Convenient synthesis and isolation of trifluoromethylthio-substituted building blocks

Various aryl-, heteroaryl-, and alkyl mercaptanes (RSH, 1a–r) were treated with a slight excess of NaH suspended in DMF to make the appropriate sodium thiolates (RSNa), which then reacted with 1.3 equivalent of CF3I at room temperature for overnight to afford the appropriate trifluoromethyl sulfides (CF3SR, 2) in fair to good yields. The radical chain alkylation reaction was effective without the use of UV irradiation with all but three substrates (thiosalicylic acid, 1k; 2-mercaptobenzimidazole, 1q; and 3-mercaptopropionic acid, 1r).Steam-distillation was found as an effective and easy to upscale means for the isolation of these volatile and water immiscible sulfides. The CF3I reagent gas was conveniently weighed and delivered to the reaction mixture by the balloon technique or as a preliminary made stock solution in DMF or DMSO. The sulfides 2 obtained here were assayed by GC and characterized by 1H, 13C, 19F NMR and MS spectroscopy.

Graphical abstractThe reaction of CF3I and arenethiols gave trifluoromethyl sulfides, which were isolated by steam-distillation.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of trifluoromethyl sulfides from CF3I and mercaptanes. ► Using of CF3I stock solutions in DMF or DMSO as S-alkylating reagents. ► Steam-distillation as a means of choice for isolation of aryl/alkyl trifluoromethyl sulfides.