cm -1 1 H-NMR: (δTMS ppm in CDCl 3) 0.12 (s , 9H) 0.88 (s, 3H) 1.10 (m, 1H) 1.21 (s, 3H)
H) 1.43 (m, 1H) 1.81 (d, J = 2 Hz, 3H) 2.08 (m, 1H)
2.28 (s, 3H) 2.61 (m, 1H) 3.15 (s, 3H) 4.00 (m, 1
H) 5.81 (m, 1H) Example 5. 1-Trimethylsiloxy-3,5,5-trimethyl-1,3-
480.1 mg (2.29 mmol) of cyclohexadiene, 286 mg (2.57 mmol) of 4-methoxy-3-buten-2-one and 5 ml of methylene chloride were mixed and cooled to -5 ° C. Next, 170 mg (1.28 mmol) of aluminum chloride was added, and the mixture was stirred at 0 ° C. for 40 minutes. A saturated aqueous sodium hydrogen carbonate solution was added, the mixture was stirred for 5 minutes, extracted with ethyl acetate, washed with saturated saline, and dried over anhydrous sodium carbonate. After removing the solvent, methanol
5 ml, was added 1N-H ₂ SO ₄ 2ml, was stirred for 1 hour at 25 ° C..
After neutralization using an aqueous sodium hydrogen carbonate solution, methanol was recovered and extracted with ethyl acetate. Next, the solvent was recovered by drying over magnesium sulfate, and distilled under reduced pressure to a boiling point of 120 to 137 ° C./3 mm
377.2 mg of a Hg fraction were obtained. The product was analyzed by gas chromatography. As a result, 3-oxo-α-ionone was converted to 83.6%.
%. (Reaction yield = 67.0%)

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-63-122991 (JP, A) JP-A-56-113729 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C07C 49/647 C07C 45/29 C07C 45/71 C07F 7/18 WPI / L (QUESTEL) CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] (1) General formula Wherein X represents an alkoxy group or an acyloxy group, and an olefinic compound represented by the general formula: (Wherein, R ^{1 to} R ³ represent an aliphatic hydrocarbon group having 1 to 5 carbon atoms) in the presence of a Lewis acid, followed by treatment with an acid if desired. To produce 3-oxo-α-ionone. 2. The general formula (Where X represents an alkoxy group or an acyloxy group, and R ¹ to
R ³ represents an aliphatic hydrocarbon group having 1 to 5 carbon atoms).