Diblock Copolymers as Scaffolds for Efficient Functionalization

Diblock Copolymers as Scaffolds for Efficient Functionalization

(Parte 1 de 4)

Diblock Copolymers as Scaffolds for Efficient Functionalization via Click Chemistry

Sven Fleischmann, Hartmut Komber, and Brigitte Voit*

Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, D-01069 Dresden, Germany ReceiVed April 3, 2008; ReVised Manuscript ReceiVed May 20, 2008

ABSTRACT: A set of differentalkynecontainingdiblockcopolymersbased on 4-hydroxystyrenewas synthesized by nitroxide mediated radical polymerization (NMRP), all with excellent control over the molecular composition and narrow molar mass distribution. The diblock copolymers consist of labile protected 4-hydroxystyrene motifs in one block and bear alkyne functionalities in each repeating unit of the second block, thus making the materials candidates for polymer analogous modification reactions by a very efficient cycloaddition reaction. The use of 4-(trimethylsilylpropargyloxy)styrene as monomer proved highly advantageous compared to 4-(trimethylsilylethynyl) styrene, first because high control was kept in the NMRP process and second because there was higher accessibility in the postmodification reaction. In fact, quantitative postmodification through Cu(I)-catalyzed cycloadditionreaction of the pending propargyloxygroups with bulky adamantaneazide of the diblock copolymers was achieved, yielding microphase-separated materials with a rigid block.


During the past decade diblock copolymers have drawn high attention in the scientific world. Microphase separation of incompatible blocks leads to the formation of nanodimensioned features in the range 10-100 nm.1 The size and ordering of these nanodomains can be controlled by varying the molecular weight, the chemical structure and the molecular architecture.2 Although the mechanistic principles of the self-assembly of diblock copolymers in thin films are complex and not yet fully understood, scientists expect them to have a striking impact on nanotechnology.3 The influence of surface effects in such thin films results in nanodomains that can be more complex and different from those being observed in bulk, i.e. spheres, cylinders, lamellae, etc.4 State-of-the-art research is able to preparehighlyorienteddiblockcopolymerthin films by different approaches.5 Apart from their application in thin films, amphiphilic diblock copolymer micelles are used, e.g., as scaffolds for the preparation of cross-linked nanoparticles.6

Although, the polymers considered in the above-mentioned applications exhibit a high control over the molecular architecture, they are usually lacking defined functionalities, a fact that is directly related to ionic polymerization procedures by which most of the block copolymers investigated are currently synthesized. In order to satisfy the demand for complex and smart, further miniaturized devices in nanotechnology, new defined functional materials are required. This need can only be faced with novel methodologies. In this regard, controlled radical polymerizations (CRP) as NMRP,7 ATRP,8 and RAFT9 are excellent tools for the preparation of such highly defined, functionalblock copolymers.They tolerateless rigorousreaction conditionsand are compatiblewith a varietyof functionalgroups so that these are nowadays preferred over ionic polymerization processes. Recently, Sharpless’ click chemistry,10 a Cu(I)- catalyzed version of Huisgen’s 1,3-dipolar cycloaddition of azides and alkynes,1 has been introduced in polymer science by various groups and recent comprehensivereview articles can be found in literature.12 Click chemistry adopted to polymer analogous reactions enables to efficiently and selectively tune the functionality and morphology of a polymeric material. Generally, suitable macromolecules can be considered as scaffolds and a large variety of polymers can be created from a construction kit of a plethora of reactive substrates. Remarkably, this concept had been suggested for polymer analogous modifications via pendant active esters some time ago.13

Specifically, segmented and “clickable” diblock copolymers would allow to manufacturenanodevicesin which the functional domains could be selectively addressed in a click reaction and, thus, further modified. Only some examples for combinations of CRP and click chemistry should be depicted here from a research field which is rapidly expanding: Matjyaszewski’s group14 described the synthesis of poly(3-azidopropylmethacrylate-b-N,N-dimethylaminoethylmethacrylate) by ATRP and its polymer analogous modification with low molecular alkyne substrates. The obtained azido-functional polymers exhibited slightly broader SEC traces and, especially for high conversion, the polydispersity rose above 1.5, a fact that might be attributed to an in situ 1,3-dipolar cycloaddition reaction of the azide and the vinyl double bond of the monomer. Haddelton and coworkers15 revertedto a well defined polymerbased on propargyl methacrylate which they used as a scaffold for the preparation of synthetic glycopolymers by grafting azido-sugar derivatives along the polymer backbone. In their seminal work Hawker et al.16 demonstrated the efficiency of click chemistry in polymer analogous modifications. They were able to orthogonally functionalize macromolecules in an one-pot synthesis using the strength of Cu(I)-catalyzed 1,3-dipolar cycloadditions and a couple of selected esterification as well as amidation reactions.

In this paper, we would like to report on the synthesis of reactive, phase-separated diblock copolymers that are prone to click chemistry as well as on first results on their effective polymer analogous modification with a bulky azide. On one hand, these macromolecules represent an ideal starting point for the modular synthesis of novel polymeric materials by effective side group modifications. On the other hand, potential applications of such diblock copolymers can be found in the fast developing field of nanostructured functional thin films. Recently, we could show that block copolymers based on 4-hydroxystyrene derivatives can be prepared in high molar masses and narrow polydispersity by nitroxide mediated radical polymerization (NMRP).17,18 In particular, when one of the block consists of unprotected 4-hydroxystyrene, these block copolymers show a high tendency for phase separation,and thin films exhibiting a highly ordered nanostructure could be prepared.19 By combining the phase separation tendency of that* Corresponding author. Fax: +49 351 4658565. E-mail: voit@ipfdd.de

10.1021/ma8007493 C: $40.75 2008 American Chemical Society Published on Web 06/25/2008

type of block copolymerswith effectiveside group modification, it should be possible to create thin microphase-separated films where nanoscopic domains might be exclusively addressed by orthogonal reaction techniques.

Experimental Part

Chemicals.THF (9%, Fluka)and acetone(9.5%,Merck)were used as received, and dichloromethane (DCM, 9%, Fluka), triethylamine(9.5%, Fluka), diisopropylethylamine(DIPEA, 9%, Aldrich), diazabicycloundecene (DBU, 97.5%, Aldrich), and diethylene glycol dimethylether (diglyme, 9%, Aldrich) were dried over CaH2 and purified by fractionated distillation. The synthesis of 4-(tert-butyldimethylsilyloxy)styrene21 (1) was described else- whereandthemonomers4-(tert-butyloxy)styrene(2,TBU-oxystyrene, 9%, Aldrich)and 4-acetoxystyrene(3, 96%, Aldrich)were distilled before use. All other reagents and solvents were purchased from Aldrich and used as received. N-tert-Butyl-R-isopropyl-R-phenylnitroxide (TIPNO), 2,2,5-trimethyl-3-(1-phenylethoxy)-4-phenyl-3-

azahexane (initiator, TIPNO-Sty), and Cu(PPh3)3Br were synthesized as described elsewhere.20 Tetrabutylammonium fluoride

[(TBA)F] was available from Aldrich asa1M solution in THF containing5% water.Adamantaneazide(97%)was usedas received from Aldrich.

Measurements. Molar masses and polydispersities of polymer sampleswere determinedby gel permeationchromatography(GPC) using a 10 µm MIXED-B column (Polymer Laboratories) with polystyrene standards (Polyscience) and chloroform as eluent. 1H and 13C measurements were performed with a Bruker DRX 500 spectrometer. CDCl3 and acetone-d6 were used as solvents and internal standard (δ(1H) ) 7.26 ppm, δ(13C) ) 7.0 ppm and δ(1H)

) 2.05 ppm, δ(13C) ) 30.5 ppm, respectively). Signal assignments were verified by 2D NMR experiments. The pulse sequences included in the Bruker software package were used.

All FT-IR spectra were recorded from prepared films in transmission mode on a Bruker IFS 6 V/S. Differential scanning calorimetry(DSC) was preformedwith a DSC 7 from Perkin-Elmer as well as a DSC Q 1000 by TA Instruments with a heating rate of 20 K/min. The TGA analyses were conducted with a TGA 7 by Perkin-Elmer under nitrogen atmosphere with a heating rate of 10 K/min.

Monomer Synthesis. 4-Hydroxystyrene (4). The synthesis and characterization can be found in the Supporting Information. 4-(Propargyloxy)styrene (5). A 250 mL round-bottom flask, equipped with a condenser and a stirrer, was fed with 6.90 g (57 mmol) of freshly prepared 4-hydroxystyrene (4), dissolved in 50 mL of acetone. Then, 26.06 g (116 mmol) of potassium carbonate and 1.87 g (1 mmol) of 18-crown-6 were dispersed. The mixture was heated to reflux and 13.38 g (89 mmol) of propargyl bromide (80% in toluene) was added. The reaction was kept under nitrogen atmosphere. After 20 h the product was precipitated into 300 mL of deionized water and 80 mL of chloroform was added. The organic phase was separated, and the water phase was extracted three times with 80 mL of chloroform used each time. The organic layers were combined, dried over sodium sulfate, and evaporated. The crude product was purified by flash chromatography using n-hexane and ethyl acetate (100:1) as solvent resulting in 5.54 g (61%) of a colorless liquid.

round-bottom protection flask, equipped with a condenser and a dropping funnel, was dried in a high vacuum at 350 °C. Under a nitrogen atmosphere, 538 mg (4 mmol) of silver chloride was dispersed in 30 mL of dry dichloromethane and 5.54 g (35 mmol) of 4-(propargyloxy)styrene (5) and 6.50 g (43 mmol) DBU were added. The suspension was heated under reflux and 4.90 g (45 mmol) trimethylsilyl chloride were dropped slowly. After 18 h, complete conversion of the free alkyne was indicated by TLC so that the reaction mixture was cooled to room temperature and diluted with 60 mL hexane. The crude product was washed with a semiconcentratedsodium hydrogen carbonatesolution and with 1% HCl. The organic layer was removed, dried over sodium sulfate and evaporated. The product was isolated by column chromatography over silica gel with n-hexane and ethyl acetate (100:1) as solvent resulting in 3.38 g (42%) of a colorless oil.

Table 1. Experimental Parameters and Analytical Data for the Macroinitiators MI-x

Table 2. Experimental Parameters for the Synthesis of Protected Precursor Diblock Copolymers

Table 3. Experimental Parameters for the Synthesis of Precursor Diblock Copolymers with Random Distribution of the Alkyne Monomer 7 in the Second Block a Amount of monomer 7 in the second block in mol %.

Table 4. Kinetic Experiment for the Cu(I)-Catalyzed Addition of 1-Adamantane Azide to HP-6 and HP-7 polymer mpolymer [mg] nalkin [µmol] nazide [µmol] mCu-cat. [mg] mDIPEA [mg] conversion [%]

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(CtC) (w), 1606 (CArdCAr) (m), 1510 (CArdCAr) (s), 1251 (Ar-O-C) (s).

4-(Trimethylsilylethynyl)styrene (7). 7 was synthesized via a Sonogashirareactionfrom 4-bromostyreneas describedelsewhere.23

(Cf), 94.81 (Cg), -0.03 ppm (Ch). Polymer Synthesis. All polymerizations were carried out in

Schlenk tubes under nitrogen atmosphere at 120 °C in bulk. Macroinitiators and diblock copolymers of different molecular weights Mn,cal and block ratios, respectively, were obtained by changing the initiator to monomer ratio taking into account the degree of conversion R: i.e., nini )R *mmonomer/Mn,cal. Reaction solutionswere all degassedby four freeze-pump-thaw cyclesprior to polymerization. The polymerizations were stopped by cooling in an ice-cold bath. If not mentioned else, the samples were precipitated twice in ethanol and dried at 50 °C in high vacuum overnight.

Synthesis of Macroinitiators (MI-x). A detailed description of the macroinitiator syntheses can be found in our previous paper.18 Informationabout the characterizationis provided in the Supporting Information.

Synthesis of the Alkyne-Containing Homopolymers HP-6 and

HP-7. Poly(TMSpropargyloxystyrene) (MI-6). The general polymerizationprocedureas describedabove was applied.Initially, the Schlenk tube was carefully cleaned by repeated washing with water and acetone, thereafter flame dried in high vacuum to remove moisture and purged with nitrogen. Then, a solution of 85.4 mg (284 µmol) of initiator TIPNO-Sty in 3.5447 g (15 mmol) 6 was prepared in a vial, transferred in the Schlenk tube, degassed and polymerized. After 16 h the reaction was stopped and the polymer worked up. After drying, 1.630 g (46%) polymer could be isolated.

Scheme 1. Overview on the Monomers Used for the Syntheses of Diblock Copolymersa a The synthetic route to the alkyne monomer 4-(3′-trimethylsilylpropargyloxy)styrene (6) involves a straightforward three step synthesis. Scheme 2. Polymerization of 7 by NMRP Resulting in MI-7 That Was Subsequently Desilylated To Yield HP-7a a In analogy, 6 was polymerized to MI-6 (without TIPNO) and desilylated to HP-6.

Figure 1. Influence of the feed composition for a copolymerization of styrene and 7 on the PDI with (•) and without (2) addition of free nitroxide TIPNO.

Macromolecules, Vol. 41, No. 14, 2008 Diblock Copolymers as Scaffolds 5257

Poly(propargyloxystyrene) (HP-6). A solution of 1.1652 g of

MI-6 in THF was reacted with 5 mL of 1 M (TBA)F solution at 0 °C for 30 min. The product was recovered by precipitation from ethanol in 80% yield.

Poly(ethynylstyrene) (HP-7). This was synthesized according to a procedure developed previously in our laboratory.24 More details on synthesis and characterization can be found in the Supporting Information.

Tg ) 153 °C. General Procedure for the Synthesis of the Precursor Diblock

Copolymers pBC-x. The macroinitiators MI-x were dissolved in a minimum amount of diglyme and comonomer 6 was added to the solution. The mol number of initiator needed to obtain the diblock copolymer of a desired block ratio was calculated as described

above based on Mn,cal. of the macroinitiator (Table 2). As an example, in a vial, 566.1 mg (58 µmol) of MI-1a was completely dissolved in 962.2 mg (4.2 mmol) of 6 and 0.5 mL of diglyme. Thereafter,the solution was transferredin a Schlenk tube, degassed, and polymerized at 120 °C under nitrogen atmosphere. After 18 h, the reaction was stopped by cooling, and 0.535 g (35%) of polymer was isolated by repeated precipitation in methanol.

In case of the synthesesof precursordiblockcopolymersin which the alkyne monomer 7 is randomly distributedin the second block with styrene,the same methodologywas followed(Tables3 and 4).

(Parte 1 de 4)