Session: Heterocycles & Aromatics:

Five-membered heterocyclic rings are abundant in natural products and pharmaceuticals. Thus, continued investigation of new heterocyclic ring forming reactions are of interest to the synthetic community. Imidazolidine-2-thiones have found a diverse array of biological applications. For example, imidazolidine-2-thiones have shown analgesic, antiserotonin, and herbicidal activity, and, undoubtedly, other activities remain to be explored. Current synthetic access to this scaffold is varied. Based on a recent report of a cascade reaction involving Cu-catalyzed S-vinylation with N-(2-bromoallyl)butylamine and CS₂, it was hypothesized that isothiocyanates could undergo a similar cascade reaction involving heteroatom-vinylation to access 5-methyleneimidazolidine-2-thiones. Preliminary results show that N-(2-bromoallyl)butylamine reacts readily with phenyl isothiocyanate in the presence of CuI in one-pot to form the resulting 5-methyleneimidazolidine-2-thione in moderate yield. In the absence of CuI, the reaction stalls at the acyclic thiourea. Progress on the investigation of Cu-catalyzed heteroatom-vinylation between N-(2-bromoallyl)butylamine and isothiocyanates will be reported. Optimization of reaction conditions, catalyst screening, and substrate scope will be detailed. Additionally, the potential for an additional product to form based on rearrangement of the exocyclic methylene to yield the resulting 4-imidazoline-2-thione will be addressed. This previously unreported one-pot reaction will enhance synthetic access to important heterocycles.

Dr. Todd J Eckroat

Assistant Professor of Chemistry, Penn State Behrend

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