JPH0613510B2 - Method for producing isosafluor epoxide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method of making isosafrole epoxide.

Formula (I) Is an important compound as an intermediate for synthetic fragrances and pharmaceuticals, and is, for example, 1- (3,4-methylenedioxyphenyl) propanone-2 obtained by acid-catalyzed isomerization reaction of isosaflor epoxide. Is 3- (3,4-dihydroxyphenyl) -2-
It is useful as an intermediate for the production of drugs such as methylalanine.
In addition, 1- (3,4-methylenedioxyphenyl) propane-1,2-diol obtained by treating isosaflor epoxide in an acidic aqueous solution is useful as an intermediate for the synthetic perfume heliotropin.

Conventionally, as a method for producing such isosafluor epoxide, 1) a method in which isosaflor is brominated and then treated with an alkali (Barnes, RA; Int. Congr. Essent. Oila. [Pap.])
6th (1974) 182 7pp).

2) A method of reacting isosaflor with metachlorobenzoic acid (J. Tuji; Tetrahedron Letters, 23 3085 (1982)).

3) Method of electrolytically oxidizing isosaflor (Japanese Patent Laid-Open No. 60-48982)
Issue).

Methods such as are known.

However, the method of 1) uses a large amount of bromine, and the method of 2) uses an expensive oxidizing agent, and it is hard to say that either method is industrially advantageous. Further, the method 3) requires an electrolyzer, and it is necessary to overcome many difficulties as an industrial manufacturing method.

On the other hand, a method of epoxidizing an olefinically unsaturated compound with a mixture of hydrogen peroxide and nitrile is already known (for example, GBPayne, JOC26,659, (1960)), but methylenedioxy group is oxidized in isosafurol. It is easy to obtain isosafrole epoxide in good yield, and in fact, there is no example of obtaining isosafrole epoxide by this method.

Therefore, as a result of investigations for industrially producing isosafrole epoxide, the present inventors have found that isosafrole is epoxidized in a mixture of hydrogen peroxide solution and specific nitriles under specific reaction conditions. By doing so, it was found that isosafluor epoxide can be easily obtained in high yield, and the present invention has been completed.

That is, the present invention has the formula (II) Isosafrole represented by hydrogen peroxide solution and general formula
(III) R—C≡N (III) (wherein R represents a methyl group or a phenyl group) in a mixture with a nitrile represented by the reaction temperature of 15 to 45
The present invention provides a method for producing an isosafrole epoxide represented by the above formula (I), which comprises epoxidizing at pH 8 to 10.5 at a temperature of ° C.

In the method of the present invention, examples of the nitriles include acetonitrile and benzonitrile, and acetonitrile is preferable.

Such nitriles are used in an equimolar amount or more, usually 1.1 mol times or more, with respect to isosafurol, and the nitriles can also be used as a solvent.

The concentration of hydrogen peroxide water is not particularly limited, but is 30 to 6
It is preferably in the range of 0% by weight, and the amount used is equimolar or more, preferably 1.1 to 2 with respect to isosaflor.
It is mole times. Use in excess of 2 moles has no adverse effect on the reaction, but it is economically disadvantageous.

When a solvent is used, the solvent is not particularly limited as long as it is inert to the reaction, and various organic solvents are used, but alcohol solvents such as methanol and ethanol are preferably used.

In this reaction, the reaction temperature is 15 to 45 ° C, preferably 2
It is 0-40 degreeC.

If the reaction temperature is lower than 15 ° C., no problem occurs in terms of reaction, but the progress of the reaction is extremely slow and it takes a long time to complete the reaction, which is industrially disadvantageous. Also, the reaction temperature is 45 ℃
If it exceeds, not only waste of hydrogen peroxide is caused, but also various by-products are formed to reduce the yield, which is industrially disadvantageous.

The reaction is carried out in the pH range of 8 to 10.5.

When the pH is lower than 8, the reaction progresses slowly and the reaction yield decreases, and when the pH exceeds 10.5, the decomposition of hydrogen peroxide becomes violent, and a large amount of hydrogen peroxide is required, which is industrial. Is disadvantageous to

Incidentally, adding sodium carbonate or the like as a buffering agent to the reaction system is an effective means, and the amount used in that case is 0.5 to 20 g per 1 mol of isosaflor.

Further, since the pH of the reaction system becomes acidic as the reaction progresses, it is necessary to adjust the pH by adding an alkali in order to maintain the pH of 8 to 10.5. The alkali is preferably sodium hydroxide or potassium hydroxide, and these are usually used as an aqueous solution.

Thus, according to the method of the present invention, isosaflor epoxide can be easily obtained in good yield.

Hereinafter, the present invention will be described with reference to examples.

Example 1 Isosaflor 100 g (0.617 mol), acetonitonil 50.6 g (1.23 mol), 60% hydrogen peroxide water 54 g (0.
952 mol), 200 g of methanol and 5 g of 20% aqueous sodium carbonate are charged into a flask equipped with a stirrer, thermometer, reflux condenser and pH electrode, and stirred at 30 ° C.
And

With the progress of the reaction, the pH of the reaction system is maintained at 10 by adding 30% sodium hydroxide aqueous solution.

The reaction is completed in 20 hours. During this period, the consumption amount of the 30% sodium hydroxide aqueous solution was 12 g.

After completion of the reaction, the reaction mixture is concentrated, then 45 g of a 30% aqueous sodium hydroxide solution is added, and the mixture is vigorously stirred.

After 2 hours, the reaction mixture was separated, and 115.8 g (content 89.2%) of isosaflor epoxide was obtained from the oil layer. Yield 9
3.8%.

If purification is required, it can be distilled further.

Examples 2 to 5 Reaction and post-treatment were carried out in the same manner as in Example 1 except that the reaction conditions shown in Table 1 were used to obtain isosafluor epoxide. The results are shown in Table-1.

Example 6 In a flask similar to that used in Example 1, isosafrole
100 g (0.617 mol), 400 g of acetonitrile and 2
Charge 5 g of 0% sodium carbonate aqueous solution, and bring to 30 ° C. with stirring. To this, 70 g of 60% hydrogen peroxide water (1.23
5 mol) is added dropwise in 30 minutes.

After 1 hour, 2 hours, and 3 hours from the start of the reaction, 30 g (0.529 mol) of 60% hydrogen peroxide solution is added.

The reaction is completed in 10 hours. During this period, a 30% aqueous sodium hydroxide solution is used to adjust the pH of the reaction system to 10.

After completion of the reaction, the same treatment as in Example 1 was carried out to obtain 110.3 g of isosafrole epoxide (content: 87.5%). Yield 87.
5%.

Example 7 In a flask similar to that used in Example 1, isosafrole
50.0 g (0.309 mol), benzonitrile 38.0 g (0.368 mol), 60% hydrogen peroxide water 27 g (0.368 mol), methanol 100 g and 20% sodium carbonate aqueous solution 2.5
Charge g and bring to 30 ° C. with stirring. While continuing stirring at the same temperature, the pH of the reaction system is maintained at 9.5 using a 30% aqueous sodium hydroxide solution.

The reaction is completed in 4 hours and 30 minutes.

During this period, the consumption of 30% aqueous sodium hydroxide solution was 5.7.
It is g.

After completion of the reaction, the reaction mixture is concentrated, 30% aqueous sodium hydroxide solution (22.5 g) is added, and the mixture is vigorously stirred. After 2 hours, the aqueous layer is separated, 100 g of n-hexane is added to the oil layer, and benzamide crystals are removed by filtration. The oil layer is concentrated to obtain 62.4 g of isosaflor epoxide (content: 78.9%).
The yield is 89.4%.

Comparative Examples 1 to 4 The reaction and post-treatment were carried out in the same manner as in Example 1 except that the reaction conditions shown in Table 2 were used to obtain isosafluor epoxide. The results are shown in Table-2.

Claims (1)

[Claims] 1. A mixture of isosafrole with hydrogen peroxide and a nitrile represented by the general formula R-C≡N (wherein R represents a methyl group or a phenyl group) at a reaction temperature of 15 to 45.
Formula characterized by epoxidation at ℃, pH 8 ~ 10.5 A method for producing isosafluor epoxide represented by.