Catalytic etherification of N-protected tris(hydroxymethyl)aminomethane for the synthesis of ligands with C3 symmetry

The synthesis of two nonadentate ligands based on a N,N-dibenzylated-tris(hydroxy)methylaminomethane framework is described. The key step consists in tris-etherification of the precursor with elaborated pyridine and bipyridine derivatives and this was greatly improved by the introduction of catalytic amounts of tetrabutylammoniumiodide to the reaction mixture in DMF at room temperature. Analysis of the alkylation rates and an X-ray crystal structure of a bis-alkylated intermediate strongly support the presence of a tight intramolecular hydrogen bond, preventing a fast third alkylation step. The two acidic ligands were successfully prepared by combining a sequence of carboalkoxylation and hydrolysis of the corresponding esters. Both ligands react with europium and terbium chloride salts to generate water luminescent mononuclear complexes.