DE289274C - - Google Patents
Info
- Publication number
- DE289274C DE289274C DENDAT289274D DE289274DA DE289274C DE 289274 C DE289274 C DE 289274C DE NDAT289274 D DENDAT289274 D DE NDAT289274D DE 289274D A DE289274D A DE 289274DA DE 289274 C DE289274 C DE 289274C
- Authority
- DE
- Germany
- Prior art keywords
- allyl
- norcodeine
- chloroform
- allyldihydronorcodeine
- dissolved
- 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.)
- Active
Links
- 229950004392 Norcodeine Drugs 0.000 claims description 9
- HKOIXWVRNLGFOR-KOFBORESSA-N Norcodeine Chemical compound O[C@H]([C@@H]1O2)C=C[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 HKOIXWVRNLGFOR-KOFBORESSA-N 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N Carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M Sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims 2
- 229940099678 Norco Drugs 0.000 claims 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims 1
- RZVAJINKPMORJF-UHFFFAOYSA-N p-acetaminophenol Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 1
- 235000010288 sodium nitrite Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HFEHLDPGIKPNKL-UHFFFAOYSA-N Allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229930006677 A03BA01 - Atropine Natural products 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N Atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 Atropine Drugs 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N Cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N Morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 230000001476 alcoholic Effects 0.000 description 1
- 230000003042 antagnostic Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229930014694 morphine Natural products 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001184 potassium carbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001225 therapeutic Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
KAISERLICHESIMPERIAL
PATENTAMT.PATENT OFFICE.
PATENTSCHRIFTPATENT LETTERING
- M 289274 KLASSE 12j». GRUPPE- M 289274 CLASS 12j ». GROUP
Patentiert im Deutschen Reiche vom 11. Mai 1915 ab.Patented in the German Empire on May 11, 1915.
Es wurde gefunden, daß dem aus Norcodein durch Behandeln mit allylierenden Mitteln erhältlichen, bisher unbekannten N-Allylnorcodein und dem auf gleiche Weise aus Dihydronorcodein darstellbaren, ebenfalls bis jetzt nicht beschriebenen N-Allyldihydronorcodein wertvolle therapeutische Eigenschaften zukommen. Währenddem das O-Allylnorcodein und sein Hydrierungsprodukt selbst in großenIt has been found that the one obtainable from norcodeine by treatment with allylating agents, hitherto unknown N-allyl norcodeine and that in the same way from dihydronorcodeine N-allyldihydronorcodeine which can be represented, likewise not described up to now have valuable therapeutic properties. Meanwhile the O-allyl norcodeine and its hydrogenation product itself in large quantities
ίο Dosen keine wesentlichen Erscheinungen beim Kaninchen hervorrufen, haben sich die N-allylierten Verbindungen, wie durch eingehende Versuche festgestellt wurde, als energische Antagonisten des Morphins erwiesen, welche die bis jetzt für diesen Zweck empfohlenen Mittel, z. B. das Atropin, bei weitem in bezug auf ihre Wirkung überragen.ίο doses no significant appearances when Rabbits evoke the N-allylated compounds, as determined by in-depth Experiments found proved to be vigorous antagonists of morphine, which the means recommended up to now for this purpose, e.g. B. atropine, by far excel in their effect.
114 Teile Norcodein (Patent 286743, Beispiel 2; Ber. d. D. ehem. Ges. 47 [1914], S. 2043ff) werden in 300 Teilen warmem Chloroform gelöst, dazu 34 Teile Allyljodid gegeben und das Ganze 3 Stunden auf 60° erwärmt. Nach dem Erkalten saugt man den entstandenen Kristallbrei (jodwasserstoffsaures Norcodein) ab, spült mit Chloroform nach und destilliert aus dem Filtrat das Chloroform ab. Den Rückstand löst man in möglichst wenig 10 prozentiger Salzsäure warm auf und läßt einige Stunden stehen. Gegebenenfalls noch vorhandenes, unverändertes Norcodein kristallisiert dann als Chlorhydrat aus und wird abfiltriert. Die Base wird durch Zusatz von viel Kaliumcarbonat zur Chlorhydratlösung abgeschieden, mit Äther ausgezogen, der Äther114 parts of norcodeine (patent 286743, example 2; Ber. d. D. former Ges. 47 [1914], pp. 2043ff) are dissolved in 300 parts of warm chloroform, 34 parts of allyl iodide are added and the whole thing heated to 60 ° for 3 hours. After cooling down, suck the resulting one Crystal pulp (norcodeine), rinsed with chloroform and distilled the chloroform from the filtrate. The residue is dissolved in as little 10 percent as possible Warm hydrochloric acid and leave to stand for a few hours. Possibly still available, unchanged norcodeine then crystallizes out as hydrochloride and is filtered off. The base is separated out by adding a lot of potassium carbonate to the chlorohydrate solution, undressed with ether, the ether
mit entwässertem Natriumsulfat getrocknet und abdestilliert. Der Rückstand, welcher nach dem Erkalten erst eine glasige Masse bildet, kristallisiert nach einiger Zeit in zu Büscheln vereinigten weißen Nadeln. Das N-Allylnorcodein ist in den gebräuchlichen organischen Lösungsmitteln, wie Alkohol, Benzol, Chloroform, leicht löslich.dried with dehydrated sodium sulfate and distilled off. The residue, which Forms a glassy mass after cooling, crystallizes in after a while Tufts of united white needles. The N-allyl norcodeine is in common organic solvents such as alcohol, benzene, chloroform, easily soluble.
Zur Darstellung des Chlorhydrates löst man die Base in wenig absolutem Alkohol auf, setzt die berechnete Menge alkoholische Salzsäure zu und fällt mit trockenem Äther. Man filtriert die weißen Flocken unter Ausschluß von Feuchtigkeit ab und trocknet die Verbindung im Toluolbad bei vermindertem Druck. Das Chlorhydrat des N-Allylnorcodeins ist in Wasser und Alkohol sehr leicht löslich.To prepare the chlorohydrate, the base is dissolved in a little absolute alcohol and then set the calculated amount of alcoholic hydrochloric acid and falls with dry ether. Filter the white flakes off with exclusion of moisture and dry the compound in a toluene bath at reduced pressure. The hydrochloride of N-allyl norcodeine is in Very easily soluble in water and alcohol.
114 Teile Dihydronorcodein (hergestellt nach dem Verfahren des Patents 286743, Beispiel 4, durch Behandeln von Acetyldihydronorcodein mit Bromcyan und Verseifen des erhaltenen Reaktionsproduktes, eine feste weiße Masse vom Schmelzpunkt 184 °) werden in wenig Chloroform gelöst und mit 34 Teilen Allyljodid im zugeschmolzenen Rohr 7 bis 8 Stunden im Wasserbad erwärmt. Es erfolgt eine Kristallabscheidung; zur Abscheidung der tertiären Base wird eingedampft, der Rückstand warm in Schwefelsäure gelöst, die Lösung vom unverbrauchten Allyljodid durch Filtrieren getrennt, Soda zugesetzt, mit Chloroform ausgeschüttelt und das Chloroform verdampft. Der Rückstand wird wieder in Schwefelsäure gelöst und die unveränderte sekundäre Base114 parts of dihydronorcodeine (manufactured according to the method of Patent 286743, Example 4, by treating acetyldihydronorcodeine with cyanogen bromide and saponification of the reaction product obtained, a solid white mass melting point 184 °) are dissolved in a little chloroform and mixed with 34 parts of allyl iodide heated in the fused tube for 7 to 8 hours in a water bath. A crystal separation takes place; to deposit the tertiary Base is evaporated, the residue is dissolved warm in sulfuric acid, the solution from Unused allyl iodide separated by filtration, soda added, extracted with chloroform and the chloroform evaporates. The residue is redissolved in sulfuric acid and the unchanged secondary base
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE289274C true DE289274C (en) |
Family
ID=544317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DENDAT289274D Active DE289274C (en) |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE289274C (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2741612A (en) * | 1956-04-10 | N-substttuted dffiybronormorphine | ||
| US2741609A (en) * | 1956-04-10 | N-chjchjchj | ||
| US2741617A (en) * | 1953-02-05 | 1956-04-10 | Merck & Co Inc | N-substituted dihydronorcodeinone |
| WO2009078988A1 (en) * | 2007-12-17 | 2009-06-25 | Mallinckrodt Inc. | Sinomenine derivatives and processes for their synthesis |
-
0
- DE DENDAT289274D patent/DE289274C/de active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2741612A (en) * | 1956-04-10 | N-substttuted dffiybronormorphine | ||
| US2741609A (en) * | 1956-04-10 | N-chjchjchj | ||
| US2741617A (en) * | 1953-02-05 | 1956-04-10 | Merck & Co Inc | N-substituted dihydronorcodeinone |
| WO2009078988A1 (en) * | 2007-12-17 | 2009-06-25 | Mallinckrodt Inc. | Sinomenine derivatives and processes for their synthesis |
| US8461337B2 (en) | 2007-12-17 | 2013-06-11 | Mallinckrodt Llc | Sinomenine derivatives and processes for their synthesis |
| AU2008338970B2 (en) * | 2007-12-17 | 2013-08-22 | SpecGx LLC | Sinomenine derivatives and processes for their synthesis |
| US8614224B2 (en) | 2007-12-17 | 2013-12-24 | Mallinckrodt Llc | Sinomenine derivatives and processes for their synthesis |
| CN101896464B (en) * | 2007-12-17 | 2014-12-10 | 马林克罗特有限公司 | Sinomenine derivatives and processes for their synthesis |
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