EP0000009B1 - Verfahren zur Oxydation von Chinin zu Chininone und Chinidinone. - Google Patents
Verfahren zur Oxydation von Chinin zu Chininone und Chinidinone. Download PDFInfo
- Publication number
- EP0000009B1 EP0000009B1 EP78400019A EP78400019A EP0000009B1 EP 0000009 B1 EP0000009 B1 EP 0000009B1 EP 78400019 A EP78400019 A EP 78400019A EP 78400019 A EP78400019 A EP 78400019A EP 0000009 B1 EP0000009 B1 EP 0000009B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- quininone
- quinidinone
- quinine
- solution
- oxidation
- 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.)
- Expired
Links
- 0 *C(c1ccccc1)c1ccccc1 Chemical compound *C(c1ccccc1)c1ccccc1 0.000 description 2
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
- C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine
Definitions
- the present invention relates to an oxidation process of the Oppenauer type with a new reagent and its application to the manufacture of quininone and quinidinone, intermediates for the synthesis of quinidine.
- the quininone and quinidinone differentiated by the asymmetric carbon isomerism at C s of the quinuclidine nucleus are generally two forms in equilibrium, which explains the phenomena of mutarotation in solution hitherto observed.
- the quininone formed is found in the presence of variable amounts of impurities, mainly: quinine, quinidine, epiquinine, epiquinidine, quinicine (quinotoxin ), which has the effect of reducing the reaction yield, the by-products formed having to be separated and purified before being recycled (it is noted in particular that the presence - even in small proportions - of epibases considerably reduces the crystallization yields of quinine and quinidine from their saturated solutions.
- impurities mainly: quinine, quinidine, epiquinine, epiquinidine, quinicine (quinotoxin )
- the reaction being carried out in enolic form it is necessary to introduce a base of PK sufficient to enolate all of the ketone forms contributing to the reaction.
- a base of PK sufficient to enolate all of the ketone forms contributing to the reaction.
- An amount of 2 to 7 equivalent moles has proved necessary in the various experiments described in the literature.
- the bases used, because of their PKI are the alcoholates, and mainly the sodium, potassium and aluminum alcoholates, methyl, ethyl, isopropyl and tert-butyl alcohols.
- the object of the invention is mainly to use a base having the ideal characteristics PK and compatibility which is an "in situ" derivative of the ketone used as proton acceptor.
- Ketyls are prepared by simple addition of the alkali metal to a solution of ketone in an appropriate aromatic solvent.
- a “Ketyl” obtained by interaction of an alkali metal with a diphenylketone, more particularly with benzophenone or fluorenone, will therefore be used as the quinine oxidant.
- the reaction of quinine and "Ketyl” is carried out in a solvent medium; said solvent is selected from aromatic hydrocarbons, C 6 -C 9 saturated cyclic hydrocarbons, C 6 -C 9 or aliphatic hydrocarbons corresponding to naphtha or gas oil cuts.
- the xylene solution is treated with water (20 ml), then extracted with 100 ml of sulfuric acid diluted to 20%.
- the cold sulfuric solution is neutralized by adding ammonia.
- the crystals that form are composed of quinidinone; as quininone and quinidinone are in equilibrium in the oil obtained, the precipitation of quinidinone has the consequence of shifting said equilibrium towards the production of quinidinone.
- the cold sulfuric solution is neutralized by adding ammonia. Decanting oil. It is separated and crystallized by seeding and appropriate treatment.
- the mixed solutions are kept at reflux for 5 hours.
- a “Ketyl” fluorenone solution is produced from 9 g of fluorenone in anhydrous toluene.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Claims (3)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7718398 | 1977-06-15 | ||
FR7718398A FR2394545A1 (fr) | 1977-06-15 | 1977-06-15 | Procede de fabrication de quininone et de quinidinone, intermediaires de synthese de la quinidine |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0000009A1 EP0000009A1 (de) | 1978-12-20 |
EP0000009B1 true EP0000009B1 (de) | 1980-07-23 |
Family
ID=9192140
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP78400019A Expired EP0000009B1 (de) | 1977-06-15 | 1978-06-14 | Verfahren zur Oxydation von Chinin zu Chininone und Chinidinone. |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0000009B1 (de) |
DE (1) | DE2860032D1 (de) |
FR (1) | FR2394545A1 (de) |
IE (1) | IE46935B1 (de) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1165604B (de) * | 1957-12-18 | 1964-03-19 | Chininfabrik Braunschweig Buch | Verfahren zur sterischen Umlagerung von Chinaalkaloiden |
FR2332278A1 (fr) * | 1975-11-19 | 1977-06-17 | Nativelle Sa Ets | Procede de transformation stereochimique des alcaloides du quinquina |
FR2332279A1 (fr) * | 1975-11-19 | 1977-06-17 | Nativelle Sa Ets | Procede d'oxydation des alcaloides du quinquina |
-
1977
- 1977-06-15 FR FR7718398A patent/FR2394545A1/fr not_active Withdrawn
-
1978
- 1978-06-14 DE DE7878400019T patent/DE2860032D1/de not_active Expired
- 1978-06-14 EP EP78400019A patent/EP0000009B1/de not_active Expired
- 1978-06-15 IE IE120478A patent/IE46935B1/en unknown
Also Published As
Publication number | Publication date |
---|---|
IE781204L (en) | 1978-12-15 |
EP0000009A1 (de) | 1978-12-20 |
FR2394545A1 (fr) | 1979-01-12 |
DE2860032D1 (en) | 1980-11-13 |
IE46935B1 (en) | 1983-11-02 |
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