Preparation of triazamacrocycles containing only secondary amine functions using both tosyl and boc protecting groups

1,8,15‐Triazacycloheneicosane ( 1 ); 1,9,17‐triazacyclotetracosane ( 2 ) and 1,10,19‐triazacycloheptacosane ( 3 ) were prepared by treating the appropriate N,N ‐bis(ω‐bromoalkyl)toluenesulfonamide 8–10 with the appropriate N,N ′‐ditosyl‐α,ω‐diaminoalkane 11–13 in dimethylformamide using sodium hydride as the base followed by phenol and 33% hydrobromic acid in acetic acid to remove the tosyl protecting groups. 2‐Allyloxymethyl‐4,11,18‐ triazaoxacycloheneicosane ( 4 ) was prepared in two ways. First, N,N′,N″‐ tritosylbis(hexamemylene)triamine ( 18 ) was treated with 2‐allyloxymethyl‐3‐oxa‐1,6‐hexanediol ditosylate ( 23 ) and cesium carbonate in dimethylformamide followed by sodium amalgam to remove the tosyl protecting groups. The second preparation of 4 was done by treating the tri‐BOC analog of 18 with 23 followed by hydrochloric acid in isopropyl alcohol to remove the BOC protecting groups. The overall yields of 4 using these two processes were very close.