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AT246129B - Process for the preparation of new 3- (5-nitro-2-furyl) -4H-1,2,4-triazoles - Google Patents

Process for the preparation of new 3- (5-nitro-2-furyl) -4H-1,2,4-triazoles

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Publication number
AT246129B
AT246129B AT1021464A AT1021464A AT246129B AT 246129 B AT246129 B AT 246129B AT 1021464 A AT1021464 A AT 1021464A AT 1021464 A AT1021464 A AT 1021464A AT 246129 B AT246129 B AT 246129B
Authority
AT
Austria
Prior art keywords
sep
nitro
furyl
new
triazoles
Prior art date
Application number
AT1021464A
Other languages
German (de)
Original Assignee
Norwich Pharma Co
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 Norwich Pharma Co filed Critical Norwich Pharma Co
Application granted granted Critical
Publication of AT246129B publication Critical patent/AT246129B/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/70—Nitro radicals
    • C07D307/71—Nitro radicals attached in position 5
    • C07D307/72—Nitro radicals attached in position 5 with hydrocarbon radicals, substituted by nitrogen-containing radicals, attached in position 2
    • C07D307/74—Nitro radicals attached in position 5 with hydrocarbon radicals, substituted by nitrogen-containing radicals, attached in position 2 by hydrazino or hydrazono or such substituted radicals

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

  

   <Desc/Clms Page number 1> 
 



  Verfahren zur Herstellung von neuen   3- (5-Nitro-2-furyl)-4H-l, 2, 4-triazolen   Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von neuen    3- (5-Nitro-2-furyl) -4H-     1, 2, 4-triazolen   der allgemeinen Formel I : 
 EMI1.1 
 in welcher R Wasserstoff oder eine niedere Alkylgruppe bedeutet. 



   Diese Verbindungen sind hochwirksame antibakterielle Mittel, welche schon in sehr geringen Dosierungen gegen gram-positive und gram-negative Bakterien, wie z. B. Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Proteus vulgaris und Erysipelothrix insidiosa wirken. Sie können daher mit den üblichen Trägersubstanzen und Adjuvantien zu Desinfektionsmitteln (in Form von Pudern, Sprays, Suspensionen, Lösungen, Tabletten, Salben usw. ) verarbeitet werden. 



   Die neuen Verbindungen besitzen jedoch nicht nur einen in vitro-Effekt, es konnte vielmehr gezeigt werden, dass durch orale Verabreichung dieser Substanzen an mit pathogenen Mikroorganismen (z. B. 



  Staphylococcus aureus, Salmonella typhosa, Escherichia coli) infizierte Tiere der Tod derselben verhindert wird. Verabreicht man z. B. an Mäuse, die mit tödlichen Mengen der genannten Bakterien infiziert sind, die neuen Verbindungen peroral in einer Dosierung von 40 bis 150 mg/kg, so werden die Todesfälle völlig verhindert. Da bei Verabreichung der neuen Nitrofuran-Verbindungen hohe antibakterielle Serumspiegel entstehen, stellen diese Substanzen wertvolle systemische Chemotherapeutica dar. 



    Das erfindungsgemässe Verfahren zur Herstellung der neuen 3- (5-Nitro-2-furyl)-4H-l, 2, 4-triazole der Formel I ist dadurch gekennzeichnet, dass man ein N-Acylamido-5-nitro-2-furamidin der Formel II :    
 EMI1.2 
 in welcher R die oben angegebene Bedeutung hat, mit wasserabspaltenden Mitteln behandelt. Als wasserabspaltende Mittel sind z. B. geeignet : Phosphoroxychlorid und Eisessig. Um die Reaktion zu beschleuni-   gen, kann erhitzt werden. 



  In den folgenden Beispielen ist das erfindungsgemässe Verfahren näher erläutert.   



   Beispiel   1 : 3-Methyl-5- (5-nitro-2-furyl)-4H-1, 2, 4-triazol.   



   Methode A :
Eine Lösung von 51, 0 g (0, 24 Mol)   N-Acetamido-5-nitro-2-furamidin   (F.   224-225  C)   in 200 ml   Phosphoroxychlorid wird 1 h unter Rückfluss erhitzt. Nach dem Abkühlen giesst man das Reaktionsgemisch in Eiswasser und rührt eine weitere Stunde. Das Rohprodukt wird abfiltriert, mit kaltem Wasser gewaschen und an der Luft getrocknet. Auf diese Weise erhält man 23, 3 g (= 50% d. Th. ) 3-Methyl-5- (5-nitro-2- furyl) -4H-I, 2, 4-triazol. Nach Umkristallisieren aus wässerigem Äthanol schmelzen die blassgelben Nadeln   bei   254, 5-256  C   (Zers. ). 
 EMI1.3 
 
<tb> 
<tb> 



  Analyse <SEP> (CH. <SEP> N <SEP> ) <SEP> Berechnet <SEP> : <SEP> C <SEP> 43, <SEP> 30% <SEP> H <SEP> 3,12% <SEP> N <SEP> 28,86%
<tb> Gefunden <SEP> : <SEP> C <SEP> 43, <SEP> 36% <SEP> H <SEP> 3, <SEP> 28% <SEP> N <SEP> 28, <SEP> 78% <SEP> 
<tb> 
 

 <Desc/Clms Page number 2> 

 
 EMI2.1 
 
Eine Lösung von 80, 0 g (0, 35 Mol) N-Propionamido-5-nitro-2-furamidin [F.   207-207, 5     C) in 240 ml Eisessig wird zirka 4   h unter Rückfluss   erhitzt. Man behandelt das heisse Reaktionsgemisch mit Tierkohle, saugt ab und verdünnt das Filtrat mit dem gleichen Volumen Wasser. Nach dem Abkühlen filtriert man das rohe 3-Methyl-5-(5-nitro-2-furyl)-4H-1,2,4-triazol ab und wäscht es mit kaltem Wasser. Die Substanz kann aus verdünnter Essigsäure umkristallisiert werden ; die erhaltenen hellbraunen Nadeln schmelzen bei 181, 5-183, 5  C.

   Ausbeute : 37, 7 g (=   51, 5%   d. Th.). 
 EMI2.2 
 
<tb> 
<tb> 



  Analyse <SEP> (C8H8N4O3) <SEP> Berechnet: <SEP> C <SEP> 46,15% <SEP> H <SEP> 3,87% <SEP> N <SEP> 26,92%
<tb> Gefunden <SEP> : <SEP> C <SEP> 46,08% <SEP> H <SEP> 3,94% <SEP> N <SEP> 26,84%
<tb> 
 
 EMI2.3 
 weiteres Umkristallisieren steigt der Zersetzungspunkt auf   259-260   C.   
 EMI2.4 
 
<tb> 
<tb> Analyse <SEP> 9C6H4N4O3) <SEP> Berechnet: <SEP> C <SEP> 40, <SEP> 01% <SEP> H <SEP> 2, <SEP> 24% <SEP> N <SEP> 31,31%
<tb> Gefunden <SEP> : <SEP> C <SEP> 40,00% <SEP> H <SEP> 2, <SEP> 26% <SEP> N <SEP> 31,53%
<tb> 




   <Desc / Clms Page number 1>
 



  Process for the preparation of new 3- (5-nitro-2-furyl) -4H-l, 2, 4-triazoles The present invention relates to a process for the preparation of new 3- (5-nitro-2-furyl) -4H- 1, 2, 4-triazoles of the general formula I:
 EMI1.1
 in which R denotes hydrogen or a lower alkyl group.



   These compounds are highly effective antibacterial agents, which even in very low doses against gram-positive and gram-negative bacteria, such as. B. Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Proteus vulgaris and Erysipelothrix insidiosa act. They can therefore be processed into disinfectants (in the form of powders, sprays, suspensions, solutions, tablets, ointments, etc.) with the usual carrier substances and adjuvants.



   However, the new compounds not only have an in vitro effect, it has also been shown that oral administration of these substances to pathogenic microorganisms (e.g.



  Staphylococcus aureus, Salmonella typhosa, Escherichia coli), the death of infected animals is prevented. If you administer z. B. on mice that are infected with lethal amounts of the bacteria mentioned, the new compounds perorally in a dosage of 40 to 150 mg / kg, the deaths are completely prevented. Since high antibacterial serum levels arise when the new nitrofuran compounds are administered, these substances are valuable systemic chemotherapeutic agents.



    The inventive method for the preparation of the new 3- (5-nitro-2-furyl) -4H-l, 2, 4-triazoles of the formula I is characterized in that an N-acylamido-5-nitro-2-furamidine is used Formula II:
 EMI1.2
 in which R has the meaning given above, treated with dehydrating agents. As dehydrating agents are z. B. suitable: phosphorus oxychloride and glacial acetic acid. Heating can be used to accelerate the reaction.



  The process according to the invention is explained in more detail in the following examples.



   Example 1: 3-methyl-5- (5-nitro-2-furyl) -4H-1, 2, 4-triazole.



   Method A:
A solution of 51.0 g (0.24 mol) of N-acetamido-5-nitro-2-furamidine (mp 224-225 ° C.) in 200 ml of phosphorus oxychloride is refluxed for 1 h. After cooling, the reaction mixture is poured into ice water and stirred for a further hour. The crude product is filtered off, washed with cold water and air-dried. In this way, 23.3 g (= 50% of theory) of 3-methyl-5- (5-nitro-2-furyl) -4H-1,2,4-triazole are obtained. After recrystallization from aqueous ethanol, the pale yellow needles melt at 254.5-256 ° C. (decomp.).
 EMI1.3
 
<tb>
<tb>



  Analysis <SEP> (CH. <SEP> N <SEP>) <SEP> Calculated <SEP>: <SEP> C <SEP> 43, <SEP> 30% <SEP> H <SEP> 3.12% <SEP > N <SEP> 28.86%
<tb> Found <SEP>: <SEP> C <SEP> 43, <SEP> 36% <SEP> H <SEP> 3, <SEP> 28% <SEP> N <SEP> 28, <SEP> 78% <SEP>
<tb>
 

 <Desc / Clms Page number 2>

 
 EMI2.1
 
A solution of 80.0 g (0.35 mol) of N-propionamido-5-nitro-2-furamidine [F. 207-207, 5 C) in 240 ml of glacial acetic acid is heated under reflux for about 4 h. The hot reaction mixture is treated with animal charcoal, filtered off with suction and the filtrate is diluted with an equal volume of water. After cooling, the crude 3-methyl-5- (5-nitro-2-furyl) -4H-1,2,4-triazole is filtered off and washed with cold water. The substance can be recrystallized from dilute acetic acid; the light brown needles obtained melt at 181, 5-183, 5 C.

   Yield: 37.7 g (= 51.5% of theory).
 EMI2.2
 
<tb>
<tb>



  Analysis <SEP> (C8H8N4O3) <SEP> Calculated: <SEP> C <SEP> 46.15% <SEP> H <SEP> 3.87% <SEP> N <SEP> 26.92%
<tb> Found <SEP>: <SEP> C <SEP> 46.08% <SEP> H <SEP> 3.94% <SEP> N <SEP> 26.84%
<tb>
 
 EMI2.3
 further recrystallization increases the decomposition point to 259-260 C.
 EMI2.4
 
<tb>
<tb> Analysis <SEP> 9C6H4N4O3) <SEP> Calculated: <SEP> C <SEP> 40, <SEP> 01% <SEP> H <SEP> 2, <SEP> 24% <SEP> N <SEP> 31 .31%
<tb> Found <SEP>: <SEP> C <SEP> 40.00% <SEP> H <SEP> 2, <SEP> 26% <SEP> N <SEP> 31.53%
<tb>

Claims (1)

PATENTANSPRUCH : Verfahren zur Herstellung von neuen 3-(5-Nitro-2-furyl)-4H-1,2,4-triazolen der allgemeinen Formel I. EMI2.5 in welcher R Wasserstoff oder eine niedrige Alkylgruppe bedeutet, dadurch gekennzeichnet, dass man ein N-Acylamido-5-nitro-2-furamidin der Formel II : EMI2.6 in welcher R die oben angegebene Bedeutung hat, mit wasserabspaltenden Mitteln, insbesondere Phosphoroxychlorid und Eisessig, behandelt. PATENT CLAIM: Process for the preparation of new 3- (5-nitro-2-furyl) -4H-1,2,4-triazoles of the general formula I. EMI2.5 in which R denotes hydrogen or a lower alkyl group, characterized in that an N-acylamido-5-nitro-2-furamidine of the formula II: EMI2.6 in which R has the meaning given above, treated with dehydrating agents, in particular phosphorus oxychloride and glacial acetic acid.
AT1021464A 1964-01-09 1964-12-02 Process for the preparation of new 3- (5-nitro-2-furyl) -4H-1,2,4-triazoles AT246129B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US33664364A 1964-01-09 1964-01-09

Publications (1)

Publication Number Publication Date
AT246129B true AT246129B (en) 1966-04-12

Family

ID=23317025

Family Applications (1)

Application Number Title Priority Date Filing Date
AT1021464A AT246129B (en) 1964-01-09 1964-12-02 Process for the preparation of new 3- (5-nitro-2-furyl) -4H-1,2,4-triazoles

Country Status (4)

Country Link
AT (1) AT246129B (en)
DK (1) DK104463C (en)
ES (1) ES306495A1 (en)
FR (2) FR1084E (en)

Also Published As

Publication number Publication date
DK104463C (en) 1966-05-23
ES306495A1 (en) 1965-03-01
FR3944M (en) 1966-02-21
FR1084E (en) 1903-05-25

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