4- Cholestene-3,6-dione

A soln. of B-nor-4-cholestene-3,6-dione in ethanol containing coned. HGl refluxed 30 min. with amalgamated tin and a few crystals of HgGlg B-nor-coprostane-3,6-dione. Y almost 100%. W. G. Dauben, G. A. Boswell, and W. Templeton, J. Org Ghem. 25, 1853 (1960) method, also quinols from quinones, s. J. P. Schaefer, J. Org. Chem. 25, 2027 (1960). 

Weakly fluorescent zones were visible under long-wavelength UV light (X = 365 i (Fig. 1). Cortisone (h/ f 0-5), dienestrol (h/ f 10-15), 4-androstene-3,17-dione (It 50-55) and 4-cholesten-3-one (h/ f 60-65) had an ochre fluorescence. Diethylsti estrol (h/ f 10-15), 17a-ethinyl-l,3,5-estratriene-3,17B-diol (h/ f 25-30) and estro (h/ f 35-40) had a blue emission. 

Fig. 1 Fluorescence scan of a chromatogram track with 1 ng cortisone (1), 100 ng dienestrol (2X 300 ng 17a-ethinyl-l,3,5-estratriene-3,17B-diol (3), 100 ng estrone (4) and 1 ug each of 4-androstene-3,17-dione (5) and 4-cholesten-3-one (6) A. before immersion in Triton X-100, B. after immersion followed by brief drying, C after heating to 120 °C for 10 minutes and D. for a further 20 minutes to increase the fluorescence.

A4-Cholesten-3,6-dione is sensitive to air oxidation under certain conditions, particularly in alkaline solution. If the protective procedure specified is not followed the reaction product may be deep red and tarry. 

The residual solution contains a little cholesterol, 0.2-0.3 g. of A4-cholesten-3,6-dione, and small amounts of products derived from the oxidation of cholestanol and other companions. 

Mauthner and Suida 2 isolated, as one of three neutral products resulting from the oxidation of cholesterol with aqueous chromic acid in acetic acid solution, the substance later identified as A4-cholesten-3,6-dione. The present procedure is based upon results of a reinvestigation of the oxidation by a low-temperature, non-aqueous procedure.3... 

The treatment of 5-cholesten-3-one with oxygen in the presence of cupric nitrate or cupric acetate in pyridine and triethylamine in methanol furnishes 5-cholesten-3,6-dione in 75% yield [61]. 4,4,14a-Trimethyl-A -... 

Exhaustive dichromate oxidation of cholesterol and removal of an extensive acidic fraction leaves a mixture of A -cholestene-3,6-dione and several monoketones and other neutral products. Repeated extraction of a solution in petroleum ether with... 

Cupric nitrate-Pyridlne. This complex in the presence of triethylamine as base catalyzes the reaction of A -cholestene-3-one with molecular oxygen to form A -cholestene-3,6-dione. The yield is about twice that (4>tained by dichromateoxidation. ... 

In exploring, as a model case, the conversion of A -cholestene-3-one (3) into cholestane-3,6-dione (7), a Merck group" converted 750 mg. of the 3-ethyleneketal (4) into the 5a,6a-epoxide (5) by reaction with perbenzoic acid and treated a solution of (5) in tetrahydrofurane with 3 N aqueous perchloric acid solution at room temperature to effect hydrolysis of both the ethyleneketal group at Cd and the 5a,6o -epoxide group. Treatment of (6) with base effected dehydration and isomerization to the... 

In anhydrous acetic acid—benzene.This solvent mixture, introduced by one of us in a study of the oxidation of cholesterol, has these advantages benzene is abetter solvent for the sterol than acetic acid less acetylation occurs oxidation can be conducted in homogeneous solution at temperatures ranging from 0° to 121°. ° Experiments conducted in this way led to isolation of no less than six neutral products and two diacids derived from cholesterol (and not from its companions). A procedure for the preparation of A -cholestene-3,6-dione includes a novel procedure for workup. A mixture of dichromate and acetic acid was heated and swirled to effect solution and cooled to 15°. A solution of cholesterol in benzene was cooled to... 

The finding of Windaus" that a yellow product of oxidation of cholesterol later characterized us A"-cholestene-3,6-dione (7) Is reduced quantitatively by zinc and acetic acid to the colorless dione (8) provided useful evidence of structure (7). 

For oxidation of testosterone to the dione it was found best to follow the procedure outlined in the formulation. Oxidation of cholesterol by a similar procedure afforded A -cholestene-3-one in 66% yield. 

Isomerization of a,(i-unsaturated ketones and esters. Schering chemists57 observed that 6)S-bromo-A4-cholestene-3-one (1) on reductive debromination with zinc in aqueous ethanol is converted into A -choleslene-3-onc (2), but that some isomerization to the conjugated ketone occurs simultaneously. However, it was possible to obtain the noncortjugated ketone in 25% yield. The cross-conjugated ketone 6/8-bromo-A1,4-androstadiene-3,17-dione (3) was converted into A1,r,-androstadiene-3,17-dione (4). 

Photochemistry of diones began with Klinger s 82> report of the sunlight reactions of benzil and phenanthrenequinone with diethyl ether but reactions of diones with ethers have been investigated to a very limited extent since then. The reported reactions include biacetyl (dioxane 20>), benzil (diethyl ether 82>, dioxane 128>), tetramethyltetralindione (73, dioxane 60>), tetrachloro-o-benzoquinone (dioxane 128>), acenaphthene-quinone (dioxane 128>) and phenanthrenequinone (diethyl ether 82>, di-isopropyl ether 127>, di-n-butyl ether 127>, tetrahydrofuran 128>, dioxane 128>, anisole 128>, methoxycholestane (86) 128>, methoxy-5-cholestene 128>). 

Reduction of enediones. A4-Cholestene-3,6-dione (1) is reduced by chromous chloride in either THF or acetone to 5/3-cholestanone-3,6-dione (2).3 Note that reduction with zinc and acetic acid gives the more stable 5a-cholestane-3,6-... 

Chlorotrifluoromethylcarbene, 223 N-Chlorourethane, 60, 61 AM-Cholestadiene-3,6-dione, 60 5a-Cliolestane-3,6-dione, 60 5oCholestane-2a , 3a-oxide, 135 5CfrCholestane-2j3,3(3-oxide, 135 5(3-Cholestanone-3,6-dione, 60 A4-Cholestene-3,6-dione, 60, 65 Al-5/3-Cholestene-3,6-dione, 60 A4-Cholestene-3-one, 98 A4-Cholestene-4-one, 60 -Cholestene-a-epoxide, 116 A5-Cholestenone, 65 Cholesteryl acetate, 35, 171 Cholesteryl acetate dibromide, 40 Chromic acid, 54, 246 Chromic anhydride, 54-57, 150 Chromic anhydride-Acetic acid, 56 Chromic anhydride-Dimethylformamide, 56 Chromic anhydride-Pyridine complex,... 

Oxygenation. Brackman et al.1 found that cupric acetate complexed with an amine (pyridine was used) in the presence of abase such as triethylamine functions as a homogeneous catalyst in methanol for the air oxidation of A5-cholestenone to A4-cholestene-3,6-dione in 75% yield. The reaction is applicable to a,fi- and fi.y-aldehydes and ketones for example ... 

Photooxidation of 3-morphohno-2-cholestene (4) at -78° give a 1 1 mixture of 3-morpholino-3-cholestene-2-one (5) and cholestane-2,3-dione (6). 

Deoxygenation of ketosteroids. The deoxygenation of ketones with this combination has been extended to ketosteroids. A -Cholestene can be obtained in about 70% yield from 5a-cholestane-3-one with trimethylchlorosilane and zinc dust in THE at reflux. The reaction fails with 6-, 7-, 12-, 17-, and 20-ketones. This result suggests that a very bulky intermediate is involved. Thus it is possible to selectively deoxygenate diketones. For example, A -5a-cholestene-7-one can be prepared from 5a-cholestane-3,7-dione (72% yield). ... 

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