The Mechanism of Formation of Amide‐Based Interlocked Compounds: Prediction of a New Rotaxane‐Forming Motif

Abstract

Molecular modeling of four different reagent systems shows that the (free) energies of supramolecular interactions in the gas phase and in solution can explain the different reaction products (i.e., various sized macrocycles, catenanes, and linear oligomers) that are formed in classic amide-catenane-forming reactions. Self-assembly of the catenanes requires the formation of ordered intertwined chains and is driven by bifurcated hydrogen bonds, with pi stacking only playing a lesser role. The understanding gained from the computational study was used to predict the possibility of a new rotaxane-forming system that does not permit catenane formation. The predictions were confirmed by the successful synthesis and characterization (including X-ray crystallography) of two novel rotaxanes.

Anion Binding versus Intramolecular Hydrogen Bonding in Neutral Macrocyclic Amides

“…This is in contrast to what was found in many condensations of isophthalic acid dichloride with longer and more rigid amines, where specific hydrogen‐bonding interactions involving linear intermediates directed the course of the reaction and led to the preferential formation of, for example, catenanes or rotaxanes 21. 22, 33, 34 The above‐described method of synthesis of the macrocyclic tetraamides suffers from low yields and problems with separation of the desired tetraamides from the larger macrocyclic products. However, these difficulties are compensated by the fact that this is a one‐pot synthesis and that each such reaction affords at least three interesting macrocycles that are potential anion receptors, that is, tetraamides ( 6 : 31.9 %, 7 : 15.0 %, 8 : 11.4 %), hexaamides ( 9 : 24.6 %, 11 : 1.8 %) and octaamides ( 12 : 15.7 %, 14 : 2.8 %).…”

“…The isophthalamide fragments play different roles at various stages of these syntheses by switching between their three basic conformations to satisfy the needs of interacting partners 33. 34…”

Conformer Distribution in Rotaxanes Containing Nonsymmetric Threads: A Systematic Approach

“…This indicates that this interaction is not just a consequence of the main NH ··· O interaction. Previous studies, have reported this kind of system as bifurcated, using a geometric approach, neglecting the possibility of CH ··· O participation in the stabilization of the system.…”

Versatile control of the submolecular motion of di(acylamino)pyridine-based [2]rotaxanes

“…Taking into account the better H-bond acceptor ability of the pyridine N -oxide function ( 1b ) compared to the less basic pyridine ring ( 1a ), 14 this lower yield of the interlocked compound seems to indicate that the geometrical organization of the H-bond acceptors of 2b are moving away from the ideal one for an efficient templation, highlighting the optimal spatial arrangement in the amide macrocyclization chemistry developed by Leigh and co-workers. 15 On the other hand, the protonation of 1a promotes a 180° rotational isomerization of the amide groups 16 a of 1c for adopting an alternative double s- cis conformation which is stabilized by a bifurcated hydrogen bond (see inset of Scheme 1 for its molecular structure in the solid state). This thread conformation in the rotaxane 2c would be responsible for the striking change in the ring dynamics of 2a following its protonation (see below).…”