CH330018A

CH330018A - Process for the production of new polyureas

Info

Publication number: CH330018A
Authority: CH
Inventors: Robert Dr Neher
Original assignee: Ciba Geigy
Priority date: 1954-07-13
Filing date: 1954-07-13
Publication date: 1958-05-15

Description

  

  



  Verfahren zur Herstellung neuer Polyharnstoffe
Gegenstand der Erfindung ist ein Verfahren zur   Herstellung von Polyharnstoffen, wel-       che die Gruppierung  (-ph-NH-CO-NH-)    enthalten, worin Ph f r einen mindestens durch eine freie oder veresterte Sulfogruppe substituierten Phenylenrest steht, und wobei innerhalb der Verbindung jeder beliebige Rest Ph mit einer weiteren Harnstoffgruppe oder einer freien Aminogruppe verbunden ist, sowie ilirer Salze. Dabei bedeutet n eine ganze Zahl gr¯¯er als 2. Eine veresterte Sulfogruppe ist insbesondere eine mit Methylalkohol ver  esterte Sulfogrtlppe.    Diese Polyharnstoffe können weitere Substituenten tragen, so insbesondere an den   Phenylenresten vorzugsweise    Me  thylgruppen    oder zusätzliche freie oder veresterte Sulfogruppen.

   Auch die einzelne Verbindung kann gleiche oder verschiedene Reste Ph enthalten.



   Besonders wertvoll sind Polyharnstoffe der oben genannten Art, worin Ph ein durch eine freie oder veresterte   Sulfogruppe substituier-    ter   Phenylen- (1,    4)-Rest ist, der vorzugsweise keine weiteren Substituenten trÏgt oder durch eine Methylgruppe substituiert ist, und n eine solehe Zahl darstellt, dass das Molekulargewicht   zwisehen    104 und 106 liegt.



   Es können auch Gemische der genannten Polyharnstoffe mit verschiedenem   Molekular-    gewicht. hergestellt werden.



   Die neuen Verbindungen besitzen wertvolle pharmakologische Eigenschaften. So zeigen sie eine ausgeprägte   Anti-Virus-Wirkung.   



  Sie sollen als Heilmittel, insbesondere bei durch Viren an Menschen und Tieren verursachten Krankheiten, oder als Zwischenproduite für die Herstellung von   Heilmitteln    Verwendung finden. So wird durch die genannten Verbindungen in einer   Konzentra-    tion von 10-6 die Vermehrung von Influenzaoder New   Castle-Disease-Virus    in bebrüteten Hühnerembryonen gehemmt. Ihre Verabfol  gung an Laboratoriumstiere    (z. B. Kaninchen) verursacht eine deutliche Veränderung der Gewebe und des Blutes im Sinne einer Herabsetzung der   Empfänglichkeit    f r Virus.



   Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man Verbindungen der Formel    II2N-Ph-NH2    oder    II2NT¯    (-ph-NHCONH-)n-Ph-NH2 worin Ph die oben gegebene Bedeutung besitzt und n eine ganze Zahl kleiner als 3 bedeutet, mit durch Kondensation mit zwei primären Aminogruppen die Harnstoffgruppie  rung-NI3-CO-NI3-bildenden    Verbindungen behandelt. Demgemäss lässt sich ein Amin der obigen Formel z. B. mit einem   Dihalogenid    der Kohlensäure, wie Phosgen, vorzugsweise in wässrigem, besonders saurem l¯sung ein   pg von    weniger weniger als aufweist, wobei ein   grauviolettes    Produkt ausfällt.

   Es wird   abgenutscht,    mit Wasser gewaschen und bei 80    getroeknet.    Das so erhaltene   hellgrau-    violette Produkt mit einem Zersetzungspunkt von über   350 ,    dessen Ammoniumsalz in Wasser gut löslich ist, entspricht einem Gemisch von Polyharnstoffen der Formel
EMI2.1     
 wobei innerhalb der Verbindmg jeder Ben  zolsulfonsäurerestmiteiner    weiteren   Harn-    stoffgruppe oder einer freien Aminogruppe verbunden ist. Die mittlere Diffusionskonstante D beträgt   40 10-T.    In der Ultrazentrifuge lassen sich folgende hauptsächliche Sedimentationskonstanten bestimmen : S20 =   6,      6.10-13,77.10-isund450.10-13.   



  Das spezifische Volumen   1-V@ ist    zu 0, 4 ermittelt. Das erhaltene Produkt setzt sich daher hauptsÏchlich aus Polyharnstoffen der genannten Formel von den mittleren Molekulargewichten von etwa 10000, 117000 und 980000 zusammen.



  



  Process for the production of new polyureas
The invention relates to a process for the production of polyureas which contain the grouping (-ph-NH-CO-NH-), in which Ph stands for a phenylene radical substituted by at least one free or esterified sulfo group, and where within the compound each any radical Ph is connected to a further urea group or a free amino group, as well as its salts. Here, n means an integer greater than 2. An esterified sulfo group is in particular a sulfo group esterified with methyl alcohol. These polyureas can carry further substituents, in particular methyl groups or additional free or esterified sulfo groups on the phenylene radicals.

   The individual compound can also contain identical or different Ph radicals.



   Particularly valuable are polyureas of the type mentioned above, in which Ph is a phenylene (1,4) radical which is substituted by a free or esterified sulfo group and preferably carries no further substituents or is substituted by a methyl group, and n is such a number represents that the molecular weight is between 104 and 106.



   Mixtures of the polyureas mentioned with different molecular weights can also be used. getting produced.



   The new compounds have valuable pharmacological properties. So they show a pronounced anti-virus effect.



  They are intended to be used as remedies, especially for diseases caused by viruses in humans and animals, or as intermediate products for the manufacture of remedies. Thus, the compounds mentioned in a concentration of 10-6 inhibit the reproduction of influenza or New Castle disease virus in incubated chicken embryos. Their administration to laboratory animals (e.g. rabbits) causes a marked change in the tissue and blood in the sense of a decrease in susceptibility to the virus.



   The process according to the invention is characterized in that compounds of the formula II2N-Ph-NH2 or II2NT¯ (-ph-NHCONH-) n-Ph-NH2 in which Ph has the meaning given above and n is an integer less than 3 with the urea grouping-NI3-CO-NI3-forming compounds are treated by condensation with two primary amino groups. Accordingly, an amine of the above formula z. B. with a dihalide of carbonic acid, such as phosgene, preferably in aqueous, particularly acidic solution has a pg of less than less than, with a gray-violet product precipitating.

   It is suction filtered, washed with water and dried at 80. The light gray-violet product obtained in this way with a decomposition point of over 350, the ammonium salt of which is readily soluble in water, corresponds to a mixture of polyureas of the formula
EMI2.1
 wherein within the compound each benzene sulfonic acid residue is linked to a further urea group or a free amino group. The mean diffusion constant D is 40 10-T. The following main sedimentation constants can be determined in the ultracentrifuge: S20 = 6, 6.10-13,77.10-is and 450.10-13.



  The specific volume 1-V @ is determined to be 0.4. The product obtained is therefore mainly composed of polyureas of the formula mentioned with average molecular weights of about 10,000, 117,000 and 980,000.

Claims

PATENT CLAIM Process for the production of new polyureas with more than two urea groups, characterized in that compounds of the formula H2N-Ph NH2 or II2N (-Ph-NHCONH-) ri-Ph-NH2 in which Ph stands for at least one free or esterified sulfo group substituted phenylene radical and n stands for an integer less than 3, treated with compounds which form the urea group-NH-CO-NH-forming by condensation with two primary amino groups.

SUBClaims l. Process according to patent claim, characterized in that the reaction is carried out with a dihalide of carbonic acid.

React medium, if necessary with heating.

Depending on the method of operation, the new compounds are obtained in the form of the free sulfonic acids, their esters or their salts. Esters and salts can be converted into the free acids in the usual way, while on the other hand from the free acids in a manner known per se by reaction with bases such as metal hydroxides or metal hydroxides, e.g. B. alkali or alkaline earth metal hydroxides or ammonia, the corresponding salts or by esterification, eg. B. with diazomethane, the esters are obtained.

If mixtures of polyureas are formed according to the process, these can be prepared by known methods, e.g. B. physical processes, are separated from each other; however, it can also be advantageous to use the mixtures as such, since they can have an effect that is improved by synergistic effects.

The starting materials used according to the method are known or can be obtained by methods known per se. Instead of the free amines, compounds can also be used as starting materials which react like free amines under the reaction conditions; It is also possible to use mixtures of different amines, whereby compounds are formed in which different radicals R are present in the same molecule. The starting materials used are preferably those which lead to the compounds identified above as being particularly valuable.

The invention is described in the following example. The temperatures are given in degrees Celsius.

Example 25 g of p-phenylenediamine-2-sulfonic acid are dissolved in 400 cubic meters of water with the addition of the calculated amount of 2N NaOH (PH7) and treated with a solution of 68 g of crystalline. Sodium acetate in 150 cubic meters of water is added. Phosgene is then slowly introduced with vigorous stirring or vibration until the reaction 2. Process according to patent claim and dependent claim 1, characterized in that it is reacted with phosgene.

3. The method according to claim and the subclaims 1 and 2, characterized in that the reaction is carried out in an aqueous medium.

4. The method according to patent claim and the dependent claims 1-3, characterized in that p-phenylenediamine-2-sulfonic acid is used as the starting material.