Chromium trioxide degradation

Tertiary alcohols are usually degraded unselectively by strong oxidants. Anhydrous chromium trioxide leads to oxidative ring opening of tertiary cycloalkanols (L.F. Fieser, 1948). 

Oxidation of ecgonine (2) by means of chromium trioxide was found to afford a keto acid (3). This was formulated as shown based on the fact that the compound undergoes ready themnal decarboxylation to tropinone (4)The latter had been obtained earlier from degradative studies in connection with the structural determination of atropine (5) and its structure established independently. Confirmation for the structure came from the finding that carbonation of the enolate of tropinone does in fact lead back to ecgonine. Reduction, esterification with methanol followed by benzoylation then affords cocaine. 

It is known that preparation of the oxidant salt under anhydrous conditions is explosion-prone [1], but during repetition of a supposedly safe preparative method [2], recommended for large-scale use [3], ignition and a violent explosion occurred. Use of more water to dissolve completely the chromium trioxide, and a reaction temperature below 25°C, are recommended [4], During a study by TGA of the thermal degradation of the salt, too-rapid heating of the samples led to explosions with lire [5],... 

Irreversible degradation of the porphyrin nucleus can be accomplished with oxidants such as chromium trioxide or potassium permanganate. As shown in Scheme 3, the products from the Cr03 reaction are maleimides, and this procedure has been used extensively for structure elucidation, and for tracking down the fate of isotopic labels in biosynthetic studies (B-75MI30702). In the absence of side chains such as formyl and vinyl, which are labile towards Cr03, it is possible to identify the various substituents on porphyrin subunits. 

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%. 

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