New diazadi(and tri)thia-21-crown-7 ethers containing 8-hydroxyquinoline side arms

A series of macrocyclic diazadi(and tri)thiacrown ethers containing two 5-substituent-8-hydroxyquinoline side arms have been synthesized from the corresponding macrocyclic diazadi(and tri)thiacrown ethers. The crown ethers were obtained by reduction of the proper macrocyclic di(and tri)thiadiamides by borane-tetrahydrofuran or by sodium borohydride-boron trifluoride ethyl etherate-tetrahydrofuran. The yields for the reduction of diamides by sodium borohydride-boron trifluoride ethyl etherate-tetrahydrofuran were higher than those by borane-tetrahydrofuran. The following four methods were used to prepare macrocycles bearing two 8-hydroxyquinoline side arms: (1) Mannich reaction with 8-hydroxyquinoline; (2) Reductive amination with 8-hydroxyquinoline-2-carboxaldehyde using sodium triacetoxyborohydride as the reducing agent; (3) Cyclization of N,N'-bis(8-hydroxyquinolin-2-ylmethyl)-1,2-bis(2-aminoethoxy)ethane (38) with bis(alpha-chloroamide) 5; and (4) A step-by-step process wherein macrocyclic trithiadiamide 11 was reduced by lithium aluminum hydride-tetrahydrofuran to the cyclic monoamide 36, which smoothly reacted with 5-chloro-8-hydroxyquinoline to produce monosubstituted-macrocyclic monoamide 39.