Fast Nucleophilic Approach to Exhaustively Substituted Porphyrin Derivatives at the “Eastern Half”

Abstract

meso-Tetraarylporphyrin chelates (of Zn²⁺, Ni²⁺, and Cu²⁺) are easily available from parent porphyrins. Their reactions with nitric acid (yellow fuming HNO₃, d = 1.52, diluted to 25%–50%), under optimized conditions in CHCl₃ at room temperature, can be carried out selectively, thus giving mainly β,β-dinitro-substituted moieties (usually two or three isomers of the above complexes). These intermediates (obtained in overall yields of up to 73%), upon the reaction with carbanions bearing a leaving group X at the reactive center, afford the target products, the ones of vicarious nucleophilic substitution (VNS) of hydrogen. This approach allows the synthesis of porphyrin derivatives exhaustively β-substituted in the so-called “Eastern half”, starting from a simple meso-tetraarylporphyrins. These types of products are sought in anticancer photodynamic therapy (PDT). Thus, the above two-step procedure including very attractive VNS reaction gives hydrophilic or amphiphilic moieties that seem to be potential PDT agents with unique structures, being practically unavailable by any other alternative methods.