Article Cite This: Macromolecules 2018, 51, 5713−5719 Alcohol- and Water-Tolerant Living Anionic Polymerization of Aziridines § ‡ § ‡ § † § Tassilo Gleede, , Elisabeth Rieger, , Lei Liu, Camille Bakkali-Hassani, Manfred Wagner, † † § § Stephané Carlotti, Daniel Taton, Denis Andrienko, and Frederik R. Wurm*, § Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany † Laboratoire de Chimie des Polymeres̀ Organiques (LCPO), Universitéde Bordeaux, IPB-ENSCBP, 16 av. Pey Berland, 33607 PESSAC Cedex, France *S Supporting Information ABSTRACT: Living anionic polymerization gives access to well-defined polymers, but it demands strict purification of reagents and solvents. This work presents the azaanionic polymerization (AAROP) of aziridines as a robust living polymerization technique, with the ease of controlled radical polymerizations. AAROP does not require inert atmosphere and remains living in the presence of large amounts of water or alcohols. Mesyl-, tosyl-, or brosyl-activated aziridines were polymerized with up to 100-fold excess of a protic impurity with respect to the initiator and still being active for chain extension. This allowed the preparation of polyols by anionic polymerization without protective groups, as only minor initiation occurred from the alcohols. The tolerance toward protic additives lies in the electron-withdrawing effect of the activating groups, decreasing the basicity of the propagating species, while maintaining a strong nucleophilic character. In this way, competing alcohols and water are only slightly involved in the polymerization, making living anionic polymerization an easy-to-conduct technique to well-defined polyamides and -amines. ■ INTRODUCTION dispersed phase and is the only strategy for conducting an ionic Living anionic polymerization (LAP) is the best technique to polymerization in the presence of protic solvents. Unfortu- control molar mass, chain-end fidelity, and to achieve well- nately, it cannot suppress termination or transfer reactions, as fi 1,2 reported for the aqueous emulsion polymerization of cyclic de ned (co)polymers. It also provides a precise way for 11,12 13 introducing of heteroatoms in the polymer backbone.3,4 LAP siloxanes or phenyl glycidyl ether, leading to oligomers. Similar approaches of anionic polymerizations of α-carbonyl is, however, sensitive to protic impurities and, in many cases, 14 15 oxygen. Thorough drying of reagents and solvents, high- acids or glycidol in the presence of water bypass the typical Downloaded via MPI POLYMERFORSCHUNG on August 27, 2018 at 12:52:19 (UTC). vacuum, and inert gas purifications make it much more difficult anionic polymerization mechanism (e.g., by monomer- to carry out than, for example, a controlled radical polymer- activation). Organocatalyzed polymerization also circumvents See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. ization.5,6 It would therefore be beneficial to combine the typical characteristics of anionic polymerization, and recently, robustness of the controlled radical polymerization with the we demonstrated that carbenes allow NH-selective initiation of precision of the living ionic polymerization. activated aziridines with 2-methylaminoethanol as initiator to synthesize polysulfonamides with a single terminal hydroxyl Ionic polymerizations can be terminated by moisture, protic 16 7 group for further modifications. solvents, or CO2. In the epoxide polymerization, water or fi alcohols act as initiator, and only low-molecular-weight We present the rst living anionic polymerization that − products are obtained.8 10 Importantly, protic impurities at proceeds in open air and in the presence of large amounts of concentrations above the initiator concentration inhibit the protic impurities, such as water and alcohols. The azaanionic ring-opening polymerization (AAROP) is chosen as a unique propagation, which makes protecting groups essential (e.g., for fi alcohols). technique to access well-de ned polysulfonamides or -amines A robust LAP that can tolerate protic solvents, especially (Scheme 1). The exceptional tolerance toward water and alcohols during water, while maintaining the living character, is not known. To fi circumvent the demanding conditions of LAP, emulsion the polymerization allows, for the rst time, the ability to work polymerization elegantly exploits the hydrophobic nature of monomers and polymers and separates the active chain end Received: June 21, 2018 from the protic aqueous phase. As a result, the polymerization Revised: July 10, 2018 takes place at the interface or inside of the hydrophobic Published: July 23, 2018 © 2018 American Chemical Society 5713 DOI: 10.1021/acs.macromol.8b01320 Macromolecules 2018, 51, 5713−5719 Macromolecules Article Scheme 1. Schematic Overview of the A-AROP with Protic Additives Showing the Dormant Polymer Species and Active Polymer Species without strict inert gas conditions and to use solvents without pKb-value of the growing chain end and the propagation rate vigorous purification. The tolerance toward alcohol groups constants. For sulfonyl-aziridines, both factors can be tuned by further allows polymerizing monomers containing unprotected the choice of the activating group that influences the basicity of hydroxyl groups to synthesize polyols without using any the azaanionic chain end and at the same time the propagation protective groups (see below). Such polyols might be rates and thus controls the chance of initiation of protic interesting for the preparation of polyurethanes or for impurities in the reaction mixture. We selected three different antifouling surface coatings. In contrast to the robustness of monomers, in order of their increasing propagation rates and the tosylated and mesylated aziridines in this report, Rupar and different nucleophilicity of the chain end: 2-methyl-N-mesyl- co-workers recently showed that when using aziridines with 2- aziridine (MsMAz, 1) 2-methyl-N-tosylaziridine (TsMAz, 2), nitrosulfonyl activation group, even small amounts of 2-methyl-N-brosylaziridine (BsMAz, 3)(Scheme 1).27 Mono- nucleophilic impurities can cause spontaneous polymer- mers 1−3 have all been previously shown to undergo AAROP ization.17 This further underlines the chemical versatility of under an inert environment. sulfonamide-activated aziridines. Polysulfonamides, prepared from the AAROP of sulfonyl- ■ RESULTS AND DISCUSSION activated aziridines, have been first polymerized via living 18 Strikingly, we found that polymerizations could be carried out polymerization in 2005. The monomer family has been in open vials (SI, Section D) in DMF (without any purification significantly expanded since then,19,20 and new methods were Đ ≤ − or drying), resulting in narrowly distributed PAz ( 1.11, Mn developed to polymerize sulfonamides via organocatalytic21 24 25−27 28 = 4400), which remained living and allowed further chain or anionic polymerization in solution and in emulsion. extension, proving the living nature under such wet conditions, After cleavage of the sulfonyl groups, polysulfonamides are an 26,29 without recognizable initiation of water and achieving the alternative pathway to linear polyethylene imine (LPEI), targeted degree of polymerization (Figure S31 and SI, Section which, together with hyperbranched PEI (hbPEI), is a standard 30−33 F), polyaziridines with molar masses of Mn = 4400 to 3600 synthetic cationic transfection agent. were obtained by varying the amount of added water from 1 to The role of the sulfonamide activating groups is 2-fold: they 27 100 equiv. Additionally, the AAROP followed living character- control the microstructure of copolymers, as well as regulate istics in reactive solvents, which would inhibit other anionic Đ the nucleophilicity and basicity of the active chain end. The polymerizations (P(2)50 was prepared in acetone ( = 1.16, Đ latter allows tuning reaction tolerance to additives, protic Mn = 6400), ethyl acetate ( = 1.18, Mn = 3700) and iPrOH Đ solvents, or nucleophilic functionalities in the monomers, ( = 1.23, Mn = 2500). The low dispersity from the polymers which is the focus of this contribution. We believe that the ease prepared in open air or such solvents prove that the AAROP is ff “ of conducting a living anionic polymerization to access well- una ected by CO2 and O2 remains living in non-conven- defined polyamines will contribute to diverse fields, such as tional” solvents of anionic polymerization (Figure S25, S30, gene delivery or the preparation of chelating agents or polyols S31). for polyurethane fabrication. In order to understand the influence of chain-end and To control the polymerization of sulfonyl aziridines, all monomer reactivity on the control of the A-AROP, (1) and previously published articles highlighted the necessity to (2) were polymerized in the presence of protic additives. strictly avoid moisture, impurities and the protection of Different amounts (1−1000 equiv relative to the initiator) of nucleophilic monomer functionalities. Preparation of the water (H2O), methanol (MeOH), ethanol (EtOH), and experiment was thus conducted in a glovebox or with Schlenk isopropanol (iPrOH), which usually act as transfer or techniques under an inert gas atmosphere.21,22,25,26 Concern- terminating agents for other anionic polymerizations, were ing the water content of solvents, an in situ distillation from added to the reaction medium. The maximum amount of each elemental sodium or calcium hydride is established for anionic additive was limited