PAMAM dendrimers Michael addition reaction

Since mild activation conditions appear to be important, a number of solution activation conditions were tested. PAMAM dendrimers are comprised of amide bonds, so the favorable conditions for refro-Michael addition reactions, (low pH, high temperature and the presence of water) may be able to cleave these bonds. Table 1 shows a series of reaction tests using various acid/solvent combinations to activate the dendrimer amide bonds. Characterization of the solution-activated catalysts with Atomic Absorption spectroscopy, FTIR spectroscopy and FTIR spectroscopy of adsorbed CO indicated that the solution activation generally resulted in Pt loss. Appropriate choice of solvent and acid, particularly EtOH/HOAc, minimized the leaching. FTIR spectra of these samples indicate that a substantial portion of the dendrimer amide bonds was removed by solution activation (note the small y-axis value in Figure 4 relative... 

Several studies have shown that the amide bonds that comprise the PAM AM dendrimer backbone are relatively unstable and begin decomposing at temperatures as low as 75 °C [45,50,52,56-58]. The low onset temperature of dendrimer decomposition is not surprising given that PAMAM den-drimers can undergo retro-Michael addition reactions at temperatures above 100 °C [16]. Far more forcing conditions are required to fully activate the catalysts, which suggests that the dendrimer decomposes into various surface species that continue to poison the nanoparticle surfaces. 

The first and still dominant route to synthesize PAMAM dendrimers is via the divergent growth approach as reported by Tomalia etal in 1985. It involves a Michael addition reaction between a core, comprising primary amines, and an excess of methyl acrylate (Figure 17). Once the reaction has reached completion, an aminolysis step of the methyl esters with an excess of a-alkanediamines yields the first-generation PAMAM... 

The synthesis of radially layered poly(amidoamine-organosilicon) (PAMAMOS) copolymeric dendrimers starts from amine terminated PAMAM dendrimers, which, in turn, are obtained by a well-known excess-reagent divergent growth method that involves a reiterative sequence of (a) Michael addition reactions of methyl acrylate (MA) to primary amines, and (b) amidation of the resulting methyl ester intermediates with ethylenediamine (EDA), as shown in Reaction Scheme 1 (39-41). These PAMAM dendrimers are commercially obtained from Dendritech Inc., (Midland, MI) and they can be used for PAMAMOS preparation without any further purification. The synthesis then involves another Michael addition reaction, this time of a silylated acryl ester, such as (3-acryloxypropyl)dimethoxymethylsilane, as shown in Reaction Scheme 2 (4). 

PAMAM dendrimers are synthesized in a multistep process. Starting from a multifunctional amine (for example ammonia, ethylenediamine, or tris(2-amino-ethyl)amine) repeated Michael addition of methylacrylate and reaction of the product with ethylenediamine leads to dendrimers of different generation numbers [1,9]. Two methylacrylate monomers are added to each bifunctional ethylenediamine generating a branch at each cycle. Unreacted ethylenediamine has to be completely removed at each step to prevent the initiation of additional dendrimers of lower generation number. Excess methylacrylate has also to be removed. Bridging between two branches of the same or of two different dendrimers by ethylenediamine can also be a problem, and has to be avoided by choosing appropriate reaction conditions. 

Crosslinking of amine- or hydroxy-terminated PAMAM dendrimers using cyclic anhydride - amine or cyclic anhydride - hydroxy addition reactions was employed for preparation of crosslinked thin films of very low permeability [73], Polyanhydrides, such as maleic anhydride-methyl vinyl ether copolymers, were used as crosslinking components. In the case of amine-terminated PAMAM, crosslinking and chemical stability were further increased by imidization of the maleamic acid groups retro-Michael eliminations were followed by Michael additions to further crosslink the film. 

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. 

The Michael addition is a very efficient reaction that has been widely applied for dendrimer synthesis due to a small amount of side reactions and mild reaction conditions, poly (amido amine) (PAMAM) or poly(propylene imine) (PPI) dendrimers are two well-known examples that rely on the Michael addition. Long et al. reviewed the synthetic approaches to linear, cross-linked, and branched polymers via step-growth Michael polyaddition.Thermally stable, high-Tg poly... 

---