Recent Advances in the Synthesis of Isothiocyanates Using Elemental Sulfur

Isothiocyanates (ITCs) are biologically active molecules found in several natural products and pharmaceutical ingredients. Moreover, due to their high and versatile reactivity, they are widely used as intermediates in organic synthesis. This review considers the best practices for the synthesis of ITCs using elemental sulfur, highlighting recent developments. First, we summarize the in situ generation of thiocarbonyl surrogates followed by their transformation in the presence of primary amines leading to ITCs. Second, carbenes and amines afford isocyanides, and the further reaction of this species with sulfur readily generates ITCs under thermal, catalytic or basic conditions. Additionally, we also reveal that in the catalyst-free reaction of isocyanides and sulfur, two-until this time overlooked and not investigated-different mechanistic pathways exist.

Automated summary

This review discusses the best practices for the synthesis of ITCs using elemental sulfur, including the in situ generation of thiocarbonyl surrogates and the reaction pathways of carbenes and amines to form isocyanides, which further react with sulfur to generate ITCs. Additionally, it reveals the existence of two previously overlooked and uninvestigated mechanistic pathways in the catalyst-free reaction of isocyanides and sulfur.