CH207499A - Process for separating the carbonyl compounds obtainable in the side chain degradation of steroids. - Google Patents

Description

  

  Process for separating the carbonyl compounds obtainable in the side chain degradation of steroids. The separation of the homologous carbonyl compounds and their derivatives obtainable in the direct or stepwise degradation of the side chains of steroids offers, in a known manner, e.g. B. carried out by fractional crystallization, great difficulties.

    Even with the usual sparingly soluble carbonyl reagents, no useful separation of the carbonyl compounds among themselves can be achieved and the precipitated products always contain a certain amount of non-carbonylic components such as starting materials and oxidation intermediates. Since the ring carbonyl compounds obtained as the main product of the oxidation cannot be isolated quantitatively in this way, the recovery of the secondary carbonyl compounds is made more difficult.



  It has now been found that a separation of homologous saturated or unsaturated carbonyl compounds obtainable in the side chain degradation of steroids by reaction with such carbonyl reagents which, in addition to the groups capable of condensation with the carbonyl groups, also contain salt-forming groups,

       Separation of the condensation products and subsequent cleavage of the same are possible if crude or prepurified mixtures of such homologous carbonyl compounds are reacted with the carbonyl reagents mentioned and the mixture of the condensation products obtained is split up fractionally to give the carbonyl compounds.



  Mixtures of homologous saturated or unsaturated carbonyl compounds which can be subjected to the present process are, for example, those as they are used in the side chain oxidation of, for example, cholestanols, cholesterol, stigma sterol, cinchol, sitosterol, ergosterol, bile acids or stereoisomers of these compounds, respectively their halides or hydrohalides, their derivatives, such as esters or ethers,

      the corresponding core carbonyl compounds respectively. their enol derivatives. how enol esters or enol ethers arise.



  Suitable carbonyl reagents are, for example: basic hydrazides such as trialkylammonium or pyridinium fatty acid hydrazides or their salts, eg. B. Trimethylammoniumessigsäurehy drazid - chloride or acid hydrazides such as the arylhydrazine sulfonic acids.



  The present process permits vain separation of carbonyl compounds from one another, since the reaction products can be cleaved at different speeds with the carbonyl reagents used. The process is such that the neutral oxidation mixture is fully reacted, for example, with basic hydrazides at elevated temperature and, after removal of non-carbonylic compounds, the ketones released at different hydrogen ion concentrations are extracted.

   The hydrazones of the methyl ketones generally disintegrate even in weakly acidic solution, whereas those of the ring ketones are not yet split in this medium. The separation of the reaction products succeeds according to the different solubility caused by the presence or absence of salt-forming groups, eg. B. in solvents like @Vasser. Glycerines, glycols on the one hand and ethers, benzene and the like on the other hand. The present process can also be used with other cleaning or cleaning. Separation methods, such as B.

   Crystallization, conversion into derivatives, selective adsorption and the like combined who.



  The new process thus makes it possible to isolate, in a simple manner, the extraordinarily valuable carbon film compounds formed by incomplete side chain degradation and to increase the yield of ring ketones formed by complete side chain degradation.

           Example <I> 1: </I> The neutral components obtained in the oxidation of cholesterol dibromide acetate and subsequent debromination are reacted in a methyl alcoholic solution containing glacial acetic acid with the chloride of trimethylammonium acetic acid hydrazide by boiling for half an hour . The solution is poured into enough ice-containing water that the aqueous solution still contains 10 to 20 alcohol.

   Is this a finite neutralization? 11-sodalization with cooling / 1o of the acetic acid and the non-ketonic components are obtained by exhaustive extraction with ether.

   The aqueous solution is then brought with n-acetic acid to a p1, which lies between the turnover points full litmus red and congo red. At. With this acidity, the hydrazones of the methyl ketones, namely of the Pregneiioloiacetate and Norcholestenolone Acetate, are cleaved and the latter is then isolated by extraction in finite ether.

   The mother liquor is acidified with Wein- @ iurf, solution until the Congo turns gray. The new fission products are also taken up in ether, the ether solution is washed with sodium carbonate solution and water and dried over sodium sulphate.

    From the back of the ether extract, the durell fractional recrystallization from 1Vlethatiol, the noreliolestenolonaeetat, which melts at 141st to 1.42nd, and the acetate of the Pregnololis from h '. 146 to 147 kept pure.

   After acidifying the tartaric courage. Lye finitely strong hydrochloric acid is again extracted exhaustively with ether and from this extract the irans dehydroandrosterone acetate which melts at <B> 170 </B> to <B> 1 </B> (2) is obtained.



  It is also possible to work in an anhydrous medium, in such a way that the methylalkolioliselie reaction solution of the basic fluoride zone with hydroxyl-containing solvents such as glycol. Glycerin ete. offset. The hydrazones dissolve in the latter and the non-ketonic components can be mixed with non-hydroxyl-containing agents, e.g.

   B. ether, to be drawn from. The fractional cleavage of the dissolved then takes place in the manner described above.



  <I> Example 2: </I> A methyl alcoholic solution of the neutral fractions freed from the starting material obtained in the oxidation of cholestenone with chromic acid are mixed with 10% glacial acetic acid and the chloride of trimethylammonium acetic acid hydrazide. After boiling for half an hour, the solution is poured into so much ice water that the alcohol content of the aqueous solution does not exceed 20%. Part of the acetic acid is now neutralized and, after extraction with ether, the weakly acetic acid solution is mixed with enough tartaric acid solution that Congo is colored gray.

   Pregnendione from F. <B> 120 '</B> and norcholestedione, which melts at <B> 128' </B>, is obtained by extraction with ether and subsequent crystallization from dilute alcohol. The tartaric mother liquor is then acidified with strong hydrochloric acid and again subjected to an exhaustive ether extraction. The ether solution is washed with sodium bicarbonate solution and water and dried over sodium sulfate. After evaporation of the solvent, pure androstenedione with a melting point of 173 to 174 'is obtained by recrystallization from hexane or aqueous alcohol.

    <I> Example 3: </I> The oxyketone mixture obtained in the oxidation of cholesterol dibromide acetate, subsequent debromination and saponification is in an alcoholic solution containing 10% glacial acetic acid with the chloride of pyridinium acetic acid hydrazide for one hour Cooking implemented. The solution is poured into enough ice-containing water that the aqueous solution still contains 10 to 20 alcohol.

   The acetic acid is then neutralized with 2N sodium hydroxide solution, while cooling, and the non-ketonic components are recovered by exhaustive extraction with ether. Acetic acid is then added to the mother liquor to make the Congo gray. The fission products absorbed in the ether are washed neutral and dried. From the residue of the ether extract, after recrystallization from alcohol, mainly norcholestenone with a melting point of 127 to 128 is obtained.

   The aqueous mother liquor is now acidified to the Congo with 2N hydrochloric acid. After work-up, pregnenolone fractions with F. 188 to 193 are isolated from the cleavage products formed at this acidity.



  The mother liquor mixed with concentrated hydrochloric acid is left to stand for some time and then subjected to an exhaustive extraction with ether. The trans-dehydroandrosterone which melts at 142 and 148 is obtained from this ether extract.



  The adjustment of the hydrogen ion concentration can of course also be achieved with other means commonly used for this purpose.

 

Claims (1)

PATENT CLAIM: Process for the separation of homologous saturated or unsaturated carbonyl compounds obtainable during side chain degradation of steroids by reaction with carbonyl reagents which contain groups capable of condensation with the carbonyl groups as well as salt-forming groups, separation of the condensation products and subsequent cleavage thereof marked, that crude or prepurified mixtures of such homologous carbonyl compounds are reacted with the carbonyl reagents mentioned and the mixture of the condensation products obtained is split up fractionally to give the carbonyl compounds.