JPS5929680A - Preparation of rose oxide - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a material for rose-based, or geranium-based blended perfume, by subjecting 3-methyl-3-buten-1-yl acetate and a 3-methylbutanal to radical addition reaction, reducing the addition product, subjecting it to ring formation. CONSTITUTION:A compound shown by the formula I which is prepared as a by-procut in a large amount in isoprene industry and a 3-methyl-butanal shown by the formula II (R is H, or ethoxy) are subjected to radical addition reaction, to give a ketoacetate shown by the formula III. 1 mole of the compound shown by the formula III is reduced with >=2 moles of sodium boron hydride in methanol at 55-65 deg.C to give a diol derivative shown by the formula IV, which is subjected to ring formation to give the desired compound shown by the formula V. EFFECT:The final product is easily purified, and has high content of cis form having improved fragrance.

Description

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

It was discovered in rose oxide and rose oil from Bulgaria, and today it is an indispensable material for rose- and geranium-based fragrances.

Therefore, in recent years, various methods for industrially synthesizing rose oxide have been attempted. Among these synthesis methods, there is a method that makes full use of 3-methyl-3-buten-1-yl acetate, which is produced in large quantities by Isogren Industries.
(C, F, Carbers) and others.
, F, 5cott, Tetrah-edron Le
tt, 1976.1625).

This synthesis method for Calpers is carried out based on the reaction formula below, but it has the disadvantage that the final product contains many compounds and is difficult to purify. It was something that I had.

Therefore, as a result of intensive research, the inventors found that although the easily available raw material 3-methyl-3-butene-1-'+ruacetate gold was used, there was no drawback of purification in the Calpers synthesis method described above. This is an industrially advantageous process for producing rose oxide that does not require any oxidation reactions.

That is, the gist of the present invention is that 3-methyl-3-butene-1-
Ef-ketoacetate 1 is produced through the radical addition reaction of ylacetate and 3-methylputaner/I/or its ethoxy derivative, and after reducing the ketoacetate, it is hydrolyzed or, without going through the entire hydrolysis step, This is a method for producing rose oxide, which is characterized by cyclization.

Hereinafter, all steps of the present invention will be described in detail in the Examples section.

First, we will discuss the radical addition reaction.

The radical addition reaction is carried out based on Formula 11.

(I) (I[a) R=OC2Hs (
nla) R=OC2H5(I[b) R=H(Ib)
R=H 5- In a TT flask equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser, 6.49 (0.05 mol) of 3-methyl-3-buten-1-yl acetate (I) and 3-ethoxy-3 -Methylbutanal (I[a) 39no (0°3m
ol) A gold pot was heated to 90 to 100°C under a stream of dry nitrogen. - 10,000, prepare all this solution separately, and this solution 4
5.49 and 0.5 mo of benzoyl peroxide (0,002 mo
l) k dissolved. This benzoyl peroxide solution was added dropwise into the above-mentioned heated solution over a period of 2 hours, and stirring was continued for 6 hours while maintaining the above-mentioned temperature.

The reaction mixture was cooled to room temperature, poured into a 5% aqueous solution of sodium carbonate, and extracted with ether. After that, the ether layer was washed with fully saturated saline, and then sodium sulfate (
The ether was distilled off. The residual oil was distilled under reduced pressure to obtain fraction 1 with a boiling point bμm 12-118℃/2 mHp.
0. :lt-obtained 'f'Co This fraction had a single peak on the gas chromatography I Daraffy*, and MSllR and N
The yield of 7-nitoxy 3.7-dimethyl-5-oxooctyl acetate (Illa), which was confirmed from the MR spectrum, was 40%.

Similarly, 3-methyl-3-buten-1-yl acetate (
The reaction between I) and 3-methylbutanal (I[b) produces 3
．． 7-dimethyl-5-oxooctyl aceter) (II
lb (bp, 108 to 42% b rate) was obtained.

In the above radical addition reaction, 3-
Methyl-3-buten-1-yl acetate) (I), 3
- Ketoacetate (Illa or Ib) is produced by the reaction of methylbutanal (IIa) or u-t with the ethoxy derivative ([b), but it is suitable for reaction when the reaction molar ratio is IXI:6. there were.

61 as a by-product in this radical addition reaction.
6-ethoxy 3,6-dimethyl hebutyl acetate and 3,6-dimethyl hebutyl acetate are produced by the addition of an alkyl radical generated from an aldehyde to 3-methyl-3-buten-1-yl acetate (1). , and the resulting phenyl radical was added to 3-methyl-3-buten-1-ylacetate (I) to form 7j3-methyl-4-phenylbutylacetate (0 then ketoacetate) (Ina The reduction reaction of and mb) will be described.

This reduction reaction is carried out according to equation (2).

(lla) R=OC2H5(IVa) R=OC2H
5(IIlb) R=H(IVb) R=H 7-Nitoxy (31.7-dimethyl-5-oxooctyl acetate) in a flask equipped with a stirrer, temperature needle and reflux condenser.
(Illa) 2.69 (0.01 mol) and methyl alcohol 30- were added, and while keeping the reaction source [t-5°C or lower, sodium borohydride (hereinafter abbreviated as SBH) 0.2 fi (0,005 mol) )! r added. After continuing to stir at the above temperature for 3 hours, the reaction mixture was poured into a 100% trithiosulfuric acid aqueous solution and extracted with ether.

This ether layer was washed in the same manner as in the radical addition reaction, dried, and then removed from the ether chamber. The residual oil was separated using total column chromatography. A single peak was detected by gas chromatography at 7j eluted from benzene-ethyl acetate solvent, and 7j was detected from MS, I+R, and NMR spectra.
-Nitoxy (3,7-dimethyl-5-hydroxyoctyl acetate) (P/a). At that time, the yield tI'X was 2.5 mm, and the yield 1) was 96%.

Similarly, 3,7-dimethyl-5-hydroxyoctyl acetate (Pub) (yield: 95%) was obtained from 3,7-dimethyl-5-oxooctyl acetate (Ib).

Next, hydrolysis of acetomonohydroxy (Va and 1Vb) will be described.

Margin below 9- This hydrolysis rX is carried out according to equation (3).

(Va) R=OC2H5(Va) R=OC2H5(
]Vb) R=H(Vb) R=H Stirrer, reflux condenser, 7-nitoxy 13.7-dimethyl-5-hydroxyoctylacetate (II/a) 6.49 (0.03 mol) in a gold tipped flask and 40% of a 10% NaOH aqueous solution were added thereto and gently refluxed for 3 hours. After the reaction mixture was cooled to room temperature, an aqueous solution of trithiosulfuric acid was added to neutralize the mixture, and the mixture was extracted with ether.

Ether layer? After washing with saturated brine, it was dried over sodium sulfate (anhydrous) and evaporated with ether.

The residual oil was separated using total column chromatography.

At this time, a single peak of 7t'% eluted from the ethyl acetate solvent was detected by gas chromatography and MS.

It was completely confirmed from the 10-IRX NMR spectrum that it was 7-nitoxy3.7-dimethyloctane-1.5-diol (Va). At this time, the yield t'j was 4.9y, which was 95cm.

Similarly, 3,7-dimethyl-5-hydroxyoctyl acetate (fVb) 9.3.7-dimethyloctane-1
, 5-diol' (Vb) (yield: 95).

Similarly, this method can also be omitted by performing the next step 9 in the water decomposition step. For example, in the reduction reaction of 7-nitoxy 3,7-dimethyl-5-oxooctyl acetate (IHa), 7-nitoxy 3,7-dimethyl-5-hydroxyoctylacetate (Va) is completely abbreviated as 7-nitoxy 3, 7-dimethyloctane-1,5-diol (V
ast - can be obtained directly.

That is, ketoacetate (Illa)'i in methanol,
Reduction of rareacetate (F/a)k can be obtained with SBH, but the F products differ depending on the reaction temperature and reaction temperature of this reduction reaction.

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

Therefore, when the reaction was carried out at 50 to 60°C using 5BH1- in an amount more than twice the molar amount of the ketoaceter (Illa), diol (Va)' could be obtained with a yield of 96%.

In other words, it was possible to omit the mechanical water decomposition step.

This can be done similarly for ketoacetate (Ilb) by omitting the aceter) (lVb) t-to obtain the entire diol (Vb)! ! Ta.

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

Margin below This cyclization reaction is carried out according to formula (4).

(Va) R=OCzHs (Va) (
Wb) (Vb) R=H 7-nitoxy-3,7-dimethyloctane-1,5-diol (Va) in a flask equipped with a stirrer and a reflux condenser.
7.5F (0,034 mol), 10 sulfuric acid aqueous solution 20
Add 1ml of benzene and 20ml of benzene, and boil and reflux for 8 hours.

After cooling the reaction solution to room temperature, add 100 m of saturated brine.
The mixture was separated into an oil layer and an aqueous layer. The oil layer was washed with saturated brine, dried over sodium sulfate (anhydrous), and then distilled off with benzene. The entire residual oil was distilled under reduced pressure to obtain a fraction 3. with a boiling point of 85-88°C/18101H9. If
Two peaks were collected in this fraction by gas chromatography, and each of these peaks was separated by column chromatography.

These peaks were confirmed to be rose oxide (I%a), male cis-rose oxide, and trans-rose oxide from the gas chromatogram retention time, MS, and IR spectrum. The peak area ratio of rose oxide and trans-rose oxide on gas chromatography was 90:
10, and the yield as a mixture of these was 60.

The synthesis of dihydrorose oxide (Wb) is carried out as follows.

3,7-dimethyloctane-1,5-diol (Vb
) 7.0'! (0.04 mol), para-toluenesulfone 0. 50 ml of Sl and xylene were added, and the mixture was stirred for 6 hours while removing all of the generated water. After reaction 88℃/
191 mHf, yield 61%) was obtained fC. Concerning 14- Well, the gas chromatogram retention time, MS and IR spectra were identical to the sample obtained by hydrogenating rose oxide, so we were able to confirm this.

The ratio of cis-dihydrorose oxide to trans-dihydrorose oxide based on the peak area of the gas chromatogram was 60:40.

The above cyclization reaction can also be carried out as follows by omitting the hydrolysis step described above.

First, the synthesis of rose oxide (V[a) will be described.

aceter) (■a) Total 1 (By treating with EJ sulfuric acid aqueous solution, cis and trans-rose oxides were obtained with a yield of 60 cm. As in this reaction, de-ethoxylation reaction and cyclization reaction were carried out simultaneously. Sulfuric acid is best for
) The reaction did not proceed with glutoluenesulfonic acid or boron trifluoride ether complex salt0? The synthesis of lkK dihydrorose oxide (V[b) will be described.

Cyclization of aceter) (II/b) is aceter) (■a)
Unlike the case, the reaction did not proceed with sulfuric acid, and the highest yield of dihydrorose oxide (wb) was obtained when p-toluenesulfonic acid was used as a catalyst. Due to the cyclization conditions of this dihydrorose oxide (Wb), the ratio of the cis-form and the trans-form is greatly different. It was 60:40. The cyclization reaction also proceeded by heating with triborate boron ether complex salt in tetrahydrofuran, but the yield was only 20%. At this time, the production ratio of cis isomer to trans isomer was 90:10.

In the present invention described in detail above, 3-methyl-3-buten-1-yl acetate, which is an extremely easily available raw material, is used, and the final product is easy to purify and has a mild aroma. It is an industrially useful production method, as it has as many as 90 cis isomers, which are said to be unconventional, and does not require any oxidation step during the process.

Claims (1)

[Claims] (1) Is there a radical addition reaction between 3-methyl-3-buten-1-yl acetate and 3-methylbutanal or its ethoxy derivative (9-ketoacetate)? 1. A method for producing rose oxide, which comprises producing ketoacetate, reducing the ketoacetate, and then converting the ketoacetate. (2) A radical addition reaction between 3-methyl-3-butyn-1-yl acetate and 3-methylbutanal or its ethoxy derivative produces 9-ketoacetate,
A method for producing rose oxide, which comprises completely reducing the ketoacetate, followed by hydrolysis, and then cyclization. (3) 3-methyl- in the above radical addition reaction
3-Buten-1-yl acetate and 3-methyl! The reaction molar ratio with tanal or its ethoxy derivative is l:
6. The method for producing rose oxide according to claim 1 or 2, characterized in that: (4) In the above reduction reaction, the reaction molar ratio of sodium borohydride to ketoacetate is 2 times or more, and the reaction is carried out in methanol at a reaction temperature of 55 to 65°C to completely generate diol, and then ring The method for producing rose oxide according to claim 1, which is characterized in that: (5) producing 7-nitoxy-3゜7-dimethyl-5-hydroxyoctyl acetate in the above reduction reaction,
The method for producing rose oxide according to claim 1, characterized in that the acetate is treated with an aqueous sulfuric acid solution to carry out the de-ethoxylation reaction and the cyclization reaction at the same time. (6) In the above reduction reaction, 3,7-dimethyl-5-hydroxyoctyl acetate is produced, and the cyclization reaction is entirely carried out in the presence of cough acetate and all-paratoluenesulfonic acid. The method for producing rose oxide described in Section 1.