Synthesis of 12-Membered Tetra-aza Macrocyclic Pyridinophanes Bearing Electron-Withdrawing Groups

Authors

• Akop Yepremyan, Texas Christian University
• Magy A. Mekhail, Chapman UniversityFollow
• Brian P. Niebuhr, Texas Christian University
• Kristof Pota, Texas Christian University
• Nishanth Sadagopan, Texas Christian University
• Timothy M. Schwartz, Texas Christian University
• Kayla N. Green, Texas Christian University

Document Type

Article

Publication Date

3-25-2020

Abstract

The number of substituted pyridine pyridinophanes found in the literature is limited due to challenges associated with 12-membered macrocycle and modified pyridine synthesis. Most notably, the electrophilic character at the 4-position of pyridine in pyridinophanes presents a unique challenge for introducing electrophilic chemical groups. Likewise, of the few reported, most substituted pyridine pyridinophanes in the literature are limited to electron-donating functionalities. Herein, new synthetic strategies for four new macrocycles bearing the electron-withdrawing groups CN, Cl, NO₂, and CF₃ are introduced. Potentiometric titrations were used to determine the protonation constants of the new pyridinophanes. Further, the influence of such modifications on the chemical behavior is predicted by comparing the potentiometric results to previously reported systems. X-ray diffraction analysis of the 4-Cl substituted species and its Cu(II) complex are also described to demonstrate the metal binding nature of these ligands. DFT analysis is used to support the experimental findings through energy calculations and ESP maps. These new molecules serve as a foundation to access a range of new pyridinophane small molecules and applications in future work.

Comments

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in The Journal of Organic Chemistry, volume 85, issue 7, in 2020 following peer review. This article may not exactly replicate the final published version. The definitive publisher-authenticated version is available online at https://doi.org/10.1021/acs.joc.0c00188.

Recommended Citation

*Yepremyan, A.; *Mekhail, M. A.; Niebuhr, B. P.; Pota, K.; Sadagopan, N.; Schwartz, T. M.; Green, K. N., Synthesis of 12-Membered Tetra-aza Macrocyclic Pyridinophanes Bearing Electron-Withdrawing Groups. The Journal of Organic Chemistry 2020, 85 (7), 4988-4998. https://doi.org/10.1021/acs.joc.0c00188

Copyright

American Chemical Society