Polypropylene imine dendrimers synthesis

The history of dendrimer chemistry can be traced to the foundations laid down by Flory [34] over fifty years ago, particularly his studies concerning macro-molecular networks and branched polymers. More than two decades after Flory s initial groundwork (1978) Vogtle et al. [28] reported the synthesis and characterization of the first example of a cascade molecule. Michael-type addition of a primary amine to acrylonitrile (the linear monomer) afforded a tertiary amine with two arms. Subsequent reduction of the nitriles afforded a new diamine, which, upon repetition of this simple synthetic sequence, provided the desired tetraamine (1, Fig. 2) thus the advent of the iterative synthetic process and the construction of branched macromolecular architectures was at hand. Further growth of Vogtle s original dendrimer was impeded due to difficulties associated with nitrile reduction, which was later circumvented [35, 36]. This procedure eventually led to DSM s commercially available polypropylene imine) dendrimers. 

In 1993 we have published a method which met most of these requirements and for the first time allowed for the large-scale synthesis of dendrimers [2], Since that time, each of the steps have been optimized in the reaction scheme. In this chapter, we present state-of-the-art procedures for the large-scale production of the polypropylene imine) dendrimers. 

Dendrimers are regarded as macromolecules with a structural precision comparable to proteins or organic compounds. Accurate analysis and quantitative identification of side products are required to optimize and adjust the reaction conditions for the synthesis of DAB-dendr-(NH2)n and DAB-dendr-(CN)n. Therefore, it is a prerequisite to characterize the products obtained unambiguously. To achieve complete molecular characterization of the polypropylene imine) dendrimers and the possible side-products, NMR- and IR-spectroscopy, HPLC, GPC and electrospray mass spectrometry are used. 

Brabender-van den Berg EMMD, Meijer EW (1993) Polypropylene imine) dendrimers-large-scale synthesis by heterogeneously catalyzed hydrogenations. Angew Chem Int Ed Engl 32 1308-1311... 

Scheme 14.2 Divergent synthesis of polypropylene imine) dendrimers (A and B) and possible side reactions resulting in defects and chain termination (C missed Michael additions D cyclisation).

Polypropylene imine) dendrimers (see Scheme 1 for structure) have been constructed step by step onto an amine functionalized polystyrene [38, 130, 131]. The challenge in this synthesis is finding conditions for the polypropylene imine) synthesis under which the low MW polystyrene (MW=3200) is soluble [38]. Similar poly(imine) dendrimers with carboxylic acid end groups have also been prepared [130]. The polypropylene imine) dendrimer has also been synthesized on an amino-terminated poly(2-methyl-2-oxazoline) [132]. 

Meijer and co-workers also used a divergent dendrimer synthesis to prepare AB diblock structures (Figure 7.13B) in which the polystyrene linear block is used to initiate growth of the polypropylene imine) dendritic block [45], An amino end group had to be introduced in the polystyrene as a core for subsequent growth of the dendritic fragment via an iterative protocol of sequential... 

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