Scaling up the Synthesis of a Hydroxyquinoline-Functionalized p-tert-Butylcalix[4]arene

The optimization for an upscaled technical production of a lower rim-functionalized p-tert-butylcalix[4]arene, furnished with N4O4-donor ligands for superior solvent extraction separation between heavy and light lanthanides, is described. We demonstrate that reducing the polarity of the aprotic solvent in the (1,3)-distal esterification of p-tert-butylcalix[4]arene 1does not compromise the quality or yield of product 2. It was possible to use the technical quality educt 1, that is, without prior crystallization in toluene, in conjunction with reductions in reaction time and solvent volume. The raw diester product 2could be used, without prior recrystallization (which originally required 3 days) in the condensation reaction with hydrazine monohydrate to form hydrazide 3. Most importantly, the solvent volume required in the final condensation reaction of 3with 8-hydroxyquinoline-2-carboxaldehyde could be reduced by an order of magnitude by using chloroform. Not only was the final disubstituted product yield improved but also the purity of the final product could be ensured by preventing the precipitation of the intermediate monosubstituted product during reaction. The filtration characteristics of the final product, as well as its solvation properties during solvent extraction of lanthanides were significantly improved.