JPS5819658B2 - Production method of γ-damascone - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel method for producing γ-damascone.

γ-Damascone is a natural product contained in rose flower essential oil, and is known as a compound related to α,β-damascone.

It is also known that γ-damascone is an extremely useful compound in the preparation of rose fragrances.

Although many proposals have been made regarding methods for synthesizing this useful γ-damascone, no industrially advantageous method for synthesizing it has yet been known.

As a result of intensive research into an industrially advantageous method for producing γ-damascone, the inventors of the present invention have found a method that can obtain γ-damascone in a much shorter process and with a higher yield than conventional methods. He succeeded and filed a patent application (Japanese Patent Application No. 13010/1982).

The outline of the method is as follows. The important feature of this method is to carefully perform the Wittig reaction on the above diketone (i) to obtain the γ-damascone intermediate (II) in one step, and it generally has two ketone groups. Kokichi's method of selectively methylenating only one ketone group, that is, only the ketone group attached to a ring by subjecting a diketone to the Wittig reaction, is difficult, but has been achieved.

The inventors of the present invention continued to conduct intensive studies on an industrially advantageous method for obtaining γ-damascone, and finally arrived at a method for producing γ-damascone as described below.

That is, the present invention provides 3,3-dimethyl-1-cyclohexanone-
2-carboxylic acid ester (hereinafter referred to as ketoester)
2-methylene-6,6-dimethylcyclohexane-carboxylic acid ester (hereinafter referred to as methylene cyclohexanone form) represented by (R represents an alkyl group) was obtained by reacting methylene ylide with a Witzteich inducer. 2-methylene-6,6-
Dimethylcyclohexane-carboxylic acid ester is reacted with an allyl metal salt compound to obtain 1-buten-4-one-1-(2-methylene-6,6 dimethylcyclohexane), and then the obtained 1-butene -4-one-1-(2-methylene-6,6
-Dimethylcyclohexane) is isomerized with a base.

The production method of the present invention, including a preferred production mode of the raw material ketoester (I), can be illustrated as follows.

Next, the manufacturing method of the present invention will be explained in more detail.

The present invention is characterized in that a methylene cyclohexanone compound (It) is selectively synthesized in one step by first applying a Wittig reaction to a ketoester compound.

That is, although the ketoester compound (I) has both a ketone group and an ester group in the cyclohexane ring, in the present invention, only the carbonyl group attached to the ring is selectively converted into a methylene group without affecting the ester group.

This reaction is carried out by the action of the Wittig reagent of methylene ylide for the ketoester.

An example of the methylene ylide Wittig reagent used in the present invention is a methylene ylide Wittig reagent represented by the following general formula.

General formula % Formula % (However, R1 represents an aryl group such as a phenyl group, a P-tolyl group, or a P-methoxyphenyl group.

) Among these, methylenetriphenylphosphine ylide is most suitable as the Wittig reagent used in the present invention.

In the present invention, the methylene cyclohexane compound (n
), where it is appropriate to use a Wit t Ig reagent prepared in benzene.

That is, the Wittig reagent is dimethyl sulfoxide (D
When it is prepared in a solvent such as MSO, salts and bases are dissolved in addition to the ylide, making it impossible to obtain a solution containing only pure ylide.

Therefore, the yield of methylenecyclohexane compound ([1) is poor.

For example, when benzene is used as the extraction solvent for ylide, a pure solution of methylene ylide can be obtained and the yield of methylene cyclohexane (n) can be improved.

In this way, the present invention makes it possible to selectively obtain methylene cyclohexanone (II, 1) in one step by using a particularly desalted Wittig reagent, and to easily convert the endocyclic ketone for the ketoester into a methylene group. can be converted to .

In the present invention, next, methylene cyclohexanone compound (
n) with allyl metal chloride to form 1-butene-4-
1-(2-methylene-6,6-dimethylcyclohexane) (Illll), and allyl lithium is most suitable as the allyl metal salt compound here.

In the present invention, the cyclohexane (111) obtained above is then isomerized in the presence of a base to obtain γ-damascone (IV), which is the object of the present invention.

As the base, a strong base agent such as potassium alkoxide is used.

An important feature of the production method of the present invention is that by using a strong base such as potassium alkoxide as a catalyst, the terminal methylene is rearranged to an α,β-conjugated gumascone type without changing it.

Next, the ketoester used as a starting material in the present invention will be explained.

This ketoester is obtained by C1aisen condensation of a carbonate ester such as methylhebutenone diethyl carbonate in the presence of NaH etc. (R represents an alkyl group) as shown in the figure above. Esters can be obtained by treatment of the esters with Lewis acid catalysts such as sulfuric acid, tin tetrachloride, and the like.

Next, examples of the present invention will be shown.

Example A) Synthesis of 2-methylene-6,6-dimethylcyclohexanecarboxylic acid ester (n) from ethyl 3.3-dimethyl-cyclohaquinone-2-carboxylate 3.3-dimethyl-cyclohexanone-2-carboxylate Ethyl(I) acid! l, 0.025 mol dry benzene 20
A solution of 0.05 mol of methylenetriphenylphosphine ylide in 100 ml of benzene is gradually added to the m1 solution under nitrogen atmosphere at around 20°C.

Inject the ylide with a syringe so that it does not come into contact with air.

Stir for 15 hours and reflux for 6 hours.

The reaction layer and contents were returned to room temperature and decomposed on ice water, and the benzene layer was treated according to a conventional method to dissolve ethyl 2-methylene-6,6-dimethylcyclohexane-1-carboxylate (II).
．． Get 59.

Yield 70% B) From ethyl (II) 2-methylene-6,6-dimethylcyclohexanecarboxylate to 1-buten-4-one-1-
(2-methylene-6,6-dimethylcyclohexane) (
1.5g of lithium and 251r of dry tetrahydrofuran
The Ll solution is cooled to 0° C. in nitrogen atmosphere, and a mixture of 6 g of allyl phenyl ether and L dry ether is added dropwise after adding a small amount of biphenyl as a catalyst.

If it starts to turn blue-green at this time, cool it to -15°C and continue adding the second part for another 10 minutes.

Afterwards, return to room temperature and stir for 30 minutes. In this way, a solution of allyllithium is obtained.

Next, the above allyl lithium solution in nitrogen air was syri
(2) 2.5.9
of dry ether.

After that, the temperature was returned to room temperature, and the contents were decomposed in ice water.
Extract with hexane, dry, and distill off the hexane to obtain 1.5 g of 1-buten-4-one-1-2 (methylene-6°6-dimethylcyclohexane).

Yield 60%.

The spectral data of compound values are as follows.

IR; 2850, 2900, 2950, 3000°17
10.1640,1380,1360°1340.13
25,1315,1070°1050.910,890
,660Crn-'HNMR; δ0.9(6H,d)
, 1.00-2.3 (6H.

m), 3.00-3.2 (3H, t) 4.
7-5.2 (4H, d+t), 5.7-6.2 (LH
, m) C) Synthesis of γ-damascone (IV) 1 g of the compound obtained above was dissolved in 2 ml of dry 1-BuOH, and a small amount of potassium pieces was added to 1 = BuOH under nitrogen atmosphere for 15 minutes at room temperature. Stir.

After that, it was neutralized by adding a few drops of acetic acid, extracted with hexane, washed with water, dried, the solvent was removed, and γ-damascone (
Obtain the entire amount of IV).

Spectral data of γ-damascone (IV) are as follows.

IR; 3000, 2950, 2850, 1690゜1
670.1650, 1640, 1440°1370.1
280,1120,1180゜1070.970,89
0,660cTL-1HNMR; δ0.91(3H,s
), 0.95 (3H.

s ), 1.88 (3H, dXd), 3.22 (IH,
s), 4.7 (IH, s).

4.86 (IH, s), 6.1'8 (IH.

Claims (1)

[Claims] 3,3-dimethyl-1-cyclohexanone- represented by the formula 1 (wherein R represents an alkyl group)
The 2-methylene-6,6-dimethylcyclohexane-carboxylic acid ester represented by the following formula was obtained by reacting methylene ylide with Witzteig's reagent on the 2-carboxylic acid ester (R represents an alkyl group). Methylene-
6,6-dimethylcyclohexane-carboxylic acid ester was reacted with an allyl metal salt compound to obtain 1-buten-4-one-1-(2-methylene-6,6-dimethylcyclohexane, then obtained. 1-buten-4-one-1-(2-methylene-6,6
A method for producing γ-damascone, characterized by isomerizing γ-damascone (-dimethylcyclohexane) with a base. 2. The method for producing methylene ylide according to claim 1, wherein the Witteich reagent is produced in benzene.