Mannich Reaction as a Key Strategy for the Synthesis of Benzoazacrown Ethers and Benzocryptands

A convenient method for the synthesis of mono- and polycyclic azacrown macrocycles containing aromatic fragments using the Mannich condensation of phenols and secondary diamines has been studied. This new approach allowed the synthesis of bisphenols connected by oligoazaoxaalkane units in good yields without the need to protect the phenolic OH groups. These bisphenols (13-16) were alkylated with ditosylates of polyethylene glycols to give benzoazacrown ethers 25-30. Intermediate bisphenols 13-15 were also treated with three bis(methoxymethyl)-substituted diamines to form benzoazacrowns 10-12 containing internal phenolic functions. Phenol-containing mono- (11) and bicyclic (3, n = 1) compounds, which were synthesized via the Mannich aminomethylation process, were used as building blocks for construction of bi- (32) and tricyclic (33) ligands.