4-Thiouracil cleavage

Botta and coworkers recently developed an Oxone cleavage methodology for the solid-phase synthesis of substituted uracils (equation 57)165. Whereas some common methods of thioether cleavage, such as reduction with Na/NH3, acid catalyzed hydrolysis, heavy metal ions followed by treatment with hydrogen sulfide and iodotrimethylsilane proved to be unsuccessful for this reduction, Oxone was shown to be an efficient and selective reagent for cleavage of polymer bound thiouracils. 

The first example of a symmetric triangular mixed-valent triruthenium complex 99 has been obtained by thermal treatment of Ru(acac)2(MeCN)2 with substituted 2-thiouracil (equation 66). Although the usual coordination mode of the acetylacetonate is present in the trinuclear compound, the y-carbon atom of one of the coordinated acetylacetonato units of the parent Ru(acac)2(MeCN)2 links to a ruthenium atom forming the trinuclear network. The factors which are primarily involved in the ruthenium-mediated C—S bond cleavage of the stable thiouracyl are not clear. It was suggested that the process starts with the initial coordination of thiouracyl to ruthenium followed by cleavage of the C—S bond and subsequent nucleation. ... 

Instead of the nucleophilic N-atoms, the attempted attack of appropriate carbanions (from acetamides substituted with an electron-withdrawing group) on the C-6 position of dimethyluracil leads to the cleavage of the uracil ring. This reaction splits off dimethylurea and leads finally to the formation of tautomeric pyridine-2,6-diones, such as 2,6-dihydroxynico-tinamide. Similarly, the reaction of 1,3-dimethyl-4-thiouracil with malo-namide proceeds smoothly to give 2-hydroxy-6-mercaptonicotinamide (791A4423 81JOC846) (Scheme 136). 

Cleavage of the N-acyl thioamide moiety in the 4-thiouracil (25) gives an example for the conversion of a thiolactam into a thioamide (yield 25% equation 14). ... 

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