DE1253271B - Process for the preparation of 2-oxo-1, 2, 3, 4, 6, 7-hexahydro-11bH-benzo [a] quinolizines - Google Patents
Process for the preparation of 2-oxo-1, 2, 3, 4, 6, 7-hexahydro-11bH-benzo [a] quinolizinesInfo
- Publication number
- DE1253271B DE1253271B DEM52128A DEM0052128A DE1253271B DE 1253271 B DE1253271 B DE 1253271B DE M52128 A DEM52128 A DE M52128A DE M0052128 A DEM0052128 A DE M0052128A DE 1253271 B DE1253271 B DE 1253271B
- Authority
- DE
- Germany
- Prior art keywords
- general formula
- benzo
- hexahydro
- oxo
- quinolizines
- 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
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/203—Unsaturated compounds containing keto groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/10—Quaternary compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
- C07D455/06—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine containing benzo [a] quinolizine ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
AUSLEGESCHRIFTEDITORIAL
Int. Cl.:Int. Cl .:
C07dC07d
Deutsche Kl.: 12 ρ - 5German class: 12 ρ - 5
Nummer: 1253 271Number: 1253 271
Aktenzeichen: M 52128 IV d/12 ρFile number: M 52128 IV d / 12 ρ
Anmeldetag: 14. März 1962Filing date: March 14, 1962
Auslegetag: 2. November 1967Open date: November 2, 1967
Es ist bekannt, daß zahlreiche in therapeutischer Hinsicht wichtige natürliche Alkaloide (ζ. Β. Berberin, Emetin, Yonimbin, Rauwolfia-Alkaloide) sowie auch einige mit den genannten strukturell verwandte synthetische Produkte Chinolizin-Ringsysteme in ihrem Molekül enthalten. Zum synthetischen Aufbau solcher Verbindungen sind in der Literatur bisher nur komplizierte, aus vielen Schritten bestehende und schwache Ausbeuten ergebende Prozesse beschrieben, bei welchen der Ringschluß des Chinolizin-Ringsystems meistens durch eine Dieckmannsche Kondensation der entsprechenden Dicarbonsäureester erfolgt (»Journal of the Chemical Society«, London 1935, S. 1743; »Experientia«, Bd. 5, 1949, S. 115; Journal of the Chemical Society, London 1952, S. 650).It is known that numerous natural alkaloids (ζ. Β. Berberine, Emetine, Yonimbine, Rauwolfia alkaloids) as well as some structurally with the named ones related synthetic products contain quinolizine ring systems in their molecule. To the synthetic Establishing such connections are so far only complicated in the literature, from many steps Existing and poor yields are described processes in which the ring closure of the quinolizine ring system mostly through a Dieckmann condensation of the corresponding Dicarboxylic acid ester takes place ("Journal of the Chemical Society", London 1935, p. 1743; "Experientia", Vol. 5, 1949, p. 115; Journal of the Chemical Society, London 1952, p. 650).
Neuerlich wurden 2-Oxo-l,2,3,4,6,7-hexahydrollbH-benzo[a]chinolizine auch durch die Reaktion von substituierten Isochinolinen mit Methylvinylketon hergestellt (»Helvetica Chimica Acta«, Bd. 43, 1960, S. 583), auf diesem Wege können aber die gewünschten Chinolizinderivate nur mit sehr schlechter Ausbeute gewonnen werden; die Versuche haben gezeigt, daß in solchen Fällen als Hauptprodukt der Reaktion ein aus 2 Mol substituiertem Isochinolin und 1 Mol Methylvinylketon aufgebautes Additionsprodukt von bisher ungeklärter Struktur entsteht. 2-Oxo-1,2,3,4,6,7-hexahydrollbH-benzo [a] quinolizines were used again also produced by the reaction of substituted isoquinolines with methyl vinyl ketone ("Helvetica Chimica Acta", vol. 43, 1960, p. 583), but in this way the desired quinolizine derivatives can only be achieved with very poor results Yield can be obtained; the tests have shown that in such cases as the main product the reaction produces an addition product made up of 2 moles of substituted isoquinoline and 1 mole of methyl vinyl ketone with a structure that has not yet been clarified.
Man hat gefunden, daß 2-Oxo-l,2,3,4,6,7-hexahydro-llbH-benzo[a]chinolizine der allgemeinen Formel IIt has been found that 2-oxo-1,2,3,4,6,7-hexahydro-IIbH-benzo [a] quinolizine of the general formula I.
RiRi
CH2 '\
CH 2
>. / \ /N
>. / \ /
worin Ri bis R4 für Wasserstoff- oder Halogenatome, Alkyl- oder Alkoxygruppen stehen oder wobei R2 und R3 zusammen auch eine Methylendioxygruppe bilden können und worin R5 bis R8 Wasserstoffatome, Alkylgruppen mit geraden oder verzweigten Kohlenstoffketten mit 1 bis 10 Kohlen-Stoffatomen, Aryl- oder Aralkylgruppen sind, in einstufiger Reaktion und mit guter Ausbeute ge-Verf ahren zur Herstellungwhere Ri to R4 are hydrogen or halogen atoms, alkyl or alkoxy groups or where R2 and R3 together can also form a methylenedioxy group and where R 5 to R 8 are hydrogen atoms, alkyl groups with straight or branched carbon chains with 1 to 10 carbon atoms, aryl - Or aralkyl groups, in a one-step reaction and with good yield ge-method for the production
von 2-Oxo-l,2,3,4,6,7-hexahydro-of 2-oxo-1,2,3,4,6,7-hexahydro-
11 bH-benzo [a] chinolizinen11 bH-benzo [a] quinolizines
Anmelder:Applicant:
Magyar Tudomänyos Akademia, BudapestMagyar Tudomänyos Akademia, Budapest
Vertreter:Representative:
Dr. G. W. LotterhosDr. G. W. Lotterhos
und Dr.-Ing. H. W. Lotterhos, Patentanwälte,and Dr.-Ing. H. W. Lotterhos, patent attorneys,
Frankfurt/M., Annastr. 19Frankfurt / M., Annastr. 19th
Als Erfinder benannt:Named as inventor:
Dipl.-Ing. Chem. Dr. Denes Beke,Dipl.-Ing. Chem. Dr. Denes Beke,
Dipl.-Ing. Chem. Dr. Csaba Szäntay, BudapestDipl.-Ing. Chem. Dr. Csaba Szäntay, Budapest
Beanspruchte Priorität:Claimed priority:
Ungarn vom 28. März 1961 (1026)Hungary of March 28, 1961 (1026)
wonnen werden, wenn man quartäre 3,4-Dihydroisochinoliniumsalze der allgemeinen Formel IIare obtained if you quaternary 3,4-dihydroisoquinolinium salts of the general formula II
Χθ Χ θ
Ν® — C — R6 Ν® - C - R 6
CH-R7 CH-R 7
R8 — CH2 — CR 8 - CH 2 - C
worin Ri bis Rs die oben angegebene Bedeutung besitzen und X für das Anion einer starken Säure, z. B. für ein Halogenid- oder ein Sulfatanion, steht, in wäßriger Lösung der Einwirkung von Basen ausgesetzt werden.wherein Ri to Rs have the meaning given above own and X for the anion of a strong acid, e.g. B. for a halide or a sulfate anion, exposed to the action of bases in aqueous solution.
Es war nicht vorauszusehen, daß Chinolizinderivate der Formel I auf diesem Wege mit guter Ausbeute erhalten werden können, da bei den Verbindungen der Formel II die Möglichkeit nicht nur für eine ringschließende intramolekulare Kondensation, sondern ebenso auch für eine intermolekulare Kondensation besteht.It was not foreseeable that quinolizine derivatives of the formula I would be able to produce good yields in this way can be obtained, since the compounds of formula II the possibility not only for a ring-closing intramolecular condensation, but also for an intermolecular condensation consists.
709 680/418709 680/418
Die als Ausgangsstoffe verwendeten quartären 3,4-Dihydroisochinoliniumsalze der allgemeinen Formel II können in nicht beanspruchter Weise mit äußerst guter Ausbeute durch Umsetzung von 3,4-Dihydroisochinolinsalzen der allgemeinen Formel IIIThe quaternary 3,4-dihydroisoquinolinium salts of the general formula used as starting materials II can in an unclaimed manner with extremely good yield by implementing 3,4-dihydroisoquinoline salts of the general formula III
RiRi
N-HXN-HX
IIIIII
IOIO
bei erhöhter Temperatur mit Methylvinylketonen der allgemeinen Formel IVat elevated temperature with methyl vinyl ketones of the general formula IV
R5NR 5 N
Re'Re'
>C => C =
C —CH2R8 C —CH 2 R 8
IVIV
I IlI Il
R7 OR 7 O
erhalten werden.can be obtained.
Das auf solche Weise hergestellte, die quartären 3,4-Dihydroisochinoliniumsalze der allgemeinen Formel II enthaltende Reaktionsgemisch kann gegegebenenfalls auch unmittelbar ohne Isolierung des Ausgangsstoffes II mit Basen behandelt und so in das gewünschte Produkt übergeführt werden.The 3,4-dihydroisoquinolinium quaternary salts of the general formula prepared in this way II-containing reaction mixture can optionally also directly without isolation of the Starting material II treated with bases and thus converted into the desired product.
Es wurde schon vorgeschlagen (deutsche Auslegeschrift 1 134 678), Chinolizinderivate durch Umsetzung von 3,4-Dihydroisochinolinen mit Alkylvinylketonen herzustellen. Bei diesem Verfahren müssen die als Ausgangsstoff verwendeten substituierten 3,4-Dihydroisochinoline im basischen Medium mit den Alkylvinylketonen umgesetzt werden. Unter solchen Bedingungen treten aber unerwünschte Nebenreaktionen auf, durch welche die Ausbeuten stark herabgesetzt und das Reaktionsgemisch verunreinigt werden.It has already been proposed (German Auslegeschrift 1 134 678), quinolizine derivatives by implementation of 3,4-dihydroisoquinolines with alkyl vinyl ketones to manufacture. In this process, the substances used as starting materials must be substituted 3,4-Dihydroisoquinolines are reacted in a basic medium with the alkyl vinyl ketones. Under such conditions, however, undesired side reactions occur, which reduce the yields greatly reduced and the reaction mixture contaminated.
Die erfindungsgemäß hergestellten Chinolizinderivate werden dagegen mit sehr guter Ausbeute erhalten.The quinolizine derivatives prepared according to the invention, on the other hand, have a very good yield obtain.
Die weiteren Einzelheiten des erfindungsgemäßen Verfahrens werden durch die nachfolgenden Beispielteile b) erläutert.The further details of the process according to the invention are illustrated in the following examples b) explained.
a) 2,27 g o^-Dimethoxy-S^-dihydroisochinolinhydrochlorid werden mit 5 ml Methylvinylketona) 2.27 g of o ^ -dimethoxy-S ^ -dihydroisoquinoline hydrochloride are with 5 ml of methyl vinyl ketone
1 Stunde auf dem Wasserbad erwärmt und dann zur Trockne eingedampft.Heated on the water bath for 1 hour and then evaporated to dryness.
b) Das mit quantitativer Ausbeute erhalteneb) That obtained with quantitative yield
2 - (ß - Acetoäthyl) - 6,7 - dimethoxy - 3,4 - dihydroisochinoliniumchlorid, welches aus Wasser mit 2 Mol Kristallwasser kristallisiert und bei 142 bis 143 0C schmilzt, wird in 20 ml Wasser gelöst und die Lösung mit 5%iger Natriumcarbonatlösung alkalisch gestellt. Auf diese Weise werden 2,1 g 2-0x0-9,10-dimethoxy-1,2,3,4,6,7-hexahydrollbH-benzo[a]chinolizin (80,5% der Theorie) in kristalliner Form erhalten. Schmp. 154 bis 155 0C.2 - (ß - acetoethyl) - 6,7 - dimethoxy - 3,4 - dihydroisoquinolinium chloride, which crystallizes from water with 2 mol of water of crystallization and melts at 142 to 143 0 C, is dissolved in 20 ml of water and the solution with 5% Sodium carbonate solution made alkaline. In this way, 2.1 g of 2-0x0-9,10-dimethoxy-1,2,3,4,6,7-hexahydrollbH-benzo [a] quinolizine (80.5% of theory) are obtained in crystalline form. Mp. 154-155 0 C.
B e i s ρ i e 1 2 6j B is ρ ie 1 2 6j
a) 1,65 g 3,4-Dihydroisochinolin-hydrochlorid werden mit 3 ml Methylvinylketon 1 Stunde auf dem Wasserbad erwärmt. Dann wird das Reaktionsgemisch im Vakuum zur Trockne verdampft und der Rückstand aus Aceton umkristallisiert.a) 1.65 g of 3,4-dihydroisoquinoline hydrochloride become warmed with 3 ml of methyl vinyl ketone on a water bath for 1 hour. The reaction mixture is then evaporated to dryness in vacuo and the residue recrystallized from acetone.
b) Die auf diese Weise erhaltenen 2 g des farblosen, kristallinen 2-(/S-Acetoäthyl)-3,4-dihydroisochinoliniumchlorids (Ausbeute 85%, Schmp. 2200C) werden in Wasser gelöst und die Lösung mit wäßrigem Ammoniak bis zur alkalischen Reaktion versetzt; es werden 1,5 g 2-Oxo-1,2,3,4,6,7-hexahydrollbH-benzo[a]chinolizin (75% der Theorie) erhalten. Schmp. 78 bis 79 0C.b) The thus obtained 2 g of colorless, crystalline 2 -. (/ S-Acetoäthyl) -3,4-dihydroisochinoliniumchlorids (yield 85%, mp 220 0 C) is dissolved in water and the solution with aqueous ammonia to alkaline reaction added; 1.5 g of 2-oxo-1,2,3,4,6,7-hexahydrollbH-benzo [a] quinolizine (75% of theory) are obtained. M.p. 78 to 79 0 C.
a) 2,11 g 6,7-Methylendioxy-8-methoxy-3,4-dihydroisochinolin werden in 2 ml Äthanol unter Erwärmen gelöst und die Lösung mit einer äquivalenten Menge äthanolischer Salzsäure, dann mit 4 ml Methylvinylketon versetzt. Das Gemisch wird 1 Stunde auf dem Wasserbad erwärmt, dann im Vakuum verdampft.a) 2.11 g of 6,7-methylenedioxy-8-methoxy-3,4-dihydroisoquinoline are dissolved in 2 ml of ethanol with warming and the solution with an equivalent Amount of ethanolic hydrochloric acid, then mixed with 4 ml of methyl vinyl ketone. The mixture will Heated on the water bath for 1 hour, then evaporated in vacuo.
b) Der Rückstand wird in Wasser gelöst und die Lösung mit wäßriger Natriumcarbonatlösung bis zur alkalischen Reaktion versetzt. Durch Umkristallisieren des erhaltenen kristallinen Niederschlags aus wäßrigem Äthanol werden 2 g 2-Oxo-9,10-methylendioxy-11 -methoxy-1,2,3,4,6,7-hexahydro-11 b H-benzo[a]chinolizin (70% der Theorie) erhalten. Schmp. 133 bis 1340C.b) The residue is dissolved in water and aqueous sodium carbonate solution is added to the solution until it has an alkaline reaction. By recrystallizing the resulting crystalline precipitate from aqueous ethanol, 2 g of 2-oxo-9,10-methylenedioxy-11-methoxy-1,2,3,4,6,7-hexahydro-11 b H-benzo [a] quinolizine ( 70% of theory). Mp. 133 to 134 0 C.
a) 2,27 g o^-Dimethoxy-S^-dihydroisochinolinhydrochlorid werden mit 5 ml 2-Äthyl-l-buten-3-on und 4 ml absolutem Äthanol 1 Stunde auf dem Wasserbad unter Rückfluß erhitzt. Dann wird das Reaktionsgemisch im Vakuum zur Trockne eingedampft. a) 2.27 g of o ^ -dimethoxy-S ^ -dihydroisoquinoline hydrochloride are with 5 ml of 2-ethyl-l-buten-3-one and 4 ml of absolute ethanol for 1 hour on the water bath heated to reflux. The reaction mixture is then evaporated to dryness in vacuo.
b) Der Rückstand wird in Wasser gelöst und mit 5%iger Natriumcarbonatlösung bis zur alkalischen Reaktion versetzt. Es werden auf diese Weise 2,34 g 2-Oxo-3-äthyl-9,10-dimethoxy-l,2,3,4,6,7-hexahydrollbH-benzo[a]chinolizin (81% der Theorie) in kristalliner Form" erhalten; Schmp. 110 bis 112 0C.b) The residue is dissolved in water and mixed with 5% sodium carbonate solution until an alkaline reaction occurs. In this way, 2.34 g of 2-oxo-3-ethyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydrollbH-benzo [a] quinolizine (81% of theory) are crystalline Form "obtained; m.p. 110 to 112 0 C.
a) 5,61 g oJ-Dimethoxy-S^-dihydroisochinolinhydrochlorid (kristalline Form, mit 3 Mol Kristallwasser) werden mit 6 ml absolutem Äthanol und 10 ml 2-Isobutyl-l-buten-3-on auf dem Wasserbad 5 Stunden erwärmt. Das Reaktionsgemisch wird dann zur Trockne verdampft und der Rückstand aus Wasser umkristallisiert. 5 g 2-(/?-AcetyI-/?-isobutyl - äthyl) - 6,7 - dimethoxy- 3,4 - dihydroisochinoliniumchlorid (72% der Theorie, Schmp. 208 bis 2090C) werden erhalten.a) 5.61 g of oJ-dimethoxy-S ^ -dihydroisoquinoline hydrochloride (crystalline form, with 3 mol of water of crystallization) are heated with 6 ml of absolute ethanol and 10 ml of 2-isobutyl-l-buten-3-one on a water bath for 5 hours. The reaction mixture is then evaporated to dryness and the residue is recrystallized from water. 5 g 2 - (/? - acetyl - /? - isobutyl - ethyl) - 6,7 - dimethoxy 3,4 - dihydroisochinoliniumchlorid (72% of theory, mp 208-209 0 C.) Can be obtained.
b) Das nach a) erhaltene Salz wird in Wasser gelöst und die Lösung mit wäßriger Natriumcarbonatlösung bis zur alkalischen Reaktion versetzt. 4 g 2-Oxo-3-isobutyl-9,10-dimethoxy-l,2,3,4,6,7-hexahydro-llbH-benzo[a]chinolizin (89% der Theorie) werden in kristalliner Form erhalten. Schmp. 1250C.b) The salt obtained according to a) is dissolved in water and aqueous sodium carbonate solution is added to the solution until an alkaline reaction occurs. 4 g of 2-oxo-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-IIbH-benzo [a] quinolizine (89% of theory) are obtained in crystalline form. M.p. 125 0 C.
c) Das zur Herstellung des Ausgangsstoffs nach a) benötigte, in der Literatur bisher nicht beschriebene 2-Isobutyl-l-buten-3-on wird aus 2-Methylhexan-5-on folgendermaßen in nicht beanspruchter Weise hergestellt :c) That which is required for the production of the starting material according to a) and which has not yet been described in the literature 2-Isobutyl-1-buten-3-one is prepared from 2-methylhexan-5-one as follows in a manner not claimed :
Die mit Formaldehyd und Dimethylamin erhaltene Mannich-Base wird in Essigsäureäthylester mit Methyljodid zum entsprechenden Quartärsalz (Schmp. 180 bis 1810C) umgesetzt und dann durchThe Mannich base obtained with formaldehyde and dimethylamine is reacted in ethyl acetate with methyl iodide to give the corresponding quaternary salt (mp. 180-181 0 C) and then through
Behandlung mit verdünnter Natronlauge in das gewünschte ungesättigte Keton übergeführt; das 2-Isobutyl-l-buten-3-on siedet unter einem Druck von 13 mm Quecksilbersäule bei 53 bis 55° C \n2g = 1,4356; Schmelzpunkt des Semicarbazons 168 bis 169 0C.Treatment with dilute sodium hydroxide solution converted into the desired unsaturated ketone; The 2-isobutyl-l-buten-3-one boils under a pressure of 13 mm of mercury at 53 to 55 ° C. 2 g = 1.4356; Melting point of the semicarbazone 168 to 169 0 C.
a) 5,61 g oJ-Dimethoxy-B^dihydroisochinolinhydrochlorid (kristalline Form, mit 3 Mol Kristallwasser) werden mit 10 ml Mesityloxyd 2 Stunden auf dem Wasserbad erwärmt. Das Reaktionsgemisch wird im Vakuum zur Trockne verdampft und der Rückstand in Wasser gelöst.a) 5.61 g of oJ-dimethoxy-B ^ dihydroisoquinoline hydrochloride (crystalline form, with 3 mol of water of crystallization) with 10 ml of mesityl oxide for 2 hours warmed on the water bath. The reaction mixture is evaporated to dryness in vacuo and the Residue dissolved in water.
b) Die Lösung wird mit wäßriger Natriumcarbonatlösung bis zur alkalischen Reaktion versetzt und das derart gefällte 2-Oxo-4,4'-dimethyl-9,10-dimethoxy-l,2,3,4,6,7-hexahydro-llbH-benzo[a]chinoIizin isoliert. Schmp. 145°C.b) Aqueous sodium carbonate solution is added to the solution until it has an alkaline reaction the 2-oxo-4,4'-dimethyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-IIbH-benzo [a] quinoIizine precipitated in this way isolated. M.p. 145 ° C.
Claims (1)
/CH
/
C /
C.
R4 T
R 4
Deutsche Patentschrift Nr. 1 134 678.Considered publications:
German patent specification No. 1 134 678.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUMA001026 | 1961-03-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1253271B true DE1253271B (en) | 1967-11-02 |
Family
ID=10998369
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEM52128A Pending DE1253271B (en) | 1961-03-28 | 1962-03-14 | Process for the preparation of 2-oxo-1, 2, 3, 4, 6, 7-hexahydro-11bH-benzo [a] quinolizines |
Country Status (4)
| Country | Link |
|---|---|
| AT (1) | AT238201B (en) |
| CH (1) | CH429734A (en) |
| DE (1) | DE1253271B (en) |
| GB (1) | GB958936A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101409335B1 (en) * | 2011-08-17 | 2014-06-23 | 충북대학교 산학협력단 | Methods for Stereoselective Synthesis of Tetrabenazine |
-
1962
- 1962-03-14 DE DEM52128A patent/DE1253271B/en active Pending
- 1962-03-14 AT AT211962A patent/AT238201B/en active
- 1962-03-16 GB GB1023762A patent/GB958936A/en not_active Expired
- 1962-03-16 CH CH319062A patent/CH429734A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AT238201B (en) | 1965-01-25 |
| GB958936A (en) | 1964-05-27 |
| CH429734A (en) | 1967-02-15 |
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