A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1941, 21, 18
DOI: 10.15227/orgsyn.021.0018
Submitted by R. V. Oppenauer
Checked by J. Cason and L. F. Fieser.
1. Procedure
A carefully dried 5-l. round-bottomed flask equipped with a reflux condenser carrying a calcium chloride tube is charged with 100 g. of cholesterol (Note 1), 750 ml. of acetone (Note 2), and 1 l. of benzene (Note 3). A boiling tube is introduced to prevent bumping (Note 4), and the mixture is heated to boiling in an oil bath which is maintained at 75–85° during the reaction. A solution of 80 g. of aluminum tert-butoxide (p. 48) in 500 ml. of dry benzene is added in one portion to the boiling solution. The mixture turns cloudy and in 10–15 minutes develops a yellow color. Gentle boiling is continued at a bath temperature of 75–85° for a total of 8 hours. The mixture is then cooled, treated with 200 ml. of water and then 500 ml. of 10% sulfuric acid, shaken vigorously, and transferred to a 5-l. separatory funnel. The mixture is diluted with 1.5 l. of water and shaken for several minutes, after which the yellow aqueous layer is drawn off into a second separatory funnel and shaken out with a small amount of benzene (Note 5). The combined benzene extracts are washed thoroughly with water and dried by filtration through a layer of sodium sulfate; the solvent is evaporated, the last traces being removed by heating the residue at 60° at the water pump vacuum. The oily yellow residue solidifies when it is cooled in an ice-salt bath and scratched. For crystallization the material is dissolved in a mixture of 70 ml. of acetone and 100 ml. of methanol; the solution is allowed to cool very slowly and is seeded, for otherwise the product tends to separate as an oil. After the bulk of the material has crystallized, the mixture is allowed to stand for 1 day at 0°; the product is then collected, washed with 100 ml. of ice-cold methanol, and dried in vacuum at room temperature. The yield of almost colorless cholestenone, m.p. 77–79°, is 70–81 g. (70–81%). Recrystallization by the same method gives material melting at 78.5–80.5° with 90% recovery (Note 6) and (Note 7).
2. Notes
1. The material should be dried to constant weight at 80–100° in vacuum. Commercial cholesterol, m.p. 146–148.5°, gives satisfactory results; the yield is raised 5–10% by using cholesterol that has been purified by regeneration from the dibromide.
2. The acetone is distilled once from permanganate and twice from freshly fused potassium hydroxide.
3. The benzene is distilled over sodium.
4. If boiling stones are employed, fresh ones must be added at intervals; the boiling tube promotes smooth boiling at the bath temperature specified.
5. The troublesome emulsions sometimes encountered are easily broken by filtration from a trace of suspended solid.
6. For recovery of material in the mother liquors, the solutions are subjected to steam distillation to remove solvents and condensation products from the acetone. The process is continued until the distillate is odorless (1–2 hours), and the residual oil is dried by heating it under reduced pressure on the steam bath. From a solution in acetone-methanol (20 ml. and 50 ml., respectively) there is obtained after some manipulation (slow cooling, scratching) 3.3 g. of crude cholestenone, m.p. 72–80° (cloudy melt).
7. The yield is reduced by about 5% by halving the amounts of acetone and benzene specified and using only 50 g. of aluminum tert-butoxide.
3. Discussion
Cholestenone has been prepared by oxidation of cholesterol dibromide with chromic acid1,2 or potassium permanganate3 and subsequent debromination; by dehydrogenation of cholesterol over copper oxide;4,5 and by the method described above.6,7
This preparation is referenced from:

References and Notes
  1. Windaus, Ber., 39, 518 (1906).
  2. Bretschneider and Ajtai, Monatsh., 74, 57 (1943).
  3. Schoenheimer, J. Biol. Chem., 110, 461 (1935).
  4. Diels and Abderhalden, Ber., 37, 3099 (1904).
  5. Diels, Gädke, and Körding, Ann., 459, 21 (1927).
  6. Oppenauer, Rec. trav. chim., 56, 137 (1937).
  7. Brit. pat. 487,360 [C. A., 33, 323 (1939)].

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

sulfuric acid (7664-93-9)

Benzene (71-43-2)

methanol (67-56-1)

potassium permanganate (7722-64-7)

sodium sulfate (7757-82-6)

acetone (67-64-1)

potassium hydroxide (1310-58-3)

sodium (13966-32-0)

chromic acid (7738-94-5)

copper oxide (1317-38-0)

Cholesterol (57-88-5)


acetone-methanol (590-90-9)

Cholesterol dibromide (1857-80-3)