CH280319A - Process for the preparation of a new barbituric acid compound. - Google Patents

Process for the preparation of a new barbituric acid compound.

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Publication number
CH280319A
CH280319A CH280319DA CH280319A CH 280319 A CH280319 A CH 280319A CH 280319D A CH280319D A CH 280319DA CH 280319 A CH280319 A CH 280319A
Authority
CH
Switzerland
Prior art keywords
sep
preparation
barbituric acid
acid compound
new
Prior art date
Application number
Other languages
German (de)
Inventor
Company Eli Lilly And
Original Assignee
Lilly Co Eli
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 Lilly Co Eli filed Critical Lilly Co Eli
Publication of CH280319A publication Critical patent/CH280319A/en

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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Description

  

  Verfahren zur Herstellung einer neuen     Barbitursäureverbindung.            Geo-enstand    der vorliegenden     Erfindung     ist ein Verfahren zur     Herstellung    einer neuen       Barbitursäureverbindung,    nämlich der     Spiro-          2,3,5-triniethyley        elopentan-(1),5'-thiobarbitur-          säure.     



  Die neue     Thiobarbitursäure    besitzt     berulii-          Oende,    einschläfernde und     anästhetiselie    Eigen  schaften von     bemerkenswerter    kurzer Dauer.  Sie ist in kleinen Dosen wirksam und     zeigst.     einen weiten     Sieherheitsbereieh    zwischen  therapeutischer und toxischer Dosis. Sie ist  besonders geeignet, um durch intravenöse     Ver-          abreiehung    eine allgemeine Anästhesie von       kurzer    Dauer zu erzeugen.  



  Die neue Verbindung kann durch die     fol-          gc@n(le    Formel wiedergegeben  -erden:  
EMI0001.0022     
    Das erfindungsgemässe Verfahren ist     da-          dureli        gelzennzeielinet,    dass man     3.,1-Diea@b-          iillioxz='?,3,5-trimetlivieyelopentan    mit     Thio-          liarnstoff    kondensiert.  



  Die     neue        Barbitursäure    lässt sich in Salze       überführen,    beispielsweise mittels     Natrium-          alkoholat    in wasserfreier     Alkohollösung    oder  mit.     Natriumhydroxyd    in wässeriger Alkohol  lösung, in (las     Natriumsalz.    Für     pharmazeu-          tiselie    Zwecke wird gewöhnlich das Natrium  salz     zur    Verwendung belangen. Die neue Ver-         bindung    ist im allgemeinen in Wasser wenig  löslich und lässt sich oral verabreichen.

   Für  die subkutane Verabreichung wird die neue  Verbindung vorzugsweise in Form ihrer was  serlöslichen Salze und insbesondere des     @a-          triumsalzes    verwendet.  



       Beispiel:     Es wird ein 38 g in     495        ema    absolutem Me  thanol gelöstes Natrium und 62 g     Thioharn-          stoff    enthaltendes Gemisch hergestellt, welches  mit 141 g     1,1-Diearbäthoxy-2,3,5-trimethyley-          elopenta.n    versetzt wird. Das erhaltene Gemisch  wird während sechs Stunden unter     Rückfluss     erhitzt und     anschliessend    zur     Entfernung    des  Methanols destilliert.

   Der Rückstand wird ge  kühlt und mit     Wasser    versetzt, worauf das  wässerige Gemisch zur Entfernung von in Al  kali unlöslichem Öl wiederholt mit Äther ex  trahiert     wird.    Der Ätherextrakt wird verwor  fen. Die wässerige Lösung wird gekühlt und  unter Rühren mit verdünnter Salzsäure be  handelt, bis das Gemisch neutral reagiert. Da  bei bildet sich ein Niederschlag der     gewünseh-          ten        Spiro-2,3,5-trimethyleyclopentan-(1),5'-          thiobarbitursäure    in roher Form.  



  Der Niederschlag     wird    durch Filtrieren  isoliert, mit Wasser gewaschen und mehrmals  aus verdünntem Alkohol umkristallisiert. Die  gereinigte, kristalline Säure schmilzt bei 175  bis 177  C     (unkorr.)    und ist in -Wasser nur  wenig löslich, in Alkohol dagegen gut löslich.  



  Analyse: Gefunden     N---11,541/o;        Berech-          net:        N=71,67%.  



  Process for the preparation of a new barbituric acid compound. The subject matter of the present invention is a process for the production of a new barbituric acid compound, namely spiro-2,3,5-triniethyley elopentanoic (1), 5'-thiobarbituric acid.



  The new thiobarbituric acid has berulant, soporific and anesthetic properties of remarkably short duration. It is effective in small doses and shows. a wide range of confidence between therapeutic and toxic dose. It is particularly suitable for creating general anesthesia of short duration by intravenous administration.



  The new compound can be represented by the following formula:
EMI0001.0022
    The process according to the invention is characterized in that 3., 1-Diea @ b-iillioxz = '?, 3,5-trimethyl-yelopentane is condensed with thiolarea.



  The new barbituric acid can be converted into salts, for example using sodium alcoholate in anhydrous alcohol solution or with. Sodium hydroxide in aqueous alcohol solution, in (as the sodium salt. The sodium salt is usually used for pharmaceutical purposes. The new compound is generally sparingly soluble in water and can be administered orally.

   For subcutaneous administration, the new compound is preferably used in the form of its water-soluble salts and in particular the @ a- trium salt.



       Example: A mixture containing 38 g of sodium dissolved in 495 ema absolute methanol and 62 g of thiourea is produced, to which 141 g of 1,1-diearbethoxy-2,3,5-trimethyleyelopenta.n are added. The resulting mixture is refluxed for six hours and then distilled to remove the methanol.

   The residue is cooled and water is added, whereupon the aqueous mixture is repeatedly extracted with ether to remove oil which is insoluble in alkali. The ether extract is discarded. The aqueous solution is cooled and treated with dilute hydrochloric acid while stirring until the mixture reacts neutrally. A precipitate of the desired spiro-2,3,5-trimethyleyclopentane (1), 5'-thiobarbituric acid forms in crude form.



  The precipitate is isolated by filtration, washed with water and recrystallized several times from dilute alcohol. The purified, crystalline acid melts at 175 to 177 C (uncorrupted) and is only sparingly soluble in water, but readily soluble in alcohol.



  Analysis: Found N --- 11.541 / o; Calculated: N = 71.67%.

 

Claims (1)

EMI0002.0001 <B>PATENTANSPRUCH:</B> <tb> Verfahren <SEP> zier <SEP> Herstellung <SEP> der <SEP> Spiro-2,3,5 trimethy <SEP> 1-eyelopentaii- <SEP> (1),5'-thiobarbitursäure <tb> der <SEP> Formel: EMI0002.0002 dadureh gekennzeiehnet, class 1,1-Diearb- äthoxy-2,3,5-trimethyl-eyelopent.an mit Thio- harnstoff kondensiert. wird. EMI0002.0001 <B> PATENT CLAIM: </B> <tb> Process <SEP> zier <SEP> production <SEP> of <SEP> spiro-2,3,5 trimethy <SEP> 1-eyelopentaii- <SEP> (1), 5'-thiobarbituric acid <tb> of the <SEP> formula: EMI0002.0002 dadureh marked, class 1,1-Diearb- äthoxy-2,3,5-trimethyl-eyelopent.an condensed with thiourea. becomes. Die nette Verbindung ist eine kristalline Substanz vom Sinp. 175 bis l.77 C (unkorr.), 1s weist eine geringe Lösliehkeit in Wasser auf und ist. in Alkohol gut löslieh. The nice compound is a crystalline substance from the Sinp. 175 to 1.77 C (uncorrupted), 1s has a low solubility in water and is. Well soluble in alcohol.
CH280319D 1948-05-28 1949-05-28 Process for the preparation of a new barbituric acid compound. CH280319A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US280319XA 1948-05-28 1948-05-28

Publications (1)

Publication Number Publication Date
CH280319A true CH280319A (en) 1952-01-15

Family

ID=21841174

Family Applications (1)

Application Number Title Priority Date Filing Date
CH280319D CH280319A (en) 1948-05-28 1949-05-28 Process for the preparation of a new barbituric acid compound.

Country Status (1)

Country Link
CH (1) CH280319A (en)

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