CH223161A - Process for the preparation of (B-oxy- phenoxy-propyl) - (B'-oxy- '-N-tetrahydro-p-oxazinyl-propyl) -ether. - Google Patents

Description

  

  Process for the preparation of (P-Ogy- r-phenogy-propyl) - (P'-ogy- r'-N-tetrahydr o-p- ogazinyl-propyl) -ether:

         As is already known, the ethers of epihydrin alcohol react with organic hydroxyl compounds with splitting of the epoxy ring and binding of 1,3-dialkoxypropanols, so-called dialkylins res p.

       Diarylines. The oxidation of these secondary 1,3-dialkoxypropane alcohols to ketones is also known. Basic dialkylines and corresponding ketones, which would be valuable due to their ability to form soluble salts, complex salts and the like, are still, however; not become accessible.

   You probably already have a kind of dialkyl derivative, the amino or. Alkyl amino groups are shown. But these compounds are acid amides, namely carbamic acid esters, diethylcarbamic acid and diethylamidoxalic acid esters; they are not basic and therefore do not form salts.



  In this case, the route to amino compounds via the corresponding halogen derivatives proved to be hardly or not at all feasible.

       To represent the intermediate products, the halogenated dialkylines, so to speak, namely to react epihydrin ethers with halogen alcohols, which, however, are much more difficult or mostly react in a different direction than the parent alcohols, or you can produce soot-unsaturated dialkylines - z.

   B. such. with allyl residues - and these only halogenicrene. There, the choice is restricted and the process more complicated and costly. A simple way to synthesize dialkylin bases has now been found:

      During the action of primary and secondary amino alcohols on epihydrin ethers, the hydroxyl group reacted noticeably, giving tertiary amino alcohols and the N-acyl derivatives of primary and secondary compounds of this series, in short all amino hydroxyl compounds,

      whose amino groups are unable to split the epoxy ring, with epihydric tin ethers in; smoother. Reaction Dia.lkyline. For example, the epihydrinamyl ether (the so-called Epiamyli.n) reacts with diethylaminoethanol in the sense of the equation:

    
EMI0002.0009
         As little as the tertiary amino group in the molecule of alcohol affects the reaction; it changes, just as little does it interfere with the other reaction component, in the epihydrin ether;

      namely, it is possible to produce aminated epiarylines and react with alcohols. For example, the dimethylaminomethyl-, epiphenylin reacts (made from dimethylaminomethylphenol and epichlorohydrin)

      with benzyl alcohol nasch the equation
EMI0002.0033
    It is also possible for both reaction participants to be aminated, e.g. B. the diethylamino ethanol used according to equation (I) can be brought to reaction with the epiarylin used according to equation (II).

    The dibasic dialkyline is obtained:
EMI0002.0046
         On the other hand, you can also see polybasic dialkylines with an uneven distribution of the amino groups, z. B. from two starting materials, one of which is not aminated, the other @ dafü.r contains two or more amino groups (may be mentioned e.g.

   B. the Epihyd @ rin ethers of bis (dialkyl ami, nomethyl) phenols).



  It is surprising that these reactions not only occur, but also when using more complicated, e.g. B. cyclic amino alcohols, give sufficient to practically quantitative yields, while other substituted alcohols such.

   B. benzyl alcohol, tetrahydrofuran, etc., already react much more slowly than the parent substances, which is why a further complication was to be expected.

   The reactants, both the alcoholic and the epicyclic component, can also be substituted by alkyl, aralkyl, halogen, etc.; instead of amino alcohols, aminoglycols and the like are also used. a. m. applicable.



  The 1,3-dialkoxypropanols (or diarylogy and alcoholic arylozy propanols) are characterized as secondary alcohols by being converted into ketones. Fe is very remarkable that the oxidation can be carried out under the same conditions

          as described for the representation of the amino-group-free diogyacetone ether.



  The compounds produced in this way be seated by the presence of an alcoholic hydroxyl or hydroxyl. a Carbo @ nyl group, an amino group and two ether groups conditional properties, on the combination of their effect respectively. their use, partly as such depending on the substitution,

       especially for sedatives; Hypnotics, analgesics, etc. a., partly as intermediate products for the production of technical and pharmaceutical products.



  The subject of the present patent is a process for the production of (ss-Oxy y-phenoxy-propyl) - (ss'-oxy-y'-N-tetrahydro-p-oxazinylpropyl) -ether, characterized by that epihydrin alcohol phernyl ether is substituted with N- (ss, y-dioxypropyl) -tetrahydro-po, xazinum- g <B> 0 </B>.



  <I> Example: </I> 100 parts of epihydrin alcohol phenyl ether (epiphenylin gp. "12.5) are mixed with 300 parts of N- (ss, y-dioxyp:

  ropyl) -tetra-hydro-p = oxazine, produced from tetrahydro-oxazine (morpholine) and glycerol-a-monochlorohydrin, gp.3 149-150 ', diacetyl derivative Kp.o, 3 <B> 131-1.32 '. </B> The solution is heated to around 145-1.50 for 20 hours, then the excess starting base is driven off in a vacuum to 155,

   approximately the calculated amount is recovered.



  The reaction product is taken up in ice-cold, dilute sulfuric acid, a small addition of neutral substance is removed by extraction, the sulfate solution is made alkaline, the crude product which has separated out is collected, dried and fractionated. Up to bp <B> 170 '</B> a forerun, consisting of distilled
EMI0003.0069
  
    from <SEP> (ss-oxy-y-phenoxy-propyl) <SEP> - <SEP> tetrahydro-p oxazine, <SEP> the <SEP> sie],

   <SEP> by <SEP> partial <SEP> cleavage <SEP> the
<tb> Starting base <SEP> and <SEP> conversion <SEP> -des <SEP> Tetra hy: dro-oxazins <SEP> with <SEP> epiphenylin <SEP> formed. <SEP> The
<tb> then <SEP> between <SEP> 238 <SEP> qm.d <SEP> 2421 <SEP>
<tb> substance, <SEP> rectified <SEP> gp., <SEP> 23.9-241 <SEP>, <SEP> is
<tb>, the <SEP> (ss-Oxy-y-phenoxy-pro @ pyl) - (ss'-oxy-y'-N tetrahydro <SEP> - <SEP> p <SEP> - <SEP> oxazinyl < SEP> - <SEP> propyl) <SEP> - <SEP> ether, <SEP> one.
<tb> very <SEP> viscous, <SEP> in <SEP> the <SEP> would be <SEP>, glassy, <SEP> yellowish, ge <SEP> liquid, <SEP> slightly <SEP> soluble <SEP> in <SEP> organic <SEP> solvents <SEP> and <SEP> in <SEP> diluted <SEP> acids,
<tb> soluble <SEP> in <SEP> water. <SEP> The <SEP> salts <SEP> send <SEP> except properly <SEP> hygroscopic;

   <SEP> hydrochloride <SEP> white,
<tb> slightly <SEP> melting <SEP> crystals, <SEP> F. <SEP> <B> 60 "</B> <SEP> (under
<tb> decomposition). <SEP> The <SEP> has the new <SEP> connection <SEP>
<tb> valuable <SEP> therapeutic <SEP> properties.

 

Claims (1)

PATENT CLAIM: Process for the production of (ss-Oxy y-phenoxy-propyl) -. (Ss'-oxy-y'-N-tetrahyd @ ro-p-oxa7, ynyl-propyl) -ether, characterized in that Epiliyd @ rinalkohol-phenylether with N- (ss, y-dioxypropyl) -tetrahydmo-p-oxazine is implemented. The (ss-Oxy-y-phenoxy-propyl) - (ss'- oxy - y'- N - tetrahydro-p-oxa7iinyl-propyl) - ether is used as a very viscous, yellowish liquid of bp. l 239-241 received., which is easily soluble in organic solvents and dilute acids and also soluble in water. The salts are extremely hygroscopic; the hydrochloride forms white, easily dissolving crystals, mp 60 (with decomposition). The new compound has valuable therapeutic properties.