CH268689A - Process for the preparation of a biologically active phenylethylenediamine derivative. - Google Patents

Process for the preparation of a biologically active phenylethylenediamine derivative.

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Publication number
CH268689A
CH268689A CH268689DA CH268689A CH 268689 A CH268689 A CH 268689A CH 268689D A CH268689D A CH 268689DA CH 268689 A CH268689 A CH 268689A
Authority
CH
Switzerland
Prior art keywords
preparation
phenylethylenediamine
derivative
biologically active
beta
Prior art date
Application number
Other languages
German (de)
Inventor
Podnik Spojene Farmace Narodni
Original Assignee
Spojene Farmaceuticke Z Narodn
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Spojene Farmaceuticke Z Narodn filed Critical Spojene Farmaceuticke Z Narodn
Publication of CH268689A publication Critical patent/CH268689A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Description

  

  Verfahren zur Darstellung eines biologisch wirksamen     Phenyläthylendiaminderivates.       Aus den zahlreichen pharmakologischen  und klinischen Veröffentlichungen, z. B.  B. N.     Halpern    :     Arch.    intern.     pharmacodynamic     68339, 1942;

   T.     Gordonoff    :     Sehw.        med.Wsehr.       74693, 1944     usw.,    ist die hohe spezifische und       antihistaminischeWirksamkeit    der     -T-Phenyl-          N-benzyl-N'-diallzy        l-äthy        lendiamine    der For  mel  
EMI0001.0014     
    bekannt, worin R     Alkylgruppen    bedeutet.  



  Es wurde gefunden, dass das     N-Phenyl-N-        benzyl-N-beta-piperidinoäthylamin    der Formel  
EMI0001.0018     
    welches bisher nicht, beschrieben wurde, auch  hervorragende     antihistaminische    Wirkung  aufweist.  



  Gegenstand des vorliegenden Patentes ist.  ein Verfahren zur Herstellung dieses Stoffes,  welches dadurch gekennzeichnet ist, dass man       Benzylanilin    mit     beta-Piperidillo-äthplchlorid     kondensiert.. Die Kondensation erfolgt zweck  mässig in einer     Benzenlösung    mit     Natrium-          amid    als Kondensationsmittel. Die Kondensa  tion wird vorteilhaft zuerst bei normaler und  am Ende bei erhöhter Temperatur (100  C )  durchgeführt. Nachher wird z.

   B. aus der ab-    gekühlten     Mischung    das bei der Kondensation  entstandene     Natriumehlorid    durch     Abfiltrie-          ren    entfernt, das Filtrat mit Wasser     gewa-          sehen,    die     Benzenlösung    mit frisch ausge  brannter Pottasche     getrocknet,    das     Benzen     abgedampft und der Rest, im     1-mm-Vakuum     destilliert. Das Produkt ist ein gelbliches,  wasserunlösliches, in verdünnten Mineral  säuren unter Salzbildung lösliches öl.

   Wenn  man die Base in absolut ätherischer Lösung  mit einem oder zwei     Equivalenten    absolut       alkoholischer        Chlorwasserstofflösung    behan  delt, erhält man weisse,     kristallische,    in Was  ser gut lösliche Hydrochloride.      <I>Beispiel:</I>  In 150     em3    absoluten Benzens werden  18,5 g (etwa 0,1     Mol)        Benzylanilin    und 15 g  (etwa 0,1     Mol)        beta-Piperidino-äthylchlorid     gelöst.

   Es werden 4 g (etwa 0,1     Mol)    feinge  mahlenen     Natriumamids        -unter    Rühren suk  zessiv     zugegeben.    Das     Reaktionsgemisch    lässt  man 12     Stunden    bei Raumtemperatur stehen,  danach erhitzt man es 3 Stunden im sieden  den Wasserbade unter     Rüekflusskühlung.    Man  lässt das Gemisch bis nun nächsten Tage  stehen. Das ausgeschiedene Salz wird     abfil-          triert    und das Filtrat mit Wasser gewaschen.

    Die     Benzenschicht        wird    abgetrennt, mit frisch  ausgebrannter Pottasche getrocknet     Lind    nach  der Filtration das     Benzen    abgetrieben. Der  Rest     wird    im     1-mm-Vakuum        destilliert.    Der  Siedepunkt des Erzeugnisses beträgt 194 bis  197  C bei 1 mm. Das     Monohydrochlorid    weist  nach dem     Umkristallisieren    aus Aceton den       Schmelzpunkt    161,5 bis 162,5  C (kor.) auf.



  Process for the preparation of a biologically active phenylethylenediamine derivative. From the numerous pharmacological and clinical publications, e.g. B. B. N. Halpern: Arch. Intern. Pharmacodynamic 68339, 1942;

   T. Gordonoff: Sehw. med. very. 74693, 1944, etc., is the high specific and antihistaminic activity of the -T-phenyl-N-benzyl-N'-dialzyl-ethylenediamine of the formula
EMI0001.0014
    known, wherein R is alkyl groups.



  It has been found that the N-phenyl-N-benzyl-N-beta-piperidinoethylamine of the formula
EMI0001.0018
    which has not yet been described, also has an excellent antihistaminic effect.



  The subject of the present patent is. a process for the production of this substance, which is characterized in that benzylaniline is condensed with beta-piperidillo-ethereal chloride. The condensation is conveniently carried out in a benzene solution with sodium amide as the condensing agent. The condensation is advantageously carried out first at normal and at the end at elevated temperature (100 ° C.). Afterwards z.

   For example, the sodium chloride formed during the condensation is removed from the cooled mixture by filtration, the filtrate is washed with water, the benzene solution is dried with freshly burnt potash, the benzene is evaporated and the remainder is in a 1 mm vacuum distilled. The product is a yellowish, water-insoluble oil that dissolves in dilute mineral acids with formation of salts.

   If you treat the base in an absolutely ethereal solution with one or two equivalents of absolutely alcoholic hydrogen chloride solution, you get white, crystalline hydrochlorides which are readily soluble in water. <I> Example: </I> 18.5 g (about 0.1 mol) of benzylaniline and 15 g (about 0.1 mol) of beta-piperidinoethyl chloride are dissolved in 150 em3 of absolute benzene.

   4 g (about 0.1 mol) of finely ground sodium amide are added successively with stirring. The reaction mixture is allowed to stand for 12 hours at room temperature, then it is heated for 3 hours in the boiling water bath with reflux cooling. The mixture is left to stand for the next few days. The precipitated salt is filtered off and the filtrate is washed with water.

    The benzene layer is separated off, dried with freshly burned potash and, after filtration, the benzene is driven off. The remainder is distilled in a 1 mm vacuum. The boiling point of the product is 194 to 197 C at 1 mm. After recrystallization from acetone, the monohydrochloride has a melting point of 161.5 to 162.5 C (cor.).

Claims (1)

PATENTANSPRUCH: Verfahren zur Darstellung des N-Phenyl- N-benzyl-N-beta-piperidinoäthylamins, da durch gekennzeichnet, dass man Benzylanilin mit beta-Piperidülo-äthylchlorid kondensiert. Das Endprodukt ist ein gelbliches, basisch riechendes, viskoses Öl, Sdp. 194 bis 197 C bei 1 mm. Es gibt ein weisses, kristall. Hydro chlorid mit dem Sehmp. 161,5 bis 162,5 C (kor.). UNTERANSPRÜCHE: 1. PATENT CLAIM: Process for the preparation of N-phenyl-N-benzyl-N-beta-piperidinoethylamine, characterized in that benzylaniline is condensed with beta-piperidülo-ethyl chloride. The end product is a yellowish, basic-smelling, viscous oil, boiling point 194 to 197 ° C. at 1 mm. There is a white, crystal. Hydro chloride with the Sehmp. 161.5 to 162.5 C (cor.). SUBCLAIMS: 1. Verfahren nach Patentanspruch, da durch gekennzeichnet, dass man die Konden sation mit Natriumamid als Kondensations mittel in einem inerten Lösungsmittel durch führt und dabei bei erhöhter Temperatur ar beitet. 2. Verfahren nach Patentanspruch und Unteranspruch 1, dadurch gekennzeichnet, dass man das Reaktionsprodukt durch eine Vakuumdestillation isoliert. Process according to patent claim, characterized in that the condensation is carried out with sodium amide as the condensation agent in an inert solvent and is worked at an elevated temperature. 2. The method according to claim and dependent claim 1, characterized in that the reaction product is isolated by vacuum distillation.
CH268689D 1947-07-01 1948-06-28 Process for the preparation of a biologically active phenylethylenediamine derivative. CH268689A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CS268689X 1947-07-01

Publications (1)

Publication Number Publication Date
CH268689A true CH268689A (en) 1950-05-31

Family

ID=5451684

Family Applications (1)

Application Number Title Priority Date Filing Date
CH268689D CH268689A (en) 1947-07-01 1948-06-28 Process for the preparation of a biologically active phenylethylenediamine derivative.

Country Status (1)

Country Link
CH (1) CH268689A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2174655A1 (en) * 1972-03-06 1973-10-19 Mauvernay Ctre Rech

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2174655A1 (en) * 1972-03-06 1973-10-19 Mauvernay Ctre Rech

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