CH283645A - Process for the preparation of a new phenoxyacetamidine. - Google Patents

Description

  

  Process for the preparation of a new phenoxyacetamidine. 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
EMI0001.0005
    releasing compound converts to 4-chloro-phenoxy-acetamidine.



  The imido ethers or thioimido mers, the thioamide, amide or nitrile of 4-chloro-phenoxy-acetic acid come into consideration as starting materials. The imido or thioimido ethers mentioned are preferably reacted in the form of their salts with ammonia or as free bases with salts of ammonia.

   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 acid derivatives of 4-chloro-phenoxy-acetic acid mentioned can be obtained from the nitrile by conventional methods. The nitrile can be obtained by treating p-chlorophenol with chloroacetonitrile directly or with chloroacetic acid, its esters or amines and by transferring the intermediate products obtained, eg. B. by elimination of water from the unsubstituted amide can be obtained. The 4-chloro-phenoxy-acetamidine obtained in this way forms a hydrochloride that melts at 183 to 185C.

   It shows an excellent effect that stimulates the heart muscle and is said to be used as a remedy.



       Example <I> 1: </I> A suspension of 73.2 parts by weight of the 4-chloro-phenoxy-acetimidoä.thyl 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 4-chloro-phenoxy-acetamidine hydrochloride which precipitates is filtered off with suction. It melts. after recrystallization at 183 to 185 C.



  Instead of using the imido ether hydrochloride as in the example above, the free base can also be used. an ammonium salt, optionally dissolved in water, for example with ammonium chloride or ammonium sulfate or ammonium p-toluenesulfonate, the corresponding salt of the amidine being 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 methyl 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 following procedure here 4-chloro-phenoxyacetonitrile, obtained by alkylating p-chloro-phenol with chloro-aeetamide and subsequent dehydration from the 4-chloro-phenoxy-acetamide obtained with phosphorus pentoxide,

      is converted into the corresponding ethyl imido ether hydrochloride by treatment with equimolar amounts of absolute ethanol and hydrochloric acid in chloroform solution and dilution with ether.



  <I> Example 2 </I> In a solution of 16.8 parts by weight of 4-chloro-phenoxy-acetonitrile in 55 parts by weight of an alcoholic ammonia solution containing 6.8 parts by weight of ammonia, 0.6 parts by weight are passed with cooling Hydrogen sulfide and allowed to stand under a nitrogen atmosphere at room temperature for two to three days, with the intermediate thioamide being formed. The solvent is distilled off in vacuo. The remaining base is dissolved in a little alcohol for the purpose of purification, 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 4-chloro-phenoxy-acetamidine hydrochloride described in Example 1 is obtained.



  The reaction can be carried out at an elevated temperature, the reaction time being greatly reduced. becomes.



  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.

      <I> Example 3: </I> Zn 5.1 parts by weight of ammonia, which is dissolved in 50 parts by weight of methyl alcohol, are added 16.8 parts by weight of 4-chloro-phenoxy-acetonitrile and 5.3 parts by weight of ammonium chloride and 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 40 ° C., the ammonium chloride going into solution.

   The solvent is distilled off and the residue is recrystallized from a mixture of alcohol and 3 # ethyl ethyl ketone. The hydrochloride obtained is identical to that of Example 1.



       Example <I> 4: </I> A mixture of 20.1 parts by weight of 4-chloro-phenoxy-acetonitrile and 18.9 parts by weight of p-toluenesulfonic acid ammonium is heated to 220 to 290 ° C. for 20 to 30 minutes The reaction mass is boiled with water and the aqueous solution is separated from some resin, clarified and, after cooling with ether, freed from neutral compounds.

   Then you add concentrated potash solution and pull. the resulting base with. Ether off. After the ether has been distilled off, the base is cleaned via the hydrochloride as in Example 2.

 

Claims (1)

PATENT CLAIM: Process for the production of a new phenoxyacetamidine, characterized in that one ammonia or an ammonium salt with one of the rest EMI0002.0058 The releasing compound converts to 4-chloro-phenoxy-a.cetamidine. The amidine obtained in this way forms a hydrochloride that melts at 183 to 185 C and is said to be used as a medicinal product.