Selective Synthesis of β-Tetrabromo-N-methylporphyrin Isomers with Distinct NH-Tautomerism

The introduction of an N-Me group into the inner core of porphyrins significantly affects their functionalities, which can be regulated by NH-tautomerism and peripheral substitutions. However, systematic methods for selective peripheral substitutions of N-methylporphyrins are hardly reported, owing to their low-symmetry framework. We previously reported the selective synthesis of β-tetrabromo-²¹N-methylporphyrin (²¹N-Me₁) with an N-Me group at a brominated pyrrole through the N-methylation of β-tetrabromoporphyrin. In this work, a regioisomer of ²¹N-Me₁ (²²N-Me₁), bearing an N-Me group at a nonbrominated pyrrole, was successfully prepared through selective β-bromination of N-methylporphyrin. This regioselective β-bromination could be applied to the synthesis of a 2,3,7,8-β-tetrabromoporphyrin derivative having adjacent brominated pyrrole moieties. The two regioisomers, ²¹N-Me₁ and ²²N-Me₁, can be regarded as pseudo-tautomers of each other, and their NH-tautomerism and physicochemical properties were compared. It was revealed that these pseudo-tautomers exhibited contrasting acid-base behavior and hydrogen-bonding abilities with an alcohol, which are caused by their distinct NH-tautomerisms. This work clearly highlights the important role of peripheral substitutions and core modifications in tuning NH-tautomerism and the functionalities of porphyrinoids.