UNEXPECTED SELECTIVITY IN THE ALKYLATION OF POLYAZAMACROCYCLES

Reaction of equivalent amounts of free base polyazamacrocycles with an alkyl halide in a nonpolar, aprotic solvent affords the mono-N-alkylation product as its monohydrohalide salt in high yield with excellent selectivity. This unexpected selectivity has been explained in terms of the high affinity of the alkylated product for a single proton which attenuates the nucleophilicity of the remaining nitrogen atoms. Selectivity is dependent upon a number of factors including macrocycle ring size, solvent polarity, and the steric nature of the electrophile. The approach has allowed for a short, convergent route to bifunctional lanthanide chelators which are useful in therapeutic applications.