Author: Alfrets Daniel Tikoalu
Tikoalu, Alfrets Daniel, 2025 Solvent Induced S-S Metathesis of Trisulfides, Flinders University, College of Science and Engineering
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Polymers containing high sulfur content such as those made by inverse vulcanization have opened many opportunities for researchers to develop functional materials that can be used in many different applications such as polymers for energy storage, sorbents for toxic and precious metals, sorbents for oil spill remediation, infrared optics, adhesives, and composite materials. Inverse vulcanization is versatile to make polymer systems with sulfur rank 3 or more by altering the ratio of sulfur and alkenes starting materials. Due to its high S-S crosslink, however, polymers made by inverse vulcanization are difficult to process in common organic solvents, and pyridine is often the only solvent that can dissolve the polymers. It is thought that pyridine actually breaks the S-S bond in the polymer and converts it into soluble polymeric species. Phosphines such as tributyl phosphine can also do the similar thing but more rapidly and vigorously, which can facilitate desulfurization via an ionic mechanism.
A remarkable finding from our lab is that amide solvents such as dimethyl formamide can dissolve polysulfides made by inverse vulcanization with sulfur rank 3 or more. This result suggests that amide solvents could play a role in breaking and reforming the S-S bond in the polysulfide. A model S-S metathesis reaction employing dimethyl trisulfide and di-n-propyl trisulfide was used to test the theory. Dimethyl formamide, dimethyl acetamide, and N-methyl pyrrolidone were found to induce S-S metathesis in the trisulfide system to give a new trisulfide (methyl n-propyl trisulfide) in a reversible manner, while no reaction was observed in the disulfide analogues. This S-S metathesis reaction of organic trisulfides by amide solvents is unusual.
This thesis reported the investigation of the scope and mechanisms of the solvent induced S-S metathesis of organic trisulfides. Firstly, various organic trisulfides and tetrasulfides were synthesized and tested for the S-S metathesis. Different methods to access trisulfides were reported: 1) a trisulfide from thiosulfoxide salt (Bunte salt) and sodium sulfide, 2) a trisulfide from a thiol and sulfur dichloride (SCl2), and 3) a trisulfide from a thiol and N,N’-thiobisphthalimide (a monosulfur transfer reagent). In this thesis, three new trisulfides (diisobutyl trisulfide, di-n-hexyl trisulfide, and bis(4-methoxybenzyl) trisulfide) were reported for the first time. Secondly, the effect of various solvents on the trisulfide metathesis was explored. Dry and excess solvent were the key to rapid trisulfide metathesis. An additional experiment for S-S metathesis involving a cyclic trisulfide, norbornane trisulfide, is demonstrated.
Furthermore, in this thesis the rapid S-S metathesis chemistry was demonstrated. The preparation of an unsymmetrical trisulfide from two symmetrical trisulfides, the production of trisulfide-based dynamic combinatorial library, and the late-stage modification of a complex natural product containing trisulfide moiety, calicheamicin-γ1, can be achieved rapidly in the presence of amide solvents such as dimethyl formamide.
The mechanistic investigation of this solvent induced S-S metathesis of trisulfides was studied. Several mechanistic proposals involving radical, ionic, and thiosulfoxide intermediates were proposed. Experiments were conducted to find evidence for or against these mechanistic hypotheses. Primary evidence by electron paramagnetic resonance (EPR) suggests that no radical is present in the reaction. While TEMPO can inhibit the trisulfide metathesis reaction, other small molecules such as acids, dienophiles (i.e., maleic anhydride and benzoquinone), and water also inhibit the reaction. These results suggest that the trisulfide metathesis reaction may not follow a radical pathway. Thiosulfoxide intermediate is proposed for the metathesis reaction. However, until now this intermediate has not been directly observed and reported. Future investigations, theoretically and experimentally, are suggested in order to successfully characterise the intermediate and to understand this solvent induced S-S metathesis chemistry.
Keywords: trisulfides, S-S metathesis, dimethyl formamide, thiosulfoxide, dynamic combinatorial library, mechanism
Subject: Chemistry thesis
Thesis type: Doctor of Philosophy
Completed: 2025
School: College of Science and Engineering
Supervisor: Professor Justin M. Chalker