SYNTHESIS OF NEW PYRIDINOAZACROWN ETHERS CONTAINING AROMATIC AND HETEROAROMATIC PROTON-IONIZABLE SUBSTITUENTS

Methods for the synthesis of pyridinocrowns functionalized with variou s proton ionizable groups have been elaborated. Sixteen new ligands co ntaining pyridine rings as part of the macrocycle or as a side arm hav e been prepared. Different interactive abilities of the OH and NH func tions 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(tos yloxy)methyl)pyridine (5). Pyridinoazacrown 1 was functionalized with different proton ionizable side arms by treatment first with formaldeh yde in methanol to form the N-methoxymethyl derivative 6 and then trea ting 6 with 5-chloro-8-hydroxyquinoline or the appropriate substituted phenol. Pyridinoaza-18-crown-6 ligands containing p-methylphenol (7), p-methoxyphenol (8), p-chlorophenol (9),p-fluorophenol (10),p-cyanoph enol (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-met hoxy-2-(bromomethyl)quinol followed by removal of the protecting group s to form p-nitrophenol- and 5-chloro-8-hydroxy-2-quinolinyl-substitut ed ligands (16, 18, and 21). Macrocycles 22 and 23 containing proton i onizable triazole and phenol functions inside the macrocyclic cavity a nd a pyridine side arm were prepared by cyclization of the appropriate dihalide with '-pyridylmethyl)-3,9-dioxa-6-azaundecane-1,11-diol foll owed by cleavage of the THP or methoxy protecting groups. Preliminary complexation data show that the phenol-substituted pyridinoaza-18-crow n-6 ligands form strong complexes with various metal cations and exhib it high selectivity toward Ag+. Macrocycle 16 containing a p-nitrophen ol substituent formed a complex with benzylamine. The crystal structur es for 16 and its benzylamine complex are also given here.