Chromium trioxide, oxidation methyl ketones

In a typical Knof procedure, 3jS-hydroxyandrost-5-en-17-one acetate is epoxidized with perbenzoic acid (or m-chloroperbenzoic acid ) to a mixture of 5a,6a- and 5)5,6)5-epoxides (75) in 99 % yield. Subsequent oxidation with aqueous chromium trioxide in methyl ethyl ketone affords the 5a-hydroxy-6-ketone (76) in 89% yield. Baeyer-Villiger oxidation of the hydroxy ketone (76) with perbenzoic acid (or w-chloroperbenzoic acid ) gives keto acid (77) in 96% yield as a complex with benzoic acid. The benzoic acid can be removed by sublimation or, more conveniently, by treating the complex with benzoyl chloride and pyridine to give the easily isolated )5-lactone (70) in 40% yield. As described in section III-A, pyrolysis of j5-lactone (70) affords A -B-norsteroid (71). Knof used this reaction sequence to prepare 3)5-hydroxy-B-norandrost-5-en-17-one acetate, B-noran-... 

Grieco synthesized (326) regiospecifically from cyclopentadiene and dichloroketen and dechlorinated it to (327), which was converted into lactone (328) with aqueous HjOj and thence into (329) with di-isobutylaluminium hydride. Sequential treatment of (329) with the ylide from PhjP —Pr Br" in DMSO, which serves to introduce the cis-double bond, and oxidation gave ketone (330). After isomerization of (330) to (331), reaction with methyl-lithium gave (332) which on chromium trioxide oxidation gave cis-jasmone (Scheme 13) in 40 % overall yield. 

Oxidation of VI with chromium trioxide in acetic acid gave a methyl keto ester VII from which benzoic acid was eliminated under mild conditions to give an a,j8-unsaturated methyl ketone. When air was bubbled into an alkaline solution of the a,j8-unsaturated ketone it was... 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

Solution Ketones can be prepared by oxidation of secondary alcohols with a variety of reagents, such as CrOa (chromium trioxide) or KaCraO (potassium dichromate) with acid. The compound that is formed by oxidation of an alcohol depends upon the number of hydrogens attached to the carbon bearing the -OH group, that is upon whether the alcohol is primary, secondary or tertiary. For example, in the first problem, to synthesize the product, methyl ethyl ketone, a secondary alcohol is used that has the same number of carbon atoms as the product. In this case sec-butyl alcohol is used as the precursor. 

To obtain the product only requires one step where sec-butyl alcohol is oxidized directly to methyl ethyl ketone with chromium trioxide. 

This synthetic reaction involves oxidation of the alcohol to yield acetaldehyde. To add another carbon atom to this first product, the Grignard reagent methyl magnesium bromide (CH3MgBr) is added for methylation. Upon hydrolysis this yields a three carbon compound, isopropanol, which is a secondary alcohol. As shown previously, secondary alcohols are oxidized to ketones with chromium trioxide, thus yielding the final product, acetone. 

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