Steroids, hydrogenation ketones

In all these reactions, crystallographic studies demonstrated the crystal control responsible for formation of the observed products. Thus, the prereaction ketone oxygen-steroidal hydrogen distance is in all cases 3.4 0.5 A, the ketonic carbon-steroidal (to-be-attacked) carbon distance is of the order of 4 A, and the... 

The hydrolysis of steroid hydrogen sulphates, important to biochemists in view of the excretion of many steroid hormone metabolites as water soluble salts of hydrogen sulphates, has been studied in some detail [20,21]. It had been known for some years that ether extraction of the steroid hydrogen sulphate from acidified solutions is accompanied by hydrolysis of the sulphate in the ether phase, with liberation of the steroid alcohol. This hydrolysis was shown to follow first-order kinetics, but to be dependent in a remarkable way on the solvent. Ethers are the most effective solvents, followed by others of low polarity including benzene, esters and ketones, while water and alcohols have a strong retarding effect on hydrolysis. Neither acids nor bases produce significant catalysis, and the presence of did not result in incorporation of isotopic... 

The direction of enohsation of steroid 3-ketones was a subject of much debate from the early 1950 s, for 5a-3-ketones give A2-enols (17), and 5ji -3-ketones give mainly A -enols (18) [12, 128]. The preference for A -enolisation in the 5j8-series was fairly easily explained [128] in terms of relief of non-bonded interactions between the qa-hydrogen and the 7a- and qa-hydrogens when a trigonal centre is formed at C 4) . Recent calculations [ 126] suggest that the A -isomer is favoured by an enthalpy difference of 1.9 kcal/mole. This would result in a A8/A2 ratio of 96 4, compared with the experimentally determined 93.5 6.5. It is interesting that kineticaUy controlled enol acetylation of a 5j5 3-ketone with isopropenyl acetate The preferential Ca-formylation of 5 j -3-ketones is discussed on p. 182. Heferences p. 214... 

Saturated 5/3- and 4 -unsaturated steroid 3-ketones react with hydrogen peroxide in solution in /-butanol containing hydrochloric acid to form bishydroperoxides (5,6) in good yield. "... 

Thiophen Analogues of Steroids.— The ketone (141) was condensed with 2-(carbethoxymethyl)piperidine to give the 10-aza-l7-thia-steroid (142). With 4-oxo-4,5,6,7-tetrahydrobenzo[6]thiophen and 2-methyI-3-oxothiophen 1,1-dioxide as the precursors of rings a and B, and D, respectively, (143) was synthesized ionic hydrogenation of the 8,14-diene derived from (143) resulted... 

Steroid ketones are apparently hydrogenated in the following order C-3>C-16, C-17, C-20 C-7, C-6 > C-12 > Hindered... 

With some ketones there is a sufficient difference in the rate of loss of various a-hydrogens at the enolization step and a steric preference for the incoming deuterium during ketonization to facilitate selective exchange of certain a-hydrogens. Typical examples are the steroids. 

Interestingly enough, both protons at C-11 are exchanged quite readily in 12-keto steroids. In these compounds C-11 is the only possible enolization site where the axial (/3) proton is probably expelled first. During ketonization, the deuteron attack is more likely to occur from the less hindered a-side. By this sequence the proton which was originally at the lla-equato-rial position becomes axial and readily available for expulsion in the next enolization step. Thus, isomerization of the C-11 hydrogens may be an important reason for the facile exchange at this position. (For a more detailed discussion of the mechanism of enolization and ketonization reactions, see ref 114.)... 

If the ketone function is adjacent to a hydrogen-bearing asymmetric center, the compound can undergo epimerization. In steroids with a normal skeletal configuration (8/3, 9a, 14a) there is no detectable epimerization at C-8 or C-9 during the exchange of and 11- ketones. 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

Generally the most practical procedure for monoalkylation of steroidal ketones bearing geminal a-hydrogens is via formyl or oxalyl ketones. Some examples of the former method are described in this section. The alkylation of oxalyl ketones is described in the following section. 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

Because osmium tetroxide is expensive, and its vapors are toxic, alternate methods have been explored for effecting vic-glycol formation. In the aliphatic series, olefins can be hydroxylated with hydrogen peroxide with the use of only a catalytic amount of osmium tetroxide. Anhydrous conditions are not necessary 30% hydrogen peroxide in acetone or acetone-ether is satisfactory. The intermediate osmate ester is presumably cleaved by peroxide to the glycol with regeneration of osmium tetroxide. When this reaction was tried on a A -steroid, the product isolated was the 20-ketone ... 

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