Porphyrins and Corroles with 2,6-Pyrimidyl Substituents Irena Saltsman, † Israel Goldberg, ‡ and Zeev Gross* ,† † Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa 32000, Israel ‡ School of Chemistry, Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel * S Supporting Information ABSTRACT: Corroles and porphyrins with 2,6-pyrimidyl substituents are reported for the first time, together with the spectroscopic data and the crystal structures of the free-base porphyrin and of the phosphorus and cobalt complexes of the corrole. M etal complexes of porphyrin and corrole derivatives with basic nitrogen atoms in close proximity with their N4 coordination core are of large utility in many applications. 1 The main precursors of such complexes are compounds 1-3 of Figure 1, with either ortho-pyridyl or N-methylimidazolyl groups on their respective meso-C atoms. 2 Common to all of these examples is that they exist as a mixture of atropoisomers that differ in the relative positioning of the N atoms relative to the macrocycle plane. 2b For utilization as drug candidates, 3 they are commonly alkylated as to become water-soluble. Another consequence of the positive charges in the vicinity of the coordinated metal ion is the induction of the so-called ortho-effect, 4 which also accelerates the superoxide dismutation rate by manganese(III) porphyr- ins. 5 Alkylation does not resolve the atropoisomer issue for the ortho-pyridyl-substituted compounds 1 and 2, but methylation of tetra(N-methylimidazolyl)porphyrin (3) leads to a derivative that is a single isomer (4). 2 Within the course of our investigations on corroles as catalysts for medicine-relevant and many other applications, 6 we became interested in derivatives with meso-pyrimidyl substituents because such compounds would not suffer from the atropoisomer problem, have nitrogen atoms in the vicinity of the N4 coordination core, and could also be of sufficient solubility in water. To our surprise, neither corroles nor porphyrins with 2,6-pyrimidyl moieties were ever reported. The closest examples are tetra(3,5-pyrimidyl)porphyrins and analogous corroles with either two or three 3,5-pyrimidyl groups (Figure 1) 5 and 6, respectively. 7,8 However, the nitrogen atoms in these macrocycles are too remote from the N4 metal-coordination core to affect metal-centered processes. We now report the synthesis of corroles with one and two 2,6- pyrimidyl substituents (7 and 8), 9 including the crystal structures of the corresponding phosphorus (10) and cobalt (11) chelates of the former, 10 as well as of tetra(2,6- pyrimidyl)porphyrin (9). The latter compound was charac- terized by X-ray crystallography, and it also displays high solubility in water. The most straightforward procedure for the preparation of the target molecules would be the direct cyclo-condensation of pyrrole with 2-pyrimidinecarboxaldehyde, in a 1:1 ratio for obtaining the porphyrin and a 1:3 ratio for preferring the corrole. The synthetic toolbox for accessing this kind of products is quite large, but neither tris(2,6-pyrimidyl)corrole nor tetra(2,6-pyrimidyl)porphyrin were obtained when the reaction was performed by any of the applied reaction conditions. The attention was hence driven to the methodology promoted by Gryko, 11 which is ideal for the synthesis of A2B corroles: derivatives with a unique substituent on C10 and two identical substituents on C5 and C15 meso C atoms of the macrocycle. It consists of the condensation of 5-substituted dipyrromethane with aldehyde in a 2:1 ratio, catalyzed by an acid whose concentration must be optimized, especially when one of the reagents contains basic atoms. 11b The synthesis of corroles with one and two 2,6-pyrimidyl substituents was Received: May 3, 2015 Figure 1. Selected previously reported porphyrins and corroles with N-heterocyclic substituents. Letter pubs.acs.org/OrgLett © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.5b01297 Org. Lett. XXXX, XXX, XXX-XXX