Dendrimers repetitive synthesis

Keywords Dendrimers, linear aliphatic molecules, oligophenylenes, repetitive synthesis, supramolecular chemistry. 

Because of their high molecular weight and their defined structure, dendrimers offer themselves for studying the expression of chirality on a macromolecular level. The construction of configurationally uniform macromolecules is otherwise a complex task but can be achieved more easily with dendrimers because of repetitive synthesis from identical (chiral) building blocks. Comparison of optical rotation values and circular dichroism (CD) spectra should demonstrate what influence there is of the chiral building blocks on the structure of the whole dendrimer. 

In 1978, we reported the repetitive synthesis of noncyclic and cyclic (so called nonskid chainlike ) polyaza compounds, which were the first examples of cascade molecules (Scheme 1). Since that time, dendrimers have gained widespread attention in organic, as well as in inorganic2,3 and physical chemistry.4 In 1992, De Gennes received the Nobel prize in physics for his studies on chaos and fractals. His results are relevant for the molecular design of cascade polymers especially in their three-dimensional growth. 

Mekelburger HB, Rissanen K, Voegtle F. 1993. Repetitive synthesis of bulky dendrimers a reversibly photoactive dendrimer with six azobenzene side chains. Chem Ber 126(5) 1161 1169. 

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. 

Thus, the synthesis of dendrimers consists of two constantly repeating reaction steps. The first step deals with the linkage of a branching unit to two other units - the construction step. In the second reaction, groups are transformed, so that they can react further - the activation step. This procedure is also referred to as an iterative (repetitive) strategy.131... 

Dendrimer synthesis involves a repetitive building of generations through alternating chemistry steps which approximately double the mass and surface functionality with every generation as discussed earlier [1-4, 18], Random (statistical) hyperbranched polymer synthesis involves the self-condensation of multifunctional monomers, usually in a one-pot single series of covalent formation events [31], Random hyperbranched polymers and dendrimers of comparable molecular mass have the same number of branch points and terminal units, and any application requiring only these two characteristics could be satisfied by either architectural type. Since dendrimer synthesis requires many defined synthetic and process purification steps while hyperbranched synthesis may involve a one-pot synthetic step with no purification, the dendrimers will necessarily be a much more expensive material to produce. 

The concept of repetitive growth with branching was first reported in 1978 by Vogtle [4] (University of Bonn, Germany) who applied it to the construction of low molecular weight amines. This was followed closely by the parallel and independent development of the divergent, macromolecular synthesis of true dendrimers in the Tomalia Group [5,6] (Dow Chemical Company). The first... 

The divergent method is illustrated in Fig. 2-22 for the synthesis of polyamidoamine (PAMAM) dendrimers [Tomalia et al., 1990]. A repetitive sequence of two reactions are used—the Michael addition of an amine to an a,P-unsaturated ester followed by nucleophilic substitution of ester by amine. Ammonia is the starting core molecule. The first step involves reaction of ammonia with excess methyl acrylate (MA) to form LXIII followed by reaction with excess ethylenediamine (EDA) to yield LXIV. LXV is a schematic representation of the dendrimer formed after four more repetitive sequences of MA and EDA. 

Majoral et al.1114 reported the facile divergent synthesis of a novel P-dendrimer series (Scheme 4.27). Treatment of the sodium salt of 4-hydroxybenzaldehyde (100) with trich-lorothiophosphorus(V) gave the trialdehyde 101, which, when treated with three equivalents of the hydrazine derivative 102, quantitatively afforded the first generation dendrimer 103 possessing six P-Cl bonds juxtaposed for repetition of the sequence. Construction of the second, third, and fourth (104) generations followed this iterative sequence. Key features of this sequence included no protection-deprotection procedures and the... 

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