DE731561C - Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus - Google Patents

Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus

Info

Publication number
DE731561C
DE731561C DEK155512D DEK0155512D DE731561C DE 731561 C DE731561 C DE 731561C DE K155512 D DEK155512 D DE K155512D DE K0155512 D DEK0155512 D DE K0155512D DE 731561 C DE731561 C DE 731561C
Authority
DE
Germany
Prior art keywords
substituted
nucleus
nitrogen
hydroxyl groups
aralkyl
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.)
Expired
Application number
DEK155512D
Other languages
German (de)
Inventor
Dr Med Fritz Kuelz
Dr Clemens Schoepf
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Troponwerke Dinklage and Co
Original Assignee
Troponwerke Dinklage and Co
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Troponwerke Dinklage and Co filed Critical Troponwerke Dinklage and Co
Priority to DEK155512D priority Critical patent/DE731561C/en
Application granted granted Critical
Publication of DE731561C publication Critical patent/DE731561C/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D217/00Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02Heterocyclic 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
    • C07D217/04Heterocyclic 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 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom

Description

Verfahren zur Herstellung von im gtickstoffhaltigen Kern aralkylsubstituierten und in einem aromatischen Kern freie Hydroxylgruppen enthaltenden hydrierten Isochinolinverbindungen Das Hauptpatent 728 326 zu dem Zusatzpatent 73o 667 des vorliegenden Patents hat ein Verfahren zur Herstellung von im stickstoffhaltigen Kern aralkylsubstituierten und in einem aromatischen Kern freie Hydroxylgruppen enthaltenden hydrierten Isochinolinverbindungen, zum Gegenstand, das dadurch gekennzeichnet ist, daß man im stickstoffhaltigen Kern aralkylsubstituierte, nur in einem aromatischen Kern mindestens zwei freie, vorzugsweise in o-Stellung zueinander befindliche Hy droxylgruppen enthaltende, gegebenenfalls noch weiter, z. B. durch Kohlenwasserstoffreste, substituierte, nicht oder nur teilweise hydrierte Isochinolinverbindungen oder deren quartäre Ammoniumsalze in an sich bekannter Weise hydriert. -Das Zusatzpatent 73o 667 hat ein weiteres Verfahren zur Herstellung von im stickstofflialtigen Kern aralkylsubstituierten und in nur einem aromatischen Kern mindestens zwei freie, vorzugsweise in o-Stellung zueinander befindliche Hydroxylgruppen enthaltenden, gegebenenfalls noch weiter, z. B. durch Kohlenwasserstoffreste, substituierten hydrierten Isochinolinverbindungen zum Gegenstand, das dadurch gekennzeichnet ist, daß man von im stickstoffhaltigen Kern aralkylensubstituierten, nicht -oder nur teilweise hydrierten Isochinolinverbindungen oder deren quartären Ammoniumsalzen ausgeht und diese derart hydriert, daß sowolil die Doppelbindungen des Pyridinringes als auch die aliphatischen Doppelbindungen des Aralkylenrestes in einfache Bindungen übergeführt werden.Aralkyl-substituted method for the preparation of gtickstoffhaltigen core and in an aromatic nucleus free hydroxyl group-containing hydrogenated isoquinoline The main patent 728 326 has the addition Patent 73o 667 of the present patent is a process for the preparation of nitrogen-containing core aralkyl-substituted, and containing in an aromatic nucleus free hydroxyl groups hydrogenated isoquinoline , to the subject, which is characterized in that in the nitrogen-containing nucleus aralkyl-substituted, only in an aromatic nucleus containing at least two free, preferably in the o-position to each other Hy hydroxyl groups, optionally further, z. B. hydrogenated by hydrocarbon radicals, substituted, not or only partially hydrogenated isoquinoline compounds or their quaternary ammonium salts in a manner known per se. The additional patent 73o 667 has a further process for the preparation of aralkyl-substituted in the nitrogen-containing nucleus and containing at least two free hydroxyl groups in only one aromatic nucleus, preferably in the o-position to one another, optionally even further, e.g. B. by hydrocarbon radicals, substituted hydrogenated isoquinoline compounds to the subject, which is characterized in that aralkylenesubstituted in the nitrogen-containing nucleus, non-or only partially hydrogenated isoquinoline compounds or their quaternary ammonium salts and these are hydrogenated in such a way that both the double bonds of the pyridine ring and the aliphatic double bonds of the aralkylene radical are converted into single bonds.

Es wurde nun gefunden, daß man solche hydrierten Isochinolinverbindungen auch dadurch herstellen kann, daß man im stickstoffhaltigen Kern aralkylensubstituierte, nur in einem Benzolkern mindestens zwei freie, vorzugsweise in o-Stellung zueinander befindliche Hydroxylgruppen enthaltende, gegebenenfalls noch weiter, z. B. durch gesättigte oder ungesättigte Kohlenwasserstoffreste, substituierte Tetraliv(Iroisocliinolinverbinclungen in an sich bekannter Weise derart livclriert, daß die Aralkylensubstituenten in Äralkvlsubstittienten übergeführt werden.It has now been found that such hydrogenated isoquinoline compounds can be obtained can also be prepared by aralkylene-substituted in the nitrogen-containing nucleus, only in one benzene nucleus at least two free, preferably in O-position to one another containing hydroxyl groups, optionally also further, e.g. B. substituted by saturated or unsaturated hydrocarbon radicals Tetralive (Iroisocliinolinverbinclungen in a manner known per se colored in such a way, that the aralkylene substituents are converted into aralkylene substituents.

Die Hydrierung wird z. B. katalytisch in Gegenwart von Hydrierungsl@atalysatoren, wie Platinmohr, Platinoxyd, Palladium oder Palladiumtierkohle, oder zweckmäßig durch andere Reduktionsmittel, z. B. Jodwasserstoffsäure, vorgenommen, die eine Kohlenstoffdoppelbindung zu einer einfachen Bindung livdrieren.The hydrogenation is z. B. catalytically in the presence of Hydrogenierungsl @ atalysatoren, such as platinum black, platinum oxide, palladium or palladium animal charcoal, or expediently through other reducing agents, e.g. B. hydriodic acid made, which has a carbon double bond livdrive to a simple tie.

Die Ausgangsstoffe für das Verfahren können dadurch hergestellt werden, daß man entsprechend substituierteTetrallydroisochiiloline mit entsprechend substituierten Aralkylenhalogeniden umsetzt oder daß inan entsprechend substituierte ß-(3, 4-Dioxvl)Iienyl)-äthylamitte mit ungesättigten Aralkvleilaldehvden zu Tetrahydroisochmolinen kondensiert.The starting materials for the process can be prepared by reacting correspondingly substituted tetrallydroisochiilolines with correspondingly substituted aralkylene halides or by condensing correspondingly substituted β- (3, 4-dioxvl) iienyl) -ethylamittees with unsaturated aralkvleilaldehydes to give tetrahydroisochmolines.

Von bekannten Verbindungen kommen den erfindungsgemäß hergestellten Verbindungen Tetraliydropapaverolin und Laudanosolin nahe, die jedoch im Gegensatz zu den erfindungsgemäßen erliältlicllen Verbindungen in jedem Benzolkern je -zwei freie Hydroxylgruppen enthalten.Known compounds include those prepared according to the invention Compounds tetraliydropapaverolin and laudanosolin close, however, in contrast to the compounds according to the invention obtainable in each benzene nucleus two each contain free hydroxyl groups.

Diese beiden bekannten Verbindungen wirken weder einetisch noch analgetisch. Weiterhin sindLatidanosolin-3', 4.'-dimethvläther und Laudanosolin-a'-monoinetliylätlier bekannt, Verbindungen also, die zwar in einen Benzolkern zwei freie Hy droxyIgruppen, darüber hinaus aber ein anderen Benzolkern zwei verätherte bzw. eine verätlierte und eine freie Hydroxylgruppe enthalten. Diese beiden Verbindungen wirken stark toxisch und zeigen keine ausgeprägte analgetische Wirkung. Im Gegensatz zti den vier bekannten Verbindtin-en zeichnen sich die erfindtingsgeniiiß erhältlichen Verbindungen durch ihre guten analgetischen und einetischen Wirkungen bc@i nur geringer Toxizität aus.These two well-known compounds are neither toxic nor analgesic. Furthermore, latidanosolin-3 ', 4'-dimethyl ether and laudanosolin-a'-monoinetliyl ether known, compounds that, although two free hydroxyl groups in a benzene nucleus, in addition, however, another benzene nucleus, two etherified and one tethered and contain a free hydroxyl group. These two connections are powerful toxic and show no pronounced analgesic effect. In contrast zti the The compounds obtainable according to the invention are characterized by four known compounds due to their good analgesic and chemical effects bc @ i only low toxicity the end.

Beispiele i. Herstellung von i, 3-Diiiiethyl-2-(^,-plielvlprol>yl)-ti, 7-cüoxv-r, a, 3, .I-tetralivdroisochinolin.Examples i. Preparation of i, 3-Diiiiethyl-2 - (^, - plielvlprol> yl) -ti, 7-cüoxv-r, a, 3, .I-tetralivdroisoquinoline.

g Bromhydrat des 1, 3-Dimet@vl-2-(^@-1#henylallvl)-6, 7-dioxy-i, 2, 3, .I-tetrahydroisocliinolins vorn F. Leg bis 151`' (mit i Kristallalkohol) werden mit 5o ccin konstant siedender- Jodwasserstoffsä ure unter Zusatz von etwas Phosphor 25 Minuten 7u111 lebhaften Sieden erhitzt. Die Reduktion ist dann beendet. Man dampft im Vakuum zur Trockne, zielet den Rückstand finit viel heihein Wasser aus, filtriert, entfärbt die Lösung finit etwas schwefliger Säure, fällt die Base mit Soda und äthert aus. Aus der über Natriumsulfat gut getrockneten Ätherlösung wird mit ätherischer Salzsäure das Chlorlivdrat der in der i@berschrift genannten Verbindung erhalten, das aus Methanol mit 1 Mol. Kristallmethanol auskristallisiert, welches im @'aku@mexs@kkator bei Zimnierteinperatur noch nicht abgegeben wird. Das Chlorhydrat hat folgende Konstitution Es schmilzt bei 121 bis i23'' unter Aufschäumen und stimmt in jeder Hinsicht mit denn aus Methanol umkristallisierten Chlorlivdrat der im Patent 711 o98 beschriebenen Verbindung gleicher Konstitution überein. Analyse: C=, H_,, O, N Cl -E- C H; O H (379,7) Ber. C 66,37 H 8,oo Cl 9,23 Gef. (nach dem "-Trocknen im Exsikkator bis zur Konstanz) C 66,26 H 7,96 Cl 9,o5 2. Herstellung von r - (ß-Plienylätliyl)- 6, 7-dioxv-i, 2, 3, q.-tetrahydroisochinolin. 5 g Bromhydrat des i-(r)-Phenylvinyl)- 6, 7-dioxy-i, 2, 3,-I-tetraliydroisocliinolins vom F. 236 bis 237° «erden in Wasser gelöst und mit o,i g Platinoxyd bei Zimmertemperatur unter Wasserstoff geschüttelt. In kurzer Zeit wird die für i Mol. berechnete :Menge Wasserstoff aufgenommen: die Hydrierung kommt zum Stillstand. Man erwärmt, filtriert vom Katalysator und dampft im `-akuum zweckmäßig unter Stickstoff ein. Das in quantitativer Ausbeute zurückbleibende Bromhydrat des i-(l)'-Phenyläthyl) -6, 7-dioxy -1, 2, 3, 4-tetrahvdroisochinolins schmilzt nach dem Trocknen und Umkristallisiereil aus Äthanol/Essigester bei 79i bis 192° und gibt mit der nach Patent 726173 Beispiel 1 dargestellten Verbindung gleicher Konstitution keine Schinelzpunktsdepression.g bromohydrate of 1, 3-Dimet @ vl-2 - (^ @ - 1 # henylallvl) -6, 7-dioxy-1, 2, 3, .I-tetrahydroisocliinolins from F. Leg to 151` '(with i crystal alcohol ) are heated vigorously boiling for 25 minutes with 50 cc of constant-boiling hydriodic acid with the addition of a little phosphorus. The reduction is then ended. It is evaporated to dryness in vacuo, the residue is finely removed with hot water, filtered, the solution is decolorized with a little sulphurous acid, the base is precipitated with soda and ether is precipitated. From the ether solution, which has been thoroughly dried over sodium sulphate, with ethereal hydrochloric acid, the chloride of the compound named in the heading is obtained, which crystallizes from methanol with 1 mol of crystal methanol, which is not yet given off in the aku @ mexs @ kkator at Zimnierteinperatur. The hydrochloride has the following constitution It melts at 121 to 233 '' with foaming and corresponds in every respect to the chlorine chloride recrystallized from methanol of the compound of the same constitution described in Patent 711,098. Analysis: C =, H_ ,, O, N Cl -E-CH; OH (379.7) calc . C 66.37 H 8, oo Cl 9.23 Found (after "drying in the desiccator to constancy") C 66.26 H 7.96 Cl 9, o5 2. Production of r - (ß-Plienylätliyl) - 6, 7-dioxv-i, 2, 3, q.-tetrahydroisoquinoline. 5 g bromohydrate of i- (r) -phenylvinyl) - 6, 7-dioxy-i, 2, 3, -I-tetraliydroisocliinolins vom F. 236 to 237 ° «earth dissolved in water and with o, ig platinum oxide at room temperature shaken under hydrogen. In a short time the calculated amount of hydrogen for i mole is absorbed: the hydrogenation comes to a standstill. It is heated, the catalyst is filtered off and it is expediently evaporated in a vacuum under nitrogen. The bromohydrate of i- (l) '- phenylethyl) -6, 7-dioxy-1, 2, 3, 4-tetrahvdroisoquinoline remaining in quantitative yield melts after drying and recrystallization from ethanol / ethyl acetate at 79 ° to 192 ° and gives with the compound of the same constitution shown according to patent 726173 Example 1 no Schinelzpunktsdepression.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung von im stickstoffhaltigen Kern aralkylsubstituierten und in einem aromatischen Kern freie Hydroxylgruppen enthaltenden hydrierten Isochinolinveibindungen durch Hydrieren von im stickstoffhaltigen Kern aralkylensubstituierten, nur in einem aromatischen Kern mindestens zwei freie, vorzugsweise in o-Stellung zueinander befindliche Hydroxylgruppen enthaltenden, gegebenenfalls noch weiter, z. B. durch Kohlenwasserstoffreste, substituierten Isochinolinverbindungen nach Patent 73o 667, dadurch gekennzeichnet, daß man von den entsprechenden aralkylensubstituierten Tetrahydroisochinolinverbindungen ausgeht.PATENT CLAIM: Process for the production of nitrogen-containing Aralkyl-substituted nucleus and hydroxyl groups which are free in an aromatic nucleus containing hydrogenated isoquinoline compounds by hydrogenation of nitrogen-containing Aralkylene-substituted nucleus, only in one aromatic nucleus at least two free, preferably containing hydroxyl groups in the o-position to one another, possibly even further, z. B. by hydrocarbon radicals, substituted isoquinoline compounds according to patent 73o 667, characterized in that one of the corresponding aralkylene-substituted Tetrahydroisoquinoline compounds goes out.
DEK155512D 1939-09-03 1939-09-03 Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus Expired DE731561C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DEK155512D DE731561C (en) 1939-09-03 1939-09-03 Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEK155512D DE731561C (en) 1939-09-03 1939-09-03 Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus

Publications (1)

Publication Number Publication Date
DE731561C true DE731561C (en) 1943-02-15

Family

ID=7253287

Family Applications (1)

Application Number Title Priority Date Filing Date
DEK155512D Expired DE731561C (en) 1939-09-03 1939-09-03 Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus

Country Status (1)

Country Link
DE (1) DE731561C (en)

Similar Documents

Publication Publication Date Title
DE2540633C2 (en)
CH625252A5 (en)
DE1643296C3 (en) l-Aryl-2-alkylaminoethanols and their physiologically acceptable acid addition salts, processes for their preparation and pharmaceuticals containing them
DE2154245B2 (en) 3-hydrazino-6- (2-hydroxypropylamino) pyridazine derivatives, process for their preparation and pharmaceutical preparation containing them
DE731561C (en) Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus
DE1617610B2 (en) Process for the manufacture of an aerosol preparation for medical purposes
DE1223396B (en) Process for the preparation of trisodium salts of the zinc complexes of diaethylenetriamine-N, N. N ', N ", N" -pentaacetic acid and of triaethylenetetramine-N, N, N', N ", N" ', N "' - hexaacetic acid
DE2317183C2 (en) Benzylamine analgesics
DE962333C (en) Process for the preparation of cyclohexanone oxime
DE2164988C3 (en) 2,2-Diphenylcyclopropanecarboxylic acid ester derivatives, processes for their preparation and pharmaceuticals containing them
AT265530B (en) Process for the preparation of new isoquinoline derivatives
DE1300110B (en) Process for the preparation of 17beta- (hexahydrobenzyloxycarbonyloxy) -3-oxo-delta 4-estrene
DE728326C (en) Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus
DE936592C (en) Process for the production of a blood and urine sugar lowering preparation from trioxyflavone glucoside-containing parts of plants
DE929969C (en) Process for the catalytic hydrogenation of organic compounds
DE1188583B (en) Process for the preparation of the steroid isomers and the racemate of butane-1, 2, 3, 4-tetrol-1, 4-di- (methanesulfonate)
AT221087B (en) Process for the production of new, basic indole derivatives
DE1593807C (en) alpha ascine methyl or ethy (ester, as well as a process for their production
DE1468554C (en) 20 beta tert amino 3 alpha hydroxy (or acyloxy) 5 beta pregnane or its salts and processes for their manufacture
DE1593825C (en) Amino alcohols, their acid addition salts and process for their preparation
AT234692B (en) Process for the preparation of isoquinoline derivatives
AT226888B (en) Process for the production of nordihydrotoxiferin and its quaternization products
DE2628042B2 (en) 3-Amino-tricyclo [53.1.0.3A1 -undecane, its acid addition salts and process for the preparation of these compounds
DE730667C (en) Process for the preparation of hydrogenated isoquinoline compounds which are aralkyl-substituted in the nitrogen-containing nucleus and which contain free hydroxyl groups in an aromatic nucleus
DE878641C (en) Process for the production of higher molecular amines