Formation of Two 4-Imidazolylmethylphosphonium Salts and their Synthetic Studies Toward Histamine H3-Ligands

Abstract A simple and convenient preparation of {[1H-imidazol-4(5)-yl]methyl}triphenylphosphonium chloride (5) is described. The phosphonium salt 5 could be applied to the synthesis of 1-[1H-imidazol-4(5)-yl]-5-arylpentan- or 6-arylhexan-3-ones 4A-D exhibiting histamine H 3 -antagonistic activities via a 1,3-diazafulvene intermediate 6 generated from 5. Further, two-methylene-enlongated homolog 3 of imifuramine was efficiently synthesized, starting from Wittig olefination of aldehyde 24 using [(1-tritylimidazol-4-yl)methyl]triphenylphosphonium chloride 7.