JPS63227542A - Method for producing 4-hydroxyphenylpropionic acid compound or its ester - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing an industrially useful 4-hydroxyphenylpropionic acid compound or its ester.

[Conventional technology]

4-Hydroxyphenylpropionic acid compounds or their esters are useful as synthetic intermediates for pharmaceuticals and industrial chemicals such as antioxidants. For example, 4-hydroxyphenylpropionic acid is used as a raw material for cetraxate, a drug for peptic ulcers. There is. Among these compounds, 4-hydroxyphenylpropionic acid reduces 4-hydroxycinnamic acid obtained by condensing 4-hydroxybenzaldehyde and malonic acid, according to Chemical Abstracts Vol. 94, No. 21, 174782n. By subjecting it to a reaction, in the case of methyl 3-tertiary butyl-4-hydroxypropionate, Japanese Patent Publication No. 46-7933
It is produced by dropping methyl acrylate into a mixed solution of 2-tertiary butylphenol, sodium hydroxide and dimethyl sulfoxide under nitrogen substitution, which is similar to the method described in the above publication. ga-2
= known.

[Problem that the invention seeks to solve]

However, since the method described in the chemical abstract above requires high raw material prices and involves complicated steps such as reduction reactions, it is not easy to obtain the target product with high purity and high yield. isn't it. In addition, in the production of methyl 3-tert-butyl-4-hydroxyphenylpropionate, in addition to the high price of the raw material 2-tert-butylphenol, the other ortho position of the hydroxyl group is unsubstituted. , the purity of the reactant is poor and purification is not easy.

Thus, conventional methods for producing 4-hydroxyphenylpropionic acid compounds and their esters are not satisfactory.

[Means for solving problems]

Therefore, in order to solve the problems of the above-mentioned conventional methods, the present inventors have made extensive studies and have found a method that can easily and economically obtain a highly purified 4-hydroxyphenylpropionic acid compound or its ester. They discovered this and completed the present invention. That is, the present invention provides 3-(3,5
-ditertiary butyl-4-hydroxyphenyl)propionic acid or its ester is subjected to detertiary butylation in the presence of an acidic substance [in the formula, R1
is hydrogen or tertiary butyl, R2 is hydrogen or alkyl (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, peptyl, octyl, 2-
Straight chain or branched alkyl having 1 to 22 carbon atoms such as ethylhexyl, 1,1,4.4-tetramethylbutyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, eicosyl, and tocosyl are preferable. . ) is shown. ] It is related with the manufacturing method of the 4-hydroxyphenylpropionic acid compound or its ester represented by these.

The acidic substances used include inorganic acids such as sulfuric acid, hydrochloric acid, and perchloric acid, and organic acids such as benzenesulfonic acid, paratoluenesulfonic acid, and trifluoroacetic acid.

The reaction proceeds in a suitable solvent (benzene, toluene, chloroform, dichloroethane, etc.) under cooling or at a temperature from room temperature to the boiling point of the solvent used for 30 minutes to 24 hours. The obtained target product can be purified by conventional means such as recrystallization and chromatography.

[Action and effect of the invention]

According to the method of the present invention, readily available starting compounds are used, the reaction itself is easy, and the target product can be obtained with high purity, so it is extremely economical and advantageous compared to conventional methods. It is.

〔Example〕

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but it goes without saying that the present invention is not limited thereto.

Example 1 100 g of 3-(3,5-ditert-butyl-4-hydroxyphenyl)propionic acid methyl ester was placed in a 500 m1 four-day flask equipped with a condenser and a temperature needle. ! 12 g of sulfuric acid, 250 g of toluene, and 50 g of methanol were charged, and the mixture was stirred under reflux conditions for 12 hours. After the reaction was completed, 100 g of a 20% aqueous sodium hydroxide solution was added to the reaction solution.
After vigorous stirring, liquid separation was performed. This operation was repeated twice, and 80 g of 35% hydrochloric acid was added to the aqueous layer for the second time. Then, from the aqueous layer, 200 ml of methyl isobutyl ketone was added.
Extraction was performed twice, and the methyl isobutyl ketone layer was washed once with water and then concentrated. The remaining residue was washed with toluene, filtered, and dried.
34 g of 3-(4-hydroxyphenyl)propionic acid (yield: 60%), white crystals with a melting point of 129-131°C
I got it.

Example 2 IIl four-day flask with condenser and thermometer = 6
- 500 g of methyl 3-(3,5-ditertiary-butyl-4-hydroxyphenyl)propionate, 25 g of concentrated sulfuric acid
and 300 ml of toluene were charged, and the mixture was stirred for 2.5 hours under reflux conditions.

After the reaction was completed, the mixture was washed with water, the solvent was distilled off, n-hexane was added to the residue, the mixture was cooled on ice, and the precipitated crystals were filtered. When the crude crystals were recrystallized from n-hexane, 290 g of methyl 1(3-tertiary phthyl-4-hydroxyphenyl)propionate (yield 72
%) was obtained.

In a similar manner, 3-(3,5-di-tert-butyl-4-
From dodecyl hydroxyphenyl) propionate, dodecyl 3-(3-tert-butyl-4-hydroxydiphenyl) propionate was obtained as a pale yellow transparent viscous liquid. Also, from octadecyl 3-(3,5-ditertiary-butyl-4-hydroxyphenyl)propionate, melting point 43-45
℃ white crystals of octadecyl 3-(3-tert-butyl-4-hydroxyphenyl)propionate were obtained.

=7-

Claims (1)

[Claims] A general method characterized by detertiary butylation of 3-(3,5-ditertiary butyl-4-hydroxyphenyl)propionic acid or its ester in the presence of an acidic substance. 4-Hydroxyphenylpropionic acid compound or its Production method of ester.