JPS61194045A - Production of dihydrocinnamaldehyde derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as perfumery, economically and easily, in high yield and purity, under mild conditions, by the biochemical hydrolysis of a dihydrocinnamaldehyde enol acylate derivative in the presence of a specific catalyst. CONSTITUTION:The objective compound of formula II such as p-isopropyl-alpha- methyldihydrocinnamaldehyde (=cyclamene aldehyde) having high purity can be produced by (1) hydrolyzing the dihydrocinnamaldehyde enol acylate derivative of formula I (R1 is H or 1-6C alkyl; R2 is H or lower alkyl; R3 is lower alkyl) biochemically using a hydrolase having esterase activity such as lipase as a catalyst, at 10-60 deg.C for 1-48hr at 3-9pH controlled by a pH-buffering solution, etc., (2) extracting the resultant reaction liquid with an organic solvent, (3) removing the solvent, and (4) separating and purifying the objective compound e.g. by distillation. The compound is used as a perfume for scented product such as soap, cosmetic, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing dihydrocinnamaldehyde derivatives from their enol acylate derivatives.

Dihydrocinnamaldehyde derivatives have unique aromatic properties and are useful fragrances used in scented products such as soaps and cosmetics. p-isopropyl-α-methyldihydrocinnamaldehyde or cyclamenaldehyde, p
Typical examples include -t-butyl-α-methyldihydrocinnamaldehyde, ie, lilyaldehyde.

[Conventional technology]

Various methods are already known for synthesizing dihydrocinnamaldehyde derivatives. For example, U.S. Patent No. 184
In the method of No. 4013, cuminaldehyde and propionaldehyde are condensed to produce p-isopropylcinnamaldehyde, and then the double bond is selectively hydrogenated to synthesize cyclamenaldehyde, but the selective hydrogenation is not necessary. It is complete.

Furthermore, in the method disclosed in Japanese Patent Publication No. 33-6973, p-inpropyl-α-methylcinnamaldehyde is converted into cyclamen alcohol, which is a saturated alcohol, by a hydrogenation method, and then cyclamen aldehyde is synthesized by a dehydrogenation reduction reaction. The raw material for this method, p-inpropyl-α-methylcinnamaldehyde, is synthesized from cumene, but the method involves many steps and is extremely complicated for industrial operations.

The next simplified method is British Patent No. 850360.
There is a method disclosed in No. This method involves synthesizing enol acylate of dihydrocinnamaldehyde through a Friedel-Crafts-type reaction between a diacyl compound of an α,β-unsaturated aldehyde and cumene, and then hydrolyzing it to synthesize dihydrocinnamaldehyde. Although it is highly practical, the hydrolysis reaction requires a long time at high temperatures and is prone to side reactions due to the harsh conditions, so it is not yet perfect for practical use. Furthermore, a method of alcoholylyzing the enol acylate is also disclosed in JP-A-53-2444, but this method requires a large amount of alcohol and cannot necessarily be called an economical method.

[Problem that the invention seeks to solve]

In view of the above-mentioned prior art, an object of the present invention is to provide a method for producing dihydrocinnamaldehyde derivatives inexpensively and easily.

[Means for solving problems]

Dihydrocinnamaldehyde derivatives can be produced by biochemically carrying out the hydrolysis reaction of the enol acylate derivative in the method for producing dihydrocinnamaldehyde described in British Patent No. 850360, under mild temperature conditions and with high yield. The desired dihydrocinnamaldehyde derivative can be obtained with good results.

That is, the present invention is a method for producing a dihydrocinnamaldehyde derivative represented by the general formula, which comprises biochemically hydrolyzing the dihydrocinnamaldehyde enol acylate derivative represented by the general formula.

However, ■ and "In the formula, R1 represents hydrogen, an alkyl group having 1 to 6 carbon atoms, R2 represents hydrogen or a lower alkyl group, and R1 represents a lower alkyl group.

In the above 1 and 2, the alkyl group having 1 to 6 carbon atoms in R1 is methyl, ethyl, propyl, isopropyl,
a-butyl, isobutyl, t-butyl, n-pentyl,
These include isopentyl, neopentyl, n-hexyl, isohexyl, and the like.

Furthermore, the lower alkyl groups of R3 and R8 include methyl, ethyl, propyl and the like.

Next, the method of the present invention will be described in detail.

The method of the present invention is a method of biochemically hydrolyzing enol acylate of a dihydrocinnamaldehyde derivative to obtain the corresponding dihydrocinnamaldehyde derivative,
The enol acylate of the dihydrocinnamaldehyde derivative used here may be synthesized by any method, for example, by a Lidel-Crafts type reaction between a diacyl compound of an α,β-unsaturated aldehyde and cumene. It is purified and used to reduce isomer content. Its concentration is 1 to 50 W/w% relative to the reaction solution.
preferably from 5 to 20 w/w%.

Biochemical hydrolysis refers to hydrolysis using a hydrolase produced by living organisms as a catalyst. Any substance produced by animals, plants, or microorganisms can be used regardless of its origin as long as it has esterase activity. Such examples include α-chymotrypsin, pancreatin, lipase, and the like. It is also possible to use cells containing the enzyme, cell lysates, or culture medium IIP containing the enzyme as the enzyme source. If necessary, an enzyme stabilizer such as evaporated ethylene glycol, polyoxyalkyl ether, etc. may be added to the aqueous solution.

The reaction pH varies depending on the type of enzyme, but is preferably around the optimal reaction pH of the enzyme, usually in the range of 3 to 9, preferably 5 to 9.

In this reaction, an equimolar amount of carboxylic acid is produced along with the production of dihydrocinnamaldehyde. Therefore, to maintain the pH in the reaction solution, it is necessary to suppress the decrease by using a pH buffer as an aqueous solution, or to add an alkaline aqueous solution to the reaction solution. This is done by adding at the appropriate time.

The appropriate reaction temperature at this time is 10 to 60°C, but lower temperatures reduce the reaction rate and require more time to complete the reaction, while higher temperatures promote a decrease in enzyme activity, so it is particularly preferable. The temperature is 20 to 50°C.

The reaction time is 1 to 48 hours, but the reaction time can be shortened in any way by using a highly active enzyme, increasing its concentration, or increasing the reaction temperature.

The reaction solution obtained in this way can be extracted using a conventional separation and purification method, such as leaving the reaction solution still to separate the oil phase and distilling it to separate the target product, or extraction from the reaction solution with an organic solvent. High purity dihydrocinnamal and dehyde derivatives can be obtained by removing the solvent and then separating the target product by distillation.

As explained above, according to the method of the present invention, a highly purified dihydrocinnamaldehyde derivative can be produced under extremely mild conditions and with good yield by using a hydrolase as a catalyst.

〔Example〕

This will be explained below using examples.

Example 1 p-inpropyl-α-methyldihydrocinnamaldehyde enol acetate) 25/(0.11 mol) was added to lipase (Lipase M-AP sold by Ohno Pharmaceutical KK) 0
．． 0, 1M phosphate buffer (pH 8) containing 5 w/v%
,0) 500 ml and stirred at 37°C for 4 h.
rs reaction was performed. During the reaction, the pH of the reaction solution was maintained at 8 with a 5 w/v% NaOH aqueous solution.

After the reaction, the reaction product was extracted with chloroform, and the resulting chloroform solution was dried over anhydrous nitrogen, and the chloroform was distilled off to obtain crude i-isopropyl-α-methylcinnamaldehyde 17.51 (yield 85%). ) was obtained.

Further distillation under reduced pressure yields purified p-isopropyl-α-methylcinnamaldehyde at bpo, 584-85°C, 16.97
(yield 82%).

Example 2 Contains 0.5 w/v% of p-t-phthyl-α-methyldihydrocinnamaldehyde enol acetate) 50J' (0.2 mol) of lipase (origin: Candeda Cylindracie, sold by Sigma) The reaction mixture was added to 450 g of 0.1 M phosphate buffer (pH 8.0) and reacted for 8 hours while stirring at 37° C. while adjusting the reaction solution pH to 8.

After the reaction, the same post-treatment as in Example 1 was carried out to obtain pt-butyl-α-methyldihydrocinnamaldehyde 331 (
A yield of 79% was obtained.

Bpl, distilled under reduced pressure. A purified product (yield 75%) was obtained at 110-112°C.

Example 3 α-Methyl dihydrocinnamaldehyde enol acetate 19/(0.1 mol) was added to 60.1 MIJ containing 0.2 w/v% of creatine (sold by Ohno Pharmaceutical KK).
Add acid buffer (pH 7.0) 500+JK, 30℃
Adjust the pH of the reaction solution to 7 while stirring for 6 hrs.
Made it react.

After the reaction, the same post-treatment as in Example 1 was performed to obtain α-methyldihydrocinnamaldehyde 10.2/(yield 75%)
I got it.

It was further distilled under reduced pressure to bp4. . A purified product (yield 66%) was obtained at 77-78°C.

Claims (3)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula characterized by biochemically hydrolyzing the dihydrocinnamaldehyde enol acylate derivative represented by I ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼Production method of dihydrocinnamaldehyde derivative shown in II. However, in formulas I and II, R_1 is hydrogen, an alkyl group having 1 to 6 carbon atoms, R_2 is hydrogen or a lower alkyl group, and R
_3 represents a lower alkyl group. (2) The production method according to claim 1, characterized in that a hydrolase having esterase activity is used. (3) Temperature during hydrolysis: 10-60℃, pH: 3-9
The manufacturing method according to claim 1 or 2, characterized in that the method is carried out as follows.