BE437881A - - Google Patents

Description

       

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  Process for the preparation of valuable stilbene derivatives.



   The Applicant has found that it is possible to arrive at materials having sex hormone inactivity. when we start from compounds of the stilboestrol series of the formula:
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 in which R denotes oxy groups or groups convertible into them, and R "saturated or unsaturated alkyl radicals, while X and Y denote hydrogen atoms or oxy groups, or groups which can be converted into oxy groups or a combination of an atony of hydrogen and an oxy group or a group convertible into @

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 similar1 osbination and in which a double bond is found at the p1G oe toe z and Y.



  L8 = 1 "i'2t <; essential principle of the present invention cOdsist in the fact that one aromatic ring or both of the starting r ,, iatire are transformed into more or less hydrogenic cycles and that the oey groups or the transfOl "18ble groups are optionally converted into oy groups, into keto groups, and or that the double bonds -, sometimes present in the groups R 1 or in the intermediate gas, are simultaneously hydrogenated or subséguem! l \ 8nt.

   If we obtain, for example, compounds of the following formulas:
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 2, starting line
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 The two benzol rings are a hydrogenated benzol ring.
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 hydrogens.
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 Both. beûzol cycles a hydrogenated cyele benzol and
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 hydrogenated and both grou- an oxy group transformed into
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 oxy pes transformed into a keto group.
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 keto pes,
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 The two benzol rings a partially partial benzol ring are hydrogenated, hydrogenated.

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  The two benzol rings. A partially partially hydrogenated and hydrogenated benzol ring and a trans oxy group the two trans oxy groups. -formed in a keto group. formed into keto groups.
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  Two hydrogenated benzol rings One hydrogenated benzol ring. and an oxy group transformed into a keto group.
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   a partially hydrogenated benzol ring and a fully hydrogenated benzol ring. an oxy group transformed into a keto group. included in the invention, the oyolohexanol compounds of formulas II and III are obtained, for example, by hydrogenetion of the starting materials.

   These give, on oxidation, eyol chexenone compounds of the formulas IV and v, which can be converted, for example, by halogenation, hydrogen-halogen dissociation and possible reduction, into partially hydrogenated compounds. of formulas VI-IX. The preparation of dicyclohexanone-ethe compounds cannot, for example, be explained by the following formula:

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 EMI4.1
 .at . ): - - - Ô¯) j 1 R '-y Ô. ) 1 RI Hydrogenation.



  X Y R- 0 - - 1 (il) C.) a 'j 1 Rf Oxidation.



  X Y 0 = <\ -1 - 1- -> = o (rv)]),) J RI 1 Rf H81ogéW3tion.



  Ea housed nation.



  D.) xil .. ogé oetion HD1. Y Rai.



  0 = / \ - C - <> = 0 (XIII) R Rut Dissociation dfhydro- Dissocietion àtjjy௠E.) gene-halogen.



  Y 0 = O-y - - C 0 (VIII) RI RI Reduction.



  F.) Reduced p. ) X Reduction.



  Qj1- Of - C- <- 0j1 (VI) R 1 R 'if one wants to obtain compounds in which ionic benzol ring only of the starting material is hydrogenated and, on the other hand, the other pa s, one preferably proceeds in such a way that compounds are used in which X denotes either the hydroxyl group or a group convertible into this group, and y hydrogen, these compounds being hydrogenated, oxides, halogens, dehalogenated under hydrogen-halogen dissociation and formation of double bonds, while optionally one separates, either simultaneously or successively, X with neighboring hydrogen stoms, Y with formation of a double bond, while, by inversion,

   the only oyclohexane cycle is at

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 new flavor, This process can be explained according to the following formula:
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 AT. ) X ... - 4R () B.) R 'B.) Hydrogenation.



  XYR "/ C 'C- 1 <) -R (il) Rt R Oxyda'ci p.) Oxyda XY Î 1 (/ ## \ bzz') O-. F" 0 = 0 $., R, t 1 Rt Halogenation xpy, ORSl.



  O <) "'#"'? '". = 0 (XIII)' ¯ / Î ¯Î BB hydrogen separation - E. halogen Y 0m / -E - 1- / = 0 (VIII) reduction, F ' Réàuùtioa.



  F.) OHOiOQ "r .. 1 f y" "O-OH (VI) Reduction.



  0E +) - 0 - 0 = \ -OH (VI) Rx R Separation of 2 and there is formation at 'n double bond and oxidation. o = O = p \ '"0 = 0 (XIV R' R ...- f-ll inveraion

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 .ti R.) / '### \ h. ) 0 = -C- C- / = 0 (XV) 1.) È '. Flavoring. z E OH (lx) 2 :. ) = / -), - 1 Ri O- E <six> Reduction ELO- Î 'Ù (vil) RT RY
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 It is also possible to proceed in such a way that, as a starting metric, compounds are used in which one hydroxyl group alone can be converted into a group which transforms itself into a group which transforms itself back into a hydroxyl group. hydroxyl group, so the other hydroxyl group remains free.
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 When such compounds are subjected to oxidation, while
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 one of the hydroxyl groups is protected against attack by the oxidation agent.

   ketone alcohols are obtained as 7. ' can be transformed then, by halogenation and d6f1aJ.ogé # - tion, one alcohols etoo.i'IuessirnpJement unsaturated. If in these the ethane chain contains a double bond or if a double bond is introduced by dissociation of X and Y, this is described; t .JÍ-dev8nt, we succeed in preparing phunclic .91-cools by inversion. These reactions can be used as follows: A.)
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 x Y xi0 - / - y -; Ù - / "\ - E (1)" "1 u - 1 y Pl i - H i 1 il.) Z Y, Hyd.rogél18tiorJ., ¯¯¯: IiO- ¯¯ ¯ \ 10. (11) .



  E0- 1t ... (II).



  Rt Rtr 0xyàa iiom

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 EMI7.1
 X Y 11 iV ') 0 = \ -C - µ-.-A (IV), j; \ - D.) / Hal ogé Cl8t i Orl.



  0, 1 on (XIII) 16.



  8 3.3 /.



  Dissocietioi of hydrogèn.e- Ej h8logéne.



  Y 0 = / "C - C \ - E (XIV) '## R. ## Dissociation ds x and y with formation of a double bond, G.) zei) 0 = (\ -C 0- / \ -R (XVII) Rf R- inversion. NJ H 'R 0 = - 6-0- "R (XVIiI) R' t- I., .Ar <YllS ti SS1J ion.



  E H Eo. f - c-, 1 .-- e (u) Ef Rt
 EMI7.2
 It is also possible to obtain compounds of the formula g, o-fest ... that is to say aloooo ketones of this ring, when one starts from the appropriate cliq4toues which are converted into keto groups, in a known manner, in the derivative. Qeto or enol, for example in semi-aerbazone, aoetal or erlol-ether, etc. .. and then proceed to thydrogenation of 1t'one of the Qycles into an oyol ohexanol radical stur.g and that , fi # lemeat. we reconstitute the keto group such
 EMI7.3
 that it results, for example, from the following formula diagram:

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 he. ) X Y R-O-1 - C - / "R (1) Ê.) Y 1 Rf Hydrogenated ne ti on.



  HycLrogëoation.



  B.) - 4: 1 y 1 / ### \ zizi) R- (,, -> -9 - 1 c- <1 \ ##) ". R (II) RI R i.) Oxidation.



  &.) XY aj) -6 - S- \ = 0 (IV), Jt Transformation into "rivés monooét oniquest L.) for example e no'L-ether, ¯ XY 1e) = 0 (XIX) z .. > - J - 1 0- 1 \ = 0 (XIX) fit Rêâuo-Gion,, 1> 1.) El l RI Reduction. 1 / ¯¯¯ i Y z - / - é - j ± - j 1 / - 01 (xx) \ -.oh xyz.) N 'R' Reconstruction of the grou .. pe aeto, la.) ZY here.) / ### \ / ## \ ¯Q 0 = () - - l) - OH (X) "- R Iy t"
 EMI8.2
 com "ls starting materials can, preferably, serve the dialcoy.eti7.boestrols, including the radicals 81.GO; \ '1.68 cotltien- rll.1t jvsqu'a ci 10.: J" tÙ'1lE: .S' the ci.-roo, 1E ::, P &: cti8ulidremC (lt lE 'di- ", th;) - 1stilooes ::: l'c, 1 ci SIS esters the oxypeuve groups ce- pC..1J.Lllt é: 3, -, ll'Tllt be rCr; "p '<: Jcés by other radicaug, which pi-'uv & was trb.1.s ::

  crrljS ci oxy groups, 30Gi. ^, lE ,, for example, halogen, gāu3osiâes or ethers radicals, etc.
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 that can be processed before. during or after the reactions
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 tions oonf ormes to the inventioa. and, if necessary, in gro-apes- oxy

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 according to known methods. The Qxy groups of the starting materials can also be substituted in various ways;
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 for example, one oxy group can be substituted by an 80ethyl radical and the other by a propio ± yl radical etc. One can also use, as the starting materials, monoderivatives of dislaoYlst11bestrols.

   When using the materials -:.-.-
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 starting point, in which X and Y form a double bond ,,
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 , or in which tr denotes unsaturated alkyl radicals, it is natural that the hydrogenation of these dou-
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 The bonds are also saturated.
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 l the place of stilbene compounds stated t we can also
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 to employ those materials in which X and Y represent oxy groups or groups convertible into oxy groups, particularly halogen or combinations thereof
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 groups with hydrogen, such mezières are :, for example ,,. described in the application of e b re Ve;

   German soh.117367
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 IVc / 12q.
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 The hydrogen # 1iion of the starting materials is carried out
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 before methods known per se, for example in solution of
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 Ice vinegar with hydrogen in the presence of a platinum catalyst or other suitable hydrogenation catalyst. It can be carried out equally well with hydrogen generated by the natal route, ytique, however that one then uses as catalysts both precious and non-precious metals, as with the aid of nascent hydrogen.

   Suitable as, for example, son-c catalysts, supported or unsupported nickel catalysts, palladium or plateable slurry and the like. for hydrogenation by means of 1hYdrogen
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 between, for example, in question zinc dust follow
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 in alcoholic solution, such as ethanol.



  Methods of this kind are described, for example, in douben.peyl "Methoden der orgB nischen Chemiet ', free edition Z, page 7. et seq. (19925), particularly

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 page,., 6 and following.



  I, T oxid.at 100. of the oxy groups in products hydrogenated to 'J (c; 1Joaiques groups, is carried out optionally according to methods known per se, preferably above all when only double bonds are present. do not be attacked4Jea
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 following the oxidation phase exchange process, such as
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 d0cri1, more explicitly in German patent application 1 3h, 1¯iO 098 ivo / 18 o, for compounds of the storine series (see r.IE, erWelr1 a 12, chmid1J, 1, ieb10s Ann8l en, Book 444: , page 2n. ev ponndori ', zcizsc'ar, f, éilogeii.Ché,; ie,' ¯book, 9, page ià8), Cet tc; h1; J (lg (s (t'sii he helps aes aldehydes or ceionates in the presence of a'i # i cooii Ls rb08111CJl) OS, COr11'fle ac ITisopropy18te aluminum and cLu J1'1 Ur ï: there is tG of r, W [; t1Gsiu'11 or others.



  Other 'ú8chOClGS a.'oxidation are found, by eyeaple, d "Gs, -¯ov> ea -, ;; ej / 1,' I, 'Jcrhodefi der. Crgsnischen Chérie", 3rd edi- L'lori, book i., pD! 1E. ;:, ç, et seq. (1925), particularly 1) U: 0; 8 e ", 7 /., i, 8.



  11 :, huloÓe: 1 <nlO: l sT ciiccuue following the usual methods, prci'rencE: with bromine in an organic solvent, in particular per I make qub 7 Tcn dissolves the intermediates aetoni- Sbs in a Sn'l8 ' 1.1, organic, -Freeze of ether, chloroform, vinegar! - ice, benzol, acetic anhydride, etc. ct that '!' we introduce a calculated quantity of halogen, by 6: 'C'i: plc of bromine, ohl ore, chlorinated iodine in the form of i- liquid or vapor or also dissolved in an organic solvent, except for one of those mentioned above, depending on the reaction course of Cd1.> If employed, the reaction can be completed by itself. ! S or by refrigeration.

   Likewise, it is also possible to reduce the quantity of halogen to be used once, or else, 7.I-it can be introduced gradually in drops while cooling. The reaction can be completed. additionally in the presence of a catalyst, such as, for example, hydrogen-helo-

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 gene, alcohol, etc., or with the addition of acid-binding agents, such as. for example, potassium acetate, calcium carbonate and / or under radiation, for example, ordinary ultra-violet or ultra-red light, a particularly suitable method of working has been found in which substance is;

   dissolved in chloroform, after which and after adding a concentrated solution of ice vinegar
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 and hydrobromide, the appropriate amounts of a solution of bromine in ice vinegar are made slowly with vigorous stirring.



  Such h8logoetion methods are described, for example, in Roubea-weyllMethoden der orga nisahen Chemie ", 5th edition, book 2, page 533 et seq. (1925).



  As a dehalogenation agent, it is possible to use ammonia, or better still organic bases. Pyridine and piperidine are particularly suitable for this purpose, but the reaction can also be accomplished with other bases, such as ghinolin. aliphatic or aromatic amines.
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 dimethY1.mine. aliphenyiamine, dimethylaniline, etc. The treatment with these preferably anhydrous bases is carried out optionally in the presence of a suitable solvent, in such a way.
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 Then the halogenated ketones are heated with these bases or boiled in the reflux refrigerator apparatus.

   through
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 the addition of materials which are capable of binding the separated halogenated hydrogens, without which react with the starting materials, such as, for example, by the addition of calcium carbonate and the like, can be suppressed. 'affecting
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 isomerizing and resilient, binding free ha7.ogenic hydracids which may be present. These methods of halogenated hydacid separation are also found in Houben-y7ey1 IIMethoden der organischen Chemie ", Semé édit ion, book 2 page 3zà et seq. (1935).

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  Dos composed of formulas XIV and XVII, i.e.
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 poses which still contain apart from one or more dou-
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 The bonds in rings, a double bond in the 9 chain-chain 1? te.rml> ôixire, can optionally be transformed by i triileme.it with agents which produce a '81.ï; ß1e se-clii conversion. $ 8nt Clx = Ud;:; ##### C = Cp -CR2X 6.1 Lvrtie'.s aromatic compounds, for example formulas VII, IX and XII. such ageats are known to 1, 'wingman.

   It is a question here in particular of acetic diacid and of its derivatives, encircled the acetic anhydride, the acids ha7.ogeno-a kétic es, cO: ùmE. the acids s ch1 ora cetia uos, and trichloroacetiques, 7 are organic balls and compounds of acids such as the hydracid acids hal 0; 2) (188. phosphoric halides and other rrbF; s enoore, CCI'j- 1 cites, for example, in "Reports", book 180 (, 7), page 128b and 81Ji'18ntes, and in J.ïueke! T! ThsorGt.Grurlrllug811 d. Or, .zJ Cl, <.; hErrSieTt, 2nd edition, first '' drunk, page ;; 8 and following (1934).

   As water separating agents are; "púrtiQ1Jl H, CE:" j1é-Llt appropriate known products
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 such as sulfuric acid and others, (see
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 t'útr8 other llOub8,1 - ': Teyl!' i;, ethoden der r o rge n 1 S àh e 11 Ch e m 1 e ", 2.ùm edition, 2bffi8 book, page 744 and following (1922).



  The following examples will serve to explain the inventive idea without this being limited by this fact.
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 example 1¯; ¯
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 U.1C solution of 10 gr. of diëthylstilboestrol in 200om3 of ice-wine is stirred in the presence of 2 gr. of catalyst to platinum oxide and hydrogen, until 7 mol. of hydrogen have 8E :, absorbed.

   After filtration to remove the catalyst, and evaporation of the glacial vinegar in the life, the residue is heated with 200 Qm3 i of a caustic lye 131 ... 00011que- at 5 µm in the reflux apparatus, by dilution, a ciài

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 Fication and ether extraction of this solution gives tetradéoehydro-stilboestrol as a clear oil, which can be used without further ado for subsequent repetitions.



  Yield 9 gr.



   The 9 gr. of substance obtained above are dissolved in 100 cm3 of ice vinegar. This solution is then added
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 The solution is a solution of acetic ghromic acid which contains 5 atoms of active oxygen. After standing for 8z hours at room temperature, the solution is poured into water and extracted with itether. The ethereal extract is washed until neutral and evaporated to dryness. the diketone is then obtained in the form of a clear oil.
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 The diketone is dissolved again without further purification in 150 ounces of ice vinegar and in this solution, after adding a few drops of ice-brominated 7-hydrogen, it is introduced by drops and with stirring a 2.1 mol solution. of bromine in 50 cm3 of ice vinegar.

   Stirring is continued until the bromine color has dissipated, by di-
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 lution of the solution and extraction with ether, the bromide is isolated.



   The dibromide thus obtained is dissolved in 200 cm3 of pyridi-
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 ne anhydrous and the solution is b91.tiHt, e "for 6 hours, in the reflux apparatus. After evaporation of the pyridine in vacuo, the residue is treated with water * and ether and, after binding. After drying and drying, the ethereal solution is evaporated. The dark oil obtained is distilled under high vacuum with the addition of
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 dtua little sodium cllectate, with a view to purifying, and then the distillate is purified further by fractional chromatographic adsorption, so that diethy? di3yc7 0- he: x: tonylGthalle is obtained as a clear oil. In the androgenic activity test, this substance was found to be highly active.

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    Example 2:
A suspension of 15 gr. of di- (a-oxyphenyl) -diethylethane in 500 cm3 of ice vinegar, is stirred at 20 for three days, in the presence of 3.7 gr. of platinum oxide and hydrogen. The calculated quantity of hydrogen is thus absorbed.



  Then, the ice vinegar is removed in vacuo and the residue is boiled for four hours, with 100 ounces of methyl alcohol potash at 205, in the reflux device, in order to saponify the acetate that sometimes forms. then diluted with water and the methyl alcohol evaporated as much as possible. by extraction with ether of the alkaline solution, the hydrogenation product is recovered in the form of a clear viscous oil, 10 g are obtained. of di- (cyclohexanonyl). diethylethene and the alkaline solution, after acidification, 4 g of the starting material.



   10 gr. of the perhydrogenated material are dissolved in 130 cm3 of ice vinegar. In this solution, a solution of 5 gr is allowed to flow dropwise at 10, with vigorous stirring. chromic anhydride in 10 cm3 of water and 100 cm3 of ice vinegar. The mixture is left to stand overnight at room temperature. It is then diluted very strongly with water and extracted three times with ether. the ethereal solution is washed to neutrality several times with a 5% bicarbonate solution. After evaporation of the ether, a somewhat dark oil is obtained with a characteristic odor. Yield of di- (cyclohexanonyl) -diethylethane 7.2 gr.



   The crude product which separated (7.2 g) is distilled under high vacuum.



  1.-Fraction with boiling point 90 - 105 / 0,001 mm colorless oil 5,2 gr.



  2, -Fraction at boiling point 120 0.001 mm. colorless oil -, 5 gr ..

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 After prolonged rest, most of the fraction of
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 oristallized. Petroleum ether-ether gives color prisms with a melting point of 86-87. Analysis shows that we are in front of the desired diketone of the formula lSH30Q.2 ′ 180 mg. of diketone we obtain, with out4 gr. of t4dinitro-phenylhyàrazine, 340 mgr. of dihydrazone, D's nis01 hot, it crystallizes in small yellow bars with a melting point of 249 with strong decomposition. It is very hardly soluble in the usual solvents in cold and in heat. From the analysis
 EMI15.2
 you are in front of a dihydra z one.



  To the solution of 4.Q g of fraction 1 in 100 μm of chloroform, a solution of 1.75 cm3 of bromine in 50 cm3 of chloroform is allowed to enter dropwise at 00, with vigorous stirring. In a short time, the first drops of bromine are consumed with the formation of brominated hydrogen. The chloroform is then evaporated under vacuum at 30. and the residue is boiled in the reflux apparatus for six hours, with 100
 EMI15.3
 gm3 of dry pyridina. (Oil bath temperature 130 "). The pyridine is removed in vacuo and the residue is poured into ether and esu. The ether solution is washed to neutrality several times with dilute sulfuric acid and then with
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 a solution of bis # arl38te and Iteau.

   After evaporation of the dry therate solution, a dark colored oil remains.



  This is distilled under high vacuum. boiling point at
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 Q, 00'1 mm 85 - 95. Yield of di "(gyelohexsnonyl) -diëthyleth8" ne: 1m78 gr.
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 The colorless oil obtained is active in Iteswï au capon with 1.5 mgr.?Uch.



    Example 3:
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 23 gr. of di ... (oxyphoid rJ²1) -dithyltha ne oily isomer dissolved in 300 cm3 of ice vinegar, are stirred for three days with hydrogen at room temperature, in

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 presence of 5 gr. of platinum oxide, a somewhat greater quantity of hydrogen is absorbed than that calculated. After subsequent treatment as described above, 18.6 g are obtained. of the hydrogenation product and 2 gr. of starting material.



   The solution of 18.6 gr. of hydrogenated substance is dissolved in 200 cm3 of ice vinegar, with 9.5 gr. chronic anhydride, dissolved in 10 cm3 of water; 100 cm3 of ice vinegar at 10 are then added. The mixture is left to stand at room temperature for 18 hours. After treatment according to the above, an oil is obtained with a fragrance similar to honey (14 gr), which, under high vacuum, turns to 95 - 120 in a light yellow top. Yield 7.27 gr.



   In a solution of 7.27 gr. of this oil in 125 cm3 of chloroform, is introduced by drops, at 0 and with stirring, a solution of 2.55 cm3 of bromine in 50 cm3 of chloroform. The bromine is very quickly consumed. The chloroform is removed under vacuum and the residue is boiled in the reflux apparatus for six hours, with 100 cm3 of anhydrous pyridine. After working up as in Example 2, a dark colored oil is obtained, which is distilled under high vacuum, between 80 and 100 / 0.001 mm. Yield 3.9 gr. The colorless oil thus obtained is active in the Chapon test with 1.5 mgr. / UcCh.



  Example4; 14 gr. of di- (p-scétoxyphenyl) -diethyléthe in 100 cm3 of cyclohexane are hydrogenated for six hours with 15 g. of a nickel catalyst moistened with cyclchexans according to Raney. at a temperature of 200 and under a starting pressure of 130 atm.



   On cooling of the cyclohexane solution, a few colorless insoluble crystals separate. From hot methanol, colorless star-shaped deformation bars with a melting point 166 -168 are obtained. Analysis shows that

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 EMI17.1
 the cli '(scétOxY-, QYel0hexsaYl) -alethylethane of the formula 18113402 is present, the cyclohexane solution is filtered, the crystals separated are dissolved with hot meth8- nol. The 0.01 cyc10hexs ne-metha solution is then evaporated in vacuo and the residue is saponified for 3 hours with 75 cm3 of a potassium hydroxide solution with methyl alcohol at 205. It is then diluted with water and the mixture is extracted. alkaline ether solution. In this neutral part are 9.2 gr. of a colorless oily hydrogenation product.

   Then the
 EMI17.2
 alkaline solution extracted with ether is made acid-Congo and again extracted with ether. In this ethereal solution only very small amounts of starting material are found.



   The solution of 1.75 gr. of the hydrogenation product in 40 cm3 of anhydrous pyridine is added 5 gr. chloride
 EMI17.3
 3i5dinitrobenzoyl, After standing the mixture for one day, the treatment continues as usual. we obtain at, 7 gr. of c 11-clin. oily jtrobenzoate. this is dissolved in acetone and added with methanol. After one night, di-dinitrobenzoate crystallizes in a yield of 0.5 g. under
 EMI17.4
 colorless felted needle shape. ± meadows recrystellization with acetone and methanol, the melting point is close to 0. Anslyse corresponds to a compound of the formula 32H3S012N4 '
7.35 gr. of the hydrogenation product obtained above are dissolved in 100 cm3 of ice vinegar.

   In this solution, drop by drop and with vigorous stirring
 EMI17.5
 while cooling (10 ") <a solution of 3.0 gr. of ohromic anhydride in 1 * 5 cm3 of water and 100 o.m3 of ice wine. The mixture is left in the cooler, at 5 a little overnight, diluted very strongly with water and extracted three times with ether. The ethereal solution is washed several times with a solution of bicarbonate at 55 to

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 neutrality. After 0veportaiton of ether, 5.8 g are obtained. of the colorless oily oxidation product. this partially crystallizes after one night. Petroleum ether is added, the crystals are aspirated and washed several times with petroleum ether.

   The crystals are totally insoluble therein, while the oily oxidation product is very easily soluble therein. The melting point of these crystals is between 82-84. Ether and petroleum ether give colorless prisms with a melting point of 84-85. the substance obtained immediately gives, with 2,4-dinitro-phenyl0hydrazine, an egg-yolk-colored hy. Yield of pure substance 710 mgr .. the 0.5 gr solution. of diketone in 15 cm 3 of chloroform is added dropwise, to 0 and with vigorous stirring, a solution of bromine in chloroform until the amount of bromine calculated for 2 mol. Br2 is sb- sorbed. The chloroform is then evaporated under vacuum at 20-30.



  The residue, 0.8 gr. , is divided into two equal parts for the separation of the subsequent brominated hydrogen. a) separation of brominated hydrogen with collidine.



   0.4 gr. of dibromocetone are boiled with 5 cm3 of dry collidine for half an hour in the reflux apparatus. The solution, of a somewhat dark color, is then strongly diluted with ether. the ethereal solution is washed several times with dilute sulfuric acid and then .. te with a solution of sodium bicarbonate and water until. neutrality, after evaporation of the dry ethereal solution, a dark colored oil (150 mgr.) remains. High vacuum distillation gives two fractions:
1.-first jet 15 mgr., Boiling pint 125 /0.0005 mm .;
The colorless oil obtained is active in the Chapon test with 1.5 mgr / UCh.

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  8. "Second jet 15 mgr., Boiling point 150 / 0.0005 mm .; the colorless oil obtained is active in the Chapon test with, 1.5 mgr./Uch. B) separation of brominated hydrogen with pyridine.



   0.4 gr. of dibromide are boiled with 5 cm3 of dry pyridine for 6 hours in the reflux device.



  .After processing the above sum, we obtain 50 mgr. a dark colored oil, which is active in the test
 EMI19.2
 , Capon with 1.5 mgr./u0h.



  Example 5: 10 gr. of di- (p oxyphenyl) -di ethyl ethane in 100 cm3 of cygiohexane are hydrogenated for 5 hours with :) gr. of cyclohexane-moistened nickel analyzer according to Raney at 21-23215 and 140 atar. initial pressure. at the same time, it is stirred very intensely. the nickel catalysts are filtered off and the liquid is washed several times with hot methanol, the cyclohexane and methanol are removed in vacuo and the residue is rubbed with about 200 cm3
 EMI19.3
 dtether. The hydrogenated product, which is difficult to dissolve in ether, of the formula 018g42, with a yield of 490 6r .. crude melting point 160 to 1.65, then separates. After re-distilling the methanol, the substance melts at 166.

   The yield comprises 3.0 gr. After standing with the concentrated ether solution, a product dthydrc) polymeric gelation C18H34O2 with crude melting point 112-120 separates.
 EMI19.4
 element of, 1.5 gr. The crude product obtained, melting point 112%, is recrystallized from aqueous methanol, or, more preferably, from benzol. The inaoioreq / 1res small rods melt, after triple recrystallization, constantly at 117-180 ".

   This
 EMI19.5
 The hydrogenation product has the character of the polymeric cyclrogenation product at melting point 166, is very easily soluble in methanol and relatively soluble in ether.

 <Desc / Clms Page number 20>

 
 EMI20.1
 T, -ayastion of the hydrogenation proctmt (, f, 166), The solution of 2 gr. of the hydrogenation product in
 EMI20.2
 100 om3 of ice vinegar is added, at 10 <* and drop by drop, a solution of 80 mgr, of ohromic enhyclride (rectified 955 mgr.) In 10 cm3 of water and 100 cm3 of vinegar of ice- The mixture is left overnight at 5 in the cooler. It is then treated according to Example 4. a colorless oil is obtained which crystallizes for the most part little
 EMI20.3
 utime after.

   From petroleum ether-ether, diketone is obtained with a crude renation of 1.1 gr. After repeated recrystallization, the melting point is 86. The yield of pure substance is 0.87 gr.
 EMI20.4
 



  II.- Oxidation of the product of hydrogelation (mp 120).



   To the solution of 2.75 gr. of the hydrogenation product in 100 cm3 of ice vinegar, a solution of 1.35 gr. is added dropwise at 10 drops. chromic anhydride in 10 ounces of water and 100 cm3 of ice vinegar. The mixture is left to stand overnight at 5. After treatment as described for Example 4, a colorless oil is obtained with a yield of 2.3 g. From ether-petroleum ether, the solidified oil crystallizes into colorless prisms with a melting point of 85. Yield 1.3 gr.
 EMI20.5
 



  These cones obtained from the two hydro .. gunS1ilOn pi; nùres products are identical to each other depending on the melting point and the mixed melting point.



  III. "Bromuratioo. And, debromination of diketone (mp 86).



  A / In a chloroform solution.



  The solution of 2 gr. of diketone in 60 cm3 of chloro-
 EMI20.6
 form is adcL2Lionne, a -5 to -100, of a solution of osai9 om bromine in 60 caZ of chloroform, operation effected.

 <Desc / Clms Page number 21>

 
 EMI21.1
 killed at a hem, 8 1/8 h. ' and shaking strongly. After the first washing and evaporation of the chloroform solution, a slightly yellowish viscous oil is obtained, which does not oristallize, with a yield of 3.63 g. The separation
 EMI21.2
 The brominated hydrogen is carried out using 15 amine of co7lidin while heating for 4 hours in a water bath. a non-crystallizing oil is thus obtained, still having a high halogen content. This oil is then heated for 1/2 hour
 EMI21.3
 with frank collidin at 10.

   Yield: 1.6 gr. non-crystallizing oil still containing halogen and which is active on the Chapon ridge test with approximately% mgr. / UCh,
B. / In a solution of ice vinegar.
 EMI21.4
 the solution of 2 gr. of clicétoae in 100 omz of ice vinegar is added to 100 of a solution of bzz cm3 of bromine, in 50 ome of ice vinegar, op4re-uloa carried out over two hours, with vigorous stirring. By adding water to the ice vinegar solution, the bromination product separates as a colorless oil, The wine-water solution is extracted with ether and the ether solution is lifted.
 EMI21.5
 to neutrality.

   In evaporated from the ether. the oily bromination product remains, with a yield of 3.5 g. The separation of the brominated hydrogen using pyridine and collidine is carried out as described; active products are thus also obtained under the Chapon ridge test with approximately 1.5 mgr./UC ..



  Example 6
 EMI21.6
 In the conversion of α-tetholhydrobromide with sodium, an oily isomer di- (p-methoxyphn.yl) dithY1-ethane is obtained as a by-product. This oil gives, after separation of the methole, a syrupy oil not crystallized, which, after about 4 to 5 weeks, crystallizes in part. With phnol, one can easily remove, by dissolution, the fat not

 <Desc / Clms Page number 22>

 
 EMI22.1
 eristailisantes which are dark in color. we thus obtain, from 564 gr. of oil. 180 gr. of crystallize.



  From the benzolic mother liquor, we can% recover. after re-
 EMI22.2
 pos prolongs, 30 gr. of eristall.1sst; from benzol one obtains colorless prisms which melt at 127-128, the substance gives with the di- (p-oxyphenyl) -diethyl-ethB isomer at melting point 184. a remarkable depression of the point
 EMI22.3
 melting point, mixed melting point 7.15 -11.



  10 gr. of di- (p-oxyphéayl) -diéthyl..ethene isomer with melting point Ipso, in 100 oar3 of yc1ohex8ae are hydrogenated at 175-183 and 130 atm. of initial pressure with 5 gr. nickel catalyst moistened with cyclohexane and for two hours.,
 EMI22.4
 The absorption d1hya.r <gèa6 starts at 160. The nickel catalyst is then separated by filtration and the liquid is lifted several times with hot me-whaaol. The cyqlohexane and the mehanol are removed in vacuo and the residue is added with ether.



  It then separates the product of hydrogenation which is hardly soluble.
 EMI22.5
 -b7 in ether, of the formula QlaH3402 e vee yield of 4.67 gr. From cli 02V ne, one obtains prisms fa this, with melting point 1870-1880. this substance is isomeric with the hydrogenation products described in Example 5.



   L6 solution of 2.61 gr. of the isomeric hydrogenation product
 EMI22.6
 in 100 em3 of ice vinegar is added 10, drop by drop, a solution of 1.3 gr. ohromic anhydride in 13 cm3 of water and 100 cm3 of ice vinegar. The mixture remains
 EMI22.7
 in the cooler at 5, it is then treated as use. we Obtain; a colorless oil with a yield of only 2.5 g. of benzine (point of Gbu7..ition 70 -80) the oil crystallizes in colorless prisms with a melting point of 74-75. Yield of pure substance 1 , 5 gr. Analysis shows that we are faced with a diketone of
 EMI22.8
 the formula OtsH3002.

   Diketone with melting point q4 is isomeric with diketone with melting point 86 and yields with

 <Desc / Clms Page number 23>

 the latter an apparent depression of the melting point,
The solution of 1.4 gr. of isomeric diketone with a melting point 74 in 100 cm3 of chloroform is added, dropwise, to -15, a solution of 0.58 cm3 of bromine in 100 cm3 of chloroform. , after washing, drying and evaporation of the chloroform solution, a non-crystallizing oil is obtained with a yield of 2.2 g. The solution of 1.1 gr. of the bromination product is boiled for 6 hours in the reflux device in 10 cm3 of dry pyridine.

   Subsequent treatment gives 220 mgr. of a light brown oil. this oil, still containing halogen, is active in the Chapon ridge test with 1 mgr. / UCH.



  Example? 7:
140 gr. of di- (p-oxyphenyl) -diethyl-ethane isomer, according to Example 6, with melting point 128. are hydrogenated under the same conditions of Example 6. After removal of the solvent, the residue / is rubbed with ether. The hydrogenation product is then separated, which is hardly soluble in ether and has a melting point of 180-185. After standing the concentrated ether solution for a long time, a second hydrogenation product with a melting point of 128-135 is still obtained. The overall yield of hydrogenscion products is 140 g. for 92.4 mgr. of starting material.

   The hydrogenation product, melting point 135, crystallizes from benzol to colorless crystals of melting point 135. it also contains the composition C18H34O2 and is epimeric with the crystallizing product first, with melting point 187 -188, as well as isomeric with the hydrogenation products at melting point 166 and 117-120 (example 5) .



   The solution of 10 gr. of the hydrogenation product having a melting point of 128 -132 in 200 cm3 of ice vinegar is added.

 <Desc / Clms Page number 24>

 
 EMI24.1
 ted, drip. drop, at 10. of a solution of 5, o gr. in chromic hydride, in 20 cm3 of water and 200 cm3 of ice vinegar. The mixture is left in the icebox overnight at 5. The product is then treated as usual.
 EMI24.2
 crude, crystallized contains 8.4 gr.

   After double recriStallisst10a d! <J'ther-ether aE petroleum, diketone 01811300p food steadily at 7-75, the wrong / 1st onsijallize in broad and long bg ^ uonaets and is identical with the aiceione th8002, of the example 6 * The bromination and separation of hydrogen bromine is carried out as described for Example 6 and also resulting in materials of androgenic activity. which are identical to those of Example 6.



  Example 8:
 EMI24.3
 During the oxidation with llac: LcLe chromic ae 430 gr. of di- (p-cye7 ohecano, 1) -diethyl-thane (melting point 166 and 120) according to Example 5. one obtains next to the dicecone crystallized at
 EMI24.4
 melting point 8g, a slightly yellowish syrupy oil with a yield of 90g. This oil represents a mixture of ketone alcohol and diketone not completely crystallized,
 EMI24.5
 and resin. Distillation under high vacuum gives, as the first frgctioa, a slightly yellow colored t.3.on oil (bubble point 160 to 180/0> 001 mm.) With a yield of only 48.5 gr., And , as the second fraction, a light yellow oil (ebnl lition point 180-200 / 0.001 mm.) with a reading of 28.5 gr.



   48.5 gr. oil from the first fraction are dissolved in
 EMI24.6
 zoo cm3 of ether and 200 µm3 of petroleum ether are added, the solution then evolved through a 600 gr column. aluminum oxide, then washed each time with 1 free of sol-
 EMI24.7
 winds mentioned below and the filtered solution is freed from the solvent.

 <Desc / Clms Page number 25>

 
 EMI25.1
 
<tb> Test <SEP> number, <SEP> solvents. <SEP>: Residue <SEP> from <SEP> filtration <SEP> and <SEP> from
<tb>
 
 EMI25.2
 - <#. #### - # ---------- poration.



  I. Ether of 14 gr. of oil give with petroleum. di nitro ph ny3.hydra z ine un hy-
 EMI25.3
 
<tb> drazone <SEP> yellow <SEP> at <SEP> point <SEP> of <SEP> fusion
<tb>
<tb> 218-220.
<tb>
 
 EMI25.4
 II. Benzol. 7 gr. of oil, which ionizes ,. - 5 gr.
 EMI25.5
 
<tb> from <SEP> diketone <SEP> to <SEP> point <SEP> from <SEP> fusion
<tb> 186.
<tb>
 
 EMI25.6
 



  III. Benzol. 3 gr. de disetone p.3.86. IV. Ether. 5.5 gr. a mixture of dicëbo-
 EMI25.7
 
Ketone alcohol <tb> <SEP> and <SEP> <SEP>.
<tb>
 
 EMI25.8
 



  V..4 ctOr.le. 10 gr. of oil which immediately crystallizes; of btheryher of pe, ro-
 EMI25.9
 
<tb> the <SEP> on <SEP> gets <SEP> 6.5 <SEP> gr. <SEP> of alcohol
<tb> keto.
<tb>
<tb>



  VI. <SEP> Methanol, <SEP> 10 <SEP> gr. <SEP> of oil <SEP> which <SEP> gives <SEP> 1 <SEP> gr.
<tb> of <SEP> product <SEP> of hydrogenation <SEP> (m.p.
<tb>
 
 EMI25.10
 



  166-). The oily residue gives
 EMI25.11
 
<tb> a red <SEP> hydrazone <SEP>.
<tb>
 



  The ketonic alcohol from test 5 is recrystallized from ethereal and broad petroleum ether in the form of long / melting rods.
 EMI25.12
 sion 7 @ <'74 ". It has the formula 91SH3202 and probably represents a mixture of the two possible epimeric forms, because, in the oxidation with chromic acid, the mixture of the two epimeric hydrogenation products (-point of fusion 1660 and 120 was oxidized.
 EMI25.13
 It should be considered as du (p- ay olo hexa n onyi) - (p- ay 1 ohezB - .o, yZ) .3thya.-tha ne.



  The solution of 8.5 gr. of this conical oe alcohol in 50 ounces of acetic acid is heated for 2 hours at a boil.



  The residue is removed in vacuo and the residue is poured into petroleum ether. This solution is then passed through a column of aluminum oxide after concentration of the solution.
 EMI25.14
 tion to petroleum ether, we obbienô Z90 gr. of crystallize. Of benzine (boiling point qo-80) or d.16-uher of peorole (p-oyalohexsnooyl) ... (p ... a kétoxyoyolohegany.-âi, ethy3.-thane crystallizes into colorless tablets a melting point 69 -73.

 <Desc / Clms Page number 26>

 
 EMI26.1
 



  The solution of 1 gr. The ketone alcohol in 30 0013 of chlorolorm is milked to -5 * to -10 from a solution of 8 cm3 of bromine in 30 cm3 of chloroform, an operation which takes place during a hour waving. After washing and evaporating the chloroform, a yellow oil is obtained.
 EMI26.2
 ne-clear with reademenc, cL6 1.4 gr. The above bromide solution is boiled for 6 hours in the reflux apparatus with 15 µm3 of dry pyridine.

   After raising the pyr: W.1O.e under vacuum, the residue is poured into ether and the ether solution is washed with water. The product obtained after evaporation of the ether is distilled off under high vacuum for subsequent purification and thus obtained, at a temperature of about 160-180. a ketone alcohol just not
 EMI26.3
 saturated, either (p-c; yclohexenonyl) w (pooyclohexanolyl) -diéthy3. ethane as a clear oil. The product exhibits androgenic activity with 1 mgr. / v0h .. Yield.; p mgr ..



  Example 9 - Ether-petroleum ether mother liquors recovered from isomeric ketone with melting point 74 (prepared according to Example 6), after prolonged standing, a mixture of crystals of 25.5 g is obtained. This is purified by adsorption analysis. 25.5 gr. of this mixture of crystals are dissolved in 200 cm3 of ether and 200 cm3 of petroleum ether and the solution is then passed through a column of 350 g. of aluminum oxide, each time with 500 cm 3 of the solvents listed below is removed and the filtrate is freed from the solvent.
 EMI26.4
 



  Event number, ground winds. Filtration and evepo-
 EMI26.5
 
<tb> ----------------- <SEP> --------- <SEP> ration,
<tb>
<tb> I, <SEP> Ether <SEP> de <SEP> 7.1 <SEP> gr. <SEP> of <SEP> diketone <SEP> isomer <SEP> with
<tb> oil, <SEP> a little <SEP> of oil.
<tb>
<tb>



  II. <SEP> Benzol. <SEP> 8,2 <SEP> gr. <SEP> of <SEP> diketone <SEP> isomer <SEP> with
<tb> a little <SEP> of oil.
<tb>
<tb>



  III .. <SEP> Ether. <SEP> 3,2 <SEP> gr. <SEP> of oil.
<tb>
 
 EMI26.6
 



  IV. 3tin, au.5 gr. of oil which, after standing in PrQ-1.ongated Athnol, crystallizes. CttoV alcohol. ] 0% ethanol of the product ;;

 <Desc / Clms Page number 27>

 
The material recovered from test 4 is recrystallized from oyolohexane or petroleum ether-ether. a ketone alcohol is thus obtained isomer of the formula O18H32O2 in the form of needles shaped like a stole. with a melting point of 102
The bromination of the isomeric ketone alcohol and the separation of brominated hydrogen are carried out as stated for Example 8 and then also an unsaturated eetonic alcohol is obtained in the same yield as described "isomer". in example 8.



  Example 10. -
The solution of 1 gr. acetate of the ketone alcohol according to example sd in 30 cm3 of chloroform is added to -5 to -10 with a solution of 0.34 cm3 of bromine in 30 cm3 of chloroform, an operation which is carried out during d Stirring for one hour. After washing and evaporating off the chloroform, a light yellow oil is obtained with a yield of 1.35 g. This is boiled in the reflux apparatus for six hours with 15 cc of dry pyridine. Then the pyridine is distilled off in vacuo, the residue is poured into ether and the ether solution is washed with water.

   The product obtained after evaporation of the ether is distilled under high vacuum with a view to subsequent purification and it then passes to about 1600 to 180 bath temperature, (p-cyclohexenonyl) - (p-oyclohexanolylacetste) - diethyl ethane as a clear oil. Yield about 400 mgr.



  The ester exhibits the same endromene activity as the corresponding ketonic alcohol of Example 8, but exhibits, next to this, an activity which is maintained for a longer time.



  Example 11;
The solution of 1 gr. of ketone alcohol (melting point 73 -748) in 30 cm3 of chloroform is added, at low temperature and with vigorous stirring, a solution of bromine in chloroform until the amount of bromine calculated for

 <Desc / Clms Page number 28>

   2 mol. is absorbed. 1 mol. of bromine is very quickly consumed at -15 while the second mol. of bromine remains unconsumed first and destsbaorbed from elsewhere only at about 0 The chloroform solution washed to neutrality with sodium carbonate and water is dried with sodium sulphate and the chloroform is then removed under vacuum. A non-crystallizing, colorless oil remains, with a yield of 1.5 gr.



   0.75 gr. of this substance is boiled in the reflux apparatus for 7 hours with 5 cm3 of pyridine. After evaporating pyridine in vacuo, the residue is removed in ether. The ether solution is washed several times with dilute sulfuric acid, then twice with 5% caustic lye. After evaporation of the ether solution washed to neutrality, a halogen-free product is obtained with a yield of 60.3 mg.



   If the lye solution is acidified with dilute sulfuric acid, a white precipitate separates in small quantities, which is poured into ether. After evaporating! one of the ether solution washed and dried. the phenolic part of the separation of brominated hydrogen is obtained with a yield of 13.4 mg.



   Claims.

** ATTENTION ** end of DESC field can contain start of CLMS **.


    

Claims (1)

1. - proceeds for the preparation of valuable etilbene derivatives, characterized by the fact that in compounds of the stilboestrol series of the formula: EMI28.1 in which R denotes oxy groups or groups convertible into oxy groups and R 'denotes saturated or unsaturated alkyl radicals, while X and Y denote hydrogen atoms or oxy groups, that is to say groups convertible into oxy groups, or a combination of a hydrogen atom and a group <Desc / Clms Page number 29> pe oxy, that is to say a group which can be transformed into an oxy group, or in which x and y have taken place a double bond, one (or both aromatic rings of the starting material is transformed into more or less hydrogenated rings, optionally , if necessary, simultaneously or subsequently, the double bonds optionally present in the radicals r, Qu in the ethane group, in saturated bonds and, in certain cases, the groups R 'in ketone groups. 2.- method according to claim 1, characterized by the EMI29.1 makes use of etilbopttrols, 99yl, as the starting material. 3.- process according to claim 1, characterized in that the starting material is glycols EMI29.2 <, p-a.i-p-oxyphnyl-C <, p-dialo <5yl-ethylenes. 4.- process according to claim 1, characterized in that the starting material is ethanols EMI29.3 0 (p- (11-p-OiWphO-nyl-, p-alaoyl. 5.- process according to claim 1, characterized in that the chloride is used as starting material EMI29.4 c <-tP '' 'cLi "P-oxyphéQyl-O (. p-dia1 coyl-ethyl. 6. A process according to claims 1 to 5, characterized in that the starting material of compounds' o (, p-diethyl. 7. A process according to claims 1 to 6 characterized in that the starting materials are first treated with hydrogenating agents, then successively with EMI29.5 oxidizing agents. halogenation and hydrogen-halogen separating agents, and that finally, optionally, further partial hydrogenation is carried out or preferably one of the oxo groups is reduced. 8.- method according to claims 1 to 7, characterized EMI29.6 in that the starting materials are perhydrogenated, <Desc / Clms Page number 30> and that, then, the x-groups are transformed, if necessary, into oxy groups, these being then oxidized, and that in the rings having a ketonic group double bonds are introduced by halogenation and separation of hydro- gene-halogen and that, optionally and simultaneously or subsequently, the ethane bond is transformed into an ethylene bond by separation of water from hydrogen-halogen, 9. - process according to claims 1 to 8. characterized by the fact that one starts from etilbenes derivatives in which the oxy groups, located at the nucleus, are replaced totally or partially by a group which can be transformed into an oxy group, and that the latter is transformed before, during or after oxidation, preferably after the separation of halogenated hydrogen, into an oxy group, an ether or an ester group. 10. A process according to claims 1 to 9, characterized in that the oomposésp-alkoxy is used as starting material. preferably p-ethoxy compounds, 11, - proceeds according to claims 1 to 10. characterized in that one starts from phenolethers and that these are saponified directly after the hydrogenation. 12.- proceeds according to claims 1 to 11, characterized in that the starting material is hydrogenated and oxidized symmetrically to the two cycles, and then transformed into monocetone derivatives, such as semicarbazones, acetsls or enol derivatives to be subsequently subjected to reduction, the ketone group then being restored and the product thus obtained being optionally halogenated and treated subsequently. 13.- Method according to claims 1 to 11 characterized in that one starts with monophenols and that the starting material, after hydrogenation, is preferably oxidized on one side, or halogenated and / or reduced and that during or sprgs these reactions, the group being in the second cycle, is <Desc / Clms Page number 31> transformed into an oxy or ester or ether group. 14. A method according to @ claims 1 to 13, characterized in that one starts from moaophnolethers and that these are saponified after halogenation, preferably after dehalogenation. 15.- process according to claims 1 to 14, characterized in that one starts from compounds in which X and Y EMI31.1 denote ithydrogen or a group which can be separated under the formation of YVn compound $ 4thylene, which is produced in the finished product obtained by the ethylene bond by separation of water from hydrogen EMI31.2 halogenated with a cltun alcohol, etc. .. and then carried out under aromatization, a conversion of one of the cycles and that, EMI31.3 optionally, the cyclohexanone group is subsequently reduced. 16.- method according to claims 1 to 15, characterized in that one starts with ethanols and that one treats those- EMI31.4 ai, after halogenation, preferably after separation of halogenated hydrogen, with water separating agents. 17.- method according to claims 1 to 16, characterized EMI31.5 by the fact that one starts from the 4thylhalogdaures, ELO preferably from the ethyl chlorides, these being dehalognés after halogenation. 18.- method according to claims 1 to 17, characterized in that, during halogenation, is introduced into each cycle of halogen a stame /. preferably bromine. 19.- process according to claims 1 to 18, characterized in that, during the halogenation, two EMI31.6 halogen atoms in each oyolohexanoae ring and the end product is treated with an allyl converting agent. 20.- method according to claims 1 to 19, characterized EMI31.7 by the fact that one transforms the compounds cyolohexsnones ob.-held unilaterally into stable oeto or eno7 derivatives, such as ae # icarbazones. ece-such or other enol bonds, <Desc / Clms Page number 32> that they are subjected to hydrogenation in the other cycle and that, then, the keto or oxy groups are freed again. 21. - Process according to claims 1 to 20, characterized in that the oxidation is carried out according to the exchange method with ketones or aldehydes or alcoholates of aluminum or magnesium. 22.- process according to claims 1 to 21. characterized in that one transforms the oxy groups of the products obtained, either totally or partially, into organic esters, preferably into acetates.propionstes or benzoates, or that one proceeds from compounds of this kind partially esterified. 23.- Process according to claims 1 to 22, characterized in that the diethylstilboestrol is subjected to hydrogenation in ice vinegar with a platinum catalyst, that the tetradécshydrostilboetrol obtained is oxidized in a solution. of chromic acetic acid, that the diketone is halogenated with bromine in a solution of ice vinegar containing brominated hydrogen, that the dibromide is boiled with pyridine and that the di- (cyclohexenonyl ) -di0tjylethane by fractional distillation. 24.- proceeds for the preparation of valuable compounds of the diphenylethane or -ethene series. characterized in that compounds of the general formula: R. C6H4-Z-C6H4.R in which R denotes an oxy group or a group convertible into an oxy group. Z either EMI32.1 in which r 'denotes an alkyl radical. x and Y hydrogen, halogen, an oxy group Qu a group convertible into <Desc / Clms Page number 33> oxy group, and in which the two symbols may have the same or a different meaning, or in which both commonly denote a double bond between the thane-carbon atoms or EMI33.1 in which R '' denotes an alkyl radical linked by a double bond with an ethane ... carbon atom, are perhydrogenated, that in the hydrogenation products, if necessary, one or both R groups are transformed into Qxy groups, that then one or both secondary oxy groups are oxidized and then introduced, in the rings having a keto group, one or more double bonds by halogenation - preferably with bromine - and separation of halogenated hydrogen, and that, optionally, either simultaneously or subsequently, the ethane bond is converted into an ethylene bond and / or that again the double bonds introduced into the ring system are partially hydrogenated and / or that an oxo group is found in the ring system, be reduced! to an oxy group, or that an oxy group therein is oxidized to an oxo group after which, if necessary, any secondary hydroxyl groups present are esterified or etherized. 25 .... An embodiment of the process according to claim 24, characterized by the fact that the products obtained according to this method, which are twice saturated in a cycle of the system and which contain an ethene group between the cycles, are subjected to a conversion with aromatization of the doubly unsaturated ring and that, optionally, any capping group present is subsequently reduced. 26. Embodiment of the process according to claim 24, characterized in that the dic: tones obtained by hydrogenation and oxidation of the starting material, are transformed into monoketone derivatives, such as oarbazones, acé - <Desc / Clms Page number 34> such, enol drifts. that the remaining free ketone groups are reduced and then. the ketone groups are re-established from their functional derivatives and the product thus obtained is further processed. 27.- Reslisetion form of the process according to claim 24, characterized in that the hydrogenation products are oxidized unilaterally :, halogenated and that one places, by subsequent separation of halogenated hydrogen, a double bond in a ring and that, if desired, the treatment is continued according to claim 24. 28. - Process according to claims 24 to 27, characterized in that the oxidation of the hydroxyl groups into cetode groups is carried out according to the method of exchange with ketones or aldehydes and aluminum alcoholates. or magnesium. 29.- proceeds according to claims 24 to 28, characterized in that the oxy groups of the products obtained are totally or partially converted into organic esters, preferably into acetates, propionates or benzoets. 30.- process for the preparation of partially hydrogenated compounds of the dipheyl-dislcoyl-etthane series, station ctérisé by the fact that in perhydrogenated ketones of this series are in. trodbit a double bond in one or in the two nuclei in the vicinity of the keto group, for example by hydrogenation of one or both nuclei and separation; ion of halogenated hydrogen, and optionally the keto groups are reduced to oxy groups . 31. -Procédé according to claims 1 to 30, characterized in that the di- (cyclohexanonyl) -diethyl-0tgend or its isomers and epimers are halogenated, treated with halogenated hydrogen separating agents and that the reaction mixture , the di- (cyciohexenonyl) -diethyl-ethe which has formed is isolated. 32, -process according to claims 1 to 31, characterized in that the (cyclohexanonyl) - (acyloxycylohexanyl) -diethyl- <Desc / Clms Page number 35> ethane or its isomers and epimers are halogenated, processed EMI35.1 with halogenated hydrogen separating agents and the (g e7. oheunoz, p,). (a cy, o $ y cy a, ohexa ny1) -d3 ethy T.- etha ne, which was formed. is isolated and optionally saponified.