DE1058067B - Process for the preparation of choleretically active p-oxyphenylamides - Google Patents

Description

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

² XX =

-CH = CH-CO-NHX

■ OH

OH

CH = CH-CO-NH

-OH method of manufacture

of choleretically effective

p-oxyphenylamides

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 cinnamic 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 0} C and the resulting solution is acidified.

example 1

8.0 g of o-carbethoxycinnamic acid chloride were in 40 ecm dissolved anhydrous ethyl ether and a suspension of 7 g of p-aminophenol in 25 ecm anhydrous ethyl ether added at 0 ° C within 30 minutes. Stirring was continued for a further 2 hours at room temperature; finally, the mixture was heated under reflux for 1 hour. After cooling, it was filtered, and that with ether washed cakes were washed with 0.5N HCl and then with water. The N- (p-oxyphenyl) -o-carbethoxycinnamylamide was recrystallized from amyl acetate and had a melting point of 160 to 162 ° C. 4.2 g of the same were added with 120 ecm of 0.2N NaOH Treated 50 ° C until a complete solution was obtained. The N- (p-oxyphenyl) -o-oxycinnamoylamide was obtained by acidification with a melting point of 200 to 202 ° C (from aqueous ethanol).

The starting o-carbethoxycinnamic acid chloride was prepared in the following manner: 13.0 g of o-oxycinnamic acid, which were dissolved in 160 ecm 1 of N NaOH, were treated at 0 ° C. with 10.0 g of ethyl chlorocarbonate. After 30 minutes, the solution was acidified and the o-carbethoxycinnamic acid obtained, melting point 159 to 160 ° C. (from ethanol) was filtered. 10.0 g of the same were reacted at the boil with 12.0 g of PCl ₅ in 30 ecm of ligroin. After 2 hours, the ligroin applicant became:

Societa 'Farmaceutici Italia, Milan (Italy)

Representative:
Dipl.-Ing. Dipl.-Chem. Dr. phil. Dr. techn. J. Reitstötter,

Patent attorney, Munich 15, Haydnstr. 5

Claimed priority: Italy of March 10, 1955

Carlo Giuseppe Alberti, Domenico Cattapan

and Alberto Vercellone, Milan (Italy),

have been named as inventors

evaporated and the residue distilled at 15 to 16 mm (Hg) pressure. At 176 to 178 ° C the o-carbethoxycinnamic acid chloride was collected.

Example 2

The crude chloride of p-acetoxycinnamic acid derived from 5 g of p-acetoxycinnamic acid was dissolved in 50 ecm of chloroform dissolved and added dropwise to a suspension of 10.5 g of p-aminophenol in 30 ecm of anhydrous ether 0 ° C added.

As in Example 1 to give the N- (p-oxyphenyl) -p-acetoxycinnamoylamid, melting point 178-182 ° C (from 40 ° / ₀ sodium ethanol). 2.0 g of the same were treated with 30 ecm of 1N NaOH with stirring at room temperature until it was completely dissolved. Acidification gave the N- (p-oxyphenyl) -p-oxycinnamoylamide, melting point 270 to 273 ° C., of the formula

> -CH = CH-CO-NH- <

> -0H

Example 3

13.0 g of 2,4-dicarbethoxycinnamic acid chloride were anhydrous in 100 ecm of a mixture of equal parts Ethyl ether and chloroform dissolved and 8.35 g of p-amino

i \ η 909 528/412

phenol in 50 ecm of ether in the usual way in reaction brought. The N- (p-oxyphenyl) -2,4-dicarbäthoxycinnamoylamid was obtained, Melting point 174 to 176 ° C (from amyl acetate), as indicated in Example 1, saponified became. After crystallization from dilute alcohol, the N- (p-oxyphenyl) -2,4-dioxycinnamoylamide melted the formula

CH = CH CO-NH

OH

to 232 ⁰ C (decomposition), from aqueous ethanol, of the formula

at 209 to 211 ° C (decomposition).

The chloride of 2,4-dicarbethoxycinnamic acid has a melting point of 66 to 68 ⁰ C (from ligroin) and was, as indicated in Example 1, from 2,4-dicarbethoxycinnamic acid (melting point 146 to 147 ° C, from ethanol), obtained by ethoxycarbonylating 2,4-dioxycinnamic acid (see Example 1).

Example 4

From 15.0 g of carbonyl coffee acid chloride, the 4n 75 ecm Dissolved dioxane + 15 ecm chloroform and converted into 15 gSjp-aminophenol in 30 ecm of anhydrous ethyl ether% tied by following the procedure outlined in the previous examples, the carbonate des N- (p-Oxyphenyl) -3,4-dioxycinnamoylamides, melting point 285 to 290 ° C (decomposition) and from this by saponification at room temperature with 1N NaOH N- (p-Oxyphenyl) -3,4-dioxycinnamoylamide, melting point OH

> - CH = CH CO —NH- <

Claims (1)

Claim: > -OH Process for the preparation of choleretically active p-oxyphenylamides of the general formula CH = 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, characterized in that corresponding cinnamic 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 to 50 ⁰ C and acidifies the solution thus obtained. & 909 528/412 5.