Improved synthesis of symmetrically & asymmetrically N-substituted pyridinophane derivativesElectronic supplementary information (ESI) available. CCDC 1579175. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7ob02508d

• Main Authors: Wessel, Andrew J, Schultz, Jason W, Tang, Fengzhi, Duan, Hui, Mirica, Liviu M
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c7ob02508d

The N , N ′-di(toluenesulfonyl)-2,11-diaza[3,3](2,6)pyridinophane ( Ts N4) precursor was sought after as a starting point for the preparation of various symmetric and asymmetric pyridinophane-derived ligands. Various procedures to synthesize Ts N4 had been published, but the crucial problem had been the purification of Ts N4 from the larger 18- and 24-membered azamacrocycles. Most commonly, column chromatography or other laborious methods have been utilized for this separation, yet we have found an alternate selective dissolution method upon protonation which allows for multi-gram scale output of Ts N4·HCl. This optimized synthesis of Ts N4 also led to the development of symmetric R N4 derivatives as well as the asymmetric derivative N -(tosyl)-2,11-diaza[3,3](2,6)pyridinophane ( TsH N4). Using this TsH N4 precursor, different N -substituents can be added to create a library of asymmetric RR′ N4 macrocyclic ligands. These asymmetric RR′ N4 derivatives expand the utility of the R N4 framework in coordination chemistry and the ability to study the electronic, steric, and denticity effects of these pyridinophane ligands on the metal center. Reported herein is an optimized, larger-scale synthesis of symmetric and asymmetric pyridinophane tetraazamacrocycles, which are versatile ligands in coordination chemistry.