CH208253A - Process for the preparation of a B-alkyl-substituted ethylamine derivative. - Google Patents

Description

  

  Process for the preparation of an f-alkyl-substituted ethylamine derivative. It has been found that ß-alkyl-substituted ethylamine derivatives of the following formula
EMI0001.0006
    in which R, R 'and R "are identical or different alkyl radicals or R' and / or R" also represent hydrogen atoms and which have at least 11 carbon atoms in the molecule are characterized by strong peripheral paralyzing (spasmolytic) properties.



  These compounds can be prepared by methods known per se for the preparation of amines. Processes which have proven to be particularly suitable are those in which nitriles of the formula
EMI0001.0014
    or their water addition products, i.e. amides of the formula
EMI0001.0017
    to the action of reducing agents, for example nascent or catalytically activated hydrogen.

   However, the amides of the corresponding acids, which have one more carbon atom in the molecule than the amines to be prepared, can also be subjected to the known degradation methods, for example according to Hofmann, Curtius or the like.



  The spasmolytic effectiveness of the individual amines is determined by evaluating a living rabbit intestine that is kept permanently in barium-containing Tyrode solution. The individual preparations were always evaluated against novocaine chlorohydrate as a comparative preparation.

        In these experiments novocaine chlorohydrate = ij; s papaverine chlorohydrate. The following table shows that r-alky 1-substituted ethylamines, provided that the number of carbon atoms they contain is one of yours, only have a moderate peripheral paralyzing effect.

   The effectiveness increases, however, surprisingly, quite considerably if the molecule of these substances contains at least 11 carbon atoms, and there is such an increase that the amines have the same effect as papaverine. surpass it.
EMI0002.0015
  
    Effect number
<tb> Examined <SEP> Ethylamine:

   <SEP> C number <SEP> (Novocain-Chlorhydrat-1)
<tb> f @ ss-Triätbyläthylainirichlorhydrat <SEP> 8 <SEP> 7.5
<tb>; 3f @ -Ti @ ipropyliithylainirichloi-hydr-at <SEP> 11 <SEP> 50
<tb> n-Tetradecylaniine chlorohydrate <SEP> 14 <SEP> 75
<tb> Diethyl-i3-n-hexylethylamine chlorohydrate <SEP> 12 <SEP> 120
<tb> ss @ -Di-n-hexyl-ethylainin chlorohydrate <SEP> 14 <SEP> 150
<tb> iV, 3-ethyl <SEP> -diisoainyl- <ithylaniine chlorohydrate <SEP> 14 <SEP> 200
<tb> iV @ -Tri-n-butyl-ethylamine chlorohydrate <SEP> 14 <SEP> 450
<tb> i3,3 @ -Tri-isoamylätliylaniinclilorliydrat <SEP> 17 <SEP> 300
<tb> Pi @ 3-Tri-n-hexyl-ethylamine chlorohydrate <SEP> 20 <SEP> almost <SEP> ineffective The table shows

       dafa a new group of therapeutically important substances with strong spasmolytic properties has been found through the production of the previously unknown @ -ethy lainiiidei derivatives.



  The subject of the present patent is a process for the preparation of d-tri-n-butylätllylamine, which is characterized in that Ti-i-n-butylacetoniti, il is treated with hydrogen. The new compound is to be used as a drug.



  For their technical production it has proven to be most advantageous to use said nitrile in the presence of non-precious metal catalysts suitably deposited on supports, especially nickel catalysts deposited on kieselguhr, with hydrogen under pressure at elevated temperature, for example at 120 -140 to be reduced.

   If you use so-called Raney catalysts, which can be obtained by dissolving the aluminum from a nickel-aluminum alloy, for example according to the method of American patent No. 1915 473, the reduction can also be carried out at low temperatures, for example already at 70, perform.

           Example: 200 parts of tri-biitylacetonitrile (KP-4.8 1280) were added to kieselguhr in the autoclave with the addition of 20 parts of nickel catalyst, which had been reduced in the stream of hydrogen at about 450 for 1 hour 20 to 100 atni. Hydrogen pressure heated to <B> 1301 </B> until the hydrogen uptake ceased. There were added 44 liters of hydrogen. After the catalyst had been separated off, the contents of the autoclave were fractionally distilled.

             The distillation yields about 95% of theory of pure β-tri-n-butylethylamine with a b.p. 140-142 <B> 0 </B>.



  By neutralizing the base with the calculated amount of hydrochloric acid and evaporating, the hydrochloride is obtained therefrom in the form of leaflets with a melting point of 135-136 (from water).



  The nitrile can also be reduced with the same yield if it is treated with pure hydrogen in a shaker or stirred autoclave with the addition of three parts of Raney nickel catalyst at 60-70 under a pressure of 30 cm water column, as long as there is still hydrogen is taken. The reaction product is then separated from the catalyst and purified as above.

 

Claims (1)

PATENT CLAIM: Process for the preparation of an β-alkyl substituted ethylamine derivative of high spasmolytic effectiveness, characterized in that tri-n-butylacetonitrile is treated with hydrogen. The Q-tri-n-butylethylamine thus obtained boils at 135-136 'under a pressure of 13 mm, and its hydrochloride melts at 135-1360. SUBClaims 1. The method according to claim, characterized in that the reduction is carried out with the aid of catalytically activated hydrogen. 2. The method according to claim and un teran claim 1, characterized in that nickel catalysts that are deposited on supports are used as catalysts. 3. The method according to claim and un teran claim 1, characterized in that a nickel catalyst is used as the catalyst, which was obtained by dissolving the aluminum from a nickel-aluminum alloy. 4. The method according to claim and un teran claim 1, characterized in that the catalytic reduction is carried out under pressure and at elevated temperature.