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

Abstract

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.

Conformer Distribution in Rotaxanes Containing Nonsymmetric Threads: A Systematic Approach

“…The macrocycles are comprised of two 1,4‐phenylene units that are connected by two isophthalamide units . The synthetic approach to prepare the [2]rotaxanes was carried out by a five‐component clipping methodology , , . Afterwards, a two‐step procedure was used for rotaxane synthesis: ( i ) synthesis of threads and ( ii ) interlocked molecules.…”

“…Clegg et al demonstrated equilibria between rotamers in different solvents. Martinez‐Cuezva et al, reported the quantification of conformers by 1 H NMR analysis without the identification of each form and the reasons that influence the proportions. Leigh et al showed that [2]‐ and [3]catenanes move in discrete steps between different binding sites on the larger ring; this movement occurs with the change of conformers.…”

“…These unique characteristics have led to rapid advances in the synthesis of these systems . In general, diamides are effective templates for obtaining rotaxanes in a five‐component clipping reaction, because amide threads can be good hydrogen‐bond acceptors , …”

“…Studies of the conformations of rotaxanes have focused mainly on determining the existence of conformers in solution. These studies revealed equilibria between rotamers in different solvents and led to the quantification, of conformers by using NMR spectroscopy. Additionally, Chatterjee et al reported a light‐switchable molecular shuttle in which the proportion of conformations change depending on external stimuli.…”

A Versatile Axle for the Construction of Disassemblage Rotaxanes

“…Literature results show that an external stimulus can reduce the stability of pseudorotaxane (a rotaxane with one blocking group)/rotaxanes, promoting disassemblage. For example, Martinez-Cuezva et al promoted the dethreading of a [2]rotaxane using heat, flash vacuum pyrolysis, or microwave radiation [14]. Leung showed that reducing the interaction strength between axle and wheel via deprotonation or switch of solvent accelerated disassemblage [15].…”