Author ORCID Identifier:
0000-0001-8222-7206
Date of Graduation
9-2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Chemistry (PhD)
Degree Level
Graduate
Department
Chemistry & Biochemistry
Advisor/Mentor
He, Maggie
Committee Member
Matthias McIntosh
Second Committee Member
Nan Zheng
Third Committee Member
Suresh Kumar Thallapuranam
Keywords
acetals; arena-based macrocycles; bridge-functionalized pillararenes; Friedel-Crafts reaction; macrocycles; Pillar[n]arenes
Abstract
Pillar[n]arenes are macrocyclic compounds consisting of ‘n’ hydroquinone units linked by para-methylene bridges. Since their first report of facile synthesis 17 years ago, pillararenes have attracted significant interest due to their versatile functionality, electron-rich cavity, crystalline nature, and planar chirality. These unique properties have enabled a broad range of practical applications, including small molecule separation, formation of one-dimensional and two-dimensional channels, drug delivery systems, and enhanced emissive and fluorescent properties. The ease of synthesis of pillararenes has been one of the key factors in their widespread adoption and continued exploration in supramolecular chemistry and material science. Despite the efficiency and broad substrate scope of traditional pillararene synthesis, it relies exclusively on paraformaldehyde as the source of methylene bridges. However, paraformaldehyde releases formaldehyde, a known carcinogen, at ambient conditions causing safety concerns. In this study, we demonstrated that cyclic and acyclic acetals of formaldehyde serve as safer and nonaqueous alternatives to paraformaldehyde. This novel approach preserves the efficiency and simplicity of traditional pillararene synthesis while significantly improving safety by reducing formaldehyde exposure. Using paraformaldehyde for pillararene synthesis does not allow for substitutions on the methylene bridge of pillararenes. This limitation can be addressed by employing acetals. This study demonstrated that using cyclic acetals of acetaldehyde as the bridge source allowed for the synthesis of methyl-substituted-methine-bridged pillar[6]arenes. Notably, introducing a methine bridge introduced chiral centers and shifted the thermodynamic equilibrium towards one stereoisomer of the corresponding pillar[6]arene, providing access to a stereoselective synthetic protocol for pillar[6]arene with an improved yield of 43%. This strategy significantly enhances the safety profile of pillararene synthesis and expands the structural diversity of pillararenes. This broadened diversity could lead to more applications across various fields.
Citation
Machireddy, B. (2025). Synthesis of Pillar[n]arenes and Bridge-Functionalized Pillar[n]arenes via Cyclic and Acyclic Acetals. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/5852
