Org. Synth. 1967, 47, 25
DOI: 10.15227/orgsyn.047.0025
CHOLANE-24-AL
Submitted by John G. Moffatt
1
Checked by Robert Fairweather and Ronald Breslow.
1. Procedure
Cholane-24-ol (1.033 g., 3 mmoles) (Note 1) is dissolved by gentle warming in 10 ml. of anhydrous benzene (Note 2) in a 50-ml. flask, and 10 ml. of rigorously dried dimethyl sulfoxide (Note 3) is added. To the clear solution are added 0.24 ml. (3.0 mmoles) of anhydrous pyridine (Note 4), 0.12 ml. (1.5 mmoles) of distilled trifluoroacetic acid, and 1.85 g. (9 mmoles) of dicyclohexylcarbodiimide (Note 5), in that order. The flask is tightly stoppered and left at room temperature for 18 hours (Note 6). Benzene (30 ml.) is then added, and the crystalline dicyclohexylurea is removed by filtration (Note 7) and washed with benzene. The combined filtrates and washings are extracted three times with 50-ml. portions of water (Note 8) to remove the dimethyl sulfoxide. The organic layer is dried with sodium sulfate and evaporated to dryness under reduced pressure. There is obtained 2.12 g. of syrup which partially crystallizes. Thin-layer chromatography of this material (Note 9) shows a very intense spot of cholane-24-al, traces of starting material, and two compounds near the solvent front as well as excess carbodiimide (Note 9).
The crude product is dissolved in benzene-hexane (1:1) and applied to a column containing 125 g. of silicic acid (Note 10). Elution with the same solvent gives traces (less than 5 mg. each) of the two fast-moving components in fractions 2 and 4 (125-ml. fractions) and chromatographically pure cholane-24-al in fractions 5–8 (Note 11). Evaporation of the pooled fractions yields 870 mg. (84%) of the pure crystalline aldehyde, m.p. 102–104°. Recrystallization from 5 ml. of acetone raises the melting point to 103–104° (Note 12).
The compound gives a crystalline 2,4-dinitrophenylhydrazone, m.p. 163–164°, from ethanol.
2. Notes
1.
Available from Aldrich Chemical Company.
2.
Dried by storage over
calcium hydride.
3.
Dried by distillation under reduced pressure and storage for several days over Linde Molecular Sieves Type 4A.
4.
Dried by distillation from, and storage over,
calcium hydride.
5.
The dry, crystalline material may be obtained from Aldrich Chemical Company. If the reagent is at all oily at room temperature, it should be distilled under reduced pressure, b.p.
140° (5 mm.).
6.
Crystalline
dicyclohexylurea (m.p.
234°) starts to separate after a short time. The checkers found a decrease in yield if this is allowed to run longer; a yield of 54% was found in a 22-hour reaction time.
7.
Roughly
0.6–0.8 g. of the urea is usually obtained, m.p.
232–234°. The excess
dicyclohexylcarbodiimide remains in the
benzene. The oxidation is generally less satisfactory if less than 2.5 molar equivalents of carbodiimide is used.
8.
Some further
dicyclohexylurea tends to separate at the interface during the first extraction, and a clean separation of the layers near the interface is aided by mild centrifugation.
9.
On Merck Silica G using
benzene as the solvent and
5% ammonium molybdate in 10% sulfuric acid followed by brief heating at 150° to develop the spots. Under these conditions
cholane-24-al has an
Rf of 0.76 while
cholane-24-ol has
Rf 0.19;
dicyclohexylcarbodiimide streaks between 0.3 and 0.5.
10.
Merck silica gel with 0.05–0.20 mm. particles obtained from Brinkman Instruments Inc. and packed in a
3-cm. diameter column under
benzene-hexane (1:1).
11.
The fractions were examined by thin-layer chromatography of 25–50 μl. aliquots as in
(Note 9). The checkers found that
cholane-24-al is found in fractions 4–7.
12.
The compound is very soluble in most organic solvents. In order to get a high recovery, it is necessary to complete the crystallization in the deep freeze. From aqueous
ethanol the aldehyde crystallized in high yield as the hemihydrate, m.p.
95°.
3. Discussion
Cholane-24-al has not been previously synthesized by other methods.
4. Merits of the Preparation
The oxidation reaction described is a very general one that may be used for the preparation of both aldehydes and ketones
2 in high yield. The reaction conditions are extremely mild and only slightly acidic, thus allowing the preparation of otherwise very unstable compounds.
2 Of particular merit is the fact that the oxidation of primary alcohols stops selectively at the aldehyde and gives no traces of acidic products. Among the many different acids that have been examined as the proton source for this type of reaction,
2 pyridinium trifluoroacetate consistently gives the best results.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
ethanol (64-17-5)
sulfuric acid (7664-93-9)
Benzene (71-43-2)
sodium sulfate (7757-82-6)
acetone (67-64-1)
pyridine (110-86-1)
benzene-hexane (1077-16-3)
dimethyl sulfoxide (67-68-5)
calcium hydride (7789-78-8)
trifluoroacetic acid (76-05-1)
CHOLANE-24-AL (26606-02-0)
Cholane-24-ol
dicyclohexylcarbodiimide (538-75-0)
dicyclohexylurea (2387-23-7)
ammonium molybdate (13106-76-8)
pyridinium trifluoroacetate (464-05-1)
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