Steroid, chlorinated

Chlorination of steroids. Chlorination of cholesterol wi this reagent gives cholesteryl chloride, with the usual retention of configuration shown by A -3/3-ol steroids in displacement reactions. However in other cases, the chlorination is effected with an unusual stereospeciflcity. Inversion of configuration obtains when the OH group is equatorial, but substitution with retention obtains when the OH group is axial. Thus 3a- and 3 8-hydroxysteroids are converted to the same product. Examples ... 

Miscellaneous Methods. A paper describing directed catalytic steroid chlorination with a billion-fold turnover rate which was published during the year1 6 has since been retracted as the results have been found to be untenable, despite rigorous attempts to verify their validity prior to publication. The chemical community appreciates the speed with which Professor Breslow has publicly denied these results. The very significant achievements of his group in this area must not be overlooked by the chemical world simply because of the tortuous dishonesty of one research student. 

The most abundant natural steroid is cholesterol. It can be obtained in large quantides from wool fat (15%) or from brain or spinal chord tissues of fat stock (2-4%) by extraction with chlorinated hydrocarbons. Its saturated side-chain can be removed by chromium trioxide oxidation, but the yield of such reactions could never be raised above 8% (see page 118f.). 

This publication provides several examples of the use of solid-phase extractions for separating analytes from their matrices. Some of the examples included are caffeine from coffee, polyaromatic hydrocarbons from water, parabens from cosmetics, chlorinated pesticides from water, and steroids from hydrocortisone creams. Extracted analytes maybe determined quantitatively by gas (GC) or liquid chromatography (LG). 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

By similar procedures diazirines were prepared not only from simple aliphatic ketones but also from hydroxyketones and )3-aminoketones (B-67MI50800), and so were a large number of diazirines from steroidal ketones (65JA2665). Permanganate, bromine, chlorine and hypochlorite were used as oxidants. A one-step preparation of diazirines from ketones like 3-nonanone, ammonia and chlorine has been claimed in a patent (66USP3290289). 3,3-Diazirinedicarboxylic acid derivatives like (286) were obtained directly from oxime tosylates by the action of two moles of O-ethoxyamine (81AG(E)200). 

Deuteration at C-4 by Sn2 Displacement of the 6 -Chlorine in a A -Steroid with Lithium Aluminum Deuteride... 

The properties of chlorine azide resemble those of bromine azide. Pon-sold has taken advantage of the stronger carbon-chlorine bond, i.e., the resistance to elimination, in the chloro azide adducts and thus synthesized several steroidal aziridines. 5a-Chloro-6 -azidocholestan-3 -ol (101) can be converted into 5, 6 -iminocholestan-3l -ol (102) in almost quantitative yield with lithium aluminum hydride. It is noteworthy that this aziridine cannot be synthesized by the more general mesyloxyazide route. Addition of chlorine azide to testosterone followed by acetylation gives both a cis- and a trans-2iddMct from which 4/S-chloro-17/S-hydroxy-5a-azidoandrostan-3-one acetate (104) is obtained by fractional crystallization. In this case, sodium borohydride is used for the stereoselective reduction of the 3-ketone... 

The free 17j8-amine can be transformed to the 17-ketone by chlorination to the iV-chloroamine, dehydrohalogenation to the imine, and finally hydrolysis.While these latter steps proceed in reasonable yield, the overall sequence does not compare well in efficiency with the process starting with a A -20-keto steroid ... 

Since many steroidal double bonds will react with peracids, these must be protected before the enol acetylation step. Chlorination is generally satisfactory for this purpose. ... 

The Hofmann-Loeffler-Freytag reaction has been described with A-chloro-as well as A-bromoamines—the former however usually give better yields. A-chlorinated primary amines react well in the presence of Fe-(II) ions. Just like the Barton reaction, the Hofmann-Loeffler-Freytag reaction has been applied mainly in steroid chemistry. An interesting example from alkaloid chemistry is the synthesis of nicotine 12 by Loeffler ... 

Halogenation of steroid 3-ketones can lead to complicated mixtures by virtue of the fact that the kinetic enol leads to 3 halo products, whereas the thermodynamic product is that halogenated at the 4 position. Carefully controlled reaction of the 5a-androstanolone with chlorine thus leads to the 2a-chloro derivative (29). Reaction of that intermediate with O(p-nitrophenyl)-hydroxylamine affords the androgenic agent ni stremine acetate (30). ... 

The mechanism of action of CYPs is radical rather than electrophilic and the actual substitution pattern is important the role of chlorine is one of blocking rather than deactivation. Many non-steroidal anti-inflammatory drugs are substrates for the... 

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