Exploration of N-ferrocenyl substituted thioamides : synthesis, properties and reactivity
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Abstract
Electron transfer reactions are fundamental for biological processes. Since the investigation of such processes in vivo are complicated or sometimes impossible, model complexes for biological system have been developed as a valuable tool. The investigation of electron transfer processes via the use of ferrocene derivatives provides insight into the influence of the bridging unit for the rate of electron transfer. Incorporation of asymmetric bridges, such as carboxamides, provides a model for protein environments and have been studied thoroughly. The thioamide as structurally related bridging unit, however, has not yet been explored with respect to electron transfer abilities.
In this study, N-Ferrocenyl substituted thioamides are easily prepared from the parent carboxamides by the use of Lawesson’s reagent (2,4-bis(p-methoxyphenyl)-1,3-dithiaphosphetane-2,4-disulfide). Remarkably, the rotational barrier of the thioamides is high enough to observe E/Z isomerism in solution. IR and NMR spectroscopy give insight into the hydrogen bonding motif of the thioamides, as well as the secondary structure. The mixed-valent compounds of dinuclear complexes are investigated by electrochemical measurements, as well as UV/Vis and EPR spectroscopy. The electronic coupling HAB is calculated and compared to the parent carboxamides.
The reaction pathways of ferrocenium compounds in the presence of a non-nucleophilic base are studied by means of spin trapping techniques. The formation of carbon centered ferrocenyl radicals is reported and the location of the unpaired spin in the ferrocenyl radicals could be determined. This study gives insight into the reaction of ferrocenyl radicals and stabilizing effects on them as a plausible mode of action for ferrocene based (pro-)drugs.
Besides the generation of radicals N-ferrocenyl substituted thioamides show a second reactivity upon oxidation and deprotonation. A multistep reaction sequence leads to the formation of a novel N,S-heterocycle, which initiates oligomerization. Intermediates of this sequence include paramagnetic piano stool like complexes with η1-coordinated cyclopentadienyl rings, as well as super electrophilic ferrocenyl ketenimine cations, formed by elimination of hydrogen sulfide. A reaction mechanism is proposed and supported by mass spectrometry, EPR and NMR spectroscopy and DFT calculations. This work is crucial for polymeric materials with CN-backbone and heterocyclic chemistry.