Cholesterol dibromide

Cholestenone has been prepared by oxidation of cholesterol dibromide with chromic acid 1 or potassium permanganate2 and debromination, and by dehydrogenation of cholesterol over copper oxide 3 4 or by the method described above.5... 

A. Cholesterol dibromide. In a 4-1. beaker 150 g. (0.39 mole) of commercial cholesterol (Note 1) is dissolved in 1 1. of absolute ether by warming on the steam bath and stirring with a stout glass rod the solution is then cooled to 25°. A second solution is prepared by adding 5 g. of powdered anhydrous sodium acetate (0.06 mole) (Note 2) to 600 ml. of acetic acid, stirring the mixture and breaking up the lumps with a flat stirring rod 68 g. (0.4 mole) of bromine is then added, and the solution is poured with... 

For success in the preparation of this labile non-conjugated ketone in high yield and purity, the intermediates, cholesterol dibromide and dibromocholestanone, should be processed further in the solvent-moist state as soon as prepared. The three reactions can be completed easily in one day. 

Cholesterol dibromide has been prepared by unbuffered 2 and buffered 3 bromination of cholesterol and oxidized to 5with acid permanganate,2 chromic acid,4 6 6... 

The cholesterol dibromide that crystallizes from the reaction solution is collected, washed free of the impurities or their dehydrogenation products, and debrominated with zinc dust, with regeneration of cholesterol in pure form. Specific color tests can differentiate between pure cholesterol and tissue cholesterol purified by ordinary methods. 

Dehalogenation, dehalohydrination. See also yS-Chloroethyl ethyl ether. The debromination of cholesterol dibromide with zinc dust requires only a catalytic amount of acetic acid and once the reaction has started it proceeds with vigor, like... 

Addition of bromine to cholesterol inititally produced 5a,6/f-dibromocholestan-3/i-ol (reference 22). Upon standing in methanol solution at room temperature for 3 days, the initial product was converted to a 4 1 mixture of 5/S,6a-dibromocholestan-3/f-ol and the 5a,6j3 isomer. The rate constant for the rearrangement was not affected by a 30-fold molar excess of cyclohexene, suggesting that the rearrangement did not occur by dissociation of the cholesterol dibromide to cholesterol and bromine. 

Cholesterol can be freed of these contaminants by preparing cholesterol dibromide, which is easily separable from the mixture and can be readily reconverted to the sterol. 

Cholesterol [57-88-5] M 386.7, m 148.9-149.4 , [a]D -35 (hexane). Crystd from ethyl acetate, EtOH or isopropyl ether/MeOH. [Hiromitsu and Kevan J Am Chem Soc 109 4501 I987. For extensive details of purification through the dibromide, see Fieser [J Am Chem SoclS 5421 1953] and Schwenk and Werthessen [Arch Biochem Biophys 40 334 7952], and by repeated crystn from acetic acid, see Fieser [J Am Chem Soc 75 4395 1953]. 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

Unsubstituted solid alicyclic alkenes have also been exposed to bromine vapor and gave 100% of pure trans dibromides, as in the case of cholesterol (123) [75] and the (milled) exo adduct 1 [22] (Scheme 14). The products 124 and 125 cannot be obtained with the same good quality from solution reactions. 

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 per cent by using cholesterol which has been purified by regeneration from the dibromide. 

Cholesterol of high quality and of recent production was employed. Cholesterol undergoes slow autoxidation in the solid state, and samples that have been in storage for a few years give lower yields of dibromide. The checkers used u.s.p. material, m.p. 149-150°, as supplied by Wilson Company, Chicago, Illinois. 

Purification of cholesterol through the dibromide completely eliminates cholestanol, 7-dehydrocholesterol, and latho-sterol (A7-cholestenol). The first crop of material from methanol-ether is also free from cerebrosterol (24-hydroxycholesterol) and 25-hydroxycholesterol, a product of autoxidation present in cholesterol that has been stored in the crystalline state for a few years with access to air. When material of highest purity is desired, only first-crop dibromide should be employed, since de-bromination of second-crop material gives sterol melting at 146-147° and giving a positive Beilstein test. 

An improved route has been described for the degradation of cholesterol to dehydroepiandrosterone,68,69 in which cholesterol is first acetylated and then bromi-nated to give the 5a,6/8-dibromide. This protected cholestane is then isomerized to the 5/3,6a-dibromide prior to chromium trioxide oxidation and zinc debromination. The yield of dehydroepiandrosterone (isolated from the reaction mixture as a 5a,6/3-dibromide) is 20%. 

Substitution reactions involving 3/S-hydroxy-A -steroids and their derivatives require special mention. Cholesterol reacts with a variety of halogenating agents, including thionyl chloride / StJ, phosphorus pentachioride [81], haHdes of aluminium or titanium [82], 2-chloro-i,i,2 trifluoroethyl di-ethylamine [83] and triphenylphosphine dibromide [55], to... 

Early steroid chemists characterised cholesterol and cholest-5-ene as their 5,6-dibromides, but the work was complicated by the isolation of two isomeric dibromides in each case. It was recognised [i] that one isomer of each pair was stable and dextrorotatory, while the other was unstable andlaevorotatory. Solutions of each isomer in chloroform were found to exhibit mutarotation [2], corresponding to the establishment of equilibria between isomeric pairs of dibromides, and it is now recognised that the position of equilibrium is determined by conformational strains, mainly arising from the large syn diaxial interaction between a 6jS-bromo substituent and the Ca9)-methyl group (Fig. 43) of, p. 10). 

Under the title Cholesterol is Stable , a sample purified via the dibromide in 1937, and stored in the dark, is reported to contain no detectable trace of impurity when examined recently. Ordinary commercial samples, however, are highly susceptible to auto-oxidation during storage- Compounds isolated from aged cholesterol include the 20a-, 24R-, 24S-, and 25-hydroperoxy-deriva-tives. ... 

Mild acid catalyst. A procedure for the preparation of A -cholestene-3-one (5) from cholesterol (1, unpurified) involves oxidation of the dibromide (2), debromination... 

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