JPH029835A - Preparation of bicyclohumulenone - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for producing bicyclohumulenone represented by the following formula (1), which is useful as a fragrance.

As described in the publication, it is a substance contained in moss and is an extremely useful compound as a fragrance, but no examples of chemical synthesis have been reported.

(Problem to be solved by the invention) Bicyclohumuleno/ is expected to be used as a fragrance material due to its unique aroma, but it has not been produced industrially because no chemical synthesis method is known. The current situation is that there is no such thing. The present invention provides a method for the chemical synthesis of bicyclomurenones.

(Means for solving the problem) The above problem is solved by the formula (prior art) Bicyclohymulenonha, JP-A-61-126013
A compound represented by the formula (hereinafter referred to as compound (II)) is reacted with a compound represented by the formula (hereinafter referred to as compound (to)) in the presence of a strong basic substance to obtain a compound represented by the formula (1). This problem can be solved by obtaining picyclohumlenone.

Strong basic substances used in the method of the present invention include hydrides of alkali metals or alkaline earth metals such as sodium hydride, lithium hydride, calcium hydride, n-butyllithium, +1@e-butyllithium, etc. alkyllithium, potassium t-butoxide, etc.
These include potassium alkoxides such as potassium ethoxide and potassium methoxide. What is the amount of strong basic substances used?

Usually, it is 1 to 10 mol per 1 mol of the compound (I[0).

Although there is no particular restriction on the ratio of compound (II) and compound (2) used in the method of the present invention, in order to advance the reaction efficiently, compound (I[D It is preferable to use 1 to 3 moles of.

The reaction of the present invention is usually carried out in the presence of a solvent.

The solvent is not particularly limited as long as it is inert under the reaction conditions, but preferred solvents include hydrocarbons such as n-hexane, cyclohexane, benzene, and toluene;
Examples include ethers such as dioxane, tetrahydrofuran, and diethyl ether, and aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, and trimethylacetamide.

The reaction temperature is usually -70 to 60°C, but a more preferred temperature range is 0 to 30°C.

Next, the method for producing compound (II) will be explained.

A compound represented by the formula (ID is a formula (in which R represents a lower alkyl group and Ts represents a tosyl group) (hereinafter referred to as compound (b)) is reacted with lithium bistrimethylsilylamide. This can be achieved by adding an acid and then a base. In the formula (transformation), R represents a lower alkyl group such as methyl, ethyl, n-propyl, isopropyl, etc.

In the reaction between compound (1) and lithium bistrimethylsilylamide, 1 to 5 mol of lithium bistrimethylsilylamide P is usually used per 1 mol of the compound. The reaction temperature can usually be carried out at 0 to 120°C,
A more preferable reaction temperature is 50 to 100°C. This reaction is usually carried out in the presence of a solvent. The solvent is not particularly limited as long as it is inert under the reaction conditions, but preferred solvents include hydrocarbons such as n-hexane, cyclohexane, benzene, and toluene, and ethers such as dioxane, tetrahydrofuran, and diethyl ether. and aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, and dimethylacetamide. Lithium bistrimethylsilylamide used in this reaction can be easily obtained by mixing n-butyllithium and bistrimethylsilylamine.

After the reaction is completed, the reaction solution is quenched with an aqueous solution of a weakly acidic substance such as ammonium chloride or ammonium sulfate, extracted with a suitable organic solvent, and the solvent is distilled off to proceed to the next step.

There are no particular restrictions on the extraction solvent used here, but examples include n-hexane, cyclohexane, diethyl ether,
Diisopropyl ether and the like are used.

Compound (It) can be obtained by reacting compound (1) with lithium bistrimethylsilylamide by the method described above, adding an acid, and then adding a base and allowing the reaction to occur. The acid used here is preferably a strong acid such as p-toluenesulfonic acid, sulfuric acid, hydrochloric acid, trifluoroacetic acid, or tungstic silicoic acid. The amount of acid used is a catalytic amount, which is sufficient, and is usually used in an amount of 0.1 to 5 molti based on compound (1). Examples of the base include sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium carbonate, potassium hydroxide, and lithium hydroxide. The amount of the base used is usually at least 1 molar, preferably 1 to 5 times the molar amount of the compound (conversion). The reaction temperature is usually carried out in the range of -30 to 30°C.

Next, the method for producing the compound (good) will be explained.

The compound (goods) is obtained by cyanohydrinizing the compound represented by the formula (hereinafter referred to as compound (to)) in the presence of an acidic catalyst. (has the same meaning as ) (hereinafter referred to as compound M).

In the cyanohydrination reaction of compound (v), methods used in ordinary cyanohydrin synthesis can be employed. Examples include a method of reacting an alkali metal cyanide such as sodium cyanide or potassium cyanide with an acid such as sulfuric acid or hydrochloric acid, or a method of reacting with trimethylsilyl/anide followed by acid treatment.

The compound (good) can be obtained by reacting the cyanohydrin of the compound (V) with the compound (2) in the presence of an acidic catalyst. In this reaction, it is preferable to use an excess of Compound M, and usually 1 to 5 moles of Compound M are used per 1 mole of cyanohydrin. Examples of the acidic catalyst used here include true acid such as sulfuric acid, hydrochloric acid, and phosphoric acid, benzenesulfonic acid, p-toluenesulfonic acid, and methanesulfone Mnato'D sulfonic acid. The amount of these acidic catalysts used may be catalyst 1, and usually the compound (V
) 0.0001 to 0.0 per mole of cyanohydrin
It is 5 moles.

The reaction temperature is usually -20 to 50°C. A solvent is not particularly required in this reaction, but any solvent can be used as long as it is inert under the reaction conditions. Preferred solvents include n-
Examples include hydrocarbons such as hexane, benzene, and Toluev fZ, chlorinated hydrocarbons such as nochloromethane, chloroform, and carbon tetrachloride, and saturated ethers such as diethyl ether and tetrahydrofuran.

Examples of the present invention will be shown below and explained in more detail.

Practical Example 1 (Synthesis of cyclohiemrenone) 20 ml (0.5 mmol) of sodium hydride (suspended in mineral oil, containing 60% of the active ingredient) was placed in a flask and heated under a nitrogen stream. -After washing with hexane, n-
Hexane was distilled off. Add 1d of dry dimethyl sulfoxide to the flask, add 44 ml (0.2 mmol) of trimethyl sulfoquinonium iodide, and heat at 10°C for 20
It was allowed to react for a minute. In it, compound (lI) 20 W (
0.1 mmol) was dried, and a solution dissolved in 1M f/:,) methyl yv sulfoxide was added, followed by reaction at room temperature for 10 minutes. To the reaction solution were added 1 d of a 5% aqueous ammonium chloride solution and 1 d of a 5% aqueous sodium sulfate solution, and the mixture was extracted with ether. The extracted organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica dull column chromatography to obtain 78 mg (0.04 mmol) of bicyclohumuleno.

Example 2 (Synthesis of compound (n)) Bistrimethylsilylamide/1.1d (5,17mmo
1) was dissolved in 20ml of dry dioxane, and 1.76N n-butyllithium 2,6 was added therein at 10°C.
ml (4.68 mmol) was added. After stirring the reaction mixture at 10°C for 1 hour, compound (R=C,,H
5) 560 ml (1.17 mmol) of dioxane solution was added dropwise over 3 hours at 80° C. under a nitrogen stream.

After the dropwise addition was completed, the mixture was stirred at 80° C. for an additional 30 minutes. The reaction-completed solution was quenched with an aqueous solution of ammonium chloride, and then extracted with diethyl ether. The organic layer was dried over magnesium sulfate and then concentrated under reduced pressure.

Add 3 ml of methanol to the obtained residue and incubate at 0°C.
-) 1 mg of luenesulfonic acid was added and stirred for 30 minutes. After adding 10 ml of diethyl ether #1 to the obtained reaction solution, the mixture was washed with a 5M aqueous solution of 2000 ml of hydroxide, and further dried over magnesium sulfate. After concentrating under reduced pressure, the residue was purified by silica dull column chromatography to obtain compound (It) 210 da. The yield from compound (1) was 87%.

Example 3 (Synthesis of compound (1) (R=c2H5)) Compound (V) 450''9 (1,19 mmol), trimethyl cyanide 0.47 ml (3,57 mmol)
A mixture of 1 ffl) and 18-crown-6KCN was stirred at 0°C for 10 minutes. 3M of tetrahydrofuran and 0.3M of IN hydrochloric acid were added to the reaction mixture, and the mixture was stirred at room temperature for 5 minutes. The resulting mixture was extracted with ether, washed with brine, and then dried over magnesium sulfate. It was further concentrated under reduced pressure, leaving 470 kg of cyanohydrin as a residue.
I got it.

The obtained nine crude cyanohydrins were dried and dissolved in nine benzene 10M, and 0.14 ml of ethyl vinyl ether was added thereto.
(1.43 mmol) was added. This mixture contains p-
) 5In9 luenesulfonic acid was added and reacted at 0°C for 10 minutes. Add 10ml of 5% NaHCO5 aqueous solution to the reaction solution.
was added and extracted with ether. The extracted organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica dull column chromatography to obtain compound 462 Q (0.99 mmol
) was obtained. The yield from compound (7) was 83.

(Effects of the Invention) According to the present invention, an industrially possible chemical synthesis method for vinclohyemrenone, which is expected to be used as a fragrance material, is provided.

Patent applicant RiRashi Co., Ltd.

Claims (1)

[Claims] 1. Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼...... (II) A compound represented by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼... (II) In the presence of a strong basic substance, ...(III) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ......(I) A method for producing bicyclohyumrenone, which is characterized by reacting with the compound shown by. 2. The compound represented by formula (II) has the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ...... (IV) (In formula (IV), R represents a lower alkyl group, and Ts represents a tosyl group. 2. The method according to claim 1, wherein the compound is reacted with lithium bistrimethylsilylamide, followed by addition of an acid and then a base. 3. The compound represented by the formula (IV) is converted into the formula R_1OCH=CH_2 in the presence of an acidic catalyst after cyanohydrinizing the compound represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼......(IV) ...(VI) (In formula (VI), R_1 has the same meaning as in formula (IV).) Method.