DE1064528B - Process for the preparation of choleretically active p-oxyphenylamides - Google Patents

Description

GERMAN

The invention relates to the preparation of choleretically active p-oxyphenylamides of the general Formula:

X " X /

> - CH- CO - NH- (

> —OH

wherein R ₁ and or or R _{2 denote} a hydrogen atom or one or in both cases hydroxyl or nitro groups. It consists in that corresponding phenylethyl acetic acid halides, in which any hydroxyl groups present are protected by acyl radicals, in an inert anhydrous organic solvent at temperatures of about 0 to 40 ° C with an anhydrous suspension of p-aminophenol in ethyl ether, expediently in the presence of an inorganic one or organic, hydrogen halide binding agent or a corresponding excess of p-aminophenol, the reaction mixture is dissolved with 1 to 3 equivalents of a dilute aqueous caustic alkali solution at temperatures between about 0 to 50 ° C and the resulting solution is acidified.

The acyl chlorides can be prepared in a known manner from the corresponding acids by heating for 1 to 3 hours in inert solvents, such as hydrocarbons, chlorinated hydrocarbons, with PCl ₅ or SOCl _2.

In some cases the chlorides crystallized on cooling or evaporation of the solvent; in the in general, however, it is liquid products that have to be distilled in vacuo. Sometimes they are Chlorides decompose at boiling point, then they are used as you get them from the reaction obtained after removing the excess reactant and the solvent.

example 1

From 10.0 g of phenylethyl acetic acid, 10.0 g of PCl ₅ in 40 ecm of ligroin (2 hours under reflux) gave phenylethyl acetic acid chloride (melting point 107 to 109 ° C. at 14 mm Hg). The chloride obtained - 7.5 g - was dissolved in anhydrous ethyl ether and added to a suspension of p-aminophenol (9 g) in anhydrous ethyl ether (60 ecm) at 0 ° C. within 30 minutes. The mixture was stirred for a further 2 hours at room temperature and finally heated under reflux for 1 hour. After cooling, it was filtered and the cake, washed with ether, was washed with dilute II Cl and then with water. The product obtained (12.75 g) was then concentrated from aqueous alcohol. Mau method of manufacture

of choleretically effective

p-oxyphenylamides

Applicant:

Societä Farmaceutici Italia,
Milan (Italy)

Representative:

Dipl.-Ing. Dipl.-Chem. Dr. phil. Dr. techn. J. Reitstötter, Patent attorney, Munich 15, Haydnstr. 5

Claimed priority:
Italy 10 March 1955

Carlo Giuseppe Alberti, Domenico Cattapan

and Alberto Vercellone, Milan (Italy),

have been named as inventors

receives the N- (p-oxyphenyl) -a-phenylbutyrylamide, Melting point 155 to 156 ° C, the formula:

> —CH -CO

Co H _s

NH

OH

Yield: 5.0 g.

Example 2

The crude chloride of p-nitrophenylethyl acetic acid, which is obtained from 5 g of p-nitrophenylethyl acetic acid by proceeding as described in Example 1, was treated with 5.0 g of p-aminophenol in ether (20 ecm), as already described , brought into reaction. The N- (p-oxyphenyl) -a- (p-nitrophenyl) -butyrylamide, melting point 162 to 164 ° C (from aqueous ethanol), of the formula:

NO, - <

-CH-CO -NH

C, H ₅

- OH

Yield: 4.6 g.

At game 3 _t

The crude chloride of p-acetoxyphenylethyl acetic acid (starting from 13.5 g of p-acetoxyphenylethyl acetic acid) was dissolved in 30 ¹ ecm of chloroform and

909 610,400

with 13 g of p-aminophenol in 36 ecm anhydrous Ethyl ether reacted, the N- (p-oxyphenyl) -α- (p-acetoxyphenyl) butyrylamide, Melting point 163 to 165 ° C (from aqueous ethanol) was obtained. Yield: 16 g. Subsequently, the obtained Product (10.0 g) with dilute sodium hydroxide solution (96 ecm of NaOH) until completely dissolved Treated at room temperature (30 minutes) or at 50 ° C (10 minutes).

Acidification gives the N- (p-oxyphenyl) -a- (p-oxyphenyl) -butyramide. Melting point 180 ° C (from aqueous ethanol) of the formula:

Yield: 5.8 g.

Claims (1)

Claim: Process for the preparation of choleretically active p-oxyphenylamides of the general Formula: - CH-CO —NH- > —CH-CO —NH- < C ₂ H ₅ > —OH wherein R ₁ and or or R ₂ denote a hydrogen atom or one or in both cases hydroxyl or nitro groups, characterized in that corresponding phenylethyl acetic acid halides, in which hydroxyl groups may be protected by acyl radicals, in an inert anhydrous organic solvent at temperatures from about 0 to 40 ° C with an anhydrous suspension of p-aminophenol in ethyl ether, expediently in the presence of an inorganic or organic, hydrogen halide binding agent or a corresponding excess of p-aminophenol, the reaction mixture with 1 to 3 equivalents of a dilute brings aqueous caustic alkali solution into solution at temperatures between about 0 and 50 ° C and acidifies the solution thus obtained. > 909 610/400 8.