CH377347A - Process for the production of new N-substituted piperidines - Google Patents
Process for the production of new N-substituted piperidinesInfo
- Publication number
- CH377347A CH377347A CH1290662A CH1290662A CH377347A CH 377347 A CH377347 A CH 377347A CH 1290662 A CH1290662 A CH 1290662A CH 1290662 A CH1290662 A CH 1290662A CH 377347 A CH377347 A CH 377347A
- Authority
- CH
- Switzerland
- Prior art keywords
- piperidine
- benzyl
- reacted
- halide
- formula
- Prior art date
Links
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
- C07D211/14—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 hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- 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
- C07D211/18—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- 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
- C07D211/18—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—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 substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
-
- 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
- C07D213/20—Quaternary compounds thereof
-
- 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
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- 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
-
- 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
- C07D213/32—Sulfur atoms
-
- 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
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent 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
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
Verfahren zur Herstellung neuer N-substituierter Piperidine
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung neuer N-substituierter Piperidine der Formel I
EMI1.1
in welcher A eine Alkylenbrücke mit 1-3 Kohlenstoffatomen, B eine Alkylenbrücke mit 2-3 Kohlenstoffatomen, R und R'niedere Alkylgruppen oder R und R'zusammen mit dem N-Atom einen hetero- cyclischen Rest, R"Wasserstoff oder eine entweder in 2-Stellung oder in 3-Stellung des Piperidinringes befindliche niedere Alkylgruppe und R1 eine gegebenenfalls substituierte Phenylgruppe bedeuten, das dadurch gekennzeichnet ist, dass eine Piperidinver- bindung der Formel II
EMI1.2
mit einer Verbindung der Formel III
EMI1.3
in welcher X ein Chlor-,
Brom-oder Jodatom bedeutet, in Gegenwart mindestens eines Siquivalentes eines Säureakzeptors umgesetzt wird.
Erfindungsgemäss herstellbare Verbindungen können als aktive Bestandteile pharmazeutischer Prä- parate verwendet werden, die menschlichen Organismen zur Verbesserung der Blutzirkulation in den Herzgefässen und der Funktion der Herzgefässe zugeführt werden können, falls diese beeinträchtigt sind.
Dar ber hinaus zeigen erfindungsgemäss herstellbare Verbindungen eine antiatheroscierotische Wirkung in menschlichen Organismen und potenzieren die antihypertensive Wirkung der Veratrum-alkaloide, wie durch klinische Versuche festgestellt werden konnte.
Erfindungsgemäss herstellbare Verbindungen stellen in Form der freien Base entweder Flüssig- keiten hohen Siedepunktes oder weisse kristalline Feststoffe mit niedrigem Schmelzpunkt dar, sind in Wasser unlöslich, löslich in wässrigen Mineralsäuren oder organischen Säuren, wobei aus diesen erhaltenen wässrigen Lösungen durch Verdampfung des Wassers die Säureadditionssalze erhalten werden können, und sind in polaren und unpolaren L¯sungsmitteln, wie beispielsweise niedrigen aliphatischen Alkoholen, Chloroform, Benzol und Petroläther, löslich.
Die Strukturformel der einfachsten erfindungsgemäss herstellbaren Verbindung, nämlich des 4-Benzyl-1-(¯-dimethylaminoÏthyl)-piperidns, ist
EMI1.4
Der Piperidinring kann ebenso wie die Phenyl- alkylgruppe RA-niedere Alkylgruppen als Substi- tuenten aufweisen. Solche Substituenten im Piperidin- ring aufweisende Verbindungen stellen vollkommene Aquivalente von im Pyridmnng unsubstituierten Ver- bindungen dar.
Erfinduogsgemäss herstellbare N- (Dialkylamino- alkyl)-piperidine werden auch als 4-Phenylalkyl-1- (dialkylaminoalky !)-piperidine bezeichnet und Beispiele für solche Verbindungen sind
4-p-ChlorphenylÏthyl-1-(¯-diisopropyl aminoäthyl)-piperidin,
4-(3,4-MethylendioxyphenylÏthyl) 1-(γ-piperidinopropyl)-piperidin, 4- (3, 4, 5-Trimethoxy-phenyläthyl)-3-äthyl-
1- (, B-diäthylaminoäthyl)-piperidin,
4-(α-Phenylpropyl)-1 -(γ-pyrrolidinopropyl)- piperidin,
4-(¯-Phenylpropyl)-1-(¯-diÏthylaminopropyl) piperidin, 4-(α -PhenylÏthyl)-1 -(¯-piperidinopropyl)- piperidin.
Die Säureadditionssalze erfindungsgemäss herstellbarer Verbindungen können in iiblicher Weise durch Umsetzung der freien Basen mit den gebräuch- lichen anorganischen Säuren, z. B. SalzsÏure, BromwasserstoffsÏure, JodwasserstoffsÏure, SchwefelsÏure oder Phosphorsäure, oder den gebräuchlichen organischen SÏuren, wie z. B. EssigsÏure, GerbsÏure, ZitronensÏure, MalonsÏure, ¯thansulfonsÏure, Cyclohexylsulfaminsäure und dergleichen hergestellt werden. Diese Salze stellen völlige Äquivalente der freien Basen dar und sind lediglich besonders geeignete Verabreichungsformen.
Beispiel 1
4-Benzyl-l- (-dimethytaminoäthyI)-piperidin
Eine Lösung von Dimethylaminoäthylchlorid, welche aus 180 g (1, 25 Mol) Dimethylaminoäthyl chlorid-hydrochlorid erhalten wurde, in Xylol, wurde tropfenweise ei. ner auf Rückfluss erhitzten Suspension von 175 g (1, 0 Mol) 4-Benzylpiperidin, 104 g (0, 75 Mol) Kaliumcarbonat und 80 g (0, 75 Mol) Natriumcarbonat in 250 cm3 Xylol zugesetzt. Die erhaltene AufschlÏmmung wurde 20 Stunden auf Rückfluss erhitzt, gekühlt, worauf so lange Wasser r zugesetzt wurde, bis alle anorganischen Salze in L¯sung gegangen waren. Die wässrige Schicht wurde sodann verworfen und die Xylollösung eingeengt.
Der erhaltene ölige Rückstand wurde destilliert, wobei entsprechend einer 53, 5 /oigen Ausbeute 132 g 4-Benzyl-1- (} 5-dimethylaminoäthyl)-piperidin bei einem Siedepunkt von Kp = 110-114°C bei 0, 1 mm Hg und einem Brechungsindex n24D = 1, 5160 erhalten wurden.
Beispiel 2
4-Benzyl-1-(¯-dimethylaminoÏthyl)-piperidin
Eine Suspension, bestehend aus 28, 0 g (0, 16 Mol) 4-Benzylpiperidin [(W. L. C. Veer und St. Goldschmidt, Rec. Trav. Chim. 65. 793 (1946) ; C. A.
41, 3101 (1947)], 34, 6 g (0, 24 Mol) -Di- methylaminoäthylchlorid-Hydrochlorid und 50 g wasserfreiem, pulverförmigem Natriumcarbonat und 200 cm3 n-Butylalkohol wurde unter R hren 24 Stunden auf Rückfluss erhitzt. Anschliessend wurde gekühlt und filtriert, worauf das Filtrat im Vakuum eingeengt wurde. Der Rückstand wurde hierauf mit Äther verdünnt, der erhaltene Niederschlag abfiltriert und das Filtrat im Vakuum eingeengt. Bei Vakuumdestillation wurde eine geringe Menge eines Vorlaufes und, entsprechend einer Ausbeute von 31% der Theorie, 12, 3 g 4-Benzyl-1-(,-dimethylamino- äthyl)-piperidin erhalten.
Das 4-Benzyl-l- B-dimethyl- aminoäthyl)-piperidin besass einen Siedepunkt Kp = 135-140 C bei 0, 5 mm Hg und einen Brechungsindex n 24 = 1, 5167.
Analyse :
Berechnet : N (basisch) 11, 37
Gefunden : 11, 22
Das Dihydrochlorid des 4-Benzyl-1-(¯-dimethyl aminoäthyl)-piperidins wurde in üblicher Weise hergestellt und besass einen Schmelzpunkt von 270¯ C.
Analyse :
Berechnet : C C60, 18%; H 8,84 %; Cl 22,21 %
Gefunden : 60, 50 8, 71 22, 11
Weitere erfindungsgemäss herstellbare 4-Phenylalkyl-1-dialkylaminoalkyl-piperidine werden in der folgenden Tabelle angegeben :
Tabelle
C Wasserstoff Chlorion Verbindung physikalische Konstinten Gew.%Gew.%Gew.%Gew.%Gew.% Gew.% berechnet gefunden berechnet gefunden berechnet gefunden 4-PhenylÏthyl-1- Kp. 123-153¯ C - - - - - (¯-dimethyl-aminoÏthyl)- bei 0,6 mm Hg piperidin n 25D = 1,5125 Dihydrochlorid Fp. 279 C 61, 25 61, 34 9, 07 9, 11 21, 27 21, 20 4-Benzyl-l-(¯-diÏthyl- Kp. 111-126¯ C aminoäthyl)-piperidin bei 0, 1 mm Hg n 21 = 1, 5130 - - - - - Dihydrochlorid Fp.
237-239¯ C 62, 23 61, 80 9, 29 9, 28 20, 41 20, 42 4-Benzyl-l-(γ-dimethyl- Kp. 130-133¯ C aminopropyl)-piperidin bei 0, 15 mm Hg D = 1, 5123------ Dihydrochlorid Fp. 280-282¯ C 61, 25 61, 37 9, 07 9, 12 21, 27 21, 33
Process for the production of new N-substituted piperidines
The present invention relates to a process for the preparation of new N-substituted piperidines of the formula I.
EMI1.1
in which A is an alkylene bridge with 1-3 carbon atoms, B an alkylene bridge with 2-3 carbon atoms, R and R 'lower alkyl groups or R and R' together with the N atom a heterocyclic radical, R "hydrogen or either in The lower alkyl group in the 2-position or in the 3-position of the piperidine ring and R1 is an optionally substituted phenyl group, which is characterized in that a piperidine compound of the formula II
EMI1.2
with a compound of the formula III
EMI1.3
in which X is a chlorine,
Bromine or iodine atom means, is implemented in the presence of at least one equivalent of an acid acceptor.
Compounds which can be prepared according to the invention can be used as active constituents of pharmaceutical preparations which can be supplied to human organisms to improve the blood circulation in the cardiac vessels and the function of the cardiac vessels if these are impaired.
In addition, compounds which can be prepared according to the invention show an antiatherosclerotic effect in human organisms and potentiate the antihypertensive effect of the Veratrum alkaloids, as has been established by clinical trials.
Compounds which can be prepared according to the invention are in the form of the free base either liquids with a high boiling point or white crystalline solids with a low melting point, are insoluble in water, soluble in aqueous mineral acids or organic acids, the aqueous solutions obtained from these being given the acid addition salts by evaporation of the water and are soluble in polar and non-polar solvents such as lower aliphatic alcohols, chloroform, benzene and petroleum ether.
The structural formula of the simplest compound which can be prepared according to the invention, namely 4-benzyl-1- (¯-dimethylaminoÏthyl) piperidine, is
EMI1.4
The piperidine ring, like the phenylalkyl group, can have RA lower alkyl groups as substituents. Compounds of this type which have substituents in the piperidine ring represent perfect equivalents of compounds which are unsubstituted in the pyridine ring.
N- (dialkylaminoalkyl) piperidines which can be prepared according to the invention are also referred to as 4-phenylalkyl-1- (dialkylaminoalkyl) piperidines and are examples of such compounds
4-p-chlorophenylethyl-1- (¯-diisopropyl aminoethyl) piperidine,
4- (3,4-methylenedioxyphenylethyl) 1 - (γ-piperidinopropyl) piperidine, 4- (3, 4, 5-trimethoxyphenylethyl) -3-ethyl-
1- (, B-diethylaminoethyl) piperidine,
4 - (α-phenylpropyl) -1 - (γ-pyrrolidinopropyl) -piperidine,
4- (¯-phenylpropyl) -1- (¯-diÏthylaminopropyl) piperidine, 4 - (α-phenylÏthyl) -1 - (¯-piperidinopropyl) piperidine.
The acid addition salts which can be prepared according to the invention can be prepared in the usual way by reacting the free bases with the customary inorganic acids, e.g. B. hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid or phosphoric acid, or the common organic acids such. B. acetic acid, tannic acid, citric acid, malonic acid, ¯thanesulfonic acid, cyclohexylsulfamic acid and the like can be produced. These salts are complete equivalents of the free bases and are merely particularly suitable forms of administration.
example 1
4-Benzyl-1- (-dimethytaminoethyl) -piperidine
A solution of dimethylaminoethyl chloride, which was obtained from 180 g (1.25 mol) of dimethylaminoethyl chloride hydrochloride, in xylene, was added dropwise to egg. A refluxed suspension of 175 g (1.0 mol) of 4-benzylpiperidine, 104 g (0.75 mol) of potassium carbonate and 80 g (0.75 mol) of sodium carbonate in 250 cm3 of xylene was added. The resulting slurry was heated to reflux for 20 hours, cooled, after which water was added until all the inorganic salts had gone into solution. The aqueous layer was then discarded and the xylene solution was concentrated.
The oily residue obtained was distilled, with 132 g of 4-benzyl-1- (} 5-dimethylaminoethyl) piperidine at a boiling point of bp = 110-114 ° C. at 0.1 mm Hg and corresponding to a 53.5% yield a refractive index n24D = 1.5160 were obtained.
Example 2
4-Benzyl-1- (¯-dimethylaminoÏthyl) piperidine
A suspension consisting of 28.0 g (0.16 mol) of 4-benzylpiperidine [(W. L. C. Veer and St. Goldschmidt, Rec. Trav. Chim. 65, 793 (1946); C.A.
41, 3101 (1947)], 34.6 g (0.24 mol) dimethylaminoethyl chloride hydrochloride and 50 g of anhydrous, powdered sodium carbonate and 200 cm3 of n-butyl alcohol were heated to reflux with stirring for 24 hours. It was then cooled and filtered, whereupon the filtrate was concentrated in vacuo. The residue was then diluted with ether, the resulting precipitate was filtered off and the filtrate was concentrated in vacuo. Vacuum distillation gave a small amount of a first run and, corresponding to a yield of 31% of theory, 12.3 g of 4-benzyl-1 - (, - dimethylamino-ethyl) piperidine.
The 4-benzyl-1-B-dimethylaminoethyl) piperidine had a boiling point bp = 135-140 ° C. at 0.5 mm Hg and a refractive index n 24 = 1.5167.
Analysis:
Calculated: N (basic) 11, 37
Found: 11, 22
The dihydrochloride of 4-benzyl-1- (¯-dimethyl aminoethyl) piperidine was prepared in the usual way and had a melting point of 270¯ C.
Analysis:
Calculated: C C60, 18%; H 8.84%; Cl 22.21%
Found: 60, 50 8, 71 22, 11
Further 4-phenylalkyl-1-dialkylaminoalkyl-piperidines which can be prepared according to the invention are given in the following table:
table
C hydrogen chlorine ion compound physical constants wt.% Wt.% Wt.% Wt.% Wt.% Wt.% Calculated found calculated found calculated found 4-PhenylÏthyl-1 Kp. 123-153¯ C - - - - - (¯ -dimethyl-aminoethyl) - at 0.6 mm Hg piperidine n 25D = 1.5125 dihydrochloride m.p. 279 C 61, 25 61, 34 9, 07 9, 11 21, 27 21, 20 4-benzyl-1- (¯ -diÏthyl- bp. 111-126¯ (aminoethyl) piperidine at 0.1 mm Hg n 21 = 1.5130 - - - - - dihydrochloride mp.
237-239¯ C 62, 23 61, 80 9, 29 9, 28 20, 41 20, 42 4-Benzyl-1- (γ-dimethyl- bp 130-133¯ C aminopropyl) piperidine at 0.15 mm Hg D = 1,523 ------ dihydrochloride m.p. 280-282¯ C 61, 25 61, 37 9, 07 9, 12 21, 27 21, 33
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US59305856A | 1956-06-22 | 1956-06-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
CH377347A true CH377347A (en) | 1964-05-15 |
Family
ID=24373189
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH623361A CH372305A (en) | 1956-06-22 | 1957-01-31 | Process for the preparation of new pyridine derivatives |
CH1290662A CH377347A (en) | 1956-06-22 | 1957-01-31 | Process for the production of new N-substituted piperidines |
CH4217057A CH374664A (en) | 1956-06-22 | 1957-01-31 | Process for the production of new bisquaternary ammonium compounds |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH623361A CH372305A (en) | 1956-06-22 | 1957-01-31 | Process for the preparation of new pyridine derivatives |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH4217057A CH374664A (en) | 1956-06-22 | 1957-01-31 | Process for the production of new bisquaternary ammonium compounds |
Country Status (3)
Country | Link |
---|---|
CH (3) | CH372305A (en) |
FR (1) | FR1242810A (en) |
GB (1) | GB842996A (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4797411A (en) * | 1986-07-18 | 1989-01-10 | Farmitalia Carlo Erba S.P.A. | Cycloalkyl-substituted 4-pyridyl derivatives and use as aromatase inhibitors |
JP2005526831A (en) * | 2002-04-09 | 2005-09-08 | アステックス テクノロジー リミテッド | Pharmaceutical compounds |
-
1956
- 1956-11-12 GB GB3512459A patent/GB842996A/en not_active Expired
-
1957
- 1957-01-31 CH CH623361A patent/CH372305A/en unknown
- 1957-01-31 CH CH1290662A patent/CH377347A/en unknown
- 1957-01-31 CH CH4217057A patent/CH374664A/en unknown
- 1957-04-16 FR FR736500A patent/FR1242810A/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
FR1242810A (en) | 1960-10-07 |
CH372305A (en) | 1963-10-15 |
CH374664A (en) | 1964-01-31 |
GB842996A (en) | 1960-08-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE2845499A1 (en) | ALKANOYLPROLIN DERIVATIVES AND THEIR HOMOLOGES, THEIR PRODUCTION AND USE | |
DE1948144C3 (en) | 1 - (I -Keto-tetrahydronaphthyl-5-oxy) ^ -hydroxy-S-alkylaminopropanes, process for their preparation and pharmaceutical composition based on them | |
DE2313258A1 (en) | PROCESS FOR THE PREPARATION OF BUTYROPHENONE DERIVATIVES AND THEIR SALTS NEW BUTYROPHENONE DERIVATIVES, THEIR SALTS AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS | |
CH377347A (en) | Process for the production of new N-substituted piperidines | |
DE1493454C3 (en) | 1 -Aryloxy ^ -hydroxy-S-isopropylaminopropane and their salts, as well as their production and pharmaceuticals based thereon | |
DE1545714A1 (en) | New N-aralkyl-piperidyl-1,3-dioxolanes and processes for making the same | |
DE540697C (en) | Process for the preparation of diamines acylated on one side | |
DE1228262B (en) | Process for the production of new pyrrolidine derivatives and their salts | |
US2838516A (en) | 2-(thienyl methyl) piperidines | |
DE1078578B (en) | Process for the preparation of theophylline derivatives | |
AT206896B (en) | Process for the preparation of new racemic or optically active morpholine derivatives and their salts | |
DE964048C (en) | Process for the production of new, antihistamine active piperazine offshoots | |
DE961348C (en) | Process for the production of new 4- (phenylamino) piperidine compounds | |
AT361933B (en) | METHOD FOR PRODUCING NEW 5,11- DIHYDRO-6H-PYRIDO (2,3-B) (1,4) - BENZODIAZEPINE-6-ON DERIVATIVES AND THEIR SALTS | |
DE829167B (en) | Process for the preparation of new basic derivatives of immodibenzyl | |
AT222649B (en) | Process for the preparation of new piperidine derivatives | |
DE2166258C3 (en) | Amino alcohols, processes for their production and medicinal preparations containing these compounds | |
AT225192B (en) | Process for the production of new piperidine derivatives and their salts | |
AT242137B (en) | Process for the preparation of new derivatives of 4-aminobutyn- (2, 3) -ol-1 and their salts | |
DE1242231B (en) | Process for the preparation of new ester-like piperidine compounds | |
DE1060866B (en) | Process for the preparation of therapeutically useful pyrazolone derivatives | |
DE1108226B (en) | Process for the preparation of hypotensive phenylpiperazines | |
DE1166206B (en) | Process for the preparation of 4-azaphenthiazine derivatives | |
DE1003738B (en) | Process for the preparation of 1,4-aralkylpiperazines | |
DE1137439B (en) | Process for the preparation of substituted morpholines |