Dethreading of Tetraalkylsuccinamide-Based [2]Rotaxanes for Preparing Benzylic Amide Macrocycles

The dethreading of a series of succinamide-based [2]rotaxanes bearing benzylic amide macrocycles is reported herein. These transformations proceeded quantitatively either under flash vacuum pyrolysis, conventional heating, or microwave irradiation. Studying the size complementarity of the stoppers at the ends of the thread and the cavity of the macrocycle allowed us to set up the best substituents for implementing the extrusion of the thread from the interlocked precursors. A variety of (1)H NMR kinetic experiments were carried out in order to evaluate the rate constants of the dethreading process, the half-life times of the rotaxanes, and the influence of temperature and solvents on these processes. The use of dibutylamino groups as stoppers yielded the rotaxane precursor in a reasonable yield and allowed the quantitative deslipping of the rotaxane. The overall process, including the rotaxane formation and its further dethreading, has been exploited for preparing benzylic amide macrocycles enhancing, in most cases, the results of the classical (2 + 2) condensation and other reported stepwise syntheses. The kinetics of the dethreading process is fairly sensitive to the electronic effects of the substituents on the isophthalamide unit or to the electronic nature of the pyridine rings through a conformational equilibrium expanding or contracting the cavity of the interlocked precursor.