Thermal Safety and Structure-Related Reactivity Investigation of Five-Membered Cyclic Sulfamidates

Five-membered cyclic sulfamidates are very valuable electrophiles in organic synthesis and readily used on a multikilogram scale. However, their thermal degradation is underreported and might lead to unforeseen and undesirable safety events. In addition, ring or nitrogen substitution can have a tremendous influence on cyclic sulfamidate reactivity toward bases and therefore impact the overall safety assessment of a process. An understanding of such behavior is therefore of high importance in the industry while designing a synthetic route, as a change of, e.g., a protecting group can increase the thermal safety of a step on scale. We report herein the thermal degradation investigation as well as the structure-related reactivity exploration of cyclic sulfamidates, including their use in combination with strong bases. The design of a predictive model to rapidly assess the thermal hazard based on collected data and selected molecular descriptors is also presented.