CH609663A5 - Process for the preparation of novel phenylalkenols - Google Patents
Process for the preparation of novel phenylalkenolsInfo
- Publication number
- CH609663A5 CH609663A5 CH1485575A CH1485575A CH609663A5 CH 609663 A5 CH609663 A5 CH 609663A5 CH 1485575 A CH1485575 A CH 1485575A CH 1485575 A CH1485575 A CH 1485575A CH 609663 A5 CH609663 A5 CH 609663A5
- Authority
- CH
- Switzerland
- Prior art keywords
- compounds
- formula
- known per
- manner known
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 239000000203 mixture Substances 0.000 claims abstract description 11
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 239000007858 starting material Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- -1 aliphatic ketones Chemical class 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000010306 acid treatment Methods 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 239000012429 reaction media Substances 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 206010030113 Oedema Diseases 0.000 claims description 2
- VSKBCRUQHHGABO-UHFFFAOYSA-N [Al].[H][H].[H][H].[H][H] Chemical compound [Al].[H][H].[H][H].[H][H] VSKBCRUQHHGABO-UHFFFAOYSA-N 0.000 claims description 2
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 claims description 2
- DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000003849 aromatic solvent Substances 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000006227 byproduct Substances 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 230000001678 irradiating effect Effects 0.000 claims description 2
- 229910052987 metal hydride Inorganic materials 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 230000003285 pharmacodynamic effect Effects 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003460 sulfonic acids Chemical class 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 2
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 claims description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000460 chlorine Chemical group 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Chemical group 0.000 description 2
- 239000000654 additive Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/512—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being a free hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Phenylalkenols of the formula <IMAGE> in trans form, in which either Y is cyclohexyl and R1 is methyl or Y is phenyl and R1 is ethyl, are prepared by reducing the carbonyl group of compounds of the formula <IMAGE> and, if required, converting the resulting compound into the trans form. The compounds have antiinflammatory effects and can be employed in antiinflammatory compositions.
Description
**WARNUNG** Anfang DESC Feld konnte Ende CLMS uberlappen **.
PATENTANSPRUCH
Verfahren zur Herstellung von Phenyl-alkenolen der Formel I
EMI1.1
in Transform, worin entweder Y Cyclohexyl und R1 Methyl oder Y Phenyl und R1 Äthyl bedeuten, dadurch gekennzeichnet, dass die Carbonylgruppe von Verbindungen der Formel II
EMI1.2
worin R1 und Y obige Bedeutung besitzen, in einem inerten organischen Lösungsmittel und unter wasserfreien Bedingungen reduziert und die erhaltene Verbindung nötigenfalls in die Transform übergeführt wird.
Gegenstand der Erfindung ist ein Verfahren zur Herstellung neuer Phenylalkenole der Formel I
EMI1.3
in Transform, worin entweder Y Cyclohexyl und R1 Methyl oder Y Phenyl und R1 Äthyl bedeuten.
Das Verfahren ist dadurch gekennzeichnet, dass die Carbonylgruppe von Verbindungen der Formel II
EMI1.4
worin R1 und Y obige Bedeutung besitzen, in einem inerten organischen Lösungsmittel und unter wasserfreien Bedingungen reduziert und die erhaltene Verbindung nötigenfalls in die Transform übergeführt wird.
Die Reduktion von Verbindungen der Formel II erfolgt auf eine für die Reduktion von aliphatischen Ketonen zu aliphatischen sekundären Alkoholen übliche Weise, beispielsweise mit Hilfe eines komplexen Metallhydrides, wie Natriumaluminium-diäthyl-dihydrid oder Lithium-aluminium-tri-tbutoxyhydrid. Die Reduktion erfolgt in einem inerten organischen Lösungsmittel, beispielsweise einem Äther, wie Di äthyl äther, Tetrahydrofuran oder Dioxan, oder einem aromatischen Lösungsmittel, wie Benzol, Toluol oder Pyridin. Die Reaktionstemperatur beträgt zweckmässigerweise von -10 bis +40 C, vorzugsweise von 5 bis + 15 C.
Die erhaltenen Verbindungen der Formel I können auf an sich bekannte Weise isoliert und gereinigt werden.
Die Verbindungen der Formel I treten als geometrische Isomere auf und können als reine cis- oder trans-Isomere oder als Isomeren-Gemische erhalten werden. Letztere können auf an sich bekannte Weise in die einzelnen Isomere aufgetrennt werden. Die Verbindungen werden üblicherweise in reiner transisomerer Form oder in Form von Isomeren Gemischen erhalten, worin die transisomere Form vorherrscht, beispielsweise in einem Ausmass von 60-95 %, vorzugsweise von 70-95 %, insbesondere von 80-95 %.
Die Verbindungen der Formel II, die im Verfahren als Ausgangsverbindungen verwendet werden, können hergestellt werden, indem man Verbindungen der Formel III,
EMI1.5
worin R1 und Y obige Bedeutung besitzen, mit Säuren behandelt.
Die Säurebehandlung von Verbindungen der Formel III erfolgt unter Verwendung eines starken Protonisierungsmittels als Säure -Quelle in Gegenwart von Hydroxy-, niedrigen Acyloxy- oder niedrigen Alkoxyionen. Geeignete Protonisierungsmittel sind beispielsweise Mineralsäuren, wie Chlorwasserstoffsäure, Bromwasserstoffsäure oder Schwefelsäure, und aromatische niedrige Sulfonsäuren, wie p-Toluolsulfonsäure. Geeignete Hydroxy-, niedere Acyloxy- (mit 2-4 Kohlenstoffatomen) und niedere Alkoxy-(mit 1-4 Kohlenstoffatomen)-Anionen erhält man durch Zugabe von niederen Alkanolen, wie Methanol, Estern, wie Äthylorthoformiat und organischen Säuren und Anhydriden, wie Essigsäure oder Essigsäureanhydrid. Falls erwünscht, kann ein Überschuss solcher Mittel als Reaktionsmedium verwendet werden. Das Reaktionsmedium kann jedoch ebenfalls durch ein inertes organisches Lösungsmittel gebildet werden.
Die Umsetzung erfolgt zweckmässigerweise bei Temperaturen von 10-100" C, vorzugsweise von 15-35 C. Falls Chlorwasserstoffsäure oder Bromwasserstoffsäure für die Reaktion verwendet werden, erhält man ein Gemisch der erwünschten Verbindungen der Formel II, und es bilden sich als Nebenprodukte 4 substituierte Phenyl-4-alkyl-2-chlor-(oder Brom)-1,3-butadiene.
Die Verbindungen können auf an sich bekannte Weise getrennt werden.
Die erhaltenen Verbindungen der Formel II können auf an sich bekannte Weise isoliert und gereinigt werden.
Die Verbindungen der Formel III sind entweder bekannt oder können auf an sich bekannte Weise aus zugänglichen Ausgangsverbindungen hergestellt werden.
Wie oben angegeben, treten die Verbindungen der Formel I als geometrische Isomere auf.
Die geometrische Isomerieform der nach obigem Verfahren erhaltenen Verbindungen der Formel I hängt von der Konfiguration der Ausgangsverbindungen und den genauen Reaktionsbedingungen ab. Beispielsweise erhält man Verbindungen der Formel I, insbesondere oder überwiegend in Trans Form, falls man von Verbindungen der Formel II ausgeht, die insbesondere oder überwiegend eine Trans-Form besitzen. Zu Verbindungen der Formel II, die sich insbesondere oder überwiegend in Trans-Form befinden, gelangt man direkt unter Verwendung des obigen Verfahrens, das die Säurebehandlung von Verbindungen der Formel III zum Gegenstand hat.
Eine weitere Möglichkeit, die Ausgangsverbindungen insbesondere oder überwiegend in Trans-Form zu erhalten, besteht darin, dass man erhaltene Verbindungen mit UV-Licht bestrahlt und die hierbei gebildeten Isomerengemische anschliessend auf an sich bekannte Weise trennt.
Bestimmte Formen der Verbindungen der Formel I, die nach obigem Verfahren erhalten werden, können ebenfalls, beispielsweise durch UV-Bestrahlung, in ihrer Konfiguration verändert und die erhaltenen isomeren Gemische falls erwünscht auf an sich bekannte Weise getrennt werden.
Die Verbindungen der Formel I besitzen pharmakodynamische Eigenschaften. Insbesondere besitzen die Verbindungen eine entzündungshemmende Wirkung, wie dies beispielsweise den Resultaten des bekannten Carrageenanödem
Test bei der Ratte zu entnehmen ist. Die Verbindungen der Formel I können deshalb als entzündungshemmende Mittel verwendet werden.
Die geeignete tägliche Dosis beträgt von 70-1500 mg, die zweckmässigerweise in kleineren Dosen von 17,5-750 mg 24mal täglich oder in Retardform verabreicht werden.
Die Verbindungen können zusammen mit üblichen pharmazeutischen verträglichen Verdünnungsmitteln oder Trägerstoffen und gegebenenfalls zusammen mit anderen Zusätzen in Form von Tabletten oder Kapseln verabreicht werden.
In dem Schweizer Patent 596 122 wird ein Verfahren zur Herstellung von anti-inflammatorischen Wirkstoffen der Formel
EMI2.1
beschrieben, worin
R Wasserstoff, Fluor, Chlor oder Brom und Rl Alkyl mit 1-3 Kohlenstoffatomen bedeuten,
Y für Brom, Jod, Isobutyl, tert.-Butyl, Cyclohexyl, Cyclohexenyl oder für einen Rest der Formel
EMI2.2
worin R5 Wasserstoff, Fluor, Chlor, Brom oder Alkoxy mit 1-4 Kohlenstoffatomen bedeutet oder für einen Rest der Formel
EMI2.3
steht,
worin
R6 und R7 gleichartig oder verschieden sind und je Alkyl mit 1-3 Kohlenstoffatomen bedeuten oder
R6 und R, zusammen eine -(CH2)n-Gruppe, worin n 4 die -CH2-CH2-O-CH2-Gruppe oder die -CH2-CH=CH-CH2-Gruppe oder eine -CH2-CH2-NR8-CH2CH2-Gruppe, worin R8 Wasserstoff oder Alkyl mit 1-3 Kohlenstoffatomen bedeutet, bilden.
Verbindungen, die in der transisomeren Form vorliegen, werden bevorzugt.
Gemäss der vorliegenden Erfindung werden nun zwei weitere Wirkstoffe der obigen Formel erhalten, welche ebenfalls anti-inflammatorische Eigenschaften besitzen: - trans-4-(p-Cyclohexylphenyl)-3 -penten-2-ol, Smp. 73-74 C und - trans-4-(p-Biphenyl)-3-hexen-2-ol, Smp. 73-74C.
Diese Verbindungen können analog Beispiel 1 des vorgenannten Schweizer Patentes unter Verwendung von entsprechenden Mengen geeigneter Ausgangsmaterialien hergestellt werden.
** WARNING ** Beginning of DESC field could overlap end of CLMS **.
PATENT CLAIM
Process for the preparation of phenylalkenols of the formula I.
EMI1.1
in transform, in which either Y is cyclohexyl and R1 is methyl or Y is phenyl and R1 is ethyl, characterized in that the carbonyl group of compounds of the formula II
EMI1.2
in which R1 and Y have the above meanings, reduced in an inert organic solvent and under anhydrous conditions and the compound obtained is, if necessary, converted into the transform.
The invention relates to a process for the preparation of new phenylalkenols of the formula I.
EMI1.3
in transform, in which either Y is cyclohexyl and R1 is methyl or Y is phenyl and R1 is ethyl.
The method is characterized in that the carbonyl group of compounds of formula II
EMI1.4
in which R1 and Y have the above meanings, reduced in an inert organic solvent and under anhydrous conditions and the compound obtained is, if necessary, converted into the transform.
Compounds of the formula II are reduced in a manner customary for the reduction of aliphatic ketones to aliphatic secondary alcohols, for example with the aid of a complex metal hydride such as sodium aluminum diethyl dihydride or lithium aluminum tri-butoxyhydride. The reduction is carried out in an inert organic solvent, for example an ether such as diethyl ether, tetrahydrofuran or dioxane, or an aromatic solvent such as benzene, toluene or pyridine. The reaction temperature is conveniently from -10 to +40 ° C., preferably from 5 to + 15 ° C.
The compounds of the formula I obtained can be isolated and purified in a manner known per se.
The compounds of the formula I occur as geometric isomers and can be obtained as pure cis or trans isomers or as isomer mixtures. The latter can be separated into the individual isomers in a manner known per se. The compounds are usually obtained in pure trans isomeric form or in the form of isomeric mixtures in which the trans isomeric form predominates, for example in an amount of 60-95%, preferably 70-95%, in particular 80-95%.
The compounds of the formula II which are used as starting compounds in the process can be prepared by adding compounds of the formula III,
EMI1.5
where R1 and Y are as defined above, treated with acids.
The acid treatment of compounds of the formula III is carried out using a strong protonating agent as the acid source in the presence of hydroxy, lower acyloxy or lower alkoxy ions. Suitable protonizing agents are, for example, mineral acids such as hydrochloric acid, hydrobromic acid or sulfuric acid, and aromatic lower sulfonic acids such as p-toluenesulfonic acid. Suitable hydroxy, lower acyloxy (with 2-4 carbon atoms) and lower alkoxy (with 1-4 carbon atoms) anions are obtained by adding lower alkanols such as methanol, esters such as ethyl orthoformate and organic acids and anhydrides such as acetic acid or acetic anhydride. If desired, an excess of such agents can be used as the reaction medium. However, the reaction medium can also be formed by an inert organic solvent.
The reaction is conveniently carried out at temperatures of 10-100 ° C., preferably 15-35 ° C. If hydrochloric acid or hydrobromic acid are used for the reaction, a mixture of the desired compounds of formula II is obtained and 4 substituted phenyls are formed as by-products -4-alkyl-2-chloro (or bromo) -1,3-butadienes.
The connections can be separated in a manner known per se.
The compounds of the formula II obtained can be isolated and purified in a manner known per se.
The compounds of the formula III are either known or can be prepared in a manner known per se from accessible starting compounds.
As indicated above, the compounds of the formula I occur as geometric isomers.
The geometric isomerism of the compounds of the formula I obtained by the above process depends on the configuration of the starting compounds and the precise reaction conditions. For example, compounds of the formula I are obtained, in particular or predominantly in the trans form, if one starts out from compounds of the formula II which in particular or predominantly have a trans form. Compounds of the formula II, which are in particular or predominantly in the trans form, can be obtained directly using the above process, which relates to the acid treatment of compounds of the formula III.
Another possibility of obtaining the starting compounds, in particular or predominantly in the trans form, consists in irradiating the compounds obtained with UV light and then separating the isomer mixtures formed in this way in a manner known per se.
Certain forms of the compounds of the formula I which are obtained by the above process can likewise be changed in their configuration, for example by UV irradiation, and the isomeric mixtures obtained can, if desired, be separated in a manner known per se.
The compounds of the formula I have pharmacodynamic properties. In particular, the compounds have an anti-inflammatory effect, as is the case, for example, with the results of the known carrageenan edema
Test can be found in the rat. The compounds of formula I can therefore be used as anti-inflammatory agents.
The suitable daily dose is 70-1500 mg, which are conveniently administered in smaller doses of 17.5-750 mg 24 times a day or in sustained-release form.
The compounds can be administered together with customary pharmaceutically acceptable diluents or carriers and optionally together with other additives in the form of tablets or capsules.
The Swiss patent 596 122 describes a process for the production of anti-inflammatory active ingredients of the formula
EMI2.1
described in which
R is hydrogen, fluorine, chlorine or bromine and Rl is alkyl with 1-3 carbon atoms,
Y stands for bromine, iodine, isobutyl, tert-butyl, cyclohexyl, cyclohexenyl or for a radical of the formula
EMI2.2
in which R5 is hydrogen, fluorine, chlorine, bromine or alkoxy having 1-4 carbon atoms or is a radical of the formula
EMI2.3
stands,
wherein
R6 and R7 are identical or different and each represent alkyl with 1-3 carbon atoms or
R6 and R, together a - (CH2) n- group, wherein n 4 is the -CH2-CH2-O-CH2- group or the -CH2-CH = CH-CH2- group or a -CH2-CH2-NR8-CH2CH2 -Group in which R8 is hydrogen or alkyl having 1-3 carbon atoms.
Compounds that exist in the trans isomeric form are preferred.
According to the present invention, two further active ingredients of the above formula are now obtained, which likewise have anti-inflammatory properties: trans-4- (p-cyclohexylphenyl) -3-penten-2-ol, melting point 73-74 ° C. and - trans -4- (p-Biphenyl) -3-hexen-2-ol, m.p. 73-74C.
These compounds can be prepared analogously to Example 1 of the aforementioned Swiss patent using appropriate amounts of suitable starting materials.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1485575A CH609663A5 (en) | 1975-11-17 | 1975-11-17 | Process for the preparation of novel phenylalkenols |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1485575A CH609663A5 (en) | 1975-11-17 | 1975-11-17 | Process for the preparation of novel phenylalkenols |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH609663A5 true CH609663A5 (en) | 1979-03-15 |
Family
ID=4404347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1485575A CH609663A5 (en) | 1975-11-17 | 1975-11-17 | Process for the preparation of novel phenylalkenols |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH609663A5 (en) |
-
1975
- 1975-11-17 CH CH1485575A patent/CH609663A5/en not_active IP Right Cessation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2742547C2 (en) | ||
| DE1543427C3 (en) | ||
| CH616136A5 (en) | Process for the preparation of novel polyene compounds | |
| CH494730A (en) | Dibenzo cycloheptenes | |
| DE2439294A1 (en) | NEW PHENYL ALKENOLS AND ALCANOLS AND PROCESS FOR THEIR PRODUCTION | |
| DE2424806A1 (en) | ANTI-COAGULANTIES, METHOD FOR MANUFACTURING AND USING them | |
| DE69029433T2 (en) | Cycloaliphatic carbinols and their use as starting compounds for the preparation of furan derivatives | |
| DE1223974B (en) | Fragrance compositions | |
| DE2505446A1 (en) | NEW ORGANIC COMPOUNDS AND PROCEDURES FOR THEIR PRODUCTION | |
| DE2622611C2 (en) | Fragrance mixtures, processes for their production and their use as fragrances | |
| DE1942521A1 (en) | Cyclopropanecarboxylic acid derivatives and processes for their preparation | |
| CH591415A5 (en) | 3-(Tri-substd. benzoyl) propionic acids - as relaxants or spasmolytics for the gall bladder | |
| AT203485B (en) | Process for the production of new dinitrophenyl methacrylates | |
| DE1134784B (en) | Fragrance | |
| DE1468279A1 (en) | Process for the preparation of dibenzocycloheptenes | |
| AT356645B (en) | METHOD FOR PRODUCING NEW PHENYLBUTENONE | |
| DE1493323B2 (en) | 1- (P-HYDROXYPHENYL) -2-PHENYL-6METHOXY-3,4-DIHYDRONAPHTHALIN, ITS PHARMACOLOGICALLY APPROPRIATE SALT AND METHOD FOR PREPARING THESE COMPOUNDS | |
| DE956950C (en) | Process for the preparation of isomeric 1, 1, 6-trimethyl-6-oxyoctahydronaphthalenes | |
| AT215973B (en) | Process for the production of unsaturated acids | |
| DE2705602A1 (en) | PROCESS FOR MANUFACTURING AN UNSATATULATED KETONE | |
| AT256844B (en) | Process for the preparation of new 6,11-dihydrodibenzo- [b, e] -thiepinen | |
| CH605528A5 (en) | Phenyl-alkenone and phenyl-alkadiene deriv. prodn. | |
| AT373254B (en) | METHOD FOR PRODUCING NEW 5-SUBST.-10,11-DIHYDRO-5H-DIBENZO (A, D) -CYCLOHEP EN-5,10-IMINES AND THEIR SALTS AND OPTICAL ISOMERS | |
| CH410931A (en) | Process for the preparation of 5-oxy-dibenzocycloheptene derivatives | |
| DE2720321A1 (en) | NEW BENZOFURAN AND BENZOXE PINE DERIVATIVES |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PLZ | Patent of addition ceased | ||
| PL | Patent ceased |