CH210765A - Process for the preparation of an oxyketone ester of the androsten series. - Google Patents
Process for the preparation of an oxyketone ester of the androsten series.Info
- Publication number
- CH210765A CH210765A CH210765DA CH210765A CH 210765 A CH210765 A CH 210765A CH 210765D A CH210765D A CH 210765DA CH 210765 A CH210765 A CH 210765A
- Authority
- CH
- Switzerland
- Prior art keywords
- oxidizing agent
- double bond
- halogen
- agent
- oxidation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- -1 oxyketone ester Chemical class 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 3
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 title description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 17
- 239000007800 oxidant agent Substances 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 239000012433 hydrogen halide Substances 0.000 claims description 5
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000005751 Copper oxide Substances 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001443 androstenes Chemical class 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 229910000431 copper oxide Inorganic materials 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000013067 intermediate product Substances 0.000 claims description 2
- 210000001625 seminal vesicle Anatomy 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 201000010653 vesiculitis Diseases 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 3
- 230000001419 dependent effect Effects 0.000 claims 3
- 230000000694 effects Effects 0.000 claims 2
- 239000007858 starting material Substances 0.000 claims 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 229960000583 acetic acid Drugs 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 1
- 229950009148 androstenediol Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical class [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007256 debromination reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Darstellung eines Ozyketonesters der Androstenreihe. Es wurde ,gefunden, dass man zu einem Oxyketonester der Androstenreihe gelangen kann, wenn man die Doppelbindung des 45.6-Androstendiol-(3,17)-17-iso-butyrat der Formel
EMI0001.0007
vor der folgenden Einwirkung des Oxyda tionsmittels schützt, auf das so erhaltene Zwisehenprodukt ein Oxydationsmittel ein wirken lässt und hierauf die Kohlenstoff doppelbindung unter Verschiebung in 4,5- Stellung regeneriert.
Das so gewonnene 44,5-Androstenol-(17)- on-(3)-iso-butyrat der Formel
EMI0001.0014
bildet farblose Kristalle vom F. 134-136'. Wie Versuche ergaben, gelingt es- leicht, den Ketoester entweder durch direkte Kri stallisation oder durch Bereitung schwer lös licher Derivate in reiner Form abzuscheiden.
Solche schwer lösliche Derivate erhält man zum Beispiel durch Umsetzung des Keto- esters mit den üblichen Ketonreagenzien wie Semicarbazid, Thiosemicarbazid, Hydroxyl- amin, Aminoguanidin, Phenylhydrazinen,
neutralen oder basisehen Acylhydraziden. Durch Einwirkung hydrolytisch wirkender Mittel werden die zwecks Reinigung des Oxyketons hergestellten Verbindungen wie der in ihre Komponenten gespalten, Geeignete Oxydationsmittel sind zum Beispiel 6wertige Chromverbindungen wie Chromsäure in Eisessig, ferner liupferoxyd, Permanbanat und dergleichen.
Der Schutz der Kohlenstoffdoppelbindunb erfolgt zum Beispiel durch Anlagerung von Halogen bezw. Halogenwasserstoff an den @n#bangs- stoff. Nach erfolgter Oxydation wird die Kohlenstoffdoppelbindung unter Verschie- bünb in 4.5-Stellunb regeneriert.
Die Ent fernung des Halogens kann in bekannter Weise zum Beispiel durch Zinkstaub und Essigsäure oder Benzol, durch ka.t.alytisch angeregten "Tasserstoff oder dureh Behan- deln mit Alkalijodiden und die des Halogen- wasserstoffes zum Beispiel durch tertiäre Basen wie Pyridin oder Dimetliylanilin oder durch Umsetzen
mit Salzen von Carbonsäu- ren, wie z. B. All.:aliacetaten, erfolgen.
Die erhaltene Verbindung ist am Kapau nenka.mm und an der Samenblase wirksam. Sie soll therapeutische Verwendung finden. Beispiel: <B>3,7</B> b Js,s-Androstendiol-(3,17)-17-iso-bu- tyrat werden in 50 cm' Eisessig gelöst. Nun gibt man unter Kühlung tropfenweise so lange Brom-Eisessib-Lösung zu, als sofort Entfärbunb eintritt.
Schliesslich wird eben falls in der Kälte 1,0 b Chromtrioxyd, gelöst in 30 cm' 90@ iber Essigsäure, zugefügt und das Ganze über Nacht bei Zimmertemperatur stehen belassen. Dann giesst man in 1 Liter Wasser, saugt das ausgefallene Produkt ab und wäscht mit viel Wasser nach.
Das so erhaltene bromierte Keton nimmt. man zur Entbromun- in 50 cm' Eisessig auf, gibt 20 b Zinkstaub zu und erhitzt unter inten sivem Schütteln 12 'Minuten am siedenden Wasserbade.
Dann wird durch Glasfilter ab- besaubt, mit wenig heissem Eisessig nach gewaschen, die Lösung mit Wasser gekillt und mit Äther ausgezogen. Die mit verdünn ter Sodalösung und Wasser gewaschene Ätherlösung liefert beim Eindampfen einen Rückstand, aus dem sich zum Beispiel über das schwer lösliche Semicarba.zon das 44,5- Androstenol-(17)-on-(3)-iso-butyrat isolieren lässt,
das n < cli LTinkristallisieren aus Hexan bei 134-136 schmilzt.
Zur Oxydation kann inan an Stelle von Chromsäure zum Beispiel auch Kupferoxyd verwenden.
Matt durch Brom lässt sich die Doppel- bindung ziem Beispiel auch durch Chlor ,schützen.
Process for the preparation of an ocyketone ester of the androsten series. It has been found that an oxyketone ester of the androstene series can be obtained by removing the double bond of 45.6-androstenediol (3,17) -17-isobutyrate of the formula
EMI0001.0007
protects against the subsequent action of the oxidizing agent, allows an oxidizing agent to act on the intermediate product obtained in this way and then regenerates the carbon double bond by shifting it to the 4,5 position.
The 44,5-androstenol- (17) -on- (3) -iso-butyrate of the formula obtained in this way
EMI0001.0014
forms colorless crystals from F. 134-136 '. Experiments have shown that it is easy to separate the ketoester in pure form either by direct crystallization or by preparing poorly soluble derivatives.
Such poorly soluble derivatives are obtained, for example, by reacting the keto ester with the usual ketone reagents such as semicarbazide, thiosemicarbazide, hydroxylamine, aminoguanidine, phenylhydrazines,
neutral or basic acyl hydrazides. By the action of hydrolytic agents, the compounds produced for the purpose of purifying the oxyketone are split into their components. Suitable oxidizing agents are, for example, hexavalent chromium compounds such as chromic acid in glacial acetic acid, as well as liupferoxyd, permanbanate and the like.
The carbon double bond is protected, for example, by the addition of halogen or. Hydrogen halide to the @ n # fear substance. After oxidation has taken place, the carbon double bond is regenerated with a shift in the 4.5 position.
The removal of the halogen can be carried out in a known manner, for example, by zinc dust and acetic acid or benzene, by ka.t.alytically excited hydrogen or by treatment with alkali iodides and that of the hydrogen halide, for example by tertiary bases such as pyridine or dimethylaniline or through implementation
with salts of carboxylic acids, such as B. All.:aliacetaten.
The compound obtained is effective on the Kapau nenka.mm and the seminal vesicle. It should find therapeutic use. Example: <B> 3.7 </B> b Js, s-Androstenediol- (3.17) -17-isobutyrate are dissolved in 50 cm 'glacial acetic acid. The bromine-glacial sessib solution is then added dropwise with cooling for as long as the color changes immediately.
Finally, 1.0 b of chromium trioxide, dissolved in 30 cm. Of acetic acid, is also added in the cold and the whole is left to stand overnight at room temperature. It is then poured into 1 liter of water, the product which has precipitated is filtered off with suction and washed with plenty of water.
The brominated ketone thus obtained takes. glacial acetic acid is added to the debromination in 50 cm, 20 g of zinc dust are added and the mixture is heated in a boiling water bath for 12 minutes with intensive shaking.
Then it is dusted off through a glass filter, washed with a little hot glacial acetic acid, the solution is cooled with water and extracted with ether. The ether solution washed with dilute soda solution and water yields a residue on evaporation from which, for example, 44,5-androstenol- (17) -one- (3) -iso-butyrate can be isolated via the sparingly soluble semicarba.zon,
the n <cli LTin crystallization from hexane melts at 134-136.
Instead of chromic acid, for example, copper oxide can also be used for oxidation.
The double bond can be protected matt by bromine, for example also by chlorine.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH210765T | 1935-06-18 | ||
| CH208082T | 1935-06-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH210765A true CH210765A (en) | 1940-07-31 |
Family
ID=25724483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH210765D CH210765A (en) | 1935-06-18 | 1935-06-18 | Process for the preparation of an oxyketone ester of the androsten series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH210765A (en) |
-
1935
- 1935-06-18 CH CH210765D patent/CH210765A/en unknown
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