Article pubs.acs.org/Macromolecules
Synthesis of High Generation Dendronized Polymers and Quantification of Their Structure Perfection Hao Yu, A. Dieter Schlüter,* and Baozhong Zhang* Department of Materials, Laboratory of Polymer Chemistry, ETH Zürich, HCI G523, Vladimir-Prelog Weg 5, 8093 Zürich, Switzerland S Supporting Information *
ABSTRACT: The sixth generation (g = 6) dendronized polymer (DP) PG6 was synthesized on a 2 g scale with Pn ∼ 500 in 60% chemical yield and with a coverage degree of 87−90% using a recently developed “n + 2” approach from its structurally virtually perfect, deprotected g = 4 congener dePG4. This synthesis represents the first fully reliable access to a g = 6 representative of this DP series and was therefore used for the synthesis of two higher generation representatives, the g = 7 and g = 8 DPs, PG7 and PG8, which are the highest g DPs ever reported. The structure perfection of the obtained DPs was analyzed by the conventional UV-labeling method and compared with the results from TGA, with which the amount of cleaved-off Boc-protecting groups was quantified. The accuracy of the TGA method was assessed as ±3% by using a Boc-containing dendron and well-characterized low generation DPs as reference. For the high generation DPs obtained by “n + 2” approach the TGA results confirmed the UV-determined coverages. For PG7, the TGA result slightly exceeds the error range (3.3%), which may suggest a possible overestimation of the coverage determined by UV quantification. AFM imaging shows a so far uncommon inhomogeneous appearance for PG7 and PG8, which may be a result of structural defects in both DPs.
1. INTRODUCTION Dendritic macromolecules have been the subject of immense interest since their theoretical prediction.1 They are generally synthesized in one of two ways, the first of which is the one-pot polymerization of branched monomers, which leads to hyperbranched polymers. While this method is fast and costeffective, the obtained macromolecules are structurally illdefined and polydisperse.2 In contrast, there are convergent and divergent (step-by-step) procedures which result in bettercontrolled dendrimers3 and dendronized polymers (DPs).4 By the divergent method, the molecular structures and related properties are quantized by generation numbers and can be tuned.5 Also, the conversion for each step can in principle be quantified, which is critical for an understanding of these macromolecules at the molecular level. The convergent and divergent methods have been successfully applied to the production of low to medium generation dendrimers and DPs and have furnished nearly perfect molecular structures. These structures are more open for low generations and approach the closed packed state for high generations. Properties can change discontinuously when passing from more open to more closed.6 In divergent synthesis and when the generation is high, the large number of postpolymerization modification steps required leads to an increasing amount of defects.7 This becomes more serious the closer one gets to the tightly packed maximum generation (gmax), the so-called De Gennes dense packing limit. For dendrimers it has been reported that they can be © 2014 American Chemical Society
synthesized beyond gmax, though at a price of structural imperfection.8 For their DP counterparts, however, all reported cases thus far did not go beyond the sixth generation, which should be below gmax.9 It was therefore of obvious interest to explore higher generations and see whether the synthetic and analytical tools available are still robust enough to explore these macromolecules with their near dense-packed structures. This would shed some light on whether the theoretical packing limit is synthetically approachable and even surpassable and, if so, whether structure analytics could still be performed. Thus, the phenomenon of global steric hindrance, or in other words the sterically induced stoichiometry (SIS), is what is at the heart of this publication.10 Previously, we have reported a DP with g = 5 (PG5), the largest ever synthesized linear macromolecule, using a divergent synthesis protocol based on a modified Merrifield amide coupling.11 The conversion of each dendronization step was quantified to be near 100% by a UV-labeling method.12 With the same divergent synthesis, PG6 was attempted with partial success,9c which however led to two unexpected observations: (1) PG6 always has short main chain lengths (GPC, AFM) irrespective of the lengths of the starting material; (2) the structure perfection of PG6 as quantified by a UV labeling Received: April 18, 2014 Revised: June 11, 2014 Published: June 19, 2014 4127
dx.doi.org/10.1021/ma500821n | Macromolecules 2014, 47, 4127−4135
Macromolecules
Article
Scheme 1. Synthesis of PG6−8 by the “n + 1” and “n + 2” Approaches and Structures of the Dendronization Agents, the Active Esters DG1 and DG2a
a
Note that the structures of PG6−PG8 cannot be given in full because of their sizes.
method using the Sanger reagent is lower than used for lower g DP (approximately 88% instead of near 100%). The first observation is due to main chain scission which occurs on the level of the precursor of PG6, the deprotected polymer dePG5. It was suggested that this scission is likely due to the large steric and charge repulsion present in dePG5.13 Despite the various reaction conditions tested, it is still impossible to completely avoid this unfavorable reaction from happening. Previously we have reported a new “n + 2” approach to produce low generation DPs (PG3−5) efficiently.14 It is based on the use of a second generation dendronization reagent (DG2) rather than the commonly used first generation analogue DG1. This reagent in principle offers a solution to the problem with chain scission because if applied to the synthesis of PG6, dePG4 will be the starting material rather than the delicate dePG5. Since dePG4 is perfectly stable at room temperature, it was thus expected that the use of DG2 would provide direct access to the desired PG6 with the same chain length and chain length distribution as the starting PG4. Note that PG6 was not only of interest in itself but that it is the key point for accessing even higher g DPs. Besides circumventing the chain scission problem, the use of DG2 is also expected to be more effective in terms of cost and time, thus offering a “large scale” PG6 production. Regarding the second observation, we reasoned that the reduced reaction efficiency may reflect the nearness of gmax which for DPs discussed here was estimated to be 6.1 < gmax < 7.1.15 DPs at and beyond gmax are expected to be tightly packed with little residual “internal
voids”. With the absence of voids, chemical reactions inside a DP will be almost impossible. This also regards the reaction between the Sanger reagent and any nondendronized amine group eventually present. Though this reagent is smaller than DG1, there will still be a point where it cannot reach the targeted amines anymore, which are buried somewhere within the branches. Thus, applicability of this otherwise powerful method cannot be simply taken for granted. To nevertheless start approaching dense structures, we had to develop an independent method to quantify structure perfection which would not rest on an unhindered diffusion of reagents into branches. This method was found to be thermogravimetric determination of the Boc-protecting groups. It has been reported decades ago that Boc groups quantitatively decompose upon thermolysis at 180−185 °C.16 Quantification of the number of Boc groups in bulk polymer materials using TGA has also been reported.17 While the UV labeling method aims at quantifying unreacted amines, measuring the loss of Boc groups in TGA experiments provides comprehensive quantitative information because of the fixed relation between nondendronized amines and the number of Boc groups which are missing because of this nondendronization. For each nondendronized amine, two or four Boc-groups are missing depending on whether the growth reaction was carried out with DG1 or DG2, respectively. Before relying on such a method, however, it needed to be validated using a model compound and well-investigated DP samples. 4128
dx.doi.org/10.1021/ma500821n | Macromolecules 2014, 47, 4127−4135
Macromolecules
Article
Figure 1. (a) GPC (in DMF) elution curves of PG6, starting PG4 and the reaction mixture at different times from 1 to 30 days. (b) Evolution of the GPC elution times (peak) for the conversion from dePG4 to PG6. Note that PG4 was taken as the starting point (0 day).
−10 °C. This led to complete removal of the tertbutyloxycarbonyl (Boc) groups. PG2−5 were synthesized by attaching DG1 (Scheme 1) onto dePG1−4 by Merrifield-type amidation.14 2.2. Synthesis of PG6 by a “n + 2” Approach. Synthesis of PG6 was reported earlier by a conventional divergent approach (“n + 1” approach).9c However, this previously obtained PG6 always had shorter main chain lengths than its low generation precursors. This was rationalized by an unexpected main chain scission during the acidic deprotection of a precursor PG5.13 To circumvent this problem and improve on the synthetic efficiency, we applied a “n + 2” approach by grafting a larger dendronization agent (DG2, Scheme 1) onto a low g dePG4. This resulted directly in PG6. Gratifyingly, this new approach produced PG6 without noticeable chain scission on ∼2 g scale with 60% yield in only 35 days, while the “n + 1” approach, in addition to the main chain scission issue, returned ∼18% yield on a
