CH218515A - Process for the preparation of testosterone. - Google Patents
Process for the preparation of testosterone.Info
- Publication number
- CH218515A CH218515A CH218515DA CH218515A CH 218515 A CH218515 A CH 218515A CH 218515D A CH218515D A CH 218515DA CH 218515 A CH218515 A CH 218515A
- Authority
- CH
- Switzerland
- Prior art keywords
- testosterone
- preparation
- solution
- acid
- action
- Prior art date
Links
- 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 title claims description 12
- 229960003604 testosterone Drugs 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 239000012433 hydrogen halide Substances 0.000 claims description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 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 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 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
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 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
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 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)
- Steroid Compounds (AREA)
Description
Verfahren zur Darstellung von Testosteron. Es wurde gefunden, dass man Testosteron in der Weise darstellen kann, dass man in einem Amin der Formel
EMI0001.0003
die in 3-Stellung befindliche Hydroxylgruppe durch die Einwirkung eines Oxydationsmittels zur Oxogruppe oxydiert, daraufhin durch die Einwirkung eines Halogenierungsmittels und die Abspaltung von Halogenwasserstoff eine Doppelbindung erzeugt und die Aminogruppe mit Hilfe von salpetriger Säure in die Hy- droxylgruppe überführt.
Die chemischen und physiologischen Eigen schaften des Testosterons sind bekannt. Beispiel: 5 g 3-Acetoxyätiocholanylcarbonsäure(17) werden, in gleicher Weise wie im Schweizer Patent Nr. 207799 für die 3-Acetoxyätio- cholenylcarbonsäure beschrieben ist, in das zugehörige Chlorid übergeführt und zum ent sprechenden Amin abgebaut.
Zu einer Lösung von 3 g Oxyätiocholanyl- aminacetat in Eisessig wird eine Chromsäure- Eisessiglösung (0,85 g Chromsäure) einfliessen gelassen und die Oxydationsmischung 24 Stun den bei<B>151</B> C aufbewahrt.
Nach Hinzufügen von Zinkstaub wird der geringe Überschuss von Chromsäure zerstört, die Lösung im Vaku um eingedampft, der Rückstand mit Wasser versetzt, mit Natriumcarbonatlösung alkalisch gemacht und das freie Oxoamin ausgeäthert. Nach Trocknen der ätherischen Lösung wird das Oxoamin als Acetat gefällt.
1,5 g. des so erhaltenen 3-Oxoätiocholanyl- aminacetates werden nun mit Eisessig gelöst, zur Lösung einige Tropfen Bromwasserstoff- säure hinzugefügt und<B>0,69</B> g Brom in 10 crn3 Eisessig tropfenweise einfliessen gelassen.
Die Reaktionslösung wird im Vakuum eingedampft, der Rückstand in Alkohol gelöst und auf die im Schweizer Patent Nr. 207799 beschriebene Weise die Aminogruppe des 3-Oxo-4-brom- ätiooliolanylaminacetats mit Natriumnitrit und Essigsäure auf dem Wasserbad verkocht.
Die Reaktionslösung wird mit Wasser verdünnt, ausgeäthert und der Rückstand der ätheri schen Lösung mit Silberacetat und Eisessig eritbromiert. Durch Zugabe von Wasser und lrinkristallisieren aus Hexan erhält man nun das Testosteron vom Schmelzpunkt<B>1510</B> C.
Process for the preparation of testosterone. It has been found that testosterone can be represented in the way that it can be in an amine of the formula
EMI0001.0003
the 3-position hydroxyl group is oxidized to the oxo group by the action of an oxidizing agent, then a double bond is generated by the action of a halogenating agent and the elimination of hydrogen halide, and the amino group is converted into the hydroxyl group with the aid of nitrous acid.
The chemical and physiological properties of testosterone are known. Example: 5 g of 3-acetoxyethiocholanylcarboxylic acid (17) are converted into the associated chloride and degraded to the corresponding amine in the same way as is described in Swiss patent no. 207799 for 3-acetoxyethio- cholenylcarboxylic acid.
A chromic acid-glacial acetic acid solution (0.85 g chromic acid) is allowed to flow into a solution of 3 g of oxyethocholanylamine acetate in glacial acetic acid, and the oxidation mixture is kept at 151 C for 24 hours.
After adding zinc dust, the slight excess of chromic acid is destroyed, the solution is evaporated in vacuo, the residue is mixed with water, made alkaline with sodium carbonate solution and the free oxoamine is extracted with ether. After the ethereal solution has dried, the oxoamine is precipitated as acetate.
1.5 g. of the 3-oxoethiocholanylamine acetate obtained in this way are now dissolved with glacial acetic acid, a few drops of hydrobromic acid are added to the solution and 0.69 g of bromine in 10 cc of glacial acetic acid is allowed to flow in dropwise.
The reaction solution is evaporated in vacuo, the residue is dissolved in alcohol and the amino group of the 3-oxo-4-bromoetiooliolanylamine acetate is boiled with sodium nitrite and acetic acid on a water bath in the manner described in Swiss Patent No. 207799.
The reaction solution is diluted with water, extracted with ether and the residue of the ethereal solution is eritbrominated with silver acetate and glacial acetic acid. By adding water and crystallizing it from hexane, testosterone with a melting point of <B> 1510 </B> C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE218515X | 1936-06-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH218515A true CH218515A (en) | 1941-12-15 |
Family
ID=5831351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH218515D CH218515A (en) | 1936-06-11 | 1937-06-11 | Process for the preparation of testosterone. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH218515A (en) |
-
1937
- 1937-06-11 CH CH218515D patent/CH218515A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE894396C (en) | Process for the preparation of 1- (o-, m- or p-oxyphenyl) -1-oxy-2-aralkylamino-ethanes | |
| CH218515A (en) | Process for the preparation of testosterone. | |
| DE890796C (en) | Process for the production of diacetylene glycols | |
| DE684498C (en) | Process for the preparation of androstandiol of the formula C HO | |
| AT52528B (en) | Process for the preparation of a sparingly soluble formaldehyde zinc sulfoxylate. | |
| AT141503B (en) | Process for the preparation of ethers of 1- [3'.4'-Dioxyphenyl] -2-aminopropanols- (1). | |
| DE932796C (en) | Process for the preparation of saturated and unsaturated 17-oxy-20-ketones of the pregnane series | |
| DE879098C (en) | Process for the preparation of ring-substituted saturated or unsaturated androstanol- (17) -onen- (3) or their 17-derivatives | |
| AT157241B (en) | Process for the preparation of androstandiol- (3.17) or its stereoisomers. | |
| DE699033C (en) | Process for the preparation of putrescine | |
| DE1186851B (en) | Process for the preparation of Endo-2, 3-epoxy-1, 4, 5, 6, 7, 8, 8-heptachlor-3a, 4, 7, 7a-tetrahydro-4, 7-methanoindane | |
| DE739085C (en) | Process for the preparation of ª ‡ -dicarbonyl compounds of the cyclopentanopolyhydrophenanthrene series | |
| AT158937B (en) | Process for the preparation of androstandione (3.17) and its stereoisomers. | |
| AT158270B (en) | Process for the preparation of androstandiol- (3.17) or its stereoisomers. | |
| CH188987A (en) | Procedure for displaying Pregnendion-3.20. | |
| CH170698A (en) | Process for the preparation of m-oxyphenylaminopropanol chlorohydrate. | |
| CH233771A (en) | Process for the preparation of a dioxyacetone diether. | |
| CH163397A (en) | Process for the preparation of 1-p-oxyphenyl-2-N-methyl-amino-ethanol-1. | |
| CH271777A (en) | Process for the production of biotin. | |
| CH191458A (en) | Process for the preparation of a carboxylic acid ester containing the pyridine nucleus. | |
| CH197784A (en) | Method for the preparation of D5,6-trans-Androstenediol-3,17. | |
| CH214539A (en) | Process for the preparation of an alcohol of the cyclopentanopolyhydrophenanthrene series. | |
| CH222491A (en) | Process for the preparation of 3-acetoxybisnorcholanyl-acetoxymethyl-ketone. | |
| CH233773A (en) | Process for the preparation of a dioxyacetone diether. | |
| CH156413A (en) | Dye paste, in particular for stuff printing, from leuco vat dye preparations. |