Linear Polyethyleneimine: Optimized Synthesis and Characterization – On the Way to “Pharmagrade” Batches

Abstract The synthesis of linear polyethyleneimine (LPEI) by acidic hydrolysis of poly(2‐ethyl‐2‐oxazoline) is studied and optimized to reach the highest degree of hydrolysis within the shortest time range using a microwave synthesizer. In addition, the purification procedure is significantly improved; the fast batch processing combined with an excellent control of the actual heating time represents a well‐suited alternative to the conventional synthesis on the way to “pharmagrade” PEI. The developed protocol for the preparation of methyl and proton‐initiated LPEIs shows a high reproducibility, and the identity and purity of the LPEIs is proven by means of 1 H NMR and IR spectroscopy as well as MALDI‐TOF‐ and ESI‐Q‐TOF‐MS. magnified image