JPS6029714B2 - Manufacturing method of rose oxide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing rose oxide.

Rose oxide was discovered in Bulgarian rose oil, and today it is an indispensable substance for rose- and geranium-based fragrances.

Therefore, in recent years, various methods for industrially synthesizing rose oxide have been attempted.

Among these synthetic methods, there is a method that utilizes 3-methyl-3-buten-1-yl acetate, which is produced in large quantities in the isoprene industry, and was reported by Carbe et al. Scott, Te
trahedronLett. , 1976, 1625)
has been done. This synthesis method of carverse is carried out based on the reaction formula below, but this synthesis method has the disadvantage that the final product contains many compounds and is difficult to purify. It was something.

As a result of extensive research, the present invention has been developed without the drawbacks of purification in the carvers synthesis method described above, even though it uses 3-methyl-3-buten-1-yl acetate, which is an easily available raw material, and which does not require an oxidation reaction. The present invention has completed an industrially advantageous method for producing rose oxide that does not require the production of rose oxide.

That is, the gist of the present invention is that the first invention generates ketoacetate through a radical addition reaction between 3-methyl-3-buten-1-yl acetate and 3-ethoxy-3-methylbutanal, and reduces the ketoacetate. Further, if necessary, a corresponding diol is generated by further hydrolysis treatment, and the diol is treated with sulfuric acid to perform deethoxylation and cyclization to obtain rose oxide. A radical addition reaction between the same starting materials 3-methyl-3-buten-1-yl acetate and 3-methylbutanal produces the ketoacetate, which is then reduced and, if necessary, further hydrolyzed. The method is characterized in that a corresponding diol is produced by subjecting it to the following steps, and the diol is cyclized with balarthrene sulfonic acid to obtain dihydrorose oxide. Hereinafter, the present invention will be described in detail based on examples in the order of steps.

First, we will discuss the radical addition reaction.

The radical addition reaction is performed based on formula '1).

3-Methyl-3-buten-1-yl acetate (
1) 6.4 hol (0.08 hol) and 3-ethoxy-3
-Methylbutanal (roa) 39 liters (0.3 hol) was added and heated to 90 to 100 qo under a stream of dry nitrogen. On the other hand, prepare another one of this solution, and this solution 45.4
In the evening, 0.5 liters (0.00 liters) of penzoyl peroxide was dissolved. This penzoyl peroxide solution was added dropwise into the above-mentioned heated solution over a period of 2 hours, and heating was continued for 6 hours while maintaining the above-mentioned temperature. After cooling the reaction mixture to room temperature,
The mixture was poured into 5% aqueous sodium carbonate solution and extracted with ether. After washing the ether layer with saturated saline,
Dry over sodium sulfate (anhydrous) to remove ether. The residual oil is distilled under reduced pressure to a boiling point of bp. 112-118qC
A fraction of /2 Yanagi Hiyo 10.3 was obtained. This fraction showed a single peak on gas chromatography and MS, I
It was confirmed from the R and NMR spectra that it was 7-ethoxy 3,7-dimethyl-5-oxooctyl acetate (ma). The yield of (ma) at this time was 40%. Similarly, in the reaction of 3-methyl-3-buten-1-yl acetate (1) and 3-methylbutanal (0b), 3,7-dimethyl-5-oxooctyl acetate (mb) (bp.108-11 is 0 /3 side sun and sunset, yield 4
2%).

In the above radical addition reaction, 3-
Methyl-3-pten-1-yl acetate (1) and 3
- Ketoacetate (mb or ma) by reaction with methylbutanal (rob) or its ethoxy derivative (roa)
was produced, and the optimum reaction molar ratio was 1:6.

Incidentally, the by-products in this radical addition reaction are:
6-ethoxy 3,6-dimethylheptyl acetate, 3,6-dimethylheptyl acetate, and 3-Methyl-4-phenylbutylacetate was produced by the addition of phenyl radicals generated from penzoyl peroxide to 3-methyl-3-buten-1-ylacetate (1).

Next, the reduction reaction of ketoacetate (ma and dish b) will be described.

This reduction reaction is carried out according to the '2} formula.

A flask equipped with a thermometer, a thermometer, and a reflux condenser was charged with 2.6 mA (0.01 mol) of 7-ethoxy 3,7-dimethyl-5-oxooctyl acetate (ma) and 30 mA of methyl alcohol, and the reaction was carried out. While keeping the temperature below 5° C., 0.2 liters (0.00 mol) of sodium borohydride (hereinafter abbreviated as SBH) was added. 3 at the above temperature
After continuing to incubate for an hour, the reaction mixture was reduced to 3% of 100'
It was poured into an aqueous sulfuric acid solution and extracted with ether. This ether layer was washed in the same manner as in the radical addition reaction described above, and after drying, the ether was distilled off. The residual oil was separated using column chromatography. The product released from the benzene-ethyl acetate solvent showed a single peak on gas chromatography, and the M
From the S, IR, and NMR spectra, 7-ethoxy 3,
7-dimethyl-5-hydroxyoctyl acetate (W
It was confirmed that a). The yield at that time was 96% in 2.5 days. Similarly, 3,7-dimethyl-5-hydroxyoctylacetate (Wb) (yield 95%) was obtained from 3,7-dimethyl-5-oxooctyl acetate (mb). Furthermore, acetomonohydroxy (
The hydrolysis of Wa and Wb) will be described.

This hydrolysis is carried out according to the formula {3'.

Add 7-ethoxy to a flask equipped with a reflux condenser.
3,7-dimethyl-5-hydroxyoctyl acetate (Na) 6.4 mol (0.03 mol) and 10% NaO
40 g of an aqueous H solution was added thereto, and the mixture was gently refluxed for 3 hours. After the reaction solution was cooled to room temperature, a 3% aqueous sulfuric acid solution was added to neutralize it, and the mixture was extracted with ether. The ether layer was washed with saturated brine and then dried over sodium sulfate (anhydrous) to remove the ether. The residual oil was separated using column chromatography. At this time, what was taken out from the ethyl acetate solvent showed a single peak on gas chromatography, and M
S, IR, NMR subect to 7-ethoxy-3,7-
It was confirmed that it was dimethyloctane-1,5-diol (Va). At this time, the yield was 4.9 yen and the yield was 95%.
Met. Similarly, 3,7-dimethyloctane-1,5-diol (Vb) (yield 95%) was obtained from 3,7-dimethyl-5m hydroxyoctyl acetate (Wb).

Note that this hydrolysis step can also be omitted as follows.

For example, in the reduction reaction of 7-ethoxy-3,7-dimethyl-5-oxooctyl acetate (ma), 7-
Ethoxy-3,7-dimethyl-5-hydroxyoctyl acetate (Wa) can be omitted to directly obtain 7-ethoxy-3,7-dimethyloctane-1,5-diol (Va). That is, acetate (Na) can be obtained by reducing ketoacetate (ma) with SBH in methanol, but the products of this reduction reaction vary depending on the reaction temperature.

In other words, in the reduction reaction mentioned above, the reaction temperature is low (
5℃ or lower), acetate (Wa) was obtained, but when the reaction temperature was 20 to 40℃, acetate (Wa) was obtained.
A mixture of a) and diol (Va) was obtained.

*Therefore, more than twice the molar amount of S as ketoacetate (ma)
When the reaction was carried out using BH at 50 to 60°C, diol (Va) could be obtained with a yield of 96%.

In other words, the hydrolysis step could be omitted.
Diol (Vb) could be obtained by omitting acetate (Wb) in the same manner for ketoacetate (mb).

Next, the cyclization reaction of diols (Va and Vb) will be described.

This cyclization reaction is carried out according to Formula 41.

Add 7-ethoxy to a flask equipped with a simulator and a reflux condenser.
3,7-dimethyloctane-1,5-diol (Va)
7.5 minutes (0.034 mol), 10% sulfuric acid aqueous solution 20
Added 20 g of benzene and 20 g of benzene, and boiled and refluxed for 8 hours.
After the reaction solution was cooled to room temperature, it was poured over 10 saturated brine solutions to separate it into an oil layer and an aqueous layer. The oil layer was washed with saturated brine, dried over sodium sulfate (anhydrous), and then benzene was distilled off. Distill the residual oil under reduced pressure to reduce the boiling point to bp
．． 3.1 fractions of 85-8800/18 fractions were obtained.
This fraction showed two peaks in gas chromatography, and each was separated by column chromatography.
These peaks were confirmed to be rose oxide (Wa), cis-rose oxide and trans-rose oxide, respectively, based on gas chromatogram retention time, MS and IR spectra. The peak area ratio in the gas chromatogram of cis-rose oxide and trans-rose oxide was 90:10, and the yield as a mixture thereof was 60%.

Further, dihydrorose oxide (b) is synthesized as follows.

3,7-dimethyloctane-1,5-diol (Vb
), 0.2 moles of p-toluenesulfonic acid, and 50 moles of xylene were added, and the mixture was stirred for 6 hours while removing the produced water.

After the reaction, dihydrorose oxide (Wb) was treated in the same manner as in the synthesis of rose oxide (Ma) for 3.8 hours (average: 8
6-88 qC/19 Yanagi Hiyo, yield 61%) was obtained. This product could be confirmed because its gas chromatogram retention time, MS and IR spectra matched those of a standard product obtained by hydrogenating rose oxide. In addition, the ratio of cis-dihydrorose oxide and trans-dihydrorose oxide according to the peak area of the gas chromatogram is 60:4.
It was 0. The above cyclization reaction can also be carried out as follows by omitting the above-mentioned hydrolysis step. First, the synthesis of rose oxide (Wa) will be described.

By treating acetate (Wa) with a 10% aqueous sulfuric acid solution, cis and trans rose oxides were obtained in a yield of 60%.

Sulfuric acid is optimal for carrying out the de-ethoxylation reaction and the cyclization reaction simultaneously as in this reaction, and the reaction did not proceed with para-toluenesulfonic acid or boron trifluoride ether anchor salt. Next, the synthesis of dihydrorose oxide (Wb) will be described.

Unlike the case of acetate (Wa), the cyclization of acetate (Wb) does not proceed with sulfuric acid, and the cyclization of dihydrorose oxide (machi b) was obtained.

The production ratio of cis and trans isomers of this dihydrorose oxide (cho b) varies greatly depending on the cyclization conditions, and when para-toluenesulfonic acid is used, the ratio of cis and trans isomers is approximately 60:40. Met. Further, this cyclization reaction proceeded even when heated with trihydric boron ether tsuba salt in tetrahydrofuran, but the yield was 20%. The production ratio of cis isomer and trawas isomer at this time was 90:10. As described in detail above, the present invention uses 3-methyl-3-buten-1-yl acetate, which is an extremely easily available raw material, and the final product is easy to purify, and the cis isomer is said to have an excellent aroma. It is an industrially useful manufacturing method, as it has a high content of 90% and does not require an oxidation step during the process.

Claims (1)

[Claims] 1 3-methyl-3-buten-1-yl acetate and 3
- generating a ketoacetate through a radical addition reaction with ethoxy-3-methylbutanal, and generating the corresponding diol by reducing the ketoacetate and, if necessary, further hydrolysis treatment; A method for producing rose oxide, which comprises treating the diol with sulfuric acid to perform de-ethoxylation and cyclization. 2 3-methyl-3-buten-1-yl acetate and 3
- Generate a ketoacetate by a radical addition reaction with methylbutanal, and generate the corresponding diol by reducing the ketoacetate and, if necessary, further hydrolysis treatment, and convert the diol into para- - A method for producing dihydrorose oxide, which comprises carrying out cyclization with toluenesulfonic acid. 3. Rose oxide according to claim 1, wherein the reaction molar ratio of 3-methyl-3-buten-1-yl acetate and 3-ethoxy-3-methylbutanal in the radyl addition reaction is 1:6. Production method. 4. The method for producing dihydrorose oxide according to claim 2, wherein the reaction molar ratio of 3-methyl-3-buten-1-yl acetate and 3-methylbutanal in the radyl addition reaction is 1:6. . 5. The reduction is carried out in methanol at a reaction temperature of 55 to 65° C. with a reaction molar ratio of sodium borohydride to ketoacetate of 2 times or more and a reaction temperature of 55 to 65° C. Production method.