CH314569A - Process for the preparation of an anesthetic - Google Patents
Process for the preparation of an anestheticInfo
- Publication number
- CH314569A CH314569A CH314569DA CH314569A CH 314569 A CH314569 A CH 314569A CH 314569D A CH314569D A CH 314569DA CH 314569 A CH314569 A CH 314569A
- Authority
- CH
- Switzerland
- Prior art keywords
- piperidino
- anesthetic
- preparation
- dimethyl
- melting point
- Prior art date
Links
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung eines Anästhetikums Von Aminoalkoholen abgeleitete Ester der Carbanilsäure mit Alkyl- oder Alkoxygruppen in 2,6- oder 2,4,6-Stellung des Phenylrestes besitzen ausgezeichnete anästhetische Eigen schaften, wie hohe Wirksamkeit, geringe Toxi zität und gute Stabilität der Lösungen ihrer Salze, was sie sowohl für die Oberflächen- als auch für die Injektionsanästhesie geeignet macht.
Ein entscheidender Faktor für die Wirksamkeit und Stabilität dieser Ester ist die symmetrische Anordnung der Substituen- ten im Phenylkern der Carba-nilsäure, und Untersuchungen haben ergeben, da.ss besonders die Carbanilsäureester von Alkoholen von der Art von Piperidinoalkanolen und Dialkyl- aminoalkanolen günstige Eigenschaften auf weisen.
Die Verbindungen entsprechen der Formel
EMI0001.0022
in der R1 und % Alkyl- oder Alkoxygruppen, R. Wasserstoff, Alkyl oder eine Alkoxygruppe, R4 eine verzweigte oder uriverzweigte, ge sättigte oder ungesättigte Kohlenwasserstoff kette mit höchstens 6 Kohlenstoffatomen und R,,
und R6 Alkylgruppen oder zusammen mit dem Stickstoff einen gesättigten heterocycli- schen Ring bedeuten.
Diese Anästhetika lassen sich wie folgt herstellen: Ein Arylisoeyanat der Formel
EMI0001.0041
wird zuerst bei Zimmertemperatur und dann bei erhöhter Temperatur mit einem Amino- alkohol der Formel
EMI0001.0045
umgesetzt. Der Aminoalkohol kann auch in Form eines Salzes Anwendung finden.
Die Reaktion setzt beim Zusammenbringen äquivalenter Mengen der beiden Komponen ten spontan ein. Da, sie ausgesprochen exo- thermisch ist, sollte man kühlen und vorzugs weise in einem indifferenten Lösungsmittel arbeiten. Um die Reaktion zu Ende zu brin gen, sollte man noch 1-2 Stunden auf etwa 100 C erhitzen. Das Reaktionsprodukt, der substituierte Carbanilsäureaminoalkyl'ester, lässt sich leicht. isolieren, falls ein Lösungsmittel verwendet wurde, z.
B. durch Extraktion mit verdünnter Salzsäure. Die Salzsäurelösung kann dann mit Aktivkohle und Natriumdithionit nach Ein stellung des pH der Lösung auf 6,5 gereinigt werden. Die Base kann dann durch Aus fällung mit Ammoniak gewonnen werden.
Gegenstand des vorliegenden Patentes ist nun ein Verfahren zur Herstellung von 2,6- Dimethyl - carbanilsäure - ss - piperidino - äthyl- ester, welches dadurch gekennzeichnet ist, dass man 2,6-Dimethyl-phenyl-isocyanat mit ss- Piperidino-äthja.lkohol umsetzt.
An Stelle des Piperidino-äthylalkoholskann man auch ein Salz dieser Base verwenden. _ <I>Beispiel</I> Zu einer Lösung von 147 Teilen 2,6-Di- methyl-phenyl-isocyanat in 200 Teilen Benzol gibt man unter Rühren und Kühlen 129 Teile ss-Piperidino-äthylalkohol. Nachdem alles bei etwa 50 C zugegeben und die Reaktion abge klungen ist, erhitzt man die Lösung 2 Stunden lang unter Rückflusskühlung zum Sieden, worauf man den gebildeten 2,
6-Dimethyl- carbanilsänre-ss-piperidino-äthylester mit ver dünnter Salzsäure extrahiert. Die Salzsäure- lösung wird nach Einstellen des pH-'#Vertes auf etwa 6,5 mit 20 Teilen Aktivkohle und 1 Teil Natriumdithionit behandelt. Bei vor sichtigem Ausfällen mit Ammoniak wird der freie Ester als weisser, kristalliner Nieder schlag erhalten. Er schmilzt bei 80-82 C.
Das Hydroehlorid ist ein weisses Kristall pulver mit Schmelzpunkt zwischen 167 bis 169 C.
Process for the preparation of an anesthetic Esters of carbanilic acid derived from amino alcohols with alkyl or alkoxy groups in the 2,6- or 2,4,6-position of the phenyl radical have excellent anesthetic properties, such as high effectiveness, low toxicity and good stability of their solutions Salts, which makes them suitable for both surface and injection anesthesia.
A decisive factor for the effectiveness and stability of these esters is the symmetrical arrangement of the substituents in the phenyl nucleus of the carbanilic acid, and studies have shown that especially the carbanilic acid esters of alcohols of the type of piperidinoalkanols and dialkylaminoalkanols have favorable properties point.
The compounds correspond to the formula
EMI0001.0022
in which R1 and% are alkyl or alkoxy groups, R. is hydrogen, alkyl or an alkoxy group, R4 is a branched or urebranched, saturated or unsaturated hydrocarbon chain with a maximum of 6 carbon atoms and R ,,
and R6 denote alkyl groups or together with the nitrogen denote a saturated heterocyclic ring.
These anesthetics can be made as follows: An aryl isoeyanate of the formula
EMI0001.0041
is first at room temperature and then at elevated temperature with an amino alcohol of the formula
EMI0001.0045
implemented. The amino alcohol can also be used in the form of a salt.
The reaction starts spontaneously when equivalent amounts of the two components are brought together. Since it is extremely exothermic, you should cool and preferably work in an inert solvent. In order to bring the reaction to the end, it should be heated to about 100 C for another 1-2 hours. The reaction product, the substituted carbanilic acid aminoalkyl ester, can be easily. isolate if a solvent was used, e.g.
B. by extraction with dilute hydrochloric acid. The hydrochloric acid solution can then be cleaned with activated charcoal and sodium dithionite after adjusting the pH of the solution to 6.5. The base can then be obtained by precipitation with ammonia.
The present patent now relates to a process for the preparation of 2,6-dimethyl-carbanilic acid-ss-piperidino-ethyl ester, which is characterized in that 2,6-dimethyl-phenyl-isocyanate is used with s-piperidino-ethy. converts alcohol.
A salt of this base can also be used in place of the piperidino-ethyl alcohol. _ <I> Example </I> To a solution of 147 parts of 2,6-dimethylphenyl isocyanate in 200 parts of benzene, 129 parts of β-piperidino-ethyl alcohol are added with stirring and cooling. After everything has been added at about 50 C and the reaction has subsided, the solution is heated to boiling under reflux for 2 hours, whereupon the 2 formed
6-Dimethylcarbanilsänre-s-piperidino-ethyl ester extracted with dilute hydrochloric acid. After adjusting the pH to about 6.5, the hydrochloric acid solution is treated with 20 parts of activated charcoal and 1 part of sodium dithionite. If carefully precipitated with ammonia, the free ester is obtained as a white, crystalline precipitate. It melts at 80-82 C.
The hydrochloride is a white crystal powder with a melting point between 167 and 169 C.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE314569X | 1951-07-14 | ||
| SE281251X | 1951-12-28 | ||
| CH309717T | 1952-07-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH314569A true CH314569A (en) | 1956-06-15 |
Family
ID=27178329
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH314569D CH314569A (en) | 1951-07-14 | 1952-07-14 | Process for the preparation of an anesthetic |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH314569A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995031449A1 (en) * | 1994-05-17 | 1995-11-23 | Sanofi | Novel 3,5-dimethylpiperidin-1-ylalkyl esters |
-
1952
- 1952-07-14 CH CH314569D patent/CH314569A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995031449A1 (en) * | 1994-05-17 | 1995-11-23 | Sanofi | Novel 3,5-dimethylpiperidin-1-ylalkyl esters |
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