DE1190466B - Process for the preparation of piperazine derivatives - Google Patents

Process for the preparation of piperazine derivatives

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Publication number
DE1190466B
DE1190466B DEC25449A DEC0025449A DE1190466B DE 1190466 B DE1190466 B DE 1190466B DE C25449 A DEC25449 A DE C25449A DE C0025449 A DEC0025449 A DE C0025449A DE 1190466 B DE1190466 B DE 1190466B
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naphthyl
tetrahydro
piperazine
amine
general formula
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German (de)
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Dr Adolf Stachel
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Cassella Farbwerke Mainkur AG
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Cassella Farbwerke Mainkur AG
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Priority to DEC25449A priority Critical patent/DE1190466B/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Description

Verfahren zur Herstellung von Piperazinderivaten Es wurde gefunden, daß man Piperazinderivate der allgemeinen Formel worin R einen geraden oder verzweigten Alkylrest, einen Oxyalkyl-, Methoxyalkyl-, Alkenyl-, Cycloalkyl-, Aralkyl-, Aryl- oder Alkoxyarylrest bedeutet, und ihre Salze erhält, wenn man in an sich bekannter Weise entweder a) ein N,N - Bis - (ß - halogenäthyl) -1,2,3,4 - tetrahydro-naphthyl-(2)-amiri der allgemeinen Formel worin Hal ein Halogenatom bedeutet, mit einem Amin der allgemeinen Formel R - NH2 gegebenenfalls in Anwesenheit eines säurebindenden Mittels umsetzt oder b) 1,2,3,4 - Tetrahydro - naphthyl - (2) - amin mit einem Amin der allgemeinen Formel kondensiert oder e) das Piperazinderivat der Formel mit einer Halogenverbindung der allgemeinen Formel R - Hal gegebenenfalls in Anwesenheit säurebindender Mittel umsetzt und gegebenenfalls anschließend die erhaltenen Basen mit anorganischen oder organischen Säuren in Salze überführt.Process for the preparation of piperazine derivatives It has been found that piperazine derivatives of the general formula in which R is a straight or branched alkyl radical, an oxyalkyl, methoxyalkyl, alkenyl, cycloalkyl, aralkyl, aryl or alkoxyaryl radical, and its salts are obtained if either a) an N, N - is obtained in a manner known per se. Bis - (ß - haloethyl) -1,2,3,4 - tetrahydro-naphthyl- (2) -amiri of the general formula where Hal denotes a halogen atom, reacts with an amine of the general formula R - NH2, optionally in the presence of an acid-binding agent, or b) 1,2,3,4 - tetrahydronaphthyl - (2) - amine with an amine of the general formula condensed or e) the piperazine derivative of the formula with a halogen compound of the general formula R - Hal, optionally in the presence of acid-binding agents, and optionally then converting the bases obtained into salts with inorganic or organic acids.

Die neuen Verbindungen sind teils gut destillierbare Ule, teils kristallisierte Substanzen. Sie können als Arzneimittel, z. B. als Antihypertonika, verwendet werden.Some of the new compounds are easily distillable and some are crystallized Substances. They can be used as drugs, e.g. B. as antihypertensive agents.

Erfindungsgemäß herstellbare Piperazinderivate wurden bezüglich ihrer blutdrucksenkenden Wirkung an mit Urethan narkotisierten Katzen geprüft und mit dem bekannten, in gleicher Weise wirksamen [2 - (Octahydro -1- azocinyl) - äthyl] - guanidin - Sulfat verglichen. Die Blutdruckregistrierung erfolgte mit einem Quecksilbermanometer. Die Verbindungen wurden intravenös injiziert. Die Ergebnisse sind in folgender Tabelle zusammengefaßt, wobei wie folgt bewertet wurde: ++ Blutdrucksenkung um 10 bis 25% + + + Blutdrucksenkung um 25 bis 500% nach 15 Minuten ++++ Blutdrucksenkung ummehr als 500,1a Toxizität Blutdruckbeeinflussung Verbindung LDsn glkg i. v. Dosis Bewertung Maus mg/kg i. v. 1. 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-(o-methoxyphenyl)- 1,0 ++-r piperazindihydrochlorid .................................. 0,026 2,0 + + - + 2. 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-cyclohexyl-piperazin- 1,0 +t + dihydrochlorid .......................................... 0,024 2,0 +++ 3. 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-sec.butyl-piperazin- dihydrochlorid .......................................... 0,019 2,0 + + + 4. 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-n-butyl-piperazin ..... 0,02 2,0 + + + 4,0 +++ 0,5 + + 5. [2-(Octahydro-l-azocinyl)-äthyl]-guanidin-sulfat .............. 0,034 1,0 +@ 2,0 + Beispiel 1 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-n-propyl-piperazin Ein Gemisch von 27,2g (0,1 Mol) N,N-Bis-(ß-chloräthyl)-1,2,3,4-tetrahydro-naphthyl-(2)-amin und 17,7 g (0,3 Mol) n-Propylamin in 100 ccm Alkohol wird 12 Stunden unter Rückfluß gekocht. Dann wird das Lösungsmittel zum größten Teil abdestilliert, der Rückstand mit 100 ccm Wasser verrieben und abgesaugt. Die so erhaltene farblose Substanz wäscht man mit Wasser und trocknet sie. Aus wenig Alkohol umkristallisiert, erhält man das 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-n-propyl-piperazin in farblosen Kristallen; F. 192 bis 194°C; Ausbeute: 20,5 g (79,5%).Piperazine derivatives which can be prepared according to the invention were tested with regard to their antihypertensive effect on cats anesthetized with urethane and compared with the known, equally effective [2- (octahydro-1-azocinyl) -ethyl] -guanidine-sulfate. The blood pressure was recorded with a mercury manometer. The compounds were injected intravenously. The results are summarized in the following table, the evaluation being carried out as follows: ++ lowering blood pressure by 10 to 25% + + + Reduction of blood pressure by 25 to 500% after 15 minutes ++++ lowering blood pressure by more than 500.1a Toxicity Influence of blood pressure Connection LDsn glkg iv dose rating Mouse mg / kg iv 1. 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4- (o-methoxyphenyl) - 1.0 ++ - r piperazine dihydrochloride .................................. 0.026 2.0 + + - + 2. 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] - 4-cyclohexyl-piperazine-1.0 + t + dihydrochloride .......................................... 0.024 2.0 +++ 3. 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4-sec.butyl-piperazine- dihydrochloride .......................................... 0.019 2.0 + + + 4. 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] -4-n-butyl-piperazine ..... 0.02 2.0 +++ 4.0 +++ 0.5 ++ 5. [2- (Octahydro-l-azocinyl) ethyl] guanidine sulfate .............. 0.034 1.0 + @ 2.0 + Example 1 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] -4-n-propyl-piperazine A mixture of 27.2 g (0.1 mol) N, N- Bis- (ß-chloroethyl) -1,2,3,4-tetrahydro-naphthyl- (2) -amine and 17.7 g (0.3 mol) of n-propylamine in 100 cc of alcohol are refluxed for 12 hours. Most of the solvent is then distilled off, and the residue is triturated with 100 cc of water and filtered off with suction. The colorless substance thus obtained is washed with water and dried. Recrystallized from a little alcohol, 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] -4-n-propyl-piperazine is obtained in colorless crystals; M.p. 192 to 194 ° C; Yield: 20.5 g (79.5%).

Zur Herstellung des Dihydrochlorids löst man 1 Mol der Base in wenig Alkohol und versetzt mit 2 Mol alkoholischer Salzsäure. Die abgeschiedenen Kristalle werden aus Alkohol umkristallisiert; F. 286 bis 288'C (Zersetzung).To prepare the dihydrochloride, 1 mol of the base is dissolved in a little Alcohol and mixed with 2 mol of alcoholic hydrochloric acid. The deposited crystals are recrystallized from alcohol; F. 286 to 288 ° C (decomposition).

Beispiel 2 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-n-butyl-piperazin Ein Gemisch von 27,2 g (0,1 Mol) N,N-Bis-(fl-chloräthyl)-1,2,3,4-tetrahydro-naphthyl-(2)-amin, 7,3g (0,1 Mol) n-Butylamin und 20,2 g (0,2 Mol) Triäthylamin wird in 100 ccm Alkohol 10 Stunden unter Rückfluß gekocht. Dann destilliert man das Lösungsmittel zum größten Teil ab und versetzt den Rückstand mit 100 ccm Wasser. Das ausgeschiedene 1- [1',2',3',4'-Tetrahydro- naphthyl -(2')]-4-n - butylpiperazin wird abgesaugt, mit Wasser gewaschen und getrocknet. Aus wenig Alkohol umkristallisiert, erhält man es in farblosen Kristallen; F. 137 bis 139°C; Ausbeute: 22 g (85%).Example 2 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] -4-n-butyl-piperazine A mixture of 27.2 g (0.1 mol) of N, N -Bis- (fl-chloroethyl) -1,2,3,4-tetrahydro-naphthyl- (2) -amine, 7.3 g (0.1 mol) n-butylamine and 20.2 g (0.2 mol) Triethylamine is refluxed for 10 hours in 100 cc of alcohol. Most of the solvent is then distilled off and 100 cc of water are added to the residue. The precipitated 1- [1 ', 2', 3 ', 4'-tetrahydronaphthyl- (2')] -4-n-butylpiperazine is filtered off with suction, washed with water and dried. Recrystallized from a little alcohol, it is obtained in colorless crystals; Mp 137-139 ° C; Yield: 22 g (85%).

Das Dihydrochlorid wird wie im Beispiel 1 angegeben hergestellt. Man erhält farblose Kristalle; F. 295 bis 296°C (Zersetzung).The dihydrochloride is prepared as indicated in Example 1. Man receives colorless crystals; M.p. 295 to 296 ° C (decomposition).

Beispiel 3 1-[1',2',3',4'-Tetrahyoro-naphthyl-(2')]-4-(3"-methoxypropyl)-piperazin Ein Gemisch von 62 g (0,2 Mol) N,N-Bis-(ß-chloräthyl)-1,2,3,4-tetrahydro-naphthyl-(2)-amin-chlorhydrat und 72 g (0,8 Mol) 3-Methoxy-propylamin wird in 200 ccm Alkohol 8 Stunden unter Rückfluß gekocht. Dann destilliert man das Lösungsmittel ab und versetzt den Rückstand mit 200 ccm Wasser. Man extrahiert zweimal mit je 150 ccm Benzol. Die vereinigten Benzolextrakte wäscht man mit 100 ccm Wasser. Nach Trocknen über Glaubersalz wird das Lösungsmittel abdestilliert und der Rückstand einer Vakuumdestillation unterworfen. Das 1-[1',2',3', 4'-Tetrahydro-naphthyl-(2')]-4-(3"-methoxypropyl)-piperazin geht bei Kp.0,a = 160 bis 165°C als farbloses, dickes ih über; Ausbeute: 25 g (87%).Example 3 1- [1 ', 2', 3 ', 4'-Tetrahyoro-naphthyl- (2')] - 4- (3 "-methoxypropyl) -piperazine A mixture of 62 g (0.2 mol) of N, N-bis (ß-chloroethyl) -1,2,3,4-tetrahydro-naphthyl- (2) amine chlorohydrate and 72 g (0.8 mol) of 3-methoxypropylamine is taken in 200 cc of alcohol for 8 hours Refluxed. The solvent is then distilled off and the residue is added with 200 ccm of water. It is extracted twice with 150 cc of benzene each time. The United Benzene extracts are washed with 100 cc of water. After drying over Glauber's salt it becomes the solvent is distilled off and the residue is subjected to vacuum distillation. The 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4- (3 "-methoxypropyl) -piperazine works at bp 0, a = 160 to 165 ° C as a colorless, thick ih over; Yield: 25 g (87%).

Das Dihydrochlorid bildet weiße Kristalle; F. 269'C (Zersetzung). Beispiel 4 1-[1',2',3'.4'-Tetrahydro-naphthyl-(2')]-4-(o-methoxyphenyl)-piperazin 24,8 g (0,1 Mol) N,N-Bis-(i3-(Zhloräthyl)-o-anisidin und 44,1 g (0,3 Mol) 1,2,3.4-Tetrahydro-naphthyl-(2)-amin werden in 100 ccm Alkohol 12 Stunden unter Rückfluß gekocht. Dann destilliert man das Lösungsmittel ab und verreibt den Rückstand mit 100 ccm Wasser. Der farblose Niederschlag wird abgesaugt, mit Wasser gewaschen und getrocknet. Aus Alkohol umkristallisiert, erhält man so das 1 -[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-(o-methoxyphenyl)-piperazin in farblosen Kristallen; F.87'-'C ; Ausbeute: 24 g (800;o).The dihydrochloride forms white crystals; F. 269'C (decomposition). Example 4 1- [1 ', 2', 3'.4'-Tetrahydro-naphthyl- (2 ')] - 4- (o-methoxyphenyl) -piperazine 24.8 g (0.1 mol) N, N- Bis- (i3- (chloroethyl) -o-anisidine and 44.1 g (0.3 mol) 1,2,3,4-tetrahydro-naphthyl- (2) -amine are refluxed in 100 cc of alcohol for 12 hours The solvent is distilled off and the residue is triturated with 100 cc of water. The colorless precipitate is filtered off with suction, washed with water and dried. Recrystallized from alcohol, 1 - [1 ', 2', 3 ', 4'-tetrahydro is obtained -naphthyl- (2 ')] - 4- (o-methoxyphenyl) -piperazine in colorless crystals; F.87' - 'C; Yield: 24 g (800; o).

Das Dihydrochlorid bildet farblose Kristalle; F. 245'C (Zersetzung).The dihydrochloride forms colorless crystals; F. 245'C (decomposition).

Beispiel 5 1-[1',2',3'.4'-Tetrahydro-naphthyl-(2')]-4-(t3-oxyäthyl)-piperazin Ein Gemisch von 43,2 g (0,2 Mol) 1-[1',2',3',4'-Tetrahydro - naphthyl - (2')] - piperazin, 16 g (0,2 Mol) Äthylenchlorhydrin und 20,2 g (0,2 Mol) Triäthylamin wird in 200 ccm trockenem Xylol 10 Stunden unter Rückfluß gerührt. Nach Erkalten versetzt man mit 200 ccm Wasser, trennt die wäßrige Schicht ab und destilliert das Xylol nach dem Trocknen über Glaubersalz im Wasserstrahlvakuum bei 40°C ab. Den Rückstand, ein 01, destilliert man im Hochvakuum. Das 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-(ß-oxyäthyl)-piperazin geht bei Kp.o,4 = 178 bis 180°C als farbloses, dickes 01 über, das nach längerem Stehen kristallisiert; Ausbeute: 21 g (810!o).Example 5 1- [1 ', 2', 3'.4'-Tetrahydro-naphthyl- (2 ')] - 4- (t3-oxyethyl) -piperazine A mixture of 43.2 g (0.2 mol) of 1 - [1 ', 2', 3 ', 4'-Tetrahydro - naphthyl - (2')] - piperazine, 16 g (0.2 mol) of ethylene chlorohydrin and 20.2 g (0.2 mol) of triethylamine is in 200 ccm of dry xylene was stirred under reflux for 10 hours. After cooling, 200 cc of water are added, the aqueous layer is separated off and the xylene is distilled off after drying over Glauber's salt in a water jet vacuum at 40.degree. The residue, an 01, is distilled in a high vacuum. The 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4- (β-oxyethyl) -piperazine is colorless at bp 0.4 = 178 to 180 ° C , thick 01 over, which crystallizes after standing for a long time; Yield: 21 g (810! O).

Das Dihydrochlorid bildet weiße Kristalle; F. 256 bis 258°C (Zersetzung).The dihydrochloride forms white crystals; M.p. 256 to 258 ° C (decomposition).

Der benötigte Ausgangsstoff wurdefolgendermaßen hergestellt Ein Gemisch von 294 g (2 Mol) 1,2,3,4-Tetrahydronaphthyl-(2)-amin und 312 g (1 Mol) N,N-Bis-(ß - bromäthyl) - amin - hydrobromid wird in 500 ccm wasserfreiem Butanol 18 Stunden unter Rühren rückfließend gekocht. Nun gibt man 106 g (1 Mol) wasserfreie Soda zu und destilliert das Butanol mit Wasserdampf ab. Der Destillationsrückstand wird mit 1,51 Wasser versetzt, mit verdünnter Salzsäure neutralisiert und ausgeäthert. Die wäßrige Schicht stellt man mit 40%iger Natronlauge stark alkalisch und extrahiert dreimal mit 500 ccm Benzol. Die vereinigten Benzqlextrakte werden zuerst mit Wasser und dann mit 200 ccm 40%iger Natronlauge gewaschen. Nach dem Trocknen über Glaubersalz destilliert man das Lösungsmittel ab und fraktioniert den Rückstand im Vakuum. Das 1-[1',2',3',4'-Tetrahydro - naphthyl - (2')] - piperazin geht bei Kp.o,.a = 145 bis 155'C als dickes, gelbliches UI über.The required starting material was prepared as follows: A mixture of 294 g (2 mol) 1,2,3,4-tetrahydronaphthyl- (2) -amine and 312 g (1 mol) N, N-bis- (ß-bromoethyl) -amine - hydrobromide is refluxed for 18 hours with stirring in 500 cc of anhydrous butanol. 106 g (1 mol) of anhydrous soda are then added and the butanol is distilled off with steam. The distillation residue is mixed with 1.5 liters of water, neutralized with dilute hydrochloric acid and extracted with ether. The aqueous layer is made strongly alkaline with 40% sodium hydroxide solution and extracted three times with 500 cc of benzene. The combined benzene extracts are washed first with water and then with 200 cc of 40% sodium hydroxide solution. After drying over Glauber's salt, the solvent is distilled off and the residue is fractionated in vacuo. The 1- [1 ', 2', 3 ', 4'-tetrahydro - naphthyl - (2')] - piperazine changes to a thick, yellowish UI at bp. O, .a = 145 to 155 ° C.

In analoger Weise wie in den vorstehenden Beispielen beschrieben, wurden folgende Verbindungen hergestellt: 1-[ 1',2',3',4'-Tetrahydro-naphthyl-(2') ]-4-isobutyl-piperazin-dihydrochlorid F. 305°C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-sek.butyl-piperazin-dihydrochlorid F. 290'C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-isohexyl-piperazin-dihydrochlorid F. 287°C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-isoheptyl-piperazin-dihydrochlorid F. 288 ° C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-(3"-oxypropyl)-piperazin-dihydrochlorid F. 270°C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-(2"-oxy-1 ",1 "-dimethyläthyl)-piperazindihydrochlorid F. 261°C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-allyl-piperazin-dihydrochlorid F. 268'C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-cyclohexyl-piperazin-dihydrochlorid F. 317°C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-benzyl-piperazin-dihydrochlorid F. 283'C (Zersetzung) 1-[l',2',3',4'-Tetrahydro-naphthyl-(2')]-4-fl-phenyläthyl-piperazin-dihydrochlorid F. 308'C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-benzhydryl-piperazin-dihydrochlorid F. 232°C (Zersetzung) 1-[1',2',3',4'-Tetrahydro-naphthyl-(2')]-4-o-äthoxyphenyl-piperazin-dihydrochlorid F. 264°C (Zersetzung)In a manner analogous to that described in the preceding examples, the following compounds were prepared: 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] -4-isobutyl-piperazine dihydrochloride F. 305 ° C (decomposition) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4-sec.butyl-piperazine dihydrochloride F. 290'C (decomposition) 1- [ 1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] - 4-isohexyl-piperazine dihydrochloride m.p. 287 ° C (decomposition) 1- [1 ', 2', 3 ', 4 '-Tetrahydro-naphthyl- (2')] - 4-isoheptyl-piperazine dihydrochloride F. 288 ° C (decomposition) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2') ] -4- (3 "-oxypropyl) -piperazine dihydrochloride mp 270 ° C (decomposition) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4- ( 2 "-oxy-1", 1 "-dimethylethyl) piperazine dihydrochloride F. 261 ° C (decomposition) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] - 4- allyl-piperazine dihydrochloride m.p. 268'C (decomposition) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] -4-cyclohexyl-piperazine dihydrochloride mp 317 ° C (Decomposition) 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] - 4-benzyl-piperazine-dihydroc chloride F. 283'C (decomposition) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] -4-fl-phenylethyl-piperazine dihydrochloride F. 308'C (decomposition ) 1- [1 ', 2', 3 ', 4'-tetrahydro-naphthyl- (2')] -4-benzhydryl-piperazine dihydrochloride F. 232 ° C (decomposition) 1- [1 ', 2', 3 ', 4'-Tetrahydro-naphthyl- (2')] - 4-o-ethoxyphenyl-piperazine dihydrochloride F. 264 ° C (decomposition)

Claims (1)

Patentanspruch: Verfahren zur Herstellung von Piperazinderivaten der allgemeinen Formel worin R einen geraden oder verzweigten Alkylrest, einen Oxyalkyl-, Methoxyalkyl-, Alkenyl-, Cycloalkyl-, Aralkyl-, Aryl- oder Alkoxyarylrest bedeutet, und von ihren Salzen, d a d u r c h gekennzeichnet, daß man in an sich bekannter Weise entweder a) ein N,N-Bis-(ß-halogenäthyl)-1,2,3,4-tetrahydro - naphthyl - (2) - amin der allgemeinen Formel worin Hal ein Halogenatom bedeutet, mit einem Amin der allgemeinen Formel R - NH2 gegebenenfalls in Anwesenheit eines säurebindenden Mittels umsetzt oder b) 1,2,3,4 - Tetrahydro - naphthyl - (2) - amin mit einem Amin der allgemeinen Formel kondensiert oder e) das Piperazinderivat der Formel mit einer Halogenverbindung der allgemeinen Formel R - Hal gegebenenfalls in Anwesenheit eines säurebindenden Mittels umsetzt und gegebenenfalls anschließend die erhaltenen Basen mit anorganischen oder organischen Säuren in Salze überführt. In Betracht gezogene Druckschriften Journ. Chem. Soc., 1949, S. 2831 bis 2834; Experientia, 15 (1959), S.267; H e 1 w i g, Mgderne Arzneimittel (l956), S. 79.Claim: Process for the preparation of piperazine derivatives of the general formula wherein R is a straight or branched alkyl radical, an oxyalkyl, methoxyalkyl, alkenyl, cycloalkyl, aralkyl, aryl or alkoxyaryl radical, and of their salts, characterized in that either a) an N , N-bis (ß-haloethyl) -1,2,3,4-tetrahydro - naphthyl - (2) - amine of the general formula where Hal denotes a halogen atom, reacts with an amine of the general formula R - NH2, optionally in the presence of an acid-binding agent, or b) 1,2,3,4 - tetrahydronaphthyl - (2) - amine with an amine of the general formula condensed or e) the piperazine derivative of the formula with a halogen compound of the general formula R - Hal, optionally in the presence of an acid-binding agent, and optionally then converting the bases obtained into salts with inorganic or organic acids. Publications considered Journ. Chem. Soc., 1949, pp. 2831-2834; Experientia, 15 (1959), p.267; H e 1 wig, Mgderne Arzneimittel (1956), p. 79.
DEC25449A 1961-11-07 1961-11-07 Process for the preparation of piperazine derivatives Pending DE1190466B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0000395A1 (en) * 1977-07-18 1979-01-24 Sandoz Ag 2-Piperazinotetraline derivatives, their preparation and their use as medicines
WO2010012817A2 (en) * 2008-08-01 2010-02-04 Laboratorios Del Dr. Esteve, S.A. 5ht7 receptor ligands and compositions comprising the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0000395A1 (en) * 1977-07-18 1979-01-24 Sandoz Ag 2-Piperazinotetraline derivatives, their preparation and their use as medicines
WO2010012817A2 (en) * 2008-08-01 2010-02-04 Laboratorios Del Dr. Esteve, S.A. 5ht7 receptor ligands and compositions comprising the same
WO2010012817A3 (en) * 2008-08-01 2010-04-15 Laboratorios Del Dr. Esteve, S.A. 5ht7 receptor ligands and compositions comprising the same

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