Organic Syntheses, CV 2, 191
[β-Cholestanol]
Submitted by W. F. Bruce
Checked by Louis F. Fieser, R. P. Jacobsen, and M. S. Newman.
1. Procedure
(
A)
From Cholesterol.—
One hundred grams (0.26 mole) of commercial cholesterol is crystallized from
250 cc. of glacial acetic acid, using
1 g. of Norite if required, and the purified material (Note
1) is transferred, conveniently without being dried, to a
hydrogenation vessel equipped with a
thermometer and a heating device (Note
2).
Three hundred cubic centimeters of purified glacial acetic acid (Note
3) and
0.5 g. of platinum oxide are added, and the hydrogenation is conducted at 65–75° at a slight positive pressure. The total amount of
hydrogen usually is absorbed in two to four hours (Note
4). After the
hydrogen has been replaced by air the solution is filtered hot and the product is obtained by crystallization and concentration. The total yield of air-dried, partially acetylated
dihydrocholesterol, m.p.
130–135°, is
85–90 g.
Unless a specially purified product (see below) is desired, the crude material is heated for three hours on the
steam bath with
400 cc. of alcohol and a solution of
25 g. of sodium hydroxide in 100 cc. of water. After cooling, the product is collected, washed, and crystallized from
500 cc. of alcohol. The yield is
75–80 g. (
75–80 per cent of the theoretical amount), and a well-dried sample (Note
5) melts at
140–141°.
Submitted by J. O. Ralls
Checked by Louis F. Fieser, R. P. Jacobsen, and M. S. Newman.
1. Procedure
(
B)
From Cholesteryl Acetate (Note
6).—
Five grams of cholesteryl acetate (Note
7) and
0.1 g. of platinum oxide are suspended in
25 cc. of absolute ether and
50 cc. of purified glacial acetic acid (Note
3), and the hydrogenation is conducted at room temperature at a slight positive pressure. The reaction is complete in ten to fifty minutes. The solution is filtered, using
ether to dissolve any crystallized material, and, after removing the solvent by distillation at reduced pressure, the residue is either saponified as above or purified in the following manner.
Purification by the Method of Anderson and Nabenhauer.
1—A solution of
20 g. of crude, partially or completely acetylated dihydrocholesterol in
200 cc. of carbon tetrachloride is placed in a
separatory funnel and treated with
100 cc. of acetic anhydride. About
5 cc. of concentrated sulfuric acid is added dropwise through the stem of the inverted funnel with cooling and shaking until there is no further increase in color. A blue or green color develops, the intensity depending on the amount of
cholesterol present in the sample. After fifteen to twenty minutes about 10 cc. of water is added, by drops and with cooling and gentle shaking until two distinct layers form. The
carbon tetrachloride solution (upper layer) is separated and washed free of acid with
sodium chloride or
sodium carbonate solution (pure water gives emulsions). After drying with
sodium sulfate, the solvent is removed by distillation at diminished pressure and the residue is saponified as above with alcoholic alkali and crystallized from alcohol. The purified
dihydrocholesterol weighs
12–14 g. and melts, after thorough drying (Note
5), at
142–143°. It gives a faint Liebermann-Burchard reaction (Note
8) only after ten to fifteen minutes.
2. Notes
1. The dry weight of the crystallized material is
90–95 g. Some samples may require recrystallization.
2. A suitable arrangement for heating the hydrogenation vessel is described in
Org. Syn. Coll. Vol. I, 1941, 61. An alternative arrangement is the following: a
round-bottomed long-necked flask is supported at the top by a two-piece clamp with a loosened checknut, connected below to an eccentric, and heated in motion by means of a stationary
microburner.
4. The catalyst sometimes loses its activity when about half of the theoretical amount of
hydrogen has been absorbed, probably because of the poisoning action of impurities not removed from the commercial
cholesterol. If this happens the addition of one or two 0.2-g. portions of catalyst usually suffices to bring the reaction practically to completion.
5. The sterol forms a hydrate from which the water is eliminated only after thorough drying, as in vacuum at 100°.
6. The acetyl derivative is more easily reduced than the free sterol.
3. Discussion
This preparation is referenced from:
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