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

meso ‐Tetraarylporphyrin chelates (of Zn 2+ , Ni 2+ , and Cu 2+ ) are easily available from parent porphyrins. Their reactions with nitric acid (yellow fuming HNO 3 , d = 1.52, diluted to 25%–50%), under optimized conditions in CHCl 3 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.