CH254803A

CH254803A - Process for the preparation of a new carboxylic acid.

Info

Publication number: CH254803A
Authority: CH
Inventors: Aktiengesellschaft Cilag
Original assignee: Cilag Ag
Priority date: 1946-11-07
Filing date: 1946-11-07
Publication date: 1948-05-31

Description

  

  Verfahren zur Darstellung einer neuen     Karbonsäure.            1Js        wurde    gefunden,     da.ss        Karbon:säuren          (ler        allgemeinen        Formel     
EMI0001.0009     
    in welcher R ein Wasserstoffatom, einen Al  ky 1- und einen     Ary        lrest    bedeuten kann, wert  volle therapeutische Eigenschaften     auf-,vei-          sen.-    So entfalten :sie zum     Beispiel    eine starke  a     ntibakt:

  erielle    Wirksamkeit gegen     Otitis-          stämmeund    eignen sich in gelöster Form       namentlich    zur äusserlichen Behandlung der       Otitis        media,        purulenta..    Die Verbindungen  sollen     als    Arzneimittel und als     Z#xvischenpro-          dukte    Verwendung finden.  



  Gegenstand des Patentes     isst    ein Verfah  ren zur Darstellung einer     Karbonsäure,        wel-          ebes    dadurch gekennzeichnet ist, dass     man          1,4'-Diamino-diphenylstilfon    mit einer     Mono-          halogenessigsä        ure    umsetzt, wobei unter Ab  spaltung von     Halogenwasserstoff        4-Carboxy-          nietliyl <  < mino    - 4' -     a.mino    -     cliphenylsulfon        ent-          ;

  telit.    Die     Umsc-tzung    wird zweckmässig in       alkalisehein        Medium    vorgenommen, dessen PH  zwischen. 8,0 und 10,0 liegt. In besonders  nuten     Ausbeute        bildet    :sich die neue Verbin  dung,     trenn    das     31edium        während    der ganzen  Dauer der Reaktion auf einem PH von wenig  stens annähernd 9 gehalten wird.

   Auf 1     Mol          4,4'-Diamino-dipbenylsulfon,    werden vorteil  haft     wenigstens    annähernd 2 Mole der     Mono-          halogenessigsä        ure        verwendet.       <I>Ausführungsbeispiel:</I>    Zu einer kochenden Lösung von 24,8 g 4,4'  Diamino-diphenylsulfon in     G'00    cm" Wasser  gibt man langsam unter Rühren ein Gemisch  einer mit Natronlauge auf ein     pH    von 9 einge  stellten Lösung von 18,9 g     14lonochlore:ssigsäure     in 90<I>ein'</I> Wasser und einer solchen von 16,8 g       Natriumbikarbonat    in 200 ein' Wasser.

   Nach  beendeter Reaktion wird das     unveränderte          Diamino-diphenylsulfon    (l2,4 g)     abfiltriert,     das alkalische Filtrat mit Salzsäure ange  säuert (PH 5 bis 6), das dabei ausfallende       4-Carboxymethylamnno-4'-amino-diphenylsul-          fon        abfiltriert    und mit Wasser gewaschen.  Es kann über das     Natriumsalz    gereinigt wer  den.     Ausbeute:    14,9 g, entsprechend 97,5     iö     der Theorie.

   Das     4-Ca.rboxymethylamino-4'-          amäno-diphenylsulfon    bildet farblose, mikro  kristalline Nadeln vom Schmelzpunkt 194  C,  die in Methanol, Äthanol und verdünnten       Alkalien    löslich, in     Wasser    dagegen unlös  lich sind.    Die gebildete     Karbonsäure        lä,sst    sich auch  in Form ihrer Salze, z.     B.    des Natriums oder  des     Calciums,    isolieren.



  Process for the preparation of a new carboxylic acid. It was found that carbon acids (according to the general formula
EMI0001.0009
    in which R can represent a hydrogen atom, an alkyl radical and an aryl radical, show valuable therapeutic properties - this is how they develop, for example, a strong anti-bacterial effect:

  erial activity against otitis strains and are particularly suitable in dissolved form for the external treatment of otitis media, purulenta .. The compounds are intended to be used as medicaments and as cure products.



  The subject of the patent is a process for the preparation of a carboxylic acid, which is characterized in that 1,4'-diamino-diphenylstilfone is reacted with a monohaloacetic acid, with 4-carboxy- niethyl <<with elimination of hydrogen halide mino - 4 '- a.mino - cliphenyl sulfone ent-;

  telit. The conversion is expediently carried out in an alkaline medium with a pH between. 8.0 and 10.0. The new compound is formed in particularly good yield, and the medium is kept at a pH of at least approximately 9 for the entire duration of the reaction.

   For 1 mole of 4,4'-diaminodipbenyl sulfone, at least approximately 2 moles of monohaloacetic acid are advantageously used. <I> Exemplary embodiment: </I> A mixture of a solution adjusted to a pH of 9 with sodium hydroxide solution is slowly added to a boiling solution of 24.8 g of 4,4 'diamino-diphenyl sulfone in 100 cm "of water of 18.9 g 14lonochloro: acetic acid in 90 <I> a '</I> water and one of 16.8 g sodium bicarbonate in 200 a' water.

   After the reaction has ended, the unchanged diamino-diphenylsulfone (12.4 g) is filtered off, the alkaline filtrate is acidified with hydrochloric acid (pH 5 to 6), the 4-carboxymethylamnno-4'-aminodiphenylsulfone which precipitates is filtered off and washed with water washed. It can be purified using the sodium salt. Yield: 14.9 g, corresponding to 97.5% of theory.

   The 4-Ca.rboxymethylamino-4'-amano-diphenyl sulfone forms colorless, microcrystalline needles with a melting point of 194 C, which are soluble in methanol, ethanol and dilute alkalis, but insoluble in water. The carboxylic acid formed can also be in the form of its salts, e.g. B. of sodium or calcium isolate.

Claims

PATENT CLAIM: Process for the preparation of a new carboxylic acid, characterized in that 4,4'-diamino-diphenyl sulfone is reacted with a monohaloacetic acid, so that 4-carboxy methylamino - 4'-amino - diphenyl sulfone is formed, which is colorless, Microcrystalline needles with a melting point of 194 C form, which are soluble in methanol, ethanol and dilute alkalis and insoluble in water.

SUBClaims: 1. Method according to claim, characterized in that the two starting materials are reacted in an alkaline medium. 2. The method according to claim and dependent claim 1, characterized in that the two starting materials are reacted in a medium whose pg is between 8.0 and <B> 10.0 </B>. 3.

Method according to patent claim and the dependent claims 1 and 2, characterized in that the medium is kept at a pg of at least approximately 9 for the duration of the reaction. 4. The method according to claim and dependent claim 1, characterized. that one converts the two starting materials in the presence of sodium bicarbonate at the boiling point. 5. The method according to claim, characterized in that at least approximately 2 moles of monohaloacetic acid are used per mole of 4,4'-diamino-diphenylsulfone. G.

Process according to claim, characterized in that monochloroic acid is used.