Syntheses and kinetic studies of cyclisation-based self-immolative spacers

Kinetic analysis of the disassembly of self-immolative spacers based on cyclisation processes was performed. Five compounds were synthesized belonging to two different series, and their kinetic constants were determined. Electron-donating substituents gave a slight acceleration but the main effect was steric, and the Thorpe-Ingold effect was indeed particularly effective. Comparison with the self-immolative spacers based on elimination processes showed that cyclisations gave comparable or lower rate, but the corresponding spacers are more difficult to modulate.