The synthesis of novel oxa-azamacrocycles

Novel protected oxa-azamacrocycles 6a-f, 7a,c-f have been prepared by direc t alkylation reaction between alpha,omega-bis[(2-mesitylsulfonyl)aminooxy]a lkanes 2a-c and alpha,omega-bis(tosyl)alkanediols 3a,b in the presence of K 2CO3 to give a mixture of the 1:1 (small macrocycles 6a-f) and 2:2 (large m acrocycles 7a,c-f) adducts. Another method involved the reaction between bi s (sulfonyl)amides 2a,b and omega-bromoalkanols 4a,b to give bis-alkanols 5 a,b which were subsequently condensed with 2a,b under Mitsunobu conditions to give solely large macrocycles 7a,d in high yields. Macrocycle 7d was dep rotected with HBr/HOAc to yield 8 as the tetrahydrobromide salt which was c onverted into its free base with methanolic KOH.