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

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, NO 2 , and CF 3 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.

Functionalized pyridine in pyclen-based iron(iii) complexes: evaluation of fundamental properties

“…Elemental analysis was performed by Canadian Microanalytical Service Ltd. L1–L6 were synthesized using previously published procedures and isolated as water soluble trihydrochloride salts. 3 , 23 , 29 …”

“…The protonation constants of the ligands were obtained from previously reported data. 29 The stability constants of the metal complexes were determined using the direct pH-potentiometric method by titrating samples with 1 : 1 metal-to-ligand ratios (the number of data pairs were between 100–250), allowing 1 min for sample equilibration to occur. The protonation and stability constants ((log β ) = [ML]/([M][L])) were calculated from the titration data with the PSEQUAD program.…”

“… 28 Finally, our group has recently synthesized a series of ligands with electron-withdrawing groups (EWG) ( L3–L6 ) to diversify pyridinophane chemistry and allow the development of this library. 29 …”

Assembly of Polyiodide Networks with Cu(II) Complexes of Pyridinol-Based Tetraaza Macrocycles

“…Nevertheless, only few examples of pyridine-substituted derivatives of L1 , L1-Me , and L1-Me 3 , bearing both electron-donating and electron-withdrawing groups, have been reported, so far. 29 , 46 − 48 Among these, only L2-Me 3 ( Figure 1 ) has been used for the preparation of polyiodides, in the absence of metal ions, leading to the [H 2 L2-Me 3 (I 7 ) 2 ] compound featuring diprotonated ligand molecules segregated into boxes formed by couples of tripodal I 7 – anions. 29 Analysis of its crystal structure led us to believe that the formation of these rare I 7 – anions is due to the capacity of (H 2 L2-Me 3 ) 2+ to act as a supramolecular templating agent, molding the heptaiodide anion around itself.…”

“…The L2 -based ligands reproduce the progressive N-methylation of the L1 -based analogues, while the presence of the para −OH group introduces two additional factors: (i) the possibility of intermolecular interactions (formation of oligomeric complexes or coordination polymers) via coordinative/hydrogen bonding of deprotonated/protonated −OH groups and (ii) alteration of the electronic properties of the pyridine ring brought about by this para substituent. With respect to the latter, the para −OH group increases the electron density on the pyridine ring, 48 a phenomenon that would seem to generate an adverse environment for the stabilization of polyiodide anions. Nevertheless, metal coordination to the pyridinol nitrogen atom facilitates the deprotonation of this −OH group and the polarization of the ring electron density toward the N-coordinated metal ion, through the stabilization of the ketone ligand form.…”