CH449012A

CH449012A - Process for the production of choline nicotinate and choline ester nicotinates

Info

Publication number: CH449012A
Application number: CH789565A
Authority: CH
Inventors: Imhoff Eduard
Original assignee: Globopharm Ag
Priority date: 1965-06-03
Filing date: 1965-06-03
Publication date: 1967-12-31

Description

  

  
 



  Verfahren zur Herstellung von   Cholinnicotinat    und   Chohnesternicotinaten   
Die Herstellung von Cholinnicotinat nach bekannten Verfahren, nämlich durch Umsetzung äquivalenter Mengen von Trimethylamin, Nicotinsäure und   ithy-    lenoxyd einereits, resp. Anlagerung von Nicotinsäure an frisch zubereitete Cholinbase andererseits, ergeben Cholinnicotinat als   bräurllichgelbes      Ö1,    welches schwierig zu reinigen und beinahe nicht zur Kristallisation zu bringen ist. Es   wurde    nun gefunden, dass man ein sehr reines Cholinnicotinat in nahezu quantitativer Ausbeute erhält, wenn man Silbernicotinat mit vorzugsweise frisch   umknstallisiertem    Cholinhalogenid umsetzt.

   Das Verfahren eignet sich auch zur Darstellung von Cholinesternicotinaten aus den entsprechenden   Cholinesterhalogeniden.   



   Beispiel 1
Silbernicotinat wird in Wasser in Form einer feinen Emulsion aufgeschlemmt und mit einer äquivalenten Menge von frisch umkristallisiertem Cholinchlorid in wässriger Lösung versetzt. Nach ca. 24 Stunden wird vom ausgeschiedenen Silberchlorid abfiltriert, und die Lösung im Vacuum eingedampft. Das auf diese Weise hergestellte   Chollnnicotinat    ist ein beinahe farbloses   Ö1,    welches sich unter   Luftabschluss    nach einigen Tagen zu einer weissen   Kristahmasse    verfestigt.



   Beispiel 2
In Wasser emulgiertes Silbernicotinat wird mit einer äquivalenten Menge   Nicotinoylchollnjodid    in wässriger Lösung versetzt. Die Abscheidung des Silberjodids ist nach ca. 10 Stunden beendet. Nach Filtration und Eindampfen der wässrigen Lösung im   Vacuum    wird das   Nicotinoylcholinmcotinat - eine    neue Verbindung - in Form eines farblosen Öls erhalten, welches unter Luftabschluss nach 2 Tagen mit 2 Mol Wasser kristallisiert. Fp:   62"    C.



   Beispiel 3
Silbernicotinat wird, wie unter Beispiel 1 und 2 aufgeführt, in Wasser emulgiert und mit einer äquivalenten Menge in Wasser gelöstem Acetylcholinchlorid versetzt. Die Umlagerung erfolgt langsamer als bei Beispiel 2. Nach Abfiltrieren vom gebildeten Silberchlorid und Eindampfen der wässrigen Lösung im Vacuum wird die neue Verbindung Acetylcholinnicotinat als gelbliches, dünnflüssiges   Ö1    erhalten.  



   PATENTANSPRUCH
Verfahren zur Herstellung von Cholinnicotinat und Cholinesternicotinaten, dadurch gekennzeichnet, dass Cholinhalogenide, resp. Cholinesterhalogenide mit Silbernicotinat umgesetzt werden. 

**WARNUNG** Ende DESC Feld konnte Anfang CLMS uberlappen**.



   



  
 



  Process for the preparation of choline nicotinate and choline ester nicotinates
The production of choline nicotinate by known processes, namely by reacting equivalent amounts of trimethylamine, nicotinic acid and ithylene oxide on one hand, respectively. Addition of nicotinic acid to freshly prepared choline base, on the other hand, results in choline nicotinate as a brownish yellow oil, which is difficult to purify and almost impossible to crystallize. It has now been found that a very pure choline nicotinate is obtained in an almost quantitative yield if silver nicotinate is reacted with preferably freshly converted choline halide.

   The method is also suitable for the preparation of choline ester nicotinates from the corresponding choline ester halides.



   example 1
Silver nicotinate is slurried in water in the form of a fine emulsion and an equivalent amount of freshly recrystallized choline chloride in aqueous solution is added. After about 24 hours, the precipitated silver chloride is filtered off and the solution is evaporated in a vacuum. The chollnnicotinate produced in this way is an almost colorless oil which solidifies to a white crystal mass after a few days in the absence of air.



   Example 2
Silver nicotinate emulsified in water is mixed with an equivalent amount of nicotinoylcholic njodide in aqueous solution. The deposition of the silver iodide is complete after about 10 hours. After filtration and evaporation of the aqueous solution in a vacuum, the nicotinoylcholine mcotinate - a new compound - is obtained in the form of a colorless oil, which crystallizes with 2 mol of water after 2 days in the absence of air. Mp: 62 "C.



   Example 3
Silver nicotinate is, as listed under Examples 1 and 2, emulsified in water and mixed with an equivalent amount of acetylcholine chloride dissolved in water. The rearrangement takes place more slowly than in Example 2. After filtering off the silver chloride formed and evaporating the aqueous solution in a vacuum, the new compound acetylcholine nicotinate is obtained as a yellowish, low-viscosity oil.



   PATENT CLAIM
Process for the production of choline nicotinate and choline ester nicotinates, characterized in that choline halides, respectively. Choline ester halides are reacted with silver nicotinate.

** WARNING ** End of DESC field could overlap beginning of CLMS **.

Claims

** WARNING ** Beginning of CLMS field could overlap end of DESC **.

Process for the preparation of choline nicotinate and choline ester nicotinates The production of choline nicotinate by known processes, namely by reacting equivalent amounts of trimethylamine, nicotinic acid and ithylene oxide on one hand, respectively. Addition of nicotinic acid to freshly prepared choline base, on the other hand, results in choline nicotinate as a brownish yellow oil, which is difficult to purify and almost impossible to crystallize. It has now been found that a very pure choline nicotinate is obtained in an almost quantitative yield if silver nicotinate is reacted with preferably freshly converted choline halide.

The method is also suitable for the preparation of choline ester nicotinates from the corresponding choline ester halides.

example 1 Silver nicotinate is slurried in water in the form of a fine emulsion and an equivalent amount of freshly recrystallized choline chloride in aqueous solution is added. After about 24 hours, the precipitated silver chloride is filtered off and the solution is evaporated in a vacuum. The chollnnicotinate produced in this way is an almost colorless oil which solidifies to a white crystal mass after a few days in the absence of air.

Example 2 Silver nicotinate emulsified in water is mixed with an equivalent amount of nicotinoylcholic njodide in aqueous solution. The deposition of the silver iodide is complete after about 10 hours. After filtration and evaporation of the aqueous solution in a vacuum, the nicotinoylcholine mcotinate - a new compound - is obtained in the form of a colorless oil, which crystallizes with 2 mol of water after 2 days in the absence of air. Mp: 62 "C.

Example 3 Silver nicotinate is, as listed under Examples 1 and 2, emulsified in water and mixed with an equivalent amount of acetylcholine chloride dissolved in water. The rearrangement takes place more slowly than in Example 2. After filtering off the silver chloride formed and evaporating the aqueous solution in a vacuum, the new compound acetylcholine nicotinate is obtained as a yellowish, low-viscosity oil.

PATENT CLAIM Process for the production of choline nicotinate and choline ester nicotinates, characterized in that choline halides, respectively. Choline ester halides are reacted with silver nicotinate.