Anomalous reactivity of benzopinacolone towards 4-phenylthiosemicarbazide, a nucleophile endowed with alpha-effect
(2019) Journal of Medicinal and Chemical Sciences — Vol. 2, n° 1, p. 17-20 (2019)
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- 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 N-thiobenzoyl-thiosemicarbazide.
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Kassehin, C. U., Adjibode, S. A., Bautista, O., Gbaguidi, F. A., Leclercq, J., McCurdy, C. R., Frédérick, R., & Poupaert, J. (2019). Anomalous reactivity of benzopinacolone towards 4-phenylthiosemicarbazide, a nucleophile endowed with alpha-effect. Journal of Medicinal and Chemical Sciences, 2(1), 17-20. https://doi.org/10.26655/JMCHEMSCI.2019.6.3 (Original work published 2019)