Cumene peroxide rearrangement

Another BMS example, shown in Scheme 11.14, uses a cumene peroxide rearrangement to prepare 6-hydroxy-5-methyl-3H-pyrrolo[2,l-f [l,2,4]triazin-4-one, an intermediate for protein kinase inhibitors (brivanib). The terhary alcohol is converted to the hydroperoxide in situ with H2O2 and reacted with aqueous meth-anesulfonic acid as a catalyst to cause rearrangement [31]. 

Almost all of the cumene produced is consumed by the cumene peroxidation process to phenol and acetone. Aspects of this process resemble the peroxidation processes to propylene oxide already described, except that in this case the final products are formed by an intramolecular rearrangement of the same molecule that is peroxidized rather than by a reaction of a perox-idized molecule with a second component, propylene. In the first stage of the cumene to phenol process a suspension of purified cumene in a dilute solution of sodium carbonate in water is heated to about 110°C under slight pressure. Air is blown through this suspension until about 25% of the cumene has formed the hydroperoxide (Eq. 19.49). 

By contrast with the conditions for aldehydes, ketones have been oxidised to phenols by methodology essentially that of the cumene-hydroperoxide rearrangement. In the naphthalenic series, treatment of the derived t-alcohol shown with excess 90% hydrogen peroxide followed by stirring of the mixture with a little 4-toluenesulphonic acid for 6 hours at 22 C gave the phenolic product, 2-hydroxy-3-methoxy-5,6,7,8-tetrahydronaphthalene in 85% yield (ref.45). 

No readily acceptable mechanism has been advanced in reasonable detail to account for the decomposition of hydroperoxides by metal dialkyl dithiophosphates. Our limited results on the antioxidant efficiency of these compounds indicate that the metal plays an important role in the mechanism. So far it seems, at least for the catalytic decpmposition of cumene hydroperoxide on which practically all the work has been done, that the mechanism involves electrophilic attack and rearrangement as shown in Scheme 4. This requires, as commonly proposed, that the dithiophosphate is first converted to an active form. It does seem possible, on the other hand, that the original dithiophosphate could catalyze peroxide decomposition since nucleophilic attack could, in principle, lead to the same chain-carrying intermediate as in Scheme 4 thus,... 

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