Bromination of cholesterol

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... 

Prelab Exercise Explain how the process of bromination and debromination of cholesterol can free it from impurities. Write a detailed mechanism for the bromination of cholesterol, taking care to consider the stereochemistry of the product. 

Why does not acetate ion attack the intermediate bromonium ion to give the 5-acetoxy-6-bromo compound in the bromination of cholesterol ... 

Havinga and Bots (1954) were the first to describe a method for the preparation of C -labeled cholecalciferol. Cholecalciferol-3-C was obtained by irradiation of 7-dehydrocholesterol synthesized from labeled cholesteryl acetate. The photochemical conversion from 7-dehydrocholesterol to cholecalciferol is accompanied by the formation of several other products such as lumisterols, tachysterols, and prechole-calciferol. A solution of NaNOs in water (0.4 ) effectively absorbs ultraviolet rays of wavelengths shorter than 250 mji which are supposed to promote die formation of side products. In order to minimize the formation of overirradiation products the ethereal solution of 7-dehy-drocholesterol-3-C is irradiated till 44.5% has been converted. The Havinga-Bots irradiation vessel, unique in itself, consists of three annular chambers made of quartz enclosing the irradiating lamp. 7-Dehydrocholesterol-3-C has been prepared recently from diolesterol-3-C (Kulkami et al., 1963) by the appKcation of an isocaproate adaptation (Nes et al., 1956) of the allylic bromination of cholesterol with 2V-bromosuccinimide followed by dehydrobromination. 

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. 

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. 

The bromination of a double bond is an important and well-understood organic reaction. In the present experiment it is employed for the very practical purpose of purifying crude cholesterol through the process of bromination, crystallization, and then zinc dust debromination. 

FIGURE 24.10 The products formed by the reaction of cholesterol with (a) moleculor bromine, (bj molecular hydrogen, ond (cj acetic acid. 

Many strategies have been followed to control levels of serum cholesterol. A compound that incorporates the carbon skeleton of cholesterol itself, colestolone, is thought to inhibit cholesterol synthesis in a late step in its biosynthesis by acting as a product feedback inhibitor. The synthesis starts with bromination of the allylic C position in cholesterol benzoate 22-1 by means of A-bromosuccinimide (22-2) (Scheme 8.22). Dehydrobromination, for example with collidine, leads to the endocyclic 5,7-diene 22-3. In the presence of strong acid, the bonds migrate to form the transoid... 

Bromination of acetal (98) and dehydrobromination gave unsaturated acetal (99) <83AQ2io>. Hemiacetals, (e.g., (100)), have been synthesized for use as covalent carriers and for the preparation of liposomes containing dicetyl phosphate, cholesterol, and trypsin <87GEP(0)3619883>. Bis-hemiacetal (101) could be obtained by the reaction of hexafluoroacetylacetone and glycol, but this compound decomposes on standing <67NKZ470>. 

The hydroxy-group of cholesterol is protected either as the acetate or benzoate. Bromination in the allylic position by Karl Zieglers method using N-hro-mosuccinimide or l,3-dibromo-5,5-dimethylhydantoin, then dehydrobromina-tion with 2,4,6-collidine and hydrolysis gives 7-dehydrocholesterol. Photolysis of 7-dehydrocholesterol and ergosterol, respectively, with a mercury vapour lamp in an inert solvent (e.g. peroxide-free diethyl ether, methanol, cyclohexane... 

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. 

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