Communication

1895

Summary: The ring-opening cationic polymerization of 2-ethyl-2-oxazoline was performed in a single-mode microwave reactor as the rst example of a microwave-assisted living polymerization. The observed increase in reaction rates by a factor of 350 (6 h ! 1 min) in the range from 80 to 190 8C could be attributed solely to a temperature effect as was clearly shown by control experiments and the determined activation energy. Because of the homogenous microwave irradiation, the polymerization could be performed in bulk or with drastically reduced solvent ratios (green chemistry).

Monomer conversion, represented by the ratio ln{[M0]/[Mt]}, plotted against time for six temperatures in the range from 80 to 180 8C, and polymerization reaction vials, showing an increase in yellow color for those reactions performed (well) above and below 140 8C, indicating side reactions.

Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living Polymerization of 2-Ethyl-2-Oxazoline
Frank Wiesbrock, Richard Hoogenboom, Caroline H. Abeln, Ulrich S. Schubert*
Laboratory of Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology and Dutch Polymer Institute (DPI), P.O. Box 513, 5600 MB Eindhoven, The Netherlands E-mail: u.s.schubert@tue.nl

Received: August 12, 2004; Revised: September 2, 2004; Accepted: September 3, 2004; DOI: 10.1002/marc.200400369 Keywords: activation energy; green chemistry; 2-oxazoline; ring-opening polymerization; single-mode microwave system

Introduction
Since their introduction at the beginning of the new millennium, single-mode microwave reactors have found their way into chemical laboratories all over the world.[1,2] Besides the impressive increase in reaction rates observable for a plethora of reactions, these single-mode systems allow for accurate control of temperature and pressure inside the reaction vial, rendering reproducibility and a facilitated scale-up of the reactions performed.[3] Furthermore, by the fast and direct heating of the reactants, numerous reactions have been reported to give higher yields and an improved purity of the desired products when carried out under microwave irradiation. As an additional consequence, reactions can be performed in reduced solvent amounts (green chemistry).
Macromol. Rapid Commun. 2004, 25, 18951899

Contrary to their well-established use in a steadily growing number of organic reactions, it is only very recently that polymer chemists have discovered single-mode microwave systems as new reaction devices. The rst sets of polymerization reactions have been performed under microwave irradiation. The corresponding ndings show the advantages of microwave irradiation for the polymer synthesis, above all, the increased reaction rates and improved polymer properties.[46] Surprisingly, and in contrast to controlled radical polymerizations,[7] living ionic polymerizations that represent an important class of controlled polymerization techniques have not been investigated so far. To obtain data for this important type of reaction, we chose the living cationic ring-opening polymerization (CROP) of 2-ethyl-2-oxazoline as a rst example (Scheme 1).[8] Its investigation began in 1966,[9]
2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

DOI: 10.1002/marc.200400369

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Scheme 1. Schematic representation of the cationic ring-opening polymerization of 2-ethyl-2-oxazoline initiated by methyl tosylate.

and ever since, fuelled by its promising potential applications like micellar catalysis, drug delivery, or hydrogels,[10,11] numerous attempts aiming at an increase of reaction rates (normally in the range between 10 to 20 h) and molecular weights have been reported.[11] However, no real break-through has been achieved so far.

10; reaction time of 100 s). For the second reaction step, the additional 2-ethyl-2-oxazoline (80 units per TsOMe) was added without additional solvent (reaction time of 800 s).

Results and Discussion

A rst kinetic investigation on the cationic ring-opening polymerization of 2-ethyl-2-oxazoline (EtOx) initiated with methyl tosylate (TsOMe) showed that the speed of the polymerization increases with temperature and is, in contrast to conventional heating, not limited to the boiling point of acetonitrile (82 8C). At 80 8C, the typical temperature for conventional heating, the conversion rate only reaches 59% within 1 h independently of the heating source (microwave irradiation or conventional heating); completion of the polymerization takes 6 h. At 190 8C, on the other hand, the pressure inside the vial reaches 11 bars and the reaction is completed in less than 1 min. Going beyond temperatures of 140 8C, however, induces (minor) side reactions[12] as indicated by the increasing yellowish color of the reaction liquids. The polydispersity index (PDI) values actually stay below 1.2 even for the reaction temperature of 200 8C, exhibiting only a minor increase compared to the standard 1.1 of this series. Consequently, because of the higher reaction temperatures attainable with the single-mode microwave system, the polymerization is accelerated by factors of 350 (80 ! 190 8C) and 70 (80 ! 140 8C), respectively. The living nature of this polymerization was proven in the temperature range between 80 and 180 8C by monitoring the time dependence of the conversion rates and the number-average molecular weights (M n ) of the corresponding polymers for six representative temperatures (Figure 1 and 2). The power supplied to maintain the reaction temperature was found to be independent of the conversion, exhibiting a comparable absorption of the microwave irradiation by the monomer and the polymer in the presence of acetonitrile. The monomer conversion at a given temperature (obtained by GC and represented by the ratio ln{[M0]/ [Mt]}) depends linearly on time, illustrating the rst order kinetics of the polymerization reaction (Figure 1, left). A control experiment at 140 8C with conventional heating in a high-pressure NMR tube revealed the same reaction speed (Figure 1, open symbols) and afforded polymers with analogous properties. In addition, the livingness of the polymerization is successfully illustrated by the linear dependence of the number-average molecular weights (M n )
2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Experimental Part
Materials and Instrumentation All chemicals, except for acetonitrile (Biosolve LTD), were purchased from Aldrich. 2-Ethyl-2-oxazoline (over BaO) and methyl tosylate were distilled and stored under argon. Aceto nitrile was dried over molecular sieves (3 A). Reactions were carried out in capped reaction vials uniquely designed for the single-mode microwave system Emrys Liberator (Biotage, formerly PersonalChemistry). These vials were heated, allowed to cool to room temperature, and lled with argon prior to use. All experiments were performed on 2 mL solutions; the polymerizations were terminated by quenching the reaction mixtures at the favored times with water. Gas chromatography (GC) measurements (for the determination of the conversion) were performed utilizing an Interscience Trace GC with a Trace Column RTX-5 connected to a PAL autosampler. For the injection of polymerization mixtures, a special Interscience liner with additional glass wool was used. Gel permeation chromatography (GPC) was performed on a Shimadzu system with a SCL-10A system controller, an LC-10AD pump, an RID-10A refractive index detector, and a PLgel 5 mm Mixed-D column at 50 8C using a chloroform/ triethylamine/isopropyl alcohol (94:4:2) mixture as eluent at a ow rate of 1 mL min1 (polystyrene calibration). Microwave-Assisted Polymerizations of 2-Ethyl-2-Oxazoline Unless indicated otherwise, solutions with an initial 2-ethyl2-oxazoline concentration of 4 M and a ratio of [EtOx]/ [TsOMe] 60 were used in the polymerization reactions; consequently, a typical stock solution (4 M) with a volume of 25 mL was composed of 9.914 g of 2-ethyl-2-oxazoline, 0.3104 g of methyl tosylate, and 11.707 g of acetonitrile. This stock solution was divided into different vials. For each investigated temperature, six polymerizations were performed with different reaction times. For the concentration series in the range from 4 to 9.9 M, the ratio of [EtOx]/[TsOMe] was kept at a value of 60. In the case of the chain extension experiments (at 140 8C), the rst block was prepared in acetonitrile solution (4 M, [EtOx]/[TsOMe]
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Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living Polymerization of 2-Ethyl-2-Oxazoline

1897

Figure 1. Left: Monomer conversion, represented by the ratio ln{[M0]/[Mt]}, plotted against time for six temperatures in the range from 80 to 180 8C. Right: Chain extension polymerization (M n 1 000 and 9 000, respectively).

on monomer conversion (Figure 2, left). Minor deviations from the overall linearity are observable for the low and high temperatures of the investigated range (80 and 180 8C), which might be a consequence of the occurrence of sidereactions.[12] For 140 8C, on the other hand, side reactions have been found to be repulsed to a minimum, and the number-average molecular weights perfectly comply with the theoretical values. All polymers exhibit remarkably low polydispersity indices (PDIs ca. 1.1). The nal proof for the livingness of the microwave polymerization was provided by chain extension experiments at 140 8C. The GPC traces before and after the second monomer addition clearly demonstrate the existence of living chain ends, allowing for the preparation of a 9 kDa polymer (PDI 1.17) from a 1 kDa (pre-)polymer (PDI 1.10), or, in terms of monomer units: to incorporate 90 monomers into each polymer chain in a two-step process (10 80) (Figure 1, right). The reaction rates kp for the different temperatures were calculated from the slopes of the ln{[M0]/[Mt]} plot (assuming that the standard kinetic analysis[13] is still valid under microwave irradiation). The resulting Arrhenius plot

(Figure 2, right) yields an activation energy of 73.4 kJ mol1, which is in excellent agreement with previous reported literature values for similar systems that range from 68.7 to 80.0 kJ mol1.[8a,14] This also indicates that for this polymerization system the microwave device only serves as a very efcient heating device and that there are no intrinsic microwave effects.[15] In the literature, a controversial discussion has arisen whether the increase in reaction speed and the improved purity of the products upon exposition to microwave irradiation not only originate from the fast and direct heating of the reactants, but also from so-called microwave effects.[1] Apart from our observations that conversion rates at 140 8C are independent of the heating device (microwave irradiation vs. conventional heating) and that the activation energy has a characteristic value, the observed acceleration in the range from 110 to 190 8C (60 min ! 1 min, factor 60) perfectly complies with the calculated factor (equal to 54) from the Arrhenius equation. Consequently, the increase in reaction speed is purely caused by thermal effects, as expected when utilizing a good microwave absorbing solvent

Figure 2. Left: Number average molecular weights (M n ) plotted against the conversion. Right: Corresponding Arrhenius plot.
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F. Wiesbrock, R. Hoogenboom, C. H. Abeln, U. S. Schubert

Figure 3. Left: M n and PDI values observed for a concentration series (4 to 9.9 M). Right: GPC traces (in CHCl3/NEt3/iPrOH) of two selected polymers.

like acetonitrile. Unfortunately, the effect of direct microwave absorption by the monomer could not be investigated since the cationic ring-opening polymerization of 2-oxazolines only proceeds in polar solvents. In addition to the increased reaction rates of the living polymerization and the resulting shorter reaction times, further investigations were aimed at performing the polymerization in reduced solvent amounts (green chemistry). Therefore, a series of 4 to 9.9 M solutions of the monomer (9.9 M represents bulk polymerization) was subjected to polymerization at 140 8C. The reaction times for completion can be calculated with the aid of the determined activation energy; the molecular weights were determined by GPC (Figure 3, left). The formation of polymers with number-average molecular weights of the favored 6 000 is observable for all samples. The PDI values, on the other hand, increase with the concentration of the monomer to a maximum of 1.18 for the bulk situation, representing a border case of a controlled living polymerization mechanism. The shoulder of the corresponding peak (Figure 3, right) might be generated by chain transfer reactions and subsequent chain coupling;[12] the reaction liquid, however, stays colorless. We strongly assume that our success in going to bulk polymerization while maintaining low PDI values is a direct effect of the fast, direct, and homogenous heating of the microwave system, pushing side reactions to a minimum. In addition, the changed solvent properties resulting from heating above the boiling point might also decrease the occurrence of side reactions.

(80 to 180 8C). In addition, the polymerization could be carried out in less diluted solutions under microwave irradiation, still yielding polymers with narrow molecular weight distributions. The improvements result from thermal effects; additional microwave effects are not discernible. Future investigations will be directed towards up-scaling issues as well as the polymerization of other 2-oxazolines. Special attention will be given to the accelerated synthesis of block copolymers.

Acknowledgements: The authors thank the Dutch Polymer Institute (DPI), the Nederlandse Wetenschappelijk Organisatie (NWO), and the Fonds der Chemischen Industrie for nancial support and Biotage for the collaboration.

Conclusion
In conclusion, the single-mode microwave system has proven to be a powerful device for performing the living cationic ring-opening polymerization of 2-ethyl-2-oxazoline, overcoming the long reaction times characteristic for that reaction when carried out under conventional heating. The living character of the polymerization is retained under microwave irradiation at all investigated temperatures
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[1] For general reviews, see for example: [1a] D. Adams, Nature 2003, 421, 571; [1b] H. E. Blackwell, Org. Biomol. Chem. 2003, 1, 1251; [1c] C. O. Kappe, A. Stadler, in: Microwaves in Organic Synthesis, A. Loupy, Ed., Wiley VCH, Weinheim, Germany 2002, pp. 405433; [1d] S. Barlow, S. R. Marder, Adv. Funct. Mater. 2003, 13, 517; [1e] A. Lew, P. O. Krutzik, M. E. Hart, A. R. Chamberlin, J. Comb. Chem. 2002, 4, 95; [1f] N. Kuhnert, Angew. Chem. 2002, 114, 1943; Angew. Chem. Int. Ed. 2002, 41, 1863. [2] For applications in solid phase synthesis, see for example: [2a] C. O. Kappe, Curr. Opin. Chem. Biol. 2002, 6, 314; [2b] W.-M. Dai, D.-S. Guo, L.-P. Sun, X.-H. Huang, Org. Letters 2003, 5, 2919; [2c] B. M. Glass, A. P. Combs, in: HighThroughput Synthesis, I. Sucholeiki, Ed., Marcel Dekker, New York 2001, pp. 123128. [3] [3a] A. Stadler, B. H. Youse, D. Dallinger, P. Walla, E. van der Eycken, N. Kaval, C. O. Kappe, Org. Proc. Res. Dev. 2003, 7, 707; [3b] S. T. Chen, S. H. Chiou, K. T. Wang, J. Chem. Soc., Chem. Commun. 1990, 11, 807. [4] For a recent review, see: F. Wiesbrock, R. Hoogenboom, U. S. Schubert, Macromol. Rapid Commun. 2004, 25, 1739. [5] [5a] K. R. Carter, Macromolecules 2002, 35, 6757; [5b] A. Kahn, S. Hecht, Chem. Commun. 2004, 300.
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