CH300714A - Process for the preparation of a substituted cumalic acid ester. - Google Patents

Process for the preparation of a substituted cumalic acid ester.

Info

Publication number
CH300714A
CH300714A CH300714DA CH300714A CH 300714 A CH300714 A CH 300714A CH 300714D A CH300714D A CH 300714DA CH 300714 A CH300714 A CH 300714A
Authority
CH
Switzerland
Prior art keywords
substituted
preparation
acid ester
water
ester
Prior art date
Application number
Other languages
German (de)
Inventor
F Hoffmann- Aktiengesellschaft
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of CH300714A publication Critical patent/CH300714A/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D309/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/34Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D309/36Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C07D309/38Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

  

      Verfahren        zur        Herstellung        eines        substituierten        Cumalinsänreesters.       Es     wurde        gefunden,    dass     Cumalinsäuren     und deren Ester, die in 4- und     6-Stellung     durch einen     Alkylrest    substituiert sind, ins  besondere solche, bei denen die     Alkylreste     mehr     als    ein     C-Atom        aufweisen,    bemerkens  werte antibakterielle Wirkung zeigen.

   So ver  mag die     4,6-Dibutylcumalinsäure    das Wachs  tum von     Mycobacterium        Plilei    in syntheti  schem Milieu noch in einer Verdünnung von       15        y        pro        cmj        zu        90-%        und        dasjenige        von        Sta-          phylococcus        aureus    zu 65     %    zu hemmen. Die  neuen Verbindungen sollen als Arzneimittel  verwendet werden.  



  Die neuen     Verbindungen    können in an  sich     bekannter        Weise    durch     Kondensation    der  Homologen des     Acetessigesters    unter dem Ein  fluss von     hochkonzentrierten,        vorzug@veise    was  serfreien Mineralsäuren, insbesondere Salz  säure oder Schwefelsäure,     erhalten    werden.  Die Kondensation mit Schwefelsäure     führt     zu einem     Gemisch    von freier Säure und  Ester, das durch     fraktionierte    Destillation im  Hochvakuum     getrennt    werden     kann.     



       Gegenstand    des Patentes ist     nun    ein Ver  fahren     zur    Herstellung von     4,6-Dibutyl-euma-          linsäitreäthylester,    das dadurch gekennzeich  net ist, dass man auf     Valeryl-essigsäureäthyl-          ester    bei gewöhnlicher Temperatur eine hoch  konzentrierte Mineralsäure     einwirken    lässt,  das Reaktionsprodukt mit Wasser verdünnt,  die wässerige Lösung mit einem mit     Wasser     nicht     misehbaren    Lösungsmittel extrahiert  und aus dem Extrakt den Ester isoliert.

      <I>Beispiel:</I>  10 Gewichtsteile     Valeryl-essigsäureäthyl-          ester    werden mit 25     Gewichtsteilen    konzen  trierter     Schwefelsäure    versetzt     und    das Ge  misch 10 Tage bei     Zimmertemperatur    aufbe  wahrt.

   Hernach wird die Lösung in Wasser  gegossen und mit     Äther        ausgeschüttelt.    Der  aus der Ätherlösung nach     Trocknen    und Ab  dampfen des Äthers erhaltene     4,6-Dibutyl-          camalinsäureäthylester        destilliert    unter einem  Druck von 0,05 mm bei     144-146     C und stellt  ein gelbes Öl dar:

    Als zweite     Fraktion    vom     Siedepunkt          C'     mm 150  C     erhält    man ein gelbes Öl, -das  beim Erkalten halbfest wird und die     4,6-Di-          butyl-cumalinsäure        darstellt.  



      Process for the preparation of a substituted cumalinic acid ester. It has been found that cumalic acids and their esters which are substituted in the 4- and 6-positions by an alkyl radical, in particular those in which the alkyl radicals have more than one carbon atom, show a remarkable antibacterial effect.

   Thus, 4,6-dibutylcumalic acid is able to inhibit the growth of Mycobacterium Plilei in a synthetic medium even at a dilution of 15% per cm1 and that of Staphylococcus aureus to 65%. The new compounds are intended to be used as drugs.



  The new compounds can be obtained in a manner known per se by condensation of the homologues of the acetoacetic ester under the influence of highly concentrated, preferably water-free mineral acids, in particular hydrochloric acid or sulfuric acid. The condensation with sulfuric acid leads to a mixture of free acid and ester, which can be separated by fractional distillation in a high vacuum.



       The subject of the patent is now a process for the production of 4,6-dibutyl-eumalinsäitreäthylester, which is characterized in that a highly concentrated mineral acid is allowed to act on valeryl-acetic acid ethyl ester at ordinary temperature and the reaction product is diluted with water , the aqueous solution is extracted with a solvent that cannot be measured with water and the ester is isolated from the extract.

      <I> Example: </I> 10 parts by weight of ethyl valeryl acetate are mixed with 25 parts by weight of concentrated sulfuric acid and the mixture is kept for 10 days at room temperature.

   Then the solution is poured into water and shaken out with ether. The ethyl 4,6-dibutyl camalinate obtained from the ether solution after drying and evaporation of the ether is distilled under a pressure of 0.05 mm at 144-146 C and is a yellow oil:

    A yellow oil is obtained as the second fraction with a boiling point of C mm 150 C, which becomes semi-solid on cooling and represents 4,6-di-butyl-cumalic acid.

 

Claims (1)

PATENTAINTSPRUCH Verfahren zur Herstellung von 4,6-Di- butyl - rumalinsäureäthylester, dadurch ge kennzeichnet, dass man auf Valeryl-essigsäure- äthylester bei gewöhnlicher Temperatur eine hochkonzentrierte Mineralsäure einwirken lässt, das Reaktionsprodukt mit Wasser ver dünnt, PATENTAIN CLAIM Process for the production of 4,6-di-butyl-rumalinic acid ethyl ester, characterized in that a highly concentrated mineral acid is allowed to act on valeryl acetic acid ethyl ester at normal temperature, the reaction product is diluted with water, die wässerige Lösung mit einem mit Wasser nicht mischbaren Lösungsmittel ex trahiert und aus dem Extrakt den gesuchten Ester isoliert. Die neue Verbindung ist ein gelbes Öl, das bei 144-146 C/0,05 mm siedet. the aqueous solution is extracted with a water-immiscible solvent and the desired ester is isolated from the extract. The new compound is a yellow oil that boils at 144-146 C / 0.05 mm.
CH300714D 1951-10-18 1951-10-18 Process for the preparation of a substituted cumalic acid ester. CH300714A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH300714T 1951-10-18

Publications (1)

Publication Number Publication Date
CH300714A true CH300714A (en) 1954-08-15

Family

ID=4490811

Family Applications (1)

Application Number Title Priority Date Filing Date
CH300714D CH300714A (en) 1951-10-18 1951-10-18 Process for the preparation of a substituted cumalic acid ester.

Country Status (1)

Country Link
CH (1) CH300714A (en)

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