1.6 5-Oxo-3,5-seco-A-norcholestan-3-carbonsäure (2 Stufen)

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1 1.6 5-xo-3,5-seco-A-norcholestan-3-carbonsäure (2 Stufen) C C C C C 3 C Al[C(C 3 ) 2 ] 3 3 C NaI 4, KMn 4 - C 2 C 8 17 = 3 C C 3 3 C C C C Zeitbedarf: 7 8 d Cholest-4-en-3-on (1/10 der riginalvorschrift) Ausgangsverbindungen, Reagenzien, Lösungsmittel Signalwort azard Toluol (getrocknet) Gefahr 225, 304, 361, 373, 315, 336 Precautionary P210, P301 + P310, P331, P302 + P352 Calciumsulfat wasserfrei (Drierite ) Cholesterol Cyclohexanon Achtung 226, 332 Aluminiumtriisopropylat Gefahr 228 P210 Kalium-Natrium-Tartrat (= Rochellesalz = Seignette-Salz)

2 tert-butylmethylether Gefahr 225, 315 P210, P302 + P352 Essigsäure-ethylester Gefahr 225, 319, 336, EU066 P210, P240, P305 + P351 + P338 Ethanol Gefahr 225 P210 Alte Kennzeichnung: Ausgangsverbindungen, Reagenzien, Lösungsmittel R-Sätze S-Sätze Toluol (getrocknet) F Calciumsulfat wasserfrei (Drierite ) Cholesterol Cyclohexanon Xn Aluminium-triisopropylat F Kalium-Natrium-Tartrat (= Rochellesalz = Seignette-Salz) tert-butylmethylether F, Essigsäure-ethylester F, Xi Ethanol F riginalvorschrift aus rganic Syntheses 1) To a 5-l. three-necked flask, equipped with a sealed mechanical stirrer, a dropping funnel, and a take-off reflux condenser, are added 2 l. of sulfur free toluene and two boiling chips. The openings of the dropping funnel and the condenser are protected by drying tubes containing Drierite. A portion (200 ml.) of the toluene is distilled from the flask (take-off cock open) in order to dry the system by azeotropic distillation; then 100 g. (0.26 mole) of cholesterol and 500 ml. of cyclohexanone (Note 1) are added to the flask. After an additional 50 ml. of toluene has been distilled, a solution of 28 g. (0.14 mole) of aluminum isopropoxide (Note 2) in 400 ml. of dry toluene (Note 3) is added dropwise over a period of 30 minutes. During this time toluene is distilled at a rate slightly greater than the rate of addition of catalyst solution, so that when the addition is complete about 600 ml. of toluene has distilled, and the murky orange-colored reaction mixture is then allowed to cool to room temperature. Four hundred milliliters of a saturated aqueous solution of potassium-sodium tartrate (Note 4) is added to the mixture, and the organic layer becomes clear and orange. The stirrer assembly is removed, and the mixture is steam distilled until about 6 l. of distillate has been collected. The residual mixture is cooled and extracted successively with one 300-ml. portion and two 100-ml. portions of chloroform *). The combined extracts are washed with two 100-ml. portions of water and dried over anhydrous magnesium sulfate. The chloroform *) is removed by distillation on the steam bath at reduced pressure (water aspirator). The residual viscous amber oil (Note 5) is dissolved by heating in 150 ml. of methanol **). When the solution has cooled to about 40 C, seeds of cholesterone are added, and the flask is wrapped with a small towel to ensure slow cooling (Note 6). After the bulk of the material has crystallized, which requires several hours, the mixture is stored at 0 C overnight (Note 7). The product is collected by suction filtration, washed with ml. of methanol **) previously cooled in an ice-salt bath, then dried at reduced pressure, first at room temperature and finally at 60 C. The yield of

3 light-cream colored 4 -cholesten-3-one is g. (81 93 %), m.p C. Recrystallization from methanol **) gives material melting at C. in 90 % recovery (Note 8). *) Ersetzen Sie Chloroform durch ein Gemisch aus tert-butylmethylether / Essigsäureethylester (1:1)! **) Ersetzen Sie Methanol durch Ethanol! Notes 1. Commercial cholesterol, m.p C, is satisfactory if dried at reduced pressure at 100 C for 48 hours. The cyclohexanone is simply distilled before use, b.p C. 2. Directions for the preparation of aluminum isopropoxide are given by Young, artung and Crossley (J. Am. Chem. Soc., 1936, 58, 100). This compound is also commercialy avalaible. Turbidity of the catalyst solution is to be expected and is not detrimental. 3. Toluene is dried satisfactorily by distilling about 20% of it and using the residue, which is cooled with protection from moisture. 4. Either Rochelle or Seignette salt is satisfactory. The tartrate ion serves to keep the aluminum ion in solution. 5. Prolonged heating is not necessary, since the chloroform *) remaining with the residual oil does not hamper the crystallization. 6. Seed crystals may be obtained by transferring a few drops of the solution to a small test tube, then cooling and scratching. rdinarily the cholestenone will separate as an oil from a solution saturated much above 50 C. In this event, rather than working with larger volumes of methanol **), small portions of chloroform *) may be added to the solution to lower the saturation temperature to a point at which seed crystals do not turn to oil. The best yield of good crystalline product is realized by inducing crystallisation at the highest possible temperature in order to obtain a large initial crop of crystals. A second crop is difficult if not impossible to obtain by direct crystallisation. The towel should be placed around the flask only after crystallisation, rather than oil formation, is assured. The towel is carefully removed occasionally during the first hour to ascertain whether oil is forming on top of the crystals. If so the solution is warmed slightly in order to redissolve the oil but not the crystals. The product is quite impure if it first separates as an oil which later crystallizes. 7. If initial crystallisation is not induced at 40 C or above, a further period of cooling in an ice-salt bath is necessary to obtain the best yield. 8. In order to avoid large volumes, it is recommended that 700 ml. of methanol **) be employed to recrystallize 90 g. of cholestenone and either chloroform *) or acetone be used to increase the solubility of cholestenone to the required amount.

4 xidation von Cholest-4-en-3-on mit Natriumperiodat und Kaliumpermanganat Ausgangsverbindungen, Reagenzien, Lösungsmittel Signalwort azard Precautionary Kaliumcarbonat Achtung 315, 319, 335 P302 + P352, P305 + P351 + P338 Cholest-4-en-3-on tert-butanol Gefahr 225, 332, 319, 335 P210, P305 + P351 + P338, P403 + P233 Natriumperiodat Gefahr 271 P210 Kaliumpermanganat Gefahr 272, 302, 410 P210, P273 käufliche 38 40proz. Natriumbisulfit-Lauge (= Natriumhydrogensulfit-Lauge) konz. Schwefelsäure (96proz. = 18 M) Achtung 302, EU031 P262 Gefahr 290, 314 P280, P301 + P330 + P331, P309, P310, P305 + P351 + P338 tert-butylmethylether Gefahr 225, 315 P210, P302 + P352 Cyclohexan Gefahr 225, 304, 315, 336, 410 P210, P240, P273, P301 + P310, P331, P403 + P235 Alte Kennzeichnung: Ausgangsverbindungen, Reagenzien, Lösungsmittel R-Sätze S-Sätze Kaliumcarbonat Xi 36/37/ Cholest-4-en-3-on tert-butanol F, Xn Natriumperiodat 8 Kaliumpermanganat, Xn, N / Natriumbisulfit-Lösung Xn (38 40proz.)

5 konz. Schwefelsäure C tert-butylmethylether F, Cyclohexan F, Xn, N / riginalvorschrift aus Canadian Journal of Chemistry 2) Potassium carbonate (28 g.) in water (800 ml.) was added with vigorous stirring to a solution of cholestenone (50 g.) in tert-butanol-water azeotrope (3 l.), followed by 500 ml of a solution prepared from sodium metaperiodate (200 g) and water (2.5 l.), and then 50 ml. of 0.8% aqueous potassium permanganate. The remainder of the periodate was added at the rate of 110 ml/minute for 10 minutes, and then at 30 ml/minute for the next 30 minutes. Permanganate solution was added when necessary to maintain the permanganate color, 50 ml being usually required after the first 5 minutes and a further 75 ml at intervalls over the next 30 minutes. After 2 hours, the excess permanganate was destroyed with sodium bisulphite. The resultant iodine-colored solution was concentrated at reduced pressure to a volume of about 4 l., cooled to 4 C, acidified with ice-cold 50 % sulfuric acid, and extracted with ether *) (2.5 l., 1.5 l., and 1.5 l.). The etheral *) extract was washed with sodium bisulphite solution until free from iodine, with water until neutral, and dried (magnesium sulphate). It was then concentrated to 700 ml, diluted with petroleum ether **), and further concentrated to 250 ml. After standing for 8 hours at room temperature and 8 hours at 4 C, the solution yielded white needles ( g) of keto acid, m.p C (literature m.p C). The mother liquors, on being concentrated to about 60 ml and chilled, gave after several days a second crop of impure acid, from which pure acid ( g), m. p C, was obtained by recrystallization from ether *)-petroleum ether **). *) Ersetzen Sie Diethylether durch tert-butylmethylether! **) Ersetzen Sie Petrolether durch Cyclohexan! Literatur 1) J. F. Eastham, R. Teranishi, rg. Synth. Coll. Vol. 1963, 4, ) J. T. Edward, D. older, W.. Lunn, I. Puskas, Can. J. Chem. 1961, 39, 599.

AQA Chemistry A-level

AQA Chemistry A-level Required Practical 10 Preparation of a pure organic solid, test of its purity, and preparation of a pure organic liquid Reflux Reflux: continuous boiling and condensing of a reaction