KR950013468B1 - Preparation of p-alkoxy-ñô-phenyl acrylic acid - Google Patents

Abstract

This relates to a manufacturing method of p-alkoxy-beta-phenylacrylic acid of formula. In formula, R1 is C1-3 hydrocarbon. This compd. is prepared by debromohydrogenation of 1-bromo-2-(4-methoxyphenyl)propionic acid with base in an organic solvent. The solvent is such as chloroform, dichloromethane and tetrahydrofuran, the reaction temp is 15-100deg.C, and the reaction time is 10-24hrs. The ratio of the reactant and the base is 1:2-1:10 eq.

Description

Method for producing p-alkoxy-β-phenylacrylic acid

The present invention relates to a method of preparing a compound of the following structural formula: p-alkoxy-β-phenylacrylic acid.

In the formula, R ₁ represents a hydrocarbon group having 1-3 carbon atoms.

The compound of the above structural formula is used as a raw material intermediate of pharmaceuticals and cosmetics.

Looking at the reaction process of the method according to the conventional manufacturing method, Organic Reaction Vol. 1 210p Synthesis 177 (87) as follows.

In the formula, Ar represents an aryl group.

The method of the reaction process is economical because the price of acetic anhydride is cheap, but when the substituent of the benzene ring is alkoxy, the yield is lower than 30% is a problem. (For manufacturing method, see Comparative Example 1.)

There is also a method according to Journal of Chemical Society 1470 (54), USP 2,734,904 and UK 1,064,116.

In this case, the reaction process using malonic acid is as follows.

In the formula, Ar represents an aryl group.

According to this method, p-methoxybenzaldehyde, malonic acid, pyridine, piperidine, etc. are mixed and refluxed, cooled, acidified with concentrated hydrochloric acid, the precipitate is filtered, washed with dilute hydrochloric acid and water, and recrystallized from acetic acid to be β-. Phenyl acrynic acid can be obtained.

However, when using malonic acid, the yield is good, but the price of malonic acid is too expensive to be economical.

The gist of the present invention is as follows.

The reaction substance 1-bromo-2- (4-methoxyphenyl) propionic acid is subjected to a dehydrobromination reaction using a base under an organic solvent to prepare p-alkoxy-β-phenyl acrylic acid as a target substance. This reaction is represented by the following equation.

In the formula, R ₁ represents a hydrocarbon group having 1-3 carbon atoms.

1-Bromo-2- (methoxyphenyl) propionic acid, which is a reactant of the above formula, can be synthesized by various known techniques as mentioned in Organic Reaction Vol, 250p.

As the organic solvent, chloroform, dichloromethane, tetrahydrofuran and the like are used.

The reaction temperature is 15-100 ° C., and the reaction time is 10-24 hours, and the addition ratio of 1-bromo-2- (4-methoxyphenyl) propionic acid and base is 1: 2-1: 10 equivalent. .

If the reaction temperature is more than 100 ℃ side reaction may occur, the reaction is too slow below 15 ℃.

In addition, in the case of trialkylamine, more than 10 equivalents does not help improve the yield of the reaction, but rather side reactions occur, and there is no reaction effect at less than 2 equivalents.

Example 1

1) Preparation of 1-bromo-2- (4-methoxyphenyl) propionic acid

12.3 g (0.1 mol) of 4-methoxyaniline is added to the flask, 200 ml of acetone is added to dissolve, and 32 ml (0.3 mol) of 48% hydrobromic acid is added dropwise thereto. After cooling to 10 ° C. or lower, 20 ml of an aqueous solution containing 6.9 g (0.1 mol) of sodium nitrite is added thereto.

After cooling again to 15 ° C., 106 g (1.74 mole) of acrylic acid and 0.1 g (0.0007 mole) of copper bromide were added sequentially, followed by distillation under reduced pressure after 30 minutes to remove acetone, and 300 ml of water was added thereto. The precipitate was filtered and recrystallized with water and formic acid to obtain 18.1 g (yield: 70%) of 1-bromo-2- (4-methoxyphenyl) propionic acid.

2) Preparation of 4-methoxy-β-phenylacrylic acid

Into a flask, a mixed solution of 259 g (1 mol) of 1-bromo-2- (4-methoxyphenyl) propionic acid and 700 ml of chloroform, and a mixed solution of 404 g (4 mol) of triethylamine and 300 ml of chloroform for 1 hour at room temperature After dropping, reflux for 13 hours.

After the reaction, the mixture was distilled under reduced pressure to remove chloroform, acidified with 18% hydrochloric acid solution, and the formed solid was filtered. The filtered solid was recrystallized from water and ethanol to give 167 g of 4-methoxy-β-phenylacrylic acid (yield: 94%). Got.

Example 2

; Preparation of 4-ethoxy-β-phenylacrylic acid

In a flask, a mixed solution of 273 g (1 mol) of 1-bromo-2- (4-ethoxyphenyl) propionic acid and 750 ml of dichloromethane was mixed with a solution of 303 g (3 mol) of triethylamine and 300 ml of dichloromethane at room temperature for 1.5 hours. After the addition, the mixture was refluxed for 11 hours, and the same procedure as in Example 1 was performed to obtain 173 g of 4-methoxy-β-phenylacrylic acid (yield; 90%).

Comparative Example 1

; Preparation of 4-methoxy-β-phenylacrylic acid

27 g (0.2 mole) of 4-methoxybenzaldehyde, 30 g (0.3 mole) of 95% acetic anhydride, and 12 g (0.12 mole) of powdered potassium acetate were added and refluxed at 170-175 ° C. for 5 hours. The reaction solution is poured into 1200 ml of water and unreacted 4-methoxybenzaldehyde is removed by steam distillation.

13 ml of concentrated hydrochloric acid was added to the mixture, and the mixture was stirred for a while. After cooling to room temperature, solid was precipitated. Is obtained.

Summarizing the reaction process (Mochanism) of the present invention as follows.

In the formula, R ₁ represents a hydrocarbon group having 1-3 carbon atoms, R represents a hydrocarbon group having 1-2 carbon atoms.

Claims (4)

P-alkoxy-β of formula (I) characterized by dehydrobromination reaction of 1-bromo-2-phenylpropionic acid of formula (II) with trialkylamine of formula (III) in an organic solvent A process for producing phenylacrylic acid. In the formula, R ₁ represents a hydrocarbon group having 1-3 carbon atoms, R represents a hydrocarbon group having 1-2 carbon atoms. The method for producing p-alkoxy-β-phenylacrylic acid of formula (I) according to claim 1, wherein the organic solvent is chloroform, dichloromethane or tetrahydrofuran. The process for producing p-alkoxy-β-phenylacrylic acid of formula (I) according to claim 1, wherein the reaction temperature is 15-100 ° C. The p-alkoxy- of formula (I) according to claim 1, wherein 2-10 equivalents of trialkylamine of formula (III) is used relative to 1 equivalent of 1-bromo-2-phenylpropionic acid of formula (II). Method for producing β-phenylacrylic acid.