Mechanically driven stainless steel-initiated activation of S-H bonds to construct disulfides
Xujuan Huang1,2, Shiming Zhang1,2
1Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University Zunyi 563000 China smzhang@zmu.edu.cn.
Abstract:
Disulfides are important scaffolds in biologically active molecules and pharmaceuticals; however, their traditional synthesis method relies on costly precious metals, toxic solvents, oxidants, and harsh reaction conditions. Herein, we report a mechanochemical strategy enabling solvent-, oxidant-, catalyst-, and auxiliary abrasive-free construction of disulfides via stainless steel-induced S-H activation. Stainless steel nanoparticles (SS NPs) generated during ball milling facilitated efficient oxidative coupling of thiols under ambient conditions, achieving 41-99.9% yields within 30-90 minutes. The mechanistic studies confirmed the synergistic radical-mediated pathway dominated by iron species, effectively suppressing over-oxidation. This green approach eliminated environmental burdens while offering broad substrate tolerance, advancing sustainable disulfide synthesis for pharmaceutical and material applications.
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