CH303080A - Process for the preparation of a heterocyclic polymethylene-bis-quaternary ammonium salt. - Google Patents
Process for the preparation of a heterocyclic polymethylene-bis-quaternary ammonium salt.Info
- Publication number
- CH303080A CH303080A CH303080DA CH303080A CH 303080 A CH303080 A CH 303080A CH 303080D A CH303080D A CH 303080DA CH 303080 A CH303080 A CH 303080A
- Authority
- CH
- Switzerland
- Prior art keywords
- bis
- polymethylene
- heterocyclic
- preparation
- quaternary ammonium
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- YXWQTVWJNHKSCC-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCN1 YXWQTVWJNHKSCC-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- -1 (1,2,3,4-tetrahydro-6,7-dimethoxy-1- (3,4-dimethoxy-benzyl) -isoquinolyl) decane Chemical compound 0.000 description 1
- CKJCTZAIDVFHCX-UHFFFAOYSA-N 1,10-diiododecane Chemical compound ICCCCCCCCCCI CKJCTZAIDVFHCX-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960002362 neostigmine Drugs 0.000 description 1
- LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical group [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung eines heterocyclischen PoIymethylen-bis-quaternären Ammoniumsalzes. Vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung eines heterocycli- schen Polymethylen-bis-quaternären Ammo- niiunsalzes mit Curare ähnlichen Eigenschaf ten.
Das Verfahren ist dadurch gekennzeich- net, dass man ein a,co-Decamethylendihalogenid mit Tetrahydropapaverin-hydrohalogenid um setzt und das entstandene Umsetzungsprodukt in das Dimethosulfat überführt. Die so er haltene Verbindung von der Formel
EMI0001.0015
schmilzt bei 172 bis 174 C.
Die Umsetzung wird zweckmässig durch längeres Kochen am Rückfloss in einem iner- ten Lösungsmittel wie Benzol oder Äthylalko- hol vorgenommen.
Die neue Verbindung soll zu pharmazeuti schen Zwecken Verwendung finden.
Zur Erläuterung der Erfindung diene folgendes Beispiel: Eine Mischung von Decamethylen-di-jodid (11.,8 g), Tetrahydropapaverinhydrojodid (29,7 g, 2 Mol -I- 5%), wasserfreies Kalium- carbonat (15 g) und<B>95%</B> Alkohol (360 ml) wurden während 104 Stunden am Rückfloss gekocht. Der Alkohol wurde hierauf abdestil- liert, und jegliches zurückgebliebenes Wasser wurde durch azeotrope Destillation mit Benzol entfernt.
Der Rückstand wurde hierauf, so weit als möglich, in heissem, trockenem Benzol gelöst, filtriert und das Lösungsmittel zurück gewonnen (die letzten Reste -desselben wurden unter Vakuum entfernt). Der ölige Rückstand wurde darauf in der minimalen Menge wasser freien Alkohols gelöst und mit trockenem alkoholischem Chlorwasserstoff bis zu kongorot angesäuert.
Nach dem Abkühlen wurde das entstandene Dihydrochlorid abfiltriert, mit kaltem Alkohol gewaschen und getrocknet, wobei 25,6-g eines Rohmaterials (Smp. 236 bis 238 C) erhalten wurden. Dieses wurde aus 500 ml siedenden Wassers umkristallisiert, wobei das Dihydrochlorid des a,co-Bis-(1,2,3,4- tetrahydro-6,7-dimethoxy-1- (3,4-dimethoxy- benzyl)-isochinolyl)
-decan als farbloses Pulver (Smp. 242 bis 244 C unter Zersetzung) erhalten wurde. Ausbeute 20,5 g (76 %). Gefunden: C, 66,7; H, 7,75; N, 3,2; Cl, 7,95; Berechnet: C50H700gN2C12 C, 66,9; H, 7,9; N, 3,1; Cl, 7,9 %. Das so erhaltene Dihydrochlorid (20 g) wurde in siedendem Wasser (700 ml) gelöst, mit Natriumhydroxyd alkalisch gemacht, mit Natriumchlorid gesättigt und das sich aus scheidende braune Öl mit heissem Benzol extra hiert.
Die Benzollösung wurde mit festem Kaliumhydroxyd geschüttelt, filtriert und auf etwa 100 ml konzentriert. Eine Lösung von Dimethylsulfat (8,45 g, 50% überschuss) in trockenem Benzol (25 ml) wurde hinzu gefügt und das Gemisch während 48 Stunden am Rückfluss gekocht. Das Benzol wurde dann vom abgeschiedenen gummiartigen Feststoff dekantiert und der letztere dreimal durch Dekantieren mit heissem Benzol gewaschen.
Nach Vakuumtrocknung wurde der bröckelige Rückstand in heissem, wasserfreiem Alkohol gelöst, zur warmen Lösung Äther zugegeben und das Gemisch der langsamen Kristalli sation überlassen. Nach zwei weiteren Um kristallisationen erhielt man als Produkt ein cremefarbiges, körniges Pulver (10 g), wel ches bei 172 bis 174 C schmolz, nachdem es bei 164 bis 166 C sich dunkel gefärbt hatte. Gefunden: C, 60,1; H, 7,75; N, 2,6; S, 5,9; Berechnet: C54IIsoOisN2S2 C, 60,2; H, 7,5; N, 2,6; S, 5,95 %.
Pharmakologische Untersuchungen haben ergeben, dass die gemäss vorliegender Erfin dung hergestellte Verbindung bei Katzen be merkenswerte paralysierende Wirkung hervor ruft, vergleichbar derjenigen von Tiibociirarin- dimethyläther. Als Gegenmittel gilt Neo- stigmin.
Process for the preparation of a heterocyclic polymethylene-bis-quaternary ammonium salt. The present invention relates to a process for the preparation of a heterocyclic polymethylene-bis-quaternary ammonium salt with curare-like properties.
The process is characterized in that an α, co-decamethylene dihalide is reacted with tetrahydropapaverine hydrohalide and the resulting reaction product is converted into the dimethosulfate. The resulting compound from the formula
EMI0001.0015
melts at 172 to 174 C.
The reaction is expediently carried out by refluxing for a long time in an inert solvent such as benzene or ethyl alcohol.
The new compound is intended to be used for pharmaceutical purposes.
The following example serves to illustrate the invention: A mixture of decamethylene di-iodide (11th, 8 g), tetrahydropapaverine hydroiodide (29.7 g, 2 mol -I- 5%), anhydrous potassium carbonate (15 g) and < B> 95% alcohol (360 ml) was refluxed for 104 hours. The alcohol was then distilled off and any remaining water was removed by azeotropic distillation with benzene.
The residue was then, as far as possible, dissolved in hot, dry benzene, filtered and the solvent recovered (the last residues of the same were removed under vacuum). The oily residue was then dissolved in the minimum amount of anhydrous alcohol and acidified to Congo red with dry alcoholic hydrogen chloride.
After cooling, the dihydrochloride formed was filtered off, washed with cold alcohol and dried, whereby 25.6 g of a raw material (mp 236-238 ° C.) were obtained. This was recrystallized from 500 ml of boiling water, the dihydrochloride of a, co-bis (1,2,3,4-tetrahydro-6,7-dimethoxy-1- (3,4-dimethoxy-benzyl) -isoquinolyl)
decane was obtained as a colorless powder (m.p. 242 to 244 C with decomposition). Yield 20.5g (76%). Found: C, 66.7; H, 7.75; N, 3.2; Cl, 7.95; Calculated: C50H700gN2C12 C, 66.9; H, 7.9; N, 3.1; Cl, 7.9%. The dihydrochloride thus obtained (20 g) was dissolved in boiling water (700 ml), made alkaline with sodium hydroxide, saturated with sodium chloride and the brown oil which separated out was extracted with hot benzene.
The benzene solution was shaken with solid potassium hydroxide, filtered and concentrated to approximately 100 ml. A solution of dimethyl sulfate (8.45 g, 50% excess) in dry benzene (25 ml) was added and the mixture was refluxed for 48 hours. The benzene was then decanted from the deposited gummy solid and the latter washed three times by decanting with hot benzene.
After vacuum drying, the crumbly residue was dissolved in hot, anhydrous alcohol, ether was added to the warm solution and the mixture was allowed to slowly crystallize. After two further recrystallizations, the product obtained was a cream-colored, granular powder (10 g) which melted at 172 to 174 C after it had turned dark at 164 to 166 C. Found: C, 60.1; H, 7.75; N, 2.6; S, 5.9; Calculated: C54IIsoOisN2S2 C, 60.2; H, 7.5; N, 2.6; S, 5.95%.
Pharmacological investigations have shown that the compound prepared according to the present invention has a remarkable paralyzing effect in cats, comparable to that of tiibociirarin dimethyl ether. The antidote is neostigmine.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB303080X | 1950-10-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH303080A true CH303080A (en) | 1954-11-15 |
Family
ID=10305569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH303080D CH303080A (en) | 1950-10-24 | 1951-10-09 | Process for the preparation of a heterocyclic polymethylene-bis-quaternary ammonium salt. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH303080A (en) |
-
1951
- 1951-10-09 CH CH303080D patent/CH303080A/en unknown
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