Effective synthesis of new benzo-fused macrocyclic and thiamacrocyclic dilactams and related pyrazolo-fused macrocycles

In the current study, we examined the synthetic potential of new bis(aldehydes), linked to aliphatic spacers via phenoxy linkage, as versatile building blocks for the synthesis of new macrocyclic dilactams. The target macrocycles were prepared, in 65%–72% yields, by the cyclocondensation of N,N′-(alkane-1,ω-diyl)bis(2-cyanoacetamide) with the appropriate bis(aldehydes) in dioxane in the presence of few drops of piperidine at reflux for 4 h. Using the precursors for bis(2-cyanoacetamide), linked to aliphatic cores via thioethers, a new series of thiamacrocyclic dilactams were prepared, in 60%–66% yields, under the previous reaction conditions and at reflux for 5 h. Next, we examined the synthetic potential of the new dilactams derivatives as key synthons for the preparation of new dipyrazolo-fused macrocycles. After treating the appropriate dilactams with hydrazine hydrate in DMF at reflux for 6 h, the previous macrocycles were prepared in 50%–57% yields.