Degradation by oxidation with chromium trioxide

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],... 

Unsevine (LXXXVIII) (mp 173°-174° [aJi, -t-170° in CHCI3) formed hydrobromide (mp 180°-183°), oxalate (mp 192°-194°), and methiodide (mp 249°-250°) salts (99). Oxidation of unsevine with either silver oxide (98) or chromium trioxide (56) afforded nivaline. Additional degradations of nivaline and unsevine follow the classic patterns established in the homolycorine and hippeastrine structural elucidations. Unsevine is oxidized by potassium permanganate to hydrastic acid (97, 100, 101). Hofmann degradation of either nivaline or unsevine affords the methine base LXXXIX (97, 100). In the case of unsevine, this reaction must... 

Simple pyrroles are generally easily attacked by chemical oxidising agents, frequently with complete breakdown. When the ring does survive, maleimide derivatives are the commonest products, even when there was originally a 2- or 5-alkyl substituent. This kind of oxidative degradation played an important part in early porphyrin structure determination, in which chromium trioxide in aque-... 

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