CS198169B2 - Process for preparing derivatives of alpha-phenylpropionic acid - Google Patents

Description

(54) A method for producing α-phenyipropanoic acid derivatives

The present invention provides a process for the preparation of α-phenylpropionic acid derivatives of the formula I

CH ₃

CHCOOH

CW ₃

CHCHO

where

R represents an alkyl group having 2 to 5 carbon atoms, such as an ethyl group, a butyl group or preferably an isobutyl group, or a cycloalkyl group having 3 carbon atoms.

Polish patent 68 998 and DE 2 404 160 disclose processes for the preparation of [alpha] -phenylpropionic acid derivatives by the oxidation of [alpha] -phenylpropionaldehyde derivatives of the general formula II with R as defined above with silver oxide or potassium permanganate.

An important disadvantage of oxidizing α-phenylpropionaldehyde derivatives with silver oxide is that a large excess of expensive silver oxide must be used, which must then be recovered, making the process uneconomical and difficult to carry out. The yield of the oxidation reaction described in DE 2 404 160, in which 2- (4-isobutylphenyl) propionaldehyde is oxidized with silver nitrate, is barely 57%. A disadvantage of oxidizing α-phenylpropionaldehyde derivatives with potassium permanganate is the necessity of removing the resulting manganese dioxide from the reaction medium as well as

198189 and the low yield of the acid produced, which is caused by side reactions accompanying the oxidation of the aldehyde group, in particular by the partial oxidation of the alkyl group bound as a substituent on the phenyl core.

It has now been found that the compounds of the formula I can be prepared in a novel manner.

The process according to the invention makes it possible to avoid all the drawbacks of the aforementioned patents, such as the use of expensive silver compounds or the formation of by-products using potassium permanganate.

The process according to the invention is highly advantageous, since an easily available sodium chlorite is used as the oxidizing agent, which makes it possible to produce pure α-phenylpropionic acid derivatives on an industrial scale.

The process according to the invention for the preparation of α-phenylpropionic acid derivatives of the general formula I, wherein R is as defined above, characterized in that the β-alkyl-α-phenyl-propionaldehyde of the general formula II

CP ₃ cvcvo

where

R is as defined above, oxidized with sodium chlorite in the presence of aminosulfonic acid or sulfuric acid, or a mixture of both, in a mixture of water and an organic solvent, preferably a mixture of water with ethanol or a mixture of water and dioxane, 100 ° C, preferably at 20 ° C.

The oxidation is preferably carried out for 2 to 12 hours. As the organic solvent used in admixture with water, in addition to ethanol or dioxane, for example, methanol, tert-butanol and the like can be used. The α-phenylpropionic acids produced by the process according to the invention are preferably recrystallized from hexane or a suitable gasoline fraction.

The α-phenylpropionic acid derivatives of the general formula (I) obtained by the process according to the invention are characterized by advantageous pharmacological effects, in particular against inflammatory and febrile conditions.

The process according to the invention is illustrated by the following examples.

He did

To a mixture of 12.6 g of aminosulfonic acid and 19 g of p-isobutyl-α-phenylpropionaldehyde in 200 ml of water was added a solution of 12.1 g of sodium chlorite in 100 ml of water, which was then stirred at room temperature for 4 hours. After alkalization, the solution was extracted with diethyl ether and the aqueous layer acidified. The precipitated p-isobutyl-α-phenylpropionic acid is dried and recrystallized from hexane. 12.8 g of product are obtained, m.p. 75-77 ° C.

Example 2

To a mixture of p-isobutyl-α-phenylpropionaldehyde (38 g) and concentrated sulfuric acid (10 ml) in water (500 ml) was added sodium chlorite (25 g) and the mixture was stirred at room temperature for 12 hours. After alkalization, the reaction mixture was extracted with benzene. The aqueous layer is acidified, the precipitated acid is filtered off with suction and dried. Recrystallization from legroin gave 25 g of p-isobutyl-α-phenylpropionic acid, m.p. 74-75 ° C.

Example 3

To a mixture of 19 g of p-isobutyl-α-phenypropionaldehyde, 6 g of aminosulfonic acid and 1 ml of concentrated sulfuric acid in 300 ml of water was added 12.1 g of sodium chlorite in 100 ml of water, and the resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was then basified with toluene and the aqueous layer acidified. The precipitated acid is filtered off with suction, dried and recrystallized from petroleum ether. 13.2 g of p-isobutyl-α-phenylpropionic acid, m.p. 74 DEG-76 DEG C., is obtained.

Example 4

To a mixture of 19 g of p-isobutyl-α-phenylpropionaldehyde and 12.6 g of aminosulfonic acid in 200 ml of water and 100 ml of dioxane is added a solution of 12.1 g of sodium chlorite in 100 ml of water. The reaction mixture was then stirred at room temperature for 6 hours. After alkalization, the reaction mixture was extracted with methylene chloride and the aqueous layer was acidified.

The precipitated acid is filtered off with suction and dried. Recrystallization from hexane gave 12.4 g of p-isobutyl-α-phenylpropionic acid, m.p. 74-75 ° C.

Example 1 a d 5

To a mixture of 19 g of β- (cyclopropylamethyl) -α-phenylpropionaldehyde and 12.6 g of aminosulfonic acid in 150 ml of water and 150 ml of ethanol was added a solution of 12.1 g of sodium chlorite in 100 ml of water. The mixture was stirred at room temperature for 6 hours. After alkalization, the reaction mixture was extracted with chloroform. The aqueous layer was acidified and extracted twice with diethyl ether. The ether extracts were combined and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was distilled5

The fraction boiling at 120 to 122 ° C at a pressure of 67 Pa was collected. 10 g of p- (cyclopropylmethyl) -α-phenylpropionic acid are obtained.

Example 6

To a mixture of 16 g of p-ethyl-n-phenylproplonaldehyde with 12.6 g of aminosulfonic acid in 200 ml of water was added a solution of 12.1 g of sodium chlorite. The resulting mixture was stirred at 50 ° C for 2 hours, cooled to 20 ° C, basified and extracted with benzene. The aqueous layer was acidified and the precipitated p-ethyl-α-phenylpropionic acid was filtered off. After drying, it is recrystallized from hexane to give 14.0 g of the title compound, m.p. 70-72 ° C.

Example 7

The procedure was as in Example 1, but the reaction mixture was stirred at 10 ° C for 6 hours. Recrystallization from hexane yielded 12.3 g of product, m.p. 76-77 ° C. Example 8

The procedure was as in Example 1, but the reaction mixture was stirred at 75 ° C for 1 hour. Recrystallization from ligroin gave 12.8 g of product, m.p. 75-77 ° C.

Claims (1)

SUBJECT A process for the preparation of .alpha.-phenylpropionic acid derivatives of the formula I CHCOOW OF THE INVENTION where R represents a (C 2 -C 5) alkyl or (C 3 -C 3) cycloalkyl group, characterized in that the β-alkyl-α-phenylpropionaldehyde of the general formula (II): R is as defined above, oxidized with sodium chlorite in the presence of aminosulfonic acid or sulfuric acid or a mixture of both, in a mixture of water and an organic solvent, preferably a mixture of water with ethanol or a mixture of water and dioxane, ° C, preferably at 20 ° C.