DD148631A5 - METHOD OF SELECTIVELY ALKYLATING A 3- (2,4-DIHYDROXYPHENYL) CYCLOALKANONE - Google Patents
METHOD OF SELECTIVELY ALKYLATING A 3- (2,4-DIHYDROXYPHENYL) CYCLOALKANONE Download PDFInfo
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- DD148631A5 DD148631A5 DD78218654A DD21865478A DD148631A5 DD 148631 A5 DD148631 A5 DD 148631A5 DD 78218654 A DD78218654 A DD 78218654A DD 21865478 A DD21865478 A DD 21865478A DD 148631 A5 DD148631 A5 DD 148631A5
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- German Democratic Republic
- Prior art keywords
- arh
- dihydroxyphenyl
- cycloalkanone
- carbon atoms
- methyl
- Prior art date
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- -1 2,4-DIHYDROXYPHENYL Chemical class 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims abstract description 13
- 230000002152 alkylating effect Effects 0.000 title claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000005804 alkylation reaction Methods 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000029936 alkylation Effects 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims abstract description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract 2
- 229910052794 bromium Inorganic materials 0.000 abstract 2
- 125000005905 mesyloxy group Chemical group 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SGJBIFUEFLWXJY-UHFFFAOYSA-N 1-(dibutoxymethoxy)butane Chemical compound CCCCOC(OCCCC)OCCCC SGJBIFUEFLWXJY-UHFFFAOYSA-N 0.000 description 1
- RWNXXQFJBALKAX-UHFFFAOYSA-N 1-(dipropoxymethoxy)propane Chemical group CCCOC(OCCC)OCCC RWNXXQFJBALKAX-UHFFFAOYSA-N 0.000 description 1
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 1
- HJIQNULRLPDBIJ-UHFFFAOYSA-N 3-(2,4-dihydroxyphenyl)cyclohexan-1-one Chemical compound OC1=CC(O)=CC=C1C1CC(=O)CCC1 HJIQNULRLPDBIJ-UHFFFAOYSA-N 0.000 description 1
- VUEQAXHGKCKXFV-UHFFFAOYSA-N 4-phenylbutyl methanesulfonate Chemical compound CS(=O)(=O)OCCCCC1=CC=CC=C1 VUEQAXHGKCKXFV-UHFFFAOYSA-N 0.000 description 1
- ZWXBHANUTLAJCB-UHFFFAOYSA-N 6-phenylhexyl methanesulfonate Chemical compound CS(=O)(=O)OCCCCCCC1=CC=CC=C1 ZWXBHANUTLAJCB-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 1
- ZFLRDIUZHADLSV-UHFFFAOYSA-N heptan-2-yl methanesulfonate Chemical compound CCCCCC(C)OS(C)(=O)=O ZFLRDIUZHADLSV-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical group CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/117—Esters of phosphoric acids with cycloaliphatic alcohols
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Abstract
Die Erfindung betrifft ein Verfahren zur selektiven Alkylierung eines 3-(2,4-Dihydroxyphenyl)cycloalkanons mit 5 bis 8 Kohlenstoffatomen in der Cycloalkylkomponente an der 4-Hydroxygruppe. Erfindungsgemaesz wird das obige Cycloalkanon zunaechst mit enem Alkohol mit 1 bis 4 Kohlenstoffatomen umgesetzt.Das dabei erhaltene Ketal wird sodann mit einer Verbindung W-Z-Y- alkyliert.Hierbei sind bezeichnet mit W: Wasserstoff, Pyridyl o. Formel W&ind1! = Wasserstoff,Fluor o. Brom,Z: Alkylen mit 1 bis 13 Kohlenstofatomen;Y: Chlor,Brom,Mesyloxy o. Tosyloxy.Im abschlieszenden dritten Verahrensschritt wird das alkylierte Produkt des zweiten Schrittes mit verduennter Saeure behandelt u. damit deketalisiert.The invention relates to a process for the selective alkylation of a 3- (2,4-dihydroxyphenyl) cycloalkanone having 5 to 8 carbon atoms in the cycloalkyl moiety at the 4-hydroxy group. According to the invention, the above cycloalkanone is first reacted with an alcohol having from 1 to 4 carbon atoms. The ketal thus obtained is then alkylated with a compound W-Z-Y-. Here, W is hydrogen, pyridyl, or formula W & ind1! = Hydrogen, fluorine or bromine, Z: alkylene having 1 to 13 carbon atoms, Y: chlorine, bromine, mesyloxy or tosyloxy. In the concluding third process step, the alkylated product of the second step is treated with dilute acid u. deketalized with it.
Description
1271955 -ι- 218 654 1271955- ι-218 654
Verfahren zur selektiven Alkylierung eines 3-(2,4-Dihydro-Process for the selective alkylation of a 3- (2,4-dihydroxy)
xyphenyl)cycloalkanonexyphenyl) cycloalkanones
Die Erfindung betrifft ein Verfahren zur selektiven Alkylierung eines 3-(2>4-Dihydroxyphenyl)cycloalkanons, das bei der Herstellung von anaigetischen 3-/2-Hydroxy-4-(substituierten) phenyl_7cycloalkanonen und -cycloalkanolen mit Vorteil angewendet v/erden kann.The invention relates to a process for the selective alkylation of a 3- (2> 4-dihydroxyphenyl) -cycloalkanone, which can be used with advantage in the preparation of anaigetic 3- / 2-hydroxy-4- (substituted) phenyl_7cycloalkanonen and -cycloalkanolen.
In der prioritätsgleichen Patentanmeldung AP AkOaus der die vorliegende Anmeldung ausgeschieden wurde, ist die Herstellung der vorgenannten 3-/2-Hydroxy-4-(substituierten) pheny^/cycloalkanone und -cycloalkanole beschrieben.In the priority same patent application AP AkO from which the present application has been eliminated, the preparation of the aforementioned 3- / 2-hydroxy-4- (substituted) pheny ^ / cycloalkanone and cycloalkanols is described.
" ", :' ι; ι η ~ η * c *> '*J c- ο ν "", : ι; ι η ~ η * c *>'* J c- ο ν
L· J.v^M. i j'j b*ο *j ( ο ο ( . - 2 - L · Jv ^ M. i j'j b * ο * j ( ο ο (. - 2 -
-2- 218 654-2- 218 654
Bei diesem Verfahren kann u.a. ein .,Verfahren zur Alkylierung eines 3~(2,4-Dihydroxyphenyl)cycloalkanons zur Anwendung kommen.In this method, i.a. a., Process for the alkylation of a 3 ~ (2,4-dihydroxyphenyl) cycloalkanone are used.
Ziel der Erfindung;Aim of the invention ;
Mit der Erfindung soll ein günstiges Verfahren zur selektiven Alkylierung eines 3-(2,4-Dihydroxyphenyl)cycloalkanons mit 5 bis 8 Kohlenstoffatomen in der Cycloalkylkomponente an der 4-Hydroxygruppe zur Verfugung gestellt werden.The invention seeks to provide a convenient process for the selective alkylation of a 3- (2,4-dihydroxyphenyl) cycloalkanone of 5 to 8 carbon atoms in the cycloalkyl moiety at the 4-hydroxy group.
Darlegung des Wesens der Erfindung; Darlegun g of W esens of the invention;
Das erfindungsgemäße Verfahren umfaßt als ersten Schritt die Umwandlung des 3-(2,4-Dihydroxyphenyl)cycloalkanons in ein Ketal mit einem Alkohol mit 1 bis 4 Kohlenstoffatomen in Gegenwart einer Säure wie Schwefelsäure, p-Toluolsulfonsäure oder Chlorwasserstoff unter Bedingungen, durch die das als Nebenprodukt vorhandene Wasser entfernt v/ird. Ein bevorzugtes Verfahren besteht in der Umsetzung des 3-(2,4-Dihydroxyphenyl)cycloalkanons mit einem Orthoameisensäureester in Lösung mit einem Alkohol, der der Alkoholkomponente des Orthoameisensäureesters entspricht. Trimethylorthoformiat und Methanol sind bevorzugte Reaktanten in Verbindung mit konzentrierter Schwefelsäure, wasserfreiem Chlorwasserstoff oder Ammoniumchlorid als Katalysator. Als zweiten Schritt umfaßt das erfindungsgemäße Alkylierungsverfahren das Alkylieren des Produktes des ersten Verfahrensschrittes mit einer Verbindung der Pormel W-Z-X, worin Y aus der Chlor, Brom, Mesy1oxy und Tosyloxy umfassenden Gruppe ausgewählt ist, Z aus der aus -(alkp)- bestehenden Gruppe ausgewählt ist, worin (alk2) Alkylen mit 1 bis 13 Kohlenstoffatomen ist und W aus der aus Wasserstoff, Pyridyl undThe process according to the invention comprises, as a first step, the conversion of 3- (2,4-dihydroxyphenyl) cycloalkanone into a ketal with an alcohol of 1 to 4 carbon atoms in the presence of an acid, such as sulfuric acid, p-toluenesulphonic acid or hydrogen chloride, under conditions as described Byproduct existing water removed v / ird. A preferred method is the reaction of 3- (2,4-dihydroxyphenyl) cycloalkanone with an orthoformate in solution with an alcohol corresponding to the alcohol component of the orthoformate. Trimethyl orthoformate and methanol are preferred reactants in conjunction with concentrated sulfuric acid, anhydrous hydrogen chloride or ammonium chloride as the catalyst. As a second step, the alkylation process of the present invention comprises alkylating the product of the first process step with a compound of the Pormel WZX wherein Y is selected from the group consisting of chloro, bromo, mesyloxy and tosyloxy, Z is selected from the group consisting of - (alkp) in which (alk 2 ) is alkylene having 1 to 13 carbon atoms and W is selected from hydrogen, pyridyl and
-3- 218 6 54-3- 218 6 54
umfassenden Gruppe ausgewählt ist, .wobei W. für Wasserstoff, Fluor oder Chlor bedeutet, in Gegenwart eines Säureakzeptors, z.B. Natrium- .oder Kaliumcarbonat.in which W is hydrogen, fluorine or chlorine, in the presence of an acid acceptor, e.g. Sodium or potassium carbonate.
Das so alkylierte Ketal wird sodann in einem dritten Verfahrensschritt in an sich bekannter Weise durch Behandeln mit wäßriger Säure deketalisiert.The alkylated ketal is then deketalized in a conventional manner by treatment with aqueous acid in a third step.
An einigen Beispielen soll die Erfindung nachfolgend näher erläutert werden.In some examples, the invention will be explained in more detail below.
ß-(2,4-Dihydroxyphenyl)cyclohexanomethylketal Zu einer eine Temperatur von 0 0C aufweisenden Lösung aus 7|0 g (33>O mMol) 3-(2,4-Dihydroxyphenyl)cyclohexanon in 100 ml Methanol und 15 ml Trimethylorthoformiat wurden 10 Tropfen konzentrierte Schwefelsäure gegeben. Das Reaktionsgemisch wurde anschließend drei Stunden ohne Kühlung gerührt, so daß die Temperatur auf Raumtemperatur ansteigen konnte, und'anschließend durch die Zugabe eines Überschusses von festem liatriumhydrogencarbonat abgeschreckt. Das Reaktionsgemisch wurde unter reduziertem Druck eingedampft und der Rückstand in 200 ml Wasser/250 ml Äther gelöst. Der Ätherextrakt wurde einmal mit 150 ml gesättigtem liatriumhydrogencarbonat gewaschen, über Magnesiumsulfat getrocknet und eingedampft. Der ölige Rückstand wurde aus Äther-Pentan auskristallisiert und ergab 5,74 g (77 %) der Titelverbindung mit einem Schmelzpunkt von 129 bis 130 0C. β- (2,4-Dihydroxyphenyl) cyclohexanomethyl ketal To a temperature of 0 0 C having solution of 7 | 0 g (33> O mmol) of 3- (2,4-dihydroxyphenyl) cyclohexanone in 100 ml of methanol and 15 ml trimethyl orthoformate were Added 10 drops of concentrated sulfuric acid. The reaction mixture was then stirred for three hours without cooling, so that the temperature could rise to room temperature, and then quenched by the addition of an excess of solid sodium hydrogencarbonate. The reaction mixture was evaporated under reduced pressure and the residue was dissolved in 200 ml of water / 250 ml of ether. The ether extract was washed once with 150 ml of saturated sodium bicarbonate, dried over magnesium sulfate and evaporated. The oily residue was crystallized from ether-pentane to give 5.74 g (77 %) of the title compound having a melting point of 129 to 130 ° C.
r TT 'S PMR :d qDC1 1,4 - 2,5 (m, Methylene), 3,20 (m, Methin), 3,50 (s, OMe), 5,58 (s, OH), 6,38 (dd, J = 8 und 2 Hz, ArH), 6,48 (s, überlappt 6,38) und 6,87 (d, J = 8 Hz).r TT 'S PMR: dq DC1 1.4-2.5 (m, methylene), 3.20 (m, methine), 3.50 (s, OMe), 5.58 (s, OH), 6, 38 (dd, J = 8 and 2 Hz, ArH), 6.48 (s, overlapping 6.38) and 6.87 (d, J = 8 Hz).
IR: (IiBr) -3289, 1629,. 1613 und 1597 cm"1.IR: (IiBr) -3289, 1629 ,. 1613 and 1597 cm " 1 .
MS: 220 (M+), 205, 203, 188, 177, 161 und 136.MS: 220 (M + ), 205, 203, 188, 177, 161 and 136.
-4- 218 654-4- 218 654
Analyse: Berechnet für C13H16O3: C, 70,89; H, 7,32 %. Gefunden: C, 70,79; H, 7,34 %.Analysis: Calculated for C 13 H 16 O 3 : C, 70.89; H, 7.32%. Found: C, 70.79; H, 7.34%.
Durch die Wiederholung dieser Verfahrensweise,jedoch unter Verwendung von Triäthyl-, Tri-n-propyl- oder Tri-n-butylorthoformiat anstelle von Trimethylorthoformiat und Äthyl-, n-Propyl- oder n-Butylalkohol anstelle von Methanol entstehen die entsprechenden Äthyl-, n-Propyl- und n-Butylketale.By repeating this procedure, but using triethyl, tri-n-propyl or tri-n-butyl orthoformate instead of trimethyl orthoformate and ethyl, n-propyl or n-butyl alcohol instead of methanol, the corresponding ethyl, n Propyl and n-butyl ketals.
3-/2-Hedroxy-4-(4-phenylbutfyloxy)phenyl7cyclohexanonmethylketal 3- / 2-Hedroxy-4- (4-phenyl-lbut f yloxy) phenyl7cy clohexanonmet h ylketal
Ein Gemisch-aus 5,03 g (22,8 mMol) 3-(2,4-Dihydroxyphenyl)-cyclohexanonmethylketal, 10,1 g (73,2 mMol) wasserfreiem Kaliumcarbonat und 6,12 g (26,8 mMol) 4-Phenylbutylmethan-Bulfonat in 25 ml N,N-Dimethylformamid wurde 4 Stunden lang auf 85 bis 100 0C gehalten. Das Reaktionsgemisch wurde gekühlt, und es wurden 200 ml Wasser/200 ml Äther zugesetzt. Der Ätherextrakt wurde zweimal mit 200 ml Wasser gewaschen, über Magnesiumsulfat getrocknet und zu einem Öl eingedampft. Das Öl wurde mit Hilfe von Säulenchromatografie auf 400 g Silicagel unter Eluieren mit einem 2:1-Gemisch von Pentan und Äther gereinigt und ergab 7,4 g (92 %) der Titelverbindung in Porm eines Öles.A mixture of 5.03 g (22.8 mmol) of 3- (2,4-dihydroxyphenyl) cyclohexanone methyl ketal, 10.1 g (73.2 mmol) of anhydrous potassium carbonate and 6.12 g (26.8 mmol) of 4 Phenylbutylmethane-Bulfonat in 25 ml of N, N-dimethylformamide was maintained at 85 to 100 0 C for 4 hours. The reaction mixture was cooled and 200 ml of water / 200 ml of ether was added. The ether extract was washed twice with 200 ml of water, dried over magnesium sulfate and evaporated to an oil. The oil was purified by column chromatography on 400 g of silica gel eluting with a 2: 1 mixture of pentane and ether to give 7.4 g (92 %) of the title compound in the form of an oil.
PMR:cT ™? 2,63 (m, Benzylmethylen), 3,33 (s, OCH-),PMR: cT ™? 2.63 (m, benzylmethylene), 3.33 (s, OCH-),
3 ^ 3 ^
3,85 (bt, J = 6 Hz, OCH2), 6,42 (dd, J = 8 und 2 Hz, ArH), 6,50 (bs, überlappt tf 6,42, ArH), 6,92 (d, J = 8 Hz, ArH) und 7,30 (s, PhH)3.85 (bt, J = 6 Hz, OCH 2 ), 6.42 (dd, J = 8 and 2 Hz, ArH), 6.50 (bs, overlaps tf 6.42, ArH), 6.92 ( d, J = 8 Hz, ArH) and 7.30 (s, PhH)
IR: (CHCl3), 1623 und 1590 cm"1 IR: (CHCl 3 ), 1623 and 1590 cm -1
MS: m/e 352 (M+) und 91MS: m / e 352 (M + ) and 91
Analyse: Berechnet für C23H28O-: C, 78,37; H, 8,01 %, Gefunden: C, 78,34; H, 8,07 %* Analysis: Calculated for C 23 H 28 O: C, 78.37; H, 8.01 %, Found: C, 78.34; H, 8.07 % *
-5- 218 654-5- 218 654
Die folgenden Verbindungen wurden in ähnlicher Weise hergestellt, jedoch v/urde das passende Mesylatderivat anstelle von 4-Phenylbutylmethansulfonat verwendet.The following compounds were prepared in a similar manner, but the appropriate mesylate derivative was used instead of 4-phenylbutyl methanesulfonate.
3-/2'-Hydroxy-4~(2-hept.YloxrY)phenyl7c.yclohexanonmethylketal3- / 2'-hydroxy-4 ~ (2-r hept.Ylox Y) phenyl7c.yclohexanonmethylketal
6,13 g, 75 %) in Porm eines Öles aus 5,7 g (25,9 mMol) 3_(2,4-Dihydroxyphenyl)cyclohexanonmethylketal und (2-Heptyl) methansulfonat (6,2 g 32,3 mMol).6.13 g, 75 %) in the form of an oil of 5.7 g (25.9 mmol) of 3 (2,4-dihydroxyphenyl) cyclohexanone methyl ketal and (2-heptyl) methanesulfonate (6.2 g, 32.3 mmol).
IR: (CHCl3) 1637 und 1600 cm"1.IR: (CHCl 3 ) 1637 and 1600 cm -1 .
MS: m/e 318 (M+), 286, 274, 220, 204 und 178.MS: m / e 318 (M + ), 286, 274, 220, 204 and 178.
PtIR: cT ^1 0,90 (m, Methyl), 1,18 (d, J = 7 Hz, Methyl), 3,03 (m, Methin), 3,35 (s, KeO), 4,14 (m, Methin), 6,35 (m, ArH) und 6,68 (d, J = 8 Hz, ArH).PtIR: cT ^ 1 0.90 (m, methyl), 1.18 (d, J = 7Hz, methyl), 3.03 (m, methine), 3.35 (s, KeO), 4.14 ( m, methine), 6.35 (m, ArH) and 6.68 (d, J = 8 Hz, ArH).
3-/2-Hydroxy-4-(2-octyloxy)phenyl7cyclohexanonmethylketal in Form eines Öls (5,03 g, 58 %) von 3-(2,4-Dihydroxyphenyl)cyclohexanonmethylketal (5,7 g, 25,9 mMol) und 2-0ctyl)methansulfonat (7,3 g, 35,1 mMol).3- / 2-Hydroxy-4- (2-octyloxy) phenyl-7- cyclohexanone methylated as an oil (5.03 g, 58 %) of 3- (2,4-dihydroxyphenyl) cyclohexanone methyl ketal (5.7 g, 25.9 mmol) and 2-0ctyl) methanesulfonate (7.3 g, 35.1 mmol).
IR: (CIICl3) 1639 und 16OO cm"1.IR: (CIICl 3 ) 1639 and 1600 cm " 1 .
MS: m/e 332 (M+), 300, 289, 272 und 220.MS: m / e 332 (M + ), 300, 289, 272 and 220.
PKR: d ^1 0,87 (m, Methyl), 3,09 (m, Methin), 3,36 (s OMe), 4,20 (m, Methyl), 6,30 (m, ArII) und 6,80 (d, J = 8 Hz, ArH).PKR: d ^ 1 0.87 (m, methyl), 3.09 (m, methine), 3.36 (s OMe), 4.20 (m, methyl), 6.30 (m, ArII) and 6 , 80 (d, J = 8 Hz, ArH).
3-/2~Hydroxy-4-(2-nonyloxy)phenyl7cyclohexanonmethylketal (5,23 g, 59 %) in Porm eines Öls von 3-(2,4-Dihydroxyphenyl) cyclohexanonmethylketal (5,7 g, 25,9 mMol) und (2-Iionyl) methansulfonat (7,9 g, 35,5 mMol). 3- / 2-Hydroxy-4- (2-nonyloxy) phenyl-7-cyclohexanone methyl ketal (5.23 g, 59 %) in the form of an oil of 3- (2,4-dihydroxyphenyl) cyclohexanone methyl ketal (5.7 g, 25.9 mmol) and (2-ionyl) methanesulfonate (7.9 g, 35.5 mmol).
IR: (CHCl3) 1634 und 1590 cm"1.IR: (CHCl 3 ) 1634 and 1590 cm -1 .
MS: m/e 346 (M+), 314, 220, 188 und I6I.MS: m / e 346 (M + ), 314, 220, 188 and I6I.
KIR: cT ^1 0,87 (m, Methyl), 3,10 (m, Methin), 3,39 (s, OMe), 4,22 (m, Methin), 6,36 (m, ArH) und 6,80 (d, J = 8 Hz, ArH).KIR: cT ^ 1 0.87 (m, methyl), 3.10 (m, methine), 3.39 (s, OMe), 4.22 (m, methine), 6.36 (m, ArH) and 6.80 (d, J = 8 Hz, ArH).
218 654218 654
3-/2-Hydroxy-4-(4-phenyl)butoxy)phenyl7cyclohexanonmethylketal in Form eines Öls (5,1 g, 57 %) von 3-(2,4-Dihydroxyphenyl)cyclohexanonmethylketal (5*7 g> 25,9 mMol) und 2-(4-Phenylbutyl)-methansulfonat (8,Og, 35,0 mMol). IR: (CHCl ) 1639 und 1603 cm"1 3- / 2-hydroxy-4- (4-phenyl) butoxy) phen yl7cyclohexano nm ethyl ketal of 3- (2,4-dihydroxyphenyl) cyclohexanonmethylketal (in the form of an oil (5.1 g, 57%) 5 * 7 g > 25.9 mmol) and 2- (4-phenylbutyl) -methanesulfonate (8.0 g, 35.0 mmol). IR: (CHCl) 1639 and 1603 cm -1
MS: m/e 352 (M+), 320, 220 und 188.MS: m / e 352 (M + ), 320, 220 and 188.
HSR:S QPQ1 1,29 (d, J = 6 Hz, Methyl), 3,07 (m, Methin), 3,38 (s, OMe), 4,26 (m, Methin), 6,30 (m, ArH), 6,80 (d, J = 9 Hz, ArH) und 7,16 (s, Ph).HSR: S QPQ 1 1.29 (d, J = 6 Hz, methyl), 3.07 (m, methine), 3.38 (s, OMe), 4.26 (m, methine), 6.30 ( m, ArH), 6.80 (d, J = 9 Hz, ArH) and 7.16 (s, Ph).
3-/~2~Hydroxy-4- (2- (6-phenyJJhgxylpxy) phenyl7cycl ohexanonme thylketal (5,3 g, 54 %) in Form eines Öls von 3-(2,4-DihydroxyphenyDcyclohexanonmethylketal (5,7 g, 25,9 mMol) und 2~(6-Phenylh.exyl)methansulfonat (9,0 g, 35,5 mMol). 3- / 2- 2-Hydroxy-4- (2- (6- pyrene- yl xyloxy) phenyl) -cyclohexyl thyl ketal (5.3 g, 54 %) as an oil of 3- (2,4-dihydroxyphenyldcyclohexanone methyl ketal (5, 7 g, 25.9 mmol) and 2 ~ (6-phenylhexyl) methanesulfonate (9.0 g, 35.5 mmol).
IR: (CHCl3) 1634 und 1597 cm"1.IR: (CHCl 3 ) 1634 and 1597 cm -1 .
MS: m/e 380,2342 (M+, C25H32O3), 220,1088, 188,0986 und 177,0550.MS: m / e 380.2342 (M + , C 25 H 32 O 3 ), 220.1088, 188.0986 and 177.0550.
PIvIR: cT ™S 1,26 (d, J = 6 Hz, Methyl), 3,10 (m, Methin),PIvIR: cT ™ S 1.26 (d, J = 6 Hz, methyl), 3.10 (m, methine),
3,40 (s, OMe), 4,22 (m, Methin), 6,30 (m, ArH), 6,83 (d, J = 9 Hz, ArH) und 7,18 (s, Ph).3.40 (s, OMe), 4.22 (m, methine), 6.30 (m, ArH), 6.83 (d, J = 9Hz, ArH), and 7.18 (s, Ph).
[3~/2"-Hydroxy-4,- (4-phenylbutyloxy) phenyl7cyclohexanon [ 3 ~ / 2 "-hydroxy-4 , - (4-phenylbutyloxy) -phenylcyclohexanone
Ein Gemisch aus 6,8 g (19,3 mMol) 3-/^-Hydroxy-4-(4-phenylbutyloxy) pheny].7cyclohexanonmethylketal, 100 ml 21ί Chlorwasserstoff säure und 60 ml Dioxan wurde eine Stunde lang unter Rückfluß gekocht. Das Reaktionsgemisch wurde gekühlt und zu 300 ml Äther/500 ml gesättigtem Natriumchlorid gegeben. Der Ätherextrakt wurde einmal mit 500 ml gesättigtem Natriumchlorid und 500 ml gesättigtem Neitriumhydrogencarbonat gewaschen, über Magnesiumsulfat getrocknet und zu einem Öl eingedampft. Das Öl vnirde mit Hilfe der Säulenchromatografie auf 400 g Silicagel unter Eluierung mit einem 1:1-GemischA mixture of 6.8 g (19.3 mmol) of 3 - / ^ - H ydroxy-4- (4-phenylbutyloxy) phenyl] .7cyclohexanonmethylketal, 100 ml acid 21ί hydrogen chloride and 60 ml of dioxane was boiled for one hour under reflux. The reaction mixture was cooled and added to 300 ml of ether / 500 ml of saturated sodium chloride. The ether extract was washed once with 500 ml of saturated sodium chloride and 500 ml of saturated sodium bicarbonate, dried over magnesium sulfate and evaporated to an oil. The oil was purified by column chromatography on 400 g of silica gel eluting with a 1: 1 mixture
— 7 —- 7 -
.7. 218 654, 7 . 218 654
von Äther und Cyclohexan gereinigt und ergab 6,4 g (98 %)der Titelverbindung in Form eines Öls.Purified of ether and cyclohexane to give 6.4 g (98 %) of the title compound as an oil.
PMR: (F ^1 2,69 (m, Benzylmethylen), 3,90 (bt, J = 6 Hz, -OCH2), 6,25 - 6,5 (m, ArH), 6,82 (d, J = 8 Hz, ArH) und 7,20 (s, PhH).PMR: (F ^ 1 2.69 (m, benzylmethylene), 3.90 (bt, J = 6 Hz, -OCH 2 ), 6.25-6.5 (m, ArH), 6.82 (d, J = 8 Hz, ArH) and 7.20 (s, PhH).
IR: (CHCl3) 3571, 3333, 1718 (schwach), 1626 und 1595 cm"1. LIS: m/e 388 (H+), 320, 310, 295, 268 und 91.IR: (CHCl 3 ) 3571, 3333, 1718 (weak), 1626 and 1595 cm -1 . LIS: m / e 388 (H + ), 320, 310, 295, 268 and 91.
Die folgenden Verbindungen wurden in der gleichen Weise aus den passenden Ketalen von Beispiel 2 hergestellt:The following compounds were prepared in the same manner from the appropriate ketals of Example 2:
3-/4\.(2-Heptyloxy)-2-hydroxyphenyl7cyclohexanon (4,7 g, 82 %), in Form eines Öls aus 6,0 g (18,8 ml.Tol) des entsprechenden Methylketals. 3- / 4 \. (2-Heptyloxy) -2-hydroxyphenyl-7-cyclohexanone (4.7 g, 82 %) , as an oil of 6.0 g (18.8 mL, thol) of the corresponding methyl ketal.
IR: (CHCl3) 3636', 3390, 1724 (schwach), 1639 und 1600 cm"1.IR: (CHCl 3 ) 3636 ', 3390, 1724 (weak), 1639 and 1600 cm -1 .
MS: m/e 304 (M+), 206, 188, 171, 163 und 137.MS: m / e 304 (M + ), 206, 188, 171, 163 and 137.
PLIR: <f ^1 0,82 (m, Methyl), 1,25 (d, J = 6 Hz, Methyl), 4,15 (m, Seitenkettenmethin), 6,35 (dd, J = 8 und 2 Hz, ArH), 6,35 (d, J = 2 Hz, ArH) und 6,81 (d, J = 8 Hz, ArH).PLIR: <f ^ 1 0.82 (m, methyl), 1.25 (d, J = 6 Hz, methyl), 4.15 (m, side chain methine), 6.35 (dd, J = 8 and 2 Hz , ArH), 6.35 (d, J = 2 Hz, ArH) and 6.81 (d, J = 8 Hz, ArH).
3-/4-(2-0ctyloxy i)~2:rhydroxyphenyl7cyclohexanon (4,1 g, 85 %) in Form eines Öls aus 5,0 g, (15,0 ml.Iol) des entsprechenden Methylketals. 3- / 4- (2-0ctyloxy- i ) -2 : rhydroxyphenyl-7-cyclohexanone (4.1 g, 85 %) as an oil of 5.0 g, (15.0 mL, ofol) of the appropriate methyl ketal.
IR: (CHCl3) 3636, 3378, 1721 (schwach), I63I und 1595 cm"1.IR: (CHCl 3 ) 3636, 3378, 1721 (weak), 1663 and 1595 cm -1 .
MS: m/e 318 (M+), 206, 188, 178 und 161.MS: m / e 318 (M + ), 206, 188, 178 and 161.
r fm Tqr fm Tq
PMR: C J^-JJ1 0,84 (m, Methyl), 4,20 (m, Seitenkettenmethin), 6,39 (dd, J = 8 und 2 Hz, ArH), 6,39 (d, J = 2 Hz, ArH) und 6,83 (d, J = 8 Hz, ArH).PMR: CJ 1 -JJ 1 0.84 (m, methyl), 4.20 (m, side chain methine), 6.39 (dd, J = 8 and 2 Hz, ArH), 6.39 (d, J = 2 Hz, ArH) and 6.83 (d, J = 8 Hz, ArH).
3-/4-(2-ITonyloxy)-2-hydroxyphenyl7cyclohexanon (4,35 g, 89 %), in Form eines Öls aus 5,1 g (14,7 mMol) des entsprechenden Methylketals.3- / 4- (2-ITonyloxy) -2-hydroxyphenyl-7-cyclohexanone (4.35 g, 89 %) , as an oil from 5.1 g (14.7 mmol) of the corresponding methyl ketal.
IR: (CHCl3) 3584, 3367, 1709 (schwach), 1626 und 1587 cm"1. MS: m/e 332 (M+), 206, 187 und 171.IR: (CHCl 3 ) 3584, 3367, 1709 (weak), 1626 and 1587 cm -1 . MS: m / e 332 (M + ), 206, 187 and 171.
-β- 21 8 6 54-β- 21 8 6 54
HMR:(Γ ™S 0,85 (m, Methyl), 4,26 (m, Seitenketten-HMR: (Γ ™ S 0.85 (m, methyl), 4.26 (m, side chain)
methin), 6,39 (dd, J = 9 und. 2 Hz, ArH), 6,39 (d, J = 2 Hz, ArH) und 6,84 (d, J = 8 Hz, ArH).methine), 6.39 (dd, J = 9 and 2 Hz, ArH), 6.39 (d, J = 2 Hz, ArH) and 6.84 (d, J = 8 Hz, ArH).
3-/4- ( 2-( 4-Phenyl) butyloxy)-2-hydroxypheny^cyclohexanon (3>8 g, 79 %) aus 5,0 g (14,2 mMol) des entsprechenden Methylketals in Form eines Öls.3- / 4- (2- (4-phenyl) butyloxy) -2-hydroxypheny ^ cyclohexanone (3-> 8 g, 79 %) from 5.0 g (14.2 mmol) of the corresponding methyl ketal in the form of an oil.
IR: (CHCl3) 3636, 1724 (schwach), 1637 und 16OO cm"1. MS: m/e 338 (M+), 206, 188, 132, 117 und 91.IR: (CHCl 3 ) 3636, 1724 (weak), 1637 and 1600 cm -1 . MS: m / e 338 (M + ), 206, 188, 132, 117 and 91.
PMR: cT ^1 1,19 und 1,27 (d, J = 6 Hz, Methyl), 3,02 (m, Methin in Hemiketalform), 3,73 und 4,22 (m, Methin), 6,30 (dd, J =8 und 2 Hz, ArH), 6,30 (d, J = 2 Hz, ArH), 6,81 (d, J = 2 Hz, ArH) und 7,18 (s, Ph).PMR: cT ^ 1 1.19 and 1.27 (d, J = 6Hz, methyl), 3.02 (m, hemicetaline methine), 3.73 and 4.22 (m, methine), 6.30 (dd, J = 8 and 2 Hz, ArH), 6.30 (d, J = 2 Hz, ArH), 6.81 (d, J = 2 Hz, ArH) and 7.18 (s, Ph).
3~/4i-(2~(6~Phenyl)hexylo3!:,y)~2-ihyidrpxyphenyl7cyclohexanon (4,45 g, 89 %) in Form eines Öls aus 5,2 g (13,6 mMol) des entsprechenden Methylketals.3 ~ / 4 i - (2 ~ (6 ~ phenyl) hexylo 3, y!) ~ 2- hy i i drpx yphen yl7cyclo hexanone (4.45 g, 89%) (in the form of an oil from 5.2 g of 13.6 mmol) of the corresponding methyl ketal.
IR: (CHCl3) 3636, 33SO, 1718, 1637 und I6OO cm"1.IR: (CHCl 3 ) 3636, 33SO, 1718, 1637 and 1600 cm -1 .
MS: m/e 366 (M+), 206, 188 und 91.MS: m / e 366 (M + ), 206, 188 and 91.
PMR:cT ™S 1>25 (d> j = 6 HZ} Methyl)j 3>07 (mj MethinPMR: cT ™ S 1> 25 (d> j = 6HZ} methyl ) j 3> 07 ( mj methine
4,19 (m, Methin), 6,32 (dd, J = 9 und 2 Hz, ArH), 6,32 (d, J a 2 Hz, ArH), 6,78 (d, J = 9 Hz, ArIi) und 7,14 (s, Ph).4.19 (m, methine), 6.32 (dd, J = 9 and 2 Hz, ArH), 6.32 (d, J a 2 Hz, ArH), 6.78 (d, J = 9 Hz, ArIi) and 7.14 (s, Ph).
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83310277A | 1977-09-13 | 1977-09-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD148631A5 true DD148631A5 (en) | 1981-06-03 |
Family
ID=25263433
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD78207799A DD140454A5 (en) | 1977-09-13 | 1978-09-13 | PROCESS FOR PREPARING 3-STROKE BRANCHES ON 2-HYDROXY-4- (SUBSTITUTED) -PHENYL SQUARE BRACKETS TO CYCLOAL CANNON |
| DD78218654A DD148631A5 (en) | 1977-09-13 | 1978-09-13 | METHOD OF SELECTIVELY ALKYLATING A 3- (2,4-DIHYDROXYPHENYL) CYCLOALKANONE |
| DD78218214A DD148334A5 (en) | 1977-09-13 | 1978-09-13 | PROCESS FOR PREPARING SUBSTITUTED CYCLOHEXANDIONES (1.3) |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD78207799A DD140454A5 (en) | 1977-09-13 | 1978-09-13 | PROCESS FOR PREPARING 3-STROKE BRANCHES ON 2-HYDROXY-4- (SUBSTITUTED) -PHENYL SQUARE BRACKETS TO CYCLOAL CANNON |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD78218214A DD148334A5 (en) | 1977-09-13 | 1978-09-13 | PROCESS FOR PREPARING SUBSTITUTED CYCLOHEXANDIONES (1.3) |
Country Status (11)
| Country | Link |
|---|---|
| JP (4) | JPS5538367A (en) |
| BE (1) | BE870404A (en) |
| CS (1) | CS216502B2 (en) |
| DD (3) | DD140454A5 (en) |
| HU (1) | HU181937B (en) |
| PL (5) | PL123771B1 (en) |
| PT (1) | PT68543A (en) |
| RO (5) | RO77296A (en) |
| SU (1) | SU991944A3 (en) |
| YU (1) | YU215478A (en) |
| ZA (1) | ZA785180B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4486609A (en) * | 1981-03-16 | 1984-12-04 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
| US4933475A (en) * | 1980-09-19 | 1990-06-12 | Pfizer, Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
| US4285867A (en) | 1980-09-19 | 1981-08-25 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
| US4835192A (en) * | 1980-09-19 | 1989-05-30 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
| US4831059A (en) * | 1980-09-19 | 1989-05-16 | Pfizer Inc. | Producing analgesia with pharmacologically active 2-hydroxy-4-(substituted) phenyl cycloalkanes derivatives |
| US4331602A (en) | 1980-09-19 | 1982-05-25 | Pfizer Inc. | Pharmacologically active 4-[2-hydroxy-4-(substituted]phenyl)naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor |
| US4921994A (en) * | 1980-09-19 | 1990-05-01 | Pfizer Inc. | Pharmacologically active 2-hydroxy-4-(substituted) phenyl cycloalkanes and derivatives thereof |
| US4591225A (en) * | 1985-01-14 | 1986-05-27 | Molex Incorporated | Arrangement for interconnecting a printed circuit board with a multi-conductor cable |
| GB9007762D0 (en) * | 1990-04-05 | 1990-06-06 | Beecham Group Plc | Novel compounds |
| WO2007127711A2 (en) * | 2006-04-24 | 2007-11-08 | Allergan, Inc. | Abnormal cannabidiols as agents for lowering intraocular pressure |
| UA101004C2 (en) * | 2007-12-13 | 2013-02-25 | Теракос, Инк. | Derivatives of benzylphenylcyclohexane and use thereof |
-
1978
- 1978-09-12 PL PL1978227878A patent/PL123771B1/en unknown
- 1978-09-12 YU YU02154/78A patent/YU215478A/en unknown
- 1978-09-12 PL PL1978227879A patent/PL122834B1/en unknown
- 1978-09-12 PT PT68543A patent/PT68543A/en unknown
- 1978-09-12 ZA ZA00785180A patent/ZA785180B/en unknown
- 1978-09-12 PL PL1978227876A patent/PL122765B1/en unknown
- 1978-09-12 HU HU78PI638A patent/HU181937B/en unknown
- 1978-09-12 BE BE190419A patent/BE870404A/en not_active IP Right Cessation
- 1978-09-12 PL PL1978209554A patent/PL121079B1/en unknown
- 1978-09-12 PL PL1978227877A patent/PL122835B1/en unknown
- 1978-09-13 RO RO7898209A patent/RO77296A/en unknown
- 1978-09-13 RO RO7898210A patent/RO77297A/en unknown
- 1978-09-13 CS CS785911A patent/CS216502B2/en unknown
- 1978-09-13 DD DD78207799A patent/DD140454A5/en unknown
- 1978-09-13 RO RO7898208A patent/RO77170A/en unknown
- 1978-09-13 DD DD78218654A patent/DD148631A5/en unknown
- 1978-09-13 RO RO7899162A patent/RO76721A/en unknown
- 1978-09-13 DD DD78218214A patent/DD148334A5/en unknown
- 1978-09-13 RO RO7898207A patent/RO77321A/en unknown
- 1978-12-13 JP JP15404978A patent/JPS5538367A/en active Granted
-
1980
- 1980-01-28 SU SU802875550A patent/SU991944A3/en active
- 1980-06-26 JP JP55087229A patent/JPS5930693B2/en not_active Expired
- 1980-06-26 JP JP55087228A patent/JPS5930692B2/en not_active Expired
- 1980-06-26 JP JP55087227A patent/JPS605579B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5639035A (en) | 1981-04-14 |
| PL209554A1 (en) | 1979-06-04 |
| PL122835B1 (en) | 1982-08-31 |
| RO76721A (en) | 1982-10-11 |
| ZA785180B (en) | 1979-08-29 |
| JPS5930693B2 (en) | 1984-07-28 |
| RO77296A (en) | 1981-06-22 |
| JPS605579B2 (en) | 1985-02-12 |
| RO77170A (en) | 1981-06-22 |
| BE870404A (en) | 1979-03-12 |
| PL123771B1 (en) | 1982-11-30 |
| PL122765B1 (en) | 1982-08-31 |
| HU181937B (en) | 1983-11-28 |
| CS216502B2 (en) | 1982-11-26 |
| JPS5538367A (en) | 1980-03-17 |
| SU991944A3 (en) | 1983-01-23 |
| RO77297A (en) | 1981-06-22 |
| DD148334A5 (en) | 1981-05-20 |
| JPS5930692B2 (en) | 1984-07-28 |
| YU215478A (en) | 1983-06-30 |
| JPS5753352B2 (en) | 1982-11-12 |
| PL121079B1 (en) | 1982-04-30 |
| JPS5639031A (en) | 1981-04-14 |
| PL122834B1 (en) | 1982-08-31 |
| DD140454A5 (en) | 1980-03-05 |
| RO77321A (en) | 1981-08-17 |
| PT68543A (en) | 1978-10-01 |
| JPS5639036A (en) | 1981-04-14 |
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