DE1174323B - Process for the preparation of 2, 4-Dioxy-2H-3, 4-dihydro-pyrido [2, 3-e] [1, 3] oxazine - Google Patents
Process for the preparation of 2, 4-Dioxy-2H-3, 4-dihydro-pyrido [2, 3-e] [1, 3] oxazineInfo
- Publication number
- DE1174323B DE1174323B DEG36389A DEG0036389A DE1174323B DE 1174323 B DE1174323 B DE 1174323B DE G36389 A DEG36389 A DE G36389A DE G0036389 A DEG0036389 A DE G0036389A DE 1174323 B DE1174323 B DE 1174323B
- Authority
- DE
- Germany
- Prior art keywords
- oxazine
- pyrido
- dihydro
- dioxo
- 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
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 title description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229940091173 hydantoin Drugs 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- DXMYTBSZYATUTO-UHFFFAOYSA-N 2H-1,3-oxazine hydrochloride Chemical compound Cl.O1CN=CC=C1 DXMYTBSZYATUTO-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- RYEZWKNZOAAHPL-UHFFFAOYSA-N imidazolidine-2,4-dione;hydrate Chemical compound O.O=C1CNC(=O)N1 RYEZWKNZOAAHPL-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
AUSLEGESCHRIFTEDITORIAL
Internat. Kl.: C 07 dBoarding school Class: C 07 d
Nummer:
Aktenzeichen:
Anmeldetag:
Auslegetag:Number:
File number:
Registration date:
Display day:
Deutsche KL: 12 ρ-10/10German KL: 12 ρ-10/10
G 36389 IVd/12 ρ
13. November 1962
23.JuIi 1964G 36389 IVd / 12 ρ
November 13, 1962
July 23, 1964
überraschenderweise wurde gefunden, daß man 2,4-Dioxo-2H-3,4-dihydro-pyrido[2,3-e][l,3]oxazin der FormelSurprisingly, it has been found that 2,4-dioxo-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine the formula
OsOs
und seine Salze erhält, indem man auf 5-[Furyl-(2')]-hydantoin der Formeland its salts are obtained by adding to 5- [furyl- (2 ')] - hydantoin the formula
IIII
bei Raumtemperatur oder tieferer Temperatur in Gegenwart einer Säure und eines Lösungs- oder Verdünnungsmittels Chlor oder Brom einwirken läßt und gegebenenfalls anschließend das erhaltene Salz des 2,4-Dioxo-2H-3,4-dihydro-pyrido[2,3-e][l,3]-oxazins durch Zugabe von Wasser oder einer Base in die freie Verbindung überführt. Diese Reaktion ist unerwartet und bisher noch nicht beschrieben.at room temperature or lower temperature in the presence of an acid and a solution or Lets the diluent chlorine or bromine act and then optionally the obtained Salt of 2,4-dioxo-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine by adding water or a base transferred into the free connection. This reaction is unexpected and has not yet been described.
Besonders gut eignet sich Chlor für diese Reaktion. Geeignete Lösungs- oder Verdünnungsmittel sind beispielsweise Wasser, dem ein wasserlösliches polares organisches Lösungsmittel, wie ein niederes Alkanol oder Äthylenglykol, beigefügt werden kann. Als Säure wird vorteilhaft Essig- oder Salzsäure verwendet. Chlorine is particularly suitable for this reaction. Suitable solvents or diluents are for example, water, which is a water-soluble polar organic solvent such as a lower alkanol or ethylene glycol, can be added. Acetic or hydrochloric acid is advantageously used as the acid.
Die Herstellung des als Ausgangsverbindung dienenden 5-[Furyl-(2')]-hydantoins der oben angegebenen Formel II ist bekannt (vgl. zum Beispiel Journ. Amer. Chem. Soc, 64 [1942], S. 522, und Journ. Org. Chem., 9 [1944], S. 21).The preparation of the starting compound 5- [furyl- (2 ')] - hydantoin of the abovementioned Formula II is known (cf., for example, Journ. Amer. Chem. Soc, 64 [1942], p. 522, and Journ. Org. Chem., 9 [1944], p. 21).
Das verfahrensgemäß herstellbare 2,4-Dioxo-2H-3,4-dihydro-pyrido[2,3-e][l,3]oxazin besitzt wertvolle pharmakologische Eigenschaften, insbesondere analgetische, antipyretische, antiphlogistische, muskelrelaxierende sowie bakteriostatische und fungistatische Wirksamkeit. Die Verbindung stellt aber auch ein wertvolles Zwischenprodukt dar, z. B. für die Herstellung von weiteren pharmakologisch wirksamen Stoffen sowie von Schädlingsbekämpfungsmitteln. The 2,4-dioxo-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine which can be prepared according to the process has valuable pharmacological properties, in particular analgesic, antipyretic, antiphlogistic, muscle relaxant as well as bacteriostatic and fungistatic effectiveness. But the connection makes is also a valuable intermediate, e.g. B. for the production of other pharmacologically effective Substances and pesticides.
Verfahren zur Herstellung von 2,4-Dioxy-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazin.Process for the preparation of 2,4-dioxy-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine.
Anmelder:Applicant:
J. R. Geigy A. G., Basel (Schweiz)J. R. Geigy A. G., Basel (Switzerland)
Vertreter:Representative:
Dr. F. Zumstein,Dr. F. Zumstein,
Dipl.-Chem. Dr. rer. nat. E. AssmannDipl.-Chem. Dr. rer. nat. E. Assmann
und Dipl.-Chem. Dr. R. Koenigsberger,and Dipl.-Chem. Dr. R. Koenigsberger,
Patentanwälte, München 2, Bräuhausstr. 4Patent Attorneys, Munich 2, Bräuhausstr. 4th
Als Erfinder benannt:Named as inventor:
Niels Clauson-Kaas, Kopenhagen,Niels Clauson-Kaas, Copenhagen,
Dr. Rolf Denss, Basel,Dr. Rolf Denss, Basel,
Dr. Franz Ostermayer, Riehen,Dr. Franz Ostermayer, Riehen,
Dr. Ernst Renk, Basel (Schweiz)Dr. Ernst Renk, Basel (Switzerland)
Beanspruchte Priorität:Claimed priority:
Schweiz vom 14. November 1961 (13 217)Switzerland of November 14, 1961 (13 217)
Die nachfolgenden Beispiele erläutern das erfindungsgemäße Verfahren. Die Temperaturen sind in Celsiusgraden angegeben.The following examples explain the invention Procedure. The temperatures are given in degrees Celsius.
In eine Suspension von 184 g pulverisiertem 5-[Furyl-(2')]-hydantoin in 420 ml 2 η-Salzsäure werden unter starkem Rühren bei 15° im Verlauf von IV2 bis 2 Stunden 114 g Chlor eingeleitet. Die Suspension wird hierauf sofort filtriert, der Rückstand mit 300 ml Aceton durchgerührt und wiederum filtriert. Das anfallende 2,4-Dioxo-2H-3,4-dihydropyrido[2,3-e][l,3]oxazin-hydrochlorid kann durch Waschen mit Wasser, bis das Filtrat neutral abläuft, in die Base übergeführt werden. Auch Lösen des Hydrochloride in 2 η-Natronlauge und anschließende Neutralisation mit verdünnter Salzsäure führen zur Base. Diese wird aus siedendem Wasser, Eisessig oder Pyridin unter Zusatz von Kohle umkristallisiert und schmilzt dann bei 280°. Die Verbindung gibt keine Eisenchloridreaktion (in Methanol) und mit einer Lösung von 2,4-Dinitrophenylhydrazin in 2 n-Salzsäure keine Fällung; Ausbeute: 25 bis 35%.In a suspension of 184 g of powdered 5- [furyl- (2 ')] - hydantoin in 420 ml of 2η-hydrochloric acid while stirring vigorously at 15 ° in the course of IV2 to 2 hours, 114 g of chlorine were introduced. The suspension is then filtered immediately, the residue is stirred through with 300 ml of acetone and again filtered. The resulting 2,4-dioxo-2H-3,4-dihydropyrido [2,3-e] [1,3] oxazine hydrochloride can be converted into the base by washing with water until the filtrate is neutral. Also solving the Hydrochloride in 2 η sodium hydroxide solution and subsequent neutralization with dilute hydrochloric acid lead to Base. This is recrystallized from boiling water, glacial acetic acid or pyridine with the addition of charcoal and then melts at 280 °. The compound does not give ferric chloride reaction (in methanol) and with a Solution of 2,4-dinitrophenylhydrazine in 2N hydrochloric acid no precipitation; Yield: 25 to 35%.
409 637/416409 637/416
In eine Lösung von 8,3 g 5-[Furyl-(2')]-hydantoin in 25 ml 6 η-Salzsäure und 25 ml Methanol wird bei 11 bis 15° innerhalb 60 Minuten gasförmiges Chlor, entsprechend einer flüssigen Menge von 3,5 ml bei — 80°, eingeleitet. Hierauf wird das entstandene 2,4-Dioxo-2H-3,4-dihydro-pyrido[2,3-e][l,3]oxazinhydrochlorid abfiltriert, mit 99%igem Äthanol gewaschen und getrocknet; Ausbeute: 25 bis 35%.In a solution of 8.3 g of 5- [furyl- (2 ')] - hydantoin in 25 ml of 6 η-hydrochloric acid and 25 ml of methanol is at 11 to 15 ° within 60 minutes of gaseous chlorine, corresponding to a liquid amount of 3.5 ml - 80 °, initiated. The resulting 2,4-dioxo-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine hydrochloride is then used filtered off, washed with 99% ethanol and dried; Yield: 25 to 35%.
5,52 g 5-[Furyl-(2')]-hydantoin-hydrat werden in 15 ml Essigsäure und 15 ml Wasser gelöst. Innerhalb 15 Minuten wird bei 19° gasförmiges Chlor, entsprechend 1,5 ml flüssigem Chlor bei —80°, eingeleitet. Nach Abkühlen auf -20° fügt man 30 ml 99%iges Äthanol, 10 ml Äther und 10 ml konzentrierte Salzsäure zu. Man läßt 10 Minuten bei —20° stehen; dann wird das ausgeschiedene 2,4-Dioxo-2H-3,4-dihydro-pyrido[2,3-e][l,3]oxazin-hydrochlorid abfiltriert, mit 99%igem Äthanol gewaschen und getrocknet; Ausbeute: 25 bis 30%.5.52 g of 5- [furyl (2 ')] hydantoin hydrate are dissolved in 15 ml of acetic acid and 15 ml of water. Within Gaseous chlorine, corresponding to 1.5 ml of liquid chlorine at -80 °, is passed in for 15 minutes at 19 °. After cooling to -20 °, add 30 ml of 99% ethanol, 10 ml of ether and 10 ml of concentrated Hydrochloric acid too. It is left to stand at -20 ° for 10 minutes; then the precipitated 2,4-dioxo-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine hydrochloride filtered off, washed with 99% ethanol and dried; Yield: 25-30%.
B e i s ρ i e 1 4B e i s ρ i e 1 4
92 g 5-[Furyl-(2')]-hydantoin werden in 210 ml 2 η-Salzsäure suspendiert und unter starkem Rühren im Verlaufe einer Stunde mit 120 g Brom tropfenweise versetzt. Das Reaktionsgemisch wird sofort nach der Bromzugabe filtriert und der Filterrückstand mit Aceton, dann Wasser gewaschen. Das erhaltene 2,4-Dioxo-2H-3,4-dihydro-pyrido[2,3-e][l,3]oxazin schmilzt nach dem Umkristallisieren aus Eisessig bei 280°. Es ist identisch mit der durch Behandeln von 5-[Furyl-(2')]-hydantoin mit Chlor gewonnenen Substanz; Ausbeute: 7 bis 10%.92 g of 5- [furyl- (2 ')] - hydantoin are suspended in 210 ml of 2η hydrochloric acid and stirred vigorously 120 g of bromine were added dropwise over the course of one hour. The reaction mixture is immediately after the The addition of bromine is filtered and the filter residue is washed with acetone and then water. The received 2,4-Dioxo-2H-3,4-dihydro-pyrido [2,3-e] [1,3] oxazine melts after recrystallization from glacial acetic acid 280 °. It is identical to the substance obtained by treating 5- [furyl- (2 ')] hydantoin with chlorine; Yield: 7-10%.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1174323X | 1961-11-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1174323B true DE1174323B (en) | 1964-07-23 |
Family
ID=4561426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEG36389A Pending DE1174323B (en) | 1961-11-14 | 1962-11-13 | Process for the preparation of 2, 4-Dioxy-2H-3, 4-dihydro-pyrido [2, 3-e] [1, 3] oxazine |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1174323B (en) |
-
1962
- 1962-11-13 DE DEG36389A patent/DE1174323B/en active Pending
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