CH278405A - Process for the preparation of a new phenoxyacetamidine. - Google Patents

Description

  

      Method of making a. new phenoxyacetamidine. The present patent relates to a process for the production of a new phenoxyacetamidine, which is characterized in that ammonia or an ammonium salt is mixed with one of the remainder
EMI0001.0007
    The releasing compound converts to 3-methylphenoxyacetamidine.



  The imido ethers or thioimido ethers, the thioamide, amide or nitrile of 3-methylphenoxyacetic acid are primarily suitable as starting materials. The imido or thioimido ethers mentioned are preferably used in the form of their salts with ammonia or as free bases. Ammonia salts. 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 mentioned of 3-methylphenoxyacetic acid can be obtained from the nitrile using conventional methods. The nitrile can be obtained by treating m-cresol with chloroacetonitrile directly or with chloroacetic acid, its esters or amides, and by transferring the intermediate products obtained, e.g. B. by splitting off water from the unsubstituted amide.



  The 3-methylphenoxyacetamidine thus obtained forms a hydrochloride which melts at 179 to 180.5. It shows an excellent effect that stimulates the heart muscle and is said to be used as a remedy.



       Example <I> 1: </I> 73.5 parts by weight of 3-methyl-phenoxy-acetothioimido-ethyl ether or 69 parts by weight of the corresponding ethylimido-ether hydrochloride are shaken with 5.44 parts by weight of ammonia in ethanol for 20 to 30 hours and the Reaction mixture diluted with petroleum ether. The 3-methylphenoxyacetamidine hydrochloride obtained is filtered off and recrystallized from a mixture of ether and ethanol. It melts at 179 to 180.5.



  Instead of using the imido ether hydrochloride as in the above example, you can also use the free base. 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 imidoether hydrobromide is used, the corresponding amide hydrobromide is obtained. If the ethyl imido ether is replaced by another ether, such as methyl or cyelohexyl ether, the corresponding alcohol is preferably used as the solvent for the conversion into amidine.



  The starting materials used in the above example are z. B. 3 - methyl - phenoxy - acetonitrile, obtained by treating a solution of ni-cresol with chloroacetonitrile in 1lethylethylketone in the presence of potassium carbonate, using the following procedure,

      is converted with ethyl mercaptan and hydrochloric acid into the 3-methylphenoVacetothioimidoäthyläther-hydrochloride or with ethanol and hydrochloric acid into the ethyl imidoether-hydrochloricl.



  <I> Example 2: </I> In the solution of 14.7 parts by weight of 3 methyl-phenoxy-acetonitrile in 55 parts by weight of an alcoholic ammonia solution, which contains 6.8 parts by weight of ammonia, 0.6 parts by weight of sulfur are passed with cooling - hydrogen sulfide, left to stand for two to three days under a nitrogen atmosphere at room temperature, with the intermediate thioamide being formed. The solvent is distilled off in vacuo.

   The remaining base is dissolved in a little alcohol for 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 3-methyl-phenox®r-acetamidine hydrochloride described in Example 1 is obtained.



  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 hydrochloric acid and stirring the suspension until the latter disappears. <I> Example 3: </I> To 5.1 parts by weight of ammonia, dissolved in 50 parts by weight of ethyl alcohol, are added 14.7 parts by weight of 3 -'- # ethyl-pheno2 # vaeetonitrile and 5.3 parts by weight of ammonium chloride, and 0.3 Parts by weight of hydrogen sulfide with cooling.

   The mixture is then stirred for a few hours at 20 and 8 hours at 35 to 40, the ammonium chloride going into solution. The solvent is distilled off and the residue was recrystallized from a mixture of alcohol-methyl ethyl ketone. The hydrochloride obtained is identical to that of 1. game example.



  <I> Example 4: </I> A mixture of <B> 17.6 </B> parts by weight of 3-14Zethyl-pheiioxy-aeetonitrile and 18.9 parts by weight of p-toluenesulfoirsaureni ammonium is heated during. 20 to 30 minutes to 220 to 290. 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 the ether has been distilled off, the base is purified using the hydrochloride as in Example 2.

 

Claims (1)

PATENT CLAIM: Process for the production of a new phenoxyacetamidine, characterized in that ammonia or an ammonium salt is mixed with the remainder EMI0002.0060 The donating compound now converts 3-methyl-phenoxy-acetamidine. The ainicline thus obtained forms a hydrochloride that melts at 179 to 780.5; it is said to be used as a remedy.