Anomalous Reactivity of Benzopinacolone Towards 4-Phenylthiosemicarbazide, A Nucleophile Endowed With Alpha-Effect

In a medicinal chemistry-driven drug discovery program aimed at synthesizing new topicallyacting trypanocidal chemotherapeutic agents to treat the african trypanosomiasis, our research group became interested in new chemical entities bearing in their center a thiohydrazide (c=s) nhnh or thiosemicarbazide nh(c=s) nhnh central template flanked on both sides by lipophilic aryl moieties. in this context, benzopinacolone was found to react as a rather unusual acylating agent via a mechanism (addition/elimination) involving addition of the nucleophile (a thiosemicarbazide derivative), formation of a resulting tetrahedral adduct, and expulsion of a trityl anion moiety as leaving group, presumably through an anchimeric assistance effect by intramolecular participation of the thioureido side-chain via hydrogen bond formation. the present incidental discovery should be considered at this level as a first inception and further work is now being directed at closely examining the detailed mechanism of this exceptional chemical pathway; in a reaction involving the unusual breaking of a carbon-carbon bond (carbon acid as leaving group) in the rate-determining step and involving the decomposition of the intermediate tetrahedral adduct to get the final unexpected nthiobenzoyl- thiosemicarbazide.