Synthesis of Macrocyclic Polymers Formed via Intramolecular Radical Trap-Assisted Atom Transfer Radical Coupling Andrew F. Voter, Eric S. Tillman,* Peter M. Findeis, and Scott C. Radzinski Department of Chemistry, Bucknell University, Lewisburg, Pennsylvania 17837, United States * S Supporting Information ABSTRACT: The synthesis of cyclic polystyrene (PSt) with an alkoxyamine functionality has been accomplished by intramolecular radical coupling in the presence of a nitroso radical trap. Linear α,ω-dibrominated polystyrene, produced by the atom transfer radical polymerization (ATRP) of styrene using a dibrominated initiator, was subjected to chain-end activation via the atom transfer radical coupling (ATRC) process under pseudodilute conditions in the presence of 2-methyl-2-nitrosopropane (MNP). This radical trap-assisted, intramolecular ATRC (RTA-ATRC) produced cyclic polymers in greater than 90% yields, possessing ⟨G⟩ values in the 0.8-0.9 range as determined by gel permeation chromatography (GPC). Thermal-induced opening of the cycles, made possible by the incorporated alkoxyamine, resulted in a return to the original apparent molecular weight, further supporting the formation of cyclic polymers in the RTA-ATRC reaction. Liquid chromatography-mass spectrometry (LC-MS) provided direct confirmation of the cyclic architecture and the incorporation of the nitroso group into the macrocycle. RTA-ATRC cyclizations carried out with faster rates of polymer addition into the redox active solution and/or in the presence of a much larger excess of MNP (up to a 250:1 ratio of MNP:C-Br chain end) still yielded cyclic polymers that contained alkoxyamine functionality. C yclic polymers present not only a synthetic challenge for polymer chemists but also offer a set of properties that often differ substantially from linear polymers. 1,2 The most well-known differences include reduced hydrodynamic radii, 3,4 increased glass transition temperatures, 5-7 and advantageous spatial orientations of pendent groups in terms of energy transfer applications. 8-11 Very recently, it has also been reported that macrocycles may be potentially useful as drug delivery vehicles, owing to increased circulation times and greater accumulation into tumors compared to otherwise identical linear polymers. 12-14 While cyclic polymers have been produced by both ring closing 15-17 and ring expansion methods, 18-20 there remains substantial interest in both new routes and improving existing methods of their production. Controlled radical polymerization techniques have found their way into synthetic routes of several macromolecular architec- tures, 21-25 and macrocycles are no exception. For example, a linear precursor polymer can be produced by atom transfer radical polymerization (ATRP) and then subjected to intra- molecular ring closure once the chain ends have been appropriately modified to be compatibly reactive. 26,27 Our group recently introduced a relatively simple method for producing cyclic polymers via a pseudodilute, intramolecular atom transfer radical coupling (ATRC) reaction of an α,ω- dibrominated precursor produced by ATRP using a dibromi- nated initiator (Scheme 1, bottom). 28 While this cyclization pathway could be adjusted to obtain near-quantitative yields of macrocycles, this closure reaction was necessarily carried out by the very slow addition of the linear precursor into a redox active solution, the principle reason being a ring closing ATRC Received: June 18, 2012 Accepted: July 31, 2012 Published: August 3, 2012 Letter pubs.acs.org/macroletters © 2012 American Chemical Society 1066 dx.doi.org/10.1021/mz300311p | ACS Macro Lett. 2012, 1, 1066-1070