DE2643473A1 - PROCESS FOR THE PREPARATION OF 1,1-DICYCLOHEXYL-2- (2'-PIPERIDYL) -AETHANE - Google Patents
PROCESS FOR THE PREPARATION OF 1,1-DICYCLOHEXYL-2- (2'-PIPERIDYL) -AETHANEInfo
- Publication number
- DE2643473A1 DE2643473A1 DE19762643473 DE2643473A DE2643473A1 DE 2643473 A1 DE2643473 A1 DE 2643473A1 DE 19762643473 DE19762643473 DE 19762643473 DE 2643473 A DE2643473 A DE 2643473A DE 2643473 A1 DE2643473 A1 DE 2643473A1
- Authority
- DE
- Germany
- Prior art keywords
- dicyclohexyl
- piperidyl
- preparation
- compound
- pyridyl
- 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 9
- 238000002360 preparation method Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 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 description 5
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
- 102100035767 Adrenocortical dysplasia protein homolog Human genes 0.000 claims 1
- 101000929940 Homo sapiens Adrenocortical dysplasia protein homolog Proteins 0.000 claims 1
- 239000007868 Raney catalyst Substances 0.000 claims 1
- 229910000564 Raney nickel Inorganic materials 0.000 claims 1
- 125000005936 piperidyl group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000005977 Ethylene Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 3
- 239000012965 benzophenone Substances 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- BMFYCFSWWDXEPB-UHFFFAOYSA-N cyclohexyl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1CCCCC1 BMFYCFSWWDXEPB-UHFFFAOYSA-N 0.000 description 2
- DEFUSPNGFCCTEU-UHFFFAOYSA-N dicyclohexylmethanol Chemical compound C1CCCCC1C(O)C1CCCCC1 DEFUSPNGFCCTEU-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 1
- -1 1-Phenyl-1-cyclohexyl Chemical group 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- TWXWPPKDQOWNSX-UHFFFAOYSA-N dicyclohexylmethanone Chemical compound C1CCCCC1C(=O)C1CCCCC1 TWXWPPKDQOWNSX-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/12—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
a,a,
T 50 564T 50 564
Anmelder: B.T.B. INDUSTRIA CHIMICA, Tribiano (Mailand/Italien)Applicant: B.T.B. INDUSTRIA CHIMICA, Tribiano (Milan / Italy)
Verfahren zur Herstellung von 1,1-Di cyclohexyl^-(2'-pip eridy])-äthanProcess for the preparation of 1,1-Di cyclohexyl ^ - (2'-pip eridy]) - ethane
Die Erfindung betrifft ein Verfahren zur Herstellung von 1,1-Dicyclohexyl-2-(2'-piperidyl)-äthan der Formel (I)The invention relates to a process for the preparation of 1,1-dicyclohexyl-2- (2'-piperidyl) ethane of the formula (I)
CH2—CH (I)CH 2 -CH (I)
Die Verbindung (I) besitzt bei der Therapie von Herzkrankheiten interessante pharmazeutische Eigenschaften. Die in der Literatur beschriebene Herstellung dieser Verbindung (vergl. z.B. GB-PS 1 025 578) ist sehr kompliziert und teuer, da die folgenden Reaktionen durchgeführt werden müssen:The compound (I) has pharmaceutical properties of interest in the therapy of heart diseases. The preparation of this compound described in the literature (cf. e.g. GB-PS 1 025 578) is very complicated and expensive, as the following reactions must be carried out:
(a) Synthese des Dicyclohexylcarbinols, z.B. aus Cyclohexyl-magnesiumbromid und Äthylformiatj(a) Synthesis of dicyclohexylcarbinol, e.g. from cyclohexyl magnesium bromide and ethyl formate
(b) Oxydation von Dicyclohexylcarbinol zu Dicyclohexylketon; (b) oxidation of dicyclohexyl carbinol to dicyclohexyl ketone;
(c) Umsetzung dieses Ketons mit Picolyllithium unter Herstellung von 1,1-Dieyelohexyl-2-(2»-pyridyl)-äthanol;(c) reaction of this ketone with picolyllithium to produce 1,1-dieyelohexyl-2- (2 »-pyridyl) ethanol;
(d) Dehydratisierung von 1,1-Dicyclohexyl-2-(2r-py-^ • ridyl)-äthanol zu 1,1-Dicyclohexyl-2-(2'-pyridyl)-äthylen und schließlich(d) Dehydration of 1,1-dicyclohexyl-2- (2 r -py- ^ • ridyl) -ethanol to 1,1-dicyclohexyl-2- (2'-pyridyl) -ethylene and finally
(e) die katalytische Hydrierung der zuletzt erwähnten Verbindung zu einer Verbindung (I).(e) the catalytic hydrogenation of the last-mentioned compound to give a compound (I).
7098-15/11447098-15 / 1144
Die Umsetzung (a) ist mit den Gefahren verbunden, die üblicherweise bei einer Grignardreaktion auftreten, wohingegen die Oxydation (b), die mit Chromsäureanhydrid durchgeführt wird, Schwierigkeiten beim Abfallwasser ergibt·The reaction (a) is associated with the dangers that usually occur in a Grignard reaction, whereas the oxidation (b) carried out with chromic anhydride gives problems with waste water
Gegenstand der Erfindung ist ein neues Verfahren zur Herstellung der Verbindung (I) durch katalytische Hydrierung einer Verbindung der Formel (II)The invention relates to a new process for the preparation of the compound (I) by catalytic hydrogenation a compound of the formula (II)
i; ■a t i; ■ at
(II )(II)
worinwherein
R eine Phenylgruppe bedeutet und R* eine Phenyl- oder eine Cyclohexylgruppe bedeutet.R denotes a phenyl group and R * denotes a phenyl or a cyclohexyl group.
Wenn in der Formel (II) R1 eine Cyclohexylgruppe bedeutet, kann die Verbindung (II), wie im folgenden Schema aufgeführt, hergestellt werden. When R 1 in the formula (II) represents a cyclohexyl group, the compound (II) can be prepared as shown in the following scheme.
a·)a ·)
COClCOCl
AlCl3 AlCl 3
709815/1144709815/1144
- H - H.
CH2LiCH 2 Li
1^JLcH2- C -1 ^ JLcH 2 - C -
s^^ ι CHp-"" C —~ OHs ^^ ι CHp- "" C- ~ OH
-H2 0-H 2 0
Die a')-Umsetzung wird so durchgeführt, wie es an · sich' für die Friedel-Crafts-Reaktion bekannt ist, wobei ein Überschuß an Benzol als Lösungsmittel verwendet wird. Das so erhaltene Phenyl-cyclohexylketon wird dann mit Picolyllithium in.einem nichtpolaren Lösungsmittel wie Benzol oder Toluol umgesetzt, und die Dehydratisierung des entsprechenden Carbinols (c1) wird bei sauren Bedingungen, beispielsweise mit Schwefelsäure oder Chlorwasserstoffsäure,bei einer Temperatur von 50 bis 1000C durchgeführt.The a ') reaction is carried out as it is known per se for the Friedel-Crafts reaction, an excess of benzene being used as solvent. The phenyl-cyclohexyl ketone thus obtained is then reacted with picolyllithium in a non-polar solvent such as benzene or toluene, and the dehydration of the corresponding carbinol (c 1 ) is carried out under acidic conditions, for example with sulfuric acid or hydrochloric acid, at a temperature of 50 to 100 ° C carried out.
Das 1 -Phenyl-1 -cyclohexyl-Z- (2* -pyridyl )-äthylen (II, worin Rf Cyclohexyl bedeutet) wird schließlich über einem Katalysator wie PtO2, Raney-Ni oder Rhodium auf Al2O, bei einem H2-Druck von 50 bis 150 at und einer Temperatur von 80 bis 1500C durchgeführt. r The 1-phenyl-1 -cyclohexyl-Z- (2 * -pyridyl) -ethylene (II, where R f is cyclohexyl) is finally over a catalyst such as PtO 2 , Raney Ni or rhodium on Al 2 O, with an H 2 pressure of 50 to 150 atm and a temperature of 80 to 150 0 C carried out. r
Bei einem weiteren, bevorzugten Herstellungsverfahren bedeuten in der Verbindung (II) R und Rf eine Phenylgruppe, Die Synthese von (II) ist dann sehr einfach und umfaßt zweit Umsetzungen: In a further, preferred preparation process, R and R f in the compound (II) are a phenyl group. The synthesis of (II) is then very simple and comprises two reactions:
7098 15/1 U47098 15/1 U4
(a") die Kondensation von Benzophenon (eine gut bekannte, im Handel erhältliche und billige Verbindung) mit Picolyllithium und(a ") the condensation of benzophenone (a well-known, commercially available and inexpensive compound) with Picolyllithium and
(b") die Dehydratisierung des so erhaltenen 1,1-Diphenyl-2-(2 «-pyridyl)-äthanols zu 1,1-Diphenyl-2-(2«- pyridyl)-äthylen, wie im folgenden Schema dargestellt.(b ") the dehydration of the 1,1-diphenyl-2- (2 «-Pyridyl) ethanol to 1,1-diphenyl-2- (2« - pyridyl) ethylene, as shown in the following scheme.
a")a ")
b»)b »)
L-CB,- C-OHL-CB, - C-OH
— C- C
* . (II), worin R=R'= Phenyl)*. (II), where R = R '= phenyl)
Die Umsetzung a") wird in nichtpolaren Lösungsmitteln wie bei a1) durchgeführt. Die Hydrierung b") wird mit PtO2, Rhodium auf Al2O3 oder Ni-Raney katalysiert .und bei einem Druck von 80 bis 150 at und einer Temperatur von 50 bis 12O0C durchgeführt.The reaction of a ") is carried out in non-polar solvents such as at a 1). The hydrogenation b") was treated with PtO 2, rhodium on Al 2 O 3 and Ni-Raney catalyzes .and at a pressure of 80 atm to 150 and a temperature from 50 to 12O 0 C carried out.
Die folgenden Beispiele erläutern die Erfindung. The following examples illustrate the invention.
Beispiel 1example 1
(a) 1,1-Diphenyl-2-(2'-pyridyl)-athanol(a) 1,1-Diphenyl-2- (2'-pyridyl) ethanol
Eine Lösung aus 7,7 g (0,08 Mol) 2-Picolin in 35 ml wasserfreiem Tetrahydrofuran wird auf -200C abgekühlt und mit einer Lösung von 0,09 Mol n-Butyllithium in 7 ml Hexan in einer Atmosphäre von trockenem Stickstoff behandelt. Das Gemisch wird 1 h bei Zimmertemperatur gerührt, dann wird eine Lösung aus 13 g (0,07 Mol) Benzophenon in 25 ml wasserfreiem Toluol zugegeben. Nach dem Rühren während 1 h bei Zimmertemperatur wird das Gemisch mit 70 ml Wasser behandelt. Der Niederschlag wird abfiltriert und getrocknet; Fp. 148 bis 1510C, Ausbeute 75%.A solution of 7.7 g (0.08 mol) of 2-picoline in 35 ml of anhydrous tetrahydrofuran is cooled to -20 0 C and a solution of 0.09 mol of n-butyllithium in 7 ml of hexane in an atmosphere of dry nitrogen treated. The mixture is stirred for 1 hour at room temperature, then a solution of 13 g (0.07 mol) of benzophenone in 25 ml of anhydrous toluene is added. After stirring for 1 hour at room temperature, the mixture is treated with 70 ml of water. The precipitate is filtered off and dried; Mp. 148 to 151 ° C., yield 75%.
(b) 1,1 -Diphenyl-2- (2f -pyridyl )*-äthylen(b) 1,1-Diphenyl-2- (2 f -pyridyl) * - ethylene
10 g 1,1-Diphenyl-2-(2'-piperidyl)-äthanol werden 15 min bei 80 bis 9O0C mit 45 ml 30&Lger Chlorwasserstoffsäure erhitzt. Nach dem Abkühlen wird das Gemisch mit 10%iger NaOH neutralisiert. Der feste Niederschlag wird filtriert und mit Wasser gewaschen. Die Ausbeute ist fast quantitativ; Fp. 113 bis 116°C« .10 g of 1,1-diphenyl-2- (2'-piperidyl) ethanol is heated for 15 min at 80 to 9O 0 C with 45 ml of 30 Lger hydrochloric acid. After cooling, the mixture is neutralized with 10% NaOH. The solid precipitate is filtered and washed with water. The yield is almost quantitative; Mp. 113 to 116 ° C «.
(c) 1,1-Dicyclohexyl-2-(2'-piperidyl)-äthan(c) 1,1-dicyclohexyl-2- (2'-piperidyl) ethane
Zu einer Lösung aus 5 g 1,1-Diphenyl-2-(2'-pyridyl)-" äthylen in 50 ml Äthanol leitet man bis zur Neutralität gasförmige HCl ein. 1 ml CH^COOH wird zugegeben und die Lösung wird bei 80 at und 1000C in Anwesenheit von 0,3 g PtO2 hydriert. Die theoretische Menge an Wasserstoff wird in 6 h absorbiert. Nach dem Abkühlen und Filtrieren wird das Lösungsmittel eingedampft. Das Hydrochlorid von 1,1-Dicyclohexyl-2-(2»-piperidyl)-äthan, Fp. 243 bis 2450C, wird in einer Ausbeute von 9050 erhalten. Aus der entsprechenden Base wird das Maleat durch Behandlung mit Maleinsäure in Äthylacetat erhalten j Fp. 186 bis 1880C. Die analytischen und spektroskopischen Werte stehen in Übereinstimmung mit den berechneten Werten. ...■'-.-To a solution of 5 g of 1,1-diphenyl-2- (2'-pyridyl) - "ethylene in 50 ml of ethanol, gaseous HCl is passed in until neutral. 1 ml of CH ^ COOH is added and the solution is heated to 80 atm and 100 0 C in the presence of 0.3 g PtO 2 was hydrogenated. the theoretical amount of hydrogen is absorbed at 6 h. After cooling and filtration, the solvent is evaporated. the hydrochloride of 1,1-dicyclohexyl-2- (2 ' -piperidyl) -ethane, mp. 243-245 0 C is obtained in a yield of 9050th the maleate is obtained from the corresponding base by treatment with maleic acid in ethyl acetate obtained j mp. 186-188 0 C. the analytical and spectroscopic values are in agreement with the calculated values. ... ■ '-.-
Das gleiehf Produkt wird unter Verwendung von 5?6igem Rhodium auf Al2O, "äTTTCatalysator bei 120 at H2 und 1000C erhalten. The product is gleiehf using 5? 6igem rhodium on Al 2 O, "äTTTCatalysator at 120 at H 2 to obtain 100 0 C.
Beispiel 2Example 2
(a) 1-Phenyl-1-cyclohexyl^-(2·-pyridyl)-äthanol(a) 1-Phenyl-1-cyclohexyl ^ - (2 · pyridyl) ethanol
Diese Verbindung wird nach dem gleichen Verfahren, Y/ie in Beispiel 1(a) beschrieben, unter Verwendung von Phenylcyclohexyl-keton (D.H. Hey und O.C. Musgrave, J,Chem.Soc.1949i 3156) anstelle von Benzophenon hergestellt. Ausbeute 72%; Fp. 142 bis 1440C.This compound is prepared by the same method, Y / ie in Example 1 (a), using phenylcyclohexyl ketone (DH Hey and OC Musgrave, J, Chem. Soc. 1949 i 3156) instead of benzophenone. Yield 72%; Mp. 142 to 144 0 C.
(b) 1-Phenyl-1-cyclohexyl-2-(2·-pyridyl)-äthylen(b) 1-phenyl-1-cyclohexyl-2- (2 · pyridyl) ethylene
20 g der gemäß Beispiel 2(a) erhaltenen Verbindung werden bei 80 bis 900C mit 60 ml 30$£iger HCl während 20 min erwärmt. Anschließend wird das Gemisch abgekühlt und mit "!Obigem NaOH neutralisiert und durch Absaugen abfiltriert. Man erhält 17 g Rohprodukt.20 g of the compound obtained according to Example 2 (a) are heated at 80 to 90 ° C. with 60 ml of 30% HCl for 20 min. The mixture is then cooled and neutralized with the above NaOH and filtered off with suction. 17 g of crude product are obtained.
(c) 1,1-Dicyclohexyl-2-(2'-piperidyl)-äthan(c) 1,1-dicyclohexyl-2- (2'-piperidyl) ethane
Das Rohprodukt von Beispiel 2(b) wird, wie in Beispiel 1(c) beschrieben, hydriert. Das Endprodukt wird in einer Ausbeute von BQ% erhalten.The crude product from Example 2 (b) is hydrogenated as described in Example 1 (c). The end product is obtained in a yield of BQ% .
7 Ο 9 8 1 5 / IU 47 Ο 9 8 1 5 / IU 4
Claims (4)
katalytisch hydriert,R 1 is a phenyl group or a cyclohexyl group,
catalytically hydrogenated,
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2776775A IT1054328B (en) | 1975-09-29 | 1975-09-29 | (1,1)-Dicyclohexyl (2)-piperidyl-ethane prepn. - by catalytic hydrogenation of corresp. ethylene cpd. in which one cyclohexyl gp. is opt. replaced by phenyl |
| IT2911975A IT1054372B (en) | 1975-11-07 | 1975-11-07 | (1,1)-Dicyclohexyl (2)-piperidyl-ethane prepn. - by catalytic hydrogenation of corresp. ethylene cpd. in which one cyclohexyl gp. is opt. replaced by phenyl |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2643473A1 true DE2643473A1 (en) | 1977-04-14 |
Family
ID=26328744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19762643473 Pending DE2643473A1 (en) | 1975-09-29 | 1976-09-27 | PROCESS FOR THE PREPARATION OF 1,1-DICYCLOHEXYL-2- (2'-PIPERIDYL) -AETHANE |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS5253867A (en) |
| CH (1) | CH599940A5 (en) |
| DE (1) | DE2643473A1 (en) |
| ES (1) | ES452277A1 (en) |
| FR (1) | FR2325641A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4191828A (en) * | 1976-04-14 | 1980-03-04 | Richardson-Merrell Inc. | Process for preparing 2-(2,2-dicyclohexylethyl)piperidine |
| US4392406A (en) * | 1981-06-22 | 1983-07-12 | Kimball International, Inc. | Switched capacitor sine wave generator and keyer |
| JPS59108603U (en) * | 1983-01-12 | 1984-07-21 | 株式会社サト−医研 | Air bladder in compression cuff for blood pressure measurement |
| JPS59156603U (en) * | 1983-04-07 | 1984-10-20 | モリト株式会社 | cuff for blood pressure monitor |
| JPS6069105U (en) * | 1983-10-20 | 1985-05-16 | テルモ株式会社 | Sphygmomanometer cuff |
-
1976
- 1976-09-27 DE DE19762643473 patent/DE2643473A1/en active Pending
- 1976-09-28 CH CH1223176A patent/CH599940A5/xx not_active IP Right Cessation
- 1976-09-29 ES ES452277A patent/ES452277A1/en not_active Expired
- 1976-09-29 JP JP11610276A patent/JPS5253867A/en active Granted
- 1976-09-29 FR FR7629250A patent/FR2325641A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5253867A (en) | 1977-04-30 |
| FR2325641A1 (en) | 1977-04-22 |
| FR2325641B1 (en) | 1980-09-26 |
| CH599940A5 (en) | 1978-06-15 |
| ES452277A1 (en) | 1977-11-01 |
| JPS5512901B2 (en) | 1980-04-04 |
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