Scale-Up Procedure for the Efficient Synthesis of Highly Pure Cyclic Poly(ethylene glycol)

Poly(ethylene glycol) (PEG) is ideally suited for the synthesis of cyclic polymers. The cyclization reaction of PEG-via its tosylate intermediate is well established. We improved the cyclization reaction and obtained cyclic raw products in high yields. The quantities of linear precursor and higher molecular weight condensation byproducts were low. The latter byproducts can be removed efficiently by classical fractionation using chloroform/heptane as solvent/non-solvent pair. For the removal of linear precursor a process was developed which comprises the quantitative oxidation of alcoholic PEG chain ends to carboxyl groups and their subsequent removal with the help of a basic ion-exchange resin. The efficient cleaning processes allowed carrying out the ring closure reaction at relatively high concentrations and so increasing sample quantities. As a result, cyclic poly(ethylene glycol) was obtained in high purity up to a molecular weight of 20 000 g/mol in quantities of several grams. In order to monitor the oxidation reaction and to prove the absence of linear chains, a H-1 NMR characterization technique was developed, which is extremely sensitive up to high molecular weights.