Article pubs.acs.org/ac
PHIP NMR Spectroscopy in Ionic Liquids: Influence of Salts on the Intensity of Polarization Signals Andreas Bröhl and Ralf Giernoth* Department für Chemie, Universität zu Köln, Greinstr. 4, D-50939 Köln, Germany S Supporting Information *
ABSTRACT: Parahydrogen-induced dynamic nuclear polarization NMR spectroscopy (PHIP) in ionic liquids leads to weak or no polarization signals, depending on the type of experiment. We demonstrate that the intensity of polarization is directly correlated to the concentration of the ionic liquids. High ion concentration is connected to fast T1 relaxation, resulting in annihilation of the polarization signals.
P
atmosphere. The NMR tube was connected to a 1.2 m glass tube with the help of a small piece of rubber tubing as connector. Degassed (“freeze-pump-thaw”) acetone-d6 and degassed IL were then inserted into the NMR tube through the rubber connector with the help of a syringe. The mixture was homogenized with the help of a vortex mixer. NMR Measurements. The construction containing a NMR tube, rubber tubing connector, and a glass tube was provided with two NMR spinners and transferred into the NMR magnet. The end of the glass tube protruded approximately 10 cm above the top of the magnet. Parahydrogen was produced by letting H2 gas pass through a U-shaped metal tube that was filled with activated charcoal and cooled with the help of liquid nitrogen. The outlet of this construction was connected to an HPLC tube which was used to bubble para-enriched hydrogen directly into the NMR tube. A sketch of this experimental setup can be found in the Supporting Information. In a typical PHIP experiment, 0.7 mL of acetone-d6 was added to 60 mg of substrate, 1 mg of catalyst, and the respective amount of salt. After placing the tube into the NMR magnet, the experiment was conducted. The spectrum was recorded on a Bruker AV400 spectrometer after a single 45° 1H pulse. T1 relaxation data have been acquired through a standard inversion−recovery experiment. All experimental procedures and additional data can be found in the Supporting Information.
HIP NMR spectroscopy (parahydrogen-induced polarization) is a powerful method for studying homogeneous hydrogenation reactions.1−6 It is conducted by hydrogenating inside the NMR magnet using para-enriched hydrogen. In this way, polarization signals arise, given that the hydrogen molecule is transferred to the substrate in a pairwise fashion. The antiphase pattern of the resulting PHIP signals contains information about the reaction mechanism, whereas a strong enhancement of the signal intensity enables the detection of intermediates and products even in very low concentration. Advancements of the method are currently focusing on selective signal enhancement for NMR tomography.7,8 Homogeneous hydrogenation reactions were among the first being studied in ionic liquids (ILs) as the solvents.9,10 To quite a surprise, even substrates with very limited solubility gave remarkable results. In the following, ionic liquids proved especially valuable for biphasic processes in which the catalyst was heterogenized in the ionic phase. Consequently, hydrogenation reactions in ILs should be perfectly suitable to be studied using PHIP NMR spectroscopy (Figure 1).
■
EXPERIMENTAL SECTION Sample Preparation. Solids (MAC and the catalyst) and, if applicable, salt were placed into an NMR tube in an argon
Received: July 10, 2014 Accepted: September 27, 2014
Figure 1. Structures of the ionic liquids that have been used in this study. © XXXX American Chemical Society
A
dx.doi.org/10.1021/ac502537z | Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
■
Article
RESULTS AND DISCUSSION To validate our experimental setup, we first focused on the standard hydrogenation substrate MAC (methyl-Z-α-acetamido cinnamic acid). PHIP hydrogenation of MAC in acetone-d6 using [Rh(cod)(dppb)][BF4] as the catalyst gave the expected polarization signals, as depicted in Figure 2.
Figure 3. Hydrogenation of MAC under PHIP conditions. Plot of the total area of the antiphase signals (i.e., intensity of polarization signals) versus the mole fraction of IL.
Because we had already performed experiments in diluted solution, we know that IL viscosity cannot have anything to do with the nonappearance of the polarization signals. To check whether the presence of a large concentration of salt is responsible for the disappearance of these signals, we repeated the experiments with varying mole fractions of LiNTf2, a crystalline salt. Indeed, the results were almost identical to the ones with ILs (Table 2 and Figure 4).
Figure 2. PHIP NMR spectrum during the hydrogenation of methylZ-α-acetamido cinnamic acid (MAC) in acetone-d6 with para-enriched hydrogen.
In the following, we hydrogenated MAC under PHIP conditions in varying acetone/IL mixtures. (The structures of the ILs are depicted in Figure 1, above.) The results are listed in Table 1. In Figure 3, we plotted the intensity of the polarization
Table 2. PHIP Hydrogenation of MAC in Acetone with Varying Mole Fractions of LiNTf2a
Table 1. PHIP Hydrogenation of MAC in Acetone with Varying Mole Fractions of ILa IL c
[C1C2im][P(C2F5)3F3]
[C1C2im][CH3SO3]d
entry
V(IL) [mL]
V(acetone) [mL]
χ(IL)
Ab
1 2 3 4 5 1 2 3 4
0 0.1 0.2 0.3 0.4 0 0.1 0.2 0.3
0.7 0.6 0.5 0.4 0.3 0.7 0.6 0.5 0.4
0 0.036 0.082 0.144 0.230 0 0.068 0.150 0.248
4.07 1.45 0.92 0.52 0 4.10 0.31 0.07 0
entry
m(salt) [mg]
χ(salt)
Ab
1 2 3 4 5 6
0 30 100 246 464 910
0 0.011 0.036 0.082 0.144 0.230
1.91 1.10 0.58 0.26 0.15 0
a
Reaction conditions: Varying amounts of LiNTf2 were added to 1 mg of catalyst ([Rh(cod)(dppb)][BF4]), 60 mg of MAC and 0.7 mL of acetone-d6 in a standard 5 mm NMR tube. bTotal area of the antiphase signals (i.e., signal intensity)
A combination of the data in one single graph in which the total intensities are normalized demonstrates the close resemblance of the two experiments (Figure 5).
a
Reaction conditions: 1 mg of catalyst ([Rh(cod)(dppb)][BF4]), 60 mg of MAC, and a mixture of acetone-d6 and IL given by χ in a standard 5 mm NMR tube. bTotal area of the antiphase signals (i.e., signal intensity). c 1-Ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate. d1-Ethyl-3-methylimidazolium methyl sulfonate.
signals (represented by the total area of the antiphase signals) versus the mole fraction of IL. The mole fraction is given as χ (IL) =
n(IL) n(IL) + n(acetone)
Obviously, the IL concentration has a strong influence on the intensity of the polarization signals. With a mole fraction of 0.23, no polarization is detectable anymore. The strong decay in the case of [C2C1im][CH3SO3] can be attributed to the strong coordination ability of the anion, deactivating the catalyst.11
Figure 4. Hydrogenation of MAC under PHIP conditions. Plot of the total area of the antiphase signals (i.e., intensity of polarization signals) versus the mole fraction of LiNTf2. B
dx.doi.org/10.1021/ac502537z | Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
Article
this case, no PHIP signals were detectable at a mole fraction of 0.23. These findings can be aligned with the very similar signal decay in the case of LiNTf2 as additive (cf. Figures 4 and 5). In the view of the sum of all our findings, the reason for the nonappearance of the PHIP signals most probably arises from the relaxation behavior at high ion concentrations. The T1 relaxation times of the protons in MAC are in the range of 4.5− 2.5 s without any additives and in the range of 1.2 s−850 ms at a LiNTf2 mole fraction of 0.23 (cf. Table 3 and Figure 7). The Table 3. T1 Relaxation Times of MAC (cf. Figure 2) at Different LiNTf2 Concentrations χ(LiNTf2)
Figure 5. Combined plot of the normalized data from Figure 2 and 3
0 0.011 0.036 0.082 0.144 0.230
To elucidate the reasons for these results, we first examined the conversion data. For this purpose, MAC was hydrogenated under the same conditions as during the PHIP experiments without any ionic additive and with a content of 23 mol % [C2C1im][P(C2F5)3F3] and LiNTf2, respectively. This mole fraction was the limit at which no polarization signals could be detected at all. We found that there is no crucial effect of the ionic additives concerning the conversion of MAC (cf. Figure 6). Therefore, a too low concentration of the hydrogenated product at high ion concentrations cannot be responsible for the lack of the polarization signals.
H-1′ 3.919 3.302 2.888 2.156 1.623 1.219
H-6 s s s s s s
4.548 3.868 3.263 2.370 1.559 904.8
s s s s s ms
H-4 4.191 3.309 3.234 2.370 1.559 904.8
s s s s s ms
H-1 2.467 2.038 1.638 1.289 929.2 967.4
s s s s ms ms
H-3′ 2.444 2.206 1.645 1.198 916.0 857.4
s s s s ms ms
Figure 7. Decay of the T1 relaxation times of the protons in MAC, the trend of the phenylic protons (H-6) is shown exemplarily.
T2 relaxation times do not seem to be affected as there is no line broadening at higher ion concentrations observed at all. Hence, we deduce that, at high ion concentrations, the polarized spin system has completely relaxed into equilibrium before the spectrum was recorded. Therefore, no NMR signals are detectable for these groups. These findings are also suitable for the explanation of the observations in recent literature, where three groups have been trying to perform PHIP hydrogenations in ionic liquids. Stark and Buntkowsky studied the hydrogenation of ethyl acrylate in ionic liquids containing the anion NTf2−.12 They were only able to detect PHIP signals in cases where the IL was present in very low concentration (substrate/IL ratio of 100:1). With high IL concentrations (where the IL could accurately be called a solvent), no PHIP was detected. The authors attributed this behavior predominantly to the high viscosity of the ionic liquid and the result of low mass transport. In contrast, Koptyug and co-workers have studied supported ionic liquid phase (SILP) hydrogenation of propyne,13 and Klankermayer and Blümich have investigated the SILP hydrogenation of propene using PHIP NMR.14 In SILP catalysis, an ionic liquid containing dissolved catalyst is applied to the surface of a solid support.15 In this fashion, poor mass transport is circumvented, making catalytic reactions in ILs more effective. The authors were indeed able to detect PHIP signals, although it is important to note that these are gas-phase
Figure 6. Conversion of MAC in the absence and presence of ionic additives, determined by 1H NMR spectroscopy. In each case, the amount of hydrogenated product is high enough to be potentially detected via PHIP NMR.
Hydrogenation experiments with Wilkinson’s catalyst resulted either in a poor solubility of the catalyst (in acetoned6 and acetonitrile-d3), a poor solubility of MAC and IL/salt (in benzene-d6) or in no conversion despite of complete solubility (in THF-d8 and DCM-d2, in the case of THF probably because of the strong coordination, deactivating the catalyst). As the primarily chosen system acetone-d6/[Rh(cod)(dppb)][BF4] resulted in good conversions, the other attempts were not taken into further consideration. As imidazolium-based ionic liquids are known for undergoing H/D exchange reactions, we noticed the possibility that parahydrogen could possibly be “deactivated” (i.e., the para/ ortho equilibrium might be shifted to the ortho form) by such exchange reactions. As a consequence, we performed the PHIP measurements of MAC with [C4C1pyrr][BF4] (1-butyl-1methylpyrrolidinium tetrafluoroborate) as additive. Also in C
dx.doi.org/10.1021/ac502537z | Anal. Chem. XXXX, XXX, XXX−XXX
Analytical Chemistry
Article
(14) Gong, Q.; Klankermayer, J.; Blümich, B. Chem.Eur. J. 2011, 17, 13795−13799. (15) Mehnert, C. P. Chem.Eur. J. 2005, 11, 50−56.
reactions, and in their experimental setup, the NMR detection took place outside the ionic phase. Still, the IL/catalyst ratio had a strong influence on the PHIP intensity. In the case of Stark and Buntkowsky, where no PHIP signals could be detected at high IL concentrations, the hydrogenated product was still in contact with the IL, leading to very fast relaxation. The cases of Koptyug and Klankermayer, respectively, both concern gas-phase hydrogenations where the hydrogenated products were not in contact with the IL during the acquisition. So, the T1 times were not shortened, and PHIP signals could be observed.
■
CONCLUSIONS In conclusion, we have demonstrated that the appearance of polarization signals in PHIP NMR spectroscopy can be suppressed in the presence of high ion concentrations, most probably due to fast T1 relaxation.
■
ASSOCIATED CONTENT
S Supporting Information *
Additional experimental data. This material is available free of charge via the Internet at http://pubs.acs.org.
■
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Phone: +49-221-4703094. Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS We thank Deutsche Forschungsgemeinschaft (DFG) for funding via the Special Priority Programme 1191 “Ionic Liquids”, the “Fonds der Chemischen Industrie” for a graduate fellowship for A.B., and Andrea Kuchenbuch for providing the artwork for the table of contents.
■
REFERENCES
(1) Bowers, C. R.; Weitekamp, D. P. J. Am. Chem. Soc. 1987, 109, 5541−5542. (2) Eisenschmid, T. C.; Kirss, R. U.; Deutsch, P. P.; Hommeltoft, S. I.; Eisenberg, R.; Bargon, J.; Lawler, R. G.; Balch, A. L. J. Am. Chem. Soc. 1987, 109, 8089−8091. (3) Pravica, M. G.; Weitekamp, D. P. Chem. Phys. Lett. 1988, 145, 255−258. (4) Giernoth, R.; Hübler, P.; Bargon, J. Angew. Chem. 1998, 110, 2649−2651. (5) Duckett, S. B.; Sleigh, C. J. Prog. Nucl. Mag. Res. 1999, 34, 71−92. (6) Hübler, P.; Giernoth, R.; Kümmerle, G.; Bargon, J. J. Am. Chem. Soc. 1999, 121, 5311−5318. (7) Reineri, F.; Santelia, D.; Viale, A.; Cerutti, E.; Poggi, L.; Tichy, T.; Premkumar, S. S. D.; Gobetto, R.; Aime, S. J. Am. Chem. Soc. 2010, 132, 7186−7193. (8) Waddell, K. W.; Coffey, A. M.; Chekmenev, E. Y. J. Am. Chem. Soc. 2011, 133, 97−101. (9) Chauvin, Y.; Mussmann, L.; Olivier, H. Angew. Chem. 1995, 107, 2941−2943. (10) Suarez, P. A. Z.; Dullius, J. E. L.; Einloft, S.; deSouza, S. Z. Polyhedron 1996, 15, 1217−1219. (11) Lungwitz, R. Ph.D. Thesis, Chemnitz University of Technology: Chemnitz, Germany, Feb. 11, 2011. (12) Gutmann, T.; Sellin, M.; Breitzke, H.; Stark, A.; Buntkowsky, G. Phys. Chem. Chem. Phys. 2009, 11, 9170−9175. (13) Kovtunov, K. V.; Zhivonitko, V. V.; Kiwi-Minsker, L.; Koptyug, I. V. Chem. Commun. 2010, 46, 5764−5766. D
dx.doi.org/10.1021/ac502537z | Anal. Chem. XXXX, XXX, XXX−XXX
