SU457210A3 - Method for producing benzoyl- (3-phenyl) -2-propionic or benzoyl- (3-phenyl) acetic acid - Google Patents

Description

(54) METHOD FOR OBTAINING BENZOIL- (3-PHENYL) -2PROPIONAL OR BENZOIL- (3-PHENYL) -LUXE

ACID

one

The invention relates to a method for producing benzoyl- (3-phenyl) -acetic or benzoyl- (3-phenyl) -2-propionic acid of general formula I

sn-soon

Ri,

wherein R represents a hydrogen atom or a methyl radical, and R represents a hydrogen or halogen atom,

which are used as physiologically active compounds.

A known method for producing benzoyl- (3-phenyl) -2-propionic and benzoyl- (3-phenyl) -acetic acids of the general formula

WITH -rpV CH-COOH V Pi

where Rl is a hydrogen atom or an alkyl residue containing 1-4 carbon atoms, and the benzene rings can sometimes be replaced with one or more halogen atoms or residues of alkyloxy or alkylthio-alkyls containing 1-4 carbon atoms or trifluoromethyl residues, consisting of

that 3-methylbenzophenone in a solution of methylene bromide is treated with ultraviolet rays and bromine at the boiling point of the solution, followed by release of 3-bromomethylenebenzophenone, the effect on which

sodium cyanide get 3-benzoylphenylacetonitrile.

The 3-benzoylphenylacetonitrile thus obtained is hydrolyzed in the presence of sulfuric acid to 3-benzoylphenylacetic acid.

with its subsequent selection.

In the case of (3-benzoylphenyl) -2-propionic acid, the synthesis is increased in two stages.

3-benzoylphenylacetonitrile obtained

in the manner described, sodium ethoxide is exposed and

SbN5OSbN4SNYA SOOS2N5,

acting on methyl iodide, get the ethyl ester of 3-benzoylphenyl-2-propionic acid. The resulting ester is hydrolyzed in the presence of sulfuric acid to obtain (3-benzoylphenyl) -2-propioic acid.

The resulting acids with nitric bases can be converted to metal salts or additive salts.

The known method is multistage and uses a large number of deficient and highly toxic reagents.

In order to simplify the process, a method is proposed for producing benzoyl- (3-phenyl) -acetic and benzoyl- (3-phenyl) -2-propionic acids of the general formula

AT

sn-soon

in which R is a hydrogen atom or halogen, and RI is a hydrogen atom or a methyl radical, by treating a nitrile of the general formula

C10C

where RI has the reduced value

benzene or halobenzene in the presence of anhydrous aluminum chloride, followed by hydrolysis of the resulting product in the presence of mineral acids or alkalis and isolation.

The hydrolysis of nitriles can be carried out by conventional methods of converting the nitride to the corresponding acid.

It is desirable to heat the nitrile in water or an organic solvent, for example methanol or ethanol, in the presence of a base, for example caustic soda or potassium, or an acid, for example sulfuric. Preferred inert atmosphere, such as nitrogen.

The acids of general formula I can be converted to metal salts or to additive salts with nitrogen bases.

Example 1

A. In a suspension of 16.4 g of anhydrous aluminum chloride in 50 cm of anhydrous benzene, a solution of 11.9 g of (chloroformyl-3-phenyl) -2-propionitrile in 20 cm of anhydrous benzene is added. The reaction mixture is heated under reflux for 1 hour. After cooling, the reaction medium is hydrolyzed with 100 g of crushed ice containing 10 cm 10 n. hydrochloric acid.

After settling, the organic layer is washed with distilled water, it is dissolved on anhydrous sodium sulphate, filtered, then enriched in a dry way under reduced pressure. 14 g of (benzoyl-3-phenyl) -2-propionitrile, melting at 49 ° C, are thus obtained.

After recrystallization in 35 cm of isopropyl oxide, 11.8 g of (benzoyl-3-phenyl) -2-propionitrile are obtained, melting at 51 ° C.

B. A solution of 1.2 tons (benzoyl-3-phenyl) -2-propionitrile in 10 cm of a mixture of methanol and water

(volume, 1: 1), containing 0.3 g of potassium hydroxide in tablets (85%), is heated under reflux for 24 hours. After cooling, the solution obtained is concentrated under

reduced pressure (20 mm Hg. Art.) at 50 ° C. The precipitate obtained is dissolved in 30 cm of distilled water and the resulting solution is washed twice with 20 cm of diethyl ether. The aqueous phase is acidified with 2 cm 10 n. salt

acid. The crystallized product is filtered, washed with 10 cm of distilled water, then dried.

Thus, 0.9 g of benzoyl- (3-phenyl) -2-propionic acid is obtained, melting

at 92 ° C.

Example 2

A. In a suspension of 16.7 g of aluminum chloride in 120 cm of anhydrous chlorobenzene, 11.5 g of chloroforyl-3-phenylacetonitrile are added over 20 minutes. The reaction mixture is heated under reflux for 3 hours. After cooling, the reaction mixture is hydrolyzed with 300 g of crushed ice containing 60 cm of concentrated hydrochloric acid (d, l9).

After extraction (three times) of 100 cm of ether, the organic layer is washed with distilled water, dissolved on anhydrous sodium sulphate, then concentrated under reduced pressure (20 mmHg) at 50 ° C. 16.7 g of (chloro-4-benzoyl) -3-phenylacetonitrile, melting at 93 ° C, are thus obtained.

B. A suspension of 16.5 g of (chloro-4-benzoyl) -3phenylacetonitrile in 150 cm 3 n. caustic soda is heated under reflux in

for 18 hours. After cooling, the solution is diluted with 600 cm of water, then acidified with the addition of 50 cm of concentrated hydrochloric acid (, 19). The crystallized product is isolated by filtration, washed four times with 50 cm of water, then dried.

14.7 g of (chloro-4-benzoyl) -3-phenylacetic acid, melting at 1440 ° C, are thus obtained. After recrystallization in 100 cm of benzene, 12 g of (chloro-4-benzoyl) -3-phenylacetic acid, melting at 148 ° C, are obtained.

Subject invention

The method of obtaining benzoyl- (3-phenyl) -2-propionic or benzoyl- (3-phenyl) -acetic acids of the general formula

where RI is a hydrogen atom or methyl, 60R is a hydrogen atom or halogen,

using the hydrolysis of nitriles in the presence of mineral acids and alkalis and the isolation of products by known methods, characterized in that, in order to simplify the process, the nitriles of the general formula

Cloc

where Ri is a hydrogen atom or methyl,

reacted with benzene or halobenzene in the presence of

aluminum chloride.

Priority signs: 03.12.71 when RI is methyl. 10/16/22 with RI - hydrogen.