Macromonomers see their origins in the double-stage convergent method described first in 1991. These building blocks allow the synthesis of higher generation dendrimers in fewer steps and with narrower dispersity. Dendrimers based on a number of monomer units, including phenylacetylene, polyesters, polyamides, and oligo(thienylethynylene)s, have been synthesized using this method. However, despite the advantages of this synthetic route, the method is used much less often than the standard divergent or convergent strategies.
Our recent success with large-scale, divergent routes to low-generation triazine dendrimers led us to examine the use of a so-called macromonomer to acccess larger structures. In addition, the method reported installs these two generation using a two-step-per-cycle strategy.
The routes to dendrimers, in the extreme, rely on convergent, divergent, or combined convergent/divergent approaches. These routes have their own advantages and disadvangtes. Divergent methods have successfully been used to synthesize high generation dendrimers, notably PAMAM, up to generation 10. Historically, the products of these syntheses have been difficult to define. Here, each generation requires the successful reaction of increasingly large numbers of peripheral groups. Intuition suggests that the limits of unique monodispersity are defined by the limits of the analytical methods employed. Still, the route has been successfully employed by many including recent examples of phosphorous containing dendrimers from Caminade and Majoral, and the thiolene dendrimers from Hawker. Recently, we described a divergent route to generation five triazine dendrimers, that relied on a three-steps-per-generation iterative cycle. Both poor reaction yields and the onset of impurities arose at generations 4 and 5 due in part to solubility issues.
Alternatively, the convergent method pioneered in 1990 by Hawker and Fréchet offers advantage over the divergent approach in that fewer reactions—often the coupling of two dendrons—are required during each reaction. However, this approach is often limited to lower generation dendrimers because steric hinderance increases with each increasing generation, notably when two or more dendrons are attached to a core in the final step. Still, the convergent approach has been accepted as a useful method for synthesizing polyamides, polyesters, poly(ether ketones), carbohydrates, and triazines.
Using a macromonomer, first, third and fifth generation triazine dendrimers can be prepared using a divergent approach. The nine step process to the fifth generation target relies on an iterative two-reactions-per-generation strategy to yield the desired material in ~48% overall yield. This target displays 96 surface groups. NMR spectroscopy and mass spectrometry show exceptionally narrow polydispersity is achieved using this strategy.
7. Organoiron Routes to a New Dendron for Fast Dendritic Syntheses Using Divergent and Convergent Methods. V. Sartor, L. Djakovitch, J.-L. Fillaut, F. Moulines, F. Neveu, V. Marvaud, J. Guittard, J.-C. Blais, D. Astruc, J. Am. Chem. Soc. 1999, 121, 2929 – 2930. Construction of Giant Dendrimers Using a Tripodal Buiding Block. J. Ruiz, G. Lafuente J. Ruiz, G. Lafuente, S. Marcen, C. Ornelas, S. Lazare, E. Cloutet, J.-C. Blais, D. Astruc. J. Am. Chem. Soc., 2003, 125, 7250 – 7257. Organometallic Chemistry at the Nanoscale: Dendrimers for Redox Processes and Catalysis. D. Astruc. Pure Appl. Chem. 2003, 75, 461 – 48.
9. Encapsulation and Stabilization of Gold Nanoparticles with “Click” Polyethyleneglycol Dendrimers. E. Boisselier, A. K. Diallo, L. Salmon, C. Ornelas, J. Ruiz, D. Astruc J. Am. Chem. Soc. 2010, 132, 2729–2742. Nanoscopic Assemblies Between Supramolecular Redox Active Metallodendrons and Gold Nanoparticles: Syntheses, Charaterization and Selective Recognition of H2PO4 -, HSO4 - and Adenosine-5’-Triphosphate (ATP2-) Anions. M.-C. Daniel, J. Ruiz, S. Nlate, J.-C. Blais, D. Astruc. J. Am. Chem. Soc. 2003, 125, 2617 – 2628.
Synthesis: Most syntheses of dendrimers involve the repetitious alternation of a growth reaction and an activation reaction. Many dendrimer syntheses rely upon traditional reactions, such as the Michael reaction 1, 2 or the Williamson ether synthesis 10, whilst others involve the use of modern techniques and chemistry, such as solid-phase synthesis 11, organotransition-metal chemistry 1, organosilicon 12 chemistry, organo-phosphorus chemistry 13, or other contemporary organic methodologies 14. Dendrimers are generally prepared using either a divergent method or a convergent one.
Reactions under a convergent approach need a relatively longer time compared to that of the divergent method. In addition to the divergent and convergent approaches, various alternative preparation methods have been developed that aim to reduce the number of synthetic and purification steps and increase yields, such as the double-stage convergent growth approach 17, double-exponential dendrimer growth approach 18 and orthogonal coupling 19.
The use of macromonomers in the synthesis of triazine dendrimers offers rapid access to odd generation targets. While divergent and convergent routes can afford low generation structures reliably, issues with solubility and the high number of reaction steps required previously limited the robustness of these methods beyond generation 3 materials. Here, the generation 5 dendrimers, 7 and 8, are synthesized in half the number of steps at 48% overall yield. Even generation materials can also be accessed. The targets show a monodisperse structure confirmed by MALDI-TOF MS even though the technique is often unsuccessful for these species in this mass range. This approach proves simple and reliable, and is predicted to successfully extrapolated to larger scale syntheses.