DE1180743B - Process for the dehydration of 3-keto steroids - Google Patents
Process for the dehydration of 3-keto steroidsInfo
- Publication number
- DE1180743B DE1180743B DEN21195A DEN0021195A DE1180743B DE 1180743 B DE1180743 B DE 1180743B DE N21195 A DEN21195 A DE N21195A DE N0021195 A DEN0021195 A DE N0021195A DE 1180743 B DE1180743 B DE 1180743B
- Authority
- DE
- Germany
- Prior art keywords
- keto steroids
- dehydration
- keto
- steroids
- dicyano
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 8
- 230000018044 dehydration Effects 0.000 title claims description 4
- 238000006297 dehydration reaction Methods 0.000 title claims description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- DNXUGBMARDFRGG-UHFFFAOYSA-N 3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile Chemical compound O=C1C=CC(=O)C(C#N)=C1C#N DNXUGBMARDFRGG-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 150000004054 benzoquinones Chemical class 0.000 claims 1
- JWMFYGXQPXQEEM-WZBAXQLOSA-N pregnane Chemical class C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 JWMFYGXQPXQEEM-WZBAXQLOSA-N 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000004053 quinones Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- -1 3-keto-17ß-hydroxyandrostane-17-propionate Chemical compound 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- MOVRKLZUVNCBIP-RFZYENFJSA-N cortancyl Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O MOVRKLZUVNCBIP-RFZYENFJSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- RAJWOBJTTGJROA-WZNAKSSCSA-N 5alpha-androstane-3,17-dione Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 RAJWOBJTTGJROA-WZNAKSSCSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- 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
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F26—DRYING
- F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
- F26B19/00—Machines or apparatus for drying solid materials or objects not covered by groups F26B9/00 - F26B17/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- General Engineering & Computer Science (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Dehydrierung von 3-Ketosteroiden Die Erfindung bezieht sich auf ein Verfahren zur Herstellung von 41,4-3-Ketosteroiden durch Behandlung eines im Ring a gesättigten 3-Ketosteroids mit 2,3-Dicyan-1,4-benzochinon, das in 5- und/oder 6-Stellung durch Chlor substituiert sein kann.Method of Dehydrating 3-Keto Steroids The invention relates to refers to a method of making 41,4-3-keto steroids by treatment a in the ring a saturated 3-keto steroid with 2,3-dicyano-1,4-benzoquinone, which in 5- and / or 6-position can be substituted by chlorine.
Aus der britischen Patentschrift 854 343 ist es bekannt, daß 41,4- oder 41.4.3-3-Ketosteroide hergestellt werden können durch Behandlung der entsprechenden 44- oder 44,3-3-Ketosteroide mit 2,3-Dicyan-1,4-benzochinon oder einem durch Chlor in 5- und/oder 6-Stellung substituierten Derivat davon. Dementsprechend bezieht sich diese Umwandlung ausschließlich auf die l (2)-Dehydrierung von 3-Ketosteroiden, die schon eine oder zwei Doppelbindungen in x- oder a,y-Stellung zu der 3-Ketogruppe besitzen.From British patent specification 854 343 it is known that 41.4- or 41.4.3-3-ketosteroids can be prepared by treating the appropriate 44- or 44,3-3-keto steroids with 2,3-dicyano-1,4-benzoquinone or one by chlorine derivative thereof substituted in the 5- and / or 6-position. Correspondingly relates this conversion is exclusively due to the l (2) -dehydrogenation of 3-keto steroids, which already have one or two double bonds in the x or a, y position to the 3-keto group own.
Es wurde nun festgestellt, daß unter dem Einfluß dieser Gruppe von Chinonen A', 4-3-Ketosteroide aus 3-Ketosteroiden, die im Ring A vollständig gesättigt sind, hergestellt werden können.It has now been found that under the influence of this group of quinones A ', 4-3-keto steroids can be prepared from 3-keto steroids which are completely saturated in ring A.
Sowohl die Tatsache, daß das in der obigen britischen Patentschrift beschriebene Verfahren streng auf die Dehydrierung von 3-Ketosteroiden beschränkt ist, die schon eine Doppelbindung im Ring A besitzen, als auch die bekannte Tatsache, daß unter dem Einfluß gewisser Chinone eine oder mehrere Doppelbindungen in Verbindungen eingeführt werden können, die schon eine Doppelbindung besitzen, bestätigt den Eindruck, daß das Vorliegen einer Doppelbindung in dem zu oxydierenden System eine wichtige Bedingung für die Dehydrierung mittels eines Chinons ist.Both the fact that the above British patent The method described is strictly limited to the dehydration of 3-keto steroids which already have a double bond in ring A, as well as the well-known fact that under the influence of certain quinones one or more double bonds in compounds which already have a double bond confirms the impression that that the presence of a double bond in the system to be oxidized is an important one A condition for dehydration using a quinone is.
Es war deshalb überraschend, daß auch 3-Ketosteroide, die im Ring A vollständig gesättigt sind, mit gewissen Chinonen in die entsprechenden d 1.4-3-Ketosteroide umgewandelt werden können.It was therefore surprising that 3-keto steroids were included in the ring A are completely saturated, with certain quinones in the corresponding d 1.4-3-ketosteroids can be converted.
Das erfindungsgemäße Verfahren ist von großem praktischem Wert, da mit dessen Hilfe alle Arten leicht zugänglicher 3-Ketosteroide, die im Ring A gesättigt sind, in einer Reaktionsstufe in Verbindungen umgewandelt werden können, die zu der sehr wichtigen Gruppe der 41,4-3-Ketosteroide gehören.The method of the invention is of great practical value since with the help of which all kinds of easily accessible 3-keto steroids that are saturated in ring A. are, can be converted into compounds in a reaction stage that lead to belong to the very important group of 41,4-3-ketosteroids.
Das Verfahren wird durchgeführt, indem man das entsprechende Steroid einige Zeit mit dem entsprechenden Chinon in Berührung hält, vorzugsweise bei einer höheren Temperatur, in Gegenwart eines organischen Lösungsmittels.The procedure is carried out by taking the appropriate steroid keeps in contact with the corresponding quinone for some time, preferably with one higher temperature, in the presence of an organic solvent.
Im vorliegenden Verfahren wird vorzugsweise das 2,3-Dicyan-5,6-dichlor-1,4-benzochinon verwendet. Beispiel 1 Zu einer Lösung von 10g Allodihydrocortison-21-acetat in 150 ml Dioxan werden 20 g 2,3-Dichlor-5,6-dicyanbenzochinon zugegeben, wonach die Mischung 12 Stunden am Rückfluß erhitzt wird. Danach wird sie gekühlt und filtriert, wonach das Filtrat zu 20m1 verdampft und gleich darauf mit Wasser auf 200 ml verdünnt wird. Die erhaltene wäßrige Mischung wird mit Chloroform extrahiert und der Extrakt mit 1 n-Natriumhydroxyd und danach mit Wasser gewaschen, bis er neutral ist. Anschließend wird der Chloroformextrakt zur Trockne eingedampft und der Rückstand aus Äthylacetat umkristallisiert. Man erhält 5,8 g Prednison-21-acetat mit einem Schmelzpunkt von 225 bis 230°C.In the present process, 2,3-dicyano-5,6-dichloro-1,4-benzoquinone is preferred used. Example 1 To a solution of 10 g of allodihydrocortisone-21-acetate in 150 ml of dioxane, 20 g of 2,3-dichloro-5,6-dicyanobenzoquinone are added, after which the mixture Is refluxed for 12 hours. After that it is cooled and filtered, after which the filtrate is evaporated to 20m1 and immediately thereafter diluted to 200 ml with water. The aqueous mixture obtained is extracted with chloroform and the extract with 1 n sodium hydroxide and then washed with water until neutral. Afterward the chloroform extract is evaporated to dryness and the residue from ethyl acetate recrystallized. 5.8 g of prednisone-21-acetate with a melting point of 225 to 230 ° C.
In entsprechender Weise wird 1 g Dihydrocortison-21-acetat in Prednison-21-acetat umgewandelt. Ausbeute: 0,51 g Beispiel 2 Eine Lösung von 1 g 3,17-Diketoandrostan in Benzol wird 14 Stunden in Gegenwart von 2 g 2,3-Dichlor-5,6-dicyanbenzochinon am Rückfluß erhitzt, wonach die Mischung mit Äther verdünnt und filtriert wird. Das Filtrat wird mit 2 n-Natriumhydroxyd und dann mit Wasser bis zur Neutralität gewaschen und schließlich auf Natriumsulfat getrocknet. Das Filtrat wird zur Trockne eingedampft und der Rückstand aus wäßrigem Aceton umkristallisiert. Man erhält 0,48 g 41.4-3,17-Diketoandrostadien mit einem Schmelzpunkt von 136 bis 138'C. In ähnlicher Weise wird das 3-Keto-17ß-hydroxyandrostan-17-propionat indie entsprechende d 1.4-Verbindung mit einem Schmelzpunkt von 146°C umgewandelt.In a corresponding manner, 1 g of dihydrocortisone-21-acetate is converted into prednisone-21-acetate converted. Yield: 0.51 g. Example 2 A solution of 1 g of 3,17-diketoandrostane in benzene is 14 hours in the presence of 2 g of 2,3-dichloro-5,6-dicyanobenzoquinone heated to reflux, the mixture is diluted with ether and filtered. The filtrate is treated with 2N sodium hydroxide and then with water until neutral washed and finally dried over sodium sulfate. The filtrate becomes dry evaporated and the residue recrystallized from aqueous acetone. 0.48 is obtained g 41.4-3,17-diketoandrostadiene with a melting point of 136 to 138 ° C. In Similarly, the 3-keto-17ß-hydroxyandrostane-17-propionate is used in the corresponding d 1.4 compound with a melting point of 146 ° C converted.
Beispiel 3 Zu einer Lösung von 5 g 3,20-Diketo-llx,i7x-dihydroxy-16a-methyl-21-acetoxy-5a-pregnan in 75m1 Dioxan werden 10g 2,3-Dichlor-5,6-dicyanbenzochinon zugegeben, wonach die Mischung 5 Stunden am Rückfluß erhitzt wird. Danach wird entsprechend dem im Beispiel 1 beschriebenen Verfahren weiterbehandelt und 2,78 g d 1.4-3,20-Diketo-11 x, 17a, 21-trihydroxy-16a-methylpregnadien-21-acetat mit einem Schmelzpunkt von 138 bis 142°C erhalten.Example 3 To a solution of 5 g of 3,20-diketo-11x, 17x-dihydroxy-16a-methyl-21-acetoxy-5a-pregnane 10g of 2,3-dichloro-5,6-dicyanobenzoquinone are added in 75m1 of dioxane, after which the The mixture is refluxed for 5 hours. After that, according to the example 1 and 2.78 g of d 1.4-3,20-diketo-11 x, 17a, 21-trihydroxy-16a-methylpregnadiene-21-acetate with a melting point of 138 to Preserved 142 ° C.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL261183 | 1961-02-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1180743B true DE1180743B (en) | 1964-11-05 |
Family
ID=19752873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEN21195A Pending DE1180743B (en) | 1961-02-13 | 1962-02-13 | Process for the dehydration of 3-keto steroids |
Country Status (3)
| Country | Link |
|---|---|
| CH (1) | CH404652A (en) |
| DE (1) | DE1180743B (en) |
| GB (1) | GB927158A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108912193B (en) * | 2018-07-25 | 2020-05-19 | 岳阳环宇药业有限公司 | Production process and production device of medroxyprogesterone acetate |
| CN108912191B (en) * | 2018-07-25 | 2020-05-19 | 岳阳环宇药业有限公司 | Estradiol production process and production device |
-
1962
- 1962-02-05 GB GB436062A patent/GB927158A/en not_active Expired
- 1962-02-08 CH CH154062A patent/CH404652A/en unknown
- 1962-02-13 DE DEN21195A patent/DE1180743B/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CH404652A (en) | 1965-12-31 |
| GB927158A (en) | 1963-05-29 |
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