Periodate oxidation active methylene groups

The oxidation of active methylene groups by periodate both in acyclic... 

The oxidation of an activated methylene grouping is somewhat slower than the other periodate reactions.14 Sprinson and Chargaff89 found that... 

Periodate oxidation of activated methylene groups (ArCHRC02H -> ArCOR)... 

The analogous oxidation of active methylene groups formed during the oxidation of a variety of carbohydrates by periodate has been considered in detail.22... 

Huebner et al. studied the stoichiometry and approximate rates of oxidation of a number of compounds containing an active methylene group. They found that not all such compounds are oxidised by periodate, and that in general one of the activating groups must be -CHO or -COOH for oxidation to occur. Thus diethyl malonate, ethyl acetoacetate, and cyanoacetic acid are not oxidised. Acetylacetone and other acyclic 1,3-diketones are oxidised very slowly, but cyclic 1,3-diketones are readily oxidised (Wolfrom and Bobbitt ). The first step in the oxidation of a compound containing an active methylene group is hydroxylation, then this is followed by further oxidation, e.g. malonic acid and 1,3-cyclohexanedione react as follows... 

The only compound containing an active methylene group whose periodate oxidation has been studied kinetically is 2-methyl-l,3-cyclohexanedione (Wolfrom and Bobbitt ). At 22.5 °C and pH 6.2 the kinetics are first-order with respect to each reactant. The same workers showed qualitatively that for the oxidation of 5,5-dimethyl-l,3-cyclohexanedione, the rate reaches a maximum between pH 5 and 6 (phosphate buffers were used). 

Apparently, photo-oxidation processes are dominant during the initial period and lead to the formation of active centers contributing to further cross-linking of macrochains. It can be assumed that methylene groups adjacent to coordination-bound tin atoms are most susceptible to photo-oxidation. 

The oxidation of some anhydroaldopento-benzimidazoles13 was found to entail uptake of more than the calculated amount of oxidant per mole. This apparent anomaly was further explored by Huebner, Ames and Bubl,14 and their work culminated in the discovery that periodate, under the usual conditions, oxidizes certain methylene carbon atoms, namely, those activated by two flanking carbonyl groups. This type of oxidation (a-hydrogen oxidation) was simultaneously observed (by Fleury and Courtois16) to occur on the periodate oxidation of malonic acid. A satisfactory reaction was obtained under the following conditions. 

Treatment of the major isomer with potassium hexamethyldisihzane (KHMDS, [(CH3)3Si]2N K ) caused the elimination of hydrogen bromide (HBr), and the oxidation of the resulting alkene with sodium periodate-ruthenium trichloride couple (NaI04/RuCl3) yielded the desired lactone, where the carbonyl group was appropriately positioned to activate the methylene a to the nitrogen for subsequent... 

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