DE278107C - - Google Patents
Info
- Publication number
- DE278107C DE278107C DENDAT278107D DE278107DA DE278107C DE 278107 C DE278107 C DE 278107C DE NDAT278107 D DENDAT278107 D DE NDAT278107D DE 278107D A DE278107D A DE 278107DA DE 278107 C DE278107 C DE 278107C
- Authority
- DE
- Germany
- Prior art keywords
- dihydromorphine
- alcohol
- solution
- morphine
- salt
- 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
- IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 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 claims description 6
- 229960005181 morphine Drugs 0.000 claims description 6
- 229930014694 morphine Natural products 0.000 claims description 6
- 239000008896 Opium Substances 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 229960001027 opium Drugs 0.000 claims description 4
- 230000001603 reducing Effects 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 238000006722 reduction reaction Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 230000002378 acidificating Effects 0.000 claims description 2
- 230000001476 alcoholic Effects 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000001264 neutralization Effects 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 claims 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 2
- OOEWZEXEJQEFJO-UHFFFAOYSA-N O.[I] Chemical compound O.[I] OOEWZEXEJQEFJO-UHFFFAOYSA-N 0.000 claims 1
- 238000004140 cleaning Methods 0.000 claims 1
- 230000000875 corresponding Effects 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 239000000155 melt Substances 0.000 claims 1
- 229940075930 picrate Drugs 0.000 claims 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 1
- 235000011121 sodium hydroxide Nutrition 0.000 claims 1
- 239000000243 solution Substances 0.000 description 6
- DZGJPYLWWJSNCT-VYKNHSEDSA-N (4R,4aR,7S,7aR,12bS)-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol;hydrochloride Chemical compound Cl.O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O DZGJPYLWWJSNCT-VYKNHSEDSA-N 0.000 description 2
- 229930013930 alkaloids Natural products 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229960005195 Morphine hydrochloride Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003197 catalytic Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- XCKKIKBIPZJUET-VYKNHSEDSA-N morphine hydrochloride Chemical compound Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XCKKIKBIPZJUET-VYKNHSEDSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000001184 potassium carbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
KAISERLICHESIMPERIAL
PATENTAMT.PATENT OFFICE.
PATENTSCHRIFTPATENT LETTERING
-M 278107-KLASSE 12/?. GRUPPE -M 278107-CLASS 12 / ?. GROUP
Für die Herstellung von Dihydromorphin ging man bis jetzt vom reinen Morphin aus, welches man einer katalytischen Reduktion unterwarf. (L. Oldenburg, Ber. 44 [1911] S. 1829 und A. Skita, »Über katalytische Reduktionen«, Stuttgart 1912, S. 24).For the production of dihydromorphine one has until now started from pure morphine, which was subjected to a catalytic reduction. (L. Oldenburg, Ber. 44 [1911] S. 1829 and A. Skita, "About catalytic reductions", Stuttgart 1912, p. 24).
Es wurde nun gefunden, daß es auch gelingt, diesen Körper durch Behandlung des durch Einwirkung von molekularem Wasserstoff in Gegenwart eines Katalysators auf saure/ neutrale wässerige oder alkoholischwässerige Opiumauszüge erhältlichen, gegebenenfalls mit einer Säure versetzten Rohproduktes mit absolutem Alkohol rein und inIt has now been found that it is also possible to treat this body by treating the by the action of molecular hydrogen in the presence of a catalyst acidic / neutral aqueous or alcoholic aqueous opium extracts available, if necessary with an acid added crude product with absolute alcohol pure and in
1S guter Ausbeute zu erhalten. Get 1 S of good yield.
Durch dieses Verfahren wird eine wesentliche Vereinfachung für die Herstellung des Dihydromorphins erzielt, da es nicht mehr notwendig ist, das Morphin, bevor es der Reduktion unterworfen wird, rein darzustellen. Die Tatsache, daß dieses Verfahren durchzuführen ist, muß als überraschend bezeichnet werden, denn es war zweifelhaft, ob es gelingen würde, aus dem Gemenge der verschiedenen hydrierten und nichthydrierten Alkaloide und den sonstigen Verunreinigungen der Reduktionslösung das Dihydromorphin in guter Ausbeute zu gewinnen.This process considerably simplifies the production of the Dihydromorphins is achieved because it is no longer necessary to reduce the morphine before it is subjected to portray pure. The fact that this procedure can be carried out is, must be described as surprising, because it was doubtful whether it would succeed would, from the mixture of the various hydrogenated and non-hydrogenated alkaloids and the other impurities in the reducing solution, the dihydromorphine in good Win yield.
Das nach diesem Verfahren erhaltene Dihydromorphin ist mit dem durch Reduktion von reinem Morphin erhaltenen Körper identisch. Es soll für pharmazeutische Zwecke Verwendung finden.The dihydromorphine obtained by this process is identical to that obtained by reduction bodies obtained from pure morphine are identical. It is intended for pharmaceutical use Find use.
500 Teile eines salzsauren Opiumextraktes, welcher 20 Teile Morphinhydrochlorid und etwa 25 Teile doppelt normale Salzsäure enthält, werden mit V100 Teil Palladiumchlorür versetzt, und in die von Luft befreite Lösung unter gelindem Überdruck bei gleichzeitigem Schütteln Wasserstoff eingeleitet. Nachdem die rasch verlaufende Absorption zum Stillstand gekommen ist, wird das ausgeflockte Palladium abfiltriert, die Lösung im Vakuum, zuletzt unter Zusatz von Alkohol, abgedampft, der Rückstand allmählich mit im ganzen 400 Teilen absolutem Alkohol ausgezogen, das zurückbleibende salzsaure Dihydromorphin in 100 Teilen Wasser gelöst und die Lösung mit Kaliumcarbonat bis zur alkalischen Reaktion versetzt. Hierauf wird die Lösung so lange mit Chloroform ausgeschüttelt, bis die wässerige Schicht keine Reaktion mit Froehdes Reagens mehr gibt. Den vereinigten Chloroformauszügen entzieht man mit 50 Teilen doppelt normaler Salzsäure das Alkaloid, verdampft diese Lösung zur Trockne und zieht j mit etwa 100 Teilen absolutem Alkohol aus. ! Der in Alkohol unlösliche Rückstand stellt j fast reines salzsaures Dihydromorphin dar. Wenn man eine wässerige Lösung des Salzes mit Ammoniak versetzt, so kristallisiert Dihydromorphin aus, welches den in der Literatur angegebenen Schmelzpunkt von 157 ° zeigt. Das zurückbleibende Dihydromorphin-500 parts of an opium extract containing hydrochloric acid, which contains 20 parts of morphine hydrochloride and about 25 parts of double normal hydrochloric acid, are mixed with 100 parts of palladium chloride, and hydrogen is introduced into the de-aerated solution under slight excess pressure while shaking at the same time. After the rapid absorption has come to a standstill, the flocculated palladium is filtered off, the solution is evaporated in vacuo, finally with the addition of alcohol, the residue is gradually extracted with a total of 400 parts of absolute alcohol, and the remaining hydrochloric acid dihydromorphine is dissolved in 100 parts of water and potassium carbonate is added to the solution until it has an alkaline reaction. The solution is then shaken out with chloroform until the aqueous layer no longer reacts with Froehde's reagent. The alkaloid is removed from the combined chloroform extracts with 50 parts of double normal hydrochloric acid, this solution is evaporated to dryness and extracted with about 100 parts of absolute alcohol. ! The residue, which is insoluble in alcohol, is almost pure hydrochloric acid dihydromorphine. If ammonia is added to an aqueous solution of the salt, dihydromorphine crystallizes out and has the melting point of 157 ° given in the literature. The remaining dihydromorphine
Claims (1)
Publications (1)
Publication Number | Publication Date |
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DE278107C true DE278107C (en) |
Family
ID=534135
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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DENDAT278107D Active DE278107C (en) |
Country Status (1)
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DE (1) | DE278107C (en) |
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- DE DENDAT278107D patent/DE278107C/de active Active
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