Oral Presentation Royal Australian Chemical Institute National Congress 2026

Ball-milling as the innovative and effective method of merging thiols with heteroallenes (132899)

Kamil Hanek 1 , Natalia Pietras 1 , Patrycja Żak 1 , Dawid Frąckowiak 2
  1. Adam Mickiewicz University in Poznań, Poznan, WIELKOPOLSKIE, Poland
  2. Centre for Advanced Technologies, Poznań, Wielkopolskie, Poland

Organosulfur compounds enjoy a large variety of different applications in medicine, pharmacy and environmental chemistry.1-2 In the field of medicinal chemistry, the reactions of thiols with heteroallenes such as –NCO and –NCS are of particular interest because they lead to materials with promising potential as pharmaceutical agents. Unfortunately most synthetic procedures for linking thiols with iso(thio)cyanates stand against the principles of green chemistry as they require high temperatures, long reaction times and toxic transition metal complexes as catalysts.3-5 Because of that the search for new protocols that would be congruent with sustainable development and would follow green transformation rules (minimizing pollution, improving energy efficiency, developing eco-friendly technologies) is of top concern. Replacement of solvents with ball mills and performance of reactions in the mechanochemical manner may be the desired answer to the above-mentioned problems since mechanochemistry creates an opportunity for development of environmentally friendly protocols of chemical syntheses, as it eliminates the need for toxic solvents and moreover, it has been already proved to be superior in organosulfur chemistry.6-7

Here we present a new efficient and eco-friendly synthetic pathway for obtaining 2-thiazolines and S-thiocarbamates, based on the mechanochemical process of addition of chloroalkyl iso(thio)cyanates to thiols catalyzed by the cheap and easily available K2CO3.

This environmentally friendly protocol makes use of commercially accessible reagents to prepare functionalized heteroallenes with yields exceeding 96% under ambient air and solvent-free conditions. The presented methodology can be successfully applied for dithiols functionalization creating opportunities for the synthesis of new symmetrically functionalized compounds. In summary, 39 compounds have been obtained and comprehensively characterized using spectroscopic methods.

A critical green metrics - process mas intensity and E-factor were calculated proving that the ball milling constitutes a superior alternative in comparison to the solvent-based synthesis.. According to literature, the mechanisms of the designed transformations have been proposed.

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