Ionic Liquids IIIA - American Chemical Society

Chapter 6

In Situ IR Spectroscopy in Ionic Liquids: Toward the Detection of Reactive Intermediates in Transition Metal Catalysis

Downloaded by CORNELL UNIV on May 30, 2012 | http://pubs.acs.org Publication Date: March 15, 2005 | doi: 10.1021/bk-2005-0901.ch006

Ralf Giernoth Institute of Organic Chemistry, University of Cologne, Greinstrasse 4, 50939 Köln, Germany

In situ IR spectroscopy is used for the in situ investigation of the mechanisms of two selected reactions. The ReactIR proves to be a versatile tool for reaction monitoring and for the on line collection of kinetic information. With this method, the direct alkylation of N-methylimidazole with 1-bromobutane can be shown to proceed via S 1 or electron transfer rather than S 2. For easy and straightforward detection and characterization of catalytically reactive intermediates in the Suzuki-Miyaura reaction, though, the method seems to be not sensitive enough, but it can help to gain insight into the reaction mechanism. N

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Ionic liquids (ILs) are well established as neoteric reaction media for organic synthesis and for transition metal catalysis in particular (1). This is mainly due to the fact that their physical and physico-chemical properties are varied substantially with the choice of anion and cation - vital properties such as miscibility with other organic solvents, solvation power, acidity, gas solubility, or viscosity (2). By wisely choosing a variety of ionic liquids with the properties needed for the intended chemical transformation, the chemist, in addition to catalyst, ligands, reaction conditions etc., now has another means for screening and fine-tuning. Therefore, ILs are sometimes called "designer solvents" (3). © 2005 American Chemical Society

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In Ionic Liquids III A: Fundamentals, Progress, Challenges, and Opportunities; Rogers, R., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

80 From the chemical literature of the past few years, it seems obvious that for almost any given chemical transformation a "matching" IL will exist that can be used as a reaction medium and that will lead to a significant enhancement of activity and selectivity. This fact has sometimes been called "ionic liquid effect" (4) - primarily because of the lack of rational explanations for this enhancement. Since it it obvious that some kind of IL effect does exist, and since it differs substantially from case to case, it will be impossible to devise a "general IL effect" - there are far too many very different ILs and far too many different reaction types with many different possibilities of solvent-solute interactions. In the beginning of IL chemistry it was believed that the promoting effect of ILs with weakly coordinating anions (such as BF " or (CF S0 )2N"") is mainly due to the fact that they are polar enough to dissolve all the reactants but do not exhibit a strong solvent shell (5). For transition metal catalysis this would lead to "naked" and thus very active catalysts. Later, on the other hand, it could be demonstrated that some ILs can actively participate in the reaction, for example by binding to the transition metal center as a ligand (d). And still, there are the cases of reactions that are not promoted by the use of ionic liquids. Therefore, our key questions are: what are the reaction mechanisms of catalytic reactions in ionic liquids? Do they differ to the ones in conventional organic solvents? What are the key intermediates? What promotes the reactions, and what inhibits them? It won't be possible to answer these questions globally, rather will they have to be answered for any single reaction of interest. We therefore believe that it is vital to develop a standard set of readily applicable in situ spectroscopic methods for the use in ionic liquid media. To that end, we wondered to what extend in situ IR spectroscopy can be applied. The ReactIR 4000 spectrometer (manufactured by Mettler-Toledo) is an FTIR spectrometer with an ATR (attenuated total reflection) probe that can be inserted directly into the reaction mixture. With this, it is possible to monitor any given reaction in situ under real reaction conditions. The resulting 3D IR plot for the synthesis of [bmimJBr (1-buty 1-3-methyl imidazolium tetrafluoroborate) is shown in Figure 1 as an example. Here, jV-methylimidazole is added to the reaction flask first, then 1-bromobutane, and finally the mixture is heated to 80 °C. At that point, a vigorous and exothermic reaction starts and is finished within minutes. The process can be analyzed afterwards with a software package (ConcIRT™) which notes the change in the IR spectra over time. By this, the number of entities is determined that occur in the reaction, together with their corresponding time-concentration-profiles and their calculated IR spectra. Therefore, it is possible to identify reactive intermediates that are not visually detectable in the IR spectra. For our alkylation reaction (cf. Figure 1), Figure 2 shows that an intermediate occurs which can, e.g., be attributed to a carbocation.


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Fiugre 1. ReactIR plot the direct alkylation ofN-methylimidazole with 1bromobutane to give the ionic liquid [bmim] Br.


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83 The reaction seems not to proceed as S 2 under these reaction conditions, which of course is highly unusual for primary alkyl halides. This can be explained, though, by the fact that 1,3-disubstituted imidazolium-based ILs (one of which is formed as the reaction product) are polar as well as protic (the 2-hydrogen in the imidazolium ring bears some acidity (7)). Polar protic media stabilize charged transition states; therefore, S 1 or an electron transfer mechanism can be favored here over S 2. The ReactIR method can conveniently be used for reaction monitoring of transition metal catalysis in ILs. As a test reaction we chose the Suzuki-Miyaura coupling of bromobenzene with phenylboronic acid as published by Welton et. al. (8), which has been reported to be not too sensitive to air. The ReactIR monitoring of the standard model reaction in [omim][Tf N] (l-octyl-3-methyl imidazolium bis-triflic amine) is shown in Figure 3. The turnover of the reaction is clearly visible, e.g., by the biphenyl bands growing in around 1633 and 1410 cm* (v -c) and around 700 cm" (ô . ). N

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Figure 3. ReactIR monitoring of a standard Suzuki-Miyaura reaction in [omim][Tf N]. Three specific bands of the product biphenyl are highlighted. 2


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The ReactIR can be used to acquire on-line kinetic information about the reactions. In this fashion, it is possible, e.g., to judge the end of the turnover while the reaction is still running. Figure 4 demonstrates the time-intensity plot for the Suzuki-Miyaura reaction corresponding to Figure 3.

Time (minutes) Figure 4. Time-intensity plotfor the Suzuki-Miyaura reaction in [omim][Tf N] as shown in Figure 3. The intensities of a specific band of one starting material (bromobenzene) and one of the product (biphenyl) in relative values are plotted versus time. 2

Although being very useful for everyday reaction monitoring, especially on the laboratory scale, ReactIR plots of this type do not reveal straightforward information about reactive intermediates in transition metal catalysis. The obvious reason for this is that the spectroscopic method must be fast and sensitive enough for the detection of short-lived intermediates being present at very low concentrations. Compared to NMR, for example, IR spectroscopy is fast: with the ReactIR a maximum of three spectra per second can be recorded (although, since it is a FT spectrometer, normally 32 to 64 spectra are accumulated prior to fourier transformation). The sensitivity, on the other hand, is probably not high enough and further limited by the ATR technique.



85 None the less, we wondered to what extend in situ IR spectroscopy of this type can be employed for mechanistic studies of the Suzuki-Miyaura reaction. One of the key questions in this reaction (and in IL chemistry in general) is about the structure of the active catalyst species (cf. Figure 5). Is is well known that imidazolium cations under basic conditions can form carbene complexes of the Arduengo type (7) with transition metals. Welton et. al. have demonstrated that under the reaction conditions a palladium imidazolylidene carbene complex can form, althougth its activity in catalysis could not be proven (9). Yet, for a closely related Heck reaction Xiao et. al have shown that a complex of this type is active as a precatalyst (6). On the other hand, we realized that tetrakistris(triphenylphosphine)palladium(0), which is used as the catalyst, is insoluable in our ILs, but it dissolves readily and completely after the addition of bromobenzene. This is in accordance with the textbook catalytic cycle for this reaction, in which the first step is the insertion of the palladium catalyst into the arene-bromine-bond (Figure 5). To find out about this and to test the applicability of the ReactIR method for this purpose, the following experiment has been carried out: First, a larger amount (SO mg) of the palladium precatalyst has been suspended in the IL (2 mL; in this case, [Ci mim][BF ] has been used, which had proven to be the best solvent for this reaction in our earlier experiments (10)). The corresponding ReactIR plot (Figure 6) shows at least some dissolved species around 700 cm* . Then, bromobenzene was added in two portions (100 + 50 μί). At this point, the spectra of bromobenzene are dominant in the IR and nothing else is visually detectable. It is noteworthy to say that under these conditions an almost clear, dark-orange solution was obtained. Keeping the solution under argon overnight resulted in a bright-white triphenylphosphine precipitate. Subsequent ConcIRT analysis gave five (calculated) IR spectra and the corresponding time-intensity plots for five (calculated) reaction partners, as depicted in Figure 7. Number 1 is bromobenzene, since the calculated spectrum corresponds perfectly with the real one, and the intensity plot shows the two steps of addition. No. 2 is the IL solvent - the calculated spectrum is of limited value, because the IL as the solvent has been subtracted from all the other spectra as the background by the ReactIR. The intensity plot shows the same, but inverse steps for the addition of bromobenzene, which is a simple dilution effect. The interpretation of the other three spectra/plots must remain guesswork. No. 3 remains almost constant or diminishes slightly in the course of the reaction while No. 4 and 5 are steadily growing in. Therefore, 3 will most probably have to be 0

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Figure 5. Two possible forms of the active catalyst for Suzuki-Miyaura coupling reactions in an imidazolium-based IL medium.

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Figure 6. ReactIR monitoring of the catalyst preforming mechanism.



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Figure 7. ConcIRT analysis of the ReactIR plot shown in Figure 6. The numbers of the calculated spectra (left) correspond to the numbers of the time-intensityplots (right). The program calculatesfivereactants, two ofwhich (No. I and 2) can unambiguously be attributed to bromobenzene and the IL, respectively. (The wave-like structure of the time-intensity plots reflects oscillations in the quality of the air generator which is used toflushthe spectrometer.)


88 attributed to Pd(PPh ) while 4 and 5 can be PPh and the active catalyst component, although it is impossible to say if this is true and which one is which. The fact that dissolution of the Pd-precatalyst only occurs after addition of bromobenzene hints to the fact that under these conditions no carbene complex is formed. Unfortunately, the Pd-carbene stretching band, unambigiously identifying this species, would occur below 650 cm , which is the physical limit of the ReactIR spectrometer. In conclusion, we have shown that in situ IR spectroscopy with the ReactIR is a valuable tool for reaction monitoring and on-line kinetics of reactions in ionic liquids. Reactive intermediates in higher concentration, although invisible by the eye, can be detected by subsequent analysis of the ReactIR plot with the software package ConcIRT. For easy and straightforward detection of reactive intermediates in transition metal catalysis, though, this method seems to be not sensitive enough. None the less, since the experimental setup is hassle-free and robust, the method can at least help getting ideas about the mechanistic details of the reaction, which will then have to be proven further by other spectroscopic techniques. The author is currently developing a setup for routine in situ NMR spectroscopy in ionic liquids. R.G. would like to thank Deutsche Forschungsgemeinschaft (DFG) for a generous Emmy Noether fellowship. 3

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References 1. Ionic Liquids in Synthesis; Wasserscheid, P.; Welton, T., Eds.; Wiley-VCH: Weinheim 2003; Chapter 5. 2. Ionic Liquids in Synthesis; Wasserscheid, P.; Welton, T., Eds.; Wiley-VCH: Weinheim 2003; Chapter 3. 3. Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed. Engl. 2000, 39, 37723789 4. For example: Ross, J.; Chen, W.; Xu, L.; Xiao, J. Organometallics 2001, 20, 138-142. 5. Welton, T. Chem. Rev. 1999, 99, 2071-2083. 6. Xu, L. J., Chen, W. P., Xiao, J. L. Organometallics 2000, 19, 1123-1127. 7. Arduengo, A. J., Harlow, R. L., Kline, M . J. Am. Chem. Soc. 1991, 113, 361-363. 8. Mathews, C. J.; Smith, P. J.; Welton, T., Chem. Commun. 2000, 1249-1250. 9. Mathews, C. J.; Smith, P. J.; Welton, T.; White, A. J. P.; Williams, D. J., Organometallics 2001, 20, 3848-3850. 10. Giernoth, R.; unpublished results.


Ionic Liquids IIIA - American Chemical Society

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