Brent A. Banasik, C. Nadala, M. Samadpour
Jan 2, 2018
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Organic Preparations and Procedures International
Abstract
Polyethylene glycols (PEGs) are polyether chemical polymers of ethylene oxide that have many applications in industry, cosmetics, medicine and chemical research. Polymerizations of PEGs are categorized statistically by molecular weight ranging from small (300 g/mol) to large (10,000,000 g/mol) with many different derivatives, branching patterns and functional groups. Recently, PEGs have been popularized for their use in drug targeting effects and as drug-polymer conjugate linkers to increase bio-availability through slow release. One decidedly important PEG derivation is poly(ethylene glycol) methyl ether amine (mPEG-amine). This is comprised of a methoxy ether initiator, polymer body and is functionalized with a terminal primary amine, with an average molecular weight of 5000 g/mol. This polymer has been attached to various drugs (e. g. atropine and procaine) and enzymes (e. g. insulin). In our laboratory, mPEG5000-amine is used to prepare immunomagnetic particles, where it was found that antibodies conjugated to carboxy-magnetic beads were significantly more efficient once rigidified with mPEG-amine polymer. The present discovery stems from our need to prepare PEG derivatives with suitable functionalities for conjugation, bulk quantities (>50 grams/month), and at a reduced cost (commercial mPEG-5000-amine, $104 USD/g, Sigma Aldrich Catalogue, 2017). The ease with which this compound can be synthesized is an important requirement. The reaction sequence we now describe requires no column chromatography and no costly reagents or overly complex reaction set-ups. Accordingly, we selected poly(ethylene glycol) methyl ether, M.W. 5000 (1) as an economical starting material (mPEG-5000-OH, $0.18 USD/g, Sigma Aldrich Catalogue, 2017). In this simple reaction sequence (Scheme 1), chlorination of 1 (50 g) with SOCl2 and pyridine refluxed in toluene and precipitation with ether produced the corresponding alkyl chloride 2 in 95% yield. Chloride