CH283647A - Process for the preparation of a new phenoxyacetamidine. - Google Patents

Description

  

  Process for the preparation of a new Phenoxyaeetamidins. The present patent relates to a process for the production of a new Phenoxy- aeetamidins, which is characterized in that ammonia or an ammonium salt with one of the rest
EMI0001.0006
    The releasing compound converts to 2,4-dimethylphenoxy-acet.amidine.



  The imido ethers or thioimido ethers, the thioamide, amide or nitrile of 2,4-dimethylphenoxyacetic acid come into consideration as starting materials. The imido or thioimido ethers mentioned are preferably used in the form of their salts.

   Ammonia or as free bases with salts of ammonia tim. The nitrile is also advantageously brought into reaction with salts of ammonia. The reaction can be carried out in the presence or absence, of diluents and / or condensation agents at lower or higher temperatures and different pressures.



       Various of the named acid derivatives of 2,4-dimethylphenoxyacetic acid can be obtained from the nitrile by conventional methods. The nitrile can be treated by treating 2,4-dimethylphenol with chloro-aeetonitrile directly or with chloroacetic acid, its esters or amides and by transferring the intermediate products obtained, eg.

   B. by - # elimination of water from the unsubstituted amide can be obtained.



  The 2,4-dimethyl-phenoxy-aeetamidine obtained in this way forms a hydrochloride that melts at 176-177C. It shows an excellent effect that stimulates the heart muscle and is said to be used as a remedy.



  <I> Example 1: </I> A suspension of 74.7 parts by weight of the 2,4-dimethyl-phenoxy-acetimido-ethyl ether hydrochloride in 130 parts by volume of abs. Ethanol is shaken with 74.5 parts by volume of ethanolic ammonia, which contains 5.44 parts by weight of ammonia, for 20 hours. A trace of ammonium chloride is filtered off, the filtrate is diluted with ether and the 2,4-dimethylphenoxyacetamidine hydrochloride which precipitates is filtered off with suction.

    After recrystallization, it melts at <B> 1 </B> .76 to 177 C.



  Instead of using the imido ether hydrochloride as in the above example, the free base can also be reacted with an ammonium salt, optionally dissolved in NN water, for example with ammonium chloride or ammonium sulfate or ammonium p-toluene sulfonate corresponding salt of the amidine is obtained.



  If the imido ether hydrobromide is used, the corresponding amidine hydrobromide is obtained. If the ethyl imido ether is replaced by another ether, such as 1Zethyl or cyclohexyl ether, the corresponding alcohol is preferably used as a solvent in the conversion into amidine.



  The starting materials used in the above example are z. B. according to the fol lowing procedure: 2,4-dimethyl-phenoxy-acetonitrile, obtained by alkylating 2,4-dimethyl-phenol with.

       Chloracetamide and subsequent elimination of water with phosphorus pentoxide is converted into the corresponding Ätliy limidoether-hydrochloride by treatment with equivalent amounts of absolute ethanol and hydrochloric acid in chloroform solution and dilution with ether.



  <I> Example 2: </I> The solution of 16.1 parts by weight of 2,4-dimethylphenoxy-aeetonitrile in 55 parts by weight of an alcoholic ammonia solution containing 6.8 parts by weight of ammonia is passed with cooling 0.6 parts by weight of hydrogen sulfide and allowed to stand for two to three days under a nitrogen atmosphere at room temperature, the intermediate thioamide being formed. The solvent is distilled off in a vacuum. The base that remains is dissolved in a little alcohol for the purpose of cleaning, one equivalent of alcoholic hydrochloric acid is added and the hydrochloride is precipitated with ether.

   After recrystallization from a mixture of alcohol and methyl ethyl ketone. the 2,4-demethyl-phenoxy-a.cetamidine hydrochloride described in the example 1.



  The reaction can be carried out at an elevated temperature, the reaction time being greatly reduced. The base can also be purified by using an equivalent amount of ammonium chloride instead of the hydrochloric acid and stirring the suspension until the latter disappears. EXAMPLE 3: To 5.1 parts by weight of ammonia dissolved in 50 parts by weight of methyl alcohol, 16.1 parts by weight of 2,4-dimethylphenoxyacetonitrile and 5.3 parts by weight of ammonium chloride are added. 0.3 parts by weight of hydrogen sulfide with cooling.

   The mixture is then stirred for a few hours at 20 ° C. and 8 hours at 35 to 10 ° C., the ammonium chloride going into solution. The solvent is distilled off and the residue is recrystallized from a mixture of alcohol and methyl ether ketone. The hydrochloride obtained is identical to that of Example 1.

    <I> Example 4: </I> A mixture of 19.2 parts by weight of 2,4-dimethylphenoxyacetonitrile and 18.9 parts by weight of p-toluene, sulfonic acid ammonium is heated to 220 to 290 ° C. for 20 to 30 minutes The reaction mass is boiled with water, the aqueous solution is separated from some resin, clarified and, after cooling with ether, freed from neutral compounds. Concentrated potash solution is then added and the resulting base is extracted with ether.

   After distilling off the Uher, the base becomes like in the example? Purified over the hydrochloride.

 

Claims (1)

<B> PATENT CLAIM: </B> Process for the production of a new plienoxy-aeetamidine, characterized in that ammonia or an ammonium salt is mixed with the remainder. EMI0002.0060 The releasing compound is converted to 2,4-dimethylphenoxyacetamidine. The amidine thus obtained forms a hydrochloride which melts at 176 to 177 C and is said to be used as a medicinal product.