Introduction of Terminal Azide and Alkyne Functionalities in Polymers

Dr. Joost A. Opsteen

Material Matters 2008, 3.3, 66.

Dr. Joost A. Opsteen Institute for Molecules and Materials Radbound University Nijmegen, The Netherlands

Click chemistry, and the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in particular, is a powerful new synthetic tool in polymer chemistry and material science. Success of the CuAAC in the engineering of (bio)polymer architectures stems, in part, from the possibility of introducing the required azide and alkyne functionalities at predetermined locations in macromolecular building blocks, is a result of advances in controlled polymerization techniques.

Controlled polymerizations result in polymers with well-defined end-groups, which can be subsequently converted into terminal azide and alkyne functionalities. Examples demonstrating conversion of the hydroxyl terminus of poly(ethylene glycol) (PEG) ( 295906) into an azide or an alkyne terminal polymer are depicted in Scheme 1. The azide functionality can be introduced by treating the alcohol with pyridine ( 676772) and tosyl chloride (TsCl) ( 240877) to afford the easily substitutable tosyl-activated alcohol, which is subsequently reacted with sodium azide (NaN3) ( 438456) to provide the terminal azide polymer. The alkyne is introduced on PEG via esterification with pentynoic acid ( 232211) in the presence of 1-ethyl-3- (3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) ( E7750) and 4-dimethylaminopyridine (DMAP) ( 522805) (Scheme 1).¹

Scheme 1. Transformation of the hydroxyl terminus of poly(ethylene glycol) into azide and alkyne functionalities.

The atom transfer radical polymerization (ATRP) process generally yields halide-terminated polymers and therefore this method can be exploited for further functionalization due to the inherent susceptibility of halides to undergo nucleophilic substitution reactions.² For example (Scheme 2), after ATRP, the terminal bromide of polystyrene (PS) can be quantitatively exchanged for an azide moiety by treatment with azidotrimethylsilane (Me₃SiN₃) ( 155071) and tetrabutylammonium fluoride (TBAF) ( 216143).^1,3

Scheme 2. Polystyrene prepared by ATRP contains a bromide end group which can be readily substituted for an azide.

Success of post-polymerization end-group modification procedures depends on suppression of termination reactions during polymerization. Additionally, the end-group manipulation must be quantitative to prevent incomplete introduction of the desired functionality. Functional initiators can be useful in implementing a quantitative introduction of the functionality, with the condition that no side reactions occur during the polymerization process.

An example of using a functional initiator to incorporate an alkyne functionality is shown in Scheme 3. The alkyne bearing α-bromoester initiator is protected with a TIPS protecting group to prevent complexation with the copper-catalyst during ATRP. The azide can be used for a “click” reaction and the TIPS group can be removed following polymerization, allowing the alkyne to be used for a second “click” reaction.⁴

Scheme 3. Synthesis of heterotelechelic poly(tert-butyl acrylate) comprising both a protected alkyne and an azide terminus.

References

1. Opsteen JA, van Hest JCM. 2005. Modular synthesis of block copolymers via cycloaddition of terminal azide and alkyne functionalized polymers. Chem. Commun..(1):57. https://doi.org/10.1039/b412930j

2. Coessens V, Pintauer T, Matyjaszewski K. 2001. Functional polymers by atom transfer radical polymerization. Progress in Polymer Science. 26(3):337-377. https://doi.org/10.1016/s0079-6700(01)00003-x

3. Matyjaszewski K, Nakagawa Y, Gaynor SG. 1997. Synthesis of well-defined azido and amino end-functionalized polystyrene by atom transfer radical polymerization. Macromol. Rapid Commun.. 18(12):1057-1066. https://doi.org/10.1002/marc.1997.030181209

4. Opsteen JA, van Hest JCM. 2007. Modular synthesis of ABC type block copolymers by ?click? chemistry. J. Polym. Sci. A Polym. Chem.. 45(14):2913-2924. https://doi.org/10.1002/pola.22047