50-3-Cholestanone

The benzene solution is separated and washed twice with 100 cc. of water, once with 200 cc. of 5 per cent potassium hydroxide, and twice with water, and in case the solution is not colorless it is clarified with i g. of Norite. The benzene is removed by distillation and the resulting syrup is dissolved in 300 cc. of alcohol by heating. The solution on cooling deposits cholestanone as well-formed needles. The yield of collected, washed, and air-dried material, m.p. 129-130°, is 41.5-42 g. (83-84 per cent of the theoretical amount). The addition of 80 cc. of water to the filtrate gives about 2 g. of material melting at 125-126°. 

Cholestanone has been prepared by the oxidation of dihydro-eholesterol with chromic anhydride in acetic acid solution.1 The yield is sometimes diminished as a result of the partial acetylation of the sterol. 

T. A. Spencer, R. W. Britton and D. S. Watt, J. Am. Chem. Soc., 89, 5727, (1967). These authors have shown that zinc enolates of cholestanone are formed from 2- and 4-bromocholestanones and zinc in dimethyl sulfoxide. 

The method has been applied to the reduction of cholestanone. Red uction of this ketone with the mixed reagent and no additional ketone gave 17% of the a-epimer under the equilibration conditions only 3p-ol and unreduced ketone are obtained. Reduction of coprostanone with the mixed reagent gives 94% of the 3a-ol. ... 

The hydrogenation of 5a-cholestanone (58) in methanolic hydrobromic acid over platinum gives 3j5-methoxycholestane ° (61). This compound is also obtained from the palladium oxide reduction of (58) in methanol in the absence of acid. Hydrogenation of 5 -cholestanone also gives the 3j5-methoxy product under these conditions. Reduced palladium oxides are quite effective for the conversion of ketones to ethers. The use of aqueous ethanol as the solvent reduces the yield of ether. Ketals are formed on attempted homogeneous hydrogenation of a 3-keto group in methanol. ... 

Nelson and Scliut investigated the reaction of 5a-cholestanone (lb) with diazomethane in a search for a direct, one-step preparation of A-homo ketones. Using a large excess of diazomethane generated in situ from A-methyl-nitrosourea with potassium hydroxide in ether-methanol at 0°, 5a-cholestanone (lb) is converted into the 7-membered ring homolog (3b) as the predominant product. Both theoretically possible A-homo ketones can be expected with an unsymmetrically-substituted cyclohexanone such as 5a-cholestanone (lb). 

Treatment of 5a-cholestanone (lb) in this way gives a mixture from which 7-and 8-membered ring ketones can be isolated. The yields of crude ketones are A-homo-4-one (3b), 40-50% A-homo-3-one (5b), 10% and a A-bis-homo ketone 5 %. The structure of the bis-homocholestanone has not been rigorously established. 

To establish the structure of A-homo ketone (3b) Nelson and Schut repeated the TifFeneau ring enlargement of 5a-cholestanone [(Ib) (6a) (6b) -> (7)] and obtained a ketone identical with A-homo ketone (3b). 

Iodine fluoride is a more versatile reagent than molecular fluorine in geminal fluorination of other hydrazones and related compounds under milder reaction conditions [55] Substrates fluorinated include hydrazones of simple cyclic or steroidal ketones (e g, 4 tert butylcyclohexanone, 70%, 3 cholestanone, 70%), W methyl and A/N dimethylhydrazones [R2C=NNH(CH3) 70%, R2C=NNC(CH3)2, 50%], semicarbazones (R2C=NNHCONH2, 25-50%), and 2,4-dinitrophenylhy-drazones [R2C==NNH-C6H3-2,4(N02)2, 25-50%]... 

N-acyl enaminc (104, R = CHjCHj) gave an unstable enamine (106) which decomposed readily to 3-cholestanone. The steroidal N-acetyl enamines (107 and 108, R = C HjCHj) can be reduced by lithium aluminum hydride in tctrahydrofuran to the corresponding enamines (109, R = CJH5CH2) in 90 and 68% yield, respectively 100). Attempts to reduce the enamide (107, R = CH3) led to the formation of the impure enamine (109, R = CHj), which decomposed to the hydroxy ketone (110). 

LiAlH4 as this avoids protonation of the enolate and the production of any over-reduction products. Cholest-4-en-3-one may be reduced to cholestanone (5a 5/8,1 19) with alkali-metal carbonyl chromates. The studies on intramolecular hydride shifts on hydroxy-ketones and -aldehydes have been extended. " The hydride shifts were examined in a number of y- and 5-hydroxy-carbonyI compounds by heating the substrates with alkaline alumina containing D2O. Exchange of protons on the carbon a to both oxygen functions signals the intramolecular hydride shift typically, the hemiacetals (95) and (96) each incorporate up to six deuterium atoms. The general conclusion, in common with literature precedent, is that, whereas 1,5-shifts are common, 1,4-shifts are rare. 

A dipolar cycloaddition of a steroidal nitrile oxide to trifluoropropene, followed by reductive hydrolysis, was used to prepare the trifluoromethyl cholestanone... 

The 5/ -isomer is also obtained in acidic medium but the rate is slower than the base promoted hydrogenation. A solution of 0.4 g of cholestenone in 30 ml of acetic acid containing 0.2 ml 3 N hydrobromic acid is hydrogenated over 0.1 g of prereduced palladium oxide. After work-up and recrystallization of the product, 0.36 g of 5/ -cholestanone is obtained.112... 

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