A Novel, Mercury-Free Synthetic Pathway for Trifluromethylthio-Substituted Metallocenes

A novel synthetic pathway for trifluoromethylthioferrocene (3), which does not involve the use of toxic mercury(II)-based reagents, is described. The novel approach involves first the treatment of the commercially available bromoferrocene (1a) with NaSCN in the presence of copper(+I) to yield thiocyanatoferrocene (1), and then the reaction of 1 with the Rupper-Prakash reagent and tetrabutylammonium fluoride (TBAF) to give 3 in an overall yield of 60%. This approach could be extended for the preparation of thiocyanato-(4) and trifluoromethylthio-ruthenocene (7), which are herein both reported for the first time. Interestingly, diferrocenyl disulfide (2a) and diruthenocenyl disulfide (5) could be isolated as side-products during the synthesis of 3 and 7, respectively. All new compounds were unambiguously characterized by (1)H, (13)C, and (19)F NMR spectroscopy, mass spectrometry, cyclic voltammetry, elemental analysis, as well by X-ray crystallography for 1, 4, 4b, 5, 6, and 7. 1-7 were further tested for their toxic activity on cervical cancer (HeLa) and noncancerous (MRC-5) cell lines. All organometallic compounds were found either to be nontoxic or to have a moderate toxicity toward the cell lines used in this study. DOI: https://doi.org/10.1021/ic403169z Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-98808 Accepted Version Originally published at: Hess, Jeannine; Konatschnig, Sandro; Morard, Sandra; Pierroz, Vanessa; Ferrari, Stefano; Spingler, Bernhard; Gasser, Gilles (2014). Novel, mercury-free synthetic pathway for trifluoromethylthio-substituted metallocenes. Inorganic Chemistry, 53(7):3662-3667. DOI: https://doi.org/10.1021/ic403169z A Novel, Mercury-Free Synthetic Pathway for Trifluromethylthio-Substituted Metallocenes Jeannine Hess, Sandro Konatschnig, Sandra Morard, † Vanessa Pierroz, Stefano Ferrari, ‡ Bernhard Spingler, and Gilles Gasser † Department of Chemistry, University of Zurich, Winterthurerstrasse190, CH-8057 Zurich, Switzerland. ‡ Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.