Nucleophilic Catalysis of Hydrazone Formation and Transimination:Implications for Dynamic Covalent Chemistry

摘要

Dynamic covalent chemistry (DCC) has great potential in the fields of drug discovery and materials science.However,its impact has been tempered by the slow equilibration kinetics of bonds that meet the stability requirements for these applications.A typical example,widely explored for DCC,is the hydrazone reaction.The reaction between a hydrazide and a carbonyl is chemoselective,and the equilibrium favors the hydrazone in aqueous solution.However,its equilibration kinetics are slow.To increase the dynamics of the hydrazone reaction without perturbing its chemical equilibrium,a transimination catalyst is required.Recently,we have shown that aniline effectively accelerates oxime ligation by forming in situ a highly reactive protonated aniline Schiff base.In a similar fashion,aniline should catalyze both hydrazone formation and hydrolysis,which would facilitate rapid transimination of hydrazones under aqueous conditions.Here we show that the equilibration kinetics of hydrazone formation and transimination can be significantly accelerated by using aniline as a nucleophilic catalyst.