Synthesis of New Pyridinoazacrown Ethers Containing Aromatic and Heteroaromatic Proton Ionizable Substituents

Article abstract of DOI:10.1021/jo00124a022

Methods for the synthesis of pyridinocrowns functionalized with various proton ionizable groups have been elaborated.Sixteen new ligands containing pyridine rings as part of the macrocycle or as a side arm have been prepared.Different interactive abilities of the OH and NH functions of 3,9-dioxa-6-azaundecane-1,11-diol (3) in strong base allowed the synthesis of pyridinoazacrowns 1 and 2 by cyclization with 2,6-bis((tosyloxy)methyl)pyridine (4) and THP-protected 4-hydroxy-2,6-bis((tosyloxy)methyl)pyridine (5).Pyridinoazacrown 1 was functionalized with different proton ionizable side arms by treatment first with formaldehyde in methanol to form the N-methoxymethyl derivative 6 and then treating 6 with 5-chloro-8-hydroxyquinoline or the appropriate substituted phenol.Pyridinoaza-18-crown-6 ligands containing p-methylphenol (7), p-metoxyphenol (8), p-chlorophenol (9), p-fluorophenol (10), p-cyanophenol (11), 2-formyl-4-bromophenol (12), or 5-chloro-8-hydroxyquinoline (13) groups were prepared by this process.Pyridinoazacrowns 1 and 2 were alkylated with 2-hydroxy-5-nitrobenzyl chloride or 5-chloro-8-methoxy-2-(bromomethyl)quinoline followed by removal of the protecting groups to form p-nitrophenol- and 5-chloro-8-hydroxy-2-quinolinyl-substituted ligands (16, 18, and 21).Macrocycles 22 and 23 containing proton ionizable triazole and phenol functions inside the macrocyclic cavity and a pyridine side arm were prepared by cyclization of the appropriate dihalide with 6-(2'-pyridylmethyl)-3,9-dioxa-6-azaundecane-1,11-diol followed by cleavage of the THP or methoxy protecting groups.Preliminary complexation data show that the phenol-substituted pyridinoaza-18-crown-6 ligands form strong complexes with various metal cations and exhibit high selectivity toward Ag(1+).Macrocycle 16 containing a p-nitrophenol substituent formed a complex with benzylamine.The crystal structures for 16 and its benzylamine complex are also given here.