New Macrocyclic Ligands. XV. Isomeric, Benzylated and Xylyl-Linked Macrocyclic Ligands Derived from Selectively Protected N₃O₂-Donor Rings

Kyoung Ju Park, Jin-Ho Kim, George V. Meehan, Tomoko Nishimura, Leonard F. Lindoy, Shim Sung Lee, Ki-Min Park and Il Yoon

Abstract

Direct alkylation of the N₃O₂-macrocycle 1,12,15-triaza-3,4 : 9,10-dibenzo-5,8-dioxacycloheptadecane (1) with benzyl bromide in the presence of sodium hydrogen carbonate (in the respective molar ratios 1.0 : 2.0 : 1.3) led to a mixture of the mono-, bis-, and tris-N-benzylated derivatives (2)–(6) which were separated using their differential solubilities in warm acetone, fractional crystallization, coupled with column chromatography on silica gel. The X-ray structure of the symmetrical dibenzylated product (4) (as its HNO₃ salt) is described. In a parallel study, N-protection of (1) using 1.7 molar equivalents of di-tert-butyl dicarbonate (Boc)₂O yielded a mixture from which the symmetrical and unsymmetrical di-protected isomers (8) and (9) were separated by chromatography. Reaction of the symmetrically protected derivative (8) with benzyl chloride in the presence of excess sodium carbonate, followed by removal of the Boc groups, provided an alternative route to the corresponding (symmetrical) mono-N-benzylated macrocycle (2). A similar strategy, involving the use of α,α′-dibromo-p-xylene as a dialkylating agent, was employed to bridge a pair of N-diprotected macrocycles of type (8) or (9) to yield isomeric linked products (12) and (14), respectively. Deprotection of the resulting bis-macrocyclic products gave the 'central' and 'side' linked ligands (13) and (15), respectively.

Australian Journal of Chemistry 55(12) 773 - 778 (2002) doi:10.1071/CH02164