CH248964A - Process for the preparation of a new synthetic, estrogenic agent. - Google Patents
Process for the preparation of a new synthetic, estrogenic agent.Info
- Publication number
- CH248964A CH248964A CH248964DA CH248964A CH 248964 A CH248964 A CH 248964A CH 248964D A CH248964D A CH 248964DA CH 248964 A CH248964 A CH 248964A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- estrogenic agent
- new synthetic
- triphenylethylene
- new
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- 239000000262 estrogen Substances 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 5
- MKYQPGPNVYRMHI-UHFFFAOYSA-N Triphenylethylene Chemical group C=1C=CC=CC=1C=C(C=1C=CC=CC=1)C1=CC=CC=C1 MKYQPGPNVYRMHI-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000003389 potentiating effect Effects 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- -1 p-anisyl Chemical group 0.000 description 3
- QMPKJVBRCQVFLL-UHFFFAOYSA-N 1,1,2-triphenylethanol Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)CC1=CC=CC=C1 QMPKJVBRCQVFLL-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- LSLTUAIHOGSOKB-UHFFFAOYSA-M [Br-].CCOC1=CC=C([Mg+])C=C1 Chemical compound [Br-].CCOC1=CC=C([Mg+])C=C1 LSLTUAIHOGSOKB-UHFFFAOYSA-M 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
- C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring
- C07C39/215—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring containing, e.g. diethylstilbestrol
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung eines neuen synthetischen, oestrogenen Mittels. Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung eines neuen, syn thetischen oestrogenen Mittels, eines substi- tuierten Triphenyläthylens der Formel
EMI0001.0014
Erfindungsgemäss wird diese neue Ver bindung dadurch erhalten,
dass man das Triphenyläthylen der Formel
EMI0001.0017
nach der Auflösung in einem inerten orga nischen Lösungsmittel mit der mindestens annähernd äquimolekularen Menge Brom zur Umsetzung bringt.
Zweckmässig verwendet man einen ge ringen Überschuss an Brom, beispielsweise 2 oder 5 % mehr als den theoretischen Wert. Ein grosser Überschuss ist zu vermeiden, da dies zu höher bromierten Produkten führen würde. Als zur Durchführung der Umsetzung geeignete Lösungsmittel seien beispielsweise Tetrachlorkohlenstoff, Eisessig, Nitrobenzol und Chlorbenzol erwähnt.
Das substituierte Triphenyläthylen, der Ausgangsstoff für das erfindungsgemässe Verfahren, kann leicht durch Wasserentzug aus dem entsprechend substituierten Triphe- nyläthanol, z. B, durch Erhitzen desselben mit einem Dehydratisierungsmittel, wie bei spielsweise Schwefelsäure, Acetylehlorid oder Phosphortribramid, dargestellt werden.
Das substituierte Triphenyläthanol selbst kann seinerseits durch Grignard-Reaktion aus einem geeignet substituierten Desogy- benzoin und p-Anisyl- oder p-Phenetyl- Mab,onesiumbromid erhalten werden. So kann man z. B. Desogyanisoin und p-Phenetyl- Magnesiumbromid verwenden.
Eine beson ders bequeme Darstellungsmethode besteht darin, dass man p-Äthoxy-p'-methoxy-benzo- phenon mit einem Benzyl-Magnesiumhalo- genid umsetzt.
Die neue Verbindung stellt ein wirk sames oestrogenes Mittel dar, das die uner wartete Eigenschaft aufweist, dass es bei der Einnahme durch den Mund wirksamer ist, als wenn es durch Injektion eingeführt wird. Die Erfindung sei durch das folgende Beispiel, in welchem die Teile Gewichtsteile bedeuten, erläutert. Beispiel: 16,5 Teile a-p-Anisyl-a-p-phenetyl-ss-phe- nyläthylen werden in 150 Teilen Eisessig gelöst.
Diese Lösung wird bei 20-30 C ge rührt und mit 8,2 Teilen Brom versetzt, welches in 82 Teilen Eisessig gelöst wurde. Nun wird das Reaktionsgemisch während 24 Stunden stehengelassen und hierauf mit Wasser verdünnt. Der gebildete Niederschlag stellt rohes a-p-Anisyl-a-p-phenetyl-ss-phe- nyl-bromäthylen dar. Dieses wird aus Äthyl- alkohol umkristallisiert, worauf es bei 78'C schmilzt.
Der Ausgangsstoff, das a-p-Anisyl-a- p-phenetyl-P-phenyl-äthylen, wird vorteil= haft durch Kochen am Rückfluss von a-p- Anisyl-a-p-phenetyl-;B-phenyl-äthanol mit einem Überschuss an Acetylchlorid herge stellt. Auf diese Weise wird dieses Produkt in Form einer zähflüssigen Flüssigkeit er halten, welche bei 15 mm Druck bei 240 bis 250 C siedet.
Process for the preparation of a new synthetic, estrogenic agent. The present invention relates to a process for the preparation of a new, synthetic estrogenic agent, a substituted triphenylethylene of the formula
EMI0001.0014
According to the invention, this new connection is obtained by
that you get the triphenylethylene of the formula
EMI0001.0017
after dissolution in an inert organic solvent with the at least approximately equimolecular amount of bromine to react.
It is advisable to use a slight excess of bromine, for example 2 or 5% more than the theoretical value. A large excess should be avoided, as this would lead to higher brominated products. Examples of suitable solvents for carrying out the reaction are carbon tetrachloride, glacial acetic acid, nitrobenzene and chlorobenzene.
The substituted triphenylethylene, the starting material for the process according to the invention, can easily be nylethanol by removing water from the correspondingly substituted triphenylethanol, eg. B, by heating the same with a dehydrating agent such as sulfuric acid, acetyl chloride or phosphorus tribramide, for example.
The substituted triphenylethanol itself can in turn be obtained from a suitably substituted desogybenzoin and p-anisyl or p-phenetyl Mab, onesium bromide by Grignard reaction. So you can z. B. Use desogyanisoin and p-phenetyl magnesium bromide.
A particularly convenient method of preparation consists in reacting p-ethoxy-p'-methoxy-benzophenone with a benzyl magnesium halide.
The new compound is a potent estrogenic agent which has the unexpected property that it is more effective when taken by mouth than when introduced by injection. The invention is illustrated by the following example, in which the parts mean parts by weight. Example: 16.5 parts of a-p-anisyl-a-p-phenetyl-ss-phenylethylene are dissolved in 150 parts of glacial acetic acid.
This solution is stirred at 20-30 C and treated with 8.2 parts of bromine, which was dissolved in 82 parts of glacial acetic acid. The reaction mixture is then left to stand for 24 hours and then diluted with water. The precipitate formed is crude a-p-anisyl-a-p-phenetyl-ss-phenyl-bromoethylene. This is recrystallized from ethyl alcohol, whereupon it melts at 78 ° C.
The starting material, the ap-anisyl-a-p-phenetyl-P-phenyl-ethylene, is advantageously prepared by refluxing ap-anisyl-ap-phenetyl-; B-phenyl-ethanol with an excess of acetyl chloride . In this way, this product will be kept in the form of a viscous liquid which boils at 240 to 250 ° C. at 15 mm pressure.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH248964T | 1944-11-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH248964A true CH248964A (en) | 1947-05-31 |
Family
ID=4467246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH248964D CH248964A (en) | 1944-11-06 | 1944-11-06 | Process for the preparation of a new synthetic, estrogenic agent. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH248964A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1109183B (en) * | 1956-07-23 | 1961-06-22 | Wm S Merrel Company | Process for the production of anti-estrogenic and anti-inflammatory substituted triphenylethanols |
| DE1155436B (en) * | 1956-11-06 | 1963-10-10 | Richardson Merrell Inc | Process for the preparation of 1- [p- (ª ‰ -Diaethylaminoaethoxy) -phenyl] -1, 2-diphenyl-2-chloroethylene |
-
1944
- 1944-11-06 CH CH248964D patent/CH248964A/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1109183B (en) * | 1956-07-23 | 1961-06-22 | Wm S Merrel Company | Process for the production of anti-estrogenic and anti-inflammatory substituted triphenylethanols |
| DE1155436B (en) * | 1956-11-06 | 1963-10-10 | Richardson Merrell Inc | Process for the preparation of 1- [p- (ª ‰ -Diaethylaminoaethoxy) -phenyl] -1, 2-diphenyl-2-chloroethylene |
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