Ball-Milling-Assisted Synthesis of Aromatic Isothiocyanates and Thioureas: A Green and Versatile Synthetic Approach-Review

The study provides a concise demonstration of how mechanochemical activation can simplify the synthesis of aromatic isothiocyanates and thioureas. Ball milling with KOH and CS₂ overcomes the poor conversion and selectivity observed in the investigated solution-phase experiments, while the amount of CS₂ provides a practical means of controlling product class. Under optimized conditions, a broad range of substituted anilines affords isothiocyanates in 52–97% isolated yield, with many electron-rich substrates reacting within 40–45 min. Selected in situ generated isothiocyanates can then be converted directly into unsymmetrical thioureas in 85–96% yield, whereas 1.0 equivalent of CS₂ enables formation of symmetrical thioureas in 43–97% yield. Overall, the methodology illustrates the value of solvent-free mechanical activation for improving reaction rate, simplifying work-up, and avoiding conventional harsh decomposition reagents. Its principal strengths are operational simplicity, inexpensive reagents, rapid reaction times, and the ability to access several product classes from a common starting-material platform. Its limitations—particularly the need for excess CS₂ in the isothiocyanate branch, reduced performance with strongly electron-deficient substrates, and limited scale-up information—also define clear opportunities for future research.

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