JPS6331469B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a monoterpene oxide, rose oxide, namely 2-(2'-methyl-1'-propenyl)-4-methyl-tetrahydropyran (hereinafter referred to as
This invention relates to a new and industrially advantageous method for producing rose oxide (referred to as rose oxide). More specifically, it is a novel three-step production method for optically active or racemic rose oxide using optically active or racemic citronellol as a raw material.

Specifically, (a) citronellol was anodic methoxylated in methanol using an alkali metal salt of an aromatic sulfonic acid as a supporting salt to form 2,6-dimethyl-3-
(b) This 2,6-dimethyl-3-methoxyoct-1-en-8-ol is demethanolated in the presence of a palladium or nickel complex catalyst and a base. and convert it into 2,6-dimethyl-1,3-octadien-8-ol (hereinafter abbreviated as dehydrocitronellol), and then (c) cyclize dehydrocitronellol using an acid catalyst to purify rose oxide. Regarding how to. Conventionally, various methods have been proposed for producing rose oxide using citronellol as a raw material.

For example, (1) French Patent No. 1539054 or J.
Org. Chem 35 , 1097 (1970) from citronellyl acetate to dehydrocitronellyl acetate.

(2) Dutch Patent No. 6503936 or
via citronellol epoxide as described in Helv.Chim.Acta. 48 182 (1965).

(3) The method via dehydrocitronellol described in Dutch Patent No. 6903287.

(4) Direct synthesis method by electrolysis described in Japanese Patent Publication No. 47-27511.

etc.

These known methods have disadvantages, such as using more than the same mole of highly dangerous peroxides or involving high-temperature reaction steps. In addition, the yield is generally low and it cannot be said to be an advantageous method for industrially producing rose oxide. Therefore, there has been a demand for a new method for producing rose oxide, which is useful as a raw material for fragrances, in an industrially advantageous manner.

According to the method of the present invention, high purity rose oxide can be produced in a high yield in relatively short steps and without using a large amount of reagents. This new synthetic route is represented by the following three formulas.

1st step (anodic methoxylation reaction) 2nd step (demethanolation reaction) 3rd step (cyclization reaction) In the first step, citronellol is anodic methoxylated in methanol using an alkali metal salt of an aromatic sulfonic acid as a supporting salt.

The anodic methoxylation in the present invention is carried out according to a conventional electrolytic method, and in particular, an alkali metal salt of an aromatic sulfonic acid is used as a supporting salt. This method produces a methoxylated product, 2,6-dimethyl-3-
This method not only significantly increases the yield of methoxyoct-1-en-8-ol, but also has the advantage of being able to use a supporting salt that is easy to handle and inexpensive. Among the alkali metal salts of aromatic sulfonic acids, those having a lower alkyl substituted or unsubstituted benzene nucleus as the aromatic group, and those having sodium or potassium as the alkali metal are preferred. Specific examples of excellent supporting salts include sodium benzenesulfonate, sodium p-toluenesulfonate, and the like.

The preferred concentration range of these supporting salts in the electrolyte is 0.5 to 10% by weight, more preferably 1 to 3% by weight.

The concentration of raw material citronellol in the electrolyte is not particularly limited, but a low concentration is uneconomical, and an excessively high concentration is disadvantageous because it leads to a decrease in the yield of the target methoxy compound. A range of 5 to 60% by weight, preferably 10 to 40% by weight is suitable.

When performing electrolysis according to the method of the present invention, materials such as carbon and platinum are used as the anode, with carbon being particularly preferred. In addition to carbon and graphite, metals or alloys such as platinum, aluminum, silver, copper, and steel are used as the cathode. The electrolytic cell may be either a container divided by a diaphragm or the like, or a container not divided.

When carrying out electrolysis in such a tank, the potential between the electrodes is in the range of 2 to 10 volts, and the current density is set in the range of 2 to 10 volts.
It is preferred to keep it within the range of 0.5 to 20 A/dm ² . There are no particular restrictions on the electrolysis temperature, but a temperature of 40°C or higher gives preferable results.

In order to carry out the present invention more effectively, it is desirable to vigorously stir the anolyte, and this can be easily accomplished by means such as stirring with a conventional stir bar or high-speed circulation with a pump.

2,6-dimethyl-3-methoxyoct-1-en-8-ol is obtained by separating and purifying the reaction product mixture by distillation. In the second step, the 2,6
-dimethyl-3-methoxyoct-1-ene-8
-ol is converted to dehydrocitronellol by demethanolation in an alcoholic solvent in the presence of a palladium or nickel complex and a base.

In general, various methods for synthesizing olefins by dealcoholizing ethers have been studied, and for example, the following methods are known.

(1) A method using an organic base as described in J.Am.Chem.Soc., 73 , 5708 (1951) or Chem.lett.1975, 1167.

(2) Chem.Ber., 100 , 1764 (1967) or
A method using an acid or an acidic substance as described in Syntheses, 1976 545.

etc. Both (1) and (2) have low yields of the target product and are difficult to be used industrially as demethanolization catalysts for the compounds concerned. Therefore, the present inventors have extensively searched for catalysts that can smoothly proceed with the demethanolation reaction, and as a result, they have found that palladium or nickel complexes are effective, and furthermore, they have found that the demethanolation reaction can be carried out industrially advantageously. We have established the conditions for

Next, the method will be explained in detail.

As the main catalyst, a palladium complex represented by the general formula PdL ₂ X ₂ or a nickel complex represented by the general formula NiL ₂ ' is used. Here, L means a trialkylphosphine ligand, L' means a cyclic diene ligand, and X means a halogen atom.

In the PdL ₂ X ₂ type palladium complex catalyst, the alkyl group of trialkylphosphine L is linear
Those from C ₁ to C ₁₂ are preferred. Further, it is preferable that the halogen atom X is a chlorine atom. Specific examples of excellent catalysts include bis(tri-n-butylphosphine)palladium() chloride, bis(tri-n-octylphosphine)palladium() chloride, and the like. In the above-mentioned palladium complex catalyst, palladium () halide and trialkylphosphine may be added separately to the system without preparing the complex outside the system in advance.

Among the NiL ₂ ' nickel complex catalysts, those in which the cyclic diene L' is an 8-membered ring are preferred. A specific example of an excellent catalyst is bis(cyclooctadiene)nickel 0. When using the above-mentioned nickel chains, it is advantageous to further coexist a linear C ₁ to C ₁₂ trialkylphosphine in an amount of 4 times or more the mole of the chains, as the catalyst efficiency increases significantly. As the linear C ₁ to C ₁₂ trialkylphosphine,
Particularly preferred is tri-n-butylphosphine.

As the base to coexist with palladium as the main catalyst or the nickel complex, a wide range of organometallic compounds with reducing power are used, and among them, organosodium compounds and organolithium compounds are preferred. Specific examples of particularly excellent organic bases include sodium methoxide, n-butyllithium, and the like.
The appropriate amount of these bases to be added is 2 to 6 times the mole of the palladium or nickel complex. If the amount is less than 2 times the mole, no catalytic activity will be exhibited, and if it is added more than 6 times the mole, there will be no particular increase in the effect.

As a solvent for the demethanolization reaction in the method of the present invention, a _C1 to _C4 lower alcohol or a mixture thereof can be used. Specific examples of particularly effective solvents include methanol, ethanol, isopropanol, methanol/isopropanol mixtures, and the like. The latter mixture is 1/5 to 5/1
It can be used in a composition range of 1/1, but a composition around 1/1 is particularly suitable.

The concentration of 2,6-dimethyl-3-methoxyoct-1-en-8-ol, which is the product to be demethanolated, in these alcohol solvents is 0.5 to 40
% by weight, more preferably in the range of 1 to 20% by weight.

The molar ratio of palladium or nickel complex to 2,6-dimethyl-3-methoxyoct-1-en-8-ol is between 0.1 and 2,6-dimethyl-3-methoxyoct-1-en-8-ol.
The range is 10%, but considering the reaction rate and catalyst cost, 0.5% to 2.5% is industrially advantageous.

Regarding the temperature, it is preferably in the range of 50°C to 120°C, more preferably in the range of 60°C to 100°C. 50
At temperatures below ℃, it takes a long time to complete the reaction. On the other hand,
If the temperature exceeds 120°C, the yield of the target product will decrease, which is not preferable.

Although the reaction time depends on the reaction conditions, 12 hours or less is sufficient within the above-mentioned preferred catalyst concentration and temperature range.

Furthermore, it is preferable to carry out the reaction in an atmosphere of a dry inert gas such as argon or nitrogen in order to improve the yield of the target product.

After removing the catalyst, the dehydrocitronellol obtained in the second step is purified by distillation and subjected to the cyclization reaction in the third step.

In the third and final step of producing rose oxide from citronellol, dehydrocitronellol synthesized in the second step is cyclized in the presence of an acid catalyst to produce rose oxide. This process is carried out by, for example, J.Org.
Chem. 35 . 1097 (1970) using an acid catalyst such as sulfuric acid or p-toluenesulfonic acid. In other words, the molar ratio of acid catalyst to dehydrocitronellol, which is the reaction raw material, is
0.1 to 30%, preferably 1 to 10 mol%. As the acid, both inorganic acids and organic acids can be used, but in particular 20 to 60% by weight
The use of sulfuric acid gives favorable results.

A suitable amount of water is used as a solvent, but it is not necessary to add water when using dilute acids.

The preferred range of reaction temperature is 20 to 100°C, more preferably 30 to 60°C.

The reaction time is generally within 10 hours.

The target product, rose oxide, can be obtained with high purity by rectifying the reaction product.

Note that if optically active citronellol is used as a starting material, optically active rose oxide can be obtained as the final product.

Hereinafter, specific methods of the present invention will be explained using Examples.

Identification and quantification of the product was done by IR, NMR, gas chromatography and mass spectrometry.

The yield of each reaction product means the value of the following formula.

Number of moles of product / number of moles of raw material × 100 (%) Example 1 A glass container with an internal volume of 300 c.c. was used as an electrode with a diameter of 10
Two carbon rods with a length of 30 mm and a length of 30 mm were inserted, and the poles were fixed with a distance of 2 mm. Methanol 11 in this tank
After adding 1.2 g of citronellol and 0.2 g of sodium benzenesulfonate, electrolysis was carried out at room temperature under nitrogen at a constant current of 0.25 A until F/m=3.0 was reached. During this time, the interelectrode voltage was maintained at 4 to 5 volts.

The analysis results of the reaction solution were as follows.

Citronellol reaction rate 94.6% 2,4-dimethyl-3-methoxyoct-1-
En-8-ol yield 56.4% (including a small amount of positional isomer) 2,6-dimethyl-2,3-dimethoxyoct-8-ol yield 9.5% Rose oxide yield 2.7% Methanol was extracted from the electrolytic reaction solution. After removing by distillation,
Rectification was performed under reduced pressure (2 mmHg) to obtain 2,6-dimethyl-3-methoxyoct-1-en-8-ol as a fraction at 105-107°C.

Example 2 A well-dried 50c.c. three-necked flask was equipped with a reflux condenser and a septum cap under an _N2 atmosphere.
1.0 mmol of 2,6-dimethyl-3-methoxyoct-1-en-8-ol in purified ethanol 10
cc and charged into a flask with a syringe, followed by 0.05 mmol of bis-(tri-n-butylphosphine)palladium chloride and 0.15 mmol of sodium methoxide in this order. After all the charges were completed, the temperature was raised to 80-85°C and the reaction was kept at that temperature for 5 hours while stirring with a magnetic stirrer.

The analysis results of the reaction solution were as follows.

2,6-dimethyl-3-methoxyoct-1-
En-8-ol reaction rate 92.0%, dehydrocitronellol yield 81.4% Example 3 The reaction was carried out in the same manner as in Example 2 except that 0.1 mmol of bis-(tri-n-octylphosphine)palladium chloride was used as a catalyst. I did it. The results were as follows.

2,6-dimethyl-3-methoxyoct-1-
En-8-ol reaction rate 86.5% Dehydrocitronellol yield 67.3% Example 4 Example 4 except that 0.1 mmol of palladium chloride, 0.2 mmol of tri-n-butylphosphine, and 0.3 mmol of sodium methoxide were separately added as catalysts. The reaction was carried out in the same manner as in 2. The results were as follows.

2,6-dimethyl-3-methoxyoct-1-
En-8-ol reaction rate 83.5% Dehydrocitronellol yield 66.9% Example 5 As a catalyst, 0.1 mmol of bis(cyclooctadiene)nickel 0 and 0.3 mmol of sodium methoxide
The reaction was carried out in the same manner as in Example 2, except that 0.4 mmol of tri-n-butylphosphine was added as an additive. The results were as follows.

2,6-dimethyl-3-methoxyoct-1-
En-8-ol reaction rate 54.5% Dehydrocitronel yield 32.9% Example 6 Except that 0.1 mmol of bis(tri-n-butylphosphine)palladium() chloride and 0.3 mmol of butyllithium were added as catalysts. The reaction was carried out in the same manner as in Example 2. The results were as follows.

2,6-dimethyl-3-methoxyoct-1-
En-8-ol reaction rate: 100% Dehydrocitronellol yield: 58.4% Example 7 The demethanolization reaction solution obtained using the catalyst of Example 2 was washed with water, extracted with ether, and concentrated to give 8 g of dehydrocitronellol. Pour 5 ml of 30% sulfuric acid into a 30 c.c. flask equipped with a condenser on the top.
The reaction was carried out at 60° C. for 2.5 hours with vigorous stirring using a magnetic stirrer. GC of reaction solution
The analysis results were as follows.

Dehydrocitronellol reaction rate 98.9% Rose oxide yield 98.5% The cis/trans ratio was approximately 90/10.

Example 8 Optically active citronellol [α] as a raw material
²⁰ _D -4.14゜Example 1, Example 2 using 15g of pure liquid,
When the reaction was carried out according to the method of Example 7, optically active rose oxide [α] ²⁰ _D -34.8゜pure liquid 5.3
g was obtained.

The cis/trans ratio was approximately 95/5.

Claims (1)

[Claims] 1 (a) Citronellol is anodic methoxylated in methanol with an alkali metal salt of an aromatic sulfonic acid as a supporting salt to form 2,6-dimethyl-3
-methoxyoct-1-en-8-ol, (b) then in the presence of a palladium or nickel complex and a base, the 2,6-dimethyl-3 synthesized in (a).
-Demethanolation of methoxyoct-1-en-8-ol to produce 2,6-dimethyl-1,3-
(c) In the presence of acid, 2,6-dimethyl-1,3-octadien-8-ol synthesized in (b) is cyclized to give 2-(2'- A method for producing 2-(2'-methyl-1'-propenyl)-4-methyl-tetrahydropyran using citronellol as a raw material, the method comprising obtaining methyl-1'-propenyl)-4-methyl-tetrahydropyran.