JPH0840971A - Production of hinokitiol and its intermediate product - Google Patents

Abstract

PURPOSE:To industrially advantageously produce a chemically pure hinokitiol by reducing generally readily available 6,6-dimethylfulvene as a starting raw material to selectively provide 1-isopropylcyclopentadiene as a main component and using the resultant compound. CONSTITUTION:This method for producing hinokitiol is to reduce 6,6- dimethylfulvene with a hydrogenated dialkylaluminum and selectively obtain 1-isopropylcyclopentadiene as a main component by in a method for producing hinokitiol by reducing 6,6-dimethylfulvene, affording isopropylcyclopentadiene, subjecting a dihaloketene to cycloaddition to the resultant isopropylcyclopentadiene, giving an isopropylcyclopentadienedihaloketene adduct and carrying out solvolytic rearrangement of the adduct. This method for producing the intermediate for hinokitiol is to reduce 6,6-dimethylfulvene.

Description

Detailed Description of the Invention

[0001]

The present invention relates to hinokitiol (β-, which is useful for perfumes, cosmetics, dentifrices, hair-growth agents and hair nourishing agents, etc.
Tsuyapurisin) and a method for producing an intermediate product thereof. More specifically, it relates to a method for producing hinokitiol, which comprises a step of reducing 6,6-dimethylfulvene to selectively obtain 1-isopropylcyclopentadiene as a main component.

[0002]

2. Description of the Related Art Hinokitiol (β-tsuyapricin) was prepared by Nozoe et al.
A compound that was discovered in 1936 in Hinoki, Taiwan, and whose structure was clarified in 1940.
It has a tropolone skeleton that has attracted worldwide attention as a membered-ring aromatic compound. Hinokitiol is naturally contained only in a part of wood of the Cypress family, and in Japan, it is contained in the highest amount (about 0.006%) in Aomori Hiba (Hinokiasunaro) of the Asunaro group.

Hinokitiol is listed as a standard for cosmetic raw materials, and is used as a raw material for fragrances, cosmetics, dentifrices utilizing the action of preventing alveolar pyorrhea, hair-growing / hair-restoring agents utilizing the cell activation action, and natural products are food additives. It is also approved as a thing. In addition, it has a wide range of antibacterial and antifungal properties, and because it is resistant to the formation of resistant bacteria, it is used as a food preservation material such as preservative sprays, preservative papers and films, and in recent years, it also has antibacterial and antifungal functions. It is used for fibers that have been given, and has received much attention.

Such hinokitiol products include natural extracts and chemically synthesized products. The extract is
Generally, using Hiba oil obtained by steam distillation of sawdust after sawing of Aomori Hiba as raw material, acid oil is extracted with alkali, and then acid oil is treated with phosphoric acid to obtain crude hinokitiol, which is distilled. After that, recrystallization was repeated to obtain pure hinokitiol. However, since the extract is made from Hiba oil obtained from Aomori Hiba, the supply of raw materials is limited, and it is difficult to meet a large demand. For this reason, large-scale supply of chemically synthesized products is desired.

Conventionally, as a synthetic route for a chemically synthesized product of hinokitiol, a method by a solvent-solving rearrangement reaction of a cycloaddition product of isopropylcyclopentadiene and dichloroketene is known. In this case, hinokitiol is
There is a report that it is obtained exclusively from 1-isopropylcyclopentadiene (K. Tanaka and A. Yoshikoshi, Te.
trahedron, Vol.27, pp.4889-4899.1971.).

Therefore, an attempt has been made to improve the yield of the final product, hinokitiol (β-tsuyapricin), by selectively obtaining 1-isopropylcyclopentadiene among the isomers of isopropylcyclopentadiene in the production process. Came.

As a method for selectively obtaining 1-isopropylcyclopentadiene, Japanese Patent Publication No. 51-33901 discloses a Grignard reagent synthesized by heating and refluxing metallic magnesium and ethyl bromide in a dehydrated and dried anhydrous THF solvent. After adding pentadiene and heating under reflux again to convert it into Grignard reagent of cyclopentadiene, it was cooled to 0 ° C, and isopropyltosylate synthesized from isopropyl alcohol and p-toluenesulfonyl chloride was added separately and reacted at 0 ° C for 13 hours. After that, washing, extraction and the like are carried out to synthesize a substantially pure 1-isopropylcyclopentadiene free of the isomer 2-isopropylcyclopentadiene.

Further, in Japanese Patent Publication No. 51-33901, a cycloaddition reaction with dichloroketene is carried out using this compound, and the resulting cyclopentadiene dichloroketene adduct is subjected to column purification, followed by solvolysis. A method of carrying out a reaction to obtain hinokitiol (β-tsuyapricin) is disclosed.

However, in the above reaction, metallic magnesium is used for the preparation of the Grignard reagent, and the solvent used in the reaction is extremely sensitive to water, and therefore, the metallic sodium or There is a problem that the handling is complicated, such as the need for an anhydrous solvent that has been subjected to a pretreatment such as dehydration purification using a metal reagent such as lithium aluminum hydride. In addition, these reactions can be relatively easily performed in a synthetic reaction at a laboratory level, but when it comes to industrial scale production,
It can be said that it is unsuitable for its safety or handling including the above-mentioned problems.

Therefore, an object of the present invention is to provide a method for obtaining 1-isopropylcyclopentadiene selectively as a main component by reducing easily obtained 6,6-dimethylfulvene as a starting material. Another object of the present invention is to provide a method for industrially advantageously producing chemically pure hinokitiol (β-tsuyaprisin) through this step.

[0011]

The present inventors have found that 6,6-
Various methods were investigated for the reduction of dimethylfulvene. As a result, it was found that when lithium aluminum hydride or the like was used as the reducing agent, 1-isopropylcyclopentadiene was not preferentially obtained, and conversely, 2-isopropylcyclopentadiene was slightly preferentially produced. However, since the double bond between the 5th and 6th carbons of 6,6-dimethylfulvene is a carbonyl equivalent, diisobutylaluminum hydride (hereinafter, referred to as "DIBAL-H") exerts an ability to reduce the carbonyl group. Was used as a reducing agent, it was found that 1-isopropylcyclopentadiene was highly selectively produced. The present invention has been completed based on this finding and further intensive studies.

That is, the gist of the present invention is (1) 6,6-dimethylfulvene is reduced to obtain isopropylcyclopentadiene, and dihaloketene is cycloadded to the isopropylcyclopentadiene to give an isopropylcyclopentadiene dihaloketene adduct. In the method for producing hinokitiol in which solvophilic rearrangement reaction is performed using the adduct,
A method for producing hinokitiol, characterized in that 6,6-dimethylfulvene is reduced with dialkylaluminum hydride to selectively obtain 1-isopropylcyclopentadiene as a main component, (2) dialkylaluminum hydride is diisobutyl hydride The above (1) which is aluminum
The production method described in (1) or (2) above, wherein the reduction reaction with (3) dialkylaluminum hydride is carried out in a solvent containing an ether solvent.
(4) The production method according to (3), wherein the ether solvent is tetrahydrofuran, (5) The production method according to (1), wherein the dihaloketene is dichloroketene, (6) 6,6.
A method for producing isopropylcyclopentadiene, characterized in that dimethylfulvene is reduced with dialkylaluminum hydride to selectively obtain 1-isopropylcyclopentadiene as a main component, (7) dialkylaluminum hydride is diisobutylaluminum hydride (6) The production method according to (6), (8) the reduction reaction with dialkylaluminum hydride is carried out in a solvent containing an ether solvent, (6) or (7). ) The production method according to the above (8), wherein the ether solvent is tetrahydrofuran.

The method for producing hinokitiol (β-tsuyaprisin) of the present invention is such that, in the process of producing isopropylcyclopentadiene, which is an intermediate product thereof, 6,6-dimethylfulvene is reduced with dialkylaluminum hydride to selectively give 1 -Isopropylcyclopentadiene is obtained as a main component. Hereinafter, the production method of the present invention will be described in detail according to the following synthetic scheme.

[0014]

Embedded image

First, the reduction reaction of 6,6-dimethylfulvene (Compound 1) will be described. This reaction is carried out by dissolving 6,6-dimethylfulvene in a solvent under a nitrogen stream, adding a dialkylaluminum hydride solution thereto, and appropriately cooling.

Examples of the dialkylaluminum hydride used as the reducing agent in the present invention include diisobutylaluminum hydride, diethylaluminum hydride, dimethylaluminum hydride and the like. Of these, a solution of diisobutylaluminum hydride is preferable from the viewpoint of easy availability, easy handling, safety and the like.

The amount of dialkylaluminum hydride used is usually 1.
It is 0 to 2.5 times mol, preferably 1.1 to 1.6 times mol. If it is less than this range, the reaction tends to be long, and if it is more than this range, the production ratio of 2-isopropylcyclopentadiene tends to increase.

Such a dialkylaluminum hydride is usually diluted with a solvent for safety and easiness of handling, and a diluting solvent used at that time is n-hexane, toluene or cyclohexane. , Heptane, dichloromethane, tetrahydrofuran and the like are used. Of these, especially when n-hexane is used,
1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene / 2-isopropylcyclopentadiene is more selectively produced from the two isomers of isopropylcyclopentadiene (compounds 2 and 3). The production ratio of can be increased.

The amount of the diluent solvent used is usually 15 to 60% concentration, preferably 17 to 50% concentration, based on the dialkylaluminum hydride. If it is less than this range, the reaction time tends to be long, and if it is more than this range, handling is complicated in terms of operation and there is a tendency for safety problems such as danger of ignition.

As the 6,6-dimethylfulvene used as a starting material, a commercially available product can be used, but it can be produced, for example, as follows. Cyclopentadiene obtained by thermal decomposition of dicyclopentadiene is dissolved in a solvent (for example, methanol), and a catalytic amount of a base (for example, sodium methoxide) is added to generate anion of cyclopentadiene, and then equimolar. Of acetone is added. After completion of the reaction, neutralization, extraction and washing are carried out, concentration and then vacuum distillation are carried out to easily obtain.

On the other hand, the solvent used in the reaction is not particularly limited as long as it is inert to the reduction reaction,
For example, tetrahydrofuran, dioxolane, dioxane, n-hexane, cyclohexane, dichloromethane,
Toluene or the like is used. Among them, 1-isopropylcyclopentadiene / 2 can be obtained by adding a general-purpose ether solvent such as tetrahydrofuran (hereinafter abbreviated as THF), dioxolane, dioxane, etc. to the reaction system as a reaction solvent.
-It is preferable because it increases the production ratio of isopropylcyclopentadiene and significantly increases the reaction rate.

The amount of the reaction solvent used is such that the initial concentration of 6,6-dimethylfulvene is usually 5 to 95%, preferably 20 to 50%. When the concentration is higher than this range, the production ratio of 2-isopropylcyclopentadiene tends to increase, and when the concentration is lower than this range, the reaction time tends to be long.

The reaction temperature is usually -20 to 25 ° C,
It is preferably -5 to 10 ° C. If the temperature is lower than this range, the reaction time tends to be long, and if the temperature is higher than this range, the production ratio of 2-isopropylcyclopentadiene tends to increase. In addition, the reaction time cannot be generally stated because it varies depending on the reaction temperature, the reaction solution concentration, etc.
It is about 30 hours.

By the above reduction reaction, the production ratio of 1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene usually becomes 2 to 15, and 1-isopropylcyclopentadiene (compound 2) is selectively produced as the main component. . In this case, when an ether solvent is used as the reaction solvent as described above, the production ratio becomes high. The reaction solution thus obtained is subjected to separation of the remaining reducing agent with an aqueous acid solution, washing, drying, and distillation.
After appropriate treatment such as isolation of isopropylcyclopentadiene (Compound 2), it is subjected to the next reaction step. However, in the present invention, 1-isopropylcyclopentadiene (Compound 2) can be obtained more selectively, and therefore in view of productivity, it may be used as it is without being isolated from the reaction solution.

When 1-isopropylcyclopentadiene (Compound 2) is left at room temperature for a long time after the reduction reaction, 2-isopropylcyclopentadiene (Compound 3) is produced by isomerization, so that the reaction solution is cooled at a low temperature (for example, It is preferable to store at 10 ° C or lower, preferably 0 ° C or lower).

Next, the cycloaddition reaction of isopropylcyclopentadiene will be described. In this reaction, dihaloketene is cycloadded to isopropylcyclopentadiene to obtain an isopropylcyclopentadiene dihaloketene adduct. It is carried out while adding a base solution to intermediately generate dihaloketene in the reaction system. The resulting isopropylcyclopentadiene dihaloketene adduct has three types of positional isomers (compounds 4, 5, and 6),
Each isomer leads to hinokitiol (compound 7) or γ-tsuyaprisin (compound 8).

Examples of the dihaloacetyl halide used include dichloroacetyl chloride, dichloroacetyl bromide, dibromoacetyl chloride, dibromoacetyl bromide, difluoroacetyl chloride and the like, with dichloroacetyl chloride being preferred. . The amount of dihaloacetyl halide used is based on isopropylcyclopentadiene,
Usually 0.8 to 4.0 times mol, preferably 1.0 to 2.0
It is twice the mole. If it is less than this range, the reaction to the compound (2) tends to be incomplete, and if it is more than this range, the production ratio of the compound (4) tends to decrease.

The solvent for the base solution is not particularly limited, and n-hexane, cyclohexane, toluene or the like can be used.

The reaction temperature is usually -30 to 25 ° C,
It is preferably -10 to 0 ° C, more preferably -1.
It is 0 ° C or lower. If the temperature is lower than this range, the reaction time tends to be long, and if the temperature is higher than this range, the production ratio of the compound (4) tends to decrease.

In the cycloaddition reaction of isopropylcyclopentadiene, there is a difference in the reaction rate with dihaloketene between the two isomers of 1- and 2-isopropylcyclopentadiene, and the reaction rate of 1-isopropylcyclopentadiene is higher. In addition, both reactions have different production ratios of isomers (compounds 4, 5, and 6) depending on the reaction temperature. In the above temperature range, 1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene, which is a raw material for the cycloaddition reaction The target isopropylcyclopentadiene dihaloketene adduct (Compound 4) can be obtained at a ratio exceeding the production ratio of pentadiene.

The reaction time varies depending on the reaction temperature, the concentration of the reaction solution, etc., but cannot be generally stated, but it is usually 10
It is about 20 hours.

The reaction solution obtained by the above cycloaddition reaction is washed with an aqueous acid solution, washed with water, dehydrated and dried,
After appropriate treatment such as concentration, the reaction is performed in the next reaction step. However, in the present invention, the desired isopropylcyclopentadiene dihaloketene adduct (Compound 4) can be obtained more selectively, and therefore in view of productivity, it is preferable to use the reaction solution without column chromatography purification or distillation purification. .

Next, the solvent addition rearrangement reaction of the isopropylcyclopentadiene dihaloketene adduct will be described.
This reaction is carried out by dissolving the above adduct in an acid-base-water mixed solvent and heating under reflux.

Examples of the acid-base-water mixed solvent include acetone-acetic acid-triethylamine-water mixed solvent, acetic acid-alkali acetate-water mixed solvent, acetic acid-sodium hydroxide-water and the like. Of these, a mixed solvent of acetone-acetic acid-triethylamine-water is preferable from the viewpoint of reaction time and easiness of reaction treatment step.

The mixing ratio of the mixed solvent is, for example, about acetone-acetic acid-triethylamine-water, 5: 4: 2: 1, but it is not always strictly required to be this mixing ratio.

The amount of the mixed solvent used is generally 10 to 60%, preferably 15 to 60% as the above adduct concentration.
The concentration is 30%. If the concentration is higher than this range, insoluble components tend to increase in the reaction treatment step, and if it is lower than this range, the reaction treatment step tends to be complicated.

In the above reaction, the reflux temperature of the solvent is the reaction temperature, which is usually 55 to 65 ° C., preferably 58 to 62.
℃. If the temperature is lower than this range, the reaction time tends to be long, and if the temperature is higher than this range, insoluble components tend to increase in the reaction treatment step. The reaction time cannot be generally stated because it depends on the reaction temperature, the concentration of the reaction solution, etc., but it is usually about 8 to 15 hours.

The reaction solution obtained by the solvophilic rearrangement reaction as described above is appropriately subjected to treatments such as concentration, extraction, and washing to give crude hinokitiol (β-tsuyapricin) () containing a small amount of γ-tsuyapurisin (Compound 8) ( Compound 7) can be obtained. And this crude hinokitiol (β-
(Tuyapurin) is purified by distillation to obtain a pale yellow transparent oil component, and this oil component is crystallized using ligroin to obtain chemically pure white crystalline hinokitiol (β-Tuyapuricin) containing no γ-Tuyapurin. )
Can be obtained. The solvent for crystallization is n
-Hexane, petroleum ether, etc. can also be used,
Ligroin is preferably used.

[0039]

EXAMPLES The present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not limited to these Examples.

The analysis conditions of various measuring instruments are shown below. Gas chromatograph: Shimadzu GC-8A (FID) Data processing: Shimadzu Chromatopack CR-6A Column: Shimadzu Capillary Column CBP-20,25m
× ID 0.25 mm × 0.25 μm Carrier gas: He (30 ml / min) Temperature condition: 50 → 260 ° C. (5 ° C./min) Gas chromatograph mass spectrometer: Shimadzu GC-MS Q
P-5000 Data processing: Shimadzu CLASS-5000 Mass spectrometer condition: Detection part temperature 280 ° C., EI = 70 eV Column: DB-1 30 m × ID 0.25 mm × 0.25 μm Carrier gas: He (20 ml / min) Temperature condition: 80 → 280 ℃ (5 ℃ / min)

Reference Example 1 Reduction of 6,6-dimethylfulvene with lithium aluminum hydride 2.1 g of 6,6-dimethylfulvene (0.
020 mol) to which 30.0 g of diethyl ether was added
Lithium aluminum hydride 1.14 after cooling to ℃
g (0.030 mol) was added in portions while keeping the temperature below 5 ° C. The mixture was stirred for 3 hours while keeping the reaction temperature at 10 ° C or lower. After completion of the reaction, 10 g of water was added under ice-cooling to stop the reaction, and a 2% -sulfuric acid aqueous solution was added for washing to separate the organic layer. After washing the organic layer with the same amount of water, anhydrous sodium sulfate was added and dried to obtain isopropylcyclopentadiene. This solution was analyzed using a gas chromatograph. As a result, it was found that 2-isopropylcyclopentadiene was produced with some preference. Reaction selectivity 95.0%, 1-isopropylcyclopentadiene /
2-isopropylcyclopentadiene = 0.91 (FIG. 1
Peak b / peak a).

Reference Example 2 Synthesis of 1-isopropylcyclopentadiene containing almost no isomer and synthesis of isopropylcyclopentadiene dichloroketene adduct 77 mg of ethylmagnesium bromide / diethyl ether solution (3 mol / L), 85. 6 g
THF (126.0 g) and cyclopentadiene (14.7 g, 0.222 mol) were added to (0.231 mol) 15
After heating and refluxing for an hour, the temperature was cooled to 0 ° C. or lower, and 45.5 g (0.212 mol) of isopropyl tosylate was added to TH.
The F solution was added while keeping it at 0 ° C or lower, and the mixture was stirred at 0 ° C for 28 hours. After completion of the reaction, the reaction solution was added dropwise to a 10% -ammonium chloride aqueous solution while maintaining the temperature at 10 ° C or lower, and stirred for 1 hour. Then, the organic layer was separated, the aqueous layer was extracted twice with petroleum ether, the extracted layer was combined with the organic layer, washed with water, and dried over anhydrous magnesium sulfate to obtain 1-isopropylcyclopentadiene.

When this solution was analyzed by gas chromatography, a minute peak of 2-isopropylcyclopentadiene at a retention time of 3.1 minutes and 1 minute at a retention time of 3.2 minutes were obtained.
-Given the main peak of isopropylcyclopentadiene. The ratio was about 1: 250.

This solution was cooled to 0 ° C. or below, 25.7 g (0.174 mol) of dichloroacetyl chloride was added, and after stirring for a while, 22.9 g of triethylamine (0.
A 266 mol) petroleum ether solution was added dropwise while maintaining the temperature at 0 ° C. After completion of the dropwise addition, the mixture was reacted at 0 ° C. for 12 hours, then the precipitated triethylamine hydrochloride was filtered, washed with 1N-hydrochloric acid and washed with water, dried over anhydrous magnesium sulfate, and concentrated to give isopropylcyclopentadienedichloromethane. A ketene adduct was obtained.

When this solution was analyzed using a gas chromatograph, a substantially single main peak was obtained at a retention time of 21.5 minutes and an extremely small peak was obtained at a retention time of 21.8 minutes. When this was analyzed using a gas chromatograph mass spectrometer, the main peak at a retention time of 11.9 minutes:
M / Z = 218, 203, 187, 175, 147, 1
39, 119, 108, 93, 77 Cl ₂ relative intensity ratio (C ₁₀ H ₁₂ OCl ₂ ): measured value M ⁺ : M ⁺ +2: M ⁺ +4
= 56.2: 37.2: 6.2 Calculated value M ⁺ : M ⁺ +
2: M ⁺ + 4 = 57: 37: 6; extremely minute peak at retention time of 12.0 minutes: M / Z = 218, 203, 183, 1
The peaks of 61, 139, 119, 108, 93, 77 were confirmed, and these peaks can be assigned to the cleavage pattern of the isopropylcyclopentadiene dichloroketene adduct peak without contradiction.

Example 1 Reduction of 6,6-Dimethylfulvene with DIBAL-H 6,6-Dimethylfulvene (content 99.5) under a nitrogen stream.
%) 25.2 g (0.238 mol) with n-hexane 2
After adding 5.1 g and cooling to 0 ° C., DIBAL-H / n
520 ml of hexane solution (0.93 mol / L), 3
60.6 g (0.483 mol) was added dropwise while keeping the temperature below 0 ° C. After completion of the dropping, the mixture was stirred at 0 ° C. for 1 hour, then the reaction temperature was gradually raised to room temperature and stirred overnight. 145.0 g of 35% hydrochloric acid (1.
(390 mol) was added and the mixture was cooled to 10 ° C or lower. The reduction reaction solution was added dropwise to the aqueous hydrochloric acid solution while maintaining the reaction temperature at 10 ° C or lower. After finishing the dropping, 1 while keeping the temperature below 10 ° C.
Stir for hours. After completion of stirring, the organic layer was separated and further washed twice with the same volume of water while maintaining the temperature at 10 ° C or lower. This solution was analyzed using a gas chromatograph. As a result, 1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene = 4.5 (peak b / peak a in FIG. 2), and the GC yield was 98.5%.

Using the same method, a reaction was carried out using a DIBAL-H / toluene solution and a DIBAL-H / cyclohexane solution, and analyzed using a gas chromatograph. As a result, 1-isopropylcyclopentadiene /
The production ratios of 2-isopropylcyclopentadiene were 2.8 (toluene solution) and 3.3 (cyclohexane solution), respectively, and the system using n-hexane showed the best result.

Example 2 DIBA of 6,6-dimethylfulvene with the addition of THF
L-H under reduced nitrogen gas flow, 6,6-dimethylfulvene (content 97.0%) 50.0 g (0.457 mol)
After adding 50.0 g of THF to the mixture and cooling to 0 ° C., DIBA
L-H / n-hexane solution (0.93 mol / L) 66
0 ml (0.594 mol) was added while keeping at 0 ° C. After stirring at 0 ° C. for 2 hours, the reaction temperature was kept at 10 ° C. or lower and stirring was continued for 30 hours. To the same volume of water as the reduction reaction solution, 186.0 g (1.783 mol) of 35% hydrochloric acid was added, cooled to 10 ° C or lower, and the reduction reaction solution was added dropwise while keeping the reaction temperature at 10 ° C or lower. After completion of dropping, the mixture was stirred for 1 hour while maintaining the temperature at 10 ° C or lower. After completion of stirring, the organic layer was separated and further washed with the same volume of a 3% -hydrochloric acid aqueous solution while maintaining the temperature at 10 ° C or lower. Subsequently, washing with the same volume of water was carried out twice while keeping the temperature below 10 ° C. This solution was analyzed using a gas chromatograph. As a result, the production ratio of 1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene was 14.8 (peak b / peak a in FIG. 3), and the GC yield was 99.0%.

Further, using the same method, dioxolane,
As a result of carrying out the reaction by adding dioxane or the like, the production ratio of 1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene was 7.0 to 8.0.

Example 3 Cycloaddition reaction of isopropylcyclopentadiene and dichloroacetyl chloride 1-isopropylcyclopentadiene / 2-isopropylcyclopentadiene ratio 1 obtained according to Example 2
After cooling 482.0 g of the 4.0 solution to 0 ° C., 67.4 g (0.457 mol) of dichloroacetyl chloride was added, and after stirring for a while, 69.3 g of triethylamine.
A solution of (0.684 mol) in n-hexane was added dropwise while keeping it at 0 ° C or lower. After the completion of the dropping, the mixture was reacted at 0 ° C. or lower for 2 hours, a small amount of water was added to stop the reaction, 1N-hydrochloric acid was washed and then water was washed twice, dried over anhydrous magnesium sulfate, and the solution was concentrated. An isopropylcyclopentadiene dichloroketene adduct was obtained. When this solution was analyzed using a gas chromatograph, the retention time was 2
A main peak was obtained at 1.5 minutes and a minute peak at a retention time of 21.8 minutes. These corresponded to the respective isomers of the isopropylcyclopentadiene dichloroketene adduct.

Example 4 Solvent rearrangement reaction of isopropylcyclopentadiene dichloroketene adduct 66.7 g of isopropylcyclopentadiene dichloroketene adduct obtained in Example 3 was added with acetone-acetic acid
Triethylamine-water (5: 4: 2: 1) mixed solvent 4
After dissolving in 30 g and heating under reflux for 10 hours, the reaction solution was concentrated to obtain a black oil component. To the obtained black oil component, the same volume of water was added, acidified with hydrochloric acid, and then extracted with the same volume of toluene. Next, the extracted toluene layer was washed three times with the same volume of water. The obtained toluene layer was concentrated to obtain a black oil component. Then, distillation was performed under reduced pressure to obtain a pale yellow oil component. This oil component was dissolved in ligroin and cooled to 0 ° C or lower to precipitate crystals. The precipitated crystals were filtered, washed with cold n-hexane, and dried under reduced pressure to obtain 21.7 g of white crystals.

Yield 28.0% (yield to dimethylfulvene) mp 50 to 51 ° C .; 270 MHz ¹ H-NMR (C
_{DCl 3): δ7.37~7.29 (m,} 3H) 6.96
(M, H) 2.89 (m, H) 1.27 (d, 6H);
67.5 MHz ¹³ C-NMR (CDCl ₃ ): δ171.
22, 170.86, 159.93, 137.99, 1
27.61, 123.20, 122.22, 38.8
_{5,23.30; GC-MS (C 10} H 12 O 2): M / z =
164 (M ⁺ ), 149, 136, 121, 103, 9
It was 1,77,65.

[0053]

EFFECTS OF THE INVENTION Using 6,6-dimethylfulvene, which is generally easily obtained by the production method of the present invention, as a starting material,
Of isopropylcyclopentadiene obtained by reducing this, 1-isopropylcyclopentadiene can be selectively obtained as a main component, and using it, chemically pure hinokitiol can be industrially advantageously produced. .

[Brief description of drawings]

FIG. 1 is a chart showing the results of analyzing the product obtained in Reference Example 1 using a gas chromatograph.

FIG. 2 is a schematic diagram of Example 1 in which DIBAL-H /
It is a chart which shows the result of having reacted using an n-hexane solution and having analyzed the obtained product using a gas chromatograph.

FIG. 3 is a chart showing the results of analyzing the product obtained by adding THF to carry out the reaction in Example 2 using a gas chromatograph.

Continuation of front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location // C11B 9/00 L

Claims (9)

[Claims] 1. An isopropylcyclopentadiene is obtained by reducing 6,6-dimethylfulvene, a dihaloketene is cycloadded to the isopropylcyclopentadiene to obtain an isopropylcyclopentadiene dihaloketene adduct, and then the adduct is converted to In a method for producing hinokitiol using a solvent rearrangement reaction, 6,6-dimethylfulvene is reduced with dialkylaluminum hydride to selectively give 1-
A method for producing hinokitiol, which comprises obtaining isopropylcyclopentadiene as a main component. 2. The production method according to claim 1, wherein the dialkylaluminum hydride is diisobutylaluminum hydride. 3. The production method according to claim 1, wherein the reduction reaction with dialkylaluminum hydride is carried out in a solvent containing an ether solvent. 4. The method according to claim 3, wherein the ether solvent is tetrahydrofuran. 5. The method according to claim 1, wherein the dihaloketene is dichlorketene. 6. A method for producing isopropylcyclopentadiene, characterized in that 6,6-dimethylfulvene is reduced with dialkylaluminum hydride to selectively obtain 1-isopropylcyclopentadiene as a main component. 7. The production method according to claim 6, wherein the dialkylaluminum hydride is diisobutylaluminum hydride. 8. The production method according to claim 6, wherein the reduction reaction with dialkylaluminum hydride is carried out in a solvent containing an ether solvent. 9. The production method according to claim 8, wherein the ether solvent is tetrahydrofuran.