Synthesis of polystyrene-b-poly(ethylene glycol) block copolymers by radical exchange reactions of terminal RAFT agents

Abstract

In this study, a mechanistic transformation was achieved by taking advantage of coupling reaction of reversible addition–fragmentation chain transfer (RAFT) agents. Polymers prepared by different polymerization modes were coupled to form polystyrene-b-poly(ethylene glycol) (PS-b-PEG) block copolymer. For this purpose, two prepolymers, namely azo and RAFT functional polymers were prepared independently. In the first step, a new macroazoinitiator (MI)-containing PEG units was synthesized by direct esterification of 4,4-azobis(4-cyanopentanoic acid) (ACPA) with poly(ethylene glycol) (PEG) at ambient conditions. The other component, polystyrene (PS) was synthesized by atom transfer radical polymerization and modified with a reversible addition–fragmentation chain transfer (RAFT) agent (xanthate moiety) and used as a polymeric RAFT agent for the block copolymer formation. In the block copolymerization process, polymeric radicals stemming from the thermolysis of PEG-MI were coupled with the RAFT moiety of PS. The PEG-MI, PS, PS-XANTH, and PS-PEG block copolymers were characterized by spectral analysis using FT-IR, ¹H NMR, GPC, and DSC.

Keywords:

• block copolymer
• RAFT agent
• macroazoinitiator
• poly(ethylene glycol)
• polystyrene

1. Introduction

Mechanistic transformation is an elegant methodology that combines two or more polymerization methods to form block copolymers of structurally different monomers.[1,2]12 Generally, such combinations cannot be accomplished by using individual distinct polymerization methods. Macromolecular architectures with certain physical and structural properties can be facilitated by this approach. Two main strategies; (i) the use of dual functional initiators [2,3]23 and (ii) propagating chain end switches [4,5]45 have been proposed and successfully applied. In the latter case, a direct switch of the propagating chain ends is not feasible due to the short life of active centers and thermodynamic limitations. The only successful example is reported by Endo and co-workers who prepared block copolymers by switching propagating cations into anionic species directly.[6]

A wide variety of transformation reactions have been reported. Previous efforts in this laboratory have focused on the development of the transformations involving combinations of radical systems with anionic,[7] activated monomer,[8,9]89 cationic,[10–17]1011121314151617 and condensation polymerizations.[18–20]181920 In some cases,[21–23]212223 the same polymerization mechanisms but different initiating systems were also employed.[24–27]24252627

The established controlled radical polymerization methods, namely atom transfer radical polymerization (ATRP),[28] reversible addition–fragmentation chain transfer polymerization (RAFT) [29,30]2930, and nitroxide-mediated radical polymerization [31] are extensively used in the transformation approach in combination with living ionic polymerization routes to form block copolymers with well-defined structures.[10,32–34]10323334 For example, anionic polymerization was successfully transformed to RAFT polymerization using several strategies. In most cases, anionically prepared polymers equipped with RAFT agents were used in the RAFT polymerization of a second monomer in the presence of a radical initiator.[35] The equilibrium established by the chain transfer–fragmentation steps facilitates the formation of the corresponding block copolymers. Several other coupling processes yielding various macromolecular architectures of structurally different monomers but also were reported in the literature.[36–43]3637383940414243

In this study, we introduce a different approach in which anionic polymerization was combined with ATRP through RAFT chemistry. As it will be shown, the RAFT agent incorporated at the chain ends takes part only in radical exchange reaction to form a coupled product.

2 Experimental

2.1 Materials

Ethyl 2-bromopropionate (99%, Aldrich), potassium xanthate (98%, Fluka), copper (I) bromide (98%, Acros), N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA, 99%, Aldrich), poly(ethylene glycol) (PEG) methyl ether (Me-PEG, M_n ∼ 2000 g/mol, Aldrich), N,N′-dicyclohexylcarbodiimide (DCC, 99%, Aldrich), 4-dimethylaminopyridine (DMAP, 99%, Aldrich), N,N′-dimethylformamide, methanol (Merck), toluene (Aldrich) were used as received. 4,4-Azobis(4-cyanopentanoic acid) (ACPA, 98%, Fluka) and 2,2′-azobis(isobutyronitrile) (AIBN, 98%, Fluka) were recrystallized from methanol and acetone, respectively, prior to use. Styrene (99%, Aldrich) was passed through a basic alumina column to remove the inhibitor.

2.2 Characterization

¹H NMR spectra of 5–10% (w/w) solutions of the intermediates and final polymers in CDCl₃ with Si(CH₃)₄ as an internal standard were recorded at room temperature at 500 MHz on a Agilent VNMRS 500 spectrometer. FT-IR spectra were recorded on Perkin–Elmer FT-IR spectrum one spectrometer with an ATR Accessory (ZnSe, PikeMiracle Accessory) and cadmium telluride (MCT) detector. Resolution was 4 cm⁻¹ and 24 scans with 0.2 cm/s scan speed. Differential scanning calorimetry (DSC) was performed on a Perkin–Elmer Diamond DSC. Molecular weights and polydispersities of the block copolymers were measured by gel permeation chromatography (GPC) employing an Agilent 1100 instrument equipped with a differential refractometer by using tetrahydrofuran as the eluent at a flow rate of 0.3 ml min⁻¹ at 30 °C. Molecular weights were determined using polystyrene (PS) standards.

2.3 Synthesis of polymers

2.3.1 Synthesis of ω-bromo polystyrene (PS-Br)

PS with ω-bromo functionality was synthesized by ATRP. Thus, A Schlenk tube was charged with CuBr (0.125 g, 0.87 mmol), PMDETA (0.15 g, 0.87 mmol), ethyl 2-bromopropionate (0.16 g, 0.87 mmol) and styrene (9, 09 g, 87 mmol). Three freeze–pump–thaw cycles were performed, and the tube was stirred in oil bath at 110 °C for 30 min. After the given time, the mixture was diluted with THF. Then, the copper complex was removed out by passing through a neutral alumina column, and THF was removed by rotary evaporation. The mixture was precipitated in methanol, and the solid was collected after filtration and dried at room temperature under vacuum for overnight. (M_n,_NMR: 1700, M_n,_GPC: 1660 g/mol, M_w/M_n: 1.22).

2.3.2 Synthesis of PS with ω-xanthate functionality (PS-Xant)

In a two-necked flask equipped with a stirrer, PS-Br (1.0 g, 1 eq.), potassium xanthate (0.8 g, 10 eq.) and 10 mL DMF was added under N₂ atmosphere. The reaction mixture was stirred for 18 h at room temperature and precipitated in 10-fold excess of methanol to yield PS-Xant. (M_n,GPC: 2520 g/mol, M_w/M_n: 1.15).

2.3.3 Synthesis of poly(ethylene glycol) macroazoinitiator (Me-PEG-MI)

Me-PEG (M_n:.2000 g/mol, 2.0 g, 1 mmol) and ACPA (1.4 g, 5.00 mmol) were dissolved in 15 mL of CH₂Cl₂. DMAP (0.61 g, 5.00 mmol) and DCC (1.03 g, 5.0 mmol) in 10 mL of dichloromethane were added to the solution in that order. The reaction mixture was stirred for 22 h at room temperature. The formed product was filtered, and the remaining solution was evaporated to give a viscous liquid. Finally, polymer is precipitated in 100 mL of diethylether to yield Me-PEG-MI. This process was repeated two times to purify the polymer (M_n,_NMR: 4300, M_n,GPC: 4100 g/mol, M_w/M_n: 1.16).

2.3.4 Synthesis of polystyrene-b-poly(ethylene glycol) (PS-b-PEG) block copolymers by thermal coupling

To a Schlenk tube equipped with a magnetic stirrer, PS-Xanth (0.2 g, 1 eq.), Me-PEG-MI (2.05 g, 5 eq.) were added and dissolved in 15 mL DMF. The tube was degassed by three freeze–pump–thaw cycles and placed in a thermostated oil bath at 80 °C for 4 h. The solvent was evaporated, and the resulting concentrated solution is poured into ten-fold excess ice-cold methanol/diethylether mixture (100/10) to precipitate the polymer. The polymer is further dissolved in THF and reprecipitated to purify the polymer and dried under vacuum at room temperature.

3 Results and discussion

As stated in the introduction section, in all reported transformation reactions through RAFT technique, the actual polymerization process is involved. In another words, polymers with RAFT agent functionality at the chain termini were prepared by various polymerization modes are used in the RAFT polymerization of another monomer.

Recently, Moeller and Weberskirch [44] reported a novel methodology for the preparation of telecehelics through radical exchange reaction of terminal RAFT agent and functional azo initiator. The rapid reaction of the primary radicals with RAFT agents prompted us to apply the process with polymeric radicals. Thus, polymers with ω-xanthate groups and radical generating functionalities, such as azo groups, were prepared independently. The overall procedure involves the synthesis of ω-bromo polystyrene (PS-Br) by ATRP, substitution of ω-xanthate polystyrene (PS-Xant), and its reaction with diazo-containing polyethyleneglycol (Me-PEG-MI). Scheme 1 shows the synthesis of PS-Xant, which was reported in previous studies.[45,46]4546 The ¹H NMR spectrum confirms the expected structure (Figure 1(a)).

Scheme 1 Synthesis of xanthate functional polystyrene (PS-Xant).

Figure 1 ¹H NMR spectra of (a) PS-Xanth, (b) Me-PEG and (c) Me-PEG-MI.

In a parallel step, a simple esterification procedure was conducted between a carboxylic acid functional diazo-radical initiator ACPA and commercially available anionically repaired ω-hydroxyl functional PEG to obtain Me-PEG-MI as shown in Scheme 2.

Scheme 2 Synthesis of poly(ethylene glycol) macroazoinitiator (Me-PEG-MI).

In the ¹H NMR spectrum of Me-PEG-MI, the methylene protons next to the hydroxyl groups are shifted to downfield from 3.6 to 4.25 ppm due to the esterification reaction between ACPA and PEG (Figure 1(b) and (c)).

The IR spectrum of Me-PEG-MI further demonstrates the formation of ester linkage by the disappearance of the acidic carbonyl band at 1710 cm⁻¹ of the ACPA and the presence of new ester stretching carbonyl peak –C=O at around 1736 cm⁻¹. The peak about 1100 cm⁻¹ is belonging to PEG –CH₂ vibration band.

In the final step, PS-Xant and Me-PEG-MI was coupled by thermal treatment (Scheme 3). The mechanism of the coupling process is typical radical exchange reaction of RAFT agents with azo compounds as described in the literature.[44]

Scheme 3 Synthesis of PS-b-PEG by thermally induced radical exchange reaction.

The structure of the block copolymer is confirmed by ¹H NMR spectroscopy. All characteristic peaks of the main segments are detected as shown in Figure 2.

Figure 2 ¹H NMR spectra of PS-b-PEG.

The FT-IR analysis further evidences the block copolymer structure. In Figure 3, the IR spectra of the precursor polymers and final block copolymer are presented. The aliphatic backbone of the PS at 1455 cm⁻¹ and the aromatic ring vibrations observed at around 3027, 3066, and 1608 cm⁻¹ proves that PS chains are in the block copolymers. Additionally, the presence of a new peak located at about 1100 cm⁻¹ indicates successful attachment of PEG segment into block copolymer.

Figure 3 FT-IR spectra of Me-PEG-MI, PS-Br and PS-b-PEG.

The molecular weight characteristics of the polymers were investigated by GPC. Figure 4 shows the GPC traces of the polymers at different stages. All polymers have unimodal and narrow curves that indicate no side reaction occurred throughout the process. As can be seen, the GPC curve shifts to the higher elution volumes, indicating the increase in the molecular weight after the block copolymer formation.

Figure 4 GPC traces of PEG, PS-Br, and PS-b-PEG.

Notably, all molecular weights obtained from GPC measurements are consistent with those calculated by NMR analysis. The molecular weight characteristics of the polymers at various stages are collected in Table 1.

Table 1. Molecular weight characteristics of the polymers at various stages.

Polymer	Mn,NMR^a (g mol^−1)	Mn,GPC^b (g mol^−1)	Mw/Mn^b
PEG	2010	3110	1.05
Me-PEG-MI	4300	4100	1.16
PS	1700	1660	1.23
PS-b-PEG	4090	4900	1.07

^aDetermined by ¹H NMR analysis.^bDetermined by GPC using PS standards.

The thermal property of the block copolymer is investigated by DSC under nitrogen atmosphere and compared with that of the precursor polymers (Figure 5). The DSC trace of the block copolymer showed an endothermic peak located at 53 °C indicating presence of semicrystalline PEG domain. The crystals extend of PEG segments in such block copolymers strongly depends on the molecular weight of the polyether block. Since the block copolymer is formed from PEG with molecular weight of 2000 g/mol, an intense melting transition is detected. Similar molecular weight effect accounts for the relatively lower T_g value for PS segment at 88 °C. The existence of the individual thermal transitions of both PS and PEG segments clearly indicates occurrence of microphase separation between two domains.

Figure 5 DSC trace of PS, PEG, and PS-b-PEG.

In order to demonstrate the efficiency of the applied radical exchange process, a model reaction was conducted using low molar mass azoinitiator. Thus, AIBN was used as the coupling component together with PS-Xant under identical experimental conditions. The FT-IR spectra of the obtained product exhibits a weak transition around 2200 cm⁻¹, which demonstrates the presence of nitrile functionality at the PS chain end (Figure 6).

Figure 6 FT-IR spectrum of the addition product of PS-Xant and AIBN.

4 Conclusions

We have demonstrated a new synthetic approach for the preparation of block copolymers through mechanistic transformation on the basis of radical exchange reaction between RAFT agent and polymeric radical initiator. The actual coupling process is simple and does not require polymerization reactions. Since the individual components may be prepared by independently, the described strategy can be adapted to different monomer couples to form corresponding block copolymers. Further, studies in this line are now in progress.