New methods for the step growth polymerization of polyphosphoramidates with a P-N backbone

Abstract

Polyphosphoramidates are polymers containing P in the repeating backbone and one P-N bonds on P(v). It has been a topic of interest amongst researchers due to the wide range of applications possible. Similar biopolymers, which can be found in nature, with a P-O-P or P-O-C-P backbone with a nitrogen containing substituent off of the P. Polyphosphoramidates are vital because they are commonly used in gene delivery, and tissue engineering. 1 The main aim of this research project was to create poly(diphosphorodiamidate)s with repeating P-N backbones using a step growth method to determine the feasibility of linking the P and N units together into a chain. 2 One of the benefits to creating poly(diphosphorodiamidate) with exclusively P-N backbones is the acidic instability of the P-N bond which allows for facile degradation, a useful feature in using these polymers for biomedical applications. Furthermore, the synthetic approach allows for tuning of the polymer properties via the substituents on P and N. The three methods investigated were (i) a copper catalyzed oxidative cross-coupling reaction which uses oxygen as an oxidant and eliminates water, (ii) a condensation route which uses base to precipitate the eliminated HCl, and (iii) a lithiation reaction to abstract protons from secondary amines. The methods were explored through the use of model reactions to systematically grow the polymer. We found that the aim of copper catalyst was to synthesize N-P-N bonds but instead only P-N bonds were synthesized. Adding amines in excess towards the reaction also proved to be unsuccessful. The use of triethylamine in the second method yielded very positive results. NMR spectra and ESI-MS clearly prove that P-N and N-P-N compounds were synthesized. The third and final method saw the use of n-BuLi and LDA to lithiate P-N and N-P-N compounds and reacting them with phosphates to synthesize new compounds. Results show that lithiated P-N compounds reacted with phosphates yielded P-N-P bonds. The synthesis of asymmetric P-N-P bonds were also synthesized and shown to be possible. The success of lithiation and the synthesis of an asymmetric P-N-P bond prove that these molecules can be modified or altered according to our specification. The lithiation method all allowed for the synthesis of P-N-P-N-P compounds, increased length. Two different pathways were investigated by which P-N and N-P-N compounds were lithiated to synthesize a P-N-P-N-P compound. An attempt was made to synthesize a polymer but the NMR spectra was too inconclusive to proceed further. However, lithiation has shown that it can give rise to new compounds and worth further investigation. Keywords: Phosphoramidates, polyphosphoramidates, lithiation, diisopropylamide, triethylamine, copper catalyst, oxidative dehydrocoupling, phosphazene.