CH210546A - Process for the preparation of androstenol-17-one-3. - Google Patents
Process for the preparation of androstenol-17-one-3.Info
- Publication number
- CH210546A CH210546A CH210546DA CH210546A CH 210546 A CH210546 A CH 210546A CH 210546D A CH210546D A CH 210546DA CH 210546 A CH210546 A CH 210546A
- Authority
- CH
- Switzerland
- Prior art keywords
- ether
- androstenediol
- androstenol
- solution
- process according
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 title claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 4
- 239000012362 glacial acetic acid Substances 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000003198 secondary alcohol group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- -1 hydrogen peroxide Chemical class 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- QADHLRWLCPCEKT-UHFFFAOYSA-N Androstenediol Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)O)C4C3CC=C21 QADHLRWLCPCEKT-UHFFFAOYSA-N 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 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
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- QADHLRWLCPCEKT-LOVVWNRFSA-N androst-5-ene-3beta,17beta-diol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC=C21 QADHLRWLCPCEKT-LOVVWNRFSA-N 0.000 description 1
- 229950009148 androstenediol Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 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 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000005406 washing Methods 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)
- Steroid Compounds (AREA)
Description
Verfahren zur Darstellung von Androstenol-17-on-3. Es wurde gefunden, dass man Androstenol- 17-on-3 erhält, ein Produkt von grosser phy siologischer Wirksamkeit, das entweder als solches für pharmazeutische Zwecke dient, aber auch als Zwischenprodukt zurUmwand- lung irrandere therapeutisch wertvolle Stoffe verwendet werden kann, wenn man einen 17- Äther des Androstendiols-3,17 der Einwir kung eines Oxydationsmittels unterwirft,
welches eine sekundäre Alkoholgruppe in eine Ketogruppe überzuführen vermag und die Äthergruppe durch Hydrolyse in die Hydroxylgruppe überführt.
Als Ausgangsmaterial für die Darstel lung des Androstenol-17-ons-3 haben sich der 17-Triphenyl-methyl- und der 17-Benzyl- äther als besonders günstig erwiesen.
Als Oxydationsmittel kommen alle be kannten oxydierend wirkenden Stoffe in Be tracht, wie sie zum Beispiel in Houben- Weyl "Methoden der organischen Chemie" 3. Auflage, Bd. 2, S. 47 ff (1925) angeführt sind. Kupferoxyd und Chromsäure sind je doch bevorzugte Mittel. Durchführbar ist die Umwandlung des 17-Äthers des Andro- stendiols-3,17 in den 17-Äther des Androste- nol-17-on-3 auch mit Bichromat und Säure.
Permanganat und andere Versalze, auch Peroxyde wie Wasserstoffsuperoxyd können an die Stelle der obenerwähnten Oxydations- mittel treten.
Der intermediäre Schutz der Ringdoppel bindung erfolgt zweckmässig durch Halogen anlagerung.
Die Isolierung der gebildeten Ketoverbin- dung kann mit Hilfe von Ketonreagenzien, wie z. B. Semicarbazid, Hydroxylamin, Phe- nylhydrazinen und andern, oder mit Hilfe der fraktionierten Kristallisation oder der gleichen erfolgen.
Im Falle der Verwendung des Triphenyl- methyläthers empfiehlt es sich die Hydrolyse in sauren hydrolysierenden Mitteln durch zuführen.
<I>Beispiel 7:</I> 2,65 g 17-Triphenylmethyläther des An- drostendiol-3,17 werden in Pyridin gelöst und bei Zimmertemperatur mit einer 0,8 g Brom (entsprechend 1 Mol Brom auf 1 Mol Äther) enthaltenden Tetrachlorkohlenstoff- lösung vermischt. Das Brom wird rasch auf genommen, worauf man 0,6 g Chromsäure anhydrid (entsprechend etwa 2 Atomen Sauerstoff) in wenig Wasser gelöst zusetzt.
Nachdem man die Reaktionsmischung zwei Tage bei Zimmertemperatur stehen gelassen hat, wird die grünlich gefärbte Lösung in Wasser gegossen, der Niederschlag abfiltriert und in Eisessig gelöst. Die Eisessiglösung wird mit 5 g Zinkstaub während 1 4 Stunde auf<B>80'</B> C erhitzt. Die Lösung wird vom Zinkstaub abfiltriert, mit einigen Tropfen wässriger Salzsäure versetzt und während einer weiteren halben Stunde auf dem Wasserbad erwärmt, um die Aufspaltung des Äthers zu vervollständigen. Hierauf wird die Lösung abgekühlt, in Wasser gegossen und mit Äther extrahiert.
Die ätherische Lösung wird dann nacheinander mit verdünnter Sodalösung und mit Wasser gewaschen und vom Wasser durch Trocknen mit 3llagnesium- sulfa.t befreit. Nach Verdampfung des Äthers erhält man einen Rückstand, aus dem man durch LTmkristallisieren aus Äthvlacetat das Androstenol-17-on-3, das sogenannte Testo steron in reiner Form erhalten kann.
<I>Beispiel 2:</I> 2,65 g 17-Benzyläther des Androstendiol- 3,17 werden in Py ridin gelöst und bei Zim mertemperatur mit einer 0,85 g Brom (ent sprechend 1 Mol Brom auf 1 Mol Äther) enthaltenden Tetrachlorkohlenstofflösung ver mischt. Das Brom wird rasch aufgenommen, worauf man 0,6 g Chromsäureanhy drid (ent sprechend etwa 2 Atomen Sauerstoff) in we nig Wasser gelöst zusetzt.
Nachdem man die Reaktionsmischung zwei Tage bei Zimmer temperatur stehen gelassen hat, wird die grünlich gefärbte Lösung in @V asser gegos sen, der Niederschlag abfiltriert und in Eis essig gelöst. Die Eisessiglösung wird mit 5 g Zinkstaub während 1,f Stunde auf 80 C erhitzt. Die Lösung wird vom Zinkstaub ab filtriert, mit einigen Tropfen wässriger Salz säure versetzt und während einer weiteren halben Stunde auf dem Wasserbad erwärmt, um die Aufspaltung des Äthers zu vei##oll- ständigen. Hierauf wird die Lösung abge kühlt, in Wasser gegossen und mit Äther extrahiert.
Die ätherische Lösung wird dann nacheinander mit verdünnter Soda:lösung und mitWassergewasehen und vomWasserdureh Trocknen mit llagnesiumsulfat befreit. Nach Verdampfung des Äthers erhält man einen Rückstand, aus dem nach durch LTmkristal- lisieren aus Xthylacetat das Androstenol-17- on-3, das sogenannte Testosteron in reiner Form erhalten kann.
Process for the preparation of androstenol-17-one-3. It has been found that androstenol-17-one-3 is obtained, a product of great physiological efficacy which either serves as such for pharmaceutical purposes, but can also be used as an intermediate product for converting more and more therapeutically valuable substances if one is used 17- ether of androstenediol-3,17 subjected to the action of an oxidizing agent,
which is able to convert a secondary alcohol group into a keto group and converts the ether group into the hydroxyl group by hydrolysis.
The 17-triphenylmethyl and 17-benzyl ethers have proven to be particularly favorable as the starting material for the representation of androstenol-17-one-3.
All known oxidizing substances come into consideration as oxidizing agents, such as those listed in Houben-Weyl "Methods of Organic Chemistry" 3rd Edition, Vol. 2, p. 47 ff (1925). Copper oxide and chromic acid are, however, preferred agents. The conversion of the 17-ether of androstendiol-3,17 into the 17-ether of androstenol-17-one-3 can also be carried out with bichromate and acid.
Permanganate and other oversalts, including peroxides such as hydrogen peroxide, can take the place of the above-mentioned oxidizing agents.
The intermediate protection of the double ring bond is expediently carried out by addition of halogen.
The keto compound formed can be isolated with the aid of ketone reagents, such as. B. semicarbazide, hydroxylamine, phenylhydrazines and others, or with the aid of fractional crystallization or the like.
If triphenyl methyl ether is used, it is advisable to carry out the hydrolysis in acidic hydrolysing agents.
<I> Example 7: </I> 2.65 g of 17-triphenylmethyl ether of androstenediol-3.17 are dissolved in pyridine and at room temperature with a 0.8 g of bromine (corresponding to 1 mol of bromine to 1 mol of ether) containing Carbon tetrachloride solution mixed. The bromine is quickly taken up, whereupon 0.6 g of chromic anhydride (corresponding to about 2 atoms of oxygen) dissolved in a little water is added.
After the reaction mixture has been left to stand for two days at room temperature, the greenish colored solution is poured into water, the precipitate is filtered off and dissolved in glacial acetic acid. The glacial acetic acid solution is heated to <B> 80 ° C. for 14 hours with 5 g of zinc dust. The zinc dust is filtered off from the solution, a few drops of aqueous hydrochloric acid are added and the solution is heated on the water bath for another half hour in order to complete the splitting of the ether. The solution is then cooled, poured into water and extracted with ether.
The ethereal solution is then washed successively with dilute soda solution and with water and freed from the water by drying with 3llagnesium-sulfa.t. After evaporation of the ether, a residue is obtained from which androstenol-17-one-3, the so-called Testosterone, can be obtained in pure form by crystallizing from ethyl acetate.
<I> Example 2: </I> 2.65 g of 17-benzyl ether of androstenediol 3.17 are dissolved in pyridine and at room temperature with a 0.85 g of bromine (corresponding to 1 mol of bromine to 1 mol of ether) containing carbon tetrachloride solution mixed ver. The bromine is quickly absorbed, whereupon 0.6 g of chromic anhydride (corresponding to about 2 atoms of oxygen) dissolved in little water is added.
After the reaction mixture has been left to stand for two days at room temperature, the greenish-colored solution is poured into @V water, the precipitate is filtered off and dissolved in glacial vinegar. The glacial acetic acid solution is heated to 80 ° C. with 5 g of zinc dust for 1.5 hours. The zinc dust is filtered off from the solution, a few drops of aqueous hydrochloric acid are added and the solution is heated on the water bath for another half hour in order to complete the splitting of the ether. The solution is then cooled, poured into water and extracted with ether.
The ethereal solution is then successively freed with dilute soda solution and with water washing and from water by drying with magnesium sulfate. After evaporation of the ether, a residue is obtained from which, after crystallization from ethyl acetate, androstenol-17-one-3, the so-called testosterone, can be obtained in pure form.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE210546X | 1935-08-30 | ||
| CH202972T | 1936-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH210546A true CH210546A (en) | 1940-07-15 |
Family
ID=25723876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH210546D CH210546A (en) | 1935-08-30 | 1936-08-27 | Process for the preparation of androstenol-17-one-3. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH210546A (en) |
-
1936
- 1936-08-27 CH CH210546D patent/CH210546A/en unknown
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