CH227886A - Process for the preparation of N-phenacyl-tetrahydro-p-oxazine. - Google Patents

Process for the preparation of N-phenacyl-tetrahydro-p-oxazine.

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Publication number
CH227886A
CH227886A CH227886DA CH227886A CH 227886 A CH227886 A CH 227886A CH 227886D A CH227886D A CH 227886DA CH 227886 A CH227886 A CH 227886A
Authority
CH
Switzerland
Prior art keywords
tetrahydro
oxazine
phenacyl
preparation
ether
Prior art date
Application number
Other languages
German (de)
Inventor
Albert Chemische Werke
Original Assignee
Albert Ag Chem Werke
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Albert Ag Chem Werke filed Critical Albert Ag Chem Werke
Publication of CH227886A publication Critical patent/CH227886A/en

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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
    • C07D295/10—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 doubly bound oxygen or sulphur atoms
    • C07D295/104—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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/108—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 doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

Description

  

      Verfahr    en zur Herstellung von     N-Phenacyl-tetrahydr        o-p-ogazin.       Es ist bekannt, dass man aus     a-halogen-          substituierten        Alkylarylketonen    durch Ein  wirkung von Aminen die     entsprechenden     a -     Aminoalkylarylketone    darstellen kann       (Arch.    d. Pharmazie 237 [1899] S.     234/35.     -     Ber.    62, 2425 [1925]).     Verbindungen    die  ser Art werden therapeutisch nicht ange  wandt, sondern dienen meistens als Zwischen  produkte zur Darstellung von Heilmitteln.  



  Man kann nun zu therapeutisch selbst  sehr wertvollen     Verbindungen    gelangen,  wenn man     halogen-a-substituierte        Alkylaryl-          ketone    mit     Tetrahydro-p-oxazin    umsetzt. Be  sonders gute Ausbeuten erhält man, wenn  man auf 1     Mol    der     a-Halogenalkylarylketone     2     Mol        Tetrahydro-p-oxazin        einwirken    lässt.

         Man    erhält auf diese Weise in sehr guten  Ausbeuten (80-90 %) die entsprechenden,  noch nicht     vorbeschriebenen        Tetrahydro-p-          ogazin-alkylarylketone    folgender Konstitu  tion:  
EMI0001.0027     
    wobei     R    = H oder     Alkyl        ist.    Diese Verbin  dungen besitzen neben einer sehr     geringen          Toxizität        schlafmachende    Eigenschaften, die  den     bisher    bekannten (s. o.)     a-Aminoalkyl-          arylketonen    fehlen.  



       Gegenstand    des vorliegenden Patentes ist  ein Verfahren zur Herstellung von     N-Phen-          acyl-tetrahydro-p-oxazin,    welches dadurch  gekennzeichnet ist, dass man auf     co-Halogen-          acetophenon        Tetrahydro-p-ogazin    einwirken  lässt.  



  <I>Beispiel:</I>       7u        einer    Lösung von 61g     Tetrahydro-p-          oxazin    in 250 cm' Äther gibt man allmählich      und unter guter Kühlung eine ätherische Lö  sung von 65 g     Bromacetophenon    zu. Unter       Wärmeentwicklung    scheidet sieh rasch die  Hälfte des angewandten     Tetrahydro-p-oxazins     als Bromhydrat aus. Nach einigem Stehen  wird vom abgeschiedenen     Tetrahydro-p-oxazin          abfiltriert,    der Niederschlag mit Äther nach  gewaschen und mit der berechneten Menge  wässriger Salzsäure ausgeschüttelt.

   Die salz  saure Lösung wird zum     Entfernen    des noch  vorhandenen     Bromacetaphenons    nochmals mit  Äther ausgeschüttelt und unter Kühlung mit  Natronlauge neutralisiert. Das abgeschiedene  Öl     wird    in Äther aufgenommen, mit Wasser  zweimal     ausgeschüttelt,    um eventuell gelöstes       Tetrahydro-p-oxazin    zu entfernen, und der  Äther nach dem Trocknen     abdestilliert.    Das       N-Phenacyl-tetrahydro-p-oxazin    wird auf  diesem Wege direkt rein erhalten. Ausbeute       85-90%    der Theorie.  



  Durch Behandeln einer ätherischen Lö  sung der Base mit ätherischer Salzsäure er  hält man als Fällung direkt analysenreines       N-Phenacyl-tetrahydro-p-oxazinhydrochlorid,       das bei     213-214     C     unter    vollkommener Zer  setzung schmilzt. Es stellt     ein    wirksames       Beruhigungs-    und Schlafmittel dar.



      Process for the production of N-phenacyl-tetrahydr o-p-ogazine. It is known that the corresponding α-aminoalkylaryl ketones can be prepared from α-halogen-substituted alkylaryl ketones by the action of amines (Arch. D. Pharmazie 237 [1899] p. 234/35. - Ber. 62, 2425 [1925]) ). Compounds of this type are not used therapeutically, but mostly serve as intermediate products for the preparation of medicinal products.



  Compounds which are very valuable even therapeutically can now be obtained if halogen-α-substituted alkylaryl ketones are reacted with tetrahydro-p-oxazine. Particularly good yields are obtained if 2 moles of tetrahydro-p-oxazine are allowed to act on 1 mole of the α-haloalkylaryl ketones.

         In this way, the corresponding, not previously described tetrahydro-p-ogazine-alkylaryl ketones of the following constitution are obtained in very good yields (80-90%):
EMI0001.0027
    where R = H or alkyl. In addition to a very low toxicity, these compounds have sleep-inducing properties which the previously known (see above) α-aminoalkyl aryl ketones are lacking.



       The subject of the present patent is a process for the preparation of N-phenacyl-tetrahydro-p-oxazine, which is characterized in that tetrahydro-p-ogazine is allowed to act on co-haloacetophenone.



  <I> Example: </I> 7u a solution of 61 g of tetrahydro-p-oxazine in 250 cm of ether is gradually added to an ethereal solution of 65 g of bromoacetophenone with good cooling. With the development of heat, half of the tetrahydro-p-oxazine used quickly separates out as bromine hydrate. After standing for a while, the deposited tetrahydro-p-oxazine is filtered off, the precipitate is washed with ether and extracted with the calculated amount of aqueous hydrochloric acid.

   To remove the bromoacetaphenone still present, the hydrochloric acid solution is shaken out again with ether and neutralized with sodium hydroxide solution while cooling. The deposited oil is taken up in ether, extracted twice with water in order to remove any dissolved tetrahydro-p-oxazine, and the ether is distilled off after drying. The N-phenacyl-tetrahydro-p-oxazine is obtained directly in pure form in this way. Yield 85-90% of theory.



  By treating an ethereal solution of the base with ethereal hydrochloric acid, the precipitate is directly analytically pure N-phenacyl-tetrahydro-p-oxazine hydrochloride, which melts at 213-214 C with complete decomposition. It is an effective sedative and sleeping aid.

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung von N-Phen- acyl-tetrahydro-p-oxazin, dadurch gekenn zeichnet, dass man auf co-Halogen-acetophenon Tetrahydro-p-oxazin einwirken lässt. Das aus einer ätherischen Lösung der so gewonnenen Base durch Fällen mit äthe- risclfer Salzsäure erhältliche N-Phenacyl- tetrahydro-p-oxazinhydrochlorid schmilzt bei 213-214 C unter vollkommener Zersetzung. Es stellt ein wirksames Beruhigungs- und Schlafmittel dar. PATENT CLAIM: Process for the production of N-phenacyl-tetrahydro-p-oxazine, characterized in that tetrahydro-p-oxazine is allowed to act on co-halo-acetophenone. The N-phenacyl-tetrahydro-p-oxazine hydrochloride, which can be obtained from an ethereal solution of the base thus obtained by precipitation with ethereal hydrochloric acid, melts at 213-214 ° C. with complete decomposition. It is an effective sedative and sleeping aid. UNTERANSPRUCH: Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man auf 1 Mol co-Halo- genacetophenon 2 Mal Tetrahydro-p-oxazin zugibt. SUBSTANTIAL CLAIM: Process according to patent claim, characterized in that tetrahydro-p-oxazine is added twice for 1 mol of co-haloacetophenone.
CH227886D 1937-11-06 1938-11-02 Process for the preparation of N-phenacyl-tetrahydro-p-oxazine. CH227886A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE227886X 1937-11-06

Publications (1)

Publication Number Publication Date
CH227886A true CH227886A (en) 1943-07-15

Family

ID=5866891

Family Applications (1)

Application Number Title Priority Date Filing Date
CH227886D CH227886A (en) 1937-11-06 1938-11-02 Process for the preparation of N-phenacyl-tetrahydro-p-oxazine.

Country Status (1)

Country Link
CH (1) CH227886A (en)

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