Aziridines and Azetidines: Building Blocks for Polyamines by Anionic and Cationic Ring-Opening Polymerization Polymer Chemistry
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Polymer Volume 10 Number 24 28 June 2019 Pages 3233–3402 Chemistry rsc.li/polymers ISSN 1759-9962 REVIEW ARTICLE Paul A. Rupar, Frederik R. Wurm et al. Aziridines and azetidines: building blocks for polyamines by anionic and cationic ring-opening polymerization Polymer Chemistry View Article Online REVIEW View Journal | View Issue Aziridines and azetidines: building blocks for polyamines by anionic and cationic ring-opening Cite this: Polym. Chem., 2019, 10, 3257 polymerization Tassilo Gleede,a Louis Reisman, b Elisabeth Rieger,a Pierre Canisius Mbarushimana,b Paul A. Rupar *b and Frederik R. Wurm *a Despite the difficulties associated with controlling the polymerization of ring-strained nitrogen containing monomers, the resulting polymers have many important applications, such as antibacterial and anti- microbial coatings, CO2 adsorption, chelation and materials templating, and non-viral gene transfection. This review highlights the recent advances on the polymerizations of aziridine and azetidine. It provides an overview of the different routes to produce polyamines, from aziridine and azetidine, with various Received 19th February 2019, structures (i.e. branched vs. linear) and degrees of control. We summarize monomer preparation for cat- Accepted 3rd May 2019 ionic, anionic and other polymerization mechanisms. This comprehensive review on the polymerization Creative Commons Attribution 3.0 Unported Licence. DOI: 10.1039/c9py00278b of aziridine and azetidine monomers will provide a basis for the development of future macromolecular rsc.li/polymers architectures using these relatively exotic monomers. 1. Introduction Despite being structural anlogs with comparable ring strain (Fig. 1), aziridine and oxirane have very different polymeriz- This article is licensed under a ation chemistries. Oxirane can be polymerized via a variety of a Max-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128 Mainz, mechanisms, including cationic ring-opening polymerization Germany. E-mail: [email protected] 1 2,3 bDepartment of Chemistry and Biochemistry, The University of Alabama, Tuscaloosa, (CROP) and anionic ring-opening polymerization (AROP) to Open Access Article. Published on 13 May 2019. Downloaded 7/1/2019 10:43:31 AM. Alabama 35487-0336, USA. E-mail: [email protected] form linear poly(ethylene oxide) (PEO) with high degrees of Tassilo Gleede studied Louis “Chip” Reisman III gradu- Chemistry at the Johannes ated with a B.S. in Chemistry Gutenberg-Universität Mainz from Mercer University in 2014, (Germany) and received his where he conducted research diploma degree in 2015 includ- with Prof. Adam Kiefer and ing a research stay at Prof. Caryn Seney. He recently the Brookhaven National completed his Ph.D. at the Laboratory, (New York, USA) University of Alabama under the developing positron emission supervision of Prof. Paul Rupar radiotracers for human and investigating the anionic ring- plant studies in the group of opening polymerizations of sulfo- Prof. Joanna Fowler. He joined nyl-activated aziridines and aze- Tassilo Gleede the Max Planck Institute for Louis Reisman tidines. Chip will be continuing Polymer research, Mainz, in the his career in chemistry by study- group of Dr F. R. Wurm for his PhD thesis. His research, supported ing sustainable polymers as a postdoctoral researcher in the lab of by the Deutsche Forschungsgesellschaft (DFG), focuses on the Prof. Marc Hillmyer at the University of Minnesota. living anionic polymerization of activated aziridines and their copolymerization behavior with other reactive monomers such as ethylene oxide. This journal is © The Royal Society of Chemistry 2019 Polym. Chem.,2019,10, 3257–3283 | 3257 View Article Online Review Polymer Chemistry when compared to PEO and related polymers.6,73 Polyethers, especially PEO, are produced on the scale of several million tons per year and found in many everyday applications,74 while linear polyaziridines are barely used today (Fig. 2).75 This is unfortunate as the potential structural diversity of aziridines is notably greater than oxygen-containing analogs as substitution on aziridines can occur both at the carbon and nitrogen atoms of aziridine. Use in non-viral gene-transfection has sparked renewed academic and pharmaceutical interest in PEI, especially LPEI. Fig. 1 Chemical structures of aziridine, azetidine, oxirane, and oxetane LPEI is attractive compared to hbPEI as it can have a well- and their ring-strains.10,11 defined architecture with narrow molecular weight distri- butions. This makes it ideal for structure–property relationship studies and its incorporation into polymer–drug conjugates. control. In contrast, aziridine can only polymerize via CROP However, since LPEI cannot be made from aziridine, it is to produce (hyper)branched polyethylenimine (hbPEI) instead synthesized indirectly via polyoxazolines.14 Typically, with little control over molecular weight, dispersity, and 2-oxazoline-based monomers, such as 2-ethyl-2-oxazoline, – microstructure.4 8 The situation is similar with azetidine in the presence of cationic initiators, such as stannic chloride (Fig. 1), the nitrogen analog of oxetane, which also only and boron trifluoride etherate, undergo a controlled – forms hyperbranched poly(trimethylenimine) (hbPTMI) via CROP.76 78 Conversion of poly(2-oxazoline)s to LPEI can occur – CROP.9 under acidic or alkaline conditions (Scheme 1).79 81 However, Even with the challenges in controlling its polymerization, this route to LPEI has drawbacks in that the polymerization is ffi Creative Commons Attribution 3.0 Unported Licence. the high amine density of hbPEI lends its use in a wide range di cult to control when targeting high degrees of polymer- – of applications including non-viral gene-transfection,7,12 44 ization and it is challenging to achieve quantitative removal of 37,45–52 53–63 7 anti-microbial and anti-viral coatings, CO2 capture, the acyl groups. flocculation of negatively charged fibers in paper-making The new appreciation for the applications of LPEI and un- – industries,64 66 metal chelation in waste water treatments,67 as resolved challenges associated with azirdine polymerization additives for inkjet paper production,16 as electron injection means that it remains an active area of research. Since there layers in organic light-emitting diodes,68,69 and materials tem- have been no recent reviews on aziridine polymerizations plating.70 As such, hbPEI is made industrially, initially under (Kobayashi6 was published in 1990), we feel that such a review the commercial name Polymin, and today is marketed under is warranted. This is especially true given the recent break- This article is licensed under a the trade name Lupasol® by BASF.71 Aziridine is produced at a throughs in the AROP of activated aziridines, which have yet to rate of ∼9000 t/a (2006),72 where, due to its toxicity, it is be summarized in the literature. usually converted directly into its nontoxic intermediates and This review gives a comprehensive overview on the synthesis Open Access Article. Published on 13 May 2019. Downloaded 7/1/2019 10:43:31 AM. branched polymers. of polymers based on both aziridines and azetidines. We have The lack of control over aziridine polymerizations has sig- chosen to include azetidines in this review as their polymeriz- nificantly limited the research of linear PEI (LPEI), especially ation chemistry closely mirrors that of aziridines and the Elisabeth Rieger was born in Pierre Canisius Mbarushimana 1985 in Rosenheim (Germany). studied chemistry ay Lyon She studied biomedical chem- College (US) and graduated with istry at the Johannes Gutenberg a B.Sc. degree in 2013. After – Universität Mainz (Germany), that, he pursued graduate including a stay at the studies in analytical chemistry at Brookhaven National Laboratory the University of Alabama and on Long Island (USA) in the completed his PhD in the Rupar group of Prof. Joanna Fowler. group in 2018. His research She finished her PhD in the interests consist of the anionic group of Dr F. R. Wurm at the ring-opening polymerization of Max Planck Institute for Polymer activated aziridines. Currently, Elisabeth Rieger Research in Mainz in 2018. Her Pierre Canisius he holds a senior scientist posi- research focused on the sequence Mbarushimana tion at Jordi Labs in controlled anionic polymerization of activated aziridines moni- Massachusetts. tored by real-time NMR. 3258 | Polym. Chem.,2019,10, 3257–3283 This journal is © The Royal Society of Chemistry 2019 View Article Online Polymer Chemistry Review Creative Commons Attribution 3.0 Unported Licence. Fig. 2 Epoxides vs. aziridines. General polymerization scheme and important facts about both material classes. resulting polymers are structurally similar to that of aziridine conclude with routes to aziridine and azetidine copolymers and derived polymers. We first discuss the early literature on the highlight the possibilities for functionalization or preparation CROP of aziridines and azetidines. Next, we highlight recent of various polyamine structures. Spaced through the review are work on the AROP and organocatalytic ring-opening polymeriz- summaries of the synthetic methods to synthesize the aziridine ation (OROP) of N-sulfonyl aziridines and azetidines and strat- and azetidine monomers. Detailed analysis of the literature on This article is licensed under a egies to produce linear polyamines from these monomers. We gene-transfection can be found elsewhere.84 This review will Open Access Article. Published on 13 May 2019. Downloaded