A convenient one-step synthesis of mono-N-functionalized tetraazamacrocycles

Abstract

N-Monoalkylated azamacrocycles are selectively obtained by reacting cyclam (1,4,8,11-tetraazacyclotetradecane) with equimolar amounts of Michael acceptors in chloroform in the presence of one equivalent of acid (TsOH). This chemoselective addition provides a general route to new mono-substituted azamacrocycles with various pendant groups such as sulfonic acid, ester, amide, nitrile, sugar or crown ether. The selectivity for monoaddition results from protonation of the azamacrocycles in the presence of one equivalent of acid.

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