JPS61195690A - Production of p-substituted dihydrocinnamaldehyde derivative - Google Patents

Abstract

PURPOSE:To obtain the titled derivative in high purity, from its enol acylate, by treating a mixture of p-substituted compound and o-substituted compound with a lipase originated from microorganism. CONSTITUTION:Dihydrocinnamaldehyde enol acylate is hydrolyzed in the presence of a microbial lipase acting to a mixture of p-substituted dihydrocinnamaldehyde enol acylate and o-substituted dihydrocinnamaldehyde enol acylate of formula I to effect the preferential hydrolysis of the former acylate, e.g. a lipase produced by a microbial strain belonging to Pseudomonas genus, Rhizopus genus, Aspergillus genus, Mucor genus, etc. Since the pH of the reaction liquid is lowered during the reaction, it is adjusted by the addition of an alkaline aqueous solution. The objective p-substituted dihydrocinnamaldehyde enol acylate of formula II is separated by the conventional separation and purification treatment of the resultant reaction liquid.

Description

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

P-substituted dihydrocinnamaldehyde derivatives have unique aromatic properties and are useful fragrances used in numbered products such as soaps and cosmetics.

P-inpropyl-α-methyldihydrocinnamaldehyde or cyclamenaldehyde, p-t-butyl-
Representative examples include α-methyldihydrocinnamaldehyde, ie, lilyaldehyde.

[Conventional technology]

Various methods are known for the synthesis of dihydrocinnamaldehyde derivatives, but the most simplified and excellent method is the Friedel-Crafts type reaction between an α, β, unsaturated aldehyde diacyl compound and cumene. This method involves synthesizing enol acylate of P-substituted dihydrocinnamaldehyde and then hydrolyzing it using a salt as a catalyst to synthesize P-substituted dihydrocinnamaldehyde, which is disclosed in British Patent No. 850360 and Japanese Patent Publication No. 45-23926. There is.

[Problem that the invention seeks to solve]

In the above conventional method, in the synthesis step of the enol acylate of P-substituted dihydrocinnamaldehyde (P-isomer), the enol acylate of O-substituted dihydrocinnamaldehyde <O-'A isomer) is converted into the P-isomer. However, the physical and chemical properties of the two are similar, and separating and purifying them requires a large amount of purification cost. Therefore, in the method using salt as a catalyst, not only the P-isomer but also the 0-isomer are simultaneously hydrolyzed, and it is unavoidable that each aldehyde coexists in the reaction solution. . From this reaction solution, P
A distillation purification method is usually used as a means of pure separation and purification of substituted dihydrocinnamaldehyde, but P-substituted dihydrocinnamaldehyde
Since the difference in boiling point between dihydrocinnamaldehyde and zero-substituted dihydrocinnamaldehyde is small, the yield of the desired aldehyde is low. In addition, if the yield of the target aldehyde (P-substituted product) is increased, impurities will be reduced to 0.
Since the substituted dihydrocinnamaldehyde is mixed in, the aromatic properties unique to P-substituted dihydrocinnamaldehyde will be impaired.

Furthermore, since the hydrolysis reaction in this method is carried out at a high temperature, various side reactions are likely to occur, and it is not perfect for practical use.

An object of the present invention is to provide a method for obtaining a highly purified product of P-substituted dihydrocinnamaldehyde in good yield and at low cost.

[Means for solving problems]

The present inventors have demonstrated that P-substituted and O-substituted monodihydrocinnamaldehyde enol acylate mixtures can be synthesized using hydrolytic enzymes capable of preferentially hydrolyzing the P isomer, such as Pseudomonas spp., Rh1zopus spp. , Mucor
) Genus, Aspirgillus
The present invention was completed based on the discovery that the desired P'lf-converted dihydrocinnamaldehyde could be obtained in high purity by hydrolysis using the hydrolytic enzyme Lipapi produced by the genus S) as a catalyst.

That is, the present invention has the ability to preferentially hydrolyze P-substituted dihydrocinnamaldehyde enol acylate by acting on a mixture of P-substituted dihydrocinnamaldehyde enol acylate and O-substituted dihydrocinnamaldehyde represented by the general formula! This is a method for producing a P-substituted dihydrocinnamaldehyde derivative represented by the general formula, characterized in that the enol acylate is preferentially hydrolyzed in the presence of a lipase produced by a microorganism having the following.

However, in formulas I and (2), R1 represents hydrogen, an alkyl group having 1 to 6 carbon atoms, R1 represents hydrogen or a lower alkyl group, and R3 represents a lower alkyl group.

The alkyl group having 1 to 6 carbon atoms in R1 in I and
-Butyl, isobutyl1. t-butyl, n-pentyl,
These include impentyl, neopentyl, n-hexyl, isohexyl, and the like.

(6) Furthermore, the lower alcohol groups of R2 and R3 include methyl, ethyl, propyl, and the like.

Although the mixing ratio of the O-isomer and the P-isomer of the dihydrocinnamaldehyde enol acylate (U) compound used in the present invention may be arbitrary, it is desirable that the latter ratio be higher. It is also possible to use enol acylate mixtures containing other isomers or impurities.The concentration of the enol acylate mixture is in the range of 1 to 50 w/w%, preferably 5 to 20%, based on the reaction solution.
It is w/w%.

The lipase used as a catalyst is a lipase produced by microorganisms that has the ability to preferentially hydrolyze P-substituted dihydrocinnamaldehyde enol acylate by acting on it, and it is a lipase produced by microorganisms that has the ability to preferentially hydrolyze P-substituted dihydrocinnamaldehyde enol acylate. Genus Aspergilus, Mucor
11 Hase produced by microorganisms belonging to the genus Or) is used. The purity of these enzymes does not matter, and both crude products and purified products can be used. Commercially available enzymes produced by the above-mentioned microorganisms can also be conveniently used. It is also possible to use cells containing the enzyme, cell lysates, culture P solution containing the enzyme, etc. as enzyme sources. If necessary, an enzyme stabilizer such as ethylene glycol polyoxyalkyl ether may be added to the aqueous solution.

In the cono reaction, P-substituted dihydrocinnamaldehyde is produced and equimolar amounts of carboxylic acid are produced, so the pH in the reaction solution is lowered. It is preferable to suppress the decrease.
The reaction pH is adjusted by using a pH buffer as the aqueous solution or by adding an alkaline aqueous solution to the reaction solution at appropriate times.

Although the anti-ff1 pH varies depending on the type of lipase, it is preferably around the optimal pH of the lipase, and is usually 3 to 9.

The appropriate reaction temperature at this time is 10 to 60°C, but if the temperature is too low, the reaction time will be required, and if it is too high, the activity of the enzyme will be significantly reduced, so it is preferably 20°C.
to 50°C. Moreover, it is preferable to carry out the reaction system under an inert atmosphere such as nitrogen gas.

The reaction solution 7 obtained in this way can be used in a high yield using a conventional separation and purification method, such as separating the oil phase using a reaction solution vibrator, and then separating the target product by distillation or chromatographic separation. High purity P-substituted dihydrocinnamaldehyde can be obtained.

As explained above, according to the method of the present invention, a P-substituted dihydrocinnamaldehyde enol acylate derivative can be produced using a lipase produced by a microorganism having the ability to preferentially hydrolyze a P-substituted dihydrocinnamaldehyde enol acylate derivative as a catalyst.

This will be explained below using examples.

Examples: P-isopropyl-α-methyldihydrocinnamaldehyde enol acetate 82 w/w% 0-isopropyl-α-methyldihydrocinnamaldehyde enol acetate 15 w/w%, cumene 2 w/w%, others 1 w/w A mixture having a composition of 50.9% and 0.1 M phosphate buffer (pH 8 ,0) 45 (1m
I) in the reaction solution with 5 w/v% NaOH aqueous solution during the reaction for 24 hrs with stirring at 37°C.
I maintained it at a hot 8. Also, during the reaction, nitrogen gas Y
IA! The reaction was carried out while bubbling into the reaction solution at a rate of /hr.

After the reaction, the reaction product was extracted with chloroform, the resulting chloroform solution was dried over anhydrous nitrogen, and the chloroform was distilled off to obtain 42 g of crude P-isopropyl-α-methylcinnamaldehyde. The composition of this product is P-inpropyl-α-methylcinnamaldehyde 78 w/w
%, O-isopropyl-α-methylcinnamaldehyde 1.5w/w%, P-ingrovir-α-methylcinnamaldehyde enol acetate) 0.1 w/w% or less, 0-isopropyl-α-methylcinnamaldehyde enol acetate -) 16.4 w/w%, other 4
It was w/w%. The reaction solution was distilled under reduced pressure to bp6.
Purified P-isopropyl-α-methylcinnamaldehyde 31F'& was obtained at 585°C.

Claims (1)

[Claims] General formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ P substitution represented by I - P substitution acting on a mixture of dihydrocinnamaldehyde enol acylate and O substitution - dihydrocinnamaldehyde enol acylate - A general formula characterized by hydrolyzing P-substituted dihydrocinnamaldehyde enol acylate in the presence of a lipase produced by a microorganism that has the ability to preferentially hydrolyze dihydrocinnamaldehyde enol acylate ▲ Mathematical formula, chemical formula, There are tables etc. ▼It is indicated by II. A method for producing a P-substituted dihydrocinnamaldehyde derivative. However, in formulas I and II, R_1 is hydrogen or an alkyl group having 1 to 6 carbon atoms, R_1 is hydrogen or a lower alkyl group, and R_3 is a lower alkyl group.