A Concise Synthesis of a Methyl Ester 2-Resorcinarene: A Chair-Conformation Macrocycle

Abstract

Anions are important hydrogen bond acceptors in a range of biological, chemical, environmental and medical molecular recognition processes. These interactions have been exploited for the design and synthesis of ditopic resorcinarenes as the hydrogen bond strength can be tuned through the modification of the substituent at the 2-position. However, many potentially useful compounds, especially those incorporating electron-withdrawing functionalities, have not been prepared due to the challenge of their synthesis: their incorporation slows resorcinarene formation that is accessed by electrophilic aromatic substitution. As part of our broader campaign to employ resorcinarenes as selective recognition elements, we need access to these specialized materials. In this article, we report a straightforward synthetic pathway for obtaining a 2-(carboxymethyl)-resorcinarene, and resorcinarene esters in general. We discuss the unusual conformation it adopts and propose that this arises from the electron-withdrawing nature of the ester substituents that renders them better hydrogen bond acceptors than the phenols, ensuring that each of them acts as a donor only. Density Functional Theory (DFT) calculations show that this conformation arises as a consequence of the unusual configurational isomerism of this compound and interruption of the archetypal hydrogen bonding by the ester functionality.

Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity

“…Five possible conformers have been reported: (i) crown , (ii) boat , (iii) saddle , (iv) chair , and (v) diamond ( Figure 1 ) [ 11 ]. Each of these conformations is possible, depending on aspects such as the position of the resorcinol units and the substituents in the methylene bridges; this gives rise to a library of molecules [ 11 , 12 , 13 , 14 , 15 , 16 ]. Thus, the versatility in the synthesis of polyhydroxylated platforms has allowed the incorporation of substituents, which allows the use of new strategies, such as click chemistry, for the synthesis of functionalized calixarenes/resorcinarenes.…”

Efficient Separation of C-Tetramethylcalix[4]resorcinarene Conformers by Means of Reversed-Phase Solid-Phase Extraction

“…However, sometimes under different synthesis conditions, the presence of conformer mixtures is reported, which makes it difficult to properly characterize each of the products, and there are frequent difficulties for separation since the reaction product behaves as a single compound viewed through TLC and liquid chromatography (LC), but the 1 H NMR and 13 C NMR spectrum is consistent with there being two isomers. Alternatives have been sought on this subject, trying to recrystallize the material, but they did not change the relationship of the signals or enrich the conformers . In an effort to solve these difficulties, methods for separating mixtures of conformational isomers for C -tetra­( p -hydroxyphenyl)­calix­[4]­resorcinarene have been described, where through RP-HPLC two well-resolved signals corresponding to the crown and chair isomers were found, and through the application of an RP-SPE protocol, the separation of the two stereoisomers with high purity and their subsequent characterization using techniques such as FT-IR, 1 H NMR, and 13 C NMR were achieved, which confirmed their chemical identity. , Although the derivatives of calix[4]­resorcinarene are molecules that are of great interest in the chemical and pharmaceutical field given their wide range of applications, there is a limitation in their purification stages.…”