@article { author = {Kassehin, Urbain C. and Adjibode, Steeve A. and Bautista, Oscar and Gbaguidi, Fernand A. and Quetin- Leclercq, Joëlle and McCurdy, Christopher R. and Frédérick, Raphaël and Poupaert, Jacques H.}, title = {Anomalous reactivity of benzopinacolone towards 4-phenylthiosemicarbazide, a nucleophile endowed with alpha-effect}, journal = {Journal of Medicinal and Chemical Sciences}, volume = {2}, number = {1}, pages = {17-20}, year = {2019}, publisher = {Sami Publishing Company (SPC)}, issn = {2651-4702}, eissn = {2651-4702}, doi = {10.26655/jmchemsci.2019.6.3}, abstract = {In a medicinal chemistry-driven drug discovery program aimed at synthesizing new topically-acting 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 intram-olecular 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 N-thiobenzoyl-thiosemicarbazide.}, keywords = {Benzopinacolone,Green chemistry,N-thiobenzoyl-thiosemicarbazide,Photochemistry,Trypanocidal chemotherapeutic}, url = {https://www.jmchemsci.com/article_69027.html}, eprint = {https://www.jmchemsci.com/article_69027_5639c2a37b9cf2b4101af076433bfb07.pdf} }