Linear and macrocyclic ligands containing alternating pyridine and imidazolidin-2-one units1

Abstract

Linear oligomers of alternating 2,6-disubstituted pyridine (P) and N,N′-disubstituted imidazolidine-2-one (I) units have been made rapidly and in high yield with up to nine repeating units, terminating in either pyridine or imidazolidin-2-one units, or one of each. Synthetic methods include: (1) the sodium hydride-mediated condensation of N-(tert-butyl)imidazolidin-2-one with 2,6-difluoropyridine (F-P-F) or with higher analogues such as F-PIP-F, to give IPI, IPIPI and IPIPIPI. (The tert-butyl protection is readily and quantitatively removed with acid.) (2) The caesium fluoride catalysed interaction of N,N′-[dimethyl-(1,1,3-trimethylpropyl)]-protected IPI with Bu^t-IP-F sequentially leads firstly to IPIPIPI which by the same method reacts with F-P-F to give F-PIPIPIPIP-F. (3) F-P-F also reacts with 1,2-ethylenediamine (E) sequentially to give F-PEP-F, EPEPE and F-PEPEPEP-F while similar reactions starting from F-PIP-F give EPIPE and F-PEPIPEP-F in sequence. Alternative routes examined include: (1) the interaction of F-P-F with imidazole to give 2,6-bis(imidazol-1-yl)pyridine and salts therefrom followed by (unsuccessful) oxidation. (2) The reaction of 2,6-diaminopyridine with 2-chloroethyl isocyanate followed by cyclisation to give IPI. (3) The interaction of 2,6-diaminopyridine with oxalate esters (O) to give OPO or H₂N-POP-NH₂, the latter of which was reduced to H₂N-PEP-NH₂.

Cyclisation of the linear assemblies was not successful. However macrocyclic systems were made by linking two IPI units with two ethoxyethyl or with two ethoxyethoxyethyl units. Also two F-PIP-F units were similarly reacted to give polyether-linked macrocycles. Mono- and bis-prop-2-ynylated IPI derivatives were made but could not be cyclised. Attempts to cyclise ethylenediamine and oxamide based systems were also unsuccessful. The linear and macrocyclic ligands showed calcium selectivity in a study of their metal complexing abilities.