DE1117591B - Process for the preparation of 1- (2'-Hydroxyaethyl) -3- (5-nitrofurfurylidene-amino) -imidazolidin-thione- (2) - Google Patents
Process for the preparation of 1- (2'-Hydroxyaethyl) -3- (5-nitrofurfurylidene-amino) -imidazolidin-thione- (2)Info
- Publication number
- DE1117591B DE1117591B DEN18818A DEN0018818A DE1117591B DE 1117591 B DE1117591 B DE 1117591B DE N18818 A DEN18818 A DE N18818A DE N0018818 A DEN0018818 A DE N0018818A DE 1117591 B DE1117591 B DE 1117591B
- Authority
- DE
- Germany
- Prior art keywords
- thione
- amino
- imidazolidin
- nitrofurfurylidene
- preparation
- 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.)
- Pending
Links
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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
N18818IVd/12pN18818IVd / 12p
ANMELDETAG: 25. A U G U S T 1960 FILING DATE: 25 AU GU ST 1960
BEKANNTMACHUNG
DER ANMELDUNG
UND AUSGABE DER
AUSLEGESCHRIFT: 23. NOVEMBER 1961 NOTIFICATION OF THE REGISTRATION AND ISSUE OF THE
EDITORIAL: NOVEMBER 23, 1961
Die Erfindung betrifft die Herstellung der neuen chemischen Verbindung l-(2'-Hydroxyäthyl)-3-(5-nitrofurfuryliden-amino)-imidazolidin-thion-(2) The invention relates to the production of the new chemical compound l- (2'-hydroxyethyl) -3- (5-nitrofurfurylidene-amino) -imidazolidin-thione- (2)
-CH=N-N-CH = N-N
H2CH 2 C
-C = S-C = S
^N-CH2CH2OH CH2 ^ N-CH 2 CH 2 OH CH 2
Es wurde gefunden, daß diese neue Verbindung sich durch eine hervorragende chemotherapeutische Wirksamkeit auszeichnet; so können mit Salmonella typhosa oder Eimeria tenella infizierte Tiere durch relativ geringe Mengen der neuen Substanz geheilt werden. Besonders eindrucksvoll und überraschend ist der therapeutische Erfolg, der bei Behandlung von antibioticaresistenten Staphylococcus-aureus-Infektionen erzielt wird; etwa 90% der Tiere, welche mit tödlichen Mengen dieser Staphylococcen infiziert worden waren, überlebten nach einmaliger Gabe von 105 mg/kg der neuen Verbindung.It has been found that this new compound has excellent chemotherapeutic activity excels; animals infected with Salmonella typhosa or Eimeria tenella can get through relatively small amounts of the new substance can be cured. Particularly impressive and surprising is the therapeutic success achieved in the treatment of antibiotic-resistant Staphylococcus aureus infections is achieved; about 90% of the animals infected with lethal amounts of these staphylococci survived after a single dose of 105 mg / kg of the new compound.
Während das aus der deutschen AuslegeschriftWhile that from the German interpretative document
1 005 970 bekanntgewordene N-(5-Nitro-2-furfuryliden)-l-amino-imidazolidon-(2) bei einer Dosierung von 100 mg/kg Maus überhaupt keine Wirksamkeit gegenüber Staphylococcus aureus aufweist, wird durch das Verfahrensprodukt der vorliegenden Erfindung bereits bei der halben Menge eine Überlebensrate von 50 % erzielt.1 005 970 known N- (5-nitro-2-furfurylidene) -l-amino-imidazolidone- (2) at a dosage of 100 mg / kg mouse has no activity at all against Staphylococcus aureus, is due to the process product of the present invention already has a survival rate of half the amount 50% achieved.
Das neue Nitrofuranderivat läßt sich mit den üblichen pharmazeutischen Trägersubstanzen und Adjuvantien zu Tabletten, Pulvern, Säften, Lösungen, Suspensionen, Kapseln usw. verarbeiten.The new nitrofuran derivative can be with the usual pharmaceutical carrier substances and Process adjuvants into tablets, powders, juices, solutions, suspensions, capsules, etc.
Die Herstellung der neuen Verbindung erfolgt in an sich bekannter Weise durch Umsetzung von 5-Nitrofurfurol oder dessen reaktionsfähigen Derivaten (wie z. B. dem Diacetat) mit l~(2'-Hydroxyäthyl)-3-aminoimidazolidin-thion-(2) oder dessen reaktionsfähigen Derivaten.The new compound is produced in a manner known per se by reacting 5-nitrofurfurol or its reactive derivatives (such as the diacetate) with l ~ (2'-hydroxyethyl) -3-aminoimidazolidin-thione- (2) or its reactive derivatives.
48,3 g (0,33 Mol) l-(2'-Hydroxyäthyl)-imidazolidinthion-(2) werden zu einer Mischung von 330 ecm Dioxan und 180 ecm 2 η-Schwefelsäure gegeben. Im Verlauf von 32 Minuten läßt man bei —1 bis — 60C eine Lösung von 22,7 g Natriumnitrit in 65 ecm Wasser zutropfen, rührt weitere 50 Minuten bei einer Temperatur von —2 bis +20C und gibt 725 ecm kalte48.3 g (0.33 mol) of 1- (2'-hydroxyethyl) imidazolidinthione- (2) are added to a mixture of 330 ecm of dioxane and 180 ecm 2 of η-sulfuric acid. In the course of 32 minutes is allowed at -1 to - 6 0 C is added dropwise a solution of 22.7 g of sodium nitrite in 65 cc of water, stirred for a further 50 minutes at a temperature of -2 to +2 0 C. and 725 cc of cold
2 η-Schwefelsäure hinzu. Innerhalb von 13 Minuten werden dann bei —2 bis —4° C 45,0 g Zinkstaub zugegeben, und man rührt weitere 22 Minuten bei ±3 0C.2 η-sulfuric acid added. Within 13 minutes 45.0 g of zinc dust are then added at -2 to -4 ° C, and the mixture is stirred another 22 minutes at 0 ± 3 C.
Verfahren zur HerstellungMethod of manufacture
von l-(2'-Hydroxyäthyl)-3-(5-nitrofurfuryliden-amino)-imidazolidin-thion-(2) of l- (2'-hydroxyethyl) -3- (5-nitrofurfurylidene-amino) -imidazolidin-thione- (2)
Anmelder:Applicant:
The Norwich Pharmacal Company,
Norwich, N. Y. (V. St. A.)The Norwich Pharmacal Company,
Norwich, NY (V. St. A.)
Vertreter: EL-Ch. Beythan, Rechtsanwalt,
Berlin-Lichterfelde, Gersauer Weg 9Representative: EL-Ch. Beythan, lawyer,
Berlin-Lichterfelde, Gersauer Weg 9
Beanspruchte Priorität:
V. St. v. Amerika vom 23. Oktober 1959 (Nr. 848 201)Claimed priority:
V. St. v. America 23 October 1959 (No. 848 201)
Julian G. Michels, Norwich, N. Y. (V. St. Α.),
ist als Erfinder genannt wordenJulian G. Michels, Norwich, NY (V. St. Α.),
has been named as the inventor
Man filtriert das erhaltene Reaktionsgemisch und versetzt das Filtrat mit einer Lösung von 34,8 g 5-Nitrofurfurol in 110 ecm Methanol. Es fällt ein gelber kristalliner Niederschlag aus. Man läßt die Lösung einige Zeit in der Kälte stehen, filtriert dann den Niederschlag ab und wäscht ihn mit Wasser, Alkohol und Äther. Auf diese Weise werden 73 g (78%) rohes 1 - (2' - Hydroxyäthyl) - 3 - (5 - nitrof urf uryliden - amino)-imidazolidin-thion-(2) vom F. 181 bis 184° C erhalten. Zur weiteren Reinigung kann man die Verbindung aus Nitromethan Umkristallisieren; sie schmilzt dann bei 189 bis 1920C; Ausbeute 53 g (= 56% der Theorie).The reaction mixture obtained is filtered and the filtrate is treated with a solution of 34.8 g of 5-nitrofurfurol in 110 ecm of methanol. A yellow crystalline precipitate separates out. The solution is left to stand in the cold for some time, then the precipitate is filtered off and washed with water, alcohol and ether. In this way, 73 g (78%) of crude 1- (2'-hydroxyethyl) -3- (5-nitrofurfurylidene-amino) -imidazolidin-thione- (2) with a melting point of 181 ° to 184 ° C. are obtained. For further purification, the compound can be recrystallized from nitromethane; it then melts at 189 to 192 0 C; Yield 53 g (= 56% of theory).
Zur Isolierung des l-(2'-Hydroxyäthyl)-3-aminoimidazolidin-thions-(2) geht man wie folgt vor:To isolate the l- (2'-hydroxyethyl) -3-aminoimidazolidine-thione (2) proceed as follows:
Das nach der Zinkstaubreduktion erhaltene Filtrat wird alkalisch gemacht (z. B. mit Natriumcarbonat) und filtriert. Das Filtrat wird eingedampft und der Rückstand mit einem organischen Lösungsmittel (z. B. Aceton) extrahiert. Nach Eindampfen des Extraktes erhält man in 22%iger Ausbeute einen Rückstand, der aus Chloroform umkristallisiert wird. Die Ausbeute an reinem l-(2'-Hydroxyäthyl)-3-aminoimidazolidin-thion-(2) beträgt 14% der Theorie; F. 88 bis 890C. Zur Umsetzung mit 5-Nitrofurfurol wird eine wäßrige angesäuerte Lösung dieser Verbindung mit einer alkoholischen Lösung des Aldehyds (in äquimolaren Mengen) zusammengegeben.The filtrate obtained after zinc dust reduction is made alkaline (e.g. with sodium carbonate) and filtered. The filtrate is evaporated and the residue extracted with an organic solvent (e.g. acetone). After evaporation of the extract, a residue is obtained in 22% yield, which is recrystallized from chloroform. The yield of pure 1- (2'-hydroxyethyl) -3-aminoimidazolidin-thione- (2) is 14% of theory; F. 88 to 89 ° C. To react with 5-nitrofurfurol, an aqueous acidic solution of this compound is combined with an alcoholic solution of the aldehyde (in equimolar amounts).
109 740/539109 740/539
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84820159A | 1959-10-23 | 1959-10-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1117591B true DE1117591B (en) | 1961-11-23 |
Family
ID=25302634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEN18818A Pending DE1117591B (en) | 1959-10-23 | 1960-08-25 | Process for the preparation of 1- (2'-Hydroxyaethyl) -3- (5-nitrofurfurylidene-amino) -imidazolidin-thione- (2) |
Country Status (5)
| Country | Link |
|---|---|
| BE (1) | BE596218A (en) |
| CH (1) | CH385216A (en) |
| DE (1) | DE1117591B (en) |
| GB (1) | GB909879A (en) |
| NL (1) | NL257071A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1166203B (en) * | 1961-12-06 | 1964-03-26 | Norwich Pharma Co | Process for the preparation of 3- (2-cyanoaethyl) -1- (5-nitrofurfurylidene-amino) -hydantoin |
| DE1168915B (en) * | 1961-12-06 | 1964-04-30 | Norwich Pharma Co | Process for the preparation of 3-alkenyl- and 3-alkynyl-1- (5-nitrofurfurylidene-amino) hydantoins |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL170960B1 (en) * | 1991-08-14 | 1997-02-28 | Procter & Gamble Pharma | Method of obtaining novel cyclic ureas useful as agents against arrythmia and fibrillation |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1005970B (en) * | 1953-08-10 | 1957-04-11 | Norwich Pharma Co | Process for the production of new hydrazones of the 5-nitrofuran series |
-
0
- NL NL257071D patent/NL257071A/xx unknown
-
1960
- 1960-08-25 DE DEN18818A patent/DE1117591B/en active Pending
- 1960-09-21 GB GB3240460A patent/GB909879A/en not_active Expired
- 1960-09-28 CH CH1093260A patent/CH385216A/en unknown
- 1960-10-20 BE BE596218A patent/BE596218A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1005970B (en) * | 1953-08-10 | 1957-04-11 | Norwich Pharma Co | Process for the production of new hydrazones of the 5-nitrofuran series |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1166203B (en) * | 1961-12-06 | 1964-03-26 | Norwich Pharma Co | Process for the preparation of 3- (2-cyanoaethyl) -1- (5-nitrofurfurylidene-amino) -hydantoin |
| DE1168915B (en) * | 1961-12-06 | 1964-04-30 | Norwich Pharma Co | Process for the preparation of 3-alkenyl- and 3-alkynyl-1- (5-nitrofurfurylidene-amino) hydantoins |
Also Published As
| Publication number | Publication date |
|---|---|
| BE596218A (en) | 1961-02-15 |
| NL257071A (en) | |
| GB909879A (en) | 1962-11-07 |
| CH385216A (en) | 1964-12-15 |
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