Mechanistic Studies of Imidazole Autocatalysis in 1,1′-Thiocarbonyldiimidazole-Mediated Couplings of Aniline

While investigating a 1,1′-thiocarbonyldiimidazole (TCDI)-mediated coupling in the synthesis of an aryl isothiocyanate, imidazole autocatalysis was observed. Although reported for 1,1′-carbonyldiimidazole (CDI), imidazole autocatalysis with TCDI has not been described. In this study, we explore the mechanism of imidazole autocatalysis in TCDI-mediated couplings of aniline. Notably, acids and non-nucleophilic bases were not shown to catalyze this reaction, suggesting that imidazole autocatalysis occurs via an alternative mechanism. We propose that imidazole acts as a nucleophilic catalyst leading to a more reactive cationic TCDI species. Inverse first-order kinetics with respect to imidazole anion and rapid equilibration with deuterated imidazole resulting in the release of free imidazole from TCDI support this conclusion. Increased catalytic activity with several known nucleophilic catalysts was observed, further supporting the role of imidazole as a nucleophilic catalyst. A density functional theory (DFT)-based computational model was constructed to identify other potential nucleophilic catalysts in this reaction. This model was successful in identifying several classes of nucleophilic catalysts that proved to be even more reactive catalysts for TCDI-mediated couplings of aniline compared to imidazole.