DE897561C - Process for the preparation of 4-aryl-N-alkyl-piperidine-4-carboxylic acid nitriles and esters - Google Patents
Process for the preparation of 4-aryl-N-alkyl-piperidine-4-carboxylic acid nitriles and estersInfo
- Publication number
- DE897561C DE897561C DEF3568D DEF0003568D DE897561C DE 897561 C DE897561 C DE 897561C DE F3568 D DEF3568 D DE F3568D DE F0003568 D DEF0003568 D DE F0003568D DE 897561 C DE897561 C DE 897561C
- Authority
- DE
- Germany
- Prior art keywords
- aryl
- carboxylic acid
- piperidine
- esters
- preparation
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/64—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having an aryl radical as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
Verfahren zur Herstellung von 4-Aryl-N-alkyl-piperidin-4-carbonsäurenitrilen und -estern In der Patentschrift 679 281 ist ein Verfahren zur Herstellung von spasmolytisch und analgetisch wirksamen Piperidinverbindungen geschützt, welches unter anderem in der Kondensation von Arylacetonitrilen mit Alkyl-di-(halogenalkyl)-aminen in Gegenwart eines halogenwasserstoffabspaltenden Mittels besteht.Process for the preparation of 4-aryl-N-alkyl-piperidine-4-carboxylic acid nitriles and esters In the patent specification 679 281 a process for the preparation of spasmolytic and analgesic piperidine compounds is protected, which inter alia in the condensation of arylacetonitriles with alkyl-di - (Haloalkyl) amines in the presence of a hydrogen halide-releasing agent.
Es wurde nun gefunden, daB man zu derartigen Verbindungen auch gelangen kann, wenn manHalogenverbindungen der allgemeinen Formel worin R einen substituierten oder unsubstituierten Arylrest, Y eine gesättigte zweigliedrige, gegebenenfalls alkylsubstituierte C-Atomkette und Hlg Halogen bedeuten, mit sekundären Aminoalkanolen der Formel in welcher Z für eine gesättigte zweigliedrige, gegebenenfalls alkylsubstituierte C-Atomkette steht, zur Umsetzung bringt, die Oxygruppe der erhaltenen Alkanole durch Halogen ersetzt, die entstandenen Halogenamine mit halogenwasserstoffabspaltenden Mitteln durch RingschluB in die Piperidinverbindungen überführt und gegebenenfalls die Cyangruppe am Ende oder in einer beliebigen Stufe des Verfahrens in eine Estergruppe überführt.It has now been found that such compounds can also be obtained by using halogen compounds of the general formula where R is a substituted or unsubstituted aryl radical, Y is a saturated two-membered, optionally alkyl-substituted carbon atom chain and Hlg is halogen, with secondary aminoalkanols of the formula in which Z stands for a saturated two-membered, optionally alkyl-substituted carbon atom chain, brings the oxy group of the alkanols obtained replaced by halogen, the haloamines formed with hydrogen-splitting agents by ring closure in the piperidine compounds and optionally the cyano group at the end or in any Converted stage of the process into an ester group.
Beispielsweise wird ß-Chloräthyl-benzylcyanid mit Methylaminoäthanol umgesetzt. Das hierbei entstehende N-Äthanol-methylaminoäthyl-benzylcyanid wird vermittels Säurechloriden, wie Thionylchlorid, in die zugehörige Chlorbase übergeführt und letztere vermittels Natriumamid als chlorwasserstoffabspaltendem Kondensationsmittel in die Piperidinverbindung übergeführt. Auf diese Weise entsteht das 4-Phenyl-N-methyl-piperidin-4-carbonsäurenitril. Durch Verseifung der Nitrilgruppe und Veresterung der entstehenden Carbonsäure gelangt man zu den zugehörigen Estern. Letztere Maßnahme läßt sich auch in einer beliebigen anderen Stufe des Verfahrens durchführen, z. B. unmittelbar vor dem Ringschluß.For example, ß-chloroethyl benzyl cyanide is used with methylaminoethanol implemented. The resulting N-ethanol-methylaminoethyl-benzyl cyanide is converted into the associated chlorine base by means of acid chlorides such as thionyl chloride and the latter by means of sodium amide as a condensing agent which splits off hydrogen chloride converted into the piperidine compound. In this way the 4-phenyl-N-methyl-piperidine-4-carboxylic acid nitrile is formed. By saponification of the nitrile group and esterification of the resulting carboxylic acid arrives one to the associated esters. The latter measure can also be used in any perform another stage of the procedure, e.g. B. immediately before the ring closure.
Das neue Verfahren, das mit sehr guten Ausbeuten arbeitet, umgeht die Isolierung sehr lästiger und empfindlicher Halogenbasen.The new process, which works with very good yields, bypasses the isolation of very annoying and sensitive halogen bases.
Beispiel 22 g ß-Chloräthyl-benzylcyanid werden mit 27 g Methylaminoäthanol versetzt und auf dem Dampfbad 1/2 Stunde erhitzt. Dann wird mit Wasser und Äther versetzt, der ätherische Auszug nochmals mit Wasser gewaschen, mit verdünnter Salzsäure ausgezogen und der saure -Anteil - mit- Natronlauge alkalisch gemacht. Es scheidet sich ein hellrötgefärbtes Öl ab, das mit Äther aufgenommen wird und nach dem Abdestillieren des Äthers im Vakuum bei 7 mm von 2o2 bis 2o4° siedet. Die Ausbeute beträgt 19,5 g N-Äthanol-methylaminoäthyl-benzylcyanid.Example 22 g of ß-chloroethyl benzyl cyanide are mixed with 27 g of methylaminoethanol added and heated on the steam bath for 1/2 hour. Then with water and ether added, the essential extract washed again with water, with dilute hydrochloric acid pulled out and the acidic part - made alkaline with sodium hydroxide solution. It part a light red-colored oil is produced, which is absorbed with ether and after distilling off of the ether boils in a vacuum at 7 mm from 2o2 to 2o4 °. The yield is 19.5 g of N-ethanol methylaminoethyl benzyl cyanide.
zog N-Äthanol-methylaminoäthyl-benzylcyanid werden in Alkohol gelöst, mit alkoholischer Salzsäure kongosauer gestellt und im Vakuum zur Trockne eingedampft. Der Rückstand, ein dicker Sirup, wird mit 3o ccm Chloroform versetzt, 6,5 g Thionylchlorid zugefügt und 1/2 Stunde auf dem Dampfbad gekocht. Dann wird das Chloroform abdestilliert, der Rückstand in Wasser gelöst, klar filtriert und mit Pottasche versetzt. Es scheidet sich ein Öl ab, das in Äther aufgenommen wird und nach dem Abdestillieren des Äthers i:o g N-Chloräthyl-methylaminoäthylbenzylcyanid hinterläßt. zo g N-Chloräthyl-methylaminoäthyl-benzylcyanid werden in 30 ccm Benzol gelöst, 1,9 g feingepulvertes Natriumamid zugegeben und das Gemisch nach Abklingen der rasch einsetzenden Umsetzung noch 1J2 Stunde unter Rückfluß gekocht. Das Natriumamid ist dann vollständig verschwunden. Das Reaktionsgemisch wird mit Wasser versetzt, die benzolische Lösung abgetrennt, mit verdünnter Salzsäure durchgeschüttelt, der saure Anteil wiederum abgetrennt, mit Natronlauge alkalisch gemacht, das abgeschiedene Öl mit Äther ausgezogen und der Ätherrückstand im Vakuum destilliert. Bei 8 mm und 158 bis r59° gehen 7 g 4-Phenyl-N-methyl-piperidin-4-carbonsäurenitril über, das zu einer kristallinen Masse vom Schmelzpunkt 52 bis. 53° erstarrt.pulled N-ethanol-methylaminoethyl-benzyl cyanide are dissolved in alcohol, made Congo acidic with alcoholic hydrochloric acid and evaporated to dryness in vacuo. The residue, a thick syrup, is mixed with 30 cc of chloroform, 6.5 g of thionyl chloride are added and the mixture is boiled on the steam bath for 1/2 hour. The chloroform is then distilled off, the residue is dissolved in water, filtered until clear and potash is added. An oil separates out, which is taken up in ether and, after the ether has been distilled off, leaves behind i: og N-chloroethyl-methylaminoethylbenzyl cyanide. zo g of N-chloroethyl-methylaminoethyl-benzyl cyanide are dissolved in 30 cc of benzene, 1.9 g of finely powdered sodium amide are added and the mixture is refluxed for a further 1/2 hour after the reaction, which has started rapidly, has subsided. The sodium amide is then completely gone. Water is added to the reaction mixture, the benzene solution is separated off, shaken through with dilute hydrochloric acid, the acidic portion is separated off again, made alkaline with sodium hydroxide solution, the separated oil is extracted with ether and the ether residue is distilled in vacuo. At 8 mm and 158 to r59 °, 7 g of 4-phenyl-N-methyl-piperidine-4-carboxylic acid nitrile go over, which gives a crystalline mass with a melting point of 52 to. Solidified at 53 °.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF3568D DE897561C (en) | 1942-12-29 | 1942-12-29 | Process for the preparation of 4-aryl-N-alkyl-piperidine-4-carboxylic acid nitriles and esters |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF3568D DE897561C (en) | 1942-12-29 | 1942-12-29 | Process for the preparation of 4-aryl-N-alkyl-piperidine-4-carboxylic acid nitriles and esters |
Publications (1)
Publication Number | Publication Date |
---|---|
DE897561C true DE897561C (en) | 1953-11-23 |
Family
ID=7083824
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DEF3568D Expired DE897561C (en) | 1942-12-29 | 1942-12-29 | Process for the preparation of 4-aryl-N-alkyl-piperidine-4-carboxylic acid nitriles and esters |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE897561C (en) |
-
1942
- 1942-12-29 DE DEF3568D patent/DE897561C/en not_active Expired
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