CH332712A - Process for the production of local anesthetics - Google Patents

Process for the production of local anesthetics

Info

Publication number
CH332712A
CH332712A CH332712DA CH332712A CH 332712 A CH332712 A CH 332712A CH 332712D A CH332712D A CH 332712DA CH 332712 A CH332712 A CH 332712A
Authority
CH
Switzerland
Prior art keywords
production
local anesthetics
piperidine
formula
crotonic acid
Prior art date
Application number
Other languages
German (de)
Inventor
Wilder Dr Smith Arthur Ernest
Hofstetter Emil
Original Assignee
Geistlich Soehne Ag
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 Geistlich Soehne Ag filed Critical Geistlich Soehne Ag
Publication of CH332712A publication Critical patent/CH332712A/en

Links

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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • 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
    • C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)

Description

  

   <Desc/Clms Page number 1> 
 Verfahren    zur      Herstellung   von    Lokalanästhetika   In der    Hauptpatentschrift   ist ein Verfahren zur Herstellung von Lokalanästhetika beschrieben, .wobei u. a. auch Produkte der Formel 
 EMI1.5 
 worin mindestens ein R Halogen, die andern Wasserstoff bedeuten, beschrieben sind. 



  Gemäss den Angaben in der    Hauptpatent-      sehrift   werden diese Produkte erhalten durch    Umsetzung   von    Crotonsäureaniliden   der Formel 
 EMI1.10 
 mit    Piperidin   bei 90-200  C unter Druck. Es wurde nun gefunden, dass man die Umsetzung von im Kern gegebenenfalls    halo-      genierten      Crotonsäureaniliden   mit    Piperidin   auch bei gewöhnlichem Druck, vorzugsweise    dureh   Kochen einer Mischung der beiden Komponenten am    Rüekfluss   durchfahren kann, was beim Arbeiten im technischen oder halb- technischen Massstab eine wesentliche Verbesserung bedeutet. 



  Die erfindungsgemäss erhältlichen Verbindungen besitzen eine ausserordentlich gute    anästhetische      Wirkung   bei    sehr   geringer    Toxi-      zität   und guter    Depotwirkung.   



     Beispiel   1 Teil    Crotonsäure-2,4-dichlor-anilid   und 1,7 Teile    Piperidin   werden zusammen während 2 Stunden unter    Rückfluss   gekocht. Danach    wird   das überschüssige    Piperidin   abdestilliert und der Rückstand in verdünnte Salzsäure eingegossen, wobei beim    Abkühlen   das Hydrochlorid der neuen Verbindung ausfällt. 



  Die neue Verbindung schmilzt bei 85 bis 87  C und bildet mit Säuren in Wasser leicht lösliche Salze. 



  Die    Piperidinderivate   anderer halogensubstituierter    Crotonsäureanilide   lassen sich in analoger Weise herstellen.



   <Desc / Clms Page number 1>
 Process for the production of local anesthetics In the main patent specification a process for the production of local anesthetics is described, where u. a. also products of the formula
 EMI1.5
 in which at least one R is halogen, the other is hydrogen, are described.



  According to the information in the main patent application, these products are obtained by converting crotonic acid anilides of the formula
 EMI1.10
 with piperidine at 90-200 C under pressure. It has now been found that the reaction of optionally halogenated crotonic acid anilides with piperidine can also be carried out at normal pressure, preferably by boiling a mixture of the two components on the reflux, which is a significant improvement when working on an industrial or semi-industrial scale means.



  The compounds obtainable according to the invention have an extraordinarily good anesthetic effect with very low toxicity and good depot effect.



     Example 1 part of 2,4-dichloro-anilide crotonic acid and 1.7 parts of piperidine are refluxed together for 2 hours. The excess piperidine is then distilled off and the residue is poured into dilute hydrochloric acid, the hydrochloride of the new compound precipitating on cooling.



  The new compound melts at 85 to 87 C and forms easily soluble salts with acids in water.



  The piperidine derivatives of other halogen-substituted crotonic acid anilides can be prepared in an analogous manner.

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung von Lokalanästhetika der Formel EMI1.33 <Desc/Clms Page number 2> worin R Wasserstoff oder Halogen bedeutet, dadurch gekennzeichnet, dass man ein Croton- säureanilid der Formel EMI2.3 ohne Anwendung von Druck mit Piperidin erhitzt. UNTERANSPRUCH Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass die Erhitzung mit überschüssigem Piperidin am Rüekfluss erfolgt. PATENT CLAIM Process for the production of local anesthetics of the formula EMI1.33 <Desc / Clms Page number 2> wherein R denotes hydrogen or halogen, characterized in that a crotonic acid anilide of the formula EMI2.3 heated with piperidine without applying pressure. SUBSTANTIAL CLAIM Process according to patent claim, characterized in that the heating is carried out with excess piperidine at the return flow.
CH332712D 1954-05-31 1954-05-31 Process for the production of local anesthetics CH332712A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH329569T 1954-05-31
CH332712T 1954-05-31

Publications (1)

Publication Number Publication Date
CH332712A true CH332712A (en) 1958-09-15

Family

ID=25736577

Family Applications (1)

Application Number Title Priority Date Filing Date
CH332712D CH332712A (en) 1954-05-31 1954-05-31 Process for the production of local anesthetics

Country Status (1)

Country Link
CH (1) CH332712A (en)

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