The macrocyclic tetraamides 8a-e were obtained in good yields by bis-alkylation of the potassium salts of the appropriate bisphenols 7a-c with the dihalo compounds 2a,b. Similarly, macrocyclic tetraamides with pendant hydroxy group 18a,b were prepared by the nucleophilic reaction of the potassium salts of 7a,b with the dihalo compound 10. Acylation of 18a,b with chloroacetyl chloride gave the corresponding ester 19a,b. Compounds 19a,b reacted with different secondary amines to afford the corresponding lariat macrocycles 20a-d and novel bis-macrocycle 21 in 50-65% yield.Much attention has been paid to the development of functional groups in the ring of crown ethers in an attempt to enhance the selectivity and the stability of complexes of these ligands. 1-4 For example, incorporation of an amide linkage in a polyether macrocycle has been reported to modify the binding properties of the crown ether compounds to favor alkali and alkaline earth cations. 5-12 Also, it was reported that, macrocyclic ligands with amide functional groups as binding sites show strong and selective complexation towards noble metals, 13-15 and transition metals. 16 Some substituted macrocyclic tetraamides showed high selectivity for Ag + /Pd 2+ . 17,18 Moreover, macrocyclic amides were originally regarded as valuable intermediates for the synthesis of aza-crown ethers and related compounds. [19][20][21] In addition, some acyclic diamide ligands are known to show high ion selectivity towards lithium over sodium and other alkali metal ions. 22-24 Furthermore, there is an intensive development of the lariat crown ethers concept 25 which led to the synthesis of large numbers of side-armed crown compounds, designed for uses ranging from routine (polymer-supported PTC catalysts, separation/extraction reagents, etc.) to sophisticated (application as redox switches for membrane transport, synthetic cation-conducting channels, etc.). 26 Lariat crown compounds can mimic the cation binding behavior of naturally occurring ionophores such as valinomycin, 27 where the side arm can effectively participate in the coordination and lead to higher cation-binding affinities for the new compounds compared with the parent macrocycle containing no extra donor sites. 28,29 Keeping the above facts in mind, and in continuation of my interest in the synthesis of macrocyclic ligands with amide functional groups 30-33 and bis-macrocycles, 34 I am now engaged in a project directed towards the synthesis of 27-29-membered macrocyclic tetramides, acyclic diamides and their lariat derivatives with strong donor heteroatoms in the side arm as well as the bis-macrocyclic tetraamides aiming at the increase of their cation binding affinities. In this project a new methodology for the synthesis of the target macrocycles from activated bis(chloroacetamidophenoxy)alkanes and bis-phenolic compounds was used which are easily prepared from commercially available starting materials. Thus, reaction of 1, w-bis(2-aminophenoxy)alkane hydrochlorides 1a,b with chloroacetyl chloride in DMF a...
