CH283646A - 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 phenoxyacetamidine, which is characterized in that ammonia or an ammonium salt with a remainder
EMI0001.0005
    releasing compound converts to 3,4-dimethylphenoxyacetamidine.



  The imido ethers or thioimido ethers, the thioamide, amide or nitrile of 3,4-dimethylphenoxyacetic acid come into consideration 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 3,4-dimethyl-phenoxy-acetic acid can be obtained from the Ni trile by conventional methods. The nitrile can aeetonitrile by treating of 3,4-dimethylphenol with chlorine directly or with chloroacetic acid, its esters or amides and by transferring the intermediate products obtained, eg. B. can be obtained by splitting off water from the unsubstituted amide.



  The 3,4-dimethylphenoxyacetamidine obtained in this way forms a hydrochloride which melts at 202 to 203.5.degree. It shows excellent cardiac muscle stimulating effects and is said to be used as a remedy.



  <I> Example 1: </I> A suspension of 74.7 parts by weight of 3,4-dimethylphenoxyacetimido 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 3,4-dimethylphenoxyacetamidine hydrochloride which precipitates is filtered off with suction. After recrystallization, it melts at 202 to 203.5 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 water, for example with ammonium chloride or ammonium sulfate or ammonium p-toluenesulfonate, the 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 methyl or cyclohexyl 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. according to the following procedure: 3,4-dimethyl-phenoxyacetonitrile, obtained by alkylating 3,4-dimethyl-phenol and Chloraeetamid and subsequent What is splitting off with phosphorus pentoxide, is by treating with equimolar amounts of absolute ethanol and hydrochloric acid in chloroform solution and dilution with ether converted into the corresponding ethylimido ether hydrochloride.



  <I> Example </I> N: Into a solution of 16.1 parts by weight of 3,4-dimethyl-phenoxy-acetonitrile 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 under a nitrogen atmosphere at room temperature for two to three days, the thioamide being formed as an intermediate. 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 3,4-dimethylphenoxyacetamidine 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 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 are added 16.1 parts by weight of 3,4-dimethylphenoxyaeetonitrile and 5.3 parts by weight Ammonium disorder and directs. 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 40 ° C., the ammonium chloride going into solution. The solvent is distilled off and the residue from a mixture of alcohol and ethyl ethyl ketone becomes crystalline. ized. The hydrochloride obtained is identical to that of Example 1.



  <I> Example </I> A mixture of 19.2 parts by weight of 3,4-dimethylphenoxy-acetonitrile and 18.9 parts by weight of p-toluenesulfonic acid ammonium is heated for 20 to 30 minutes to 220 to 290 ° C. The reaction mass is boiled out finely 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 CII Process for the production of a new phenoxy-aeetamidins, characterized in that one ammonia or an ammonium salt with a remainder EMI0002.0072 releasing compound converts to 3,4-dimethylphenoxyacetamidine. The amidine obtained in this way forms a hydrochloride which melts at 202 to 203.5.degree. It is said to be a remedy. Find use.