CH186447A - Process for the preparation of dihydrocodeinone. - Google Patents
Process for the preparation of dihydrocodeinone.Info
- Publication number
- CH186447A CH186447A CH186447DA CH186447A CH 186447 A CH186447 A CH 186447A CH 186447D A CH186447D A CH 186447DA CH 186447 A CH186447 A CH 186447A
- Authority
- CH
- Switzerland
- Prior art keywords
- dihydrocodeinone
- codeine
- palladium
- preparation
- dissolved
- Prior art date
Links
- 229960000240 hydrocodone Drugs 0.000 title claims description 10
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 18
- 229960004126 codeine Drugs 0.000 claims description 9
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910000510 noble metal Inorganic materials 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 229910052763 palladium Inorganic materials 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229960001410 hydromorphone Drugs 0.000 description 2
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 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 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Darstellung von Dihydrocodeinon. Im Hauptpatent ist ein Verfahren zur Herstellung von Dihydromorphinon durch Erhitzen einer Morphinlösung, zum Beispiel einer alkoholischen oder wässerigsauren Lö sung, in Gegenwart eines Edelmetallkataly- sators beschrieben. Es wurde gefunden, dass in analoger Weise auch das Homologe des Dihydromorphinons, das Dihydrocodeinon, aus Codein hergestellt werden kann.
Da Dihydro- codeinon mit Codein isomer ist, bedarf es auch hier nur der Umlagerung zweier Wasser stoffatome. Man kann die Reaktion sowohl mit grösseren wie mit kleineren Katalysator mengen durchführen.
Das Dihydrocodeinon ist an sich nicht neu; es findet Verwendung als Ausgangs- oder Zwischenprodukt für die Herstellung von Heilmitteln.
<I>Beispiel 1:</I> 1 g Codein wird in 100 cmg verdünnter Salzsäure mit 10 cm' Wasser gelöst und einige Stunden in Gegenwart von 2 g fein verteiltem Palladium am Rückflusskühler zum Sieden erhitzt. Nach dem Abfiltrieren des Palladiums wird das saure Filtrat mit Natron lauge übersättigt. Die flockig ausgeschiedene Base wird aus Äthanol umkristallisiert und schmilzt bei 194-1951. Sie zeigt mit dem auf anderem Wege hergestellten Dibydroco- deinon keine Schmelzpunktsdepression.
<I>Beispiel 2:</I> 300 g Codein werden in 2 Liter verdünnter Salzsäure gelöst und nach Zugabe von 25 g fein verteiltem Palladium einige Stunden am Rückflusskühler zum Sieden erhitzt. Nach dem Abfiltrieren des Palladiums erfolgt die Aufarbeitung in der angegebenen Weise. Aus- beute 85-95% der Theorie.
<I>Beispiel 3:</I> 6 g Codein werden in 30 cm' Wasser unter Zugabe von 4 g Weinsäure gelöst, dazu 0,5 g Palladiummohr zugefügt und unter Rück fluss 1 Stunde gekocht. Ausbeute an Dihydrocodeinon 75% der Theorie.
<I>Beispiel</I> .: 5 g Codein werden in 10 cm' verdünnter Phosphorsäure gelöst, mit 0,5 g fein verteil tem Palladium versetzt und 1 Stunde am Rückflusskühler gekocht.
Ausbeute an Dihydrocodeinon 60-700o der Theorie.
<I>Beispiel 5:</I> 21 g Codein werden in überschüssiger ver dünnter Schwefelsäure gelöst, mit 2 g Platin mohr versetzt und 1 Stunde unter Rückfluss gekocht.
Ausbeute an Dihydrocodeinon 90 % der Theorie.
<I>Beispiel 6:</I> 5 g Codein werden in 50 cm' Alkohol und nach Zusatz von 2 g Palladiummohr 3 Stunden unter Rückfluss gekocht. Nach Ab filtrieren des Palladiums wird ein Teil des Lösungsmittels abdestilliert. Beim Abkühlen kristallisiert Dihydrocodeinon in einer Menge von 3,5 g aus.
Es versteht sich von selbst, dass auch andere Säuren, wie zum Beispiel Bromwasser stoffsäure und Essigsäure, verwendet werden können.
Process for the preparation of dihydrocodeinone. The main patent describes a process for the production of dihydromorphinone by heating a morphine solution, for example an alcoholic or aqueous acidic solution, in the presence of a noble metal catalyst. It has been found that the homologue of dihydromorphinone, dihydrocodeinone, can also be produced from codeine in an analogous manner.
Since dihydrocodeinone is isomeric with codeine, only two hydrogen atoms have to be rearranged. The reaction can be carried out with both larger and smaller amounts of catalyst.
Dihydrocodeinone is not in itself new; it is used as a starting or intermediate product in the manufacture of medicinal products.
<I> Example 1: </I> 1 g of codeine is dissolved in 100 cmg of dilute hydrochloric acid with 10 cm of water and heated to boiling for a few hours in the presence of 2 g of finely divided palladium on a reflux condenser. After the palladium has been filtered off, the acidic filtrate is supersaturated with sodium hydroxide solution. The flaky base is recrystallized from ethanol and melts at 194-1951. It shows no melting point depression with the dibydrocodeinone produced in another way.
<I> Example 2: </I> 300 g of codeine are dissolved in 2 liters of dilute hydrochloric acid and, after the addition of 25 g of finely divided palladium, heated to boiling for a few hours on a reflux condenser. After the palladium has been filtered off, work-up is carried out in the manner indicated. Yield 85-95% of theory.
<I> Example 3: </I> 6 g of codeine are dissolved in 30 cm 'of water with the addition of 4 g of tartaric acid, 0.5 g of palladium black is added and the mixture is refluxed for 1 hour. Yield of dihydrocodeinone 75% of theory.
<I> Example </I>.: 5 g of codeine are dissolved in 10 cm 'of dilute phosphoric acid, 0.5 g of finely divided palladium is added and the mixture is boiled on the reflux condenser for 1 hour.
Yield of dihydrocodeinone 60-700o of theory.
<I> Example 5: </I> 21 g of codeine are dissolved in excess dilute sulfuric acid, 2 g of platinum black are added and refluxed for 1 hour.
Yield of dihydrocodeinone 90% of theory.
<I> Example 6: </I> 5 g of codeine are refluxed for 3 hours in 50 cm of alcohol and after adding 2 g of palladium black. After the palladium has been filtered off, some of the solvent is distilled off. On cooling, dihydrocodeinone crystallizes out in an amount of 3.5 g.
It goes without saying that other acids, such as hydrobromic acid and acetic acid, can also be used.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH182715T | 1935-01-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH186447A true CH186447A (en) | 1936-09-15 |
Family
ID=4431757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH186447D CH186447A (en) | 1935-01-17 | 1935-01-17 | Process for the preparation of dihydrocodeinone. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH186447A (en) |
-
1935
- 1935-01-17 CH CH186447D patent/CH186447A/en unknown
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