CH215812A - A method for producing an enol ether of a ketocyclopentanopolyhydrophenanthrene compound. - Google Patents
A method for producing an enol ether of a ketocyclopentanopolyhydrophenanthrene compound.Info
- Publication number
- CH215812A CH215812A CH215812DA CH215812A CH 215812 A CH215812 A CH 215812A CH 215812D A CH215812D A CH 215812DA CH 215812 A CH215812 A CH 215812A
- Authority
- CH
- Switzerland
- Prior art keywords
- sep
- compound
- acid
- ketocyclopentanopolyhydrophenanthrene
- producing
- Prior art date
Links
- 150000002084 enol ethers Chemical class 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- RLAHWVDQYNDAGG-UHFFFAOYSA-N Methanetriol Chemical compound OC(O)O RLAHWVDQYNDAGG-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- ULPMRIXXHGUZFA-UHFFFAOYSA-N 4-methylhexan-3-one Chemical compound CCC(C)C(=O)CC ULPMRIXXHGUZFA-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance 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
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 1
- 229960005471 androstenedione Drugs 0.000 description 1
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- GGCLNOIGPMGLDB-GYKMGIIDSA-N cholest-5-en-3-one Chemical compound C1C=C2CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 GGCLNOIGPMGLDB-GYKMGIIDSA-N 0.000 description 1
- NYOXRYYXRWJDKP-UHFFFAOYSA-N cholestenone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 NYOXRYYXRWJDKP-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- -1 isotesterone Chemical compound 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 125000002328 sterol group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 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 Herstellung eines Enoläthers einer Netocyclopentanopoly- hydrophenanthrenverbindung. Die vorliegende Erfindung betrifft ein Ver fahren zur Hertellung von Enoläthern aus Ketonen der Ketocyclopentanopolyhydrophen- anthrenreihe. Gemäss diesem Verfahren wird der Sterinkern, vorzugsweise der Ring A und /oder D, ungesättigter gemacht, wodurch wertvolle Substanzen erhalten werden, die als Zwischenprodukt zur Herstellung von heil kräftigen Präparaten und besonders von Stof fen,
die Eigenschaften der Hormone besitzen, dienen.
Man kann z. B. Ketone der Cyclopentano- polyhydrophenanthrenreihe als Ausgangsstoffe verwenden, die im Ring A in 3-Stellung oder im Ring D in 17-Stellung eine Ketogruppe enthalten. Geht man von 3-Ketonen aus, welche im Ring A z. B. entweder in 1.2- oder in 4.5-Stellung eine Doppelbindung besitzen, so erhält man Produkte mit zwei konjugierten Doppelbindungen.
Die erfindungsgemässe Umsetzung wird durchgeführt, indem man auf die Ketone z. B. Ester der Ortlioameisensäure vorteilhaft in Gegenwart einer kleinen Menge von Mineral säure, die als Katalysator wirkt, einwirken lässt. Falls sich das Gemisch erwärmt, ist es ratsam, es zu kühlen, um die heftige Reaktion abzuschwächen.
Die Reaktion lässt sich an Hand der folgenden Formelbilder, die nur den Ring A darstellen, und woselbst R einen Kohlenwasserstoffrest bedeutet, veranschau lichen
EMI0001.0025
Zuerst wird vermutlich der Diäther II gebildet, der alsbald ein Molekül Alkohol abspaltet, so dass als Endprodukt der Monoäther IH erhalten wird. Eine starke Absorption bei 240 UU zeigt an, dass beide Doppelbindungen im Ring A vorliegen.
So sind mit den 31etliyl-, Butyl-, Allyl- und andern Estern der Orthoameisensäure die Methyl-, Butyl-, Allyl- und andere Äther der Ausgangsmateriälien gewinnbar. Die er findungsgemässe Reaktion kann z. B. mit Cholestenon, Isotesteron, Androstendion, Preg- nen-19-ol-3-on und andern ähnlichen Verbin dungen ausgeführt werden.
Ausser Schwefel säure kann als Katalysator auch gasförmige ChlorwasseAtoffsäure, Bromwasserstoffsäure, Phosphorsäure oder eine andere, vorzugsweise starke -Mineralsäure, verwendet werden.
Gegenstand des vorliegenden Patentes ist nun ein Verfahren zur Herstellung einet Enol- äthers einer Ketocyclopentanopoly hydroplien- anthrenverbindung, das dadurch gekennzeich net ist, dass man Testosteronbenzoat mit Ortlio- ameisensäureäthylester umsetzt.
Beispiel: 5 g Testosteronbenzoat werden zusammen mit 20 cm' Orthoameisensäureiitbylester und 2 ein' Ameisensäure erhitzt. Beine Abkühlen kristallisiert das Material wieder aus. Dann wird 1 Tropfen konzentrierte Schwefelsäure zugefügt, das Gemisch vorsichtig auf 50' C erwärmt und ',!_ Stunde bei dieser Temperatur gehalten, worauf sich das -Material. zuerst gelb und endlich blaugrün färbt.
Beim Abkühlen wird das Reaktionsgemisch fest, man lässt es 20 Stunden stehen und filtriert von den aus geschiedenen Kristallen ab, die in Äther gelöst werden. Die Ätherlösung wird dann mit Was ser, Sodalösung und wiederum mit Wasser gewaschen und getrocknet.
Man erhält beim Verdampfen einen gelben öligen Rückstand, der zweimal aus Aceton umkristallisiert wird
EMI0002.0042
und <SEP> schöne <SEP> gliinzeude <SEP> BIiittchen <SEP> vom <SEP> Schmelz punkt <SEP> 189" <SEP> C <SEP> bildet. <SEP> Der <SEP> 3lischschmelzpunkt
<tb> mit <SEP> Testosteronbenzoat <SEP> zeigt <SEP> ein <SEP> Absinken <SEP> von
<tb> ungefähr <SEP> <B>15-20.</B> <SEP> Die <SEP> Analyse <SEP> und <SEP> Ätho xylbestimmung <SEP> zeigen, <SEP> dass <SEP> die <SEP> Verbindung
<tb> die <SEP> Formel <SEP> C<B>L#JL</B>@M;s <SEP> hat, <SEP> die <SEP> dem <SEP> folgenden
<tb> Formelbild <SEP> entspricht:
EMI0002.0043
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<tb> \ <SEP> 0 <SEP> . <SEP> COC(;Hi,
<tb> <B>G, <SEP> 115</B> <SEP> 0-
EMI0002.0044
3 <SEP> @@thos@--ll-benzo@-loy-;mchosta-2.@l-dien.
Process for the preparation of an enol ether of a netocyclopentanopolyhydrophenanthrene compound. The present invention relates to a process for producing enol ethers from ketones of the ketocyclopentanopolyhydrophenanthene series. According to this process, the sterol core, preferably ring A and / or D, is made more unsaturated, whereby valuable substances are obtained which are used as intermediate products for the production of medicinally powerful preparations and especially of substances,
possess the properties of the hormones that serve.
You can z. B. use ketones of the cyclopentano polyhydrophenanthrene series as starting materials that contain a keto group in ring A in the 3-position or in ring D in the 17-position. If one assumes 3-ketones, which in the ring A z. B. have a double bond in either the 1.2- or 4.5-position, products with two conjugated double bonds are obtained.
The inventive reaction is carried out by focusing on the ketones z. B. esters of ortlioformic acid advantageous in the presence of a small amount of mineral acid, which acts as a catalyst, can act. If the mixture warms up, it is advisable to cool it to reduce the violent reaction.
The reaction can be illustrated with the help of the following formulas, which only represent ring A and where R is a hydrocarbon radical
EMI0001.0025
First the diether II is presumably formed, which soon splits off a molecule of alcohol, so that the monoether IH is obtained as the end product. A strong absorption at 240 UU indicates that both double bonds are present in ring A.
Thus the methyl, butyl, allyl and other ethers of the starting materials can be obtained with the ethyl, butyl, allyl and other esters of orthoformic acid. He inventive reaction can, for. B. with cholestenone, isotesterone, androstenedione, pregnen-19-ol-3-one and other similar compounds are carried out.
In addition to sulfuric acid, gaseous hydrochloric acid, hydrobromic acid, phosphoric acid or another, preferably strong mineral acid, can also be used as a catalyst.
The subject of the present patent is a process for the production of an enol ether of a ketocyclopentanopoly hydroplienanthrene compound which is characterized in that testosterone benzoate is reacted with ortlio formic acid ethyl ester.
Example: 5 g of testosterone benzoate are heated together with 20 cm of ethyl orthoformate and 2 a of formic acid. After cooling down, the material crystallizes out again. Then 1 drop of concentrated sulfuric acid is added, the mixture is carefully warmed to 50 ° C. and kept at this temperature for 1 hour, whereupon the material. first yellow and finally blue-green.
On cooling, the reaction mixture solidifies, it is left to stand for 20 hours and the crystals which have separated out are filtered off and dissolved in ether. The ether solution is then washed with water, soda solution and again with water and dried.
A yellow oily residue is obtained on evaporation, which is recrystallized twice from acetone
EMI0002.0042
and <SEP> beautiful <SEP> happy <SEP> little bits <SEP> from the <SEP> melting point <SEP> 189 "<SEP> C <SEP> forms. <SEP> The <SEP> melting point
<tb> with <SEP> testosterone benzoate <SEP> shows <SEP> a <SEP> decrease <SEP> of
<tb> about <SEP> <B> 15-20. </B> <SEP> The <SEP> analysis <SEP> and <SEP> ethoxy determination <SEP> show <SEP> that <SEP> the <SEP > Connection
<tb> has the <SEP> formula <SEP> C <B> L # JL </B> @M; s <SEP>, <SEP> the <SEP> following the <SEP>
<tb> Formula picture <SEP> corresponds to:
EMI0002.0043
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<tb> \ <SEP> 0 <SEP>. <SEP> COC (; Hi,
<tb> <B> G, <SEP> 115 </B> <SEP> 0-
EMI0002.0044
3 <SEP> @@ thos @ - ll-benzo @ -loy-; mchosta-2. @ L-dien.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US215812XA | 1937-02-26 | 1937-02-26 | |
| CH209162T | 1938-02-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH215812A true CH215812A (en) | 1941-07-15 |
Family
ID=25724661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH215812D CH215812A (en) | 1937-02-26 | 1938-02-25 | A method for producing an enol ether of a ketocyclopentanopolyhydrophenanthrene compound. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH215812A (en) |
-
1938
- 1938-02-25 CH CH215812D patent/CH215812A/en unknown
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