CH267601A - Process for the preparation of a biguanide derivative. - Google Patents

Process for the preparation of a biguanide derivative.

Info

Publication number
CH267601A
CH267601A CH267601DA CH267601A CH 267601 A CH267601 A CH 267601A CH 267601D A CH267601D A CH 267601DA CH 267601 A CH267601 A CH 267601A
Authority
CH
Switzerland
Prior art keywords
biguanide
preparation
chloro
salts
biguanide derivative
Prior art date
Application number
Other languages
German (de)
Inventor
Limited Imperial Ch Industries
Original Assignee
Ici Ltd
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 Ici Ltd filed Critical Ici Ltd
Publication of CH267601A publication Critical patent/CH267601A/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/20Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
    • C07C279/24Y being a hetero atom
    • C07C279/26X and Y being nitrogen atoms, i.e. biguanides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

  

  Verfahren     zur    Herstellung eines     Biguanid-Derivates.       Gegenstand der vorliegenden Erfindung  ist ein Verfahren zur Herstellung eines     Bi-          guanid-Derivates,    nämlich des N     1-p-Chlor-          p        henyl    -     N5    -     isopropy    1-     biguanids,    welches     als          Chemotherapeutikum    oder     als    Zwischenpro  dukt für die Herstellung von     Chemothera-          peutika    nützlich ist.  



  Das     erfindungsgemässe    Verfahren ist da  durch gekennzeichnet, dass man einen     N-Iso-          propylguaiiyl-S-alkyl-isotliioharnstoff    mit     p-          Chlor-anilin    zur     Umsetzung    bringt.  



  Der als Ausgangsmaterial für das erfin  dungsgemässe Verfahren verwendete     N-Isopro-          pylguanyl-S-alky1-isotliioharnstoff    kann durch       Alkylierung    von     IsopropylgLxanyl-tIiioharn-          '    Stoff hergestellt werden.  



  Bei der Ausführung des erfindungsgemässen  Verfahrens werden die Reaktionsteilnehmer  vorzugsweise zusammen erhitzt, und zwar  zweckmässig in Gegenwart eines     Lösungs-        bzw.     Verdünnungsmittels. Der     N-Isopropylguanyl-          S-alkyl-isothioharnstoff    kann in freier Form  oder in Form seiner     Salze,    beispielsweise des  Hydrochlorids, verwendet werden. Im letzte  ren Fall wird der     Isothioharnstoff    zweck  mässig in     situ    durch Zugabe einer äquivalen  ten Menge einer basischen Substanz, wie z. B.       Natriummethylat    oder     Natriumäthylat,    in  Freiheit gesetzt..

   Ausserdem kann man auch  das     p-Chlor-anilin,    sofern dies erwünscht ist,  in Form eines Salzes verwenden.  



  Das N 1- p -     Clilor    -     phenyl    -N     5-isopropyl-bi-          guanid,    welches nach dem erfindungsgemässen    Verfahren erhalten wird, ist als     Chemothera-          peutikum    oder als Zwischenprodukt für       Chemotherapeutika        nützlich.    Es ist insbeson  dere als     Antimalariamittel    wertvoll. Es ist  eine starke Base, die mit organischen und an  organischen Säuren beständige     Salze    bildet,  die in vielen Fällen in     Wasser    leicht löslich  sind.

   Diese     Salze    können dadurch erhalten  werden, dass man das     Big        tanid    in einer wäs  serigen Lösung der     Säure    löst und hierauf  das Wasser abdampft. Zweckmässiger wer  den sie jedoch in trockener Form erhalten,  indem man die Komponenten in einem or  ganischen Lösungsmittel, beispielsweise in  Aceton oder in einem     Alkohol,    in welchem  die Salze schwer löslich sind, vermischt.

   Auf  diese Weise kann man leicht beispielsweise die  Salze mit Essigsäure, Milchsäure,     Methan-          sulfonsäure,        Methylendisalicylsäure,        Methy-          len-bis-2,3-oxynaphthoesäure    und Salzsäure  herstellen.  



  Im folgenden Beispiel bedeuten die Teile  Gewichtsteile.  



       Beispiel:          3,    Teile     N-Isopropylguanyl-S-methyl-isothio-          lia.rnstoffhy        drojodid,    1,3 Teile     p-Chlor-anilin     und 5 Teile Wasser werden gemischt und zu  sammen am     Rückflusskühler    während 18     St-Lm-          den    im Siedezustand gehalten. Das Reaktions  gemisch wird hierauf durch Zugabe von Am  moniak gegen Brillantgelb eben alkalisch ge  stellt und mit Äther extrahiert.

   Man versetzt  die wässerige Schicht mit.     Natriumhy        droxyd,         wobei     die        Biguanidbase        ausfällt,    die nach  dem     Umkristallisieren    bei 129  C schmilzt. Sie  bildet ein Hydrochlorid, das einen     Smp.    von  243 bis     244     C aufweist.



  Process for the preparation of a biguanide derivative. The present invention relates to a process for producing a biguanide derivative, namely N 1-p-chlorophenyl - N5 - isopropy 1-biguanide, which is useful as a chemotherapeutic agent or as an intermediate product for the preparation of chemotherapeutic agents is.



  The process according to the invention is characterized in that an N-isopropylguaiyl-S-alkyl-isotiiourea is reacted with p-chloroaniline.



  The N-isopropylguanyl-S-alky1-isotliourea used as the starting material for the process according to the invention can be produced by alkylating isopropylgLxanyl-thiiourea.



  When carrying out the process according to the invention, the reactants are preferably heated together, expediently in the presence of a solvent or diluent. The N-isopropylguanyl-S-alkyl-isothiourea can be used in free form or in the form of its salts, for example the hydrochloride. In the latter case, the isothiourea is conveniently in situ by adding an equivalen th amount of a basic substance, such as. B. sodium methylate or sodium ethylate, set free.

   In addition, you can also use the p-chloro-aniline, if desired, in the form of a salt.



  The N 1 - p - Clilor - phenyl - N 5 - isopropyl - biguanide, which is obtained by the process according to the invention, is useful as a chemotherapeutic agent or as an intermediate for chemotherapeutic agents. It is particularly valuable as an antimalarial agent. It is a strong base that forms salts with organic and organic acids, which in many cases are easily soluble in water.

   These salts can be obtained by dissolving the big tanide in an aqueous solution of the acid and then evaporating the water. However, it is more practical to obtain them in dry form by mixing the components in an organic solvent, for example in acetone or in an alcohol in which the salts are sparingly soluble.

   In this way, for example, the salts with acetic acid, lactic acid, methanesulfonic acid, methylenedisalicylic acid, methylene-bis-2,3-oxynaphthoic acid and hydrochloric acid can easily be prepared.



  In the following example, the parts mean parts by weight.



       Example: 3 parts of N-isopropylguanyl-S-methyl-isothio- lia.rnstoffhy drojodid, 1.3 parts of p-chloro-aniline and 5 parts of water are mixed and kept together at the reflux condenser for 18 hours in the boiling state . The reaction mixture is then made alkaline against brilliant yellow by adding ammonia and extracted with ether.

   The aqueous layer is added. Sodium hydroxide, whereby the biguanide base precipitates, which melts at 129 C after recrystallization. It forms a hydrochloride which has a melting point of 243 to 244.degree.

 

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung eines Bigzanid- Derivates, nämlich des Nl-p-Chlor-phenyl-N,- isopropyl-biguanids, dadurch gekennzeichnet, dass man einen N-Isopropylguanyl-S-alkyl- isothloharnstoff mit p-Chlor-anilin zur Um setzung bringt. Das N1-p-Chlor-phenyl-N'-isopropyl-bi- guanid ist eine starke Base vom Smp. 129 C; es bildet ein Hydrochlorid, das bei 243 bis 244 C, und ein Acetat., das bei 188 C schmilzt. PATENT CLAIM Process for the production of a bigzanide derivative, namely the Nl-p-chloro-phenyl-N, - isopropyl-biguanids, characterized in that an N-isopropylguanyl-S-alkyl isothlourea with p-chloro-aniline is used for the implementation brings. The N1-p-chloro-phenyl-N'-isopropyl-biguanide is a strong base with a melting point of 129 C; it forms a hydrochloride, which melts at 243 to 244 C, and an acetate, which melts at 188 C. Das Biguanid und dessen Salze besitzen eine starke Antimalariawirksamkeit. The biguanide and its salts have a strong antimalarial activity.
CH267601D 1946-01-07 1947-01-06 Process for the preparation of a biguanide derivative. CH267601A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB267601X 1946-01-07
GB265196X 1946-01-07
CH265196T 1947-01-06

Publications (1)

Publication Number Publication Date
CH267601A true CH267601A (en) 1950-03-31

Family

ID=27178093

Family Applications (1)

Application Number Title Priority Date Filing Date
CH267601D CH267601A (en) 1946-01-07 1947-01-06 Process for the preparation of a biguanide derivative.

Country Status (1)

Country Link
CH (1) CH267601A (en)

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