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DE936748C - Process for the production of new Schiff bases - Google Patents

Process for the production of new Schiff bases

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Publication number
DE936748C
DE936748C DEC9294A DEC0009294A DE936748C DE 936748 C DE936748 C DE 936748C DE C9294 A DEC9294 A DE C9294A DE C0009294 A DEC0009294 A DE C0009294A DE 936748 C DE936748 C DE 936748C
Authority
DE
Germany
Prior art keywords
alkyl
radical
amino
schiff bases
oxy
Prior art date
Legal status (The legal status 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 status listed.)
Expired
Application number
DEC9294A
Other languages
German (de)
Inventor
Ernst Dr Habicht
Hans Dr Suter
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cilag AG
Original Assignee
Cilag AG
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 Cilag AG filed Critical Cilag AG
Application granted granted Critical
Publication of DE936748C publication Critical patent/DE936748C/en
Expired legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/42One nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48Two nitrogen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Liquid Crystal Substances (AREA)

Description

Verfahren zur Herstellung neuer Schiffscher Basen Gegenstand der Erfindung bildet eine Reihe von neuen Schiffschen Basen von der allgemeinen Formel in welcher R1 ein Wasserstoffatom, einen Alkyl- oder Aralkylrest, eine Amino-, Alkylamino-, Alkoxy- oder Aralkoxy-, eine Thiol-, Alkyl-, Aralkylthiogruppe, eine Acyl- oder Aroylthiogruppe, R2 eine Oxy- oder Aminogruppe, R4 ein Wasserstoffatom oder einen Alkylrest, X einen geraden oder verzweigten Alkyl-oder Alkenylrest und R einen aromatischen oder isocychschen Rest, der durch Oxy-, Alkoxy-, Alkyl-, Nitro-, Amino-, Acylamino-, Alkyl- oder Dialkylamino-, Ureido-, N'-Alkylureidogruppen substituiert sein kann, bedeutet, sowie Salze solcher Verbindungen mit pharmakologisch verträglichen organischen oder anorganischen Säuren.Process for the preparation of new Schiff's bases The subject of the invention forms a series of new Schiff's bases of the general formula in which R1 is a hydrogen atom, an alkyl or aralkyl radical, an amino, alkylamino, alkoxy or aralkoxy, a thiol, alkyl, aralkylthio group, an acyl or aroylthio group, R2 is an oxy or amino group, R4 is a hydrogen atom or an alkyl radical, X a straight or branched alkyl or alkenyl radical and R an aromatic or isocyanic radical which is represented by oxy, alkoxy, alkyl, nitro, amino, acylamino, alkyl or dialkylamino, ureido, N'-alkylureido groups can be substituted, and also salts of such compounds with pharmacologically acceptable organic or inorganic acids.

Verbindungen, welche dieser vorerwähnten Formel entsprechen, besitzen wertvolle bakteriologische Eigenschaften. Sie sind beispielsweise befähigt, das Wachstum von Tbc-Keimen zu hemmen und sollen deshalb als Arzneimittel Verwendung finden.Compounds corresponding to the aforementioned formula have valuable bacteriological properties. You are for example capable of inhibiting the growth of Tbc germs and should therefore be used as a drug Find use.

Es ist bekannt, daß Benzaldehyd mit 2-Methyl-4-amino-5-aminomethylpyrimidin eine Schiffsche Base bildet (vgl. Berichte der deutschen chemischen Gesellschaft, Bd. 7o [r937], S. 2046/2047). Diese zeigt keine praktisch verwertbare tuberkulostatische und keine tuberkulocide Wirkung, während die aus araliphatischen Aldehyden und entsprechenden 5-Aminomethylpyrimidinen gebildeten Schiffschen Basen tuberkulostatisch und tuberkulocid gut bis sehr gut wirksam sind.It is known that benzaldehyde with 2-methyl-4-amino-5-aminomethylpyrimidine forms a Schiff base (see reports of the German chemical society, Vol. 7o [r937], pp. 2046/2047). This shows no practically usable tuberculostatic and no tuberculocidal effect, while those from araliphatic aldehydes and corresponding 5-aminomethylpyrimidines formed Schiff bases tuberculostatic and tuberculocid are good to very effective.

Die Herstellung der Verbindungen erfolgt nach an sich -bekannten Verfahren durch Umsetzung eines Aminomethylpyrimidins der Formel in welcher R1, R2 und R4 die bereits erwähnte Bedeutung zukommt, mit einer Verbindung, welche zur Einführung des Restes in die Aminomethylgruppe geeignet ist, worin R und X die bereits erwähnte Bedeutung zukommt.The compounds are prepared by processes known per se by reacting an aminomethylpyrimidine of the formula in which R1, R2 and R4 have the meaning already mentioned, with a compound which leads to the introduction of the remainder is suitable in the aminomethyl group, in which R and X have the meaning already mentioned.

Als Verbindungen, welche diesen Rest (III) in die Aminomethylgruppe einführen können, seien genannt die entsprechenden Aldehyde, ihre Acetale und Acylderivate und die entsprechenden Dihalogenide. Die 5-Aminomethylpyrimidine der Formel (II) können in Form der freien Base oder auch als Säuresalze zur Reaktion gebracht werden, wobei man dann vor, während oder nach Zusatz der zweiten. Reaktionskomponente die der Säure entsprechende Menge Alkali zufügt.As compounds which convert this radical (III) into the aminomethyl group can introduce the corresponding aldehydes, their acetals and acyl derivatives and the corresponding dihalides. The 5-aminomethylpyrimidines of the formula (II) can be reacted in the form of the free base or as acid salts, then before, during or after the addition of the second. Reaction component the add the appropriate amount of alkali to the acid.

Verwendet man z. B. ein Dihalogenid, so arbeitet man vorteilhaft in Gegenwart eines basischen Kondensationsmittels, wie Alkalihydroxyden, Oxyden, Karbonaten, Alkoholaten. Im allgemeinen ist das Arbeiten in einem Lösungsmittel angezeigt, jedoch nicht unbedingt erforderlich. Als Lösungsmittel eignen sich z. B. Alkohole vorzüglich.If you use z. B. a dihalide, it is advantageous to work in Presence of a basic condensing agent, such as alkali hydroxides, oxides, carbonates, Alcoholates. In general, however, working in a solvent is indicated not necessarily required. Suitable solvents are, for. B. Alcohols excellent.

Verbindungen, in denen R2 eine Aminogruppe bedeutet, besitzen wahrscheinlich die folgende Konfiguration Auf diese Struktur konnte auf Grund der für solche Verbindungen erhaltenen Absorptionsspektren mit großer Wahrscheinlichkeit geschlossen werden.Compounds in which R2 represents an amino group are likely to have the following configuration This structure could be inferred with great probability on the basis of the absorption spectra obtained for such compounds.

Beispiel 5 g 2, 6-Dimethyl-4-amino-5-aminomethylpyrimidindihydrochlorid werden in einer Lösung von 1,03 g Natrium in 50 ccm Methanol aufgeschlämmt, und die Suspension wird mit 3 g Zimtaldehyd in 15 ccm Methanol versetzt. Man erhitzt 2o Minuten zum Sieden,- verdampft das Ganze im Vakuum und verreibt den Rückstand in Wasser. Anschließend wird aus Benzol tonkristallisiert. Man erhält 3 g 5-Cinnamalaminomethyl-2, 6-dimethyl-4-aminopyrimidin [2, 6-Dimethyl-2-styryl-i', 2', 3', 4'-tetrahydropyrimido-(5', 6': 5, 4)-pyrimidin], das bei 12o bis 122° schmilzt.Example 5 g of 2,6-dimethyl-4-amino-5-aminomethylpyrimidine dihydrochloride are slurried in a solution of 1.03 g of sodium in 50 ccm of methanol, and 3 g of cinnamaldehyde in 15 cc of methanol are added to the suspension. One heats up 20 minutes to the boil - the whole thing evaporates in vacuo and rubs off the residue in water. Then it is clay crystallized from benzene. 3 g of 5-cinnamalaminomethyl-2 are obtained, 6-dimethyl-4-aminopyrimidine [2,6-dimethyl-2-styryl-i ', 2', 3 ', 4'-tetrahydropyrimido- (5', 6 ': 5, 4) -pyrimidine], which melts at 12o to 122 °.

In der gleichen Weise erhält man folgende in 2'-Stellung substituierte 2, 6-Dimethyl-1', 2', 3', 4'-tetrahydropyrimido-(5', 6': 5, 4)-pyrimidine: Substituent in 2'-Stellung Schmelzpunkt a-Amylstyryl . . . . . . . . . . . . . . . . . . 136 bis 138° a-Methylbenzyl [C.HS - CH (CH3)j- 151 bis 155° p-Nitrostyryl . . . . . . . . . . . . . . . . . . . 187 bis 188° p-Acetaminostyryl . . . . . . . . . . . . . . . 167 bis 168° (Zersetzung) In the same way, the following 2,6-dimethyl-1 ', 2', 3 ', 4'-tetrahydropyrimido (5', 6 ': 5, 4) pyrimidines are obtained: Substituent in the 2'-position. Melting point α-amyl styryl. . . . . . . . . . . . . . . . . . 136 to 138 ° α-methylbenzyl [C.HS-CH (CH3) j -151-155 ° p-nitrostyryl. . . . . . . . . . . . . . . . . . . 187 to 188 ° p-acetaminostyryl. . . . . . . . . . . . . . . 167 to 168 ° (Decomposition)

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung neuer Schiffscher Basen der allgemeinen Formel in welcher R1 ein Wasserstoffatom, einen Alkyl- oder Aralkylrest, eine Amino-, Alkylamino-, Alkoxy-oder Aralkoxy-, eine Thiol-, Alkyl- oder Aralkylthiol-, eine Acyl- oder Aroyl-thiogruppe, R2 eine Oxy- oder Aminogruppe, R4 ein Wasserstoffatom oder einen Alkylrest, X ein gerader oder verzweigter Alkyl- oder Alkylenrest, R einen aromatischen oder isocyclischen Rest, der durch Oxy-, Alkoxy-, Alkyl-, " Nitro-, Amino-, Acylamino-, Alkylamino- oder Dialkylamino-, Ureido-, N'-Alkylureidogruppen substituiert sein kann, bedeutet, sowie Salze solcher Verbindungen mit pharmakologisch verträglichen organischen oder anorganischen Säuren, dadurch. gekennzeichnet, daß man ein 5-Aminomethylpyrimidin der Formel in welcher R1, R2 und R4 die bereits definierte Bedeutung zukommt, mit einer Verbindung, welche zur Einführung des Restes wobei lt und X die oben angegebene Bedeutung haben, in die Aminomethylgruppe geeignet ist, nämlich den entsprechenden Aldehyden oder ihren Acetalen, Acylderivaten, Dihalogeniden, umsetzt, und die erhaltenen Schiffschen Basen gewünschtenfalls in ihre Salze mit pharmakologisch verträglichen Säuren überführt. Angezogene Druckschriften: Berichte der deutschen chemischen Gesellschaft, Bd.7o [z937], S.2046/2047; Chemical Abstracts, Bd. 43 [19491, S. 7051h.PATENT CLAIM: Process for the production of new Schiff bases of the general formula in which R1 is a hydrogen atom, an alkyl or aralkyl radical, an amino, alkylamino, alkoxy or aralkoxy, a thiol, alkyl or aralkylthiol, an acyl or aroyl-thio group, R2 is an oxy or amino group, R4 is a hydrogen atom or an alkyl radical, X is a straight or branched alkyl or alkylene radical, R is an aromatic or isocyclic radical which is represented by oxy, alkoxy, alkyl, "nitro, amino, acylamino, alkylamino or dialkylamino" , Ureido, N'-alkylureido groups, and salts of such compounds with pharmacologically acceptable organic or inorganic acids, characterized in that a 5-aminomethylpyrimidine of the formula in which R1, R2 and R4 have the meaning already defined, with a compound which introduces the remainder where lt and X have the meaning given above, is suitable for the aminomethyl group, namely converts the corresponding aldehydes or their acetals, acyl derivatives, dihalides, and converts the Schiff bases obtained, if desired, into their salts with pharmacologically acceptable acids. Cited pamphlets: Reports of the German Chemical Society, Vol.7o [z937], p.2046/2047; Chemical Abstracts, Vol. 43 [19491, p. 7051h.
DEC9294A 1953-03-31 1953-06-26 Process for the production of new Schiff bases Expired DE936748C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH936748X 1953-03-31

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DE936748C true DE936748C (en) 1955-12-22

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Non-Patent Citations (1)

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