Novel, Mercury-Free Synthetic Pathway for Trifluoromethylthio-Substituted Metallocenes

Abstract

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. ABSTRACT: 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 then tested for their toxic activity on a cervical cancer (HeLa) and on a non-cancerous (MRC-5) cell lines. All organometallic compounds were found to be either not toxic or to have a moderate toxicity towards the cell lines used in this study.

Preparation and One-Electron Oxidation of Decabromoferrocene

“…The oxidation of Fe +II to Fe +III increases the Fe–C bond lengths up to 0.07 Å and shortens the C–Br bonds up to 0.04 Å (Table ) and is consequently another example of the α-halogen effect, which is also observed in perhalogenated cyclopentadienyl cations . In contrast to most (poly)­halogenated derivatives ,,,− as well as perhalogenated metallocenes (M = Ru, Os) − the cyclopentadienyl ligands exhibit a staggered conformation instead of an eclipsed one in the solid state. Intramolecular interactions are mostly of halogen bond nature between halogenated ferrocene and solvent molecules, counteranions, or other halogenated ferrocene moieties (Figure , SI).…”

The self–indicating preparation of bromoferrocenes from stannylferrocenes and an improved synthesis of di-iodoferrocene

“…Halogenoferrocenes are particularly useful synthons in the preparation of a broad range of useful ferrocenes such as ferrocenylamines [ 1 , 2 ], diisocyanoferrocenes [ 3 ], trifluorothioferrocenes [ 4 ], and of course in the metathesis reaction to lithioferrocenes [ 5 , 6 ] (although lithioferrocenes to halogenoferrocenes is more common) which lead to hundreds of ferrocene-based compounds. Of the halogenoferrocenes arguably the most important are iodo- and bromo-ferrocenes because they are more reactive in standard organic coupling reactions, [ 7 , 8 ].…”