Selective Synthesis of β-Tetrabromo- <i>N</i> -methylporphyrin Isomers with Distinct NH-Tautomerism

The introduction of an <i>N-</i>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 <i>N</i>-methylporphyrins are hardly reported, owing to their low-symmetry framework. We previously reported the selective synthesis of β-tetrabromo-²¹<i>N</i>-methylporphyrin (<b>²¹<i>N</i>-Me</b>_<b>1</b>) with an <i>N</i>-Me group at a brominated pyrrole through the <i>N</i>-methylation of β-tetrabromoporphyrin. In this work, a regioisomer of <b>²¹<i>N</i>-Me</b>_<b>1</b> (^<b>2</b><b>²<i>N</i>-Me</b>_<b>1</b>), bearing an <i>N</i>-Me group at a nonbrominated pyrrole, was successfully prepared through selective β-bromination of <i>N</i>-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, <b>²¹<i>N</i>-Me</b>_<b>1</b> and <b>²²<i>N</i>-Me</b>_<b>1</b>, 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.