CH366553A - Process for the preparation of 3a-acyloxy-6ss-hydroxytropanes - Google Patents
Process for the preparation of 3a-acyloxy-6ss-hydroxytropanesInfo
- Publication number
- CH366553A CH366553A CH5773658A CH5773658A CH366553A CH 366553 A CH366553 A CH 366553A CH 5773658 A CH5773658 A CH 5773658A CH 5773658 A CH5773658 A CH 5773658A CH 366553 A CH366553 A CH 366553A
- Authority
- CH
- Switzerland
- Prior art keywords
- acyloxy
- saponification
- starts
- hydroxytropanes
- amount
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims 3
- 125000002252 acyl group Chemical group 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 229930004006 tropane Natural products 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- BKWVNPXVPQOROM-HTQZYQBOSA-N (1r,5r)-8-methyl-8-azabicyclo[3.2.1]octan-5-ol Chemical compound C1CC[C@@]2(O)CC[C@]1([H])N2C BKWVNPXVPQOROM-HTQZYQBOSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- JACRWUWPXAESPB-QMMMGPOBSA-N Tropic acid Natural products OC[C@H](C(O)=O)C1=CC=CC=C1 JACRWUWPXAESPB-QMMMGPOBSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000020176 deacylation Effects 0.000 description 1
- 238000005947 deacylation reaction Methods 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- APLLVFVOTXZBFO-UHFFFAOYSA-N valeroidine Natural products C1C(OC(=O)CC(C)C)CC2CC(O)C1N2C APLLVFVOTXZBFO-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von 3a-Acyloxy-6ss-hydroxytropanen Die Monoacylabkörnmlinge des Tropan-3a,6ss- diols sind wichtige Intermediäre zur Herstellung von 6-Tropan-3a-01 und durch diese Verbindung zur Herstellung von 6,7f-Epoxi-3a-hydroxy- bzw.
Acyl- oxytropanabkömnmlinge. Die Herstellung dieser Monoacylabkömmlinge führte weder durch teilweise Hydrolyse, noch durch teilweise Acylierung des Tropan-3a,6f-diols zum Ziele (Stoll A., Jucker E. und Lindemann A., Helvetica Chimica Acta 1953, Bd. 36, Seite 1506 und ff.).
Es wurde gefunden, dass man 3a-Acyloxy-6ss hydroxytropane herstellen kann, wenn man ein 3a,6f-Diacyloxytropan mit verdünnter, wässeriger Alkalilauge in Anwesenheit von in Wasser löslichen hydroxylfreien organischen Lösungsmitteln teilweise verseift.
Als hydroxylfreies Lösungsmittel kann man z. B. Tetrahydrofuran, Dioxan oder Dimethylformamid verwenden. Insbesondere ist die Verwendung von Aceton günstig. Eine optimale Monoacylbildung kann man bei Temperaturen zwischen 25 und 30 C errei chen.
Man verwendet vorteilhaft Alkalilauge in einer Menge, die zwischen der zur Verseifung eines Acyl- restes berechneten und deren zweifachen Menge liegt. Auf diese Weise kann man binnen kurzer Zeit 3a Acyloxy-6-hydroxytropan mit verhältnismässig guter Ausbeute neben unveränderter Diacylverbindung und neben kleineren Mengen von Diol erhalten.
Auf diese Weise kann man von 3a,6ss-Diacetoxy-tropan das 3a-Acetoxy-6ss-hydroxytropan und aus dem Diiso- valeroxytropan das 3a-Isovaleroxy-6fl=hydroxytropan gewinnen. Auf ähnliche Weise kann man aus dem Di-1-Tropasäureester des 1-3a,6ss-Dihydroxytropans das 1-3a-Tropeyloxy-6ss-hydroxytropan gewinnen, welche Verbindung mydriatische Wirkung besitzt.
Diese partielle Desacylierung konnte auf Grund der in der Fachliteratur befindlichen Angaben durch aus nicht vorausgesehen werden.
<I>Beispiel 1</I> 24 g 3a,6ss-Diacetoxytropan werden in 700 ml Aceton gelöst und zu der Lösung 1700 ml n110 NaOH hinzugefügt. Die Lösung wird 65 Minuten lang auf 30 C erwärmt, danach mit etwa 120 ml n HCl neu tralisiert. Das Reaktionsgemisch wird im Vakuum zur Trockne verdampft, der Rückstand in 200 ml Wasser gelöst, mit Kaliumcarbonat auf pH 10 eingestellt und sechsmal mit je 100 ml Chloroform die Base extrahiert.
Das Chloroform-Extrakt wird über Na triumsulfat getrocknet, das Chloroform im Wasser bad abdestilliert. Man erhält auf diese Weise ein viskoses Öl, das durch Verreiben mit eisgekühltem Äther kristallin erstarrt. Ausbeute 15,6 g, 78 % reines 3a-Acetoxy-6ss-hyrdoxytropan. Schmelzpunkt 1l7-118 .
Aus der Ätherlösung kann 3,84 g 3a,6ss- Diacetoxy-tropan zurückgewonnen werden.
<I>Beispiel 2</I> 6,5 g razemisches 3a,6ss-Diisovaleroxytropan- hydrobromid wird in ein Gemisch von 710 ml n(10 NaOH und 200 ml Aceton gelöst. Es wird bei Zimmertemperatur stehengelassen. Nach 6 Stunden wird es mit verdünnter HCl neutralisiert und unter halb von 50 C eingedampft.
Der Rückstand wird in 40 ml Wasser gelöst, die Lösung mit Kalium- carbonat auf pH 10 eingestellt und danach zehnmal mit je 50 ml Chloroform ausgeschüttelt. Die ver einigten Chloroformextrakte werden über Na2S04 getrocknet, das Chloroform abgetrieben.
Man erhält 2,5 g razemisches 3a,6ss-Dihydroxytropan-3-mono- isovalerat. Diese Verbindung kann in abs. Alkohol gelöst mit Salzsäure in das Hydrochlorid überführt werden, dessen Schmelzpunkt 180 C ist.
Diese Ver bindung ist identisch mit dem auf andere Weise her gestellten razemischen Valeroidin-hydrochlorid. Analyse: Berechnet: C = 56,25 H = 8,65 Gefunden: C = 56,22 H = 8,90 <I>Beispiel 3</I> Nach der in Beispiel 2 angegebenen Arbeitsweise kann man aus dem Di-1-Tropasäureester des 1-3a,6ss- Dihydroxytropans 3a -1- Tropeyl-1-3a,6ss-dihydroxy- tropan (Hydrobromid, Schmp. 148 , [a] D = -30 [in Wasser]) erhalten.
Process for the production of 3a-acyloxy-6ss-hydroxytropanes The monoacyl pellets of tropane-3a, 6ss-diol are important intermediates for the production of 6-tropane-3a-01 and through this compound for the production of 6,7f-epoxy-3a-hydroxy - or.
Acyloxytropane Compounds. The production of these monoacyl derivatives did not lead to the goal either by partial hydrolysis or partial acylation of the tropane-3a, 6f-diol (Stoll A., Jucker E. and Lindemann A., Helvetica Chimica Acta 1953, vol. 36, page 1506 and ff .).
It has been found that 3a-acyloxy-6ss hydroxytropane can be produced if a 3a, 6f-diacyloxytropane is partially saponified with dilute, aqueous alkali in the presence of water-soluble, hydroxyl-free organic solvents.
As a hydroxyl-free solvent you can, for. B. use tetrahydrofuran, dioxane or dimethylformamide. The use of acetone is particularly advantageous. Optimal monoacyl formation can be achieved at temperatures between 25 and 30 C.
It is advantageous to use alkali lye in an amount which is between the amount calculated for saponifying an acyl radical and twice the amount thereof. In this way, 3a acyloxy-6-hydroxytropane can be obtained within a short time in a relatively good yield in addition to unchanged diacyl compound and in addition to smaller amounts of diol.
In this way, 3a-acetoxy-6ss-hydroxytropane can be obtained from 3a, 6ss-diacetoxy-tropane and 3a-isovaleroxy-6fl = hydroxytropane from diisovaleroxytropane. In a similar way, 1-3a-tropeyloxy-6ss-hydroxytropane, which compound has a mydriatic effect, can be obtained from the di-1-tropic acid ester of 1-3a, 6ss-dihydroxytropane.
This partial deacylation could not be foreseen on the basis of the information in the specialist literature.
<I> Example 1 </I> 24 g of 3a, 6ss-diacetoxytropane are dissolved in 700 ml of acetone and 1700 ml of n110 NaOH are added to the solution. The solution is heated to 30 ° C. for 65 minutes, then neutralized with about 120 ml of n HCl. The reaction mixture is evaporated to dryness in vacuo, the residue is dissolved in 200 ml of water, adjusted to pH 10 with potassium carbonate and the base is extracted six times with 100 ml of chloroform each time.
The chloroform extract is dried over sodium sulfate, the chloroform is distilled off in a water bath. In this way, a viscous oil is obtained which solidifies in crystalline form by trituration with ice-cold ether. Yield 15.6 g, 78% pure 3a-acetoxy-6ss-hydroxytropane. Melting point 17-118.
3.84 g of 3a, 6ss-diacetoxy-tropane can be recovered from the ethereal solution.
<I> Example 2 </I> 6.5 g of racemic 3a, 6ss-diisovaleroxytropan hydrobromide is dissolved in a mixture of 710 ml of NaOH and 200 ml of acetone. It is left to stand at room temperature. After 6 hours it is with dilute HCl neutralized and evaporated below 50 C.
The residue is dissolved in 40 ml of water, the solution is adjusted to pH 10 with potassium carbonate and then extracted ten times with 50 ml of chloroform each time. The combined chloroform extracts are dried over Na 2 SO 4 and the chloroform is driven off.
2.5 g of racemic 3a, 6ss-dihydroxytropane-3-monoisovalerate are obtained. This connection can be in abs. Dissolved alcohol with hydrochloric acid can be converted into the hydrochloride, the melting point of which is 180 ° C.
This connection is identical to the racemic valeroidin hydrochloride produced in a different way. Analysis: Calculated: C = 56.25 H = 8.65 Found: C = 56.22 H = 8.90 <I> Example 3 </I> Following the procedure given in Example 2, the Di-1- Tropic acid ester of 1-3a, 6ss-dihydroxytropane 3a-1-tropeyl-1-3a, 6ss-dihydroxytropane (hydrobromide, melting point 148, [a] D = -30 [in water]) was obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUFO000287 | 1957-04-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH366553A true CH366553A (en) | 1963-01-15 |
Family
ID=10996235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH5773658A CH366553A (en) | 1957-04-01 | 1958-03-31 | Process for the preparation of 3a-acyloxy-6ss-hydroxytropanes |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH366553A (en) |
-
1958
- 1958-03-31 CH CH5773658A patent/CH366553A/en unknown
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