CH467743A - Process for the preparation of dibenzocycloheptenes - Google Patents
Process for the preparation of dibenzocycloheptenesInfo
- Publication number
- CH467743A CH467743A CH1532268A CH1532268A CH467743A CH 467743 A CH467743 A CH 467743A CH 1532268 A CH1532268 A CH 1532268A CH 1532268 A CH1532268 A CH 1532268A CH 467743 A CH467743 A CH 467743A
- Authority
- CH
- Switzerland
- Prior art keywords
- group
- carbon atoms
- compound
- formula
- alkyl
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/31—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by at least three rings
- C07C211/32—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by at least three rings containing dibenzocycloheptane or dibenzocycloheptene ring systems or condensed derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
- C07C1/24—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms by elimination of water
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
- C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Display Racks (AREA)
Description
Verfahren zur Herstellung von Dibenzocycloheptenen
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von neuen 5H-Dibenzo(a,d)cy- cloheptenen und 10,11-Dihydro-5H-dibenzo(a,d)cycloheptenen und deren Salze, weiche am Kohlenstoff der 5-Stellung durch einen Aminopropylrest substituiert sind.
Diese Verbindungen können zur Blehandlung von Gelsteskrankheiten verwendet werden, Ida sie als Mittel gegen Depressionszustände bzw. zur Aufheiterung des Gesmüts und als psychische Energiespender wirksam sind. Für solche Fälle kann die tägliche Dosis 5 bis 250 mg betragen, welche vorzugsweise in Teildosen ein genommen wird. Diese Verbindungen werden vorzugsweise in Form ihrer mit Säuren erhaltlichen Salze verabreicht.
Die nach dem erfindungsgemässen Verfahren herstellbaren Dibenzocycloheptene haben folgende Formel
EMI1.1
worin X und X' Wasserstoff; eine Alkylgruppe oder eine Aikenylgruppe mit bis zu 6 Kohlenstoffatomen; eine Perfluoralkylgruppe mit Ibis zu 4 Kohlenstoffatomen; ein Phenyl- oder substituiertes Phenylradikal, eine Acylgruppe oder eine Perfluoracylgruppe mit bis zu 4 Kohlenstoffatomen; eine Aminogruppe, eine Alkylamino- gruppe mit bis zu 4 Kohlenstoffatomen; eine Dialkylaminogruppe mit bis zu 6 ohienstoffatomen; ; eine Acylaminogruppe oder eine Perfluoracylaminogruppe oder eine Alkylsulfonylaminogruppe mit bis zu 4 Kohlenstoffatomen;
Halogen; Hydroxyl; eine Alkoxygruppe oder eine Perfluoralkoxygruppe mit bis zu 4 Kohlenstoffatomen; Cyan; Carboxy; Carbamyl; eine Alkylcarbamyl gruppe mit bis zu 5 Kohlenstoffatomen; eine Dialkyl- oarbamylgruppe mit bis zu 9 Kohlenstoffatomen; eine Carbalkoxygruppe mit bis zu 6 Kohlenstoffatomen ; Mercapto- oder eine Alkylmercaptogruppe oder eine Alkylsulfonylgruppe oder eine Perfluoralkylsulfonylgruppe mit bis zu 4 Kohlenstoffatomen; Sulfamyl; eine Alkylsulfa mylgruppe mit bis zu 4 Kohlenstoffatomen; oder eine Dialkylsulfamylgruppe mit bis zu 6 Kohlenstoffatomen und R eine Alkylgruppe mit bis zu 6 Kohlenstoffatomen bedeuten.
Die punktierte Linie zwischen den Stellungen 10 und 11 bedeutet, IdLass die Verbindungen an dieser Stelle gesättigt oder ungesättigt sein können, wobei die ge- sättigte Verbindung als die 10,11-dihydroverbindung bezeichnet wird.
Das erfindungsgemässe Verfahren zur Herstellung von Dibenzocycloheptenen der angegebenen Formel ist nur dadurch gekennzeichnet, dass man eine Verbindung der Formel
EMI1.2
mit einem Alkylbenzylamin in absolutem Alkohol zur Reaktion bringt, wobei eine Verbindung der Formel
EMI1.3
entsteht, worauf diese Verbindung in Gegenwart von Palladium und Wasserstoff hydriert wird.
Bei der Gewinnung des sekundären Amins mittels katalytischer Debenzylierung der entsprechenden Additionsverbindung kann man beispielsweise wie folgt verfahren: Man lässt die Jodverbindung langsam mit einem N-Alkylbenzylamin reagieren, so dass keine wesentliche Temperatursteigerung über Raumtemperatur erfolgt, wobei als Lösungsmittel abs. Alkohol verwendet wird.
Dann erhitzt man Idie Reaktionsmischung während 15 bis 60 min zum Rückfluss und verdampft das Lösungs- mittel. Durch Hydrierung mit Hilfe von Wasserstoff und Palladium als Katalysator findet eine selektive Debenzylierung statt, wobei das entsprechende sekundäre Amin erhalten wird.
Die freie Base lässt sich leicht in ein Säureadditions 'salz überführen, z. B. in das Oxalat. Hierbei kann man so verfahren, dass man die in warmen abs. Äthanol gelöste Base mit einer äquimolaren Menge an in Äthanol gelöster Oxalsäure umsetzt. Durch Zusatz von Äther wird das gebildete saure Salz ausgefällt und dann zweckmässig aus einer Methanol-Äthylacetat-Mischung um kristallisiert.
Die Herstellung des 3-Jo'dpropylAusgangsstoffes aus der entsprechenden Alkoxypropylverbindung mit Jodwasserstoff ist im schweizerischen Patent Nr. 464 900 näher beschrieben.
Beispiel 1
Herstellung von 5-(3-Ä'thylaminopropyl)-5H-dib enzo(a,d)cyclohepten
1. Man fügt allmählich 5-(3-Jodpropyl)-5H diblenzo- (a,d)cyclohepten einem Überschuss an N-Äthylbenzylamin in abs. Alkohol unter Rühren und Kühlung zu.
Hierauf erhitzt man die Reaktionsmischung während 30 min zum Rüdkfiuss und dampft dann den Alkohol unter reduziertem Druck ab. Den Rückstand nimmt man mit warmer verdünnter Säure auf, filtriert, macht die wässrige Schicht alkalisch und extrahiert die freigemachte Base mit Äther. Durch Verdampfung des Äthers hinterbleibt 5-(3-[N-Benzyl-N-äthylamino]-propyl)-5Hdibenzo(a,d)cyclohepten.
2. Man löst das so erhaltene Produkt in abs. Alkohol und hydriert mittels eines Palladium-Tonerdekatalysa- tors bei 40-60 C. Als Rückstand erhält man nach Abtrennung vom Katalysator und Vendampfung des Lösungsmittels das gewünschte Produkt.
Beispiel 2
Verwendet man als Ausgangsstoff die 10,1 1-Di- hydroverbindung gemäss Verfahren nach Beispiel 1, so erhält man das entsprechende 10,11-Dihydroderivat als Endprodukt, nämlich 10,11-Dihydro-5-(3-äthylaminopropyl)-dibenzo(a,d)cyclohepten.
Process for the preparation of dibenzocycloheptenes
The present invention relates to a process for the preparation of new 5H-dibenzo (a, d) cycloheptenes and 10,11-dihydro-5H-dibenzo (a, d) cycloheptenes and their salts, soft on the carbon of the 5-position are substituted by an aminopropyl radical.
These compounds can be used to treat gel disease, because they are effective as a remedy for states of depression or to cheer up the mind and as a psychic energy donor. For such cases, the daily dose can be 5 to 250 mg, which is preferably taken in divided doses. These compounds are preferably administered in the form of their salts obtainable with acids.
The dibenzocycloheptenes which can be prepared by the process according to the invention have the following formula
EMI1.1
wherein X and X 'are hydrogen; an alkyl group or an alkenyl group of up to 6 carbon atoms; a perfluoroalkyl group with ibis of 4 carbon atoms; a phenyl or substituted phenyl radical, an acyl group, or a perfluoroacyl group of up to 4 carbon atoms; an amino group, an alkylamino group with up to 4 carbon atoms; a dialkylamino group with up to 6 ohienstoffatomen; ; an acylamino group or a perfluoroacylamino group or an alkylsulfonylamino group having up to 4 carbon atoms;
Halogen; Hydroxyl; an alkoxy group or a perfluoroalkoxy group having up to 4 carbon atoms; Cyan; Carboxy; Carbamyl; an alkylcarbamyl group of up to 5 carbon atoms; a dialkyl oarbamyl group of up to 9 carbon atoms; a carbalkoxy group of up to 6 carbon atoms; Mercapto or an alkyl mercapto group or an alkylsulfonyl group or a perfluoroalkylsulfonyl group with up to 4 carbon atoms; Sulfamyl; an alkylsulfamyl group of up to 4 carbon atoms; or a dialkylsulfamyl group with up to 6 carbon atoms and R an alkyl group with up to 6 carbon atoms.
The dotted line between positions 10 and 11 means that the compounds at this point can be saturated or unsaturated, the saturated compound being referred to as the 10,11-dihydro compound.
The process according to the invention for the preparation of dibenzocycloheptenes of the formula given is only characterized in that a compound of the formula
EMI1.2
with an alkylbenzylamine in absolute alcohol to react, with a compound of the formula
EMI1.3
arises, whereupon this compound is hydrogenated in the presence of palladium and hydrogen.
When the secondary amine is obtained by catalytic debenzylation of the corresponding addition compound, the following procedure can be used, for example: The iodine compound is allowed to react slowly with an N-alkylbenzylamine so that there is no significant increase in temperature above room temperature, with abs. Alcohol is used.
The reaction mixture is then refluxed for 15 to 60 minutes and the solvent is evaporated. By hydrogenation with the aid of hydrogen and palladium as a catalyst, a selective debenzylation takes place, the corresponding secondary amine being obtained.
The free base can easily be converted into an acid addition salt, e.g. B. in the oxalate. Here you can proceed in such a way that one in warm abs. Ethanol-dissolved base is reacted with an equimolar amount of oxalic acid dissolved in ethanol. The acid salt formed is precipitated by adding ether and then recrystallized from a methanol-ethyl acetate mixture.
The preparation of the 3-jo'dpropyl starting material from the corresponding alkoxypropyl compound with hydrogen iodide is described in more detail in Swiss Patent No. 464,900.
example 1
Preparation of 5- (3-ethylaminopropyl) -5H-dib enzo (a, d) cycloheptene
1. Gradually add 5- (3-iodopropyl) -5H diblenzo- (a, d) cycloheptene to an excess of N-ethylbenzylamine in abs. Add alcohol with stirring and cooling.
The reaction mixture is then heated to the rüdkfiuss for 30 minutes and the alcohol is then evaporated off under reduced pressure. The residue is taken up in warm, dilute acid, filtered, the aqueous layer is made alkaline and the liberated base is extracted with ether. Evaporation of the ether leaves 5- (3- [N-benzyl-N-ethylamino] propyl) -5Hdibenzo (a, d) cycloheptene.
2. The product thus obtained is dissolved in abs. Alcohol and hydrogenated by means of a palladium-alumina catalyst at 40-60 ° C. The desired product is obtained as the residue after separation from the catalyst and evaporation of the solvent.
Example 2
If the 10,1 1-dihydro compound is used as the starting material in accordance with the method according to Example 1, the corresponding 10,11-dihydro derivative is obtained as the end product, namely 10,11-dihydro-5- (3-ethylaminopropyl) -dibenzo (a , d) cycloheptene.
Claims (1)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12083561A | 1961-05-24 | 1961-05-24 | |
US14022361A | 1961-09-25 | 1961-09-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
CH467743A true CH467743A (en) | 1969-01-31 |
Family
ID=26818813
Family Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH628562A CH464893A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
CH1531868A CH467744A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of 5H-dibenzo- (a, d) -cycloheptenes |
CH1532168A CH465599A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
CH1531968A CH467238A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of 5H-dibenzo- (a, d) -cycloheptenes |
CH1104067A CH464900A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
CH1532268A CH467743A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
CH1532068A CH464903A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
Family Applications Before (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH628562A CH464893A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
CH1531868A CH467744A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of 5H-dibenzo- (a, d) -cycloheptenes |
CH1532168A CH465599A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
CH1531968A CH467238A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of 5H-dibenzo- (a, d) -cycloheptenes |
CH1104067A CH464900A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH1532068A CH464903A (en) | 1961-05-24 | 1962-05-24 | Process for the preparation of dibenzocycloheptenes |
Country Status (13)
Country | Link |
---|---|
BE (1) | BE617967A (en) |
BR (1) | BR6239240D0 (en) |
CH (7) | CH464893A (en) |
CY (1) | CY354A (en) |
DE (2) | DE1593098A1 (en) |
DK (6) | DK110035C (en) |
FI (3) | FI41391B (en) |
FR (1) | FR2516M (en) |
GB (1) | GB1008263A (en) |
GT (1) | GT197016875A (en) |
MY (1) | MY6700003A (en) |
NO (1) | NO121833B (en) |
SE (8) | SE317369B (en) |
-
1962
- 1962-05-16 GB GB18913/62A patent/GB1008263A/en not_active Expired
- 1962-05-18 FI FI1007/62A patent/FI41391B/fi active
- 1962-05-21 DE DE19621593098 patent/DE1593098A1/en active Pending
- 1962-05-21 DE DE19621468212 patent/DE1468212A1/en active Pending
- 1962-05-22 BR BR139240/62A patent/BR6239240D0/en unknown
- 1962-05-22 BE BE617967A patent/BE617967A/en unknown
- 1962-05-23 DK DK232162AA patent/DK110035C/en active
- 1962-05-23 NO NO144482A patent/NO121833B/no unknown
- 1962-05-23 DK DK106164AA patent/DK107420C/en active
- 1962-05-23 DK DK106264AA patent/DK106278C/en active
- 1962-05-23 DK DK166663AA patent/DK106326C/en active
- 1962-05-23 DK DK106064AA patent/DK108151C/en active
- 1962-05-24 CH CH628562A patent/CH464893A/en unknown
- 1962-05-24 SE SE5885/62A patent/SE317369B/xx unknown
- 1962-05-24 CH CH1531868A patent/CH467744A/en unknown
- 1962-05-24 CH CH1532168A patent/CH465599A/en unknown
- 1962-05-24 CH CH1531968A patent/CH467238A/en unknown
- 1962-05-24 CH CH1104067A patent/CH464900A/en unknown
- 1962-05-24 CH CH1532268A patent/CH467743A/en unknown
- 1962-05-24 CH CH1532068A patent/CH464903A/en unknown
- 1962-05-24 SE SE13207/65A patent/SE325269B/xx unknown
- 1962-08-22 FR FR907533A patent/FR2516M/en active Active
-
1964
- 1964-02-27 DK DK97064AA patent/DK111679B/en unknown
-
1965
- 1965-05-14 SE SE635365A patent/SE318869B/xx unknown
- 1965-10-12 SE SE13209/65A patent/SE326441B/xx unknown
- 1965-10-12 SE SE13211/65A patent/SE326442B/xx unknown
- 1965-10-12 SE SE13204/65A patent/SE323364B/xx unknown
- 1965-10-12 SE SE13205/65A patent/SE326440B/xx unknown
- 1965-10-12 SE SE13210/65A patent/SE325874B/xx unknown
-
1966
- 1966-10-03 FI FI2587/66A patent/FI41646B/fi active
- 1966-10-03 FI FI2588/66A patent/FI41647B/fi active
- 1966-10-14 CY CY35466A patent/CY354A/en unknown
-
1967
- 1967-12-31 MY MY19673A patent/MY6700003A/en unknown
-
1970
- 1970-05-11 GT GT197016875A patent/GT197016875A/en unknown
Also Published As
Publication number | Publication date |
---|---|
CH465599A (en) | 1968-11-30 |
SE317369B (en) | 1969-11-17 |
CH464900A (en) | 1968-11-15 |
GT197016875A (en) | 1971-11-02 |
CH467238A (en) | 1969-01-15 |
NO121833B (en) | 1971-04-19 |
SE325269B (en) | 1970-06-29 |
MY6700003A (en) | 1967-12-31 |
CH464903A (en) | 1968-11-15 |
DE1468212A1 (en) | 1969-01-02 |
DE1593098A1 (en) | 1969-10-16 |
FI41391B (en) | 1969-07-31 |
DK106326C (en) | 1967-01-23 |
CH464893A (en) | 1968-11-15 |
BE617967A (en) | 1962-11-22 |
SE318869B (en) | 1969-12-22 |
DK106278C (en) | 1967-01-16 |
DK111679B (en) | 1968-09-30 |
SE326440B (en) | 1970-07-27 |
CH467744A (en) | 1969-01-31 |
BR6239240D0 (en) | 1973-05-24 |
DK108151C (en) | 1967-09-25 |
SE326442B (en) | 1970-07-27 |
SE323364B (en) | 1970-05-04 |
CY354A (en) | 1966-10-14 |
GB1008263A (en) | 1965-10-27 |
SE326441B (en) | 1970-07-27 |
DK110035C (en) | 1968-09-02 |
FR2516M (en) | 1964-05-11 |
SE325874B (en) | 1970-07-13 |
FI41646B (en) | 1969-09-30 |
DK107420C (en) | 1967-05-29 |
FI41647B (en) | 1969-09-30 |
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