Proton-ionizable Macrocycles Containing 1,2,4-Triazole and 4-Amino-1,2,4-triazole Subunits

Macrocycles 2 and Zb, containing a proton-ionizable 1,2,4triazole subcyclic unit, haveTeen obtained f m the appropriate 3.5disubstituted N-amino-1.2.4-triazoles and tetraethyleneglycol derivatives.The N-amino function was used as a protective group in the macrocyclization step.The method allowed the preparation of the chiral macrocycle 2 in three steps, from 2-lactic acid, in high optical purity and an overall yield of 16%.Triazolyl lone pairs of the macrocycles 2a and 2b, and of their N-aminated precursors &and lb, participate irthe cGplexation of Eu(fod1 and Pr(fodl , as well the crown ether moieties, but not N-amin8 groups whlch, when present, were found to be inside the cavity.Ion transport rates towards alkali-metal ions through a bulky chloroform phase were low and showed little selectivity.Crown compounds containing proton-ionizable functional groups have recently proved of interest in cmplexation, extraction, and transport of ions without requiring an independent counterion.The ionizable group can be attached to the ring as a pendant arm, or directly incorporated into the macrocyclic framework.Examples of the former approach, with carboxylic acids as the proton-ionizable functions have been studied mostly by Bartsch 61.,1r2whereas macrocycles containing an ionizable heterocyclic subunit within the cavity have been extensively developed more recently by Bradshaw, Izatt, and their coworkers at Brigham Young University.The heterocycles so far incorporated belong only to the 4-hydroxypyridine3-' and 1.2.4-triazole '-lo series, and the crowns synthesized were at first of the diester-polyether type (I) .3'6'8r9Despite the ease of access to structures of type (11 (high-dilution cyclization from the heterocyclic diesters or diacyl chlorides), diester-palyether heterocyclic c r m s were not devoid of scone inconvenients.Although they were found to form stable complexes with mines, annonium salts, and even water molecules, the proneness of the ester functions to hydrolyze in basic or acidic aqueous media make them unsuitable ' 47.