Synthesis and Characterization of Calixarene Tetraethers: An Exercise in Supramolecular Chemistry for the Undergraduate Organic Laboratory

Abstract

In this experiment for an introductory undergraduate organic chemistry lab, students tetraalkylate tertbutylcalix[4]arene, a bowl-shaped macrocyclic oligophenol, and examine the supramolecular chemistry of the tetraether product by proton nuclear magnetic resonance (NMR) spectroscopy. Complexation with a sodium ion reduces the conformational mobility of the macrocycle through host−guest interactions, greatly simplifying the 1 H NMR spectrum of the macrocycle and providing an excellent example of geminal coupling between the diastereotopic protons of the methylene bridges. By dealing explicitly with the organic chemistry of large molecules and host−guest complementarity, this experiment provides a useful pedagogical bridge from small-molecule organic chemistry to the biochemistry of macromolecules such as enzymes.

Solvent and Guest-Driven Supramolecular Organic Frameworks Based on a Calix[4]arene-tetrol: Channels vs Molecular Cavities

“…The asymmetric unit of the monoclinic ( P 2 1 / c ) crystal is composed of one tetrol 3 molecule complexing a sodium ion at the lower rim, one CH 3 CN guest solvent molecule, one iodide counterion, and two cocrystallized water molecules (Figure S13). In this case, the basic structural element is determined by a Na + @ 3 complex where the sodium cation is symmetrically bound to the four ethereal O atoms at the lower rim (Figure c). − Its coordination sphere is completed by an additional H 2 O molecule interacting from the bottom, which is H-bonded to the iodide anion and to a CH 3 CN molecule hosted in the cup of another calixarene molecule. The sodium coordination provokes the opening of the calixarene cup (Figure d).…”

Environmental Application of Cyclodextrin Metal–Organic Frameworks in an Undergraduate Teaching Laboratory

“…45 Although hydrophobically driven host− guest complexation is well-studied in supramolecular chemistry research, 46 it is rarely introduced in the undergraduate setting, with isolated reports of the hydrophobic effect in threedimensional protein structures 47 and supramolecular complexation reported. 48 To further understand the interaction of a cyclodextrin host with methylene blue, therefore, one-dimensional 1 H NMR spectra of γ-cyclodextrin and methylene blue were provided to students. Additionally, students measured a two-dimensional NMR spectrum of a methylene blue guest bound in a γ-cyclodextrin host (not in a MOF structure, because MOFs cannot be analyzed via solution-state NMR spectroscopy), with the spectrum from one of the student samples shown in Figure 4.…”

“…Explaining to students how the CD-MOF was able to remove methylene blue from the solution required a discussion of the supramolecular complexation properties of cyclodextrin, and in particular its ability to bind small-molecule organic guests in its interior . Although hydrophobically driven host–guest complexation is well-studied in supramolecular chemistry research, it is rarely introduced in the undergraduate setting, with isolated reports of the hydrophobic effect in three-dimensional protein structures and supramolecular complexation reported . To further understand the interaction of a cyclodextrin host with methylene blue, therefore, one-dimensional 1 H NMR spectra of γ-cyclodextrin and methylene blue were provided to students.…”

Understanding Thermodynamic Control in Covalent Self-Assembly: A Mixed Synthetic–Computational Experiment for the Undergraduate Organic-Chemistry Laboratory

“…Because self-assembly allows for the efficient formation of many bonds in one synthetic step, it can be used in the synthesis of large molecules, such as macrocycles. − In recent years, the popularity of using self-assembly for the synthesis of large organic molecules has grown. However, despite popularity in the field and a significant number of real-world applications, such as host–guest chemistry, molecular recognition, and molecular machines, organic synthesis using self-assembly is not commonly addressed in organic-chemistry laboratory courses. − Synthesis in organic-chemistry laboratory courses is commonly taught through step-by-step syntheses, despite the ability of self-assembly to reduce the number of synthetic steps required to form certain products.…”