A4-Cholestene

Dehydration products have been observed from photosensitized oxygenation reactions with cycloheptatriene (304),220 AMialin (307) 222 3/1- and 3a-hydroxy-A4-cholestenes (312a and 312b, respectively),226,227 and 2-hydroxy-10-methyl-1,9-octalin (316).226... 

The reduction of allylic systems is frequently used to generate isolated double bonds. Suitable systems are obtained from oe,/ -unsaturated ketones via allylic alcohols (ref. 185, p. 256 ref. 283, 284) for example, the preparation of A4-cholestene (135). 

Skeletal rearrangements similar to the santonin-lumisantonin rearrangement have also been reported for some 2-cyclohexenones, such as A4-cholesten-3-one413 and 4,4-dimethylcyclohexenone.414... 

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... 

Methods of preparation of A4-cholesten-3-one have been summarized in an earlier volume.3 The present modification is less laborious than the earlier method. 

The Oppenauer oxidation of cholesterol to A4-cholesten-3-one of m.p. 77-79° in 70-93% yield has been reported in these volumes.10 Isomerization of As-cholesten-3-one by a mineral acid or a base has been conducted satisfactorily only on a micro scale 6 the method of isomerization with oxalic acid has been reported.3... 

Inspection of Table 6.1 shows that the classical oxidation of sterols on the alcohol at the 3-position, using acetone as oxidant, works efficiently thanks to the migration of the alkene. Thus, the oxidation of cholesterol with acetone (E0 = 129 mV) must proceed via the thermodynamically disfavoured A5-cholesten-3-one (E0 = 153 mV) that evolves to the very stable A4-cholesten-3-one (E0 = 63 mV). In fact, acetone lacks oxidizing power for the obtention of many ketones as well as for the preparation of virtually all aldehydes. 

Add a solution of 3p-hydroxy-A4-cholestene in anhydrous ether (7 mL) over 20 min. 

Anade-Ckusenrearrai ement. Satisfactory A4-cholestene-3j -ol, m.p. 130.5-131° (from ethanol), can be prepared by the procedure of Burgstahler and Nordin a lower melting point indicates contamination with some of the 5oi-hydroxy isomer. A 50-ml. 

Preparation of enolphosphates. The reagent is used in ether solution to convert A4-cholestene-3-one (I) into the enol form for reaction with diethyl phosphoro-chloridatc and tricthylamine to give the phosphate ester (3). Reaction with lithium and ethylamine, and treatment with t-butyl alcohol then affords 5-methyl-A -coprostene (4). 

E. A4-Cholesten-3-one. A mixture of 100 g. of A5-cholesten-3-one (0.26 mole), 10 g. (0.11 mole) of anhydrous oxalic acid (Note 14), and 800 ml. of 95% ethanol is heated on the steam bath until all the solid is dissolved (15 minutes) and for 10 minutes longer, and then is allowed to stand at room temperature. If crystallization has not started after a period of several hours, the solution is seeded or scratched. After crystallization has proceeded at room temperature and then at 0-4°, the large, colorless, prismatic needles that separate are collected by suction filtration yield in the first crop 88-92 g., m.p. 81-82°, [a]o 92° chloroform... 

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