Frank Wiesbrock et al- Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living...

8/3/2019 Frank Wiesbrock et al- Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living Polymerizat

1/5

Single-Mode Microwave Ovens as New ReactionDevices: 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 NetherlandsE-mail: [email protected]

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, reac-

tions can be performed in reduced solvent amounts (green

chemistry).

Contrary to their well-established use in a steadily

growing number of organic reactions, it is only very recen-

tly that polymer chemists have discovered single-mode

microwave systems as new reaction devices. The first sets

of polymerization reactions have been performed undermicrowave irradiation. The corresponding findings 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 inves-

tigated so far. To obtain data for this important type of

reaction, we chose the living cationic ring-opening poly-

merization (CROP) of 2-ethyl-2-oxazoline as a first

example (Scheme 1).[8] Its investigation began in 1966,[9]

Summary: The ring-opening cationic polymerization of2-ethyl-2-oxazoline was performed in a single-mode micro-wave reactor as the first example of a microwave-assistedliving polymerization. The observed increase in reactionrates by a factor of 350 (6 h !1 min) in the range from 80 to190 8C could be attributed solely to a temperature effect aswasclearly shown by control experiments andthe determinedactivation energy. Because of the homogenous microwaveirradiation, the polymerization could be performed in bulk orwith drastically reduced solvent ratios (green chemistry).

Monomer conversion, represented by theratio ln{[M0]/[Mt]},plotted against time for six temperatures in the range from80 to 180 8C, and polymerization reaction vials, showing anincrease in yellow color for those reactions performed (well)above and below 140 8C, indicating side reactions.

Macromol. Rapid Commun. 2004, 25, 18951899 DOI:10.1002/marc.200400369 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication 1895


2/5

and ever since, fuelled by its promising potential applica-

tions like micellar catalysis, drug delivery, or hydro-

gels,[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.

Experimental Part

Materials and Instrumentation

All chemicals, except for acetonitrile (Biosolve LTD), werepurchased 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 reactionvials uniquelydesigned for the single-mode microwavesystem EmrysLibera-

tor (Biotage, formerly PersonalChemistry). These vials wereheated, allowed to cool to room temperature, and filled with

argon prior to use. All experiments were performed on 2 mLsolutions; the polymerizations were terminated by quenching

the reaction mixtures at the favored times with water.

Gas chromatography (GC) measurements (for the determi-nation of the conversion) were performed utilizing an Inter-science Trace GC with a Trace Column RTX-5 connected to aPAL autosampler. For the injection of polymerization mixtu-

res, a special Interscience liner with additional glass wool was

used. Gel permeation chromatography (GPC) was performedon a Shimadzu system with a SCL-10A system controller, an

LC-10AD pump, an RID-10A refractive index detector, and aPLgel 5 mm Mixed-D column at 50 8C using a chloroform/

triethylamine/isopropyl alcohol (94:4:2) mixture as eluent at aflow rate of 1 mL min1 (polystyrene calibration).

Microwave-Assisted Polymerizations of 2-Ethyl-2-Oxazoline

Unless indicated otherwise, solutions with an initial 2-ethyl-2-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 of25 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 performedwith different reaction times.

For the concentration series in the range from 4 to 9.9 M, theratio of [EtOx]/[TsOMe] was kept at a value of 60. In the caseof the chain extension experiments (at 140 8C), the first block

was prepared in acetonitrile solution (4 M, [EtOx]/[TsOMe]

10; reaction time of 100 s). For the second reaction step, the

additional 2-ethyl-2-oxazoline (80 units per TsOMe) was add-ed without additional solvent (reaction time of 800 s).

Results and Discussion

A first 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 poly-

merization increases with temperature and is, in contrast toconventional heating, not limited to the boiling point of

acetonitrile (828C). 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 1908C, 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 2008C,

exhibitingonlyaminorincreasecomparedtothestandard1.1

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 monitor-

ing the time dependence of the conversion rates and the

number-average molecular weights (Mn) of the correspond-

ing polymers for six representative temperatures (Figure 1

and 2). The power supplied to maintain the reaction temper-

ature was found to be independent of the conversion,

exhibiting a comparable absorption of the microwaveirradi-ation by the monomer and the polymer in the presence of

acetonitrile. The monomer conversion at a given temper-

ature (obtained by GC and represented by the ratio ln{[M0]/

[Mt]}) depends linearly on time, illustrating the first order

kinetics of the polymerization reaction (Figure 1, left). A

control experiment at 1408C 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 (Mn)

Scheme 1. Schematic representation of the cationic ring-opening polymerization of2-ethyl-2-oxazoline initiated by methyl tosylate.

1896 F. Wiesbrock, R. Hoogenboom, C. H. Abeln, U. S. Schubert

Macromol. Rapid Commun. 2004, 25, 1895 1899 www.mrc-journal .de 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


3/5

on monomer conversion (Figure 2, left). Minor deviations

from the overall linearity are observable for the low andhightemperatures of the investigatedrange (80 and1808C),

which might be a consequence of the occurrence of side-

reactions.[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 final 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 previousreported 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 efficient heatingdevice 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 from110 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 ex-

pected when utilizing a good microwave absorbing solvent

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

Figure 2. Left: Number average molecular weights (Mn) plotted against the conversion.Right: Corresponding Arrhenius plot.

Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living Polymerization of 2-Ethyl-2-Oxazoline 1897

Macromol. Rapid Commun. 2004, 25, 1895 1899 www. mrc-journal .de 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


4/5

like acetonitrile. Unfortunately, the effect of direct micro-

wave 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 poly-

merization 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 1408C. The reaction times for comple-

tion 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 mechan-

ism. 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.

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-oxazo-

line, 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

(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 fromthermal 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 PolymerInstitute (DPI), the Nederlandse Wetenschappelijk Organisatie(NWO), and the Fonds der Chemischen Industrie for financialsupport and Biotage for the collaboration.

[1] Forgeneral reviews, seefor example: [1a] D. Adams,Nature2003, 421, 571; [1b] H. E. Blackwell, Org. Biomol. Chem.2003, 1, 1251; [1c]C. O.Kappe,A. Stadler,in: Microwavesin 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. Letters2003, 5, 2919; [2c] B. M. Glass, A. P. Combs, in: High-Throughput Synthesis, I. Sucholeiki, Ed., Marcel Dekker,New York 2001, pp. 123128.

[3] [3a] A. Stadler, B. H. Yousefi, 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] Fora recentreview, 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.

Figure 3. Left: Mn and PDI values observed for a concentration series (4 to 9.9 M).Right: GPC traces (in CHCl3/NEt3/

iPrOH) of two selected polymers.

1898 F. Wiesbrock, R. Hoogenboom, C. H. Abeln, U. S. Schubert

Macromol. Rapid Commun. 2004, 25, 1895 1899 www.mrc-journal .de 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


5/5

[6] D. Bogdal, P. Penczek, J. Pielichowski, A. Proziak, Adv.Polym. Sci. 2003, 163, 193.

[7] [7a] D. D. Wisnoski, W. H. Leister, K. A. Strauss, Z. Zhao,C. W. Lindsley, Tetrahedron Lett. 2003, 44, 4321; [7b]G. Chen, X. Zhu, Z. Cheng, J. Lu, J. Chen, Polym. Int. 2004,53, 357; [7c] H. Zhang, U. S. Schubert, Macromol. RapidCommun. 2004, 25, 1225; [7d] W. Xu, X. Zhu, Z. Cheng,

G. Chen, J. Lu, Eur. Polym. J. 2003, 39, 1349.[8] [8a] R. Hoogenboom, M. W. M. Fijten, M. A. R. Meier,U. S.

Schubert, Macromol. Rapid Commun. 2003, 24, 98; [8b] R.Hoogenboom, M. W. M. Fijten, C. H. Abeln, U. S. Schubert,Macromol. Rapid Commun. 2004, 25, 237.

[9] [9a] D. A. Tomalia, D. P. Sheetz,J. Polym. Sci. 1966, 4, 2253;[9b] W. Seeliger, E. Aufderhaar, W. Diepers, R. Feinauer, R.Nehring, W. Thier, H. Hellmann, Angew. Chem. 1966, 78,913; Angew. Chem., Int. Ed. 1966, 5, 875.

[10] [10a] S. Kobayashi, T. Igarashi, Y. Moriuchi, T. Saegusa,Macromolecules 1986, 19, 535; [10b] R.-H. Jin, Adv. Mater.2002, 14, 889; [10c] R.H. Jin,J. Mater. Chem.2004, 14, 320;

[10d] B. Levenfeld, J. San Roman, C. Bunel, J.-P. Vairon, Makromol. Chem. 1991, 192, 793; [10e] V. Percec, T. K.Bera, R. J. Butera,Biomacromolecules 2002, 3, 272; [10f] Y.Chujo,K. Sada,T. Saegusa,Macromolecules 1993, 26,6315;[10g] S. de Vos, M. Moeller, K. Visscher, P. F. Mijnlieff,Polymer 1994, 35, 2644.

[11] K. Aoi, M. Okada, Prog. Polym. Sci. 1996, 21, 151.

[12] M. Litt, A. Levy, J. J. Herz, Macromol. Sci. Chem. 1975, 5,703.

[13] R. Hoogenboom, M. W. M. Fijten, C. Brandli, J. Schroer,U. S. Schubert, Macromol. Rapid Commun. 2003, 24,98.

[14] [14a] T. Saegusa, H. Ikeda, Macromolecules 1973, 6, 808;[14b] T. Saegusa, H. Ikeda, H. Fujii, Macromolecules 1972,5, 359.

[15] [15a] D. A. Lewis, J. D. Summers, T. C. Ward, J. E. McGrath, J. Appl. Polym. Sci. 1992, A30, 1647; [15b] J. Berlan,P. Giboreau, S. Lefeuvre, C. Marchand, Tetrahedron Lett.1991, 32, 2363.

Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living Polymerization of 2-Ethyl-2-Oxazoline 1899

Macromol. Rapid Commun. 2004, 25, 1895 1899 www. mrc-journal .de 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Frank Wiesbrock et al- Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living...

Documents

Transcript of Frank Wiesbrock et al- Single-Mode Microwave Ovens as New Reaction Devices: Accelerating the Living...